MTHFR A1298C Mutation: Some Information on A1298C MTHFR Mutations

There is little known about the A1298C MTHFR mutation.

Or so it seems.

Research seems to ignore it almost completely while the C677T MTHFR mutation gets all the attention and glory.

For those who have the A1298C MTHFR mutation, this is frustrating.

Symptoms exist and doctors are saying there is no correlation between the MTHFR A1298C mutation and your symptoms – right?

I’d like to prove them wrong – at least for the symptoms which do correlate with the A1298C MTHFR mutation.

Lets’ get started.

The MTHFR A1298C mutation may affect you if you are either:

  • Homozygous A1298C MTHFR mutation
  • Compound heterozgous A1298C + C677T MTHFR mutation

My current stance on the heterozygous MTHFR A1298C mutation is that it is very common and does not seem to pose too much concern unless there are other methylation or cytochrome mutations present. Obviously, if one leads a lifestyle which is unhealthy (smoking, high stress, toxic exposures) and consumes an unhealthy diet (refined carbs, processed meats, saturated fats), then having a heterozygous A1298C mutation may contribute to cardiovascular disease, depression, fibromyalgia and others.

Ever hear this?:

Your homocysteine levels are fine. You’ve nothing to worry about.

I know many doctors evaluate homocysteine only when it comes to MTHFR mutations.

This is absolutely incorrect.

Those with A1298C MTHFR mutations do not display elevated homocysteine unless they are combined with C677T. Even when combined with C677T MTHFR mutations, the A1298C types still do not tend to have very elevated homocysteine.

Regardless of which snp you have, either the 677 or 1298, the MTHFR enzyme’s end product, methylfolate, supports two major pathways: BH4 and Methylation.

BH4 regeneration is supported by methylfolate and SAM.

Some people say that BH4 regeneration is only done by those having the MTHFR A1298C snp – and not those with the MTHFR C677T snps.

This is incorrect.

There is not one study that shows biopterin recycling is limited to those with A1298C compared to those with C677T.

In fact, lower tetrahydrabiopterin levels are likely found more frequently in those with the 677 variant compared to the 1298. Why? Because the MTHFR 677 variant is more severe than the 1298.

The BH4 cycle is absolutely critical for these various functions:

  1. assists the breakdown of phenylalanine
  2. helps form these neurotransmitters:
    • Serotonin
    • Melatonin
    • Dopamine
    • Norepinephrine (noradrenaline)
    • Epinephrine (adrenaline)
  3. cofactor to produce Nitric Oxide (NO)

Does one see only elevated homocysteine in those with the C677T MTHFR mutation and only mood disorders in those with A1298C MTHFR?


If your BH4 cycle is not working properly due to a MTHFR mutation, you are definitely going to be expressing some symptoms either mentally, emotionally or physically – or – all together.

Once you understand the biochemical effects the MTHFR mutation causes, it becomes easy to identify possible problems.

I am going to list possible symptoms, signs and conditions associated with MTHFR mutations. Keep in mind this is not a comprehensive list. I will add to it as I think of more (or you inform me of ones that I have omitted).

Possible symptoms associated with A1298C MTHFR mutations:

  • hypertension
  • delayed speech
  • muscle pain
  • insomnia
  • irritable bowel syndrome
  • fibromyalgia
  • chronic fatigue syndrome
  • hand tremor
  • memory loss
  • headaches
  • brain fog

Possible signs associated with A1298C MTHFR Mutations:

  • elevated ammonia levels
  • decreased dopamine
  • decrease serotonin
  • decreased epinephrine and norepinephrine
  • decreased nitric oxide
  • elevated blood pressure
  • muscle tenderness
  • ulcers
  • pre-eclampsia

Possible conditions associated with A1298C MTHFR mutations:

  • fibromyalgia
  • chronic fatigue syndrome
  • autism
  • depression
  • insomnia
  • irritable bowel syndrome
  • inflammatory bowel syndrome
  • erectile dysfunction
  • migraine
  • Raynaud’s
  • cancer
  • Alzheimer’s
  • Parkinson’s
  • recurrent miscarriages

There are certain dietary, lifestyle and supplemental recommendations that help reduce the effects of the A1298C MTHFR mutation.

That is well beyond the scope of this article.

There are a few nuances making it difficult to simply give flat recommendations for all who live with the A1298C MTHFR mutation.

Remember, if you are homozygous A1298C or compound heterozygous MTHFR, the likelihood of your family members also having MTHFR mutations is very high.

Get them tested!

Again, a single copy of A1298C MTHFR does not appear to be harmful unless it is combined with the C677T MTHFR snp – known as compound heterozygous.

For now, I hope this is useful for you and has shed some light into your situation.

Please do post questions, thoughts and comments below – and share this with your friends and family.


657 Responses to “MTHFR A1298C Mutation: Some Information on A1298C MTHFR Mutations”

  1. Donna December 2, 2011 at 4:40 pm # Reply

    I am so happy that there is finally information about this disorder out! I was diagnosed in 2002, put on vitamins and a blood thinner, and that’s it. No one really knew anything about the disorder, only that it can cause miscarriages. I have been blessed with 2 healthy children. I had to have a total hysterectomy a couple days ago. After surgery, my INR level is only 1.0. I finally found a doctor who is familiar with the disorder and is going to help regulate my levels. I have already emailed her office with your website just in case. Since I am heterozygous I have actually had a lot of the problems you have listed. I would have never imagined that they could be because of this disorder. Thank you for all your hard work in finding out about this “thing”!

    • Dr Ben December 6, 2011 at 7:27 am # Reply

      Donna –

      Thank you for sharing your story.

      I am glad you found a doctor who is familiar with MTHFR.

      May I ask who it is? Readers want to know!

      In terms of the hysterectomy, when you are able, do some kegel exercises to strengthen the area. This is very helpful.

      • Lg March 9, 2015 at 12:53 pm # Reply

        Helpful for what, exactly?

    • Patrick Williams M.D. June 12, 2012 at 6:49 pm # Reply

      Dr. Ben,

      Please provide an annotated bibliography of the data you used to derive your opinions. It would bolster your status as an expert and better support your position(s)

      • Dr Ben June 12, 2012 at 7:03 pm # Reply

        Hi Patrick –

        Will do – here is my broad bibliography – I will categorize it and refine it as I have time.

        All my current articles – most recent – do have references.


        • Roberto October 30, 2013 at 3:42 pm # Reply

          Dr Ben, i’m not a Dr but i tried to read the PubMed studies you posted. I wasn t able to find a single study were it was clearly linked the A1298C with bh4 recycling impairment. If you could post the links to such specific studies you re referring to it woulb be great.

          • Dr Lynch October 30, 2013 at 7:08 pm #

            If I wrote this, I need to edit it out – I will review.

            I have looked everywhere as well and have not found it either.

            Methylfolate does help regenerating BH4 along with SAMe – but this has nothing to do with MTHFR 677 or 1298 specifically – it has to do with MTHFR itself. In my opinion, there is no ‘forward’ or ‘backward’ reaction for MTHFR.

            Methylfolate supports regenerating BH4 from BH2 and also supports recycling of homocysteine to methionine.

      • Summer Bonnet July 23, 2012 at 9:09 pm # Reply

        To the average reader, too many references are confusing (the information is confusing enough). In saying that I do see how imperative references are (sometimes better not all through the paper – for the average person/reader)

        • Dr Ben July 25, 2012 at 6:30 am # Reply

          Summer –

          References are needed to convince other medical professionals and those readers who demand support. This subject of MTHFR is fraught with contradictions and many docs do not take it seriously – so I do all I can to make it a credible and important health issue to deal with.

    • Jill March 30, 2014 at 3:58 pm # Reply

      Hi Dr.

      After an IVF chemical pregnancy I was given a thrombophilia panel.
      F II F20210A DNA Hetero
      PAI-1 4G/5G DNA Homo
      HPA1 a/bL33P DNA Hetero
      MTHFR A1298C Hetero
      MTHFR C677T Normal
      All else normal.

      I take Promises Prenatal (Ive been taking them for 2 yrs)

      Are there any supplements you would suggest taking/changing in addition to the Lovenox, baby asprin etc my Dr will have me on during round 2?

      Thank you so much!

  2. Jill December 3, 2011 at 3:34 pm # Reply

    My daughters and husband have this variant. My daughter has a speech delay and my husband has high blood pressure from a very young age. IS treatment the same?

    • Dr Ben December 6, 2011 at 6:44 am # Reply

      Jill –

      Treatment is never the same from what I’ve experienced.

      There are other factors in play which affect treatment.

      The mutations are also different – the A1298C and C677T. They require different approaches.

      A speech delay has many reasons.

      A couple reasons for speech delay:
      – Added MTR mutation
      – MTR enzyme function decreased due to mercury exposure: vaccinations, foods, environment, in utero exposure
      – low GABA
      – iron deficiency
      – B12 deficiency
      – bilingual family
      – youngest of many siblings
      – lack of interaction with other children
      – elevated ammonia (common in A1298C)
      – deficient dopamine
      – elevated histidine
      – hypothyroid
      – folate deficiency
      – food intolerances and allergies

      Husband with high blood pressure could be related to:
      – low nitric oxide (A1298C mutations)
      – decreased calming neurotransmitter production
      – heavy metals (lead especially)
      – low magnesium levels

      These are a few off the top of my head –

      Given that you posted on the A1298C article (I just noticed this! :) as I am commenting from a different area), treatment will be similar – but not the same.

      Both need to lower ammonia levels. Arginine may help and the addition of 5-HTP may help as well.

      To determine more of what may be the exact dysfunction, I highly recommend the Pediatric ION Panel. It is very comprehensive. The adult ION Panel is recommended for your husband.

      The added Neopterin/Biopterin Panel is recommended as well for both. I am almost positive this test will show an abnormality.

      Limit foods containing Phenylalanine. Strict avoidance is not necessary but limiting is good.

      Testing is not required but it sure makes it much easier from a physician’s viewpoint as guessing is very much eliminated. I highly recommend it. It is an investment that will save much time, stress and money. Continuing to guess what is needed is expensive as various supplements and medications are tried – some with side effects. This is not desired obviously.

      I would very much love the opportunity to help bring your daughter’s voice forward.

      If you’d like to schedule a consultation, please do. If you are going to order the ION Panel along with Neopterin/Biopterin Panel (and food allergy panel), then I’d wait to schedule the consult until after the results are in.

      • Elizabeth February 6, 2013 at 12:36 pm # Reply

        Hello Dr. Ben,

        I’ve read that arginine can lower blood pressure. I feel sure I need help clearing ammonia but have very low pressure. Is there a danger in taking arginine? Thanks for any insights.

  3. Nick Valo December 8, 2011 at 4:45 pm # Reply

    Both my mother and I are +/+ for the A1298C mutation.

    My mother developed Parkinson’s in her early 60’s.

    I am 40 years old and I am in very good health.

    My mother endured many years of chronic stress, which I believe was a factor in her development of Parkinson’s (along with the A1298C mutation and perhaps other factors including possibly long-term B12 deficiency).

    I am really curious if you can be +/+ for this mutation and never develop any degenerative condition from decreased BH4 or whatever other pathway it influences, or is it just a matter of time.

    I’ve heard a number of people talk about how the A1298C mutation slows down the recycling of BH2 back to BH4, but I’ve never really understood how because it’s not clearly explained by the biochemical pathways involved vs. it just influencing the folate pathway like C677T does.

    Obviously I have a vested interest in learning more about this mutation, so I applaud your blog post on it.

    • Dr Ben December 9, 2011 at 12:32 am # Reply

      Nick –

      Thanks for your comment.

      Parkinson’s can be misdiagnosed.

      Those with A1298C may have methylation issues and they typically do. This leads to increased toxicity which is a major contributor to initiating Parkinson’s.

      So if she is able to detoxify and properly methylate – in a balanced manner – her symptoms may improve.

      There is also research out there they show Parkinson-like symptoms are related to over methylation.

      Also – in A1298C – these individuals do not make dopamine very well – or serotonin – which leads to Parkison’s like symptoms. In fact, all the neurotransmitters supported by the BH4 pathway are deficient in those with Parkinson’s.

      I do not view Parkinson’s as a disease at all – rather a dysfunction. There is commonly increased toxicity combined with decreased neurotransmitter production. This is a bad combination but may improve with the right protocols.

      I firmly believe one can be homozygous A1298C and never develop any chronic illness. It is a matter of dealing with the defect properly via lifestyle, dietary and nutrients.

      • Roberto February 10, 2014 at 9:46 pm # Reply

        Dr Ben, this is quite unsettling. Does this mean that supporting methylation pathway with methyl donors like 5mthf or methylb12 can actually deplete neurotransmitters and lead to Parkinson symptoms? So why should we assume any of these supplements. Isn’t it better to leave our body how it is, instead of messing up things even more?
        I recently had a bad experience with insomnia and i’m beginning to think it has been caused by interruption of my Gaba 750 mg capsules that were terminated. If this is true this means that Gaba gave to me ‘tolerance’ and that i had a rebound effect.
        So Gaba can be dangerous in the long term use?? And what of 5htp??

      • joy August 10, 2014 at 7:34 pm # Reply

        Dr. Ben I would also like to know the implications if the homozygous 1298 mutation as I have been tested and diagnosed with this. I suffee from anxiety/depression and the inability to handle stress. My Gaba and Taurine evels were below normal. Is this caused by a methlation issue? My father has Parkinsons and is not on any protocol for methylation. He is declining in health on several meds including Carbadoba/levadoba. Where can I get information and or advice for this?

  4. Cassie December 12, 2011 at 8:36 pm # Reply

    Phenylalanine. Is this what is in diet drinks? Those give me headaches now although I used to drink them all the time with no problems.

    I’ve had hypertension mostly in the pre-hypertension range for years. I also have a chronic high pulse rate (usually in the 90s). I’m on 2 hypertensive drugs now, a beta blocker, Metoprolol, and a calcium channel blocker, Cartia Xt. Are there any hypertension drugs that are better (or worse) to take with the A1298C? I am hetero for that (along with also being hetero for FVL).

    I’ve had 2 forms of preeclampsia and also a miscarriage. My first pregnancy was the miscarriage. My blood pressure was controlled before my second pregnancy. It even dipped to record lows (also in my next 2 pregnancies) during the late 1st/early 2nd trimester. Then it skyrocketed around week 26. I delivered by emergency c/section at 29w. Baby had severe IUGR. I was diagnosed with FVL after that but “my homocysteine was normal” (i.e. They didn’t do the MTHFR test at that time, only years later after a relative was diagnosed). My 3rd pregnancy was complete molar, unrelated to FVL or MTHFR to my knowledge. My 4th was term and blood pressure remained normal and stable until 38w and I was on Lovenox. My 5th was a little more challenging. I got a superficial clot at 9w, tripled my Lovenox dose a few weeks later, was diagnosed with GDM around 30w but blood pressure had been okay. Around 36 weeks it went up a little but nothing like with my preemie. At 38w, I was diagnosed with HELLP Syndrome and my liver was already failing. I barely felt sick. Another crash c/section followed. Baby was on the small side but okay for 38w.


  5. Krista December 15, 2011 at 7:11 am # Reply

    Thank you so much for this information. I have forwarded it to my doctor, as myself & two half brothers are all hetero for the A1298C. I have numerous signs & symptoms of this mutation, but homocystiene levels have been normal. The oldest of my two brothers has a high-functioning form of autism, and the younger is ADHD. Finally, things are making some sense. My mother is yet to be tested but if I am correct on the way this works, she should be homo for A1298C, unless my dad and my brothers dads coincidentally were hetero. Hopefully this will give our family some answers, and keep me from going crazy, seeing as my most bothersome symptoms/signs have been insomnia, depression, and fibro-type symptoms.

    • Dr Ben December 15, 2011 at 7:31 am # Reply

      Krista –

      My pleasure.

      Your symptoms completely match those with a A1298C mutation.

      Supporting the BH4 cycle is done using various nutrients and you can also quite quickly improve fibro and insomnia/depression as well. I know it sounds too good to be true but I’ve done it over and over again with people. So awesome to see people get their life back!

      • Krista December 15, 2011 at 7:42 am # Reply

        I was in the process of going to see a psychiatrist because I feel like I am loosing it. I may still go see him, just to keep myself sane for a while until I can begin proper treatment and cut out some of the bad lifestyle choices I make. (Smoker, occasional drinker, sugar junkie…I know, I know….terrible)

        I was wondering if you know anything about a product manufactured by Metagenix called Vessel Care? I was recommended that by the sales rep from the company, who happens to be an RN, and also the person who suggested I get testing done for the mutation. It seems like a good blend of all of the nutrients necessary for treatment, but I’m no doctor, and the dosages could fall short. Here’s the link to the page for the product. (Sorry, not trying to plug any products, I promise…just thought it may be of interest)

        • Dr Ben December 15, 2011 at 9:11 pm # Reply

          Krista –

          I do not recommend Vessel Care as it contains cyanocobalamin. I do like Metagenics but this formulation is not good for those with MTHFR in my opinion. I never recommend cyanocobalamin.
          The B6 is also not the active form.

          Since you have A1298C – the most important thing you need to do is support ammonia metabolism and limit its production. This is done through diet, lifestyle and nutrients. It can be complicated.

          • Lou January 3, 2012 at 1:44 pm #

            What about a product that has methylcobalamin in it? Along with 5MTHF

          • Alan September 21, 2012 at 6:03 pm #

            My doctor, who is aware of MTHFR and grew suspicious after a close reading of my male hormone test results, suggested Vessel Care. She increased the recommended dosage to 2 per day when I was confirmed homozygous 1298C.

            She also suggested I try 1 Vessel Care plus 1 Ceralin Forte after the confirmation of homozygous 1298C, but I found it gave me brain fog, so I went back to 2 Vessel Care

            When I look at the Vessel Care list of ingredients, it lists Vitamin B12 (as methylcobalamin) not cyanocobalamin. Vitamin B6 (as pyridoxine HCl) which I realize is not Pyridoxal-5-phosphate.

            Perhaps the Vessel Care formulation has changed? Does that change your opinion?

            FWIW, I felt and feel fine on this regime (6+ weeks). I was already doing most of the 16 lifestyle changes suggested for MTHFR. After 3 weeks on Vessel Care I noticed that my consumption of alcohol had dropped substantially (from nearly every day to 1-2 nights per week) without any conscious effort on my part.

          • HeatherL November 11, 2012 at 1:57 am #


            What are the 16 lifestyle changes suggested for MTHFR? Are they specific to the A1298C mutation, or to all MTHFR mutations?

            Dr Ben,
            I was just diagnosed with the A1298C mutation and have severe chronic fatigue, insomnia, joint pain, and nausea. What are the various nutrients used to support the BH4 cycle?
            I have been looking over your site and want to thank you for all the information you have provided and for your hard work in helping those with MTHFR mutations!

          • Dr Ben November 13, 2012 at 11:08 pm #

            Heather –

            I believe the lifestyle changes listed for the MTHFR protocol are useful for both MTHFR variants – and even if one does not have MTHFR, these recommendations may be very beneficial.

            Nutrients to support BH4:
            – I need to write an article on this. However, they are: iron, B12, methylfolate, niacin, copper, B6, magnesium and vitamin C

          • Vania Castro December 30, 2013 at 4:18 pm #

            Dr. que tipo de dieta – aliemntação – podem ser prejudical para portador de a1289c?

            Tive um aborto retido e após diversas investigações eis que descobrimos MTHFR A1289c HETERO presente

      • Antanas August 13, 2012 at 7:01 am # Reply


        I have 1298C hetero mutation and my symptoms match this mutation description 100%.

        Could you provide more information how to improve BH4 cycle and what kind of nutrients do you speak?

        I am currently taking 5mg L-5-MTHF and 5mg MethylB12 without any effect (also without any over-methylation symptoms)

        My hormones, diet, lifestyle in check.

        “Your symptoms completely match those with a A1298C mutation.

        Supporting the BH4 cycle is done using various nutrients and you can also quite quickly improve fibro and insomnia/depression as well. I know it sounds too good to be true but I’ve done it over and over again with people. So awesome to see people get their life back!”

      • Annie February 27, 2014 at 3:13 am # Reply

        I am a bit confused as in the article you said hetero A1298C shouldn’t cause problems but in your reply to Krista who says she is hetero A1298C you say her symptoms match those with a A1298C mutation. I thought if the person is hetero A1298C this shouldn’t be the cause of depression etc? Or did you understand it that perhaps Krista meant she was compound hetero?

        I have just one copy of the A1298C mutation, I have suffered with mild depression a lot in my life and I was wondering whether my hetero A1298C could be the cause although in the article you said one copy is as far as you can see harmless? Many thanks

        • Dr Lynch March 1, 2014 at 7:19 pm # Reply

          Annie – this is an ever evolving complex subject and my views do change based on clinical and research findings. At the moment, I do not think a single A1298C MTHFR mutation is that significant. However, there are plenty of other genes in the body which may be causing issues – and MTHFR -regardless of a mutation or not – may also not be working right due to thyroid issues and/or B2 deficiency or folate deficiency upstream.

        • Steve Thompson March 1, 2014 at 10:03 pm # Reply

          Hi Annie.

          You might also ask your doctor to order a Urinary Pyrroles Analysis.

  6. Meg January 12, 2012 at 3:39 pm # Reply

    I have both A1298C and C667T – diagnosed after my son was born and 3 pregnancy losses. I have a healthy baby girl, and my son was born with a variety of issues. Short femur, enlarged heart, missing kidney, hemangioma breakouts all over his body and this is just to start. I’ve been clinically depressed since 2001, the mutation was found in 2009. I started to see a Dr for my depression and when I told him about my MTHFR his face lit up. He prescribed deplin to take with my celexa and additional suppliments. I have spent the last 10 years not knowing what happiness was, constant brain fog, stomach issues, anxiety, and nausea. What was once attributed to stomach problems and stress was finally ended with my medication. I have not had a 100% turn around, but I have had a decrease in several symtoms. Nausea has still been a number one problem on a daily basis and my leg and hands still shake when I’m not busy. The deplin after 2 weeks was night and day difference. I was able to focus..I was able to sleep..I was able to get out of my funk. I do however now have the need to clean excessively…no complaints here though :) I have spent a lot of time and money one trying to resolve these issues. I had to listen to family, drs, and friends tell me that depression is just part of life. It wasn’t it was a battle that I had to fight for my children happiness. I also know what to expect to make sure my son doesn’t have to deal with the issues I have. Now I can start to enjoy life without the aches and pains.

    • Dr Ben January 12, 2012 at 11:21 pm # Reply

      Meg –

      Thank you for sharing your story!

      I am very pleased to hear that you are improving dramatically.

      You may be overmethylated causing the nausea and hand and leg shaking. Talk with your doctor about lowering your level of Deplin.

      Adding some niacin may be helpful as well. Start low and work up. Start with a quarter of a tablet. You may get flushing but that is normal and will go away after a few days.

      The niacin is a sponge for excess methylation and is excellent for those experiencing OCD symptoms – typically.

      • Summer Bonnet July 24, 2012 at 1:02 pm # Reply

        Hi Dr Ben,
        I am MTHFR – C677T, one of my gene being abnormal. I have had three miscarriages, I am wanting to try again, but want to make sure I’m doing everything I can for the safety of the child. My doctor has put me on; Zinc 20mg twice a day – vit B6 50mg daily – Magnesium 300mg twice a day – Folinic acid (not folic acid) 800mcg twice a day.
        “Through tests I have found out my husband is A1298C Heterozygous”, he eats a reasonably healthy diet, he does not want to take vitamins, I hope his decision on this changes.
        I am worried about falling pregnant and want to make sure I am doing everything beneficial, I also want to double check your thoughts on the vit intake. I have read about baby aspirin and other things that thin the blood – the effect these may have on the baby concern me, what are your thoughts on this? What about birth defects, what are the concerns? are there health problems that may occur if the baby inherits both the mutated genes from each of us? Kind regards Summer

        • Dr Ben July 25, 2012 at 6:18 am # Reply

          Hi Summer –

          Your concerns are valid and your husband needs to change his tune about vitamins. It is not about him right now – it is about your future children. If his sperm and DNA is not as healthy as it could be, then he is affecting not only himself and his future children – but also his grandchildren and on down the line. It all begins with the parents.

          I do not agree with so much folinic and no methylfolate – I do agree that folinic acid is a good idea while trying – and during pregnancy.

          I recommend you read this article on Prenatal Supplementation and MTHFR.

          Your husband should be optimizing his health as much as possible. Yes – we are men and typically don’t care for our health nearly as well as women – but again – it is not about him right now.

          Your husband’s A1298C MTHFR mutation is not that serious – yet that does not change things or the steps he needs to take in order to optimize his health.

          The benefit of baby aspirin far outweighs the risks in my opinion.

          There are risks for your baby – absolutely – but if appropriate action is taken – then these risks drop considerably.

          Should you desire to talk more in depth, do know I am available via consults. You may schedule by calling 800-547-9812 or online here. My times are becoming more limited due to my research and writing – however – I am making myself approachable until my book is done as I know people need help.

  7. lindy January 20, 2012 at 1:46 am # Reply

    Hi Dr Ben,

    Is taking Neevo sufficient to take while trying to get pg? Regulare neevo with 1mg of acitve form of folate. I’m heterozygous a1298c. I emailed you before but still getting conflicting advice from different docters. They all think this mutation is not the cause of my 4 miscarriages (no living children).Also is anxiety a symptom of this mutation? Thanks again!

    • Dr Ben January 20, 2012 at 9:25 am # Reply

      Lindy –

      Neevo is far from enough to take while trying to get pregnant.

      You’re asking a guy who’s passion is to optimize health in unborn children. I am a real optimizer of human health and all about disease prevention. I take prenatal care very very seriously.

      Your A1298C MTHFR mutation may not be the cause of your mutation. There are many causes and unless doctors look at you as a whole instead of isolating parts of you, the cause won’t be identified.

      Anxiety is definitely an aspect of this mutation – you bet.

      I’m really hoping to get more information on this in a podcast at least soon.

  8. Kari February 14, 2012 at 6:09 am # Reply

    Hi Dr Ben,

    I am 27 years old. I exercise regularly, eat healthy, no smoking or drinking. I just found out that I am heterozygous for the MTHFR a1298c mutation. I recently had my third miscarriage, and it was discovered through blood work for the miscarriage. I have two main concerns: 1) my OBGYN is saying that she does not believe that my recurrent miscarriages are related to the mutation. She has told me that i do not need to up any vitamins whatsoever because my levels are all normal, and 2) having two healthy children, followed by three miscarriages, will I be able to have more children? Why is this happening now?

    I’m also concerned because my mom and her entire family have heart related issues, as well as fibromyalgia, and lots of stress. However, I do understand that lifestyle choices will help me with these.

    I appreciate any helpful information you can share.

    • Dr Ben February 14, 2012 at 6:32 am # Reply

      Hi Kari –

      Please read this article:

      Show your doctor this study:

      A single A1298C MTHFR mutation is not that significant unless there are other mutations present.

      Optimize your pregnancy by reading this.

      Your siblings and family may have additional MTHFR mutations. My oldest son has only one copy while my youngest has 3. It is highly variable.

    • sally May 1, 2012 at 9:42 pm # Reply

      Just for some hope…Had 2 completely normal pregnancies at age 23 and 27. Then TTC again a few years later and had 2 miscarriages in a row. Had to have d&c’s with both bc no miscarriage symptoms and dr ordered blood work and it came back with homozygous a1298c. Four weeks post d&c I still had not gotten my period so I called my doctor and they told me to take a pg test and sure enough it was positive. He got me in right away bc of the new MTHFR diagnosis. Put me on progesterone, Neevo, Diatx (Folbee), baby aspirin and heparin. Delivered a healthy baby boy 3 months ago!! Im fortunate my OB seems to believe that MTHFR was the cause of my miscarriages and was quick to act when we had the positive pg test. Good luck to you-dont give up!

  9. Vicki Jacobs February 29, 2012 at 9:51 pm # Reply

    I am so happy to have found your website Dr. Ben. My 8 yo son was just diagnosed Heterozygous for the MTHFR A1298C mutation. We see Dr. Ali Carine an integrative Ped here in Columbus, Ohio. She did a complete blood work up on him (Spectra Cell) after his regular doctor couldn’t figure out why he was so sick all the time. Last year he had pneumonia twice and was extremely run down.

    J was a late talker and also experienced lots of sensory issues as a youngster. He has since outgrown lots of them but still struggles with attentional issues in school. He has lots of difficulty processing noise, movement, crowds… He has also has lots of difficulty sleeping through the night. J suffers from extreme constipation. A few years ago we did the ALCAT test and found a dairy sensitivity but no dairy allergy. We have removed dairy from his diet. The celiac risk genes were not detected in his blood work. His Carbon Dioxide level came back a little high at 31 (Ref Range 18-27). His Vitamin D level was 35 which was a little low. Also, his B12 was low.

    J is an extremely sensitive little guy and very bothered by any kind of sensory input whether vaccines, illness, a new tooth, nitrous oxide at the dentist… He always got sick with fever, lethargy and behavioral disturbances after vaccines. We did not have any of his 5 yr. boosters done or any vaccines since. He is prone to mood swings and insomnia. Rage with dairy products is very common.

    Dr. Carine prescribed a daily probiotic, fish oil, vitamin D drops and also 3x weekly Methyl B-12 Folinic 2MG/0.8MG/012ML injections. Jackson would sometimes complain of stomach pains following the injections and increased thirst. After 2 months, J is experiencing stomach pains and twice weekly night time vomiting episodes with interrupted sleep. We give the injection in the morning. We aren’t even sure these episodes are exactly correlating to the injections. Dr. Carine thought it could be the chronic constipation so we started him on a small dose of Miralax. After a month of random night time vomiting, I stopped the injections and a belly x-ray looked normal. The GI doc at Children’s Hospital is recommending a CT scan of J’s brain which is scheduled for tomorrow. :(

    Dr. Carine also is recommending Curcumin for Jackson which I haven’t started because of his belly and sleep issues.

    This is it a nutshell. Have you ever seen a negative reaction to the B-12 injections? We are worried about J’s belly and attentional issues at school. He is very bright but having difficulty.

    And as for Mama (me). I’m sure I have the mutation in some form. I suffer from anxiety and depression, bran fog, insomnia, fatigue, infertility, endometriosis, yeast overgrowth, miscarriage… And so on.

    I’ve already spent hours on your website reading and it’s all so overwhelming. Oh, I should also say we follow an organic, whole foods diet (especially Jackson). And do lots of the things on your list.

    Any input you could give me on my baby would be greatly appreciated. We are so worried and would be very grateful. Thank you.

    • Dr Ben March 1, 2012 at 12:02 am # Reply

      Vicki –

      Has your doctor run a heavy metals blood test on him?

      B12 can cause issues in kids and adults – I’ve seen it first hand with my own and with clients – and patients.

      Giving B12 three times a week IM with folinic acid is very intense for even an adult.

      I am very cautious and proceed slowly with people now that I’ve made clients worse in the past from giving what I thought was a normal amount. Many people are very sensitive so I proceed cautiously with all nowadays.

      Your son having only 1 copy of the A1298C MTHFR mutation is only a part of the puzzle. There are other things going on making him worse which you have not uncovered yet.

      I don’t say that negatively – rather positively. It means there is still work to do and you’ll get it figured out with the right docs.

      Get him off of wheat – all of it.

      Increased thirst and vomiting may be a sign of mercury toxicity. The methylcobalamin and folininc acid may have stirred it up more than he can handle.

      A consult is likely needed so we can go into more depth with Jackson. Please call 800-547-9812 or you may begin the process of scheduling a consult online here.

      We need to get his constipation fixed…that is first. You cannot do anything until his digestion is fixed.

      • Vicki J March 1, 2012 at 12:31 pm # Reply

        Dr. Ben,

        We have not had a heavy metal test run on Jackson has he is not on the autistic spectrum. (Though he does have some sensory issues) Jackson did have a few silver fillings as a young child put in by a dentist without my realization that he was doing so. Those teeth have all fallen out though.

        The B12 shots are sub Q not IM. I still think it’s too much for his little body. Do you still think we should get him off wheat even though it didn’t come up as a sensitivity on the ALCAT or on the regular allergy test and he tested neg. for the celiac gene?

        I will schedule a consult immediately. Thank you so much for your help.

      • Vicki J March 1, 2012 at 3:10 pm # Reply

        A few more facts about Jackson before I schedule the consultation which I will do after we get the results of his CT scan today…

        I forgot to mention that Jackson’s Cysteine levels came back low as well. When we first started the B12 sub Q injections, Jackson did great for the first few weeks. He was happy, healthy and sleeping very well. Then, the tummy issues started. He began complaining of tummy upset with the shots at first and then the nausea and vomiting at night, generally not feeling good. Again, we still aren’t sure it’s related to the B 12 injections. He is as pale as a ghost with dark circles under his eyes and extremely exhausted.

        Maybe his liver is trying to process the toxins that were built up in his little body but is on overload and causing him distress? I guess we would like your opinion about what supplements we should be giving him now along with dosages and what we should be doing to get his digestive system working properly again…


        • Andrea Fredericks June 19, 2012 at 4:19 pm # Reply

          I have the exact same mutation A1298C heterozygous and the same problems as your son. My B-12 is always low and vit. D is normally around 12 which is very low. I am in my 30’s and since I was a child had stomach problems, vomiting so much my sister thought I did it on purpose to get out of work and constipation so bad it I would be in the er after a month of no bowel movements. I am highly sensitive to sound, smell, lots of people and sun. I loved being outside but the sun was so hard for me. I was always the kid that was sleeping under a tree while all my friends were playing kick ball but had a hard time sleeping at night. The really hard part is this problems was never constant. It would last for a month or a week and then seem to pass for a few months. Over the years I got sicker and the issues progressed and became more frequent. I would get small rashes that would come and go as well and again that dr.s couldnt put all the pieces together. I loved school as well but just could not focus and always felt more like I was in a dream state than reality. When I was little I started dehydrating and was prone to sun stroke easily.
          By the time I was in my 30’s I was in a high stress job and very sick. I ended up in the hospital and even though the dr’s knew something was wrong they couldn’t find out what it was. The major constant was my stomach and constipation problems. I had seen seven GI dr in 15 years so when I was referred to another I had little hope. I had also had 3 scopes up to this point. This GI dr wanted to do another one and of course I went along. This time the dr come back with different news. I came back positive for mastocytosis. It is the only disease that fit all the problems. After I was diagnosed my sister had been struggling as well with a variety of problems and tested positive for mutations in both gene mutations of the MTHFR which let me to get tested and I have a mutation in one of the genes. I have came across several other Mast Cell patients that also have tested positive for one copy of the A1298C mutation and have wondered if there might be a correlation. I dont know if this is what is wrong with your son but I just thought I would share because he sounded so much like me as a kid.
          Lastly I will say I am sorry to Dr. Lynch for this post if this is not the appropriate place to share this. I know this is a blog for the MTHRF mutation and do not want to take away from that either because I also do treatment for the mutation with compounded B-12 with Lipo injections weekly and folic acid.

          • Vicki June 19, 2012 at 7:39 pm #


            Thank you for taking the time to comment on my earlier posts. I always love reading other people’s stories regarding this mutation. I have since found out that I also have the exact form of this mutation as you and Jackson. I wish I would have had this valuable information sooner for sure.

            I’m glad to report that Jackson is doing much better! He is finally off Miralax for his constipation and is responding nicely to a morning dose of prune juice and an ultra strong probiotic in addition to omega 3, vitamin D and D-hist jr. for allergies. I think the D-Hist has been great because it has added cysteine which Jackson is also low in. He is also gluten and dairy free.

            It took us forever to find a probiotic he could tolerate. While we are not directly dealing with the low B12 in the form of supplementation with Jackson yet (he had a bad reaction to the Methyl B 12 injections), I agree with Dr. Ben… By addressing his belly issues (no good bacteria and lots of odd bad bacteria) we are indeed paying attention to the MTHFR mutation.

            We’re taking it very slowly and will see what happens. I’m thankful to have found this community of people!!



          • Dr Ben June 20, 2012 at 6:12 am #

            Vicki –

            Great to hear about Jackson ;)

            Treat the gut! Definitely the #1 starting place.

          • Dr Ben June 20, 2012 at 6:20 am #

            Andrea –

            Your comments are very welcomed and encouraged.

            Yes – this is a blog about MTHFR – but we must remember that lifestyle and dietary choices affect our genetics. Thus, what you have shared is very on point – and helpful to others.

  10. tracy reed March 14, 2012 at 5:48 pm # Reply

    Hi, perhaps you can assist me,

    My 17 yo daughter tested very high (1158) with a range 243-894 for Vitamin B12. She had been on a daily course from a provider that felt injectable MB12 would best help her. We’ve since stopped (about a year ago), but it looks like she still has plenty on board. Cleft palate, midline difficulties, many personality problems as well as develomentally delayed (but occasionally ‘comes out of it” and seems very normal). Became type 1 diabetic at 10 years of age. Many problems with controlling her glucose that is not related to food. Highly acidic/ammonia. Apple Cider Vinegar works very well on controlling that.

    She just tested positive for heterozygous 1298 A>C mthfr gene. With the research I can find, it appears to be related to BH4. Can you point me in a direction where I can research the best option to help the BH2 to BH4 conversion? I believe that is where we are having the worst problem. thanks, Tracy

  11. Anne Frances March 20, 2012 at 3:44 am # Reply

    Hello Dr. Lynch

    Thank you for this wonderful information. I have a patient with heterozygous A1298C mutation- so likely not the culprit in her overall picture- but I am wondering how you generally evaluate for a methylation or chromosome mutation? Is this common to your knowledge? Thank you for all your work!
    Anne Frances

    • Dr Ben March 20, 2012 at 4:55 am # Reply

      Hi Anne –

      Methylation defects are surprisingly common.

      I am not sure how you mean by how I generally evaluate for methylation or chromosome mutation? I typically screen for MTHFR when family history or symptoms demand it.

      Please visit the MTHFR Screening article to learn more.

  12. Lynn_M March 29, 2012 at 5:22 am # Reply

    Would midline defect conditions belong on your list? I don’t know if they’re associated with just one or with both of the common MTHFR mutations.

  13. Jennifer D April 10, 2012 at 8:12 pm # Reply

    Hello Dr. Lynch

    Im 37 years old and have 3 beautiful and healthy children. I am pregnant with my 4th child. I am 14 weeks. I had recently had an ultrasound where they measure the fluid behind the fetus neck. Also went through a full panel of blood work 28 vials :/. Dr. Had called back with results for the most part the ultrasound came back normal and ok…. from what i remember but when She started mentioning the word genetic mutation i started to panic and everyqord started blurring together .she had given me the codes to look up C677t and A1298 and i found you:). She has put me on a regimne of baby asprin and extra folic acid. She had also mentioned my thyroid levels came back low so i will be giving more blood on my next dr. Visit which is the 18th. Im just not understanding what all this means and i will go crazy until then. Im just wanting a lil more info to releive my nerves and explanation of what i need to take caution on. I dnt want to stress myself out. Im just not understanding. Hope i explained enough :) lol. Hope to hear from you soon.

    • Dr Ben April 10, 2012 at 8:47 pm # Reply


      Calm down ;) All is good!

      Extra folic acid is not what is really needed here; rather more methylfolate which is the active form of folic acid.

      Baby aspirin is great – and recommended.

      Low thyroid definitely needs to be addressed and low thyroid is tied to MTHFR partially – it can be in other words.

      Please read this article on Prenatal Supplementation with MTHFR.

      • Jennifer D April 11, 2012 at 1:34 am # Reply

        Thank you so much for answering my comment!!! I so appreciate your response!! I feel alot better. Im glad i found your site :) . If i have anymore questions or concerns i will surely ask!!

      • Lynn_M June 12, 2012 at 8:09 pm # Reply

        Could you please explain how “low thyroid is tied to MTHFR partially – it can be in other words”.

        • Dr Ben June 12, 2012 at 10:37 pm # Reply

          Lynn –

          MTHFR is related to thyroid disorders because of BH4.

          Methylfolate is needed to produce biopterin which is needed to convert tyrosine into active neurotransmitters and thyroid hormones.

          This is the connection.

          • Michelle Gagnon January 13, 2015 at 10:04 pm #

            Hi Dr Ben Lynch, I have high ammonia issues and am homo MTHFR and MTHFR A1298C among many more. I have also been found to have low tyrosine, low Isoleucine and low Aspartic acid. Can these low numbers be related to these gene mutations or other ones? Can my low tyrosine levels be affecting my thyroid? I’m presently taking 90mg of desiccated thyroid.

  14. Susan April 11, 2012 at 5:44 pm # Reply

    Dr. Ben,

    Thank you so much for this site! My daughter,who is now 21, was just diagnosed with the heterozygous A1298C gene mutation. Her history reads something like this: Stopped breathing her first day, came home on a cardio-pulmonary monitor, chronic ear infections 4 – 9 months, chronic sinus infections 9 – 24 months, chronic asthma 3 – 7 years, general anxiety disorder 12 years of age, started binge drinking at age 15, diagnosed with ADHD and dyslexia at age 17, depression/bipolar (one manic episod) at age 18, age 19 diagnosed with hypothyroidism, age 20 had to leave college due to depression/alcohol and pot abuse/talk of suicide. Last summer her psychiatrist ordered a blood test to test her folate levels and it came back very low. At that time she prescribed Deplin 7.5 along with her other meds (Lexapro, Lithium, Seroquel, Adderall, Levoxyl and birth control pills). Last week after receiving the A1298C news, her psychiatrist increased her Deplin to 15mg and prescribed Cerefolin NAC as well. My first question is, is that too much L-methylfolate to be taking? Also, she has suffered for the last several years with chronic fatigue and several periods of IBS (?). The fatigue and depression (to some extent) have recently improved after 40 sessions of Neurofeedback Therapy. But she is still struggling with school (local community college) and alcohol/pot abuse, mood swings. Can you recommend any next steps? I still feel like we haven’t gotten to the bottom of what is going on with her. Thank you, Susan

  15. Kathy April 17, 2012 at 9:25 pm # Reply

    Dr. Ben,

    I’ve read most of the information on your site but I still don’t understand if you recommend methylfolate for those who are heterozygous for A1298C. I have symptoms but it seems as though you are saying that if I only have one mutation it shouldn’t be causing symptoms. Am I understanding this incorrectly? I have Factor V Leiden also, and I found out about both mutations after a pulmonary embolism which occurred after surgery. Please advise. Thank you so much.

  16. Dr Condon April 18, 2012 at 6:04 pm # Reply

    I am a family physician who treats all kinds of patients. I starting checking MTHFR status when the Deplin rep told me a number of patient responders were positive for the mutation. Of any patients with depression add migraine – I have only had about 3 people who were negative for at least one copy of either the a or c mutation. I have been frustrated that the a mutation gets little recognition. I do recommend an l methyl folate supplement . I would like to know what patients have found to be helpful. Deplin is expensive.

    • Dr Ben April 18, 2012 at 6:13 pm # Reply

      Dr Condon –

      Have you been seeing side effects from Deplin? Do you give the 7.5 mg or 15 mg? The A1298C MTHFR mutation does need some l-methylfolate to assist in recycling their BH4 – but I think Deplin is overkill – personally. I do recommend testing them for methylfolate blood levels (from Metametrix Labs) along with their Neopterin/Biopterin levels (also from Metametrix labs). These tests will help guide your treatment plan.

      The other issue with Deplin is it lacks methylcobalamin so the potential for methyl trapping exists.

      I am still working on a protocol for the A1298C types. The difficulty is lack of research as you know.

      I also recommend evaluating:
      – histamine
      – ammonia
      – nitric oxide
      – taurine name a few.

  17. Kathy May 4, 2012 at 8:42 pm # Reply

    Dr. Ben,

    I’ve read most of the information on your site but I still don’t understand if you recommend methylfolate for those who are heterozygous for A1298C. I have symptoms but it seems as though you are saying that if I only have one mutation it shouldn’t be causing symptoms. Am I understanding this incorrectly? I have Factor V Leiden also, and I found out about both mutations after a pulmonary embolism which occurred after surgery. Please advise. Thank you so much.

  18. Allison June 6, 2012 at 4:19 pm # Reply

    Doctor, I can’t tell you how much I appreciate you posting up this information! After looking around for years, I had pretty much written off any hope of learning about my condition.

    You are SO right about emphasizing family genetic testing. My cousin suffered from infertility and miscarriages. Four years ago and finally a pregnancy that ‘stuck’, her OB/GYN (the best of the best in our area, and focusing on high-risk patients–my cousin is particular about her doctors, and only gets the Cadillacs of the local industry) sent her to a hematologist to run the gamut, after hearing about our family history. She came back Hetero-A/C for MTHFR, with Prothrombic Gene Mutation, and the OB/GYN immediately put her on Lovenox. Since her sister was also pregnant at the same time and using the same OB/GYN, she was urged to take the tests–and bam! She got the same results. That queued up all the women in the family to start taking the tests. They all have Prothrombic. They all have the Hetero-A/C combination, with the exception of my aunt, who has Homo-C. I lucked out–no Prothrombic, only a Hetero-A. (Guess my dad did something right!) All the family issues suddenly made sense–my grandmother’s miscarriages, my family’s ever-abundant Alzheimers and rheumatoid arthritis/fibromyalgia, both my mother and my hetero-a/c’s aunt having deep vein thrombosis after their pregnancies, the infertility that plagued almost every woman in my family, the hypothyroidism that was hitting various ffemale relatives… I never would’ve found this out, had it not been for the insistence of the OB/GYN to get us to talk to each other, get tested, and get aware.

    But the issue with getting aware is that there’s not much information on the MTHFR genes. What is now (semi-)affectionately nicknamed the “motherf***** gene” in the family, has barely any research. I can read up plenty about the conditions everyone else has (prothrombic, hetero-A/C, homo-C), but I can’t find anything on mine. The general consensus I read is “This is so common, you’re fine, nothing will happen to you, and if you’re paranoid, go have buy folic acid vitamins at CVS.” It just seems too simplistic, on par with saying “Your eyes are blue, big whoop.” I’m getting conflicting information from my hematologist too–that my result only raises my clotting factor 10% above the average person’s level. But if that’s the case, why is she flipping out about me being on a low-hormone birth control pill? If it’s “nothing to worry about,” why is she worrying?

    So now I have concerns. I’m 27, no smoking, only social drinking intermitantly, I exercise, am slim, have no other health issues to my knowledge, no allergies. I’m just an average nobody. So if you can help, I’d be thrilled–Is the Pill no longer an option for me? I understand there are metafolin supplements in the purest form to be ordered online–but I’m skeptical of ordering drugs or vitamins on the internet. It’s smacks of those spam emails promising Viagra for $2 a bottle. I like to hold the bottle, read the nutritional label, see the ingredients. Not just read an order-page on the company’s obviously-biased sales site. Are there options over the counter in common stores (CVS, Walgreens, etc)? Or do I have to have a costly prescription? Right now I take over-the-counter folic acid vitamins, as recommended by my doctors–but this website is now saying this is no good for anyone, that it can actually cause more problems for me and any future child I have? My mother has suggested I take pre-natal vitamins instead of my One-a-Days, but if folic acid is no good, maybe that’s a bad route too? She has Hetero-A/C with Prothrombic, so should I suggest she stop that as well?

    And non-medication related, would you suggest that all people with this condition get a medical bracelet alerting emergency workers to this condition–as it could potentially affect medical treatment like surgeries?

    I’m interested in hearing your response, as you’re coming from a very well-read, unique position. Again, bravo on the wonderful work you’re doing here. It is very much needed!

    Best regards,

    • Lynn_M June 12, 2012 at 9:13 pm # Reply


      I live in rural western Nebraska and depend on internet stores for almost all of my supplements. I’ve never had a problem and I’ve been ordering online for over a decade. Usually the prices are cheaper and availability and selection far superior to what health food stores offer.

      While you won’t be able to hold a bottle in your hand, all the internet sites I deal with have the nutritional label and list of ingredients for you to see. I know exactly what I want to order before I order, so it doesn’t matter to me what is being promoted. I would say to get over your skepticism of ordering online, as long as you’re dealing with reputable companies. As one example, gets recommended a lot, and I have been quite satisfied in my dealings with them.

      I very much doubt you’ll find what you need in Walgreens or CVS. You do not need a costly prescription. Dr. Ben has a website where he sells sublingual methylcobalamin and methylfolate, and also a combination product with added B6 called homocysteX. If you want an instore option, look for Solgar Metafolin (L-5-MTHF) and either Enzymatic Therapy or Jarrow sublingual methylcobalamin at a health food store. If the store doesn’t stock it, they might be able to order it for you.

      You’re right, neither you nor anyone else with MTHFR should take folic acid or any combination supplement or food containining folic acid. It competetively inhibits the active form of methylfolate.

  19. Marta June 15, 2012 at 9:15 pm # Reply

    Hi Dr. Ben,
    First I want to thank you for developing this website, and all the information that you are providing here. I just found out that my daughter has 1298 mutation on both genes. She has been diagnosed with PDD NOS. She improved quite a bit with GFCFSF all organic diet and with supplements that our DAN doctor prescribed, but I feel that we missing something. Wonder if this mutation is not part of the puzzle. Her speech, attention and especially her anxiety is sometimes pretty bad. She has been taking Folinic Acid orally 800 every day and methyl B12 injection once a week. We changed doctors and she prescribed her lover dose of methyl 12 injection and added folinic acid to injection and she is taking it now every other day. Since she started to take combined folinic acid and B12 injections, her speech started to slowly improve and also her sleep. But her anxiety, attention and sensory problems are still there. After reading your website, I was wondering if BH4 could help her with these issues. Also should we change Folinic Acid to L Methylfolate instead? Where can I buy BH4 supplements? I appreciate all your help!

    • Dr Ben June 15, 2012 at 10:49 pm # Reply

      Marta –

      I am not a fan of BH4 supplementation directly. I rather like to support the pathway with the nutrients it needs:
      – vitamin C
      – magnesium
      – B6
      – iron
      – copper
      – niacin
      – methylfolate

      Iron and niacin are the cofactors needed to make biopterin. [1]

      Since dopamine supports speech, it makes sense that MTHFR 1298 may be an issue here as her methylfolate levels are likely low thereby causing a deficiency of BH4 which in turn limits conversion of tyrosine to dopamine.

      There are countless reasons why her symptoms may be present – and 1298 MTHFR variant is one.

      Preferably, I would use methylfolate vs folinic acid here. I would also limit supplementation with folic acid.

      I’d also get her on the other nutrients above –
      – Magnesium
      – B6
      – Vitamin C
      – Iron (if low and commonly is in children) – measure serum ferritin

      Consider supporting her with – these suggested amounts are for children 4 yrs old or above. Follow dosage amounts by her doctor.
      ProBiota Sensitive: 1 capsule after dinner to help support lower neopterin levels
      Sublingual Active B12 with Metafolin: 1/4 tablet in the AM to start
      Magnesium Plus: 1/2 capsule in the AM and 1/2 capsule in the PM
      Optimal Liposomal Vitamin C: 1 tsp a few times daily – mixed in a little bit of water or directly by mouth
      Optimal Iron Plus Cofactors: 1 capsule every other day if serum ferritin levels are low

      Looking into these may also be beneficial:
      – Theanine

      I commonly recommend people to start with 1 supplement or 1 lifestyle/dietary change every couple days. This allows time to see the outcome – whether it be beneficial or not.

      Certain labs to consider:
      – Neopterin/Biopterin
      – Amino Acids – urinary
      – Organic Acids – urinary
      – Thyroid
      – Serum ferritin
      – CBC with chem panel
      – Digestive Stool Analysis
      – Methylation Panel

      • Tina January 6, 2013 at 3:54 pm # Reply

        I have a question about the BH4 support above. You recommend copper, however we have high Pyrrole results needing Zinc, not Copper. We run high to normal copper levels with low to low-normal zinc levels.
        My concern about the iron supplementation is that I was told that with the symptoms of Parkinson’s Disease, that we should avoid Iron. We do have low Ferritin levels, though.

      • Glenn January 14, 2013 at 12:25 am # Reply

        Hey Dr Ben.

        Thank you for posting your thoughts and recommendations for the A1298C mutation.

        I live in Norway and am almost one year into battling post-viral fatigue after the epstein-barr virus. (As well as life-long issues of food intolerances and immune issues). There’s not much help from the norwegian health system, and during a visit to a US doctor last year I was tested positive for homozygous A1298C. Since then I’ve done the 23andme-test. Recent bloodwork show I’m low on homocystein (5.9) and leukocytes-neutrophils 1.6 L(ref 1.7 – 8.2), and high on S-cobalamins 772 H(ref 175 – 700). The bloodwork is from Norway, so I’m presuming metric values and ref range..

        I am homozygous A1298C and MTHFR 03 P39P (rs2066470), as well as MTHFR SNPs rs17037396 TT, rs2274976 AA, rs13306561 CC, rs17037390 AA and rs17367504 GG (which according to SNPedia each has a frequency of only 0.90% – 2.70%).

        In addition I’m heterozygous for CBS C699T, COMT V158M & H62H, MTR A2756G, MTRR A66G, BHMT-02 -04 & -08, ACHY-01 -02 & -19.

        So far my understanding is that I need to supplement with L-Methyl-Folate, and instead of methylcobalamin use hydroxo- and adenosylcobalamin (because of my CBS?).

        I want to support my BH4 as good as possible without getting my methylation out of balance in another way.

        What dosage of niacin is usually recommended when homozygous A1298C?
        I’m worried about adding much niacin since you also state that it can be used to reduce over-methylation – making me think taking too much or any niacin can be working against my attempt to get the methylation cycle going…?

        Currently I’m taking ox bile for digestion, and molybdenum and yucca root for any ammonia and sulfur buildup..

        Greatful if you have any thoughts to share on my situation, and specifically any answer to the niacin dilemma.

  20. Ktduncan June 17, 2012 at 5:09 am # Reply

    Hi Dr Ben,
    Can you list the general sups needed for homozygous 1298?
    I can’t find this information.
    I have CBS, BHMT mtr, and mtrr mutations also, so how does this affect 1298 sups? Thank you for your help in advance.

  21. Mark June 20, 2012 at 6:54 pm # Reply

    Dr. Ben,

    What are your first recommendations for a male in his 20s who just recently received his lab results: Compound Heterozygous for A128C and C677t? Before looking for an answer to his fatigue, he was and has been an avid athlete for years with a diet that focuses on the Paleo diet as written by Loren Cordain and Joe Friel. After an injury halted his exercise, he has grown weaker with incipient eye and calf fasciculations instead of recovering. This led to the genetic test.

    With these results, what are the most cost effective supplements you would suggest to start first? A bioavailable source of folate and b12 with your line of multivitamin?

    I appreciate your thoughts and will suggest a consultation with you.

    • Dr Ben June 20, 2012 at 7:20 pm # Reply

      Mark –

      Sounds like potential electrolyte imbalances, magnesium deficiency, adrenal insufficiency.

      I would recommend the MTHFRade along with Optimal Magnesium and Pantothenic Acid.

      I also would consider 1/2 tablet of the Sublingual Active B12 with Metafolin first thing upon rising – and taking it on the mornings he feels ‘brain fog’ or ‘heavy in the head’ or otherwise not ‘sharp.’ On days he feels ‘sharp’ and ‘alert’ – skip it.

      I question his stress level also – if stress is an issue, then Ashwagandha (2 capsules in AM and 2 before bed and possibly 1 in afternoon for moderate stress OR 1 capsule TID or BID) along with Magnesium Plus (1 capsule in AM and before bed)

      The Optimal Multivitamin, ProBiota 12, Vitamin D360, Optimal Fish Oil are daily recommendations – for those that are stronger and have the ability to absorb a multivitamin. He may not be able to tolerate a multivitamin currently so I would not start out with that at the moment. Hard to say though without talking with him.

      So – to sum up – consider these first:
      MTHFRade – all day – two liters worth
      Pantothenic Acid – 1 capsule with breakfast and lunch
      Optimal Magnesium – 1 to 2 capsules three times daily
      ProBiota 12 – 1 capsule after dinner
      Sublingual Active B12 with Metafolin – 1/2 tablet to start upon rising

      Address stress and depression also.

      Addressing the MTHFR mutation at this point needs to be done cautiously which is why I recommend starting so low.

      I am available for consults should he desire to dig deeper.

      Keep me posted how he is doing -

  22. Paula June 25, 2012 at 4:22 am # Reply

    Dr. Ben, I have Parkinson’s, tremor-dominant type, now progressing and making life very difficult, 5 years after diagnosis, but had some symptoms long before that. I also have diabetes (well controlled) and also was never able to conceive. I recently learned from a forum thread on MTHFR that I’m compound heterozygous, A/G at rs1801133 and G/T at rs1801131(C677T/A1298C). I’m hoping proper treatment might improve my Parkinson’s symptoms. At my request, my Kaiser neurologist agreed to test my blood levels, but said all was normal and no prescription needed. Results were: Vit. B12 >1000; homocysteine 6.8; pyridoxine 4.1; thiamine 125; methylmalonate <0.2; folate RBC 658. However, I had already been taking OTC Solgar Metafolin and Methyl B12 for several weeks before the test, based on forum discussions on 23andMe. Should I go off them (for how long?) and retake the tests? Any comments greatly appreciated. Or, any suggestions for finding a good treating doctor in SF Bay Area, or getting Kaiser to treat? I'm confused about what to do, but am on Medicare with limited resources. Many thanks from a former Oregonian!

    • Paula June 25, 2012 at 6:07 pm # Reply

      I just noticed that you offer fee-based consults, so maybe my question above will have to be addressed that way. I will certainly consider it. But since I’m under Kaiser Medicare, I was hoping to find a Kaiser doctor who knows about MTHFR. Any general comments you could make on my questions would be much appreciated. Like, are my test results really okay, or not? I also tried your find a doctor, but no SF Bay Area ones.

      • Dr Ben June 25, 2012 at 8:34 pm # Reply

        Hi Paula –

        What are your questions on MTHFR? What test results?

        • Paula June 25, 2012 at 10:36 pm # Reply

          My questions and test results (from 23andMe and Kaiser) were included in my post, above. Sounds like you did not see them for some reason. I’ve just now sent you an email, too. Thanks much.

  23. amy July 2, 2012 at 2:04 am # Reply

    My daughter has a myriad of autoimmune immune problems and we just found out she is a homozygous 677 carrier. I am a compound 677 and 1298 and have celiac, ulcerative colitis, raynauds, antiphospholipid antibodies. We asked for her to be tested because her rheumatologist wanted her on methotrexate and I read about the mthfr gene and toxic effects from this medicine, so before we placed her on it we wanted her mthfr status. The lab she had her testing done at ONLY tests for 677, should I have her tested for the 1298 also? I feel like I should.

  24. Liz July 12, 2012 at 8:25 pm # Reply

    Dr Ben,
    I am compound Heterozygous (+ 6C77T and +A1298C) Is the protocol different then your basic protocol? I follow your basic protocol 90% of the time. I was diagnosed 1 yr ago. I take 2400mg Metagenics L 5 Methylfolate and Sublingual B-12 methocobalamin. However I can’t take a whole B-12 only 1/4-1/2 every other day.
    Is there anything extra I need to be doing or have tested?
    Thank You!

  25. fleur July 14, 2012 at 6:39 am # Reply

    Hello I”m a 23yo Female, and i just got my test results back and they say i am Homozygous for the A1298C gene mutation and the doctor tells me i have higher Homocysteine levels than the average also, but couldn’t tell me what it meant or if it put me at risk of anything. As i was reading through this i realised i am suffering from nearly all of the symptoms. How do i find a doctor that knows more about it?
    also i would like to have children one day, but wouldn’t if my gene mutation was to effect my child as seriously putting them at greater risk of neural tube defects. Saying this might sound stupid but i dont know much about this, if i used someone elses egg would my baby still be at a higher risk?

    • fleur July 14, 2012 at 7:00 am # Reply

      oh i forgot to add im in Adelaide South Australia. It Seems we’re a bit behind in treatment, if anyone knows of a doctor in adelaide that is’nt please let me know. Thankyou

      • Lizzie July 16, 2012 at 9:16 am # Reply

        Fleur – you won’t go wrong here, highly recommended:
        At Wayville, right near the showgrounds.

        Best of luck, Lizzie

        • lauren July 26, 2012 at 6:13 pm # Reply

          Hi there,

          I just found out a week ago that I am postive for the A1298c Mutation, heterozygous. What kind of doctor do you think I should go to, to get some help with this? Would love you imput!


          • Dr Ben July 27, 2012 at 6:20 am #

            Hi Lauren –

            An integrative doctor ;)

            You may find a doctor here – I trust these medical associations.

  26. Kellie Villani July 31, 2012 at 10:12 pm # Reply

    Dr. Ben,

    I just found out today that my 2 sons have tested positive for the homozygous 1298 mutation. I have been tested and am negative. So I assume my husband may be positive, however, he has not yet been tested. He will soon be, though. My elder son is autistic and I am very curious about possible treatments. I’m quite disturbed that I’ve never heard of all this before! I plan on seeing a doctor specializing in integrative medicine, but was curious about vitamin protocols, etc between now and when we see a doctor that isn’t until October 1st. Thanks for any input you may have.



    • Lynn_M August 1, 2012 at 4:58 pm # Reply

      Kellie, if you are your sons’ biological mother, it is impossible for you to be negative for the 1298C mutation and your sons to be homozygous. In order to be homozygous, someone has a receive one mutated gene from the mother and one mutated gene from the father. Most likely something is wrong with the testing or it’s been misinterpreted.

      The protocol for a 1298C mutation is pretty much the same as for the C677T mutation. In Dr. Ben’s Articles section of this website, he gives a protocol for C677T mutations.

      • Kellie Villani August 6, 2012 at 1:51 am # Reply

        Thanks for your reply. I will definitely have to call the lab that did my test to find out what the issues are. I was under the impression that maybe 2 strands had come from their father, but that makes sense. I was just confused I guess. It’s too bad that more doctors aren’t knowledgable about this. The information the boys’ pediatrician came away from this testing was that there wasn’t any protocol for a homozygous 1298 mutation diagnosis. Very sad that most doctors aren’t more knowledgable. Frustrating….

        • Kellie Villani August 7, 2012 at 2:19 am # Reply

          Ok, I finally have seen a hard copy of my test results. Yes, in fact I’m homozygous 1298! Argh. I’m so frustrated that I can’t even get my doctor to read the test results correctly. Oh well, at least I finally have an answer. Now to move on to recommendations for protocol…

  27. Denise August 1, 2012 at 2:31 pm # Reply

    Dr Ben, I appreciate your article! What nutrients would you recommend to support the BH4 cycle?

    I am homozygous for A1298C MTHFR mutation. Following 4 miscarriages I’m pregnant at age 42 on Metanx, baby aspirin, Neevo and lovenox injections (recommended to stop at 16 weeks- concerned if this is the right decision). Does someone with this mutation take baby aspirin the rest of your life?

    Also my mom was diagnosed with Parkinson’s 3 years ago (does she need B6, B9 and B12? any recommended screenings?) and my dad has had 2 siblings with Alzheimers. My brother has Hemochromatosis – sounds like this may all be related. Any supplements you can suggest would be greatly appreciated!! Looking for a better quality of life for all….

  28. Kaitlyn August 24, 2012 at 5:31 am # Reply

    Dr. Ben,
    I was just recently tested for the MTHFR mutation because of a fluke reading of an article in a magazine. This article mentioned my symptoms that I’ve been struggling with for 10+ years. I am heterozygous for both the C677T and A1298C mutations. I’ve recently gone to many doctors to try to figure out why I feel awful all the time. I have nausea, headaches, muscle pain, extreme fatigue, syncope, “brain fog,” depression, and anxiety (just to name a few symptoms!). I just had an appt with my GI doctor as a follow up for my colonoscopy/endoscopy. I have an ulcer that they found during the appt. He does not know ANYTHING about the MTHFR, nor does my internist doctor, nor my cardiologist. Where do I start? Your website is the only one that makes me feel like I’m not crazy! I know that all my symptoms are related, but I haven’t been able to prove it yet. What can I give my doctors to help them help me? I really need to get this under control, as I am going to try to get pregnant this fall (already have a healthy 2 year old). My last pregnancy was so hard on me that I need some way to improve my health. I am 27 and I eat healthy, non-smoker, non-drinker, and I would LOVE to stay away from caffeine (if I could just stay awake!!!). I am tired of being put on this prescription and that, getting my hopes up, only to have it not work. This is the ONLY thing that I can link almost all my symptoms to. Is there a study or article(s) I could send to my docs about this? Help?

  29. Barbara August 26, 2012 at 5:09 am # Reply

    I have A1298C heterozygous and all my life I been suffering from a mild form of blues. Not a full blown depression but a low level depression, low energy, overweight problems, sometimes with insomina.
    I also had a spina bifida baby.
    I understand that 1298c is not linked to spina. But was it a factor ?
    Would it be possible that my husband had the gene and passed it to our baby ? He has not been tested but he has problems with his veins.
    What can I do in terms of nutirients to correct depression, moods, irritability, low energy levels. I had once tried anti depressants and they didnt help. I do find that if I eat and sleep well, the problem seems to get better. thank you.

  30. Vanessa August 30, 2012 at 8:41 pm # Reply

    Hello, I am 24 years old and just found out that I have the Homozygous A1298C MTHFR mutation. I was wondering what you think about the correlation of this mutation and vaccines. I have read some research that suggests when people with MTHFR are exposed to more toxins than their bodies can handle then it leads to a variety of medical problems. Is there a possibility the MTHFR mutation I have may keep my body from filtering out the chemicals and toxins in vaccines? I am in the military and it seems like they are wanting to give me a new vaccine or a booster every time I turn around.

    • Lynn_M August 31, 2012 at 3:11 am # Reply

      Dr. Ben has previously addressed the childhood vaccination issue and MTHFR in a few comments. See the articles and comments at and

      I don’t recall seeing anything written by him about adult vaccinations, but you’re right in thinking the A1298C mutation will make it harder for you to detoxify from vaccinations.

      Seems like you’re in a tough position. Being in the military makes it hard to refuse all those vaccines and boosters they want to try out on you guinea pigs – oops- soldiers.

      • Vanessa August 31, 2012 at 10:40 pm # Reply


        Thanks for the information. Once I became pregnant with my daughter ( she is now 11 months) I began researching vaccines. My husband and I decided to not vaccinate and finding out just recently about my mutation, we feel even more confident in that decision. Yes, the military are guinea pigs when it comes to vaccines. We are the first to get new vaccines the CDC recommends. I was hoping that maybe this mutation could validate a medical exception for me but its hard to find a doctor or geneticist that even recognizes my mutation as a problem for concern. Guess I will just stick with detoxing after vaccinations :(

  31. Molly September 8, 2012 at 10:13 pm # Reply

    Hi Dr. Ben,

    My husband has been struggling with many mental & physical health issues for many years now. He was just tested for an MTHFR mutation & his results are heterozygous A1298c. I noticed you said that is not worrisome, unless there are other methylation or cytochrome mutations present. Do you recommend any further testing for him to make sure there are no other mutations present? What kinds of tests should he have?
    Thank you!

  32. Teresa September 24, 2012 at 11:11 pm # Reply

    Presently I am waiting for a MTHFR test kit for my daughter and I. My son is positive for two copies of the A1298C gene. I am on a beta blocker because of severe heart spasms, squeezing and racing and anxiety. Dr. Ben could you tell me if an amount as small as 500ug (which I think is .5mg) of 5-Methyltetrahydrofolate could have contributed to the sudden on set of the heart symptoms? I took this amount three days before symptoms started.

    There are two other possibilities of the cause which I am looking into (like too much thyroid medicine which I have lowered by half and it could be caused by my having been slowly weaning myself off Celexa the last two years. I have been on an anti-depressant since 1999 because of anxiety, heart racing and fluttering.

    The heart racing etc. had stopped several days after stopping the 5-Meth but started up again the following week. I am under the care of doctors and okay but wondered if you knew if that little could cause problems; for instance if I had another mutation in addition to MTHFR. Thanks for any insight. Teresa

  33. Cecilia Long September 27, 2012 at 5:38 am # Reply

    Can men have these issues too? My boyfriend had extreme fatigue problems, and is always suffering from low iron and folate levels? Doctors have checked him for various things but always find he is simply “low” on iron and folate and tell him to take pills? What should I tell them to check for? What is a good kind of doctor to see? Where are you located?

    • Teresa October 10, 2012 at 1:57 pm # Reply


      Judging from my boy who has two copies of the 1298 gene and my daughter who likely has at least one gene- they both have experienced prolonged anemia problems

    • Teresa October 10, 2012 at 2:04 pm # Reply


      Look for a naturopathic doctor whom has been through medical school. Good sources are your local health food store clerks.

  34. Vicki October 9, 2012 at 4:48 am # Reply

    My son was recently diagnosed with the C677T mutation and the A1298C mutation. He has had social anxiety that has been crippling along with depression. He was sick all the time while growing up. He is nineteen now. He was also diagnosed with pyroluria. Are there others out there with this combination of issues?

    • Teresa October 10, 2012 at 2:01 pm # Reply

      My son has two copies of the A1298C gene and has had severe social anxiety and withdrawal but no depression. It has been by experience that some times it is hard to tell the difference between depression and anxiety. Is your son on the 5-MTHF yet? Mine who is also nineteen years old has been on it for a few weeks. He has managed to land a job and is getting more assertive.

  35. Billie October 14, 2012 at 7:50 pm # Reply

    I am homozygous for the 1298 MTHFR and was ready to seek a diagnosis for Fibromyalgia or chronic fatigue when I read about Vit B therapy. I started it(seems like in all the wrong ways) but within a short time had a new lease on life. It has been a couple of months and I am starting to feel the return of minimal muscle soreness. After reading everything I can find on your site I am realizing that need the treatment specifically for 1298. How can I find this. My daughter is also homozygous but my son exhibits many of the symptoms such as anxiety, Rayauds and ADD. They are young adults and I would love for them to find ways to address this before they are my age. Help, where do we go? I have been reading about over and under methylation but find a lot of conflicting information, especially when I add the MTHFR factor.

    • Teresa October 19, 2012 at 9:11 pm # Reply

      Billie, my son also has two copies of 1298 ; we go to a naturopatic doctor but understand that there are some mainstream doctors that are beginning to explore MTHFR. I would simply call around and ask doctor’s receptionist to ask the doctor if he knows how to threat the MTHFR mutation. This would save a lot of time and trouble instant of waiting for appointments only to find out they know nothing. You could also send out multiple letters to doctors in your area. And local Health food store clerks can be helpful in finding a good open minded doctor too. Good luck.

      I too feel the same way; I don’t want my children to suffer for decades with various illnesses like I have been forced to.

      • Antanas October 20, 2012 at 5:45 am # Reply

        Its full information about methylation including A1298C



      • Wim October 20, 2012 at 8:14 pm # Reply

        Hi Dr. Ben,

        I am heterozygous A1298C + C677T MTHFR.
        I have a lot of peroxynitrite, which I think is because of low BH4. But I have high 5-MTHF! I don’t think it’s because of the C677T alone!

        I already take B12 (tried cyanobalamine and methylB12). If I take 5-MTHF, I get even more irritated than I am already (which is lowered by taking B12). If I take more B12, I get a sort of hernia back pain.
        If I take B2, I seem to need more B6.
        I feel I need to supplement iron to make enough dopamin and serotonin.
        I also have a MTRR problem, but I feel that stimulating BHMT stimulates the methionine cycle efficienctly.

        My question is: What can I take to lower 5-MTHF and raise BH4 (stimulate MTHFR)?

  36. christine g October 21, 2012 at 3:47 am # Reply

    I am so confused regarding a1298c. Most everything is about the c677t mutation and when a1298c is mentioned, it feels just lumped in.

    here’s my question that I can’t seem to find an answer to anywhere:
    Can those with the a1298c process b vitamins?

    this is what is basically stated all over the internet:
    MTHFR mutations cause problems processing b’s which lead to high homocysteine
    c677t causes problems processing b’s which leads to high homocysteine
    a1298c does not cause high homocysteine
    a1298c causes a BH4 processing problem instead

    so it sounds like those with a1298c don’t have to take active B’s because that is not a problem that they have, they have to deal with the BH4 problem instead.

    yet, it is a MTHFR defect and everywhere says, take active B’s for MTHFR defects.

    I’m so confused on this seemingly most basic protocal issue.

    Please Help!

    • Glenn December 6, 2012 at 12:43 am # Reply

      Hey Christine!

      Have you found any clarification since this posting?

      I recently found I’m homozygous a1298c as well, while looking for answers to why I’m not getting back to normal after getting mononucleosis in March. I’m currently on neurobiologix neuroimmune stabilizer, a cream with 5-mthf and methylcobalamin, but now realizing it might be the BH4 I should focus on.. I’m 28 yo and low on homocysteine (6.8).

  37. llynn October 21, 2012 at 4:47 pm # Reply

    hello, my son is 4 and has autism, speech delay…ect ect. he has the homo. a1298c mutation… is there treatment for this??? he is currently taking:

    b12 injections every other day
    super thera nu vitamin
    fish oil
    5 htp to increase low seratonin

    is this mutation serious and is there treatment???? please help me! will any treatment help my sons developmental delay?

  38. Karen October 22, 2012 at 3:42 pm # Reply

    “There are certain dietary, lifestyle and supplemental recommendations that help reduce the effects of the A1298C MTHFR mutation.

    That is well beyond the scope of this article.”

    Dr. Lynch,
    Could you please write something about dietary choices for someone who has a homozygous A1298C mutation? I am unclear as to whether the build up of folic acid occurs with this mutation, or just the C677T? I have suffered from migraines for 30 years, have had extremely low intestinal motility all my life, and mild depression. Last year I had estrogen receptive breast cancer, a lumpectomy and radiation and am currently all clear. I eat organic where possible, low wheat and low dairy.

    I have ordered your Active B12 lozenge and will introduce them slowly. Is there anything else I should do?

    My migraine doc prescribed Deplin – I am so glad I found your website before filling that prescription.

    Thank you!

    • Dr Ben October 26, 2012 at 11:12 pm # Reply

      Karen –

      ‘Low’ amounts of wheat and dairy are not recommended. I highly recommend avoiding them both completely.

      Food choices vary from person to person based; however, eating a whole foods diet without gluten and dairy is a big start.

      Eating more frequently in smaller amounts with some protein is also highly recommended. The amount of protein varies immensely from person to person.

      • Rachel Hansen November 6, 2012 at 9:58 am # Reply

        Dr. Ben,
        I’ve had problems all my life, physical and extreme anxiety, and was just diagnosed with the A1298C mutation. Is there a doctor in the Seattle area that can guide me best on treatment? I’m certain both my children have the mutation themselves and they are being seen at Seattle Children’s Hospital. I am 39. I am on my own when it comes to learning, treatment, and explaining to my doctors an dall others about my condition. I have received alot of skepticism and discrimination, even from family and “friends”. I’m so overwhelmed with all the information I’ve managed to find online. I need solid resources, a knowledgable medical team, and a plan. Anything you can do to refer me to an already knowledgable about MTHFR physican for proper tests, treament would be exceptional. Thank you for your time and care.
        Rachel Hansen
        rachel.hansn@ live com

        • Antanas November 8, 2012 at 5:21 am # Reply


          Do you have one or both copies?

          • Rachel H. November 20, 2012 at 3:39 am #

            My bloodtest report said one copy of the A kind. But I suspect I have other genetic issues unless the severity of my physical and mental symptoms is due to extreme stress and anxiety lately. I have so many of the possible symptoms. I will be seen at UW Adult Autism center as it has been recommended to me to get assessed for autism spectrum. I am sitting in the walk-in clinic now for possible pneumonia and my kids show signs too. Yuck! What med, if any, is safe for us to take, as I do know there is a list of meds we are never to take, including metals. Please advise asap!! Thank you.

  39. Kelly November 16, 2012 at 7:17 pm # Reply

    I just got back a +A1298C, I have had migraines 20+ years, diagnosed with PFO in June, diagnosed with a left vertabral dissection 2 weeks ago, put on warfarin couldn’t figure out why it’s not increasing faster, now I understand. I was a preemie and have had auto-immune issues all my life. HTN, Raynaud’s, Fatigue, IBS, Lichen Planus, Lupus, RA….High Homocysteine too. My head is just swirling right now. Glad I found this page! Even more glad it was found before I had a STROKE!!

    • Teresa Nevins December 8, 2012 at 11:29 pm # Reply

      Kelly I just read your old post about your doctor not reading your test correctly. Wow, that makes me mad. You could have continued on suffering for nothing. It just reinforces the fact that I almost always ask for a copy of my lab results and look at them myself just to make sure nothing was overlooked.

      I think the risk of stroke is just with the C677T gene isn’t it?

  40. Lawrence Glenn Landauer November 19, 2012 at 6:38 am # Reply

    It appears there is a study correlating A1298C with Glaucoma for at least some ethnic groups. and

  41. Candi December 8, 2012 at 5:20 am # Reply

    My 9 yr olds genetic testing just came back with one copy A1298c mutation. What should we supplement in your opinion? Does this type need treatment? I am getting the whole Fam tested. Dietary changes?

  42. Sarah December 8, 2012 at 1:24 pm # Reply

    Dr Ben – thank you for this, we have a doctor who listens but is not familiar at all with this mutation. I am feeling very overwhelmed right now as we have several significant health problems going on with myself, my husband and all of my children.
    I had the kids and I tested for a few things as I had a gut feeling about some health problems going on.

    My 1 year old has a double copy of the A1298C MTHFR mutation, 6 year old has one copy, and I have one copy.
    My son (3yrs) and 1 year old also have low IgA. ALL children three have lip and tongue ties. My daughter age 6 has celiacs disease as well.
    I have suffered from anxiety, depression on and off, and have “brain fog” for quite some time, my husbands family shows like a check off list of symptoms as well – breast cancer, diabetes, adhd,just to name a few. We are all on a gut healing path now. I have no idea where to turn for help, the brain fog makes researching interesting lol. Our family dr is very, very good and has noticed several of his autistic patients have the C677T mutation, but we need help with this mutation. I am very concerned about my children, esp the one year old with the double mutation. Where do we get help?
    With thanks,


    • Teresa Nevins December 8, 2012 at 11:15 pm # Reply

      Sarah, I am not Dr. Ben of course but I wanted you to know you aren’t alone with a family full of this mutant gene. Me, my daughter and my son all have two copies of the A1298C gene. My husband has at least one. I and my husband have suffered for decades with depression and anxiety and then when my children started school so did their anxiety. I knew something was genetically involved at that point. I go to a naturopathic doctor (I think that is what Dr. Ben is?) that is knowledgeable. I recently asked her again about anything genetic and she remembered this mutant gene. None of the fifteen mainstream doctors I have seen in the last eighteen years had a clue. I now have multiply medical problems, most of which I hope will resolve themselves over the next few years. We all are on the 5MTHFR pill and my son and I have started the activated B’s which my doctor has available to purchase in her office.

      At fifty-six (husband 57) I am now starting to take the 5MTHFR and activated B’s and am detoxing. It hasn’t been easy as I believe after all those years, I have a lot to detox. I have had some heart palpitations, and flu symptoms. My doctor said it may take a year to normalize my brain chemistry. I am grateful and I am hoping that this is the answer to all my decades of suffering and also that it is my hope that my children won’t have to go through all that I and my husband have had to medically. Sometimes the clerks in Health food stores are good at referring you to local, good holistic or naturopathic doctors. Good luck.

  43. Karen December 14, 2012 at 5:58 pm # Reply

    I was just told today that I have a triple mutation..heterozygous for the A 1298C and homozygous for the C 677T. Since so little is known about either how will I know how to treat them together?

    thank you

  44. Nicole December 21, 2012 at 8:29 pm # Reply

    I was just diagnosed with homozygous MTHFR A1298C after 2 miscarriages. After reading this article so many other things make much more sense to me. I also have IBS, reynauds and have suffered from ulcers. I am so glad all of these things that are seemingly unrelated can be caused by this. My doctor has recommended a baby aspirin a day when I get pregnant again. My family has a history of heart diseases and other things. Is there more that i should be doing to keep myself healthy? Will an aspirin a day help me with pregnancy or should I be asking about other treatments?

    • Teresa Nevins December 22, 2012 at 5:56 am # Reply

      Nicole, no C677T variant? I am concerned because my daughter uses the nuva ring and like birth control pills there is an increased risk of clots etc. She has two copies of A1298C, and if clots are an issue like with the 677, I am thinking she should stop using the nuva ring. I need to get this cleared up because she doesn’t want to stop using it. I need facts to impress upon her about the A1298C causing blood clots to get her off or to take aspirin etc.

      Were your miscarriages caused by blood clots then?

  45. Laura December 25, 2012 at 11:33 pm # Reply

    I have a friend that I met through an adult’s with asperger’s support group. She is pretty disabled. She has epilepsy, rapid-cycling bipolar and severe allergies. She is on a very strict GFCF diet and is extremely sensitive to any kind of gluten or casein if she accidentally ingests any. She also is experiencing pschizoeffective symptoms and has severe insomnia. I told her to get tested for this gene and she tested positive for homozygous 1298c. The doctor’s just looked at her incredulously and kind of dismissed it. We are having a really difficult time finding specialists that know anything about this gene or nutrigenomics in general. I’ve been sending her and her mother all the information I’ve researched on it and started her on a mild homeopathic regimen that worked well for me: 100 mg B6, 1mg B12, 300 mg magnesium citrate, 2500 mg l-tyrosine, 4000 mg fish oil and 6000 mg powdered vitamin c. I told her to wait a couple months before starting on folate because I figured she would have reactions when she starts detoxifying. She stuck to the regimen and when she finally started the folate, she broke out in shingles. I told her to go back off of it and we will work on a better detox regimen for her and wait a few months for the valtrex to help. We are pending on getting biopterin supplementation as well because of my concerns about her detox reactions.Though I have done tremendous amounts of research on nutrition on my own for many years and have have really taken a lot of interest in the nutrigenomics field in the last year, it’s difficult to do this with no professional background. I would really like to help her. Do you know of any specialists in the Orlando area or have any advice? Thank you for any assistance.

  46. Amanda January 1, 2013 at 10:11 pm # Reply

    Hello Dr Ben,

    I have C 677 and A 1289
    I follow your protocol religiously and have given it to my Doctor who has given the link to 15 of her patients.
    I also take your supplements – which have improved my health no end!

    My depression leads me to research and supplement Bh4 tetrahydrobiopterin.

    Do you know how I can get this in Australia?

    Thank you,


    • Michelle Shanks February 11, 2014 at 2:54 am # Reply

      hello Amanda,
      My practitioner is pretty much the methylation specialist here in Sydney. Her name is CarolynLedowsky of Northbridge Nutrition and Natural health. ph 02 99673337 I have been seeing her for over a year and we are working through my Methylation and as it turns out , my son and my husbands now.
      Hope you are feeling well.

      • Steve Thompson February 11, 2014 at 9:31 pm # Reply

        Hi Michelle.

        After seeing Carolyn for a year, are you feeling any improvement?


        • michelle Shanks February 11, 2014 at 11:34 pm # Reply

          Absolutely! Most definitely. I have made so many dietary changes and am fast becoming fluent in understanding the language of MTHFR. I am actually considering running some food workshops here in Sydney to show people what I have learnt and implemented. Carolyn has been fantastic and unrelenting in her commitment to journey with me into health. I was previously suicidal ( terrible I know ) had been diagnosed with complex PTSD and my mother passed from Cancer two years ago and it looked a lot like I was following her symptom for symptom as I became older. It has been a real journey of discovery, made much easier for Carolyns help, and commitment to understanding how I function in relation to MTHFR. I have an anomaly in that I have low levels of Homocysteine ( does any one else exhibit that symptom here on the thread, and if so, has anyone been able to confirm that it is due to a CBS uptake issue? ) and so to start with I was undiagnosed. If it were not for Carolyn’s insistence, I would never have known that I had this gene mutation. She is the Methylation warrior here in Sydney and I believe that she works with Dr Bens protocol. Every person will be different. Currently I am taking:
          MethylCobalamin 5mg one in the morning upon rising
          Polybac 8 Probiotic upon rising and at bedtime
          have just started on Activated B6 one morning
          Have just started on Riboflavin 5′-Phosphate one morning ( thyroid)
          I take two Nutrition care Nalgesic Ultra Cumerone ( due to inflammation CRP markers and cancer history with mother)
          1 x Zinc Picolinate each night ( just started, have high copper and low zinc)
          Diasporal Magnesium at bedtime
          and I am taking Multigest Enzymes to help with absorption, but predominantly when consuming red meat or meals that are carbohydrate based.
          I am also taking Defencell to help with phase 2 liver detoxification and to help with expelling excess oestrogen ( due to cancer history ) and for extra enzymes to support the liver and help with eliminating cellular waste.
          On top of all that…. ( I know) I am also taking a detox heel kit with gallium that is homeopathic.
          It has taken a while to ease into all of this with a few hiccups ( I started implementing in November after confirmed diagnosis of homozygous A1298C)
          There were a few things that really didn’t work for me, however this does seem to be working right now.
          Currently we are working on Detoxification in a big way, as I am unable to lose weight ( 92 kilos) and that is very stressful, although I am learning to make peace with it given that I now have an explanation for why my body is not doing what other peoples bodies do when they eat junk.
          Food wise……I have always eaten healthy….but now I eat to live, to nourish, to heal.
          I used to eat set foods, now my diet is very varied.
          I include NU zest products ( introduced to me by Carolyn ) and I tolerate the Pea protein powder very well but am still undecided about the good green stuff. It is really jam packed full of things.
          We are working to increase my Methionine levels, so clean proteins are essential.
          I have been activating all organic nuts seeds and pulses.
          I avoid wheat due to the fact that here in Australia, by law, all products that are wheat based must be fortified with folic acid. The exception is Organic spelt and buckwheat and ancient grains, although it pays to check with the artisan. I believe Sonoma breads and Bowen Island Bakery products do not use it.
          We eat predominantly certified organic, and grass fed, free range and hormone free, so that has meant a slight reduction in consumption of varied fruits and veg, as true organic is seasonal and somewhat restrictive, but its important in my case as I can’t eliminate toxins, and particularly can’t eliminate Folic Acid.
          We have always eaten a lot of greens, but now they are organic whenever possible.
          I very rarely eat out these days and cook everything at home.
          I have found that woolworths carry a good range of certified organic raw nuts, seeds, turkish apricots, coconut milk, brown rice, basamati rice, sultanas, buckwheat ( not actually a wheat product ), coconut, quinoa, and generally have a good range of organic produce. I buy my organic meat from Coles, cleavers brand, and there is a fabulous lamb product range from Flinders island.
          I juice, take some spirulina, use dried dates as a sweet snack, make chai seed puddings and smoothies, make our own almond milk ( supplemented with Australias own Organic almond milk ) and go to my local organic markets for other things. I have a fabulous health food store in Manly with really knowledgable Naturopathic staff and am able to buy most of the super foods, cocao, acai, chai, puffed ancient grains for cereal mixes, coconut yoghurt and kefir, brags organic mother apple cider vinegar, kombucha ginger drink, coconut amines, raw organic honey, nut milk bags, quinoa and brown rice pasta ( the best substitute I can find ) raw activated power balls….and so much more.

          Has my life changed? YES!
          Do I feel better…YES!
          Is it more work….YES…to start with…not so much now that I have it all figured out and have a routine and have my son and husband on board, who are also with the mutant gene.
          Has it been expensive….YES…..BUT not in comparison to feeling unwell and the repercussions of no diagnosis and a full blown disease occurring.
          Would I still be suffering if I hadn’t met Carolyn…..YES YES YES!
          Do I still have bad days….here and there…..but I think its a lot to do with hormones as well.
          Do I still have improvements to make…YES! I want to be eating predominantly raw whole foods and managing with minimum supplements eventually once we have a full understanding of which pathways are functioning/blocked.
          IF I can help anyone in Australia with implementing dietary changes please do contact me via this link.
          I encourage everyone with the Mutant MTHFR gene to do the work…make the changes…educate yourself….take notes…track your symptoms in relation to nutrients and dietary changes….find out about new foods that can nourish your cells and make absorption easier.
          My changes and supplements will not be the answer to any one individuals treatment, but that is how I am currently dealing with my needs.
          The best in health to everyone who has taken the time to read this.
          Regards, Michelle

          • Mary February 12, 2014 at 9:50 pm #

            Hi Michelle
            Can i have your email adres please
            Want to aks you some questions for help
            Thx Mary

          • Joel December 1, 2014 at 2:09 am #


            My name is Joel and I am from Rose Bay.

            I am so excited to read that you are having success with Carolyn. I attend her clinic and see Claire.

            I am struggling with daily dizziness/vertigo/brain fog which gets worse when I eat carbs. If love your advice. Contact me at

  47. Angela January 15, 2013 at 4:36 pm # Reply

    Dr. Ben,

    I have found some wonderful information on your website. I am an RN of 18 yrs and I have both Factor V Leiden (Hetero) and MTHFR Hetero 1298C. My 4 yr old son has been diagnosed with both also. We both suffer with Severe Migraines. Im curious what you know about CADASIL? I have just found some information regarding it. For the last 20 yrs I have been worked up for Multiple Sclerosis. I do have multiple non demyleinating areas on the left front and parietal areas. We are both currently unmedicated, I have in the past been on Coumadin, Folbic,and ASA. was on Heparin and Lovenox and ASA during pregnancies.

    Do you know any physicians for both adult and pediatric that work with the MTHFR and Factor V Leiden in the Central Florida area…..

    Secondly, My 4 yr old with the diagnosis also has a severe speech delay and has had 2 documented allerigic reactions to vaccines. Thank you in advance.

    • Dr Ben January 16, 2013 at 10:00 pm # Reply

      Angela –

      I do not know of any docs in the Florida region. Do ask Sterling Hill at if she has anyone to refer you to.

      Folbic acid is not active enough in my opinion as it does not use the active forms of nutrients. Metanx is the best prescription form of l-methylfolate along with CerefolinNAC in my opinion.

      I would look for a tongue tie in your 4 yr old. If you are unsure, look for a video on anterior and posterior tongue tie. This can cause a significant speech problem.

      I am not familiar with CADASIL.

      Do look at your B12 levels and your SAM levels. There may be other mutations and/or environmental factors causing methylation deficiencies which are affecting your myelination.

      • Jody January 20, 2013 at 5:35 am # Reply

        I have been diagnosed with both Protein S deficiency and A1298c mutation. I don’t know much about either, However, I would like to know if I should be taking any kind of vitamins that can help with my disorders while I continue my research. My mother, I’m sure was the carrier having several strokes. One leaving her paralyzed until she died of cancer several years later. She had and I have many of the side effects mentioned above. I can go on and on about the symptoms but I know your busy. Please can you help me? PS I’ve already suffered from blood clots and would love to be able to reduce the worry of another.

        • Teresa February 2, 2013 at 6:04 pm # Reply

          Jody, I am no doctor or expert, but I can share with you some things I have read. I know some people with clotting issues take a baby aspirin daily; please do research about dosage carefully. I also know that if you take hormone birth control like the pill or the nuva ring for example, it could up your risks to clots normally (let alone if you are genetically inclined to clots). I think would reconsider taking another form of birth control immediately. That is all I have learned about clots at the moment.

    • angelique February 15, 2013 at 1:45 am # Reply

      Angela, There is a Ped Doctor in St Augustine, Fl. Her name is Dr. Julie Buckley, she would be able to help you with speech delay and the MTHFR.

  48. Ruth LaVigne January 21, 2013 at 7:45 pm # Reply

    My sister recently had a testing done on her DNA to see what was going on with her health. She was diagnoised with A1298C MTHFR mutation and told to tell her 10 siblings about the findings.
    The doctor told her that each of us need to be taking a supplement called “Metabolic Maintenance – 5 MTHF 10mg 90c” this will help in this mutation for mental maintenance and other simtoms.
    She learned that with the levels she has both of our parents carried the full gene. The doctor also recommends a strict diet and lowering a toxic life style.
    The MUST have on the list from the doctor is:
    L-Methylfolate, (at least 10mg)
    Sublingual methylcobalamin (B-12)
    Vit E
    Fish Oil
    Milk Thistle
    Selenium Zinc
    NAC, MSM, SamE, Methionine, Inositol, TMG, CoQ10, Alpha lipoic acid, L-Carnitine Glutathione,
    Strong probiotics, Multi-vitamin
    Vit D3
    Vit C
    Magnesium, potassium

    But if it is with processed “folic acid” I can’t take it. WOW!

  49. Linda January 24, 2013 at 10:37 pm # Reply

    Hello, I have been tested for the A1298C mutation and I don’t understand the hetero and homo but have this mutation in both of my genes. I am taking 15mg of deplin daily and methyl B-12 daily. I still have so many of these symptoms that you mention. I am a vegetarian and really try to eat for health. I work at my health very carefully with nutrition and detoxing and so on. But I am struggling with the mental, emotional, and physical symptoms seriously. I have two young children with the same mutations. They are taking 7.5 mg deplin and the same B-12. My husband has only one mutation.
    I have serious hip pain for about 2 years and of course wonder if that is related also. I am not even sure what to ask but I need information from a KNOWLEDGEABLE source.

  50. Lis January 26, 2013 at 4:42 am # Reply

    Do you recommend that an infant take a daily low dose (250 mcg) of methylfolate if they only have a single copy of the A1298C MTHFR mutation? Could it be detrimental if they do or have potential benefits?

    • Dr Ben January 26, 2013 at 8:33 am # Reply

      Hi Lis –

      I recommend that breastfeeding mothers supplement with methylfolate, choline, EPA/DHA, their prenatal and probiotics along with vitamin D. These nutrients get into baby via breastmilk. Supplementing directly to baby can be problematic especially since they cannot communicate well. It can significant headache, muscle aches, irritability, insomnia and so on – 250 mcg for an infant with 1 copy of A1298C MTHFR mutation seems like a lot to me – however – also depends on their diet, lifestyle, environment and other genes. Do try to find a good doctor – and the find a doctor page here may be useful for you.

  51. betsy January 27, 2013 at 12:15 am # Reply

    Hello. I am 26 and was just diagnosed with (from what I understand) heterozygous A1298C after losing our child at 21 weeks gestation to severe Spina Bifida, hydrocephalus, and Chiari Malformation type II. My midwives weren’t very “in the know” about MTHFR mutations and whether they were directly connected to neural tube defects. Needless to say, I demanded the blood test after stumbling upon this website. My husband and I are going to be seeing a genetic counselor in the very near future to get him tested (as well as getting our toddler tested at some point). However, my question is regarding future pregnancies/my ongoing health. We already consume what I consider a pretty healthy diet rich in organic foods, a good mix of fruits/veggies, raw milk from grassfed jersey cattle, home grown meats and eggs, etc. We religiously take vitamins as well. (Although I’m learning that my body may not be processing them properly.) We are still mourning the loss of our angel, but would still love to have more children in the future. Other than the obvious things I’ve read (l-methylfolate, NeevoDHA), is there anything else I should do to better my odds of having a healthy baby, as well as for myself to stay healthy?

    Oh… also… my daughter has a sacral dimple. After our baby’s diagnosis and death, we had an ultrasound done to check for Spina Bifida Occulta, which they are over 90% sure it is not. (Would need an MRI to know for sure, but at this point we do not want to put a 19-month-old through it if it’s not necessary.) But she also has a significant lip tie. Is this MTHFR at work?

    Thank you for this website — it puts all the jumbles of this confusing diagnosis together.

    • Teresa February 2, 2013 at 5:51 pm # Reply

      Betsy, I cannot express how sorry I am for your loss of your baby. Please except my condolences.

      I have two copies of A1298C and both my children have two also. My daughter had a dimple also, I noticed. I could put my thumb in it but it wasn’t deep, maybe 1/8 or 1/16 deep. I later had a son that was okay too but he had speech problems and now severe social anxiety. Anyhow during both my pregnancies I took heavy duty multiple vitamins from a health food store. Read up about what does are safe during pregnancy as this was decades ago. The one a day are just a drop in the bucket, I think worthless. I believe I took calcium and folic acid during both pregnancies but I don’t remember how much (20 and 23 years ago). During my son’s pregnancy, I ate a lot of peanut butter sandwiches and milk in the middle of the night. Maybe that helped somehow? We all are on 5-MTHFR now. My children and husband are sporadic in their usage though. I am wondering now if some of my problems are directly related to a B12 deficiency. Also someone wrote somewhere that your magnesium needs go up when taking the 5-MTHFR as one is rebuilding cells in the body.

  52. Jenny January 31, 2013 at 8:16 pm # Reply

    I got my test results back today and discovered that I have a single copy of the A1298C mutation. Are there any supplements I should be taking to help with this? My B12 levels were very low, so I have been receiving Cyanocobalamin injections for several months. Now I’m wondering if I should be taking B12 in the Methylcobalamin form instead. Any insight you can offer would be appreciated. Thanks!

    • Teresa February 2, 2013 at 5:57 pm # Reply

      Jenny I am no expert but I do believe the methylocbalamin is important as it is a converted form of B12. I think I am at the point of looking into B12 also as even on 10mg of the 5-MTHFR, I am not feeling markedly better yet. Either I need more 5-MTHFR or something else. Jenny could you tell me some of the symptoms you were experiencing due to the low B12 levels? I have odd symptoms like short of breath, bad dreams, wake up with heart pounding mostly at night. Teresa

  53. Dias February 4, 2013 at 6:08 pm # Reply

    Hi. I am 34 years old and just been diagnosed with both MTHFR C677T and A1298C heterozygous mutations. Have never been pregnant but trying for a while with no success. Besides this have I also have the autoimmune hypothyroidism – called the Hashimoto’s disease. For the mutations I’ve been given folic acid but I don’t know if that’s the answer based on what I’m reading on the above lines.Can you advice me on what my next steps should be-any additional testing?

    • Teresa February 5, 2013 at 2:58 pm # Reply

      Dias look at the very top of the home page where it says “read this first”. The info will answer many of your questions.

    • Alex February 6, 2013 at 5:21 pm # Reply


      I would recommend you take a look at Chris Kresser’s posts and podcasts where he talks about Hashimoto’s and low dose naltrexone. He had a similar experience where his wife could not get pregnant, then she got diagnosed with Hashimoto’s, started on low dose naltrexone and was pregnant within 3 months.

  54. Mary Ibach February 5, 2013 at 10:13 pm # Reply

    Dr. Ben,

    I have been just been diagnosed with homozygous A1298c. This is after a LONG 4 years of trying to recover from 6 surgeries due to breast and carcinoid cancer. Breast cancer stage 1, carcinoid cancer stage 4. Western medicine says I am terminal which doesn’t sit well with me. I am currently under the care of an Ayurvedic doc in India. I have been there twice for PK.

    I have high levels of seratonin, dopamine, histamine, estrogen, progesterone etc.

    I am wondering if I should start with the B-12 lozenge or the combo B-12 & 5-methylthalenehydrofolate?

    If you want another person for your research I am certainly a candidate and would be happy to participate.

    Thanks for all your efforts, time and dedication,

    • Teresa February 7, 2013 at 1:40 am # Reply

      Mary I hope Dr. Ben is able to respond to your letter. So sorry you have been through soooo much. I have a sister-in-law recently diagnosed with carcinoid cancer. There has been some success with prolonging life with certain drugs here in the states. I definitely would get started on the MTHFR protocol as soon as possible. Miracles do happen. My sister-in-law may have the MTHFR mutation as my husband does. I told her about it but I am not sure if she is taking it seriously enough to get tested. I will contact her again. Myself and two kids both are homozgous for A1298C, my husband at least one. I am beginning to think the B12 is just as important as the 5-MTHFR.

      I will send you a white light of healing power.

      • Mary Ibach February 8, 2013 at 12:19 am # Reply

        Thank you Teresa, that is very kind of you! I have chosen not to do the drugs offered in this country as I am interested in quality, not quantity. I will start on a combo I think. Tell me what do you and your kids take? How old are your kids? We have an 8yr old son. Did you start slowly? How did you discover your A1298C? Were you having some difficulties? I do find it interesting that your sister-in-law has carcinoid. A rare form of cancer. Where does she live if you don’t mind me asking?

        • Teresa February 9, 2013 at 4:46 am # Reply

          HI Mary,

          My family and I are just starting to take 5-MTHFR. We are taking 10 mg of 5-mthfr and a converted b complex. We started with 5mg but Dr. Lynch starts lower and with B12 first. I am still having problems so have opted to do more mutant gene testing. Heart pounding and racing episodes. Dr. Lynch has a video on this website that has a great wealth of information about dosages and lots of other protocol. I would have to look for it. Perhaps you can find it before I.

          My kids are 20 and 23 and I am 57. Children need to start more slowly in smaller dozes in case of reaction. That video tells you in great detail the amounts. He likes to start with B12 first. I had been looking for something genetic for anxiety as all four of us suffer with it. I asked my naturopathic about some thing genetic again and she remembered the MTHFR mutant gene so we tested my son and then my daughter and me. I have difficulties as depression,anxiety (since 5), fibromyalgia, restless leg, fatigue.

          My sister-in-law lives in northern Colorado. Since carcinoid is rare I wonder too.

          • Teresa February 9, 2013 at 4:49 am #

            Mary just go to the home page and the video window is the first thing you see for the protocol.

          • Mary Ibach February 9, 2013 at 9:05 pm #

            Thanks for all your info Teresa! Best wishes to you and your family.

  55. Jody February 9, 2013 at 12:12 pm # Reply

    Dear Dr Lynch,

    As mentioned before Iv’e been diagnosed with A1298c mutation…. I am considering going into surgery for my knee. I’ve had several surgeries that were suppose to be “same day” procedures. However, each time the anesthetics took longer than usual to wear off so my stay was over night or longer, for observation. I’ve always been concerned about the side effect anesthetics have on me so I’ve put off the surgery for several years. The only explanation I’ve ever received was ” this happens to a small percent of people from time to time” I would like to know if there’s any connection with A1298c mutation and the use of anesthetics.

    • Lisa February 11, 2013 at 11:52 pm # Reply

      I am homozygous for the A1298c and while I don’t have a problem with anesthesia wearing off slowly I have twice had panic reactions after surgeries. The first time it was panic at bedtime that lasted for a couple of years. 3 months ago I had a surgery where I had a panic attack that night and then severe constant panic for several weeks until my doctor prescribed clonazepam which I am tapering off of now. Anesthesiologists will tell you that it is out of your system in 24 hours so cannot be having that reaction but I still think it has something to do with it maybe because of the mutation? I don’t normally have any issues with anxiety/panic, just these two times directly after surgery. Luckily I have found someone who deals with this mutation and will see her on Friday. Maybe we can figure it all out.

  56. Jill February 11, 2013 at 7:02 pm # Reply

    I was diagnosed with heterozygous a1298c 9 months ago when I lost my daughter at 17 weeks of pregnancy. After several tests on me, the baby, and the placenta, all they found was this one mutation, and I was told there was no way it caused my miscarriage. Now, a little background, I had two healthy pregnancies, a miscarriage at 11 weeks (no heartbeat), 15 months of trying to conceive (when previously I conceived easily), a daughter born at 36 weeks, another 18 months of tryIng, and my last miscarriage. That pregnancy was going great until 14 weeks when I started having migraines and kidney pain, then at 17 weeks no heartbeat. All 3 of my daughters have the same mutation, one aunt had 3 2nd trimester miscarriages before taking baby aspirin for 2 healthy pregnancies, another had pre-e with all 4 pregnancies (they have never been tested for mthfr though). My questions are: is there any way this single mutation could be tied to my losses? Were the symptoms I experienced before my loss (mainly headaches) any indication that the mutation was causing problems? Some numbers from my blood clotting panel were VERY low (protein s was one) right after my pregnancy, then went back up, could that be caused by the mutation? Also, after having my 3rd daughter, I have experienced recurrent headaches (more than 15 days per month), no Dr has been able to figure out why, maybe it’s because the mthfr started causing more problems then?? Thanks for any answers you are able to provide!

  57. Kristen February 13, 2013 at 4:17 am # Reply

    Hi Dr. Ben,

    Found out in 9/2009 that I am a compound heterozygous for C677T and A1298C. Tested due to multiple miscarriages. OB & PCP Dr. both prescribed Folic Acid 1000mcg and Baby Aspirin 81mg every day… According to them there was nothing to worry about because verbally they told me my homocysteine levels were normal, so I didn’t worry. (Of course after reviewing my test results again just now, they were low– 4.9 umol/L.) I have every symptom listed above and more except for hypertension… Then a blood test was positive for Celiac in 5/2010 and told to go on Gluten free diet (without biopsy). I felt great for a while and lost 50 lbs, but now I have started feeling badly again. My fatigue, memory loss and brain fog are getting worse the last few months. And the last few days my body has been hurting.

    Thank goodness a friend recommended your website the other day and now I see why I am feeling badly. I am still navigating your website, but was hoping you could answer a few questions:
    1. I am confused as to which supplements to take for my situation (obviously not Folic Acid!). What do you recommend?
    2. What kind of followup blood tests should I request from my PCP and how often?
    3. What kind of specialist should I see?
    4. And when is your book due to come out?

    Thank you so much for sharing your knowledge & your website!


    • Teresa February 15, 2013 at 5:34 am # Reply

      In respond to the above 4 new entries, I know that those of us that have MTHFR mutations should not ever used Nitrous oxide (laughing gas) as it is very dangerous for us, life threatening. I am not sure about general anesthesia. I did develop restless syndrome after a surgery a few years back.

      I would recommend starting your education on MTHFR mutants by watching the video on the home page of this website and than take it from there while waiting for a response from Dr. Lynch. Teresa

  58. Catherine February 24, 2013 at 9:49 pm # Reply

    Dr. Ben stated above, “Those with A1298C MTHFR mutations do not display elevated homocysteine unless they are combined with C677T. Even when combined with C677T MTHFR mutations, the A1298C types still do not tend to have very elevated homocysteine.”

    The report from Quest Diagnostics-Nichols Inst states that I am “homozygous for the A1298C mutation and negative for the C677T mutation in the MTHFR gene.” I also have been told by my doctor (okay, it was the nurse that called with the news) that my homocysteine level is too high. Contradiction?

    • Dr Ben February 27, 2013 at 4:59 pm # Reply

      Catherine –

      There are many reasons why your homocysteine levels can by high. One does not need a mutation to have this problem. You simply may be deficient in various nutrients, have other genetic issues and/or eat too much protein or have lower functioning kidneys. There are a ton of reasons.

      Research typically shows that those with 1298CC do not have elevated homocysteine – but that does not mean there are exceptions – absolutely possible.

  59. Lindsay February 25, 2013 at 7:07 pm # Reply

    Dr. Ben,

    My son was diagnosed with Autism just after his second birthday & we just learned that he tested positive for homozygous MTHFR A1298C. Could his severe speech delay eating issues and learning difficulties actually be a result of this mutation instead of Autism? In some ways he fits the autism spectrum, but in others not at all. Just a curiosity?

    • lynn February 27, 2013 at 9:44 pm # Reply

      Lindsay, my son is almost 5 and was dx with autism at age 2. He was tested by dr kalb (a dan dr) in nashville tn for the mthfr gene, and was also positive homoz. for a1298c and negative for the other i think its the c777 one. My son has a speech delay and had eating issues (gag reflex) until he was almost 2.5. if you would like to talk my email is… it seems our kiddos have a lot in common. my son is very high function ( so i think). we thought it was just sensory processsing disorder for the longest time.

  60. Paula March 1, 2013 at 3:32 am # Reply

    Hi Dr Ben,

    I am a 26year old female from Sydney. I was just diagnosed with compound heterozygous C677T and A1298C after being tested because my dad has had re-occuring blood clots due to C677T homozygous. I started getting sick 2 years ago with hair loss, severe IBS, heart palpitations, muscle soreness, i’m constantly tired and have Raynaud’s. I do not smoke or drink and generally try to lead a healthy lifestyle but am tired of struggling to function on a daily basis! my doctor said there is no link between my symptoms and these mutations but clearly there is!!!

    My question is can you or anyone recommend a doctor/specialist who is informed and takes this seriously in Sydney, Australia?

    My GP has recommended i see a Haemotologist which i will do and take folic acid, which i have read that i need to be careful with which type. I put myself on a gluten and dairy free diet and that has helped but i want to prevent things from getting worse or developing further problems late in life.

    Thank you any guidance is appreciated.

    • Lisa March 2, 2013 at 2:40 am # Reply

      Hi Paula
      You could approach a doctor on the ACNEM list and see if they can help:

      • Teresa March 9, 2013 at 3:09 am # Reply

        Lisa is there some kind of list for doctors here in the U.S. that know how to treat MTHFR ?

    • Tony March 8, 2013 at 12:01 pm # Reply

      Hello Paula,
      I live near Sydney and have recently been diagnosed with a hetero A1298C MTHFR mutation by a Mosman GP, Dr Mark Donohoe. His focus is on Chronic fatigue, and nutritional and environmental medicine and is well versed in MTHFR issues. He has placed me on Methyl B12 with Methyl-folate to soon follow. Google his name, he has a website.

      • Paula January 8, 2014 at 11:27 pm # Reply

        Hi Tony,

        I’m sorry i literally have only just seen this! how are you going? was that doctor of much help to you?

        Thank you for suggesting that site Lisa.

        • Michelle shanks August 20, 2014 at 12:37 pm # Reply

          CaPaula….Carolyn ledowsky MTHFR support Australia, she has a web site and a Facebook page and specialises in this and has learnt with Dr Ben ???I believe! she does pod casts and has a programme. She is at sailors bay road in northbridgenaturalhealth Sydney….you won’t get better help…she’s the best.

  61. Chuck March 6, 2013 at 11:29 pm # Reply

    Hi I am alittle confused about what supplements to start taking for heterozygous A1298C, 33 year old male and been dealing with fatigue, depression and anxiety for some time now. I take 10mg of lexapro but symptoms seem to get worse and just found out that I have this and saw that it can contribute to my symptoms. Thanks

    • Kathy March 8, 2013 at 5:05 am # Reply

      Chuck, I have posted this same question a couple of times and it has not been addressed. It isn’t clear from the info on the website. I think I read somewhere though that Dr Ben is working on putting more guidelines on the site for A1298C.

      • Chuck March 8, 2013 at 5:17 pm # Reply

        I started taking some 5-MTHF and TMG

  62. Maggie March 12, 2013 at 11:46 pm # Reply

    My 20 year old son has suffered with OCD for years now and we finally found a doctor that tested for MTHFR and we found that he has a Homozygous mutation A1298C. He is also suffering from depression which I figured is stemming from the OCD. She has pt him on 5_MTHF 5mg. Is this the right supplement for him?

    • Teresa March 17, 2013 at 5:37 pm # Reply

      Maggie, what a coincidence. I have a son with homo mutation A1298 and he is 20 also. We all have a double A1298 in our family. I think he suffers from some OCD too as I cannot get him off the computer (although I don’t think he would admit it); and he has anxiety and severe social anxiety on of that. I tried him on the 5-MTHFR for a few months and he doesn’t seem to think there is much difference. Now I have weaned him off and trying B12 for a while. I think, likely, like me has multiple mutant genes on the methylation pathway. It would be great if our young men could become pen (computer) pals and support each other! I am trying to convince him to do a thorough gene check with Dr. Yasko like I did. I am just starting to try and address my other mutant genes (besides the MTHFR) on the methylation pathway.

      I think that with my experience, I would have a more in depth testing of the methylation pathway genes with Dr. Yasko done for your son. Desperate times need desperate measures.

  63. Chuck March 28, 2013 at 9:51 pm # Reply

    I love how a doc post on stuff like this and get tested and then you ask qestions on his website about supplements and he never responds lol

    • Dr Ben March 28, 2013 at 11:07 pm # Reply

      Hi Chuck –

      I respond to certain questions – It is impossible for me to do all due to my time.

      There is a lot of information here – and the video is also very good to watch.

      • Mary Ibach April 8, 2013 at 10:44 pm # Reply

        With the limited time you have you choose this comment to respond to????? How unfortunate. If you don’t have the time to address these please change your site. People are looking for help here, you encourage questions and MOST go unanswered.

      • Stefanie May 1, 2013 at 9:18 pm # Reply

        Dr. Ben,

        I agree with the other readers. There is little information on this website regarding both Homo and Hetero A1298C mutations. Even though the readers are trying to help with their posts, it does lead to a lot of misinformation. Are you planning on releasing more information regarding the A1298C mutations, specifically? Also, would my eye sight problems have to do with either over or under methylation? That is a major concern of mine considering I have never had problems with my eyes before. I know you are busy, but there is obviously a large market that needs more information on the A1298C mutations.Thanks! We really do appreciate all your help!

        • Dr Ben May 1, 2013 at 10:39 pm # Reply

          Hi Stefanie –

          I also agree with the other readers ;)

          My issue with the 1298 variant is the research. When I write or speak, I require that I speak from research when it comes to something like this.

          The research does not provide much for the 1298 variant and, in fact, says it is something to not really worry about for the most part.

          I believe the homozygous 1298 MTHFR variant is something to worry about – but to what extent and why?

          I believe that those with 1298 MTHFR are able to produce methylfolate just fine – and possibly even ‘too’ fine. Research does say that the 1298 variant resides in the C terminus end of the gene which means it sits in the regulation area. MTHFR is naturally inhibited by SAMe. If SAMe levels are adequate, then MTHFR enzyme is inhibited so the folate can proceed to other areas – such as DNA base production. The issue – maybe – for those with 1298 MTHFR variants is perhaps they are pushing the methionine cycle too hard because SAMe is not inhibiting it – and thus the DNA bases are inadequately produced causing DNA strand breakage. One paper I read said that this didn’t seem to be the case – but it was one paper.

          We need to think beyond MTHFR and order tests like the 23andMe Test so we can understand more of who we are and how the genes interact.

          I will write an article on 1298 but there will likely not be a protocol.

          I also have not seen any supportive literature which says MTHFR 1298 variant requires BH4. Citations?

  64. Dawn Aronson March 29, 2013 at 9:48 pm # Reply

    my son is heterozygous A1298C. He has chronic lyme and dysautonomia secondary to lyme. He stuggles with daily sometimes incapacitating queasiness and often migraine. He is under treatment for lyme and coinfections (abx and anti parasitic suppliments) currently but not much relief from queasy feeling since 11-.2010. If he can run around it improves some but it returns as soon as he sits down and gets worse when lying down. could this be related to MTHFR issues? I think he now may be having mast cell issues as well.

  65. Sharlot Bott April 4, 2013 at 7:49 pm # Reply

    I have been diagnosed with heterozygous A1298C only. My Father had Parkinson’s and My Mother had Strokes and Dementia set in after that. They have both passed now. If I have this gene mutation from only one parent how do I know which one? What is the difference between homo and hetero in this mutation? Since both had conditions relevant to this mutation, which parent is passing on what?

  66. Howard Schultz April 8, 2013 at 12:47 pm # Reply

    Please send me, or place online, the research articles that discuss the possible symptoms associated with MTHFR A1298C mutations. Thank you. Howard Schultz

  67. KC April 10, 2013 at 3:45 pm # Reply


    I am a 36 year old active woman with healthy BMI (also have 2 healthy young children–no miscarriages). I lost partial vision in my eye 12/22/12 and it has yet to return. Reportedly my optic nerve was swollen and the damage to the nerve has left my vision “permenanty damaged.” I have had two MRIs and a spinal tap. No tumors, lesions or evidence of stroke. They ruled out MS, PTC and strokes with blood test. My thrombotic lab results came back and show me positive for a “single copy of the A1298C mutation.” What does this mean? I will also share that 2 weeks ago, I felt so compelled the my IUD (Mirena) is the cause of my vision loss, that I had it removed after having it in place 11 months. I have since found a suit against Bayer (makers of Mirena) where 100 women (with Pseudo Tumor Cerebrae) have suffered asymmetrical vision loss, migraines and nausea–that’s me!!!! Do you think their a vitamin regimen I could do to help regenerate my optic nerve?

    thanks so much for your time,

    • Lisa April 13, 2013 at 6:22 pm # Reply

      I have some nerve damage post surgery. It’s not optical but my doctor recommended Alpha Lipoic Acid and Biotin to help general nerve regeneration. I also us a lot of chia seeds for the omega 3’s which are supposed to help also. The active B’s (which you should already be taking for the A128c) are also very important. Note I am not a doctor but that is what he advised for my nerve damage.

    • Teresa April 14, 2013 at 1:41 am # Reply

      KC, here is a website about Mirena users and eye problems they have experienced.

    • Louise April 20, 2013 at 6:38 pm # Reply


      I found my way to the topic of methylation and MTHFR, and discovered this site and others, because I am searching for answers and possible treatments to sudden damage to my optic nerve that happened a little while ago.

      I was not taking any prescription medications, but I was taking several different nutritional supplements plus a steady dose of ibuprofen during my several days of monthly cramps. Anyway, something changed quite suddenly, and I don’t quite know what caused it. It could have been even as a result of a virus, or some kind of nutritional deficiency, or a sign of multiple sclerosis, or a result of physical contact with an unknown toxic substance, or even a side effect of the NSAID. My vision has not improved since, although it fluctuates up and down within a range.

      After waiting a while to see if it would get better on its own, I went to see the best opthalmologist in my town (who turned out to be expensive, very disappointing, and even unprofessional towards me in about 5 different ways) and he said I did have a lot of damage of the optic nerve and he wasn’t sure if I had optic neuritis or early-onset normal-tension glaucoma. He said it was an unusual presentation and the only patients he has had who had a similar picture were drug addicts (he didn’t expand on why, or even ask me if I took drugs – I don’t! – but I expect it’s because my test results pointed to toxic ambylopia, which isn’t always from toxins/drug addictions, but can also be from nutritional deficiencies like B12, which he didn’t explore or mention to me). He spent 10 seconds thinking about whether to say it was optic neuritis or glaucoma, settled on glaucoma, gave me a prescription for an expensive eye drop ($124 every 26 days) that has serious side effects (but when I asked him if it had any side effects, he said, “no, it has no side effects”), and then walked out the door before I could even ask him what having glaucoma means to a person, what the future progression might be like, anything like that (he didn’t explain anything to me about the diagnosis). Then his office sent me a bill for $500 when they had told me before I made my appt. that the typical charge for an appt. was $170. [I had the feeling that he fobbed me off because he simply didn’t want to spend the time and effort that looking into a complicated optic neuritis would take (MRI scan, blood tests, who knows.) His practice is a lucrative one involving a steady stream of elderly folks getting cataract surgery – I was half the age of everyone else in his teeming waiting room – and he was in and out of every consultation room in a matter of 2-3 minutes. It was like a factory rather than a precious human endeavour.]

      Anyway, I do feel that I probably have/had optic neuritis rather than glaucoma because my symptoms (and the sort of visual degradation that I suffered) fit that diagnosis better than glaucoma, or possibly I might have both (a sudden episode of neuritis overlaid on a gradually-progressing early-onset glaucoma). I am looking into finding an opthalmologist who might be younger and more open-minded (but I’ll have to drive about 75 miles for that and I don’t have my own car, nor any health insurance), and I will try to get an MRI scan to look into the neuritis idea more carefully and make sure I don’t have signs of MS in the brain (I also have vision/headache symptoms that could be from a compressive/tumor situation, which a scan would show, and which would be very important to know about, naturally).

      But for the immediate present, I am trying to look into whether there are any treatments that might recover some of my vision (that eye dr. told me there aren’t and that my optic nerve is permanently damaged, but I don’t trust his judgment or his knowledge beyond his narrow scope and presumptions), and I’ve found a host of things that in experiments have been helpful to some people.

      The methylation protocols (from Dr. Ben Lynch, Dr. Rich van Konynenburg, Freddd, Chris Kresser, even Dr. Terry Wahls, etc.) which involve the methylcobalamin type of B12, methylfolate, TMG, Potassium, etc., seem to be said to be helpful for mitochondrial health and nerve remyelination.

      I have read some studies on maritime pine bark extract (one brand name for it is Mirtogenol) that has apparently helped some people recover some vision.

      There are mentions of ginkgo biloba, omega-3 oils, bilberry, and so on helping people to recover some vision.

      I cannot vouch for anything, as I am only just beginning to look into it and have not yet purchased most of the things that I want to try. You can do some research on this – you can search on the Life Extension website under various search terms, on the Naturaleyecare site, on the Pubmed database of scientific research articles, etc.

      • Laura June 28, 2013 at 11:25 pm # Reply

        Louise, I don’t know if this will help you or not, but please find an opthomologist who is also knowledgeable of iritis or uveitis. I was diagnosed with this long after much damage to my eyes. The optho’s in my town all misdiagnosed and mis-treated my condition for many years, which caused irreversible damage. Also, I had many bouts of retinal bleeding and swelling. This may not be your condition but it’s definitely worth finding a kind and knowledgeable expert. They saved my eyesight. I have many other symptoms as well and am positive for hetero MTHFR A1298C. Good luck to you!

        • Teresa June 29, 2013 at 6:19 am # Reply


          What kind of symptoms were you having with your eyes? I have problems with dryness and floaters with mine. Also my mother has been having trouble with bleeding in an area in one of her eyes. Maybe I ought to tell her to start B12.

  68. Sarah April 17, 2013 at 2:13 am # Reply

    Dear Dr. Ben,
    I had a baby with anencephaly in July 2012. Genetic testing of this child was normal per geneticist. I was started on folic acid(4,000 a day). I then got pregnant earlier this year, but miscarried at 7 weeks. (Unable to grow cells for genetic testing). I was placed on Vit B complex and progesterone at week 5. My doctor did various tests:
    Cardiolipin IgG- elevated, IgM- normal, lupus anticoagulant profile- negative, protein c& S functional- normal, anti-throid antibodies- high (60.8), MTHFR MUT C677T- negative, MTHRF A1298C- homozygous, pro nucle 20210- negative.
    I just received all of these results today. He ordered lab tests: FACTOR V LEIDEN (F5) R506Q MUTATION, HOMOCYSTEINE, TSH. He says most likely that I will need to do daily lovenox injections, take medications for thyroid, folic acid 4x/day, and vitamin B complex. Is there anything else you recommend I get tested for and/or anything else you recommend taking preconception and during the pregnancy? Thanks for your help in advance!

  69. Stefanie April 18, 2013 at 9:38 pm # Reply

    Dr. Ben,

    I am homozygous a1298c, and currently taking 5-mthf ES (10,000mcg/dose) and Methyl Protect, which also has total of 2000mcg of folate (1000mcg as 6(S)-5-methyltetrahydrofolic acid). I fear this is too much folate, as well as it is too expensive for me to keep taking every day. Would you suggest a more appropriate dose?

  70. Leszek April 19, 2013 at 4:45 pm # Reply

    Dear Dr Ben:
    I have a single copy of A1298C and cannot wait for your complete thoughts regarding treatment recommendations.

    For over three decades I have suffered from mild cognitive decline, impaired spatial learning, exaggerated reactions to high altitude (5000 feet is enough to make me confused and disoriented) depression, anxiety, back and neck numbness, achilles tendons stiffness, mild hypothyroidism. Small blood circulation impairments of vascular origin in the brain have been confirmed by MRI.

    I also get confused after drinking unfiltered (turkish) coffee. I quit gluten, dairy, coffee, alcohol. This helped, but not much.

    It would not have occurred to me or my doctors that my problems have anything to do with MTHFR except since mid-March I had been taking 6 grams of TMG to help me with back pain and to increase my flexibility (I have been doing hot yoga for two years and was making very little progress); to my dismay, TMG resolved ALL issues, including depression, brain fog,etc.

    While trying to understand why TMG has been so dramatically helpful, I learned about MTHFR mutations. Once I tested positive for A1298C, I realized that my father suffered from excessive daytime sleepiness all his life; my brother and older son have ADHD and all kinds of food sensitivities. I am now trying to persuade them to get tested.

    All of us have had problems that are quite serious so– while I believe that heterozygous 1298 is not as bad as other MTHFR mutations discussed here — it still quite debilitating.

    I wish I could simply continue taking TMG but unfortunately it causes sleep issues — I toss and turn with a sense that any pressure on my chest is unbearable. I added active b12 (1000mcg), and tried to replace some of the TMG with methylfolate (I took 1600 mcg per day, now use only 400 mcg) but felt worse while sleep issues persisted. I take D3 (2000 IU), E (4000 IU), C (1000, at different time then TMG, B12 and methylfolate). I am considering Arginine but I wish I could have more information regarding all this.

    My doctor wants to learn about MTHFR but at this time she is not helpful.

    • Lisa April 19, 2013 at 6:14 pm # Reply

      That is really interesting, I had never heard of TMG – what time of day are you taking the TMG? You should definitely look in to one of the specialists listed on this site. Even if they are not in your area this is something that can be addressed with phone calls and blood tests, no real examination is necessary.

      • Leszek April 19, 2013 at 9:17 pm # Reply

        Trimethylglycine (TMG, betaine) is covered on this site extensively, as a part of c677t mutations protocol. It is is a remarkably inexpensive, potent and very direct methylator of homocysteine.
        Ordinary beets contain it, hence the name.
        I take it in the morning, have reduced my dose from 6 g to 4g. I regret venturing into other supplements, very much against Dr. Ben’s advice.

        Yesterday I took Inositol for the first time 1300 mg and today 650 mg and this did me in.

        I had it coming, brainless moron, thank good I have a solid medical excuse for my idiocy :).

        I came across TMG as an alternative to SAMe, which some people argue to be an effective remedy for joint pain. I know now from this site — do not use SAMe if you have A1298C mutation. On the other hand, TMG is said to increase SAMe, yet is proved revolutionary in my case.

        • Lisa April 19, 2013 at 10:25 pm # Reply

          I have hte double a1298c mutation and double COMT mutation. Because of the COMT mutation I take Sam-e and it has been helpful. I must have missed where it says we shouldn’t take SAM-e with the a1298c but there is so much info I kind of gave up digging through it all. I’ll ask my doctor about it next time I see her. So you would recommend the TMG over other things? I already have sleep issues and take Lunesta which I will be trying to taper off of in the next week or so. I also have nighttime anxiety on occasion when trying to sleep. Having the COMT mutations complicates things a big.

          • Leszek April 20, 2013 at 12:24 am #

            Dr. Ben discusses SAMe and TMG in his MTHFR presentation:


            If you cannot tolerate too much information, start around minute 31: 30 to see the whole picture.

            Concentrate harder around minute 48:00: detailed discussion of the role of TMG.

            TMG works wonders for me, however, I took no other supplements, certainly I did not take SAMe with TMG.My

            It seems to me, however, that the usefulness of TMG cannot be merely due to its ability to lower homocysteine. Mine is not that high (under 15 mmol/L), besides, A1298C hardly ever coincides with hyperhomocysteinemia. Is it possible that there is some additional pathway, that he is not discussing, through which TMG affects either BH4 levels directly or lowers ammonia levels? Seems that a trial Arginine therapy (ammonia lowering amino acid) might help to shed light on this?

            Let’s say TMG is as useful as I am experiencing it and this is not a placebo effect. Do I just keep taking it for ever? Won’t’ in cause excess methionine levels?

            Why am I not that kind of a doctor? :)

          • Leszek April 20, 2013 at 12:30 am #

            I meant: when I first felt the remarkable benefits of TMG, I was off everything else.
            And one other thing: I could not immediately find that material where he insists on avoiding SAMe with A1298C mutations. But it is there.

          • Lisa April 20, 2013 at 12:34 am #

            I’m feeling pretty good with the supplements I take now but if TMG is a better alternative I would be interested in trying it. Currently the things that bother me are mainly that my hands are pretty achy and tingly all of the time from the forearms down. I had that before and it got better for a bit but is back now. I also sometimes get a crushing tiredness out of the blue and then it goes away. Brain fog has cleared up a lot and I seem to have more energy with the active B supplementation and the other stuff I’m taking.

    • Louise April 20, 2013 at 7:01 pm # Reply

      Leszek, I don’t have much knowledge on all this stuff as I’m only new to it, but one thing that I might suggest is that you research into Potassium, which seems to be quite critical when taking some or all of the ingredients of a nutritional methylation protocol.

      Many people experience symptoms of low potassium – called hypokalemia – after just a couple of days of taking some of these supplements (like methylB12, methylfolate). It can require more than the typical amount of potassium found in the American diet (which is less than half the RDA) and than found in normal multivitamins (99 mg) to compensate for this greatly increased pressure on the body’s potassium stores from the methylation process’ being reactivated. The potassium is required for the formation of new cells, apparently.

      Not having enough potassium can cause heart palpitations, odd feelings, muscle cramps, fatigue, etc. I don’t know if the unpleasant feeling you get in your chest might be related to this. I know that it makes my chest feel strange and unwell if I’m not taking enough potassium throughout the day — and I am only trialling a tiny amount of daily B12, and no other methylation supplements.

      Hypokalemia is described to some exent on methylation discussion forums like phoenixrising, by methylation promoters like freddd, etc.

      I think that Dr. Ben Lynch discusses the topic of a greater need for potassium in a few places on his site – one is under the topic of electrolytes – he recommends to drink a powdered supplement (he calls it something -ade).

      Also, having enough magnesium is supposed to be important – it helps muscles relax, it helps many people sleep better.

      • Leszek April 22, 2013 at 8:42 pm # Reply

        I agree that potassium is great in managing side effects; my point is that I do not see much evidence (but then there is lot’s of things I don’t see) that a1298c requires L-5-MTHF. When this variant of MTHFR mutation is present, the administration of methylfolate produces side effects, which, no doubt, are best controlled with potassium. The question remains, if a1298c does not diminish — and it does not — the body’s capacity to metabolize folic acid, while impairing — as it does according to all sources I have seen — the reverse BH2 to BH4 reaction, why supplement L-5-MTHF and push forward a faulty cycle?
        These are questions, not statements. I am frustrated that this site is all about c677t; while the recommendations that are entirely appropriate for it, are superimposed on the a1298c variant, which is different and just as debilitating. I hope Dr Ben shares with us his detailed research into this soon.

        • Dr Ben May 1, 2013 at 10:45 pm # Reply

          Lesek –

          I, in no way, intend for to push the 677 recommendations to 1298. These snps affect the MTHFR enzyme differently – how differently – research doesn’t say.

          I also do not see research supporting the internet wide thought that MTHFR 1298 affects biopterin production.

          Many things affect biopterin production – well outside of a gene defect. An activated immune system is one.

          Read this great paper on Neopterin and Biopterin.

  71. Josh McKay April 21, 2013 at 1:06 am # Reply

    Hello. I have the A1298c mutation. My doctor put me on L-5 MTHF and vitamin B12 at same time. Before finding out about this mutation I have been on 5-htp and a supplement called Neuro Calm by designs for health for about two months now. I was actually starting to feel a little better mood, sleep and anxiety wise.. Until I started taking this L-5 Mthf. I’ve been on it for a week and feeling horrible. Haven’t been able to sleep, extremely nervous and anxious. Paranoid, very irritable and angry as well. I don’t know what to do… I have this mutation but I have to stop taking this stuff because it’s making me feel like this. I started off at 4000 mcg of L-5-MTHF per day.. I couldn’t sleep so I went down to 2000 mcg perday. Sleep got a little better for one night… Then started acting up again. So I just took 1000 mcg yesterday and none today. But have still been feeling horrible all day. Extremely tired at work and very anxious/ nervous, paranoid and depressed. Should I just stop taking it all together ? Or take it every other day? I don’t know what to do.

    I got off all anti-depressants about 8-9 months ago. When I got off I completely lost my libido and haven’t had any libido or been able to get an erection in that time (8-9 months) Keep in mind I’m 23 years old. Testosterone levels were normal. serotonin was low.

    • Leszek April 22, 2013 at 9:15 pm # Reply

      hang on, at least you know what is causing this.
      These are conclusions from my own experiences:
      1. TMG works, L-5-MTHF does not,
      2. After taking TMG at therapeutic doses (6 grams, that’s 8 typical 750 mg tablets) for two weeks I experienced a bear complete remission of all my symptoms: day-time sleepiness, fatigue, brain fog, anxiety, depression, achy muscles and tendons, ADHD-like symptoms (late onset, while at grad school) exaggerated response to altitude over 5000 feet, addictions; coffee causing sleepiness (except for espresso from reputable sources :).
      3. TMG caused slight chest discomfort at night, bad enough to cause insomnia. Replacing about half of TMG with, first, 400 and than 800 mcg of methylfolate made matters worse.
      4. Niacin takes care of any heart trouble and, unlike under c6777 variant, is recommended for a1298c mutation on daily basis (I gradually increased niacin to 2 grams, I take it befor going to bed).
      5. Addressing the levels of BH4, the critical substance from which key neurotransmitters are made and whose production is lowered by a1298c, is most difficult: Dr Ben recommends arginine and 5-HTP. I have followed his advice for only several days: so far, so good: my sleep improved greatly. I would recommend taking arginine two-three hours before bedtime, for it causes brief period of thirst with all its predictable consequences.
      6. I also take methylcoblamin (bioavailable b12), 1000 mcg daily, and D3 (2000 iu), in the morning, with my TMG. But that’s a no brainer.

      I have never been better, however, I suspect that all these complications are unnecessary and a direct supplementation of BH4, after lab testing, might be optimal.

      The moral is: in my opinion, MTHFR c677c treatment protocol has little to do with a1298c mutation.

      • Tina April 22, 2013 at 10:17 pm # Reply

        My son is able to take TMG with his other supplements. He is high histamine though.
        For the rest of us with the A1298C mutation, we have low to no histamine levels, which makes things worse.
        Not sure how to get around that.

      • Leszek April 23, 2013 at 2:24 am # Reply

        Given that my recovery was only bear complete, rather than near complete, obviously, I have not recovered fully :).

    • Leszek April 22, 2013 at 9:23 pm # Reply

      Keep us posted what you are doing and how you are. OK?

      • Josh McKay April 29, 2013 at 10:11 pm # Reply

        Can you take TMG, 5-htp, and Bh4 all together ? At what time in the day should you take BH4 ?

        • Leszek April 29, 2013 at 10:31 pm # Reply

          I have not used BH4 yet but have not seen any indications against taking it at the same time as other supplements.
          I know, however, that TMG should be taken in the morning.

          I heard that vitamin C is useful in a1298c treatment but should not be taken at the same time as some of the B vitamin supplements.

          Good luck, let us know how it goes.

  72. Elizabeth April 22, 2013 at 7:48 pm # Reply


    I’m sorry for your troubles health wise and with that rotten doc. Probably many of us have spent way too much $$ on poor care, finally turning to very reasonable ways to help ourselves, with the assistance of some good, caring docs. BUT for now I wanted to say that I was getting eye damage, very scary, at the worst point of B12 deficiency and many related problems, and just B12 injections (or good-quality methyl-B12 or hydroxycobalamin) helped considerably and quickly. Like a miracle actually. I know it’s more complicated than this, but you can get 5000 mg. good B12 and start on your way to being better–I hope. Good luck.

  73. Sarah May 13, 2013 at 7:43 pm # Reply

    I am homozygous for the A1289C mutation and do not have C677T mutation. I found this out almost 6 years ago when I was pregnant after telling the doc that I had three early miscarriages prior to the pregnancy. Doc told me to take a baby aspirin throughout the pregnancy and I never thought about it again. My daughter from that pregnancy has Celiac disease. I am wondering what I need to do for my own diagnosis of MTHFR mutation and what testing I should do for my daughter with Celiac. THANK YOU!!!!!! Sarah

  74. Ryan May 15, 2013 at 2:21 am # Reply

    My husband just tested positive for hetero 1298, which really surprised me because he had a stroke at 40 years old along w/a homocysteine of 60! The docs just give blood pressure & cholesterol meds and suggest OTC b12. Any advice?

  75. Rebecca Hill June 5, 2013 at 12:06 am # Reply

    Hi Dr Ben! Thank you for your information. I was recently diagnosed with this MTHFR (doc said it was heterozygous). About one month ago, I lost a baby at 37 wks and there is no diagnosis as to why. This MTHFR was the only test that came back back showing positive results. My doctor said he is going to put me on 4mg of folate a day. Do you have any opinions on that and is there anything else you could possibly recommend for a next pregnancy since I have this “thing”?!? Thank you so much in advance. :)


  76. Leszek June 10, 2013 at 10:20 pm # Reply

    I have as single copy of a1298c and a usual set of symptoms (described in my earlier comment). I made a great deal of progress on TMG alone (6 grams) but once I started replacing some of it (it caused chest tightness at night) with methyl folate (800 mcg) + B12 (hydroxocobalamin, 100mcg), while retaining 3 grams of TMG, things did not improve nearly as much as on TMG alone.

    I just discovered a1298c protocol of sorts, by a naturopath (who seems to believe in hair analysis, so be careful). I am going to give it a try. Incidentally, I have been looking for a MTFR specialist in Seattle area, so far, no luck whatsoever.

    I am going to retain my current methyl+hydroxy+tmg regime as it seems to help a bit — this new protocol also includes methyl donors — and add, in this order:

    1. NADH (supports BH2-BH4 conversion)
    2. glutamine (ammonia)
    3, yucca (ammonia).

    I hope this is going to work.

    • Leszek June 10, 2013 at 10:23 pm # Reply

      1000 not 100 mcg of b12 hydroxy, of course. I keep making such mistakes all the time, which makes me even more anxious than I already am.

  77. Nina June 15, 2013 at 4:21 am # Reply

    Dr. Ben

    I have a sibling who is highly Bipolar and anothe who is Schizophrenic. I have two other siblings who are mentally find but physically very ill (no energy, cannot lose weight, heavy set despite a careful diet, high blood pressure at a young age).

    I was informed 2 years ago tha that I am a Celiac (I changed my diet completely)and also have one copy A1298. I have thyroid, asthma, low Vitamin D and high homocystein problems and feel very weak.

    In addition to the above, I have two nephews who are autisic.

    Can you please advise what we should do. We have had a hard life with the 2 mentally ill siblings and now all the other siblings have physical health problems. Our diets are very good but we are struggling.

    We can have the others tested, but need your advice.

    Thanks you. Nina

  78. Sandy June 19, 2013 at 7:56 pm # Reply

    Dr. Ben, Just received result: MTHFR, DNA Analysis: A1298C Single mutation identified. I’m a 54 year old female, Hashimoto, complete hysterectomy. Thought I was pretty normal, then in Oct. 2011 after home remodeling and reacting to something I have now become very chemical sensitive. Also had to have A/C replaced and there was some mildew on the back side of AC vents, so I’m not sure if that could have caused something. I can’t go into stores like Walmart, Malls, new cars, xerox copies, books, newspapers so many things are making me have horrible headaches and sore throat, etc. Can this result have anything to do with this. It has been going on for over a year. Can you give me any information or guidance on what I can do. My world is getting smaller and smaller. I’m starting to react to everything it seems. Thank You!

    • Dr Ben June 19, 2013 at 9:46 pm # Reply

      Hi Sandy –

      Seems that the remodeling was a potentially toxic event.

      Consider seeing a physician trained in Environmental Medicine – such as

      Sauna, NAC, Glutathione, Glycine, Phospholipids, Magnesium, Vitamin C.

      Sauna is first pick.

      I do not think the A1298C MTHFR mutation has anything to do with your sensitivities. You likely have other genes which are causing issues.

      Consider the 23andMe Test and once you get the results, run them through MTHFR Support.

      • Sandy June 20, 2013 at 1:35 pm # Reply

        so in a nutshell what does this single mutation mean, you have to do the 23andME test to get healed? If you don’t have a medical degree, how on earth do you begin to understand this, especially when not feeling well. Feel’s like I’m falling apart and one can help me figure this out. What is NAC

        • Leszek July 17, 2013 at 7:37 pm # Reply

          NAC is N-acetyl L-cysteine, an amino acid with a acetyl group attached to it, a glutathione-promoter, powerful antioxidant, a very effective homocysteine reducing agent, useful in various psychiatric, cardiovascular and other disorders. It may improve mild cognitive decline an help control addictions. Since a1298c sufferers often have to deal with those, NAC, an inexpensive, over-the-counter remedy, might be very useful for all of us.
          I have been using it last several days and find it very effective. There are some side effects, particularly sleep disturbances, but from what I have read, this should pass. I like the sense of well being and clarity that NAC appears to restore in me.
          I concur with dr Ben regarding the need to check other polymorphisms. A single copy a1298c MTHFR, which by itself does not account for much. I am awaiting 23andME results. The remarkable effectiveness of NAC in my case might suggest an eNOS polymorphism which result in reduced ability to synthesise nitric oxide. We shall see.
          Do the 23andME.

      • Opal August 2, 2013 at 11:14 am # Reply

        Hi Dr Ben,
        I have tried to get a compounding chemist to give me methylfolate as I can’t find it at pharmacies in Australia.
        The chemist sent me this and I am unsure how to respond. I’d love to hear your thoughts if you understand what they are asking…
        “The diagram herewith shows your MTHFR gene mutation as we understand it.
        Look at the bottom left hand side and you will notice 5-CH3-THF, the yellow highlighted methyl group is needed for Homocysteine to be converted to Methionine. If this is your understanding of your problem, then please confirm that you are asking us to obtain 5-CH3-THF, the substrate of the enzyme Methionine Synthase. This substance is AKA Levomefolic Acid and other names include L-Methylfolate. You will need to tell us which salt, exactly, that you wish to take and what your dosage is to be so we can help you.”
        Thanks for your guidance Dr Ben.

        • Dr Ben August 2, 2013 at 5:24 pm # Reply

          The chemist wants to know which form of methylfolate you want. There is a glucosamine salt by Gnosis and a calcium salt by Merck. Both are good and provide the L form of methylfolate which is what you want.

          If it is expensive, you may find various delivery options of methylfolate here. Seeking Health ships internationally also.

  79. Kylie June 23, 2013 at 12:55 am # Reply

    Hi Ben wow thanks for all the info it really does help
    I was diagnosed A1298c homozygous 2 months ago and after a rough few weeks I am feeling great I take mega magnesium , metagenics neurolift and metazinc, hydrox B12 injections and vitamin D. I hav just started on the paleo diet and am trying to eradicate all toxins from my life. I have a lot of the symptoms and basically for tha past 2 years hav felt like I am 80 years old.
    As I have 2 mutations of the gene am I right that my son will also have at least one I am wondering as he is only 5 years old should I get him tested now ? I was going to wait til he was a bit older he suffers eczema, has bad allergy to mites cats and grass and is on a gluten free diet he hasn’t been tested for celiac but since we hav taken the wheat away all symptoms hav gone, does he need to be tested now and would he be put on supplements or can we just change his diet and make his life as toxic free for the time being and get him tested when he is say 10 years old unsure what to do
    Thanks kylie

    • marny June 28, 2013 at 12:46 pm # Reply

      Hi Kylie, was kind of comforting to read your post! I was just diagnosed A1298c homo this week and the more reading I do the more overwhelmed and freaked out I get!! (and im a nurse) The problem seems to be for us homozygous A1298c people, that there is not enough research and information to direct or prescribe care/supplementation. I was very interested to read that you are taking neurolift, metazinc and the b12 which is what I have also been prescribed (started the neurolift today) Great to hear you are feeling better! Am curious as to why you had a rough couple of weeks when u started the supplements…Im concerned my body is going to not like all these supplements. On another note re your little boy, I think your idea about reducing his chemical load as much as possible through diet and environment is the best idea for now. Perhaps if he needs a blood test for anything else in the near future you could ask the doctor to add on the MTHFR… I have a 9 year old daughter and am wondering the same thing…should I get her tested…

      • Kylie July 10, 2013 at 1:23 am # Reply

        Hi marny great to read your reply think the reason my first few weeks were rough my body felt like it just shut down in order for all the supplements to take effect. But I have noticed I feel a lot better but I feel like I am on a wave of feeling good then back down again and I hav huge bouts of diarrhea which I hav heard could be from the high doses of magnesium but i am trying to sort out atm. funny I should read this reply today as yesterday my son had the blood test on doctors advice but he is a legend and dealt with it like a trooper so just hav to wait and see how results turn out if there is anything we can do for him now so he doesn’t go through what I hav been through then that wil b a bonus for our family hope your supplements are working for you cheers Kylie

  80. Nicole July 22, 2013 at 6:33 am # Reply

    Dr. Ben,
    I was told about my A1298C mutation through blood tests after my 2nd miscarriage about 4 years ago. No one really understood it & I was eventually told to just take 5,000mg folic acid & baby aspirin. I’ve now had a total 4 miscarriages, 1 chemical pregnancy, & an ectopic pregnancy. So many tests through the fertility clinic kept coming up normal so I decided to do the 23andme for my own research on my health & had my husband to do it as well. I came up A1298C heterozygous as expected. The shock is my husband came up compound heterozygous! I have to believe this could be a huge cause of our miscarriages from all I’ve read. We plan to TTC in 2 months. Until then we are going on an all natural diet & both taking Thornes Methyl guard plus. I need to know what extra stuff my husband should be doing & taking to help with his condition & to hopefully avoid another loss. PLEASE help us! Thank you & I look forward to your response.

  81. Amber Pesce July 24, 2013 at 5:02 pm # Reply

    Hi, Dr. Ben,

    I have the A1298C Mutation and 03P30P mutation, but they are only +/-, and (based on 23andme, still waiting for Dr.’s MTHFR blood test), I do not have the 677 mutation.
    Based on the results below, considering the other “C” mutations listed, would you expect A1298C could still be problematic, despite the absence of MTHFR677??? Because I have problems (primary psychiatric and thyroid) that I am trying to get to the bottom of.

    MTHFR 0677T rs1801133 GG -/-
    MTHFR 03 P39P rs2066470 AG +/-
    MTHFR A1238C rs1801131 GT +/-

    COMT V158M rs4680 +/-
    COMT HH rs4633 +/-
    COMT P199P rs769224 GG -/-

    CBS c699t RS234706 AG +/-
    CBS A360A rs 1801181 AG +/-
    CBS N212N rs2298758GG -/-

    • Dr Ben July 25, 2013 at 6:29 pm # Reply

      Hi Amber –

      The research is not showing a single A1298C MTHFR mutation to be problematic.

      I am unfamiliar with the MTHFR 04 variant. I’ve been trying to find research supporting it actions but have yet seen anything. Please share if you have.

      Regardless of genetic defects, one should always evaluate the ‘functional’ aspect of your genes through proper testing and history.

      • Aurora Daniels July 27, 2013 at 12:46 am # Reply

        Hi Dr Ben,
        I have been told I am homozygous for A1289C mutation. I have tried numerous doctors to get Methylfolate but none of them understood and just told me take 5mg of folate. I have been to a naturopath who said it is really hard to get the active forms of everything I need in Australia so just gave me folinic acid, some methionine and some P5P. She said to take the same amount of these with or without pregnancy/trying to conceive. I am also taking a strong fish oil. Is this all I need? Should I be still looking for Methylfolate? How much of each should I have normally and during pregnancy/trying to conceive please? If I need other supplements do you know where I can access them in Australia as Amazon doesn’t post most supplements to Australia which is very frustrating.
        Thank you for your help!

        • Michelle Shanks March 30, 2014 at 9:16 pm # Reply

          Hello Aurora,
          I just stumbled on your post.
          Get in touch with Carolyn Ledowsky at Northbridge Natural Health in Sydney. you can link into her website.

          Carolyn is my practitioner and she specialises in MTHFR because of the prevalence of it. She can supply you with many of the items you will need. If you are not in Sydney then I am sure she can Skype with you. she has also started the first of many webinars and talks, has a Facebook page etc. you are not alone and she has a FULL understanding of MTHFR and knows many doctors that she works with and is very keen to educate the client.
          Help is just a click away!

        • Michelle Shanks March 30, 2014 at 9:17 pm # Reply

          Hello Aurora,
          I just stumbled on your post.
          Get in touch with Carolyn Ledowsky at Northbridge Natural Health in Sydney. you can link into her website.

          Carolyn is my practitioner and she specialises in MTHFR because of the prevalence of it. She can supply you with many of the items you will need. If you are not in Sydney then I am sure she can Skype with you. she has also started the first of many webinars and talks, has a Facebook page etc. you are not alone and she has a FULL understanding of MTHFR and knows many doctors that she works with and is very keen to educate the client.
          Help is just a click away!
          Kind regards,

      • Amber July 28, 2013 at 9:00 pm # Reply

        Thanks, Dr. Ben,

        I did see that you stated the A1298C is not a problem unless paired with 677, but I also saw that you said something about other cytochrome mutations making A1298C problematic, and I wasn’t sure if the CBS or COMT ones where what you were talking about there.

        My doctor was so certain I’d benefit from Deplin before even testing that she put me on 7.5mg and wanted me to ramp up to 30. Having reactions, so stopped until I can talk to her next.

        • Amber July 28, 2013 at 9:03 pm # Reply

          P.S. Was also interested since you mentioned certain lifestyle variables can affect +/- 1298, and my understanding was even without 677. Just wanting to do my diligence in case she wants me to keep taking so much Deplin!

  82. Terry July 26, 2013 at 9:55 pm # Reply

    In an effort to diagnose a condition that consisted of twelve years of hand, arm and foot contractures with very mild tremors my new doctor discovered that I have the A1289C heterozygous mutation. I do have extremely high blood pressure (taking five pills a day to maintain a 130/90 ish BP). I also had three miscarriages many years ago. I am wondering if this mutation could have anything to do with contractures????

    • Terry August 9, 2013 at 5:02 pm # Reply

      Have also just learned that my mercury levels are extremely high and have just begun chelation with DMSA.

      • denice September 10, 2013 at 12:37 am # Reply

        i have hetero 1298 and RA..only my left fingers continue to be stiff all day long unlike my right hand the stiffness goes away after 10 minutes of movement. what metals test did u do and do you have amalgam fillings which should be removed??? thx for info

  83. Barbara Leaverton July 29, 2013 at 11:17 pm # Reply

    I have the C677T & A1298C. I have been suffering with chronic sinusitis for the last two years. Also have chronic fatigue My doctor is treating me with deplin, BH4, and B12 shots for about 4 months. Have only since limited improvement. He has never discussed my diet. Could the sinus problems be related to the mutations? Also, can suggest where to look for the proper diet with this mutation?

    • Glenn July 30, 2013 at 12:23 am # Reply

      Hey Barbara.
      I’m homozygous for A1298C as well as nine other MTHFR mutations of the fourteen chosen in the MTHFRSupport Variant Report (, but haven’t yet seen anything specific about these mutations and sinusitis – although very interested to know if there are any.

      I did however suffer from chronic sinusitis and abusive amounts of antibiotics to “treat” them, from early childhood till age 19, when I finally cut out all dairy. Since then, for the last 10 years, I’ve rarely had any sinusitis issues except for when I accidentally get dairy-poisoned or very sick like the flu or the last 1,5 year of ME/CFS post EBV.. So my first advice is to anyone with sinus issues is to clean up the diet strictly for 30 days and see how they feel. The most common offenders are dairy and gluten, so I would at least remove those for a period of time and see how you feel and perform. If you want to get a bit more serious with the diet part, and I wish someone would have pointed me to this 20 years ago (when I started learning english), have a read of Robb Wolf’s Paleo suggestions, especially the paleo for autoimmunity on this place

      Hope that helps :) And maybe someone will come around with a more mutation specific answer eventually..

      • Teresa July 30, 2013 at 5:42 pm # Reply


        Perhaps you have a fungal infection? My naturalpath said any infection lasting longer than three months is likely a fungal infection.

        • Barbara Leaverton July 30, 2013 at 9:07 pm # Reply

          Thanks for the advise. Unfortunately, I have been dairy and gluten free for the last two years. It has helped the gut but not the sinusitis. My doctor has been treating me for candida yeast overgrowth for the last four months. I have seen some improvement but still have constant sinus pain and frequent flare ups. I even cut out all sugars or as much as possible for over three months. Just seems like I am missing a step.

          • CAWS August 10, 2013 at 7:12 pm #

            I was also aggressively treated with antibiotics for sinusitis and antifungals for the candida that followed for THIRTEEN years. Finally when nothing was working they found a large mass in my sphenoid sinus cavity [center of your head behind the eyes] and operated. This helped my drainage [they only found infection not a tumor] but did not fix the problem [anesthesia caused more problems]
            . FINALLY I went to an dentist and had them pull out the root canal that was on the meridian for the sphenoid and bingo. Turns out it had been INCORRECTLY drilled into my sinus cavity and the abcess [which was painless cause tooth was dead] had a drainage route into my sinus,lungs & stomach. This never showed up on xray , but a cavitat machine and thermography are good tests to get for a clue.
            Fixed the problem but my gut & systemic candida are still screwed in spite of many interventions. Considering a fecal transplant if I can find a doc that is willing. Already GF,DF, Weston Price diet.

  84. Pratima Dulloor July 31, 2013 at 2:36 pm # Reply

    I just got my daughter’s MTHFR results and it seems like she is homozygous for A1298C mutation and negative for C677T mutation. She has autism and we are doing biomedical protocol for more than 3 years now. What helps in this case and what won’t? Does this mean parents and siblings need to get tested as well for MTHFR and what it means for the family? TIA for any input.

    • lynn July 31, 2013 at 5:38 pm # Reply

      Pratima, my son is 5 homoz. for a1298c and neg for the c677t as well and he has autism. what biomed are you doing? we are as well. email me at if you would like to talk confidentially. lynn

  85. Mary September 5, 2013 at 10:44 am # Reply

    Dr Ben
    I’m hetero on A1298C and on Hemochromatose
    Can you please give me advice
    Also have Lyme Disease thx

  86. Shelley September 11, 2013 at 2:18 pm # Reply

    Hello Dr Ben,

    My Story has been going on for about 12 years… undiagnosed with some sort of Autoimmune disease. I have been to Mayo Clinic, along with rheumatologists, neurologists, and DO’s. I have joint inflammation and within the past 8 months have started with neuro issues (Dizzy Spells, etc). I am currently on Humira. I do have a Gluten Sensitivity so I went on that also. The Neurologist did a panel on me and the hits that I received were MTHFR A1298C Mutation A Homozygous. The C677T Mutation was Negative. There seems to be alot of comment about Heterozygous, what does the Homozygous mean?


  87. Nina September 11, 2013 at 6:15 pm # Reply

    My boyfriend just suffered a stroke in June at the age of 39. His thrombophilia test showed the following genetic mutations… Factor five Leiden and compound heterozygous C677T and A1298C. His brother also suffers from clotting disorders and I believe has the same issues. The 3rd sibling will be tested now as well. Their father was a Vietnam veteran and died from cancer at the age of 35. He was sprayed with agent orange and along with drs we are trying to find out if this is in fact the cause for these mutations?

  88. Toni September 12, 2013 at 2:38 am # Reply

    Hi Dr. Lynch,

    I tested heterozygous for the A1298C mutation. I’ve struggled with depression, insomnia and anxiety for 10 years, and in the past 5 years, fibromyalgia and chronic fatigue syndrome. I also have ADHD, and severe GERD. For the past 5 years, I’ve been taking L-tryptophan 3g/night for my depression and aciphex every morning for my GERD. I was wondering what treatment plan you would recommend for someone with my symptoms? Should I worry about interactions between L-tryptophan and L-methylfolate? I am also wondering if people typically feel some relief from symptoms after starting supplements? If so, after how long?

    Thank you for making such incredibly helpful information available to the public! I’ve been looking for answers to my symptoms for a decade now. It was only last week that I learned about my MTHFR mutation. Please keep doing what you’re doing :)


    • Teresa September 13, 2013 at 10:37 pm # Reply

      Hi Toni,

      I just thought I would mention that I have hypothyroidism and this can cause depression, insomnia and reflux (GERD?). At least when doctors are willing to give me enough T4 and T3 hormones to recover, it makes a difference with those three symptoms. Also untreated or undertreated hypothyroidism can cause fibromyalgia and fatique. I have a hard time finding a doctor that will let me stay on the dose I need to survive because the amount brings my TSH level down just slightly below zero and many doctors cannot handle that.

      Many doctors don’t know that too little thyroid hormone can cause anxiety and insomnia just like too much can.

  89. Janice September 17, 2013 at 10:51 pm # Reply

    My labs are back and I see my Dr Friday. She is 3 hours away so hopefully she sets me up right away. I hurt all the time, my muscles just ache and hurt, my joints hurt especially my knees. My one Dr told me he knows if I am hurting another person would not be able to function. I had severe diverticulosis and he was surprised I was even walking and then he decided he knew if I hurt it was bad.

    Here is what my labs say:

    CHOLINESTERASE, RBC 13159 9572-15031 IU/L
    CHOLINESTERASE, PLASMA 4437 2504-6297 IU/L
    RESULT see note
    This individual is heterozygous for the A1298C
    mutation and negative (normal) for the C677T
    mutation in the MTHFR gene. This result is not
    associated with coronary artery disease and venous
    thrombosis. Increased risk of coronary artery
    disease, venous thrombosis and increased plasma
    homocysteine can be caused by a variety of genetic
    and non-genetic factors not screened for by this
    assay. Consider genetic counseling and DNA testing
    for at risk family members.

    • Janice September 17, 2013 at 10:54 pm # Reply

      more of the report :

      W. Christine Spence, Ph.D., FACMG
      Director, Molecular Genetics
      Hyperhomocysteinemia is a risk factor for arterial
      disease and venous thrombosis. Homocysteine levels
      are affected by nutritional and genetic factors.
      Since MTHFR is involved in methylation of homocysteine
      to methionine, individuals with MTHFR gene mutations
      that reduce enzyme activity may develop
      hyperhomocysteinemia and thus be at elevated risk for
      vascular disease.
      The C677T [NM_005957.3:c.665C>T (p.A222V)] and A1298C
      [c.1286A>C (p.E429A)] mutations are detected by
      amplification of the selected regions of the MTHFR gene
      by polymerase chain reaction (PCR) and fluorescent
      probe hybridization to the targeted region, followed by
      melting curve analysis with a real time PCR system.
      Although rare, false positive or false negative results
      may occur. All results should be interpreted in
      context of clinical findings, relevant history, and
      other laboratory data.
      Health care providers, please contact your local
      Quest Diagnostics genetic counselor or call
      866-GENEINFO (866-436-3463) for assistance with
      interpretation of these results

  90. Candy September 19, 2013 at 3:14 am # Reply

    Dear Dr. Ben,

    My son, age 35, has been having severe health problems for nearly 2 years. Problems started with tics and escalated to verbal screaming and his entire body jerking constantly. I’m surprised he doesn’t have whiplash. Many doctors and many medications later, his tics seemed to have subsided, but he was having severe stabbing pains in his bones. His GP was the one to find that he was homozygous for A1298C. He was put on deplin and he was a new person within three days. This lasted for a couple of months. Then his tics started coming back. His medications for deplin and a blood pressure medication were both doubled and there was some improvement, but not enough for him to go back to work. His tics get worse with any kind of stress. We are currently seeing his GP weekly and having tests for all sorts of things. Our GP is very supportive and doing his best to help while we are waiting to see someone who has more experience with MTHFR. I am trying to have him eat mostly organic and get off of all processed foods. He is trying, but he has very little money due to not being able to work.

    I have never heard of tics being associated with MTHFR. I was wondering if you have ever heard of this. I do know that if my son forgot to take his deplin when he was feeling almost normal, his tics seemed to start again. He has also had problems with something like IBS, but they are getting a little better right now.

    I really would like to know if his problems could possibly be related to his being homozygous for A1298C. I have searched, but cannot find anything on the subject of tics being related to MTHFR. I figured if anyone might know if there was a link, it would be you.

    Thank you, Candy

    • Teresa September 20, 2013 at 3:47 am # Reply

      I am no doctor but I thought of electrolyte deficiencies including magnesium and calcium when you mentioned muscle jerks and bone pain. Has he had the three above tested for deficiencies?

      • Candy September 20, 2013 at 6:43 am # Reply

        I believe he has had tests for calcium and magnesium. He is requesting a copy of all his lab results when we go next week. His doctor just changed offices and there has been a bit of difficulty in getting copies. His jerks have been quite severe and the bone pain was like someone stabbing his bone with a hot needle. It would last for only a second.

        The doctor put him on a amphetamine to try for a week. He started this morning and told me that he had a little more energy today, but he hadn’t noticed any difference in his physical or verbal tics.

        I was thinking of suggesting organic coconut water for him, which may help with any electrolyte deficiencies he could have. I have some here and will give it to him when I see him tomorrow.

  91. Amber September 21, 2013 at 3:52 pm # Reply

    Dr. Ben,

    I am new to treating my A1298C (hetero). My doc is new to it too. She put me on Methyl Folate and SamE. Some sites recommend SamE, some don’t and in one of your comments you mentioned it. Do you recommend it? If not, why? I know I personally have improved since adding it to my fistful of daily pills and my mental and emotional well being deteriorate without. Am I doing my body a bad thing by taking it? Have Hashimoto’s with adrenal issues, on the Autoimmune Protocol diet so no gluten, grains, dairy, nightshades, or fake stuff. Thanks :)

    • Sandy September 22, 2013 at 4:46 pm # Reply

      Amber, would love to compare notes. That’s me to a tee!

      • Larry Alan September 24, 2013 at 2:12 pm # Reply

        Amber and Sandy, me to a tee as well, will contact you, thanks

  92. Lea Ann September 24, 2013 at 4:18 pm # Reply

    “There are certain dietary, lifestyle and supplemental recommendations that help reduce the effects of the A1298C MTHFR mutation.

    That is well beyond the scope of this article.”

    Being homozygous A1298C, I am eager to read a future article addressing the liefstyle and supplement recommendations. There is little information on A1298C compared to the other variant. I have no copies of the other variant.

    • Dr Lynch September 24, 2013 at 7:46 pm # Reply

      Lea Ann – my view on A1298C has changed. I do not think it is that significant when it is by itself.
      That said, there are countless other genes in the folate cycle which may causing significant issues – beyond MTHFR – such as MTHFS, TYMS, SHMT, MTHFD1, FOLR, etc.

      Do avoid folic acid. Use only folinic acid and methylfolate. Work with your doctor on these.

      Thank you

      • Lea Ann September 24, 2013 at 7:50 pm # Reply

        Thanks for replying – if I get the 23andMe test to find out if I have defects in any of the other genes affecting the folate cycle, how can I find a doctor who understands the folate cycle? Do you still work with clients in consultation?

      • Leszek September 24, 2013 at 8:01 pm # Reply

        Dear Doctor Lynch:
        23andme could process my sample, twice, due to insufficient DNA concentration; is there another lab that you can recommend, which provides an equally comprehensive genetic profile, and uses blood samples?


        • Steve Thompson October 16, 2013 at 9:53 pm # Reply

          Hi Leszek.

          I had the same problem, 23andme unable to extract sufficient DNA to test.

          I then bought the DNA Methylation Pathway Analysis from
          Much more expensive and it takes about 10 to 12 weeks to get results, but better than flying blind. And it’s specific to methylation.


  93. Kristofer Young, DC (@FxMedChiro) September 26, 2013 at 11:09 pm # Reply

    Dr. Ben,
    Thank you so much for helping to educate us!
    Dr. Young

  94. Kara September 30, 2013 at 9:18 pm # Reply

    Hi Ben! Love your site and so greatly admire your desire to help others!

    I just got my 23andme results back and have questions about hetero A1298C, complicated by homo CBS and hetero MAO-A. Listened to your 90 min video, which was great! However much of this is still way over my head. I believed you mentioned watching ammonia and sulfates/sulfites levels when dealing with MTHFR and CBS mutations. Any other tips for hetero MAO-A being in the mix? I deal with tremendous anxiety (diagnosed with GAD/OCD) and subsequent depression because of the high anxiety.

    I’ve already purchased 3 of your products, but want to make sure I’m not shooting in the dark here. :) If a consult is required, I’d love to be able to have one with you – please let me know how. Thank you for your expertise and dedication!!!

    VDR Bsm rs1544410 TT
    BHMT-02 rs567754 TT
    BHMT-04 rs617219 CC
    CBS A360A rs1801181 AA

    MAO-A R297R rs6323 GT
    MTHFR 03 P39P rs2066470 AG
    MTHFR A1298C rs1801131 GT
    MTRR A66G rs1801394 AG
    MTRR R415T rs2287780 CT
    BHMT-08 rs651852 CT
    SHMT1 C1420T rs1979277 AG

  95. Gina October 8, 2013 at 12:14 pm # Reply

    My lab results (2009) found that I am “positive for one copy of the A1298C mutation – heterozygous”. If I read correctly, unless the word “compound” is in the results then I have little to worry about. Is this correct.

    I like one of your other followers have had to be seen by a psychiatrist, when my ADD (diagnosed in 2007 at age 43) meds were no longer helping and I was fighting fatigue, depression, insomnia and post menopausal and weight gain. I was/am experiencing pain in my knees, toes, jaw, ear. My ADD meds were changed and I was given Viibryd for the depression. I feel like my symptoms have been “touched” but no major changes are happening. In my profession I go to clients homes and have recently felt like I am in a fog and it seems to take me longer to get there and then get the job done. I am VERY concerned about my memory. I will turn 50 in 2014 and would love to know how and where to start getting better.

    In the past 20 years I have had so many diagnosis, such as IBS, and in 2010 was being tested by MRI for MS but did not have the follow MRI due to a loss of insurance. Was told I could possibly have chronic fatigue, etc. I am also Major producer of kidney stones.

    • denice October 16, 2013 at 10:44 pm # Reply

      im 55 ,but when i was 50, i started gaining weight, high blood pressure, taking statin for high cholesterol , then in summer ’12, i was seriously depressed, and fighting FATIGUE, plus had serious memory issues, brain fog…THEN IN EARLy FALL WAS DIAGNOSED WITH RHEUMATOID ARTHRIitis. soon after found out I’m hetero for MTHFR 1298 and hoMo for MAOA MTTR BHMT CBS.. take Vit D it helps, change your diet that was a huge difference, i eat no gluten, carbs, dairy, land animals or processed foods, and refined sugar. i havent had a flare up in 8 months. i take Metanx for MTHFR. got my memeory back and feel better than ever. hope this helps

  96. Terrie October 17, 2013 at 4:52 pm # Reply


    My oldest son has autism and has been on Adderall for the past 5 years, it helps him focus, stay on task and overall he’s a much nicer person to be around.

    He was diganosed with the homozygous c677t MTHFR condition about 1 year ago. My ex-husband who moved out of state and doesn’t take care of my son, claims that my son shouldn’t be taking Adderall with this condition. My doctor and I have both asked for him to provide information that Adderall is harmful to take with this condition and he won’t.

    Can you please let me know if the Adderall is harmful and what the bad side effects may be. I have googled and tried to find information and I cannot find anything that states that Adderall is harmful to take with this condition.

    Thank you,

  97. Clare Mulham October 21, 2013 at 9:50 am # Reply

    Dr Ben, I am a naturopath and nutritionist living and working in Sydney, Australia. I have recently had a young, 26 year woman present with colon cancer- MTHFR A1228 gene mutation. Do you have any information you could provide on this?

    Many thanks in advance,

  98. Desiree October 23, 2013 at 5:21 am # Reply

    My daughter has had many health struggles for nearly all of her 10 years of life. Most of them not major, but it just doesn’t make sense to me. Her parents and siblings are all healthy and don’t really struggle with symptoms like she does. Her symptoms have included (not in this order, I’m just brainstorming the last 10 years…)
    *Waking at night and has most of her life, like she hasn’t woken up less than 20 times.
    *Has weakness in her legs (describes like they are asleep without the needles and pins feeling, feels like she can hardly control them, though it is unnoticeable to us when she walks, needs help going down the stairs at times.)
    *Kidney failure (acute) at age 3.5
    *Upset stomach often
    *infections get the best of her quickly, when siblings all get natural treatments, she usually needs the abx or otherwise.
    *Unusually tired, especially as a younger child
    *tachycardia at times
    *Has mucos/stool leak out in small amounts at times (very unnerving to her.)
    *Gets sick or has really achy legs after exercise for the last 14 months (at first had low-grade fevers with this.)
    *Colon polyp that was causing bleeding if she at gluten or corn (removed.)
    *Irritable bowel as a young child.
    I wonder if this list makes any sense to you? Her MTHFR mutation is heterozygous and A. I see that you mentioned that it is relatively common and likely not a problem. Frankly, I was hoping we were on to something. We’ve been looking for a long time. Nothing life threatening is happening, (Thank God!) but I would love for her to feel healthy and strong.

    • Elizabeth October 23, 2013 at 9:08 pm # Reply

      I hope Dr. Ben will have good answers for you. I read your post and wondered if your daughter is dairy-free. Some of the symptoms sound like milk protein allergy. (Milk protein lurks on all sorts of supplements, processed foods, etc., so it takes vigilance to really avoid all of it.) But it does sound more complex, and some of her symptoms sounds like B12 deficiency. I’ll look forward to answers other offer. Good luck to you and your daughter.

  99. Christine October 25, 2013 at 1:36 am # Reply

    I recently had my blood work done and my doctor suggested the blood test to check for this mutation. I came back positive for c677t and a1298c. I was tested because I have been exhausted my entire life. I can sleep for days and still feel exhausted. I can sleep the recommended amount of 8 hours and still exhausted. It doesn’t matter what I do or try I am just always run down and exhausted. After I get off of work I collapse when I get home. I fall asleep while driving, working, just about anywhere. I also have fibromyalgia, acute colitis (and no explanation as to why), and migraines. No one has ever been able to tell me why. I feel relieved to know why now. My doctor is confident that by taking a special kind of vitamin (something with a C) will help ease these symptoms and issues. I pray that it will. The pharmacy will have the script in by tomorrow so hopefully God willing this will be a life changing experience.

    I would like to know if there is anything else that is recommended to take or do to help my problems?

  100. Kim Kalman November 2, 2013 at 6:55 pm # Reply


    I just found out that I am Homozygous a1298c and both my children are Compound Heterozygous. I will attempt to make this brief. I was sick on and off throughout my life with symptoms no one would explain (seizures, headaches, depression severe, stomach issues, and many others). Then when I became pregnant with my son the bottom fell out. I have been sick every day since that day and he is now 9 years of age. He has been sick since birth and my daughter has as well but not as severe (she is 6). In 2001 I began to see an ND. I worked with her for years but did not have much improvement although I was doing everything right so to speak. My children also worked with her for years with little or no improvement. Finally she determined we may have Lyme. We were treated again with no improvement. There are far to many symptoms for me to list here. Hundreds. Several years ago I ran out of money and was no longer able to see here. Our health continued to decline. In November of 2011 a relative was concerned that we might die so she offered to pay for us to see a lyme doctor. We chose a LLMD/ND who also treated Chronic Inflammatory Response Syndrome or Bio-toxin Illness. We began holistic lyme treatment and did not improve. She thought we might have CIRS so we did genetic testing. My son and I have CIRS, one mutation 4-3-53. My daughter was normal although bio-toxin pathway levels were high. At that time we tested our home for mold counts with ERMI according to Shoemaker. Our home was a 19.08. We walked away and left everything behind. That was in April of 2012. We have still not been able to find low enough mold count housing at the Shoemaker recommendation of a 2. We immediately started Cholestyramine 4 times a day. My daughter could not tolerate. Our health has improved somewhat. My daughter who does not have the CIRS is doing the best out of all of us. When at a recent visit with our doctor she informed me about our MTHFR mutations even though she had been aware of them for over a year and left them untreated. She put us all on Thornes Methyl Guard Plus and some b-vitamins in addition to the other things that we are taking. I have not started the Methyl Guard Plus or B-vitamins because I was concerned about her approach especially after finding your website. We have multiple pathogneic infections like toxoplasmosis, RMSF, Herpes, Epstein Barr, intestinal parasites, just to name a few. Her approach has been for us to kill them with Byron White Formulas however we are unable to tolerate more than just a minute amount of the formulas even though we use Byron White Detox 2 3 times a day for binding along with 1 dose of Cholestyramine a day. My daughter can not handle any binders and also has difficulty with even the smallest amount of pro-biotics being used. I am the most sick out of the three of us and along with all the things we take I do theraputic coffee enemas every day just to be able to function. Here are a few of our daily symptoms (these occur daily):

    Me (MOM)
    Feeling flu-like daily
    Daily headaches
    Daily Upset stomach
    Muscle Pain
    Burning Pain
    Increased heart rate
    Lack of Appetite

    My Son
    Daily headaches
    Dark circles under eyes
    Cognitive Issues
    Frequent illness

    My daughter
    Stomach hurts daily
    Grinds teeth at night

    We eat a organic diet for the most part. We have tried every diet in the book to improve our health, weston price, vegan, egg free, dairy free, and the list goes on. Nothing has helped. I am sure that we could tweak out diets but I am not sure what to do.

    Even though our current doctor has some knowledge about the MTHFR mutations, I am concerned about her approach with us. She is very cookie cutter and treats everyone the same. I am concerned about just starting to take the Methyl Guard Plus because of our current level of toxicity. My question is, do you do consults of any kind? Do you have any suggestions for us based on our current known genetic mutations with the MTHFR and HLA-DR? I am certain that the MTHFR mutations are one of the reasons we are not improving with the standard CIRS (Shoemaker) treatment.

    Daily I feel like my body is starving for certain nutrients but I do not know which ones. We are currently living with a relative and seeking ERMI rated 2 or less housing.

  101. Leslie November 4, 2013 at 3:18 am # Reply

    Hi Dr. Ben,
    I am 30 years old. I have been a type one diabetic for almost 19 years. I had gastric sleeve two years ago. I am taking 2 multi vitamins gummy, 4 prenatal gummy, 4 calcium gummy, 1 b complex gummy, 2 fiber gummy, 1 iron supplement, 1 Prilosec, 1 Zyrtec all daily. I also take b-12 injections twice monthly. In 2004 I was diagnosed with factor five liden mutation. I was on birth control and didn’t know I had factor five. I ended up having three pulmonary embolisms. I have two children 6 years old and 4 years old. My husband and I have been trying to get pregnant for 3 years. In 2011 I had a miscarriage without any fertility meds (clomid), in September of 2012 I started taking clomid and in December I miscarried again. I continued to take the clomid and in September of 2013 my doctor told me that I wasn’t going to get pregnant without doing IVF. He has done no blood except to test my progesterone, which was normal. I have a cycle every month and ovulate every month. I recently found a long lost cousin and we got to talking. She also has type 1 diabetes for 17 years now, also has factor five and she tried to get pregnant for two years and had two miscarriages. Her doctor did some tests and they found that she tested positive for both mutations. She went on meds and is now pregnant. I am writing you to see first if this mutation is connected to factor five and second to see if I should be tested?

  102. Frances Wisniowski/ bellagunn November 9, 2013 at 1:31 am # Reply

    Overall the biggest problem with with the current research about MTHFR SNP A1298C is that researchers are focusing on homocystine levels as an indicator of MTHFR dysfunction.

    It is difficult to link A1298C with abnormal homocystine levels, A1298C does not seem to make a difference in fasting homocystine levels and even with the C677T polymorphism homocystine levels can be influenced greatly by environmental factors such as diet and supplementation.

    It is apparent that researchers need to look beyond homocystine levels as an indicator of MTHFR function.

    I am heterozygous for A1298C, my homocystine levels are low normal and I have been told that my mutation does not carry any risk; the problem with that assentation is that I have already developed an expression of disease related to A1298C.

    There are several papers that link MTHFR mutations with an increase in the risk for systemic adverse reactions to the smallpox vaccine.

    The smallpox vaccine is administered by innoculation with live vaccinia virus.

    The vaccinia virus is generally thought to carry a low mutational risk because the virus
    replicates in the cytoplasm of an infected cell not the nucleus, however the
    virus actively suppresses host DNA expression and makes significant changes
    to the physical structure of infected cells.

    Some cells appear to be resistant to infection than others; in particular human mast cells may be one of the cells that are more resilient after vaccinia virus exposure.

    Vaccinia virus complement control protein is secreted by cells that are infected by vaccinia virus. It has been shown that vaccinia virus complement control protein is up taken into uninfected human mast cells via heparin binding.

    Vaccinia virus complement control protein modulates the mast cell signaling in such a way that it shuts down the compliment control pathway; essentially acting as an immunosuppressor to help prolong viral infection.

    Vaccinia virus complement control protein does not generate infectious virons, it simply changes the way the mast cell signals.

    Vaccinia virus also stimulates the body to generate an expansion of c-Kit(hi)Sca-1+Lin- (KSL) blood cell stem cells; cell growth precedes vaccinia virus infection and is a consequence of vaccinia virus growth factor excretion.

    The KSL cells preferentially turn into cells of the lymphoid lineage but there is also an increase in myeloid linage cells. Mast cells are products of the myeloid lineage; the expansion of KSL cells by vaccinia virus growth factor stimulates the release of stem cell growth factor (SCF). SCF acts in synergy with other growth factors, including granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), erythropoietin (Epo), and granulocyte CSF (G-CSF) to stimulate growth of hematopoietic stem/progenitor cells.

    This growth stimulation triggers mast cells to undergo mitosis as the binding of stem cell factor (SCF) to mast cell c-Kit induces activation of several signaling pathways (including Src kinases, mitogen-activated protein (MAP) kinases, c-Jun N-terminal kinases (JNKs), signal transducers and activators of transcription (STATs), and phosphatidylinositol 3 (PI3)- kinase/Akt).

    Mast cells are the only terminally differentiated hematopoietic cells that express the c-Kit receptor and unlike other myeloid lineage cells, mast cells remain capable of mitotic division (the injection of SCF increases mast cell numbers near the site of injection by over 100 times). In addition, SCF promotes mast cell adhesion, migration, proliferation, and survival.

    This all works towards mast cell survival post viral exposure, albeit with altered signaling and structure due to the insertion of foreign viral DNA.

    When a cell that has been infected with viral DNA undergoes mitosis the potential is there for the foreign DNA to be included in the nucleus of the new cells. These mutations are typically remediated by DNA repair processes.

    DNA repair processes are heavily influenced by the effectiveness of the MTHFR gene and its interactions with related enzymes and allosteric inhibitors.

    MTHFR SNP A1298C is in the C-terminal domain that regulates MTHFR activity in response to allosteric inhibitors, particularly S-Adenosyl-L-methionine (SAM).

    SAM is required for cellular growth and repair. Once SAM donates its methyl group to choline, in the formation of creatine, carnitine, DNA, tRNA, norepinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). Under normal circumstances, homocysteine, in the presence of vitamin B6, vitamin B12, and folic acid (SAM’s main cofactors), will eventually be converted back into methionine, SAM, or cysteine, glutathione, and other useful substances.

    However the A1298C mutation in the C-terminal domain of MTHFR shortens the MTHFR gene, reduces its protein availability and impairs the binding of SAM.

    DNA methylation is dictated by an inverse relationship in the ratio between SAM and SAH. Under normal conditions, the binding of SAM to MTHFR leads to an allosteric inhibition of the enzyme, which, in turn, can be cancelled by increasing SAH concentrations.

    An oversupply of SAM simultaneously stimulates CBS-activity and by doing so tends to direct the homocysteine breakdown to the irreversible breakdown through transsulfuration.
    If SAM is unable to bind to MTHFR, the MTHFR gene will have reduced
    enzymatic activity which constituently results in a loss of methylation (both SAM and SAH will be low or relatively static).

    Two consequences of the loss of methylation have been proposed.

    1. Weakening of transcriptional repression in normally silent regions
    of the genome could cause the potentially harmful expression of silenced
    genes, for example those imprinted; but also inserted viral and parasitic

    2. Global demethylation of the cell also affects chromosome stability.

    Furthermore, it has been was shown that up to 10% of genes are aberrantly expressed in hypomethylated fibroblasts and that changes in gene expression (that included growth factor receptors and proteins involved in signal transduction among others) were cell-type specific.

    As previously mentioned; DNA repair genes are also affected by MTHFR driven methylation. Deficiencies of the DNA repair system (epigenetically inactivated DNA repair genes caused by aberrant methylation) result in mutation rates 100-fold greater than normal cells.

    As a consequence of exposure to vaccinia virus compounded with the presence of MTHFR SNP A1298C I have developed a somatic mutation of my mast cell c-KIT/stem cell growth factor receptor.

    This mutation is a transmembrane mutation on exon 11 that causes constituent activation of the c-KIT. C-KIT signaling as previously mentioned before causes mast cell degranulation and mitosis.

    Mast cell degranulation releases a staggering amount of pro inflammatory cytokines (most notably histamine and leukotrienes) and is implicit in the symptoms of allergic response.

    In addition to c-KIT signaling mast cells can also be activated by stress, injury, IG pathways and endogenous/dietary histamine (just to name a few pathways)

    Endogenous histamine and dietary histamine are of special significance with reflex to MTHFR SNPs that effects MTHFR function.

    Without functional MTHFR methylation, homocysteine cannot be converted to methionine.

    MTHFR catalyzes the reduction of methylenetetrahydrofolate to methyltetrahydrofolate. This is the only reaction generating methyltetrahydrofolate in the cell.

    Methionine synthase catalyzes a methyl transfer from methyltetrahydrofolate to homocysteine, generating methionine and tetrahydrofolate.

    Endogenous histidine converts to histamine (by specific L-histidine decarboxylase) or is converted to glutimate by tetrahydrofolate.

    Without adequate tetrahydrofolate greater amounts of serum histamine are created from histidine (less histadine is catabolized into glutamate), this leads to abnormal and dangerously high levels of histamine in the blood and cellular tissues.

    Mast cells degranulate in response to increased histamine levels in addition to degranulating due to constituently active c-KIT.

    Decreased MTHFR methylation also leads to decreased formation of DAO (diamine oxidase, generated via BH4 cycle which is dependant on methylfolate and SAM), which degrades serum histamine (via oxidative deamination).

    Histamine N-methyltranferase also degrades histamine (by N-methylation) specifically implicated in airway response and brain histamine levels (HNMT is active within the cells whereas DOA is active in the blood serum), however this process is also impaired by MTHFR methylation reduction.

    These issues compound each other and quickly generate toxic levels of histamine.

    My mast cell activation disease (transmembrane mutation of mast cell c-KIT) expresses symptomatically as sudden and severe anaphylaxsis without IG moderated allergic response.

    If I knew two years ago that I had the A1298C MTHFR mutation I would have refused the smallpox vaccine. At the time it was administered as a pre-deployment requirement (I am active duty military).

    Within a period of 4 months after vaccination I went from being perfectly healthy to having severe allergic type reactions to everything.

    It would literally take longer to list what I have reacted to than not. Suffice to say I am now a wheat/allium/soy/peanut/nightshade/fermented food free vegan who cannot tolerate food additives and many common household chemicals/ environmental toxins.

    All of this happened while I was in a deployed environment (I also concurrently developed a soft tissue tumor) and if it hadn’t been for my very on top of it flight doc/ surgeon there is a very good chance I would have died from anaphylactic shock as I had no idea what was happening to me.

    Even so it has been touch and go; the general medical community know next to nothing about these issues and I have been forced to do my own research to ensure my continued survival.

    My research shows the the DOD is aware of the risk that MTHFR mutations pose to military members who are required to have the smallpox vaccine (vaccines in general carry quite a bit of risk, the smallpox vaccine just happens to be on that has been actively researched in conjunction with MTHFR mutation); it has been suggested that mutational analysis pre-screening be done prior to administering the vaccine but the cost has been deemed prohibitive.

    Now I am stuck with a progressive, potentially oconogenic disease. The likelihood that the military doctors will accept the vaccinia virus as causality of my disease expression is slim to none. To do so would go against the paradigm in such a way as to expose the DOD to unacceptable risk; doesn’t mean I’m not going to try to prove it, to do otherwise is tantamount to giving up which is a complete anathema to me, but I do recognize the extreme uphill battle ahead.

    I am currently controlling my disease expression by daily dosage of H1, H2 and lukotrine antagonists. I am also taking imanitab to control my mutant c-KIT expression. These medications have given me some small measure of normalcy in the sense that I am not experiencing severe anaphylaxsis daily, but I still have symptoms and must carefully control my exposure to potential mast cells triggers.

    I would like to be able to support my methylation pathways but this seems to very tricky to do without a Dr’s supervision and as I am still active duty I find it difficult to find doctors who are willing to look into less conventional medicines.

    I have had quite the fight with my hematologist/ oncologist as it is; his mentality from the beginning was that you either have mastocytosis or you don’t, as I do not have the D816V c-kit mutation I don’t technically have mastocytosis, that doesn’t mean that I don’t have mastocytosis….. if you get my drift. The WHO criteria needs to be expanded in my opinion, but anyway I digress.

    In the meantime, if I continue with the imanitab I may eventually “outgrow” my mutant mast cell population, which would then leave me with only the MTHFR mutation to deal with. But that is not a potential outcome for quite a long time (mast cells are very long lived), so until then I console myself with research and the day to day minutia of finding something to eat that won’t kill me.

    Thanks for reading to the end, comments and insight are as always, welcome.

  103. Maria November 9, 2013 at 3:34 am # Reply

    What do you use for the BH4 supplementation?

  104. Melanie November 11, 2013 at 7:14 am # Reply

    I am homozygous 1298, had a golf ball size meningioma in a location that only occurs 2% of the time. I had it fully removed and within7 months it recurred. Always digging deeper for ways to lessen my chances for another recurrence. Also, since I have lots of CT`s and MRI`s, how can I best detox my body? Thank you

  105. Sara November 11, 2013 at 5:59 pm # Reply

    Dr. Lynch,

    I have found your site, protocols, and information on MTHFR extremely helpful, but according to the summary at the end of this article I shouldn’t find you helpful at all and if I refer my PCP to this site, he will also think that I shouldn’t bother worrying about MTHFR at all.

    My son has had a long history of health issues. Last spring, he was identified as having the MTHFR A1298C (one copy) by an Integrative Medicine doctor. He was identified after a NutrEval revealed extreme need for all the B vitamins, vitamin C, etc. but high levels of amino acids in his urine. My doctor began him on activated B vitamins as well as co-factors. I began researching everything I could about this genetic condition and have been amazed by how many people are out there suffering similar problems as my son, even some of the kiddos described in the comments section of this post who also only have the A1298C.

    My PCP has been very open to the treatments the Integrative Medicine doc is using and has been very open to learning all about MTHFR, especially since my son seems to be improving.

    I regret now that I referred my PCP to this site because this article lists the problems my son has but states they are only a valid MTHFR problem if combined with C677 and puts my son’s treatments at risk of disapproval. By reading deeply through all of these 250+ posts, I still grew very confused about where you stand on whether I should bother using these protocols or not. I gathered your most recent thoughts are that A1298C does not cause any problems, but there must be some other breakdown in the methylation cycle working in conjunction with the A1298C. Forgive me if that is not your view, but it’s buried in 250+ comments. I have sent off for a more complete look at my son’s genetics via 23andme because of this view, but it leaves me confused as to why the MTHFR protocols on activated Bs are working for my son. I seriously doubt my PCP will bother reading through all 250+ posts to figure out whether A1298C actually causes problems, how it causes problems, etc.

    Over months following the identification of my son’s A1298C, my son has started improving in ways I had been told (by mainstream docs) he would never improve so I won’t stop using the activated Bs. And, as I said, I am getting the genetic testing to further investigate his methylation pathways.

    I don’t know if you’ve updated the main article in the last 2 years, but I beg you to write a less confusing article on A1298C that clarifies or fleshes out how people with A1298C but no C677 can have so many of the methylation issues. Or, if you really truly believe that I shouldn’t waste my time giving my son the MTHFR protocol, could you just clarify that all of the symptoms/disorders associated with A1298C are actually just manifestation of the C677. Your article starts out that you think more research is needed for heterozygous A1298C and that you think there are problems, so I felt extremely discouraged and confused as I read the summary at the end.

    By the way, my son has been off gluten since age 8. When we reintroduce it, it sets off severe vomiting spells. So far he has not tested positive for any form of gluten intolerance in any test known to mankind. When I took him off gluten, it was still considered a futile attempt/waste of money by most of my doctors, but my son went through his first major improvements when we took him off of it.

    I will always treat my son with results based healthcare and if your protocol or Freddd’s protocol or Yasko’s protocol or combinations of anybody’s protocol works for my son, I will continue whether you think I actually should or not. I hope that if enough moms give the MTHFR protocols a try and find they work, then research and acceptance will follow, just as we moms forced the research and acceptance of gluten intolerance. ;)

    My personal feeling is that A1298C is just a small, insignificant dip in methylation ability, but if something overburdens the cycle such as the nitrous oxide used at my son’s birth, or the reflux meds stripping him of B12, or folic acid supplemented in the food supply… maybe that’s the reason the A1298C process gets clogged up so that the individual has moderate to major problems. So in our world of constant overburden, A1298C IS harmful, just not as harmful as C677. Potentially, A1298C is the easiest to fix which makes it the most tragic to ignore.

    I will still continue to use your site, even if my son’s A1298C is an unwanted guest, but I’d really like to see an article I can feel comfortable linking back to or referring friends to.

    • Dr Lynch November 12, 2013 at 2:39 am # Reply

      Sara –

      There are many more genes in the body than just MTHFR. The A1298C MTHFR variant does not seem to be such an issue.

      In your statement above, you mentioned nitrous oxide use. Nitrous oxide is bad for anyone who is low in B12 or methylfolate – and that means even if one has no variants of MTHFR, it will still be an issue for them.

      The biggest issue I see with people is many blame their genetics on their symptoms – it is not that simple.

      Nitrous oxide inhibits a major gene in the body (MTR/MTRR) and if one is b12 or methylfolate deficient, there will be issues – regardless if having a MTHFR variant. Those with MTHFR variants are more at risk, yes – but also so are those with a diet low in uncooked leafy greens, poor lifestyle choices and toxic environments (stuck in traffic daily, new carpet in office, scented perfumes, GMO’s, etc)

      As I tell doctors, ‘Treat the patient, not the SNP’

      • Sara November 13, 2013 at 12:30 am # Reply

        Thank you for your reply, Dr. Lynch, and your patience.

        I’m struggling with understanding what’s behind what is working and hoping to find easy to understand information that I can use to educate the people in my son’s life. The tests revealed major deficiencies and the only explanation so far is the A1298C. It will be very interesting to see if his 23andme reveals an MTR/MTRR. I don’t believe that the A1298C (or other potetial methylation genes) caused his health issues so much as they made him inefficient at clearing toxins and fighting infections. To me, that makes the variant harmful.

        Forgive me for haggling over minor semantics. I just see my son finally making strides in his health. I am terrified that someone will invalidate what little diagnosis we have and take away the treatment.

        Thank you for your time!

      • Sara December 1, 2013 at 4:51 pm # Reply

        Okay, Dr Lynch, I have to give credit where credit is due. You called it!

        I got the results back from more extensive testing. He was heterozygous for the MTR and for 7 out of 10 MTRR mutations & 7 out of 14 tested MTHFR variants. Also, homozygous, perhaps more importantly, for the MTHFS, VDR, and 4 of the NDUF7 mutations, and 2 COMT mutations. There were other issues, too, but wanted to say I get now why its important to look at the whole picture, especially with methylation genes.

        • Dr Lynch December 3, 2013 at 7:44 am # Reply

          Hey Sara –

          Yep – there is more than one gene in the human body ;)

          MTHFR is a big one – but there are plenty of others that affect how we experience life in a big way. Glad you found this out!

    • Steve Thompson November 12, 2013 at 6:36 am # Reply

      Hi Sara.

      A lot of people, including doctors, look at MTHFR in isolation. The doctor who found my MTHFR defect didn’t look any further and prescribed a particular supplement with high doses of some B vitamins. It made me very sick, very quickly. His one-size-fits-all approach did not work for me.

      To cut a long story short, I did further genetic testing around methylation, and with many, many months of reading and trialling different supplements. it seems to me that my MTHFR defect is not such a big problem by itself. (I have two copies of A1298C, as well as defects in nine other methylation related genes/enzymes.) It now looks as if the defects in my MTRR gene/enzyme are far more significant for me than the MTHFR defect. I have high Red Blood Cell Folate and high Homocysteine and even tiny doses of methyl-folate make me worse. I’m now, just in the last few days, started targeting supplements at the MTRR defect.

      Your son’s 23andme results will shed some light on what’s happening in the rest of his methylation-related biochemistry. But you’ll need to do lots of reading, and remember to be very sceptical about everything you read on the internet.

      • Sara November 13, 2013 at 1:04 am # Reply

        Hi Steve,

        I’m sorry to hear of your initial treatment but glad to hear you’re finding effective supplements now. The treatment my I.M.doc is using has worked well, but he began him low and we’ve ti trated up. He also has us start co factors one at a time to know whether they hurt or help. This has been effective since we had a few bad reactions. Also, there was a problem this week with the pharmacy so my son didn’t get one of his B 12 shots and there was a noticeable drop in his energy and he got sick. At this point, my son is on really high doses of the Bs and is doing better than he has in 2 years. I just want to have concrete reasons why so that he doesn’t lose the help. I am anxious to get the 23andme results now in order to get a more complete understanding, but I don’t know how to use those results to communicate to our PCP how essential the methylation treatment protocol is to my son, especially when the information out here on the internet is so varied. And if research has invalidated A1298C then how do I know what research is out there on the lesser known SNPs?

        • Frances Wisniowski/ bellagunn November 13, 2013 at 3:16 am # Reply

          In what way has research invalidated the effects of A1298C?

          “The MTHFR-A1298C polymorphism is located on exon 7 which codes for the Cterminal regulatory region. The observed effect of the A1298C polymorphism might be due to its location, since this region is known to regulate enzyme activity depending on adenosylmethionine levels. Our suggestion is that this
          polymorphism may lead to imbalances in MTHFR reactivity on cell damages.”

          “The data suggest that there might be a general effect of the MTHFR-A1298C polymorphism on drug-induced cell toxicity in the liver.”

          “This effect may be a consequence of inadequate cell reactivity (lack of DNA-repair) to toxic influences. Such an imbalance could lead to a tendency for apoptosis of the injured cells and in consequence to increased toxicity.”

          (ANTICANCER RESEARCH 27: 4377-4380 (2007) Pharmacogenetic Analysis of Liver Toxicity after Busulfan/Cyclophosphamide-based Allogeneic Hematopoietic Stem Cell Transplantation, Eray Goekkurt Et al.)

  106. AnonymousND November 16, 2013 at 7:22 pm # Reply

    I am a 4th year ND student and have been very interested in MTHFR because of the many patients we have had come through that have the defect. The symptoms are so varied from patient to patient that it’s mind-boggling. I did the 23 and me genetic testing mostly to see if the results are applicable for my patients in my future practice. I was absolutely amazed to find out that I am homozygous A1298C. I have never had problems with NT’s, anxiety, depression, chronic fatigue or most of the other symptoms of the defect. What I do have is a struggle with is my weight which has worsened in medical school. I have just attributed this (as has everyone else) to the high amount of stress in medical school, adrenal fatigue and excessive cortisol release. I am now wondering if my struggle with my weight could also be related to this methylation defect. Is this something you have found in your research? I do also have some brain fog at times, but I attributed this to the immense amount of information I am constantly trying to assimilate as well as my age. It’s nice to know that I might be able to get rid of the brain fog with MTHF!

  107. Sheri November 21, 2013 at 4:44 am # Reply

    My sister in law has MS with A1298C, could there be a connection?
    She has 24/7 vertigo.

    • Sheri December 9, 2013 at 2:02 am # Reply

      After a year of my SIL having vertigo, she has finally found some relief with low dose naltrexone LDN Hurray! she is also on PoDiaPn for the A1298C.
      Once I get all my tests back I will know what other mutations I have beside the 677T hetro

  108. Jessica November 22, 2013 at 2:30 am # Reply

    Thank you for the information, both my sisters just tested positive for homozygous type. I am scared.

  109. Gillian November 30, 2013 at 12:34 am # Reply

    I need some guidance please. I was diagnosed positive MTHFR. The hematologist states I do not need treatment. Yet, I display many health issues associated with this gene mutation. Here are the results, hopefully someone can tell me if this is serious or not.
    Homozygote for the NM_005957.4:c.1286A>C aka1298A>C polymorphism in the MTHFR gene. Two copies of the c.1286A>C were detected in the MTHFR gene. Normal for the NM_005957.4:c665C>T aka 677C>T polymorphism in the MTHFR.
    Does this mean I have just the 1286 gene mutation? Or do I have that as well as the 677 mutation as well? My sister is also positive and is being treated. Yet I have the same thing and my doctor is saying I am fine. Yet I am chronically fatigued, have muscle and joint pain, short term memory issues, insomnia (go figure I am exhausted and can’t sleep) occasional depression, high blood pressure, and other symptoms, and the doctors say I am fine.
    Also, I am B12 deficient and have been receiving monthly shots for the past 18 months. This has stopped the hallucinations I was having, and I no longer fall asleep at work each day (I work at an elementary school), but I still feel awful every day and my regular doctor stated I should be feeling pretty great at this point.
    If anyone has any suggestions please feel free to comment. I am feeling really lost and confused and do not know how to precede. Thanks, Gillian

    • Teresa November 30, 2013 at 11:18 pm # Reply

      Be sure and have your thyroid checked out completely for low functioning. Make sure your doctor does a total T3 and T4 not just the inaccurate TSH test. Some of your symptoms are like mine when I am low on thyroid hormone levels. Hope this helps.

  110. Deb Roby December 3, 2013 at 7:22 pm # Reply

    I have a homogenous 1298variant, but no variant at 677.

    My doctor had me on Deplin, but a test shows that my body still is not utilizing it. Suffering from high inflammation levels, high blood pressure, high blood sugar. Classic metabolic syndrome. How much can be explained by the MTHFR gene!

    A quick question: does the high ammonia levels explain why I sometimes seem to smell like skunk?

  111. Amelia December 16, 2013 at 6:39 am # Reply

    Hi Dr Ben,

    I have a homozygous 1298 mutation. My almost 2 year old son is so short he is not even on the growth chart, so less than 1 percentile. He also has horrible tooth decay, which we have been working with a naturopath to heal naturally but it is continuing to get worse. I am worried that he will soon have to go under anesthesia to treat his rotting teeth.

    He has constipation despite taking a good probiotic, and still hardly eats any solid foods, very much prefers breastmilk. He is a pretty fussy and angry little guy, sometimes happy but I think he is pretty unhappy on a frequent basis.

    We can’t find a doctor who treats children with the mthfr defects in our area. hoping you will have some advice on where to go from here. Thank you.

    • J December 18, 2013 at 4:57 pm # Reply

      Amelia, your little guy sounds a lot like my son at that age. I am homozygous for 1298. My six year old son has aspergers and adhd. I swear he would still be breastfeeding if I hadn’t weaned him, but weaning him on to solids is when our issues started escalating. We didn’t know about his food sensitivities and solids were making him sick. At age three we started dietary interventions for the whole family and supplements (from a biomed doc) for my son and he has progressed tremendously.

      For those of us who don’t know our whole genetic profile and aren’t 667, Dr. Lynch seems to advise cleaning up our diets and lifestyles first plus supplementing methyl-folate. This has made a huge impact on our family. If you aren’t already, you and your son should try going gluten free and dairy free. Then slowly switch to a whole foods diet. Its has pretty much saved our lives. My heart goes out to you and your family.

      • Dr Lynch December 18, 2013 at 6:40 pm # Reply

        J – thank you for sharing your experiences with Amelia. You are absolutely right in terms of starting with the foundations of diet and lifestyles as both affect our methylation tremendously. I cannot tell you how many times I worked with people’s lifestyle, environment and diet – along with some targeted supplementation – and they pulled out of the slump. There are those who are also still struggling despite the efforts put into lifestyle, diet, environment – but I continue to research why and how to get them to recover.

  112. Jim December 17, 2013 at 1:18 am # Reply

    Just found out I am Heterozygous A1298C and that my Vitamin B6 levels are off the charts at 173.2. Normal range shows 2.1 -21.7 ng/mL. Vitamin B12 level is 1007 and in the normal range. It appears my body is storing B6. It was suggested that I try taking SAM-e to reduce my vitamin B6 levels. Anyone have a thought they want to share?

  113. Jeffrey Philip December 19, 2013 at 5:38 pm # Reply

    I am heterozygous at the A1298C allele. While this was dismissed by my physician who initially did the testing, I can assure you that it is not benign. I suffered from severe fatigue which improved but did not go away with thyroid. I also had elevated homocysteine levels in the 12 range. On a whim I started with a methylfolate product and it was like magic. Naps gone in 48 hours!!!. Just did followup homocysteine testing and am now normal at 6.0. I recommended the same product to my dad who also has lifelong fatigue and elevated homocysteine. Naps gone, no repeat testing yet.

    This is really awesome and the response is so fast that anyone can give it a try even before testing.

  114. Carrie December 23, 2013 at 12:41 am # Reply

    Hi Dr. Ben,
    I recently met with an herbalist because of having symptoms of really low energy, high stress, depressed, foggy brain, highly irritated, low libido, rough pms, skin rashes (seems to be wheat flour), but that isn’t even definitive as I itch at odd times almost everyday… She first said “adrenal fatigue” and as we talked more about my family history, she recommended me get tested for the mthfr mutation. I have homozygous MTHFR A1298C and heterozygous for MTHFR 03 P39P. I also had homozygous for VDR Bsm, MTRR H595Y, MTRR K350A and CBS C699T. And was heterozygous for COMT H62H and COMT V158M…
    Currently I have been prescribed to get off my supplements that have the folic acid and b12 that are inactive forms. And now I am changing to femone plus and methyl folate and methyl b12.
    We are doing a 90 day cleanse right now as well that is complete with parasite herbs, fiber, probiotics and a tea. It is doing it’s job as we can tell. And our diet is great most of the time. We did have a not so good meal this afternoon while out and about and I’m bloated and a bit uncomfortable.
    Do I need to avoid tuarine?
    What else should I be doing to address all these mutations. I’m 29 years old, never had a miscarriage and have 2 little girls (my mom had 12 miscarriages and my sister has had 3 or 4 so far… among a ton of other health problems…)
    Thank you for your time as you reply. I see you have helped so many. What a blessing.

  115. Sara P January 1, 2014 at 8:14 pm # Reply

    Dr Lynch,
    Thanks for all your work!
    Do you have patients with anxiety as the only symptom of Homozygous A1298C MTHFR mutation?
    I recently received results that I have this mutation with normal homocysteine level (7 umol/L) but Vit B12 (707pg/mL) and RBC Folate (956 ng/mL).
    I’ve battled anxiety which lead to this testing. This is the only symptom or sign I have. I ordered the L-5-MTHF 1000 (Provides 1,000 mcg of pure non-racemic l-methylfolate) capsules from Seeking Health in hopes this will help me feel less anxious. Thanks!

  116. Pete January 3, 2014 at 3:59 pm # Reply

    Hi Dr. Ben,

    My 20 year old daughter has been suffering with headaches, memory loss, and concentration issues. She has had numerous MRI’s and CT Scans all of which were normal. She recently underwent neuro psychology testing and was diagnosed with ADD. Despite the ADD, she is doing well in college but feels she has to work so much harder then everyone else to get decent grades. In addition, she has Antiphospolid Syndrome. We did the 23andMe testing and it came back with many variants in the methylation cycle. She is homozygous for A1298C, AGT, DAO, BHMT-08, MTHFD1, all the MTHFR’s except C677T, NOS3, TYMS, and VDRBsm. She is heterozygous for Prothrombin 20210A, ACE, ACAT, ACHY, CBS, COMT, DHFR, GAD1, MTHFD1L, MTRR, PEMT, SHMT2, SLC19A1, and TCN1.

    Many of these are in the methylation cycle. I don’t know how common it is to have so many defects but I’m at a loss as to where to begin with so many defects. My questions are do you believe her signs and symptoms can be related to all of these defects and what do you recommend as next steps ? I’m reluctant to just do trial and error on supplements with so much going on in the methylation cycle.

    thanks in advance,

  117. Paola January 3, 2014 at 4:55 pm # Reply

    Hi Dr. Ben!
    A person that is homocygous, multiple miscarriages and has bradycardia can be related?
    Which is the diet that has to follow?
    Thanks for your help

  118. Jj Zazueta January 3, 2014 at 9:40 pm # Reply

    Hi. I’m trying to get tested for mthfr but dr wants more info. Just learned I hav late stage Lyme and am high metabolizer of pain meds and also was told positive for clotting factor v r506q mutation/ factor v-Leiden . What info can I giv my dr so I can b tested please? I suffered for bout 20 yrs severe bloody nose w clot that could unroll and cover whole palm of hand. All my 3 boys hav chronic bloody noses?? Thank u for ur time.

  119. Kim January 10, 2014 at 5:46 pm # Reply

    Dr. Ben, PLEASE HELP!

    I have had 5 miscarriages. I recently found out I am Homozygous and I am trying to find it what I might be able to do to carry a child to term. I cannot find a Dr anywhere who is educated or trained on how to treat me.

    • Teresa January 11, 2014 at 5:29 am # Reply

      Kim, where are you located?

      • kim January 11, 2014 at 2:17 pm # Reply

        Asheville, North Carolina

        • Teresa January 11, 2014 at 9:54 pm # Reply

          Kim, Here is a doctor listed under Dr. Lynch’s list of psycisians attending one of his conferences:

          North Carolina

          Marie Andersson, DC
          Sage Wellness Group
          Hendersonville, NC

          • Kim January 17, 2014 at 4:37 pm #

            Thank you. I am aware of her. Unfortunately she is a Chiropractor and cannot prescribe meds. I have to see a fertility specialist to get pregnant since I can only get pregnant through invitro. I am uncertain if I need to take a blood thinner to maintain the pregnancy. It seems at about 8 weeks gestation I loose the baby. No one can figure out why and I cannot find a fertility specialist who is educated about MTHFR.

  120. Joanna January 13, 2014 at 4:45 pm # Reply

    Back in 2008 I was diagnosed with two mutations C677T/A1298C . My cardiologist but me on warfarin but after months of trying unsuccessfully to get my levels balanced and worry about a possible blood clot in my lungs I was sent to an oncologist who also specializes in blood disorders and diseases. He took me off the warfarin and told me that it was protocol to wait until I had my first blood clot before placing me on blood thinners due to the risk of the blood thinners them self. My concern is that the first clot could be the last. Your article caught my attention as I have been diagnosed with Colitis, Fibromyalgia, Chronic fatigue syndrome, Parathyroid issues, My vitamin D levels are at 6 unless i take 50,000 iu a week, I take potassium and calcium to help with the parathyroid issue. I deal with constant muscle pain and memory issues which affect my ability to do my job well. I just want to get to the bottom of this and find a doctor who will help me get this condition under control so i can get back to enjoying my life to the fullest.

    • Joanna January 13, 2014 at 4:47 pm # Reply

      I forgot to mention i live near Canton Ohio if anyone has a doctor recommendation.

    • Teresa January 16, 2014 at 2:05 am # Reply

      Joanna you haven’t by any chance taken any fluoroquinolone antibiotics at the time your muscle pain started? Like Cipro, Levaquin, or other related drugs, because this family of anitbiotics can cause a multitude of problems in some people. The most frequent problem is tendonitis or rupture of tendons.

      • Joanna January 16, 2014 at 12:06 pm # Reply

        Due to having recurrent kidney stones and kidney infections I have taken Cipro off and on for years. The first time I had the muscle pain and spasms was back in 2000 when I had meningitis. I have had this problem since then, The best way i can describe what happens is it is like having an epileptic seizure(my dad had these) only unlike and epileptic seizure I can carry on a conversation and am fully alert the whole time. My Cardiologist thought I had MS so he did tests and found that I had the two mutations I listed above.

        • Teresa January 17, 2014 at 3:06 am # Reply

          Please be careful with this group of antibiotics as some people have become permanently disabled using them just once. Debilitating pain, heart paps, tendon ruptures, confusion, nerve damage etc. etc. etc. I wouldn’t take another one of these groups unless I was going to die. They are too risky. One round can be okay for some people but then taking them them again later can cause bad things to happen to ones body. Scary, scary antibiotics.

  121. Larisa January 14, 2014 at 5:41 pm # Reply

    Dr Ben,
    I just recently found out I am homozygous 1298. I have been experiencing muscle pain, brain fog, depression, malabsorption, fatigue, etc for 6 months and am so glad my NP thought to test me for MTHFR as it was a mystery to everyone else I saw. I am going to see a specialist to treat the MTHFR, I am waiting for my first appointment in a few weeks.

    I am wondering what are additional mutations or labs I should get tested for that would be helpful for my doctor? I am nervous about starting treatment as I’ve read it can get tricky getting started.

    Thank you so much for your time and the work you have put into this website, it has been incredibly helpful in a time of so much distress and confusion. Im sure the rest of the community agrees as well.
    P.S: I met and spoke with Becky Andrews, she is wonderful but does not take insurance. If things do not go well with the other doc I might have to go see her :)

  122. Eliza Matas January 15, 2014 at 11:13 am # Reply

    I recently had a blood test that indicated I have the A1298C mutation.
    My blood tests also indicated I had elvated Homocystiene levels but no C677T glitch.

    I’m wondering if this is the cause of my anemia, pcos and depression.

  123. Carrie January 15, 2014 at 10:39 pm # Reply

    Hi Dr. Ben,
    I recently met with an herbalist because of having symptoms of really low energy, high stress, depressed, foggy brain, highly irritated, low libido, rough pms, skin rashes (seems to be wheat flour), but that isn’t even definitive as I itch at odd times almost everyday… She first said “adrenal fatigue” and as we talked more about my family history, she recommended me get tested for the mthfr mutation. I have homozygous MTHFR A1298C and heterozygous for MTHFR 03 P39P. I also had homozygous for VDR Bsm, MTRR H595Y, MTRR K350A and CBS C699T. And was heterozygous for COMT H62H and COMT V158M…
    Currently I have been prescribed to get off my supplements that have the folic acid and b12 that are inactive forms. And now I am changing to femone plus and methyl folate and methyl b12.
    We are doing a 90 day cleanse right now as well that is complete with parasite herbs, fiber, probiotics and a tea. It is doing it’s job as we can tell. And our diet is great most of the time. We did have a not so good meal this afternoon while out and about and I’m bloated and a bit uncomfortable.
    Do I need to avoid tuarine?
    What else should I be doing to address all these mutations. I’m 29 years old, never had a miscarriage and have 2 little girls (my mom had 12 miscarriages and my sister has had 3 or 4 so far… among a ton of other health problems…)
    Thank you for your time as you reply. I see you have helped so many. What a blessing.

  124. Nancy January 17, 2014 at 2:56 pm # Reply

    Hi Dr. Ben,
    I recently took the 23and me test to get better answers about my children’s health and found out I have Compound Heterozygous. I am wondering specifically if you have come across other patients who have vitiligo and/or PANDAS and MTHFR or if this might be separate issues or PANDAS symptoms not really PANDAS but caused by MTHFR? Incidentally, my kids are not vaccinated. Any help appreciated.

    Thank you for your very informative website.

    • Susan January 26, 2014 at 2:36 pm # Reply

      Hello Nancy, I wanted to mention, both my children have PANDAS and also have MTHFR mutations. One daughter is compound heterozygous and the other is homozygous 1298c. We also have lyme disease. We started the MTHFR protocols about 6 months ago and are still working towards seeing the benefits. My homozygous daughter I think may be doing very much better regarding the PANDAS and Lyme symptoms.

  125. Heidi January 19, 2014 at 3:13 am # Reply

    I have read a few articles about your reseach. I was looking for a specialist in the Midwest – Nebraska surrounding area. I have been having severe mood swings anxiety/depression along with worsening hypothyroid problems and severe acid indigestion/gastric pain.. I have in the removed gluten and dairy from my diet in the last week and has seemed to help with the indigestion/pain but still really concerned about my lack of energy and depression. I also have slowly started L-methylfolate and active vitamin B-6 and B-12 to my supplements. I was wondering how long i can expect to feel this depressed or anxiety over nothing. I am still waiting to see a hematologist to see about a medication called metanX and draw some levels even though my type of mutation doesn’t seem to have elevated homocystine. I am wondering what my folate level is and maybe check for a build up of heavy metals.

    I just want to feel like myself again. I think my husband is getting scared I’m going to be this woman I have turned into forever…i hope not. Any insite would be wonderful plus we are trying to conceive now and have been trying since July with no success.

    Heidi Taylor RN, BSN
    30 year old homozygous a1298c
    Omaha, Nebraska

  126. Rachael January 27, 2014 at 3:28 am # Reply

    I was just diagnosed with homozygous 1298 and started on deplin 7.5mg which seemed to have no effect. My dr then increased the dose to 15mg. I feel nauseated, anxious and achey. I am a PA and have never heard of this medicine or mutation, therefore I began to research and found this site…I am now pretty freaked out to be quite honest. The only reason I was even tested was because I have started having some increased anxiety around my cycles. I have struggled with depression in the past after my mom passed away suddenly 4 years ago…i do have migraines which just started this year as well. To be honest, much of this information makes perfect sense when you study the methylation process but I am afraid that my dr is not as educated on the supplements, methylation process, detoxing, etc…I will be looking for someone with more experience with this but in the meantime, is this too much deplin without being worked up further? The only labs she did was a CBC, CMP, TSH, Lipids and MTHFR, all of Which were normal except for the MTHFR. Any help would be greatly appreciated! Thank you

    • Elizabeth January 27, 2014 at 5:00 pm # Reply

      Reading info at this site will help–seems that your doc was not being very careful. Could be you can only handle about 10 percent that much methylfolate, which is the case for many of us here–depends on other mutations and things. Scary that the doc would double such a high amount w/o looking more carefully. Hope you find good info here in the posts by Dr. Lynch and from others’ comments.

  127. Connie January 27, 2014 at 9:44 pm # Reply

    Is it possible to determine if I have A1298C MTHFR or C677T MTHFR by looking at results from a DNA test taken for genealogical purposes?

    • Elizabeth January 29, 2014 at 11:59 am # Reply

      If it’s from 23andme, you can go to wheel at top of your 23andme page and download raw data; then upload raw data at (com?) to find out, and you’ll get info on a number of SNPs besides those two.

  128. Brian Harkness January 28, 2014 at 1:37 pm # Reply

    Dr Lynch,

    are research references available giving details of the 1289C mutation, and it’s impact on BH4?

    • Brian Harkness January 28, 2014 at 2:02 pm # Reply

      also, if I am understanding this right, the reaction is
      BH2 + 5-MTHF + SAM = BH4
      Is that correct?

  129. Rocket January 29, 2014 at 3:50 pm # Reply

    Can you advise re. A person with a diagnosis of ADHD and low histamine (over methylator), recommended supplements folic acid and b12 and niacin, also prescribed ritalin independently. Should the supplements be the methyl forms or should they be avoided because of the low histamine, also what about the Ritalin, would this not exacerbate the overmethylation, very confused!

  130. Susan January 29, 2014 at 5:23 pm # Reply

    I am homozygous for A1298. I am recently pregnant (8weeks). My first pregnancy I took folgard and baby aspirin and have a healthy 2 year old. My OB recommended I take Neevo DHA this time around (methylfolate etc) and since I have begun taking it I have started bleeding. There seems to be no effect on the fetus, but given the proximity of when I started taking the new vitamins and the symptoms I can help but think there may be a correlation. Should I keep taking the methylfolate. Is there any chance that the methylfolate are causing my new symptoms? There seems to be little information about the A129 and how to treat it, and I was hoping I may find an answer her.

  131. Honor Murphy January 31, 2014 at 1:09 am # Reply

    Hello, I just found out my 21 year old has MTHFR 1298c homozygous. She had thyroid cancer less than a year ago. Both sides were involved and she also had it in 15 lymph nodes on the rt side around the thyroid. We recently started working with a functional medicine MD in Kissimmee Florida and he had this test ordered for her. As I am looking over your site I see some real things coming out that she also has struggled with besides cancer. Mostly in the cognitive and emotional areas, ADHD and problems with her emotions and nerves, irregular periods and recent skin problems acne. she is a remarkable girl despite these difficulties competing on a DI college soccer team and finishing college this May on time. I know she would like to improve and of course prevent any further illness due to this problems.

    I have three questions, 1— we have 6 other children. I am assuming they all should be tested. Is there any other things that should be looked at while we test for this?.

    2—- What do you recommend our next step is for our daughter- since we found all this information out she is on Xymogen OTC optimag, zymogenActive Nutrients which has only 200mcg of folate ( is that enough?), PHP Seleno Meth Iodine, sonTheamine by dr, choice, Prothera vitamin C 1,000mg. After reading all this information I am wondering if she should see someone who specializes more with this problem??? We live in Florida and its not too big a state for us to travel but she lives in Jacksonville and we live in Melbourne.

    3- Is it possible my husband also has the same condition and is not just heterozygous or I guess just a carrier so to speak???? He had prostate CA at 46 . I realize that we both have to at least be carriers . He has improved in so many ways since seeing our new MD however of course we want to do anything we can to prevent further chances of a return of cancer.

  132. Bridget Q February 3, 2014 at 3:22 pm # Reply

    I have 2 copies of A1298C and am 35 years old. I had a TIA during my last pregnancy which lead to testing that showed an aneurysm that I have had clipped. This is when I was diagnosed around the end of ’06 beginning of ’07 because my half sister has two copies they decided that I had to be tested. I have had IBS symptoms since I was very young. I have suffered from migraines since I was a teenager. Anxiety has been a big problem and depression off and on. I have confirmed osteoarthritis in both shoulders and my spine. My doc suspects fibromyalgia if I can ever get into a rheumatologist. I do suffer from chronic pain and fatigue, I am always tired but had trouble getting to sleep until my doc added ellivil with the clonapin I was taking. I am currently scheduled for a GI doc to scope me top and bottom for family history of ulcerative colitis and my own history of hemorrhoids that bleed occasionally, and have a referral to see a hematologist for blood work at my neurologists request. Do you think this could all possibly be linked to my mutation? What blood tests should I ask for if the hematologist is not familiar with the disorder? The neurologist wants to try giving me high doses of B vitamins to help with my migraines but wants to make sure it would be OK to do that first. I feel like I have been lost in the system having to have surgery on both shoulders last year when I originally complained of problems that could have been fixed with physical therapy 4 years prior. I need to know what to say to these people to get to a point where I don’t feel disabled with crippling pain a norm for me and my anxiety getting to the point of paralyzing me because I just don’t know where to start. Please help me in any way you can with the knowledge I need to take with me to my appointments.

    Bridget Q

    • Brian Harkness February 3, 2014 at 10:00 pm # Reply


      the usual pattern with Fibromylagia (and its sister disease Chronic Fatigue Syndrome) is that there is some disruption to more than one hormone. The pattern varies with both length of disease and disease state.

      The active form of Vitamin D is often below ‘optimal’. Cortisol,

      Thyroid Hormones, Testosterone are often abnormal but may be both low and high. They are very difficult for a doctor to interpret unless he specialises in the disease.

      Jacob Titelbaum’s book ‘Fatigue to Fantastic’ covers this in detail.

      The extent to which they are altered is also often more subtle than more doctors would recognise.

      • Bridget July 29, 2014 at 2:00 pm # Reply

        Thank you Brian,

        My vitamin D levels are low. My cortisol and thyroid hormone levels are being tested because my thyroid stimulating hormones are elevated and my thyroid and lymph nodes are swollen. Hashimoto’s disease runs in my family (my type 1 diabetic aunt has it and both her daughters have antibody levels through the roof so it will be the end result for them), so I am being tested for that as well. Thank you for your response to my post! It has been a long hard road to get my doc to do blood work, but now I am finally getting results. Maybe someday I will feel good again. Have a great day!

  133. Anne February 5, 2014 at 7:42 pm # Reply

    Hi Dr Ben,
    So glad I found this website!
    I was recently diagnosed with heterozygous A1298C mutation after having my 3rd miscarriage (though I do have a healthy boy who was born between 1st and 2nd miscarriages).
    My doctor prescribed baby aspirin and Folgard to begun taking when we start “trying” again (soon!). She said it didn’t matter if my prenatal vitamins I take have Folic Acid or active methyl folate in them, but I’m weary of this. Do you recommend a certain prenatal vitamin formula or brand? Or other advice to have future healthy pregnancies/babies?
    Thank you!

  134. Michelle shanks February 8, 2014 at 10:42 am # Reply

    I have the Homozygous A1298C, so is my 17 year old son. My husband is about to be tested. My question relates to Low Homocysteine levels.
    I have a very low Homocysteine level. I was listening to your audio and you mentioned the CBS uptake, but said you wouldn’t give details there and then.
    What does it mean for me, having low homocysteine levels, and a possible issue with the CBS uptake?
    Thank you.

  135. terri February 20, 2014 at 11:50 am # Reply

    Hi. Can someone help? I was diagnosed heterozygous for both 677 and 1298. I’m getting confused with my reading. Does that mean I got one from each parent or both from one parent? Also, I’ve been suffering with anxiety and panic attacks daily for 7 years. Stress brought them on each time. I also have pretty bad reflux and lpr symptoms since the summer when I got food poisoning or something. (Lpr is increased mucous that feels like it’s choking when it meets reflux in the mouth, swollen throat, throat spasms, etc). Could these things be from this genetic issue? I’m lactose intolerant so I avoid dairy now.

    • Michelle Shanks February 21, 2014 at 6:30 am # Reply

      hi Terri,
      I have had those throat mucus swellings and initially had no idea what they were in correlation to and thought that it might have been motor neurone starting up. I can tell you now, that i no longer have those symptoms, so there is a good chance that it could be the MTHFR, although I have rid my diet of all wheat, gluten and dairy and sugar ( I feel so much better and it hasn’t been easy, but the benefits have made the struggle worth while and I thoroughly recommend it to anyone who wants to claim their health back )…I also have previously had anxiety in all the worst debilitating forms, so understand what that must feel like for you. You are going to find that you are going to begin to feel a lot better once you get a good protocol for YOU. What works for others, won’t be your magic want, so do as the Dr says, start low, slowly and make sure you only do one thing at a time. You need to find a practitioner that has a good understanding of this, or is prepared to educate themselves to help you. Good luck and …Good Health!

  136. Liz February 21, 2014 at 5:58 am # Reply

    Very interesting reads above…thank you!
    Me – 53 y.o. Female
    Very active, use to be a body builder, very organic, non drinker, smoker
    Graves disease at 13 y.o.
    Goiter the size of a grapefruit removed age 15
    2 miscarriages in my 20’s and 30’s
    March 2013 – 30lbs weigh loss before a major flair up
    Aug 2013- Extreme muscle pain couldn’t move for 1 month
    Brain fog
    Speech/word finding issues
    Excessive Thirst
    Can’t process heavy pain medicine or alcohol or anesthesia
    Mercury Poisoning
    Connective Tissue Disease
    Elevated Thyroid Antibodies

    Only medicines are: T-4 – 135 micrograms, T-3 – 25 micrograms, 10 mg Prednisone for inflammation

    Visited many doctors since September 2013 to find out why I couldn’t move and the muscle pain and inflammation. My last stop was a Rheumatologist in February 2014 who was smart enough to test me for the following:

    ***MTHFR – Compound Heterozygous C677T/A1298c ***

    JUST DIAGNOSED TODAY – the pieces of the puzzle have finally come together!

    My son venous blood clots at age 16 for no apparent reason
    My daughter Rapid Cycle Bi – polar, drug addict, placenta previa with 2nd child
    Father Psoriasis, Obesity, Border line Diabetic
    Sister Epilepsy

    • michelle Shanks February 21, 2014 at 6:10 am # Reply

      wow Liz…thats a handful!
      You can hopefully get to feeling better quickly with the right help.
      Are you in Australia? Sydney?

      • Liz February 21, 2014 at 2:45 pm # Reply

        No Michelle, USA…My active life has come to stand still, I am scheduled to see a hematologist in March to have more blood tests. I plan on having my kids and my grand kids tested. For years all the doctors where testing me for everything except this and I have been treated for all the above, but no one has ever put the pieces together until now. I will make sure I spread the word to my friends who have similar symptoms to ask for this blood test…NO ONE needs to suffer anymore. Supplements are no strangers to me… Looking back at my life I felt the best when I was pregnant…Spirulina and Pre-natal vitamins…Imagine that. Forgot to mention my Mother, Cancer in three different places. Genetically, Eastern European and Native American.

  137. Celia February 26, 2014 at 11:32 pm # Reply

    Dear Dr. Ben, I am 61, “MTHFR – Compound Heterozygous C677T/A1298c”. Was sick for years,months at the time: IBS, nausea, terrible month-long headaches, palpitations, heart pain radiating into arm,, possible chronic Lyme/bartonella, prolonged resp. infections. At some point 2 years ago tried methylation protocol, took B supplements, and after that have high B12(1500) and folic acid levels in blood ( 2 years ago had normal mid-range levels). After last viral infection/bronchitis feel worse than even before: no strength, can’t even stand up without heart rate jumping to 150, and then my heart aches for a while and I am all shaky… So I stay in bed all day. Basic blood tests like chemistry, CBC, sugar, thyroid are OK. Heart docs were always puzzled by my complains, and do not know what causes the problem now. My Eho was always pretty normal, ECG is borderline for years with signs of pericarditis.However most docs do not believe in chronic pericarditis…or “chronic” Lyme for that matter…I recently started DOXY 200 + Rifampin 300×2, but so far no relief… I hope very much that you could recommend some course of actions for me to take. What test should be done and how to do them? Thank you. Celia.

  138. Linda Sharp March 7, 2014 at 12:09 am # Reply

    Hi Dr. Lynch! I have Lyme disease. Tested positive for two A1298C defects and my De. put me on 15mg Deplin. My lifestyle is extremely healthy, but Lyme is prevelant! Comment on defect treatment you might prescribe? Negative for C677T.

  139. Christine March 7, 2014 at 4:18 pm # Reply

    I found out recently that I am Homozygous for A1298C so my ND put me on a 5-MTHF, 1mg supplement made by Thorne Research. I am supposed to take 4 capsules per day. I have been reading a lot online about people taking B-Vitamin supplements in addition to the MTHF supplement. I asked my doctor about this and she said that I did not need the B vitamins because my bloodwork showed that I am not deficient. Do you only need to take the B Vitamins with the MTHF if you are deficient??? Can anyone help me answer this question?

  140. Elizabeth March 7, 2014 at 6:07 pm # Reply

    B12 tests are flawed–you can have adequate amounts in your body that aren’t getting into cells (also, big debate about the “normal” ranges). MMA and homocysteine tests together can better show if there’s a B12 deficiency. But could probably skip more tests, which take time and cost $$–becauseB12 even in high doses is not dangerous, so it doesn’t hurt to supplement–and best to avoid cyanocobalamin form. Some people need adenosylcobalamin, others do well with hydroxycobalamin, others with methylcobalamin. Hydroxycobalamin can be taken later in day w/o risk of disrupting sleep.

    • Terri March 7, 2014 at 10:38 pm # Reply

      How do we know which to take? My doc put me on methylcobalmin.

  141. Sadie March 8, 2014 at 2:43 pm # Reply

    Hi, I appreciate reading all of your posts. I am homozygous mthfr a1298c. I have had 2 miscarriages, a late miscarriage resulting from spina bifida and 1 healthy birth. I am pregnant for the 5th time currently 5 weeks. I am taking Folgard 2.2 twice a day, nexa plus prenatal (I was taking neevo dha with the l-methylfolate) but according to my pharmacy the manufacturer discontinued it, so taking nexa plus. Baby aspirin daily. I read information about methylcoalbamin should I be taking that? Or should I supplement with l methylfolate? My 1 successful pregnancy, I took neevo-dha, folgard 2.2 twice a day, daily baby aspirin, 40mg lovenox injections daily. Doc said lovenox isn’t really recommended for a1298c any longer. Should I supplement with l-methylfolate or methylcoalbamin?

  142. terri March 12, 2014 at 12:30 am # Reply

    Woah woah woah. Wait a minute Dr. Ben. You don’t think 1298 hetero is a big deal. I’m compound hetero 1298/677 and suffer years daily with panic and anxiety, which, if I remember correctly is caused by 1298. So does this mean you believe 1298 isn’t responsible for my mood issues, panic and anxiety and constant congestion and lpr symptoms with throat spasms? After all, these are related to 1298 but I’m heterozygous for both.

    • Dr Lynch March 12, 2014 at 2:29 am # Reply

      hi Terri – there is more than one gene in the body ;) In the beginning, I, too, was guilty of blaming everything on MTHFR; however, we need to understand there are many other genes in the body – not to mention possible disturbances from pathogens, xenobiotics, nutrient deficiencies and so on.

  143. Nena March 17, 2014 at 12:31 am # Reply

    I am •Compound heterozgous A1298C + C677T MTHFR mutation. Would you recommend following the protocol written for C677T heterozygous or •Homozygous C677T as there doesn’t seem to be a protocol for the compound situation. Help greatly appreciated. I have been struggling with Fibromyalgia and Chronic Fatigue among other things and I had no idea these mutations could be contributing to my symptoms. I’m gluten free and vegetarian. I take a curcumin supplement already and Vit D3 and a probiotic but no methyfolate. I’m wondering if the B12 Lozenge With L-5-MTHF would be the place to start?

  144. Diane March 25, 2014 at 7:58 pm # Reply

    Hello Dr.Lynch,

    I recentley diagnosed with homozygous mthfr A1298C oddly from my ear doctor. I have a couple rare inner ear conditions from a combination of barotrauma and Eustachian Tube Dysfunction that cause 24/7 dizziness, brain fog, vision issues and headaches. My Vit B12 is 260, MMA <20, homocysteine 12, Vit D 14, Ferritin 6, T3 Free 2.6, blood glucose 100. I think those were all the abnormal levels. I have had RA since I was 12 and recently was diagnosed with Sjogrens Syndrome . I also have severe GERD. I read that your wife also has severe RA but help you were able to help her by treating the mthfr. Im currently taking Simponi and even that only reduces my symptoms by 70% my Rheumy wants to to add a 2nd med but Ive decided to try to treat the RA with dealing with the mthfr. I just started seeing a specialist for this. Right now we are dealing with the T3, Ferritin, Vit D and BG. She wants to do gut testing before treating the methylation issues. Have people with RA been able to come off the biologics by just treating these mutations? Thanks!!

  145. Stefany Camba March 26, 2014 at 5:01 am # Reply

    Compound heterozygous….don’t know where to start. I also had the gene testing you recommended.

    Tried metafolin and it threw me under the bus…even 1/4 tab. Tried adding Niacin, didn’t see it helping.

  146. Heather March 28, 2014 at 10:24 pm # Reply

    I received lab results that say 2 copies of the same mutation (A1298C/A1298C) were identified. Results for C677T mutation were not identified. What, if any, is the significance of 2 copies of the same gene being identified?

    Thank you,


    • terri March 30, 2014 at 11:46 am # Reply

      Heather, it’s a homozygous polymorphism and it means that gene is functioning at about 10%.

      • Roberto March 30, 2014 at 12:20 pm # Reply

        10% a A1298c homozigous???? Are you kidding??? Where did u get this datas?? And what percentage do u think C677T works , 0%?? All a1298c and c677t homo would be already dead!!

        Anyway Dr Lynch said A1298c is no longer important for him, so i wonder why this website is still online!

        • Susan March 30, 2014 at 5:08 pm # Reply

          Roberto, will you provide the link where Dr. Lynch says A1298C is no longer important to him? I want to verify and see if he indicates homo or hetero.


          • Roberto March 30, 2014 at 7:52 pm #

            Dr Lynch September 24, 2013 at 7:46 pm # Reply
            Lea Ann – my view on A1298C has changed. I do not think it is that significant when it is by itself.
            That said, there are countless other genes in the folate cycle which may causing significant issues – beyond MTHFR – such as MTHFS, TYMS, SHMT, MTHFD1, FOLR, etc.

            Do avoid folic acid. Use only folinic acid and methylfolate. Work with your doctor on these.

            Thank you

          • Susan March 30, 2014 at 10:35 pm #

            Thanks Roberto. I found other references in these posts around the same time as the one you posted about 1298c that might imply Dr. Ben thinks homozygous a1298c is significant but to what extent is not yet known. I feel we need more information and more research to know for sure. I do know my homozygous a1298c daughter has not been as sick as my combined heterozygous daughter but she has had some significant health issues that may or may not be related. It is confusing however and I do wish he would be able to find the time in his busy schedule to update this blog for his current thoughts on a1298c.

          • Roberto April 8, 2014 at 8:35 pm #

            Susan, i must point out that i havent really understood what’s the actual opinion of Dr Ben on A1298c. I noticed he say often “single A1298C MTHFR mutation” as not-significant and maybe he means , when he use the word “single”, in fact “heterozigous”; so it is not clear if he believes that heterozigous is no more a concern or that also homozigous is no more a concern for him.
            I think Dr Ben should explain himself more clearly on this subject.

  147. Elizabeth March 30, 2014 at 3:57 pm # Reply

    Why so hostile, R.?! Pls. let this be a helpful forum where we can exchange questions and information and seek greater understanding and accept imperfection, which comes with a fledgling field that adds new knowledge almost daily and also busy lives.

    • Roberto March 30, 2014 at 4:36 pm # Reply

      because you can’t share wrong and alarming informations to people who are prone to get worried. Dr Linch is the dr here, isn’t it? So let him do his job, and do not give to people exaggerated informations, tnx

  148. Steve Thompson March 30, 2014 at 10:23 pm # Reply

    Hi Dr Ben.

    After nine months of treating my methylation defects, I’ve felt no improvement at all.

    But one thing that I have noticed is that even very small doses of folate, whether from supplements or from green leafy vegetables, seriously disturbs my sleep. I get to sleep ok but wake often and early. I had very similar sleep disturbance many years ago when a doctor experimented with Aurorix, a monoamine oxidase inhibitor, which reduced the activity of my MAO-A enzyme even further.

    My variant methylation SNPs (I’ve left out the others which are ok) are:
    MTHFR A1298C +/+
    MTRR 11 +/-
    MTRR A66G +/+
    MAOA R297R +/+
    CBS C699T +/-
    COMT H62H +/-
    COMT V158M +/-
    VDR Fok Ff
    VDR Taq Tt

    I note that you’re no longer so concerned about the MTHFR A1298C variant.

    I’ve been taking large doses of various forms of B12 to address the MTRR variant.

    I understand that the R297R is a low-activity variant of the MAO-A gene/enzyme, but why would even tiny doses of folate (less than 50mcg) have such a big effect on my sleep?

    And can you suggest any way to enhance/boost MAO-A activity?

    Thanks, Steve.

    • Roberto March 31, 2014 at 1:16 pm # Reply

      Me too i’m having the same issues. I m too A1298C ++, comt +- and maoa +. 1000 mcg of methylb12 and 500 mcg methylfolate send me in overmethylation with immediate nausea, agitation and insomnia. So i avoid it. but right now i’m on 130 mcg methylfolate, about 80-100 mcg folinic, and i take 500 mcg of hydroxy one day and 1000 mcg adenosyl the other day, but i still have sleep disturbs despite i feel no improvements during the day. I can’t take less of 1000 mcg adenosyl because i use the source naturals dibencozide of 8000 mcg each that i split into 8 small pieces,

  149. Nancy April 1, 2014 at 6:16 pm # Reply

    Gee, I really admire all of the people in this forum – all those who are trying to understand why they and their families have chronic health issues. I am in that group – 15 years. I have many of the neurological issues, sleep, pain, etc that resulted in a Dx of CFIDS/FM. I realized that my multiple issues were shared by others in my maternal line. I have led a large support group since 2001. Both me and my daughter have spina bifida occulta. No health issues with these mild anomalies of L-5. but what does it mean? As time went by doctors found more odd structural issues: scoliosis – my son, too, hemagiomas in liver/vertebrae, high arched palate- with underdevelopment of the upper palate, fnger/feet/toe anomalies, cervical ribs, one side of face slightly smaller, and more. In my family various issue come up: congenital heart issues, asthma/allergies, late descent of testicle, redundant colon ( more important than most docs appreciate), poor eyesight, etc.
    Yet, interesting, this side of the family also has great gifts – intellectual, leaders, spiritual gifts, caring/ kindness. hmmm. Found that other support group families were similar.

    My son developed sleep issues, pain, multiple issues after a well- documented infection with EBV at age 4 – 1985.

    So methylation seems important, but also think people must look at body structure- perhaps a result of a methylation issue?? Particularly – neck and pelvis/sacral issues. My life changed when I had a neck/ sacrum injury in 1998. Never recovered.

    Please check out the site of a neurological chiropractor, Michael Flanagan, DC. Also, look at “Chromosome 22q 11.2 deletions” if there are various structural issues in your family, as there are in mine.

    May we all find the healing pathway.

  150. Stefany Camba April 2, 2014 at 12:58 pm # Reply

    Are you doing private consultations? I am compound hetero and have 23 and me test results, but don’t know how to apply them to my symptoms and problems–depression, fibromyalgia, insomnia, memory issues.

  151. Jan April 2, 2014 at 7:03 pm # Reply

    What is protocol for compound heterozygous beyond dietary changes? I have had a 21 year migraine and need HELP. I am not feeling any better – been gluten free, diary free, etc. for months. I am also homozygous for Factor V Leiden. Do I follow basic protocol Part II for MTHFR homozygous?

  152. Kathleen April 2, 2014 at 8:17 pm # Reply

    I just learned that my son (turns two in 3 weeks) is Compound Heterozygous. He has one copy of C677T and one copy of A1298C.
    He has delayed speech and poor balance. He had poor eye contact and several soft signs of autism until we started a gluten-free, casein-free diet in December. Those signs have all disappeared but the speech delay remains.

    What do I need to do to treat this condition? There are no doctors in our area who specialize (or even know about) this condition and how it can impact our son’s life. Aside from reading through every page of this website (that’s on my to-do list!), what else can I do for him? What are the key things I need to be aware of in dealing with MTHFR?
    Do you do phone consultations?
    Thank you!

    • Michelle Shanks April 3, 2014 at 9:06 pm # Reply

      Hi Kathleen,
      Speech delay in boys is, I think, not an uncommon occurrence to start with…little girls just love to chat away and sing etc.
      My son is homozygous A1298C, as am I.
      He had low receptive language disorder that went undiagnosed until he was 5.
      He and I were together constantly without a lot of people around us, so we kind of had our own language and understanding for what he needed.
      He is now 17 and doing brilliantly,He is an excellent drummer, surfer, studies, advanced maths, chemistry, physics and Japanese extension, which he speaks well. who would have thought!
      This is what I want you to know:
      Whilst they are quiet and non responsive vocally, don’t think that they are not taking things in, so keep plying their world with information and stimulation, lots of background noise with taped stories they can turn pages to in their books, story cd’s in the car and learning videos where they have to repeat the speech, like Dora the explorer.
      aside from that, do you know about brain gym?it is the method used to open the pathways in the brain, basically a left brain/right brain activity. ( thats why the drumming is so brilliant) if you google brain gym you will most likely find activities you can implement and make a game of on a daily basis….a kind of physic without the $$$
      Word association is important…so each time you hand your son an item or he picks up a toy, give him the word for that item and encourage him to repeat it and make a big deal about how clever he is…praise praise praise.
      Google, the limbic system…..this is how the brain processes auditory/vocal/visual information and once you understand the correlation you will be able to watch your son to see how he is processing and work with him from that angle…my son was visual…still is, so we had to give lots of visual language cues to aid his learning, so lots of picture books and memory cards. furthermore, we had a doctor who specialised in acupuncture and she was able to use laser acupuncture to treat, basically bringing the left and right sides of the brain into balance, because in his case one side of the brain was firing faster than the other ( not the technical explanation) and his thoughts were too rapid for him to unravel and that was what was hindering him. Some days we would take him for treatment and he couldn’t string two garbled words together and afterwards he would monolog like a poet.
      Fish oil daily, the kind made palatable for kids, reduction or elimination of sugar substances, a whole food diet with lots of greens, beans, broccoli, carrots etc, no junk.
      Knowing what I know now, i would not have worried as much as i did, because the stress i put myself under to make him “perform” put him under pressure.
      Most importantly…probiotics…good gut health…..

      Obviously, not everything at once, and not everything will help….but as you have seen a vast improvement with dietary changes, I would start with a practitioner range of child specific dairy free probiotics,the powdered form, and make sure to eliminate sugar from his diet with the exception of fresh fruit. We didn’t have family around to help, but if you do, get everyone on board with what you are doing and encourage them to use very specific language interactions with him. We had over five years of speech therapy amongst all the other stuff, but you are aware of his challenge much earlier, so with some intervening measures, language specific interactions and dietary changes, you can really make a huge difference to your sons language skills. The general protocol seems to be to start with one thing and monitor. I believe that the probiotics make the most sense and wish I had known to do that for my son right up front.
      Hope some of this information helps you. try not to over worry and don’t feel alone. go and be social with your son and encourage group interactions/playtime so that he can soak up and absorb language for use later on…..( I can’t get my son to shut up now! :))) Hugs!

  153. Ann April 3, 2014 at 3:25 am # Reply

    Hi Kathleen, you might find some additional info on Thinking Moms Revolution website. Many there have had success helping their children with autism including speech. Also any yasko website. She has a forum that gets answers. Good luck

  154. Nancy April 3, 2014 at 4:03 am # Reply

    Stefany, I have the same symptoms you do, and I just am not sure what to think. Is it thyroid ( important to explore) the MTHFR mutation ( I am only heterozygous for the A1298C) or some other enzyme, or is it structure – in particular the upper neck, atlas and occiput issue. Or is it a new virus ??
    I am hoping a naturopath will help me with the MTHFR/enzyme issues and thyroid ( despite normal test results – check out site : Stop the Thyroid Madness)
    Also, check out You Tube – search for Richard van Konynenburg’s lecture on this whole issue of the methylation problems. Will definitely try some form of folate/B12, but want to do this with help of a naturopath.
    Kathleen, my son had speech issues for many years. No one could understand a word he said. In school he was in speech class and the Resource Room ( pull out). He wore the same pair of shorts all year in 4th grade. He could not do any ‘homework’ – was too stressful. We just put NO pressure on him, and gave encouragement. If he needed to stay home from school – fine. Well, about grade 6 everything started to come together. He graduated valedictorian of his large high school class – with many AP courses. Graduated magna cum laude in computer science from UCSB, got a MA degree. Has own business. Just bought a $100,000 sports car, got married, just had a little girl.
    These kids are VERY special and very sensitive – take much patience, kindness. If I had it to do over again, I would have gotten him to the best pediatric osteopath I could for some gentle craniosacral work, and consulted with a nutritionist.

    • Stefany October 12, 2014 at 7:25 pm # Reply

      Nancy…..I have been diagnosed with fibromyalgia more than 22 years ago. I tried methyl folate in very small doses, but it flares my pain so badly I stopped.

  155. SHAUNNE SOLEM April 3, 2014 at 11:03 pm # Reply

    Dr. Lynch,
    I have the combined heterozygous C667T and A1298C. I can’t find a doctor anywhere that can help me. They don’t understand the variant report from 23andme testing and I’m going downhill. I don’t know where to start for supplements and I need to do something ASAP. I have a histamine rash reaction and it doesn’t seem to matter what I eat; no rhyme or reason. Please can you tell me where to start.
    Thank you

  156. Stephanie April 6, 2014 at 1:00 am # Reply

    I have a1298c homozygous, and I have trouble with my invitations levels. Now I am confused.

  157. Pascal April 7, 2014 at 12:50 am # Reply

    Hi everyone,
    I’m 32. We found out I was 1298c homozygous after finding my B12 at 250. Regular doctors and neurologists didn t care about my low b12 as I was still in the “US range” and my other blood test and homocysteine were fine. A naturopathic doctor did care and we did the MTHFR research.
    My symptoms were pins and needles all over the body, global inflammation, trouble of balance and sensation, weird sleep patterms, extreme fatigue muscle pain …
    I ve been getting B12 injections weekly and active Bcomplex for 3 weeks, I m still struggling with chronique fatigue and muscle weakness/inflammation

    • Lynn_M April 7, 2014 at 9:26 pm # Reply

      What kind of injections are you getting? If they’re cyanocobalamin, they won’t help you. You need methylcobalamin or hydroxycobalamin.

      • Pascal April 7, 2014 at 10:52 pm # Reply

        Thank U Lynn, I m getting Methyl cobalamin 5mg/ml.

        I’m also dealing with weird redness that comes and go on my forearms with burning sensations, altered sensations and stiffness which looks like repetitive motion injuries a lot since I spend my days on the computer ( going to see a chiro who also deals with emotion release next week )

        • Lynn_M April 8, 2014 at 1:50 am # Reply

          From the symptoms you described initially, sounds like you might be have been B12 deficient for a while, possibly long enough to cause nerve damage. When you start taking B12, the serum levels go up pretty quickly, but the myelin sheath on the nerves won’t repair as quickly. You have to wait for that to turn over and be replaced before any symptoms related to that will improve. It can be a slow process. And sometimes, as the nerves reawaken, you can get unpleasant symptoms.

          Did you have the redness, burning, and stiffness before you started on the injections and active B, or did they start later?

          • Pascal April 8, 2014 at 1:57 am #

            Thank U for these great informations Lynn.
            I’ve probably had a low B-12 for a very long time, and yes I had all these symptoms before starting B-12 injections.
            I had a nerve conduction test done and nerves were very healthy.
            The good news is I have no more pins and needles and no more trouble of balance, but still some crawling/altered sensations here and there on legs and arms.
            Nobody was able to clearly tell me what the redness was so far, except that it is probably inflammation due to over used wrist/forearms at computer.

    • Roberto April 8, 2014 at 8:28 pm # Reply

      Hi Pascal. When u speak of 250 do u mean pg/ml??Or pmol/L?? 2 years ago i found out i had 154 pg/ml of b12 in blood but never had such disturbs has you refer, and it seems a lot lower than 250… Anyway cyanocobalamin shots rose my serum levels but gave not relief from the possible disturbs (mainly depression, fatigue and sleep issues). Methylcobalamin send me easily in overmethylation so i never followed a real b12 protocol. Just recently i began xydroxy and adenosil…

      • Pascal April 8, 2014 at 9:43 pm # Reply

        Hello Roberto, my b12 was 250 pg/mL

      • Lynn_M April 8, 2014 at 9:57 pm # Reply

        B12 tests measure the combined amount of active cobalamin, transcobalamin, and the inactive form of haptocorrin. It’s possible Roberto had much more of the inactive form than Pascal did, despite Roberto’s higher B12 value.

        MTHFR requires a number of cofactors in addition to methylB12 and methylfolate. Pascal should assure himself he has adequate B1, B2, B3, B5, B6 and adenosylB12.

        • Lynn_M April 8, 2014 at 9:58 pm # Reply

          I meant to say despite Pascal’s higher B12 test level.

          • Pascal April 22, 2014 at 7:09 pm #

            lots of symptoms disappeared with B12 injections and Active Bcomplex, no more pins and needles, no more trouble of balance and weird sleep patterns.

            I m still getting stiffness, weak muscles and trouble of sensations in my arms with inflammation ( after effort and computer typing )

  158. Sharlot April 7, 2014 at 9:22 pm # Reply

    Re: B12 Deficiency. I am heterozygous A1298C. Also have B-12 deficiencies among other things. The most recent test revealed Intrinsic Factor. Diagnosis Pernicious Anemia due to B-12 deficiency. Therefore doc wants me to have high serum levels above lab ranges of b-12 due to intrinsic factor. I get methyl b-12 shots and take sublingual b-12 1000mcg 2xday. She wants me to work up to 5000mcg daily. I also seem to have blood volume issues which affect other things and leave me with a myriad of symptoms.

  159. jennifer thompson April 10, 2014 at 3:57 pm # Reply

    I am confused on test results. One test says patient has normal wild type C677t (C/C) and A1298C (A/A) What does this mean? the comments from the lab says patients with this combination are expected to have normal enzyme activity. Can you explain this?

    I am confused!

    • Lynn_M April 12, 2014 at 5:51 am # Reply

      Those test results mean the patient has neither the C677T mutation nor the A1298C mutation. Wild means unmutated. In this nomenclature, the first letter (C and A, respectively, for the above 2 SNPs), is the unmutated version, and the last letter (T and C, respectively) is the mutated version.

      Nothing to be confused about, it’s all totally straightforward – no mutation means normal enzyme activity.

  160. Corina April 18, 2014 at 7:26 pm # Reply

    I was told today by my PCP that I have one Heterozygous MTHFR A1298C mutation that apparently was found in blood work back in 2009 right before I had my youngest child. I haven’t been to see my PCP since about than, & I only went today because my job had me do a wellness check for our insurance. I didn’t have a reason to go see her I never sick or had a reason to go see her and if I was sick I took someone over the counter for a slight cold etc and I was better in no time. With her telling me this, everything at this time is a blur & I couldn’t even imagine where to begin since I’ve read all the comments/stories above and I don’t have symptoms or came across a severe medical problem. I have more blood work being done for further information but I’m at the point right now just to find out more about it, what can I do, what caused it, how will I be affected, do I need to change anything at this point as far as lifestyle since I’ve been pretty healthy, are my kids affected and what should I do and what do I do from this point going forward for me and my children. At this point, I don’t want it to be something that takes over my life so I can sit here sad and depressed that I was told I have this but before I was told I was 100% I’m not one to fall back, I’m going to take in the info & bounce back even better trying to research and find out what I need to do since none of this makes sense to me. One day at a time, researching…..

    • Tracey April 19, 2014 at 1:04 pm # Reply

      I am actually homozygous for the A1298c defect and have no symptoms myself. My daughter does have symptoms though. We have not tested her but just started giving Thorne’s Methyl Guard and her symptoms have improved greatly. Good luck!

      • Pascal April 22, 2014 at 7:09 pm # Reply

        Hello Tracey, what was your daughter’s symptoms ?

  161. Elizabeth April 19, 2014 at 12:00 pm # Reply

    It sounds like the mutation is not being expressed and so is not a problem for you. It makes sense to know what to watch for if it ever gets turned on, though maybe it never will, which would be great.

    • corina April 19, 2014 at 1:20 pm # Reply

      well like I mentioned I was just told about this yesterday so everything is new and its not that it wasn’t Express or are not worried about it I guess I’m just in my early stages of getting all the information I mean about this type of condition because by the other comments I’m reading above I don’t have any of those symptoms or issues at least at the moment not saying that I want but right now I’m trying to figure out everything I can about this

  162. brenda s April 23, 2014 at 11:47 pm # Reply

    Hi Dr, Lynch,
    I see where many have asked now but there is not really a clear answer that i can find. Can you please give a basic protocol for someone who is hetro/combo as there seems to be many of us struggling with this. Thank you for all you do, Brenda

  163. Bonnie Bronaugh April 24, 2014 at 5:25 am # Reply

    4/23/14 I just found out I’m heterozygous for the A1298C mutation and negative for C677T my mom and both sisters are on Coumadin. Both my mom and older sister have blood clots. My younger sister had a a stroke. My mom has had a blood clot in her leg for 3 years. My older sister has a clot in her calf, behind her knee, multiple ones in her lungs and one by her heart. My Hemotologist told me there’s nothing I should do to prevent clots. Is this right?

  164. Corinn Whann April 29, 2014 at 12:21 am # Reply

    I have a homozygous mutation for A1298C and heterozygous for 677T. I have several autoimmune conditions- Hashimotos, psoriasis, and rhuematoid arthritis , as well as suspected Ehlers Danlos and mental health issues. ‘My homocysteine had been elevated in the past but it was checked a few years ago and it was normal.
    My son has the double heterozygous for both and has thyroid(suspected) schizophrenia, PDD and EDS. We also have cytochrome p450 2PYD null alleles. My md just prescribed me deplin to help with depression.
    Any thoughts or insight?

  165. Carol Stribula April 30, 2014 at 5:19 pm # Reply

    Hello everyone,
    I thought I had posted on here last November or December but apparently not. Our younger son, who is now 18, was diagnosed with Compound Heterozygous C677T and A1298C in October, 2013, and I was also just diagnosed with the same.

    My son has Lyme Disease, and was tested because of extreme fatigue, and has been taking 5-MTHF and two other supplements since without much improvement in his energy levels. I began taking the 5-MTHF supplement soon after he did, and almost immediately noticed a difference in my energy levels. I also switched to a proper multi-vitamin, and after learning of my diagnosis last week, began taking Methyl-Protect as well.

    I feel like with my son, his diagnosis explains a lot: needing lots of sleep (always), frequent cold/allergy symptoms (general immune system issues), speech delay (though he has no problems now and is quite smart; not a genius, but a very thoughtful and insightful learner). I think he still has some articulation issues but not always. He’s trying to eliminate gluten and dairy (though he was never fond of milk anyway — go figure), and reduce sugar. He also plans to begin exercising again next week, despite still feeling pretty lousy from the Lyme Disease, as he knows this will help eliminate toxins from his body. He’s already been accepted into the college of his choice to study elementary education and minor in Christian Leadership; we just hope and pray that he gets healed enough to be successful. He sees a specialist for the Lyme Disease; she was the one who diagnosed his MTHF issues.

    When I think back on my life, I wonder if I always had this condition, or if my genes mutated over time…does anyone know the answer to this question?

    I tended to get sick with horrible colds a few times a year, and do have a slight speech impediment (I never considered myself to have a “stutter” until my first job after nursing school, when my boss’s boss informed me of this). Then I began noticing it. I have to say; I actually think this has improved lately. I’ll have to pay more attention to this.

    I had no trouble becoming pregnant with our older son, who is now 24, and I was an “older” mom — 35 when I became pregnant with him. Four years later, when we began trying to get pregnant again, I had two miscarriages, two years in a row, but we all thought it was my age.

    After learning about my diagnosis last week, I am aware even more acutely of what a miracle baby our younger son is. Amazing!

    As I grew older (I actually turned 61 today), I never had cholesterol issues, because I kept my diet pretty clean. I did start to gain weight, had high blood pressure, and as I reached menopause, began to have insomnia and mood issues.

    To make a long story shorter, two years ago, in March of 2012, I was diagnosed with Hashimoto’s Thyroiditis (my numbers weren’t very high, but high enough) and a few months later my new Integrative Physician also diagnosed me with Adrenal Fatigue, low Vitamin D, low Selenium, low Zinc, and low Magnesium.

    Also in March of 2012 I became aware of essential oils and began using them and essential oil-infused supplements to begin supporting what my Integrative Physician eventually began prescribing. I take Nature-throid, a compounded T-3 preparation, Vitamin D, and 2 different medications for sleep, in addition to using many essential oils and essential-oil infused supplements. One of them supports my immune system and helped me get of the allergy medication I had taken for 9 1/2 years. I was also able to get off the anti-depressant I had taken for several years, a little over a year ago. I should mention that I also began using an essential oil-infused natural Progesterone serum two years ago, and added an essential oil-infused natural Estrogen product a year ago.

    In October, 2013, all of my labs were just about maximized, so in January I began on a weight-loss program, and I’m happy to say that I’ve lost 29.8 pounds as of this morning. My stamina has increased, I can stand for longer periods on my feet before they begin hurting, and my knee issues have mostly disappeared. I still have sleep issues, and still have to take two different medications, and also use essential oils and essential oil-infused supplements to aid in sleep, and sometimes I have to take more medication in the middle of the night, or I just wake up too early, like today.

    I also give my son as many essential oils as he will let me, and he’s recently begun taking Arctic Ruby Oil; not sure if that’s helping yet.

    Anyway, I’m sharing all this because I think it’s important that all of us tell our stories so we can learn from each other.

    By the way, my son has cholesterol and triglyceride issues, as well as thyroid issues (he just takes a compounded T-3 preparation, as well as an essential oil infused supplement), but it’s hard to know if these issues began because of the gene mutations or because of the Lyme Disease.

    • jennifer thompson May 1, 2014 at 2:41 pm # Reply

      You might want to consider the UBI treatments for the lyme disease. We took our 13 year old son to Dr. Hutton in Sedona AZ for a 2 week treatment.

      Read this when you get a chance:

    • Nena May 1, 2014 at 11:08 pm # Reply

      Hi Carol,
      I am also •Compound heterozgous A1298C + C677T MTHFR mutation, have similar symptoms, almost the same age (turned 62 in Oct.) and I’m a retired nurse and an essential oil user. Would love to communicate and share stories. Symptoms seem all over the board here. I really haven’t seen any questions being answered by Dr. Lynch although members provide advice as possible. If you would like to communicate you can find me on facebook and send me a private message. Nena Gallagher. I would love to hear from you. I’m just beginning this journey, my 23andMe results should be available in a few weeks and I’m scheduled with a Functional Medicine Doctor.

  166. Pascal May 1, 2014 at 6:07 pm # Reply

    I ve been treating my 1298c homozygous with B12 injections + Active BComplex for 2 months, I m better but suffering crazy altered sensations and still a bit of pins and needles and tight/weak arms . It get worse if I spend a lot of time at my computer. Does anybody know how to get rid of this ?

    • Pascal May 30, 2014 at 3:16 am # Reply

      A little update for people who would be in the same case as me ( see below for descriptions of my symptoms ).
      The b12 injections+ oral BComplex put me close to be back on track. I still have some inflammations with redness and stiffness in arms when at computer + weird sensations all over the body ( altered sensations ).
      We stopped doing B12 injections and 2 weeks later I was feeling terrible again even if my B12 level is now at 1400 ( was at 250 when symptoms appeared ) so we started B12 injections again and feeling almost well again.

  167. Desiree May 2, 2014 at 2:20 pm # Reply

    I am confused. When a test refers to having a double copy of 677 and 1298 does that mean compound heterozygous? I have been sick since birth complete with heart defect and every doctor ive seen over 25 years has called me a hypochondriac. I stumbled upon this during a routine DNA test on I enlisted in the Army in 2007 and in late 2008 suffered multiple TIA strokes at age 19. I have been relying on both the Army and now the VA to diagnose what is going on but instead they put this down as seizures with TIA. Confused?

  168. Debbie May 5, 2014 at 11:06 am # Reply

    I have written to you quite some time ago. I am very confused. I have two copies of the A1298 mutation, what does that mean? I found this out after having my thyroid removed due to cancer but I have had severe allergies my whole adult life. Started in my early thirties. I had chemical enclosure on a job. Took several years to manifest itself. I almost died from these reactions. Mouth burning, tongue swelling, breathing difficulties. I have lived in a bubble most of my adult life. It was a miracle I came through the surgery as I cannot take ant medications or supplements. Do you have any advice for me. I am really struggling since they took out my thyroid. Constantly symptomatic.

    Thank you,

  169. Matina May 14, 2014 at 1:45 am # Reply

    Hi Dr. Ben.
    I hope I am fortunate enough to get a response from you. I know I have written in the past with regard to being C677T and on failed anti depressants with bad reactions to the combination of Methlyguard and them. i believe it is the B6 P5P that I am reacting to with worsened anxiety as i have tried B12 methlycolobamin lozingers and folate in the past alone with no anxiety. I did see a huge difference in my motivation level though and like someone above I go into speedy cleaning, sorting or reorganzing modes! I recently found out though that I not only have the C677T Gene but also the A1298C. It seems that my blood work has shown good numbers with homocystiene levels in the past and no worry there. I also had a food sensitivity test done that revealed a huge sensitivity to dairy and mild to chocolate, gluten, and tomatoes. I am working at eliminating them or drastically reducing them. Though there is a concern there about calcium intake. My biggest issue is the fluctuating depression and anxiety, along with fluctuating adrenal and thyroid issues (hypothyroid) that thyroid meds and supplements seem to worsen after a week or so. I read that B12 actually helps the thyroid too. Do you think one could benefit more from the B12 shots and taking folate supplements with the antidepressants. Also what is your thought on taking a multi vitamin such as the Phyto Nutrient vitamin that has methylfolate and methylcolobamin but the B6 in the other form when one has both of these copies?

  170. Betsy Brother May 14, 2014 at 3:41 pm # Reply

    I have just started learning about possible MTHFR mutations for my family and cannot believe how little my doctors know about it. Thank you for providing so much helpful information!

    I have a question about your comments regarding saturated fat. What I am learning through the research done by Dr Price and the Weston A Price Foundation, is that saturated fats are actually critical to health, especially for those with MTHFR deficiencies, and that polyunsaturated oils and sugars are the culprits. Do you have any thoughts on this?

  171. Janet May 24, 2014 at 2:16 am # Reply

    I am Compound Heterozygous C677T/A1298c also. Let’s just say I started with chronic depression at puberty. I have ADHD. I was diagnosed with polycystic ovary syndrome around 26 and started on metformin to decrease my insulin sensitivity. I have ulcerative colitis (may be due to taking accutane which was prior to dx and tx of my pcos which largely took care of my acne). I’ve never been able to come off of anti-depressants due to recurrence.
    I’ve managed to have 3 babies out of 4 pregnancies. After my 1st pregnancy I developed periodic limb movement syndrome which has gotten significantly worse with each pregnancy and it has never resolved. I’ve taking mirapex, 0.25mg in the beginning and up to 1mg till recently. The large amount was affecting my milk supply so I have cut back to 0.25mg mirapex along with 1200mg horizant (gabapentin ER). Along with various other sleep aids I am just barely able to sleep. I do take 10mg domperidone three times daily for milk supply.
    I’ve been taking some form of l-methylfolate for the last 2-3 years. I take podiapn twice daily now. I also take a prenatal RX that has 400 of quatrafolate. My temps always run warm, up to 99.8 for no reason at all. We live with the AC on 68 degrees throughout the non-frigid months.
    My homocysteine levels are normal as well as my ferritin and thyroid (free t4 and t3, etc). I’m going to try niacin to see if it helps with the heat or flushes but I’m miserable. My lab results don’t say if my to different site mutations are on the same chromosome or not and I don’t even know if this matters. Any recommendations?

  172. Fiona May 28, 2014 at 2:01 pm # Reply

    Hi Ben
    you mention the being heterozygous for the A1298c variant will not show high homocystine but my partners levels were 13.4 with elevated cholesterol and significantly lower white blood cell count. I am presuming that there are other issues going on here

    • Dr Lynch May 29, 2014 at 4:32 am # Reply

      Hi Fiona – there are a TON of reasons for elevated homocysteine. MTHFR is just one gene in the body. You’re correct stating there are other things. BTW – high homocysteine and high cholesterol do tend to go hand in hand. Consider having him supplement with fish oil (EPA/DHA) and phosphatidylcholine – something like Optimal PC. These will help his cholesterol and lower his homocysteine.

  173. Pam H. May 29, 2014 at 2:46 am # Reply

    I recently found out I am compound heterozygous for A1298 and C677 snps. I have been very ill and getting worse (I can hardly leave the house anymore). Very weak, losing weight by the week. Although I take several supplements, I feel like the key is in finding a doctor who can help with this problem. How can I find a list of doctors in my area who is knowledgeable about this?


    • Teresa May 30, 2014 at 2:55 am # Reply

      Pam H.,

      Where do you live? If you cannot find an M.D., naturopathic doctors can be helpful.


  174. Susan May 31, 2014 at 11:13 am # Reply

    My son, 41, has had a major stroke and several milder ones. This week, we learned that he is homozygous A1298C, which has been the only abnormal test result, and they have tested everything they could think of. We need to understand what it is about A1298C that leads to blood clots, preferably before the docs insist on blood-thinners.

    Is there any evidence or suspicion that Advil or Bystolic trigger clotting? We need to know what to avoid while we are figuring this out and looking for a doc who is familiar with the MTHFR problem.


  175. Alicia June 3, 2014 at 10:47 pm # Reply

    you forgot to mention dystonia in this article – A12898C (and T677C), according to this article, causes movement disorders in general, including dystonia which I happen to have and has gotten better as I have treated MTHFR

  176. JG June 9, 2014 at 5:47 pm # Reply

    Using Livewello (and 23andme), I discovered recently that have methylation issues (homozygous mthfr a1298c, normal c677T). Over a decade ago organic acid / B-complex testing found deficiencies in B6, B1, and folic acid….however, supplementation at that time (with regular folate and b complex) made me feel strange, so I stopped. Now, after all this time I find confirmation of the methylation problem (with support issues as well).

    My issue: after restarting (slowly and progressively – 2 weeks) with b1,b2, methyl/adeno-B12, NAC, molybdenum…I added methylfolate (1000 mcg). I wasn’t expecting much of a response (…with just a1298c mutation), however the effects were fairly strong within 24 hours (energy, mild insomnia). I backed off for a few days and resupplemented (again 1 mg) with higher dosing of support (B1, B2, NAC, Mo, methyl-B12). This resulted in a milder “high” of greater mental acuity and physical energy…and….a pleasant surprise…less reactivity to seasonal allergens. With an every-other-day supplementation approach, I ended up still with mild sleep problems. So…I stopped the methylfolate and continued with the B complex (including methyl b12).

    The problem:
    I have had very significant wooziness/dizziness (4 or 5/10)…seemingly related to my vision…that has caused some concern and triggered some anxiety. (2/10). Niacin (100 mg) does not appear to work (delayed, but sustained flushing) to relieve the dizziness.

    The question:
    Is this dizziness an adverse reaction to methylfolate (i.e. over methylation), reaction to due inadequate support, or a “withdrawal” symptom (neurotransmitter decompensation)?

  177. sue June 26, 2014 at 6:30 am # Reply

    I have just been diagnosed heterozygous A1298C. I have suffered with muscle pain for 25 years. Been to numerous chiropractors, massage therapists, and doctors. I have tried everything. Finally went to a naturopath that tested me for this mutation. I have been researching on the internet and a little frustrated that so many sites act like this mutation isn’t a big deal. Believe me, I have suffered plenty with this. I eat organic and live a very clean lifestyle. No one could find anything wrong with me until this. I have just started taking Methyl-Guard, L-Tryptophan, L-Tyrosine. I was low in Chromium, Alpha Lipoic Acid, DHEA, Vitamin D, Oleic Acid and most minerals, so supplementing for that too. The first few days were awful, I felt even more exhausted and pain increased, but after a few days I had a good day and kept going. I have just begun this journey and pretty confused with everything I am reading. Why am I not low in glutathione, but I am low in Alpha Lipoic? I just want to say that being heterozygous A1298C is not a picnic for some of us. I am 64 years old and have suffered since I was in my late 30s. Thanks for listening.

  178. Stacie June 26, 2014 at 6:47 pm # Reply

    Hi there!
    I received the news today that I’m positive for Heterozygous 1298. I had recently asked my ob to test me for a mutation as I have had two miscarriages in the past 6 months. When receiving my results today, my ob said that there is no evidence that the MTHFR causes miscarriages. Which is fine, but what can I do or take to help me stay pregnant and keep the child healthy? I do have two children, one is a 4 year old girl that has Childhood Apraxia of Speech, it’s a motor planning and speech disorder, and my 2 year old girl shows no signs of having anything. I am wondering if my daughter with Apraxia should be tested for a MTHFR mutation. And if possible, a supplement to help her.
    As for me, I’m currently taking the Triveen-duo prenatals with DHA and omega 3 fatty acid. What do you recommend I take on top of this? My possible Heterozygous 1298 symptoms are memory loss, insomnia and definitely fog brain! I live a very healthy lifestyle (except my once a day Starbucks). I workout everyday, I do not smoke or drink and we eat organic and mostly gluten free. So any advice is greatly appreciated! Thank you, Stacie

  179. Stacie June 26, 2014 at 6:54 pm # Reply

    I forgot to mention above that I have had 90% of my thyroid removed due to nodules and hyperthyroidism. I am on synthroid which is closely monitored. Not sure if that has anything to do with everything but thought is let you know.

  180. Heather July 25, 2014 at 2:05 am # Reply

    Dr. Lynch,
    I have been trying to find a doctor for two years now – no luck.
    My symptoms and diseases are so much worse. I am so weak I can hardly walk up the steps.
    I want to self treat myself, I have NO other choice.

    I am Compound Heterozygote.

    I am suffering so badly with so many physical and emotional symptoms to the point that if I can not find a way to fix this that I do not know if I can continue to go on like this. I so tired of being sick and tired. I am not even living life.

    Since I can not find a doctor and I have been to doctors and scoured the internet looking – can not find one.
    The doctors I have been to prescribed me Deplin which did not help, and folbee.
    They do not know how to help and do not learn how to.

    I have to take matters into my own hands, if I dont – I cant go on like this.
    Please tell me what to take or tell me something.

    • Michelle Shanks July 25, 2014 at 5:31 am # Reply

      I wanted to cry when I read this….I really understand where you are right now. That was me, and even though you haven’t said a lot, I know exactly what you are saying.
      I doubt that Dr Lynch will get back to you soon enough, he must receive literally 1000s of messages a day.

      I want to tell you I am better, and even though right now you don’t believe it, you can be too. I know I used to think it will never get better. BUT IT DID!

      It was a long journey, but based on what I know now, I think you can have a shorter journey if you are prepared to trust that things can be better.

      I don’t think there is any one pill ever that will make this right for you, and I think that treating yourself right now and every day forward from here is the exact right thing to do. Most doctors don’t understand this and treat it from one aspect…generally a nutritionist will have a much better understanding/approach.

      This is what I wish I had done sooner.
      step 1- Fresh lemon juice in warm water upon rising EVERY morning ( repeat at bedtime) this helps clear the liver and alkalise the body.

      Step 2- Take a Vitamin B 12 in the Methylcobalamin 1MG cherry flavoured sublingual ( source naturals brand) (American you could order on line ) and let it dissolve under your tongue ( this apparently stimulates seratonin ( your feel good hormone ) and is done through the lining of the stomach, so I am told. This also helps your body in the methylation process, something that your body does not do naturally if you are MTHFR.

      Step 3- take a really good quality practitioner strength probiotic in the highest dose. You need to heal your stomach and your bowel and influx it with good bacteria so that your absorption ability increases quickly. If you have poor stomach or bowel health your body is going to struggle to absorb nutrients. I am not sure if you are in America, but am assuming you are. Find out what the BEST probiotic is.

      Step 4- Purchase a good quality plant based digestive enzyme capsule that includes bromeliad ( this is normally a derivative of pineapple) Start taking these with each meal, have some with you in your bag if you eat out. This will stimulate digestion in the stomach and will help you absorb nutrients from food, taking these REALLY made a big difference in my ability to uptake nutrients.

      Step 5- stop eating packaged food….yep…this one is a deal breaker.
      If you want to get well sooner you have to kiss goodbye anything that is processed. All that pain you are feeling, that despair, the aches, the tiredness, the lethargy the numbness, the brain fog and the depression… is fuelled by sugar, wheat, dairy, alcohol, preservatives, colourings, additives etc etc.

      When you are MTHFR your body needs these things:
      Leafy green vegetables and salads………
      in abundance.
      This is because these help you to Methylate and you want that.
      Fresh fruits and vegetables, for fibre and nutrients.
      Probiotic foods or prebiotic foods, such as coconut yoghurt, kefir, fermented foods, and on that note, you might want to take a look at Donna Schwenks face book page and visit her website or reach out to her via message…she has a whole bunch of information on probiotic and prebiotic foods that heal the gut and based on your message and what I have experienced i just feel certain that that is where you need to start.

      Give up coffee if you take it.
      Drink a minimum of 2 litres of water a day, preferably with lemon juice squeezed into it.
      avoid all stimulants, smoking, alcohol, soft drinks etc.
      SUGAR is the ENEMY here……it adds to the fatigue, the joint pain, robs your body of so much.
      I can honestly say I am not preaching, and I really hope you understand that I have lived this and when I read your message I just had to reach out.
      I have given up a lot….but I don’t miss it…in fact I can’t believe now that I am well that I did not realise that I was making myself sick. I have always eaten well/healthy, but now I really do.
      my day looks like this if it helps.
      I do the things I told you about above in that order and then I have something to eat, normally a banana and a few raw nuts that have been soaked overnight ( this makes them easier to digest ) and I dip my banana into some chia seeds for extra protein and fibre.
      I usually have a snack mid morning of an apple, some avocado mashed up with some arugala and tomato and cucumber with some cumin and chill and a pinch of celtic salt ( celtic salt is full of minerals )and if i am really hungry i mix in a boiled or scrambled organic egg.
      lunch is often a vegetable or chicken soup made from scratch, no packaged or tinned products and i try to use organic or free range chicken.
      in the afternoon i have a piece of dark chocolate ( full of magnesium ) and some raw seeds, pumpkin and sunflower and eat them together as this is a good combination with zinc.
      dinner is usually another big salad and lots of roasted veggies, like pumpkin and sweet potato and red onion and garlic, red bell peppers and carrots, all roasted in a little bit of coconut oil and some cumin. If we have meat it is always grass fed or organic.
      I always have a ginger tea after dinner or peppermint tea.

      On top of that I take the following.
      For the pain – Nalgesic Curcurmin. this is a natural product, and works really well.
      Vitamin C in a high 500mg dose….three times a day ( get a reputable brand )
      Magnesium citrate in a powder form ( I use diasporal brand ) – I take this EVERY night without fail.
      Your body has over three hundred processes in the body that require magnesium and most people are severely deficient in magnesium and will never know it.

      My health improved out of site when I started taking this Magnesium before bedtime. I sleep better than a baby now…my muscles don’t ache any more, i wake up with energy and I feel calm which helps me cope on the very rare ( now ) days that I feel not 100%.

      If this all sounds like too much to do, pick one thing and start there. do that for a week and then add in the next thing and so on until it starts to feel like a part of your day.
      I wish I could reach out and help you get through this as I hear the despair and I don’t want this information to add to that….I really really really want to encourage you to believe that it can and will get better and if you have no other course of action to take the one I suggest as a starting point. I am not a doctor of any kind, I am MTHFR and I have spent forever feeling like you feel and thought that was how life had to be.
      I will direct you to my practitioner here in Australia who is THE specialist in this field and she has been educated by Dr Lynch. Her name is Carolyn Ledowsky and her practice is MTHFR Support Australia and you can find her on Facebook and the internet in you go searching. she can Skype with you. She can better aide you with your needs for other tests and treatments if you truly wish to be well.

      I really really hope you feel better soon. don’t give up, I had, and then we found a treatment that worked for me…..and you can find one that works for you but you have to empty out your pantry, fridge and freezer and make a to do list for how you will tackle this.
      Also….get tested for copper levels.
      High copper and low zinc can really have a bad effect on your health. I have/had high copper and it makes you feel terrible, but it can be fixed.
      CRP markers ( inflamation markers)
      Candida ( a big one that will be healed by removing most sugar from the diet ( you need to keep some natural sugar in small amounts so the candida can ‘rise’ and your system can eliminate.
      Good luck xxx

      • Matina July 26, 2014 at 1:30 am # Reply

        I want to tell you thank you also for your post. I am compound MTHFR and continue to seek answers and get off of anti depressants but get ever so close and then crash into major depression. I do want to add that I also take the cherry B12 sublinguals and switched to citrate magnesium which has also helped. I have not had good luck with even low doses of folate or the B6 p5H. I notice that I feel better in some ways when I eliminate dairy and gluton products but without dairy my thyroid becomes sluggish and iodine supplements have not been easy for my sensitive reacting system either. It is a work in progress and balancing act for each of us though and we must not give up.

        • Susan July 26, 2014 at 8:27 am # Reply

          Matina, Can you explain the connection between dairy and thyroid function, please? I am on a low dose of levoxyl, but have to get off of it for several months each year. I seem to need it more in the winter than in the summer. Of course, the doctor told me I would die if I stopped taking it… far, so good. Have you tried applying iodine to your skin? If your body needs it, it will be absorbed quickly in a day or two; if not, it will take a week to fade away. That was recommended by a doctor.

          • Matina July 28, 2014 at 2:01 am #

            Dairy is a good source for iodine in small amounts. When I eat it in normal amounts such as a glass of milk, a couple of slices of cheese, etc. it seems to strangely stimulate me a little, but if I over do it and eat a lot of dairy through the day, eat fish or something rich in iodine regularly I tend to get hot flashes, along with sore muscles and joints the following day. I did have a food sensitivity test done and dairy was high on the list. I have had my tsh tested often throughout these past couple of years and the results can go from normal to overactive. In response to the overactive tests I have tried the levothyroxin twice and both times felt well for and better for about two weeks and then quickly became over medicated. Due to this I was referred to a specialist whom said that my thyoid is normal, or it seems to be each time she checks it. But that I am one of the 2 percent population whose thyoid proteins or whatever it is called, they are need to be tested through what they call dialysis and for me that means they get sent to the Mayo Clinic in NY. She says the tsh is fine to test in the regular lab but the t4 and t3 must be tested that way due to my blood. Maybe it has to do the the MTHFR I don’t know. So..I can not take medicine for it and have to careful about over stimulating it. I also have struggled with the adrenal fatigue which effects the thyoid and thus medicating the thyroid when that is an issue can backfire. So it seems to with me. I hope this helps you and I haven’t gone on to much. Might I ask what it is that seems to make you need more medicine at different times and what symptoms do you experience?

          • Susan July 28, 2014 at 2:26 pm #

            Matina, I am replying here because there was no reply button on your response to this post below. Thank you for your insight on thyroid and dairy. I will have to play with that a bit, but find the trigger for hot flashes to be of particular interest.

            I was on levothyroxine for a number of years at 100 micrograms based on TSH levels. In 2006 I became very stiff feeling like my muscles were a straight-jacket. I thought it was from too much thyroid, so I stopped taking it and gradually improved and did not need it for several years. Eventually, I became sluggish and cold and began taking it again at a lower dose and I felt better, but in the winter my face got baggy, my eyes were heavy lidded and my vision was distorted enough that I could only read large print books. Some of the vision problem was the heavy eye lids. If I taped my lids up, I could read just fine. I could read small print during the summer months.

            It seems that when a doctor is pleased with my thyroid numbers, I am about to crash with nervousness and heart palpitations. When I feel that way, I usually skip the thyroid until I start to feel cold and lethargic. This past year, I have taken thyroid at 25 micrograms most of the year going to 50 over the winter and my reading ability stayed the same. In the spring, I started having palpitations and anxiety issues, probably from low Mg. I stopped the thyroid in April after a trip to the ER where they said my thyroid and potassium were fine, they did not know what was wrong with me, but it was not a heart attack. I am beginning to add thyroid back in now at a low level.

            Thank you for your response. It gives me a lot to think about and I will bring it up with my doc when we do more thyroid tests this fall. I had read somewhere that Hashimoto’s can have a bit of the thyroid gland die and release its contents into the blood which causes spikes in the thyroid levels. That may explain some of the ups and downs during the year. Your comment about adrenal fatigue may explain a lot for me also. Thank you! Susan

          • Matina July 28, 2014 at 4:21 pm #

            No reply button on your latest response also. Not being a doctor I need to be careful how I respond to your latest comments. So I will base it on my own past experience. When my tsh numbers were in the 3.60 area I felt rather sluggish, but I have to say there were also other dynamics that may have effected those numbers-one being a fatigued adrenal problem and sluggishness from life dynamics. After being on just 25 mcg. of medicine I began to feel hot flashes, irritability and sleep issues. With in four weeks I was very witchy feeling and insisted he check my tsh levels. At that one time they came back at about 1.34 which was ‘a great number’ for the thyroid he said. Of course probably for the norm that is a great number but for me it obviously was not. So I slowly began to wean because when I tried to skip a day or two I felt what you did-cold and tired. That was probably due to throwing my thyroid off with such a severe drop in medicine. So I weaned for weeks and felt some tiredness and depression for a while-but again I am that way anyway. I eventually got off of them. I occasionally do get puffy eyes but I try to keep track of most of my foods so I can see what the problem is. Maybe for me it is just my adrenal that cause my thyroid to bounce around and get back to normal when the adrenals are stronger. As far as the ER saying your thyroid was normal while on medicine that would make perfect since because the medicine was doing that for you. That is why they check it periodically so they can make sure the medicine is keeping it balance. Going off and on does not seem to me like a very wise thing to do. Maybe you should discuss have a dialysis done while on the medicine and then if the numbers are good on the medicine seek counsel about weaning off of the medicine slowing and monitor your symptoms and then have the same test some in another 6 to 8 weeks to see if the thyroid stabalized itself and is fine or if you really do need to take something to keep it stabalized. I would also suggest you see a naturalpath about adrenal fatigue because if you have that it only complicates thyroid treaments.

          • Lynn_M July 28, 2014 at 4:58 pm #

            For Matina and Susan, in regards to your thyroid issues:

            It is an absurd proposition to try to determine the best dose of thyroid supplementation based on TSH test results. While the TSH test accurately measures the levels of TSH hormone, it does not measure actual thyroid hormones. Furthermore, if antibodies are present, they make the TSH that much more meaningless.

            For an understanding of the effect of exogenous thyroid hormone intake on the interpretation of serum TSH test results, read this introduction to the issue: Then read the full 5 page article at Another good resource for information on why TSH is usually a useless measure, except when values are above the reference range, see

          • Susan July 28, 2014 at 8:53 pm #

            This reply button is odd, but the posts appear in the proper places. I know my stopping thyroid is not advised and I have been well lectured on the subject by multiple medical people, but when I dutifully follow their directions, I end up with problems. I don’t seem to be normal in this regard. I would like to figure out the numbers at which I feel well and energetic and let those be the “good numbers”. My best guess is that MTHFR influences the rate at which I get rid of the medication and that makes it last longer in my system. Since my first symptom of excess thyroid is heart palpitations, it is an attention getter and I need to stop it when I get to that point. I have discussed this with the pharmacist also and he did the “I can’t tell you how to take the medicine, but it sounds like you are on the right track for you” line of thinking. Sometimes, skipping a day or two will help. It is odd, and everyone is different and MTHFR really accentuates the differences. An endocrinologist told me it was safe to play with the doses and timing so long as the TSH stayed below 10…..that was a step up from the “you will die” logic.

            We will see a naturopath this week, so there will be changes coming, I am sure. I talked to the naturopath by phone and got more information about MTHFR from her than I have had from several MDs over a period of months. She was a wealth of information and really knew the subject. I have had the feeling that the MDs did not have a clue about living with the problem or treating it. Thankfully, there is an Indian reservation near us and their health center employs a naturopath…..they are not allowed to practice in the state of NY, a testament to a very active medical lobby.

            From what you have shared about your history, I wonder if you really need thyroid? You are very, very sensitive. It may be that the adrenal fatigue is more of the problem and that may come and go??? It is frustrating to get all of this figured out and understood, and it seems that once we fix something, there is another problem awaiting attention. Good luck with your quest! Susan

          • Matina July 29, 2014 at 12:57 am #

            Thank you again for more information. I may or may not have thyroid issues-but if I do it may be that as you said due to this MTHFR the medicine is either absorbed poorly or to quickly for me. I am incredibly ultra sensitive to any medicine or supplements. Today I have be totally wiped out-but had haddock for supper and regained my energy a little. I have an appointment with my prescription manager and am going to request the tsh be done again and then the dialysis if that is high. I may have to try a low dose again at different times or days. We will see.
            Good luck to you also

          • Susan July 29, 2014 at 1:39 am #

            Matina, It may be interesting to keep track of how you are feeling when you have the blood tests done. I really think that super-sensitive people need to find the numbers that correlate to when they feel well and when they feel run down. It does not matter what the normal ranges are, what matters is how YOU feel and what level of support helps you maintain that feeling of well being. I discussed thyroid with a friend who is a veterinarian and she said that for sensitive dogs, she might recommend a low dose of thyroid every other day. My doc crossed her eyes at that suggestion, but the pharmacist thought it was worth trying. Have you considered that taking a small dose of anti-depressants might be what you need to maintain your new norm, rather than getting off them completely? Things change as we age and you may need just a little to stay in your normal range. Finding what works is the key. Best of luck with your appointment. Susan

          • Matina July 29, 2014 at 1:31 pm #

            susan thank you for you sensitive insight. Yes I have considered that I may need anti depressants for the rest of my life actually. The problem is…I can’t seem to get well on just that or find the right one for my chemistry. I would love to be able to just have someone to bounce more thoughts and ideas off of in a more personal way. Would you be interested in sharing emails rather than trying to find the original post every time we reply to a comment?

          • Susan July 29, 2014 at 5:49 pm #

            Matina, you can contact me at

      • Heather July 27, 2014 at 8:45 pm # Reply

        Thank you so much for your reply. You have given me so much information and hope!
        I feel like I am ” white knuckling ” through everything – through life and my body feels so ill.
        I can’t hardly think straight and it seems the older I get, the worse I get. I do not feel like I am living my life at all, just trying to survive it. I am so unhappy and have not felt joy in so long that I forget the feeling. I have no support as far as family or friends – I’m tired of my husband thinking I am lazy when the truth is; I just don’t have the energy, at all. I can not imagine living the rest of my days this way and I KNOW it has everything to do with this MTHFR. I do have stomach issues to the point its hard to eat without feeling nauseated. After I eat even the littlest amount of food, my stomach gets very upset, distended – I’m sure you know what I’m talking about. I have been on all kinds of depression medication none which have worked. I have major anxiety. Was told I have ADD, prescribed adderall which I can’t stand. I am on pain medication for back pain, have headaches about 4 out of 7 days – was put on topamax. My skin looks unhealthy like symptoms of adrenal fatigue. I have had ovarian cancer, have had veins stripped and removed my legs due to DVT, steroid injections in my neck and back…. Just to name a few off the the top of my head.
        I do not smoke or drink so that’s no problem, but I would probably never move without a cup of coffee. I will work on that.
        You have given me a wealth of information and I can not thank you enough!
        I am in America, and the doctors in my state of Ohio do not know what is going with this.

        Some of the things you mentioned I have never heard of before so I will have to look into those and see what I can come up with. I picked up some fresh lemons today. I am trying to find the sublingual Methylcobalamin 1MG and Amazon keeps coming up on searches. Im wondering if I can find something local ? Not sure. I just want to be sure I am getting the right things that you recommended/mentioned.
        I do not feel like you are preaching – at all. You are heaven sent ! The information you have given me and others are life saving. I am in despair, not feeling much hope until I heard from you and now I have a place to start. I hope we can stay connected in some way. I dont know how to exchange information (email, facebook ) on here without it being so public.

        I see the other girls here are also benefiting from your post and I am sure I speak for all who read it how truly grateful we all are.
        I am so happy for you that you are feeling so much better and are on a path of wellness :)
        I think that is wonderful ! Also, wonderful that you have a doctor there willing to learn and help her patients. That is a real blessing.
        Thank you so very much, Michelle. Thank you.

      • Paula February 3, 2015 at 2:48 pm # Reply


        Thank you for such an informative response on the Compound Heterozygous. I, too, am Compound Heterozygous and am only beginning my journey to a much healthier life. Please take a look at my story in which I wrote on January 29, 2015, on this site. I would like to know your opinion on the package food deal. Now, there are so many “all natural, gluten free” products on the market – such as snacks, cereal, granola, pastas, etc…however; all packaged. Are those okay to consume and do you think they have any nutritional value or are they just empty calories? Also, Im studying the Paleo Diet quite extensively, and am a bit confused because I have Vitiligo, an autoimmune disease. There is a different “Paleo” approach if you have an autoimmune disease abbreviated AIP. Do you think I should try to follow a diet (Paleo, Vegetarian, Vegan, AIP), or just keep it simple with an all natural diet? Thank you in advanced!!

      • Paula February 4, 2015 at 11:36 pm # Reply

        Thank you for such an informative response on the Compound Heterozygous. I, too, am Compound Heterozygous and am only beginning my journey to a much healthier life. Please take a look at my story in which I wrote on January 29, 2015, on this site. I would like to know your opinion on the package food deal. Now, there are so many “all natural, gluten free” products on the market – such as snacks, cereal, granola, pastas, etc…however; all packaged. Are those okay to consume and do you think they have any nutritional value or are they just empty calories? Also, Im studying the Paleo Diet quite extensively, and am a bit confused because I have Vitiligo, an autoimmune disease. There is a different “Paleo” approach if you have an autoimmune disease abbreviated AIP. Do you think I should try to follow a diet (Paleo, Vegetarian, Vegan, AIP), or just keep it simple with an all natural diet? Thank you in advanced!!

  181. Elizabeth July 25, 2014 at 3:51 pm # Reply


    What valuable knowledge (gained the long, hard way!) you shared. Thank you. I’m especially grateful for the reminder of lemon water every day, but you shared so much good information for Heather–and all of us.


  182. Bridget July 29, 2014 at 1:34 pm # Reply

    I was told by a hematologist when first diagnosed with 2 copies of A1298C that I could not take synthetic hormones as those in birth control. That is not a problem for me as I have had a tubal ligation and endometrial oblation. I have a swollen thyroid as well as lymph nodes in my jaw line and under arms along with elevated TSH and LDL cholesterol (when I was younger my HDL was higher than my LDL but now it is reversed in a major way). My cortisol, T3 and T4, and antibodies for Hashimoto’s disease (this autoimmune disease runs in my family) levels are being tested as we speak. My question is will it be safe to take a medicine like Levothroxin for thyroid hormone replacement therapy if the expected diagnosis of hypothyroidism is confirmed or should my doc consider a blood thinner in conjunction to be safe?

  183. Gabi July 31, 2014 at 4:48 pm # Reply

    Dr. Ben,
    First, thank you for all you do and have taught us. Like so many others I am finding hope for the first time in many years through your research and protocol. My question is:

    I am Homozygous A1298C. I occasionally take Tramadol and xanax… recently (1 month and 1/2 ago) my neuro put me on Lyrica 150mg a day. I have been experiencing all of the symptoms of Serotonin Syndrome. Is my self diagnosis completely off or could this be? Right now I am on my 2nd day of methylCobalamin and your protocol (lifestyle, etc) Do you have any suggestions for getting my serotonin down any faster? I am miserable and cannot imagine spending another day like this. I had been having myoclonus, but this week I had a big seizure which was scary to say the least. I am a prisoner to my bed and doctors here continue to guess and refer me out because they don’t know what could be causing all of this. I just ran across Serotonin Syndrome and after listening to your video (a few times) it makes sense to me that this could very possibly be what I’m experiencing. Thank you in advance.


  184. Ruth July 31, 2014 at 11:33 pm # Reply

    So what is your suggested treatment for compound heterozygous individuals? I have many of the symptoms you described above. There are not many doctors in my area that even know what MTHFR mutation is, let alone know how to treat it.

    • Heather August 2, 2014 at 4:59 am # Reply

      I have the same… Compound heterozygous.
      Also, NO doctors and the ones I have seen are not willing to take the time to learn in order to help me. I feel pretty much all alone in this. I was tested twice by two different doctors for MTHFR but then they have no idea what to do with it.
      I have so many of the problems and I wonder what my quality of life would be like if I could get the proper treatment.

    • Susan August 2, 2014 at 10:43 am # Reply

      Ruth and Heather, I just found out that I am compound heterozygous also. I ran my 23andMe results through Genetic Genie which was fine for the methyl cycle. Needing more info, and not having a clue about what I was doing, I then ran it through which gave a meaningful paragraph to each mutation, but there was conflicting info on one mutation. That bothered me, so seeking a third opinion, I ran it through There I got enough information to change my life! If you take a health survey, you get the methylation and detox analysis for free and it tells what to take and what to avoid. I paid for the full report and now have a much better understanding of this very complex topic and myself. Taking advice from a computer almost makes more sense than taking it from an ill-informed physician. Frankly, with so many mutations, one needs a computer to sort out the “take this and avoid that list”….. and some supplements made it on both lists, which probably explains why I have felt odd for so long. Right now, I feel that the 23andMe and Nutrahacker fees have been the best health dollars I have ever spent. Time will tell how useful the information is, but knowing that I have a problem in an area will help me to do what needs to be done. I seem to need to understand WHY I have to do things.

      • Steve Thompson August 2, 2014 at 10:51 pm # Reply

        Hi Susan. The information that the computer returns originally came from those same ill-informed physicians. But on a more serious note, prescribing one course of action for each single gene variant is not really useful. We are a collection of 30,000 genes, including a balance between some two dozen genes/enzymes related to methylation. Some pull in one direction while others pull in other directions. We should treat the person, symptoms and reactions to supplements, rather than the genes.

        • Susan August 2, 2014 at 11:39 pm # Reply

          Thank you Steve. Yes, we need to treat the person, not the genes. Right now, I am assimilating the information and hope to get a workable list of what I need to take, understanding why I need it. It is helpful to have the genetic information to understand that there is a problem in certain areas and how the mutation changes the expected function. Once I knew that I had a gene for Celiac Disease, it was easy to give up gluten, knowing it was a poison to my body. The Nutrahacker information brought up some supplements that I had considered taking and now have a better idea of why I might need them. It also brought up questions that need to be asked about other supplements, methyl B12 in particular. It is interesting to have so many mutations that are in conflict with one another. No wonder my doctors have not been able to figure out what to do with me. At least the results explain the complexity and point toward some answers.

  185. Heather August 3, 2014 at 2:36 am # Reply

    Susan, Steve,
    I would much rather be collaborating with a doctor, by all means. If I didn’t feel like this was playing a role with so much illness and dysfunction in my life, I would leave it alone. I feel its worth the investigation. I agree with you Mr. Steve Thompson. I believe that is the DO oath.
    I think you have to very careful if you decide to self treat. I read on the MTHFR Facebook support page – an article about how careful you have to be… You can really screw yourself up and cause a lot of problems within your cells. The only thing I am doing is taking digestive enzymes and vitamin b12 sublingual 1mg. Hopefully everything I have read about those two things, I am safe. I pray.
    I will continue to look for a doctor. Keep praying for one to come my way.

  186. Colleen August 3, 2014 at 8:20 pm # Reply

    Hello. Thanks for your great article…it was informative and easy to understand. I was tested and have the Homozygous A1298C MTHFR mutation. The C677T was negative. My Mom has Parkinson’s, which is on your list of posible conditions associated with the Homozygous A1298C MTHFR mutation. What natural supplements and or dietary recommendations do you have to help prevent/lessen me from ending up with Parkinson’s? I do take Quercetin, Acetyl-L-Carnitine, and R-Lipoic Acid as I heard these help. Thank you for your help.

  187. Michelle August 9, 2014 at 10:38 pm # Reply

    I have recently been diagnosed with the compound heterogygous. I am struggling with getting it treated. I purchased your supplement, HomocysteX. One capsule seemed too much to start with. Then my doctor gave me Deplin 15 mg. Way too much! Many side effects. With advice from someone else, I started back with the HomocysteX again but opened the capsule and took 1/4 of it. Then went up to 1/2 a few days later. I felt terrific!!! My hair, skin and mood were great! I stayed with 1/2 but after a few days I noticed my hair super dry and brittle again. It breaks off and is thinning out. My mood is still good and I have had energy again but I have also been light headed and some stomach cramping with diarrhea. I don’t know which way to go now. Do I have too much or not enough? I am also concerned with a history of IBS issues, maybe I have leaky gut and am not absorbing all of it. Am I trying to detoxify but not eliminating the toxins? I am taking a new multivitamin with folate instead of folic acid, theracummin to help with any inflammation, Omega 3’s, probiotics and I have Niacin if needed. I am also on perscribed medications from before this diagnosis. Vyvanse and Fluoxetine.I have also been on a gluten and dairy free diet for a few weeks. I am eating healthy. I do have a lot of stress in my life. Maybe that is effecting things. I teach autistic kids. I love my job but it can be stressful. Do you have any suggestions for me?

  188. Faigi August 11, 2014 at 8:57 pm # Reply

    I live in Israel where they don’t test for a 1289c. One daughter in USA has one copy, so does my husband’s niece. So we know where it comes from, at least. Another daughter displays many symptoms and my question is: can she take the folate without being tested?

  189. Connie August 13, 2014 at 5:34 am # Reply

    My husband has a mutation MTHFR 1298C. Just diagnosed with Dementia Lewy Body with parkinsonian symptoms. Dr. says no treatment for DLB. Researching possible ways to help him. What type of folic acid is recommended for A1298C mutation and dosage by IV therapy. His cysteine level showed normal. Is that the same as homocysteine. His folate level showed normal. Is that the same as folic acid. He is waisting away. Severe cognitive decline. Only 65.

  190. T.R. Morris, ND August 13, 2014 at 6:14 pm # Reply

    Hi Ben. You listed “possible symptoms, signs and conditions” associated with A1298C MTHFR mutations. Can you tell us how you developed these lists and how you may expand them? You indicated that you would “add to it as I think of more (or you inform me of ones that I have omitted).”

    Are you crowd-sourcing these lists or are they based on associations found in published literature?

  191. Elizabeth August 14, 2014 at 1:34 am # Reply

    As a longtime and very appreciative follower of Dr. Lynch’s work, I’ve seen this site attract many readers, and the poor doc would never be able to pursue research, help patients, develop high-quality supplements, travel around giving talks and workshops, and also promptly answer all the questions posed–and sometimes people get impatient or even a little snarky toward him because of it, or for other reasons. But there are clearly many very kind people who come here too who are very desperate for answers and help, and it’s been heartening to see the careful, informed sharing of knowledge in the spirit of broad patient empowerment and goodwill.

    I can’t to speak for him of course but have heard him in a number of talks and interviews and gather that much of Dr. Lynch’s findings/associations are from his past (and present?) clinical work, work with other docs engaged in the same research and clinical practice, and medical journals/research, among other sources.

  192. Joseph August 22, 2014 at 10:56 am # Reply

    Hi. My daughter is A1298c homozygous and has a mutation on CACNA1A which is causing Calcium Ion Chanel issues (effect -> Ataxia, Speech issues) in Purkinje Cells.
    Is it possible that 1298c is also affecting this? If yes what supplemental would be usefull?

  193. Margaret September 3, 2014 at 7:31 pm # Reply

    Dr. Ben, I am so thoroughly confused. I have results from 23andme, which show I am compound heterogeneous. I am not sure what B vitamin to take or not to take. I understand no folic acid; however, a PA told me to take Adenoslylcobalamin, but do I need something else?

    Also, my PA believes I may a chronic infection. Would the MTHFR mutation manifest itself as such as treatment has not been effective?

    • Dr Lynch September 3, 2014 at 7:37 pm # Reply

      Margaret – chronic infection has many causes – not just due to MTHFR. It may contribute. Adenosylcobalamin is useful but methylcobalamin is needed for many people – especially those with low methylation. Those with MTHFR may have lower methylation – depends on many factors. Chronic infections are definitely something to evaluate.

  194. Susie September 3, 2014 at 11:04 pm # Reply

    Dr. Lynch, my son is compound hetero. His autism doctor just took him off methyl donors and put him on hydroxylb12 and no folate. What can I do for folate?

  195. Tammy Merrill September 7, 2014 at 4:38 am # Reply

    I just got tested and still dont understand my results. My MTHFR C677T was in the optimal range but my MTHFR A1298C WAS IN THE HIGH risk range. The doc prescribed me
    Flobee300mg. Can you tell

    • Dr Lynch September 9, 2014 at 4:24 pm # Reply

      Tammy – that doesn’t make sense. MTHFR is a genetic polymorphism (SNP). There is no normal range. Folbee (not Flobee) is not the ideal way to support MTHFR because of the lower quality forms of nutrients. Folbee uses folic acid – and that is NOT what should be taken. I prefer nutrients that are: methylfolate, methylcobalamin, adenosylcobalamin, pyridoxal-5-phosphate and TMG. These support methylation much better than Folbee. I’ve designed HomocysteX and HomocysteX Plus which contain these forms of nutrients.

  196. Carol Sweeney September 9, 2014 at 1:35 am # Reply

    Am fascinated by all the research on methylation since being tested by a local doctor who believes in this subject matter. I tested negative for C677T and positive for one copy of A1298C. Quest Diagnostics did the lab work, but only gave a technical explanation of the concept of methylation. I assume that I must not have the more difficult combinations that others have reported. Yet I have serious cardiovascular disease somewhere in the DNA, with 10 cardiac stents currently. I was a runner for years before discovering that both coronary arteries were blocked 75 and 90 percent respectively.
    In addition, many of the symptoms/conditions that can occur for methylation I have had for years, blaming it on other reasons. I am not saying that I think methylation is now the cause, but do wonder if only one positive copy of A1298C can, in some individuals like myself, some serious health problems that apparently I have had since early childhood. All speculation on my part, but I wonder….

    • Susan September 9, 2014 at 4:56 pm # Reply

      Carol, there is a great deal to read on several MTHFR sites and MTHFR is only part of the methylation problem. May I suggest that you get a test kit from 23andMe to get a more complete genetic picture. You will probably find the answers to your cardiovascular history there. After you get the raw data from 23&Me, you need to run it through another genetic site to get useful information about health related topics. Some such sites are:,, and You will find that MTHFR is only one part of the puzzle. Best of luck to you! susan

  197. Momof2boys September 18, 2014 at 11:43 pm # Reply

    I just found out today that I tested POSITIVE for 1 copy of C677T mutation 1 copy of A1298C MTHFR genes. I’ve had thyroid issues since birth of 1st child yrs ago. When pregnant I had pre-eclampsia & HBP. Prior i was healthy. Now thyroid is going haywire & TSH came back today 7.61. What does all this mean; primarily thecompbined MTHFR genes?

  198. Sheilla September 19, 2014 at 3:19 am # Reply

    I just found out I have the A1298C mutation and not the C677T. I’ve been unsuccessfully trying to conceive for the last 3 years. My doctor put me on Optivite and 1mg methyl folate. But instead,I decided to take the optimal prenatal from seeking health. I also have insulin resistance and was started on 500 mg Metformin,working up to 1500 mg a day. I have read that Metformin can increase homocysteine. Is it the optimal prenatal enough for my supplement needs? I ve been doing okay with my old multivitamin prior to the diagnosis but I did have estrogen dominance and psm so she put me on Optivite and progesterone.
    This past month, I’ve been sick with cough in combination with hives /nasal allergies, which turned into cold with allergies. I’m not sure if there is a corollation to the mutation. I have had worse seasonal allergies these past 2 years.and I have read that high histamine is a sign of under methylation. The ton of information you come across is confusing and I’m not sure if I understand them right. Any useful advice is appreciated.

  199. Sheilla September 19, 2014 at 4:06 am # Reply

    I also want to add that I did a one day cleanse and had a flu shot before the onset of my cough. So I wonder too if that’s what caused the symptoms. But I am interested to know if mthfr mutation can cause allergy symptoms of runny nose, or hives.

  200. Rick September 19, 2014 at 5:00 pm # Reply

    Hi dr. Ben,
    Thank you for all you do for the general public, people like you are a blessing.
    I was diagnosed homozygous a1298c. Battled depression and ocd for 9 years, I’m 43.
    Tried many antidepressants that don’t seem to help much.
    My psychiatrist has me on 45 mg of Deplin (I know it’s a lot). Still on an AD also.
    I do have more energy but trouble sleeping and the obsessive thoughts are still with me every day.
    What else can I do to improve my health?

  201. Jennifer September 21, 2014 at 2:54 pm # Reply

    My oldest child was born with a neural tube defect. I insisted on being tested for MTHFR mutations before trying to conceive another child and I was told I have one copy of A1298C which was not a factor in my child’s neural tube defect. I was told to follow the normal recommendation for mom’s of children with NTDs of taking 4mg of folic acid before trying to conceive and during pregnancy.

    Should I take methyl folate instead? Should I take 4mg of it? Do I need an additional supplement to balance the large dose of folate? I am not finding any good information on what my body most needs to give a fetus the best chance at avoiding NTDs and its so vitally important I get it right.

    Any advice or links to relevant articles would be very much appreciated. The genetic counselor I saw previously didn’t seem knowledgable about my need for folic acid/folate and pretty much dismissed me by saying the mutation was not a factor.

    • Susan September 23, 2014 at 10:41 am # Reply

      Hi Jennifer,
      From what I have read, folic acid is the wrong source of folate for anyone with MTHFR mutations. Folic acid blocks the receptors so folate is actually unavailable to the body tissues even though the level in the blood appears to be high. It seems that getting this well understood and treated before becoming pregnant is vitally important. My impression is that naturopaths are best suited to understanding the needed treatment for MTHFR, so finding a good naturopath may be your next best step. Having a methylation panel to identify any other mutations is also important. MTHFR is often only part of the picture and you need to treat the whole. Best wishes to you, Susan

  202. Beth September 26, 2014 at 12:30 am # Reply

    Dr. Lynch,
    I am hetero for 1298c, as is my husband. We have had multiple miscarriages. I started seeing a doc who is knowledgable about MTHFR. She has me on 15mg of L-methylfolate and also b12 and b6 (all bioavailable forms). Does this seem like a high dosage? Is this dosgae too high to continue if I were to become pregnant again?
    Thank you for all you do.

  203. Tierra September 26, 2014 at 1:31 am # Reply

    I have just stumbled upon your website and find it very interesting.
    My nine year old daughter has mastocytosis. I have just found out that she is also homozygous for MTHFR A1298C, MTRR A66G, and CBS A360A. What I am gleening from my reading is that she could benefit with supplementation with methylfolate and methylcobalamin, however I cannot find any dosage charts for kids! She is 90 pounds so would appreciate any guidance you might have.
    Many thanks,

    • Colleen September 26, 2014 at 5:35 pm # Reply

      Tierra, go to the Life Extension web site and see if you can find anything there on dosage for methylfolate and methylcobalamin. I take both (I have 2 copies of A1298C). If you can’t find it there then contact them, they are very helpful. Hope this helps. http:/

  204. Colleen September 26, 2014 at 5:34 pm # Reply

    Tierra, go to the Life Extension web site and see if you can find anything there on dosage for methylfolate and methylcobalamin. I take both (I have 2 copies of A1298C). If you can’t find it there then contact them, they are very helpful. Hope this helps. http:/

  205. Amy September 30, 2014 at 6:14 pm # Reply

    Hey Dr. Ben, I have tried to look at the impact of being Homozygous for both C677T and A1298C and have found no literature on having both homozygous mutations. What are the implications? Anything different that I need to add to my already huge pile of pills b/c of this double whammy.


    • Lynn_M October 1, 2014 at 4:35 am # Reply


      The research I’ve read that looked at the incidence of various MTHFR mutations in their research subjects found no subjects with both homozygous mutations (4 faulty MTHFR SNPs) and a very limited number of subjects that were a combination of homozygous and heterozygous (3 faulty MTHFR SNPs).

      The researchers seemed to think that having both homozygous mutations was so lethal that the fetus could not survive. If you have both homozygous mutations, you are a very rare individual.

      • Amy October 1, 2014 at 8:59 pm # Reply

        Yes, so I have heard how rare this is. Not sure what this means for me. I have been on a successful supplement regimen but not sure what else to consider for preventive care.

        Any suggestions are welcome.

        • Lynn_M October 3, 2014 at 3:59 am # Reply

          Seems like it will be critical for you to live a very clean lifestyle with minimal stress, minimal toxic exposure, and an exemplary diet.

          Since you are such a rare bird, I imagine some MTHFR researchers might be interested in you. Perhaps you could find some of those research articles where they couldn’t find any living subjects with a compound homozygous condition and write to the authors. I don’t know if they would have any helpful advice, but maybe at least they would be interested in you as a subject, or give you leads to someone that could be more helpful.

      • Argyros October 2, 2014 at 5:44 pm # Reply

        Hey Lynn, do you have any knowledge to how common it is with the combination of homozygous A1298C and 3 (P39P) ?

        According to Yasko, P39P is expected to be even more detrimental to health than C677T – since it’s more rare and her own research/experience, which I haven’t found any other sources to yet. I do find it not as likely though, unless the combination of the ‘1298’ and ‘3’ effects are not as bad in combination as 1298 and 677..

        I’m currently diagnosed with ME/CFS, and also uncovered high levels of chronic Mercury which I’m currently being treated for – which of course raising methylation and doing chelation (DMSA & ALA) are primary. Don’t know if the mercury is due to low methylation and 1298/3-issues, or just incidental, but I do tend to believe it’s at least somewhat causal, together with other SNPs, since I’m more sick and toxified than others in my environment – and I’ve been increasingly eating healthy paleo foods the last 10 years – after getting food intolerances and “crohn’s”..

        • Lynn_M October 3, 2014 at 3:52 am # Reply

          I heard Dr. Nancy Mulligan say maybe a year ago that Dr. Yasko thought MTHFR 03 P39P had a worse impact than C677T. I am homozygous A1298C and heterozygous P39P, so I tried to find out more about P39P, but was unsuccessful at that time. There doesn’t seem to be much published about any MTHFR snps other than A1298C and C677T. So I can’t help you with that question.

          I think you’re correct in thinking your homozygous A1298C and 03 P39P are contributing factors to your high levels of mercury. You might check out the status of your glutathione uptake genes too – GSTM1 and GSTP1.


          • Argyros October 6, 2014 at 5:57 pm #

            Thanks for replying Lynn.

            Yea, it was 1-2 years ago I first read about (and heard in seminar recording) Yasko’s thought that P39P i more problematic than C677T, and the only other source was Mulligan echoing that. Recently found P39P is probably also called C116T, but not a lot of pubmed research or other popping up for that either. I guess it might just be too rare to being researched much yet.

            Will let you know if I come by any more information on it.

            My GSTM1 and GSTP1 are both fine (wildtype). I do have SOD2 homozygous mutations though (rs2758331 & rs4880), so probably something could be done to help out there as well – let’s to figure out :-|

  206. lane October 2, 2014 at 6:05 pm # Reply

    I found this site about three weeks ago after three years of internet searching for issues that began for me at that time after taking a course of antibiotics (cipro). Within a day of completing the dose I began to have severe itching all over my body as well as hives and dermatographism. Over the past three years I’ve visited numerous western doctors as well as Chinese medicine acupuncturists. I’ve found some relief using antihistamines but still the problem persists and in some ways the reactions have gotten worse in that now my lips tingle and my face flushes. Awesome to go in public sometimes. ;)

    Through my visits with MDs they found I had low platelets and elevated bilirubin…long story short no one could figure out why the low platelets and was told just to repeat the labs every six months. I did find out though that I have Gilberts syndrome (hence the elevated bilirubin). And since I’m putting it all out there not sure if it matters but during my first pregnancy with twins I developed HELLP syndrome and had an emergency C-section to save us all. That’s a bit about my medical background. When I found your site and I devoured it and saw similarities in people’s posts so when I went in coincidentally for my annual I asked my ob/gyn if she could pull blood for it. I remember saying the initials MTHFR and she’d heard of it and I was so excited I could have cried. Sure enough got the call today and I’m compound heterozygous (one copy of A1298C and one copy of C677T) My doctor recommended I start on Metanex (?) and I also had blood taken for a Spectracell micronutrient test. Plus I guess I’ll just throw it all out there…my A1C came back at 5.8 (prediabetic?) and she suggested metformin to see if we can get that back down below “normal” as a preventative (my father is a type 2 diabetic) I would like to add that I eat healthy, exercise regularly (training for a marathon right now) so its not my lifestyle that’s the root of this. I know its my genes (unless maybe high mileage running can affect that number?)
    All this to say I am happy to have a piece of my medical puzzle especially for my kids sake. One son has asthma, another has horrible eczema, the last has stomach issues, think IBS. Basically an amalgam of me. I can deal with whatever issues I have but if possible I would like to save my kids from any of my medical issues and have them be as healthy as possible. Dr. Ben or anyone that this sounds familiar to please please say something as to what way to go now that I know i’m a double mutant. Is the metanex all I need to do to “fix” myself then test the kids and go from there?
    one last thought…my sister has rheumatoid arthritis, fibromyalgia, and her son is autistic…I KNOW this is all related, it has to be…will urge them to get tested.

    • Lynn_M October 3, 2014 at 5:06 am # Reply

      Lane,! is about fluoroquinolone antibiotics causing permanent nerve damage. Sounds like you have a challenging after effect.

      I have read about a genetic susceptibility to fluoroquinolone, and the article I saw gave a specific gene that 23andMe included in their testing. I can’t find anything about it now, so I can’t give you the gene name, but if you’re interested, it might be worth searching for.

      The problem I see with Metanx is that methylcobalamin in it may not be absorbed very well because you’d be taking it orally. There seems to be some controversy over how much mB12 is absorbed when taken orally, with many people saying only 1% gets absorbed, and more conventional thinkers saying it’s fine to take it orally. If it was me, I would take additional mB12 in either sublingual, injectable, or transdermal B12 oil forms.

      Your doctor may have heard of MTHFR, but apparently she doesn’t know that metformin depletes B12. If it was me, I’d want to do more investigation of why the A1C was high before taking a drug that will compound the difficulties of adequate methylation. Maybe there is something about your diet that is unknowingly contributing to a high A1C – like allergy or food intolerance, or the wrong diet for your metabolic type. For starters, you should be avoiding gluten. There are a lot of books available about how to cure diabetes naturally.

      Fixing yourself is much more involved than taking Metanx. It sounds like your lifestyle is already excellent, but stress might be an factor for you – especially with the medical problems your children have, and your post-Cipro problems. I agree with Susan that a 23andMe test might be a good place to start, to better identify your vulnerabilities.

  207. Susan October 3, 2014 at 12:18 am # Reply

    Iane, may I suggest that you get more testing done before you start treating your problem? There is much more to this than just MTHFR and the other SNPs are often more important. Doing the 23andMe test for $99 then getting it interpreted at another site will give you a boatload of information for under $200. There are often conflicting recommendations that need to be balanced, like a SNP that needs methyl donors and another that avoids them. I had one that said to avoid metformin. From what you have shared, it sounds like your family has a lot of methylation issues. You might find Dr Amy Yasko’s site of interest for methylation and autism issues. She has several books available for download that will help you see the importance of the other SNPs beyond MTHFR. And YES, it is all related! Good luck!

  208. Tammy Dee October 4, 2014 at 8:17 pm # Reply

    Hello, I have recently discovered that I am MTHFR – Compound Heterozygous. My question is – have there been any studies that show a correlation with Degenerative Disc Disease ? I have very severe disc disease – involving pretty much my whole spine. My cervical spine is very severe with spinal cord compression and multiple osteophyte formation (bone spurs). I am only 50 yrs old – I swim and hike/walk despite the pain and eat very healthy- I do not take supplements. I am now requiring a second surgery on my neck where they are going to have to fuse me from C1 to C6 – a very risky and frightening surgery. Nobody else in my family have these problems. I have no full blooded brothers or sisters – only half. Is it possible that this mutation could have caused these issues ? Thank you in advance for your response.

  209. Caroline October 5, 2014 at 12:31 am # Reply

    Hi everyone I have had a lot of physical and emotional trauma it all started when i had my stillbirth in 2012. Found out i had blood clotting disorders strangely i tested negative to any MTHFR gene mutations so i started takign clexane i had a very bad reaction so was told to take aspirin. Fast forward to now after all teh trauma i found out through 23 and me i have a genetic mutation that doesn’t metabolise NSAIDS so 2 weeks after having baby i started vomitign up blood yes i had two bleeding duodenum ulcers if only i did the 23 and me test a few years ago, i should be dead but i survived. Went and saw a functional lyme doc he did the MTHFR test and i am homozyhous 1298c. I have all the symptoms listed here but i am also COMT++ which complicates it a little, i have high ammonia and low hymocysteine i have tried L-Arginine but that makes me worse could be from the Lyme due to the COMT++ i am sensitive to methyl donors coffee makes me jittery i don’t drink it Coq10 makes me wired so i am going to stop taking it but continue with teh activated B’s and the methyl guard i am in sydney australia so tomorrow i will call and see a professional on Methylation because i feel it’s the key to my long term health. I suspect i contracted Lyme from all teh blood transfusions i had. If anyone had any advice i would really appreciate it. I was originally diagnosed with fibromyalgia but then we discovered the lyme

  210. Elizabeth October 9, 2014 at 11:06 pm # Reply

    Dr. Lynch..
    Or someone …….. Can answer this question?

    I am compound heterozygote – with a long list of medical and mental problems such as anxiety, depression, etc. I have looked tirelessly for a doctor… NO help there.
    Recently my hair has been falling out. I am running out of time here and I NEED a doctor and with my son being newly tested, I have to find one to take care of him.
    I’m worried about him and long term knowledge and care.

    Does anyone know if hematologist work with this ? I have tried gynecologist, primary doctors, endocrinologists, dermatologist, psychologist, psychiatrist, neurologist and no help. I do not want my son to suffer the way I have been so I need to find somebody for him to give him awareness.

    I’ve read mixed things about being compound hetero ( me) and compound
    homozygous ( my son)
    My sons blood work just came back and it actually says; Two copies of MTHFR c.665>T

    So my son is compound homozygous.
    I sure hope that’s not bad, but I am reading ALL kinds of mixed information.
    Can anyone clear this up for me ?
    Is the c.665 the same as the c.677 ?

    Also, does anyone know of a doctor near , In or around cincinnati Ohio area ? ( do not need pediatrics per say , anyone willing to help , please )

    Thank you!

    • Susan October 14, 2014 at 11:07 pm # Reply

      Elizabeth, You may want to look for a naturopath or a doctor of integrative or functional medicine. Some MTHFR websites have lists of practitioners who specialize in MTHFR, also some chiropractors . I am trying a nutritional therapist who has MTHFR herself. Most medical doctors do not have the nutrition background that we need. Good luck in your search.

      • Sharon October 15, 2014 at 4:59 pm # Reply


        May I ask the location of the nutritional therapist you are seeing?


        • Susan October 15, 2014 at 5:47 pm # Reply

          Burlington VT

          She has done everything by phone so far. She may be willing to consult by phone and email????? Some people have also found MTHFR docs who do that and have had good luck with them.

  211. Serena Arbuthnot October 14, 2014 at 12:42 pm # Reply


    I have been following your website for years. I found that I am Heterozygous for Factor V Leiden (R506Q) and Homozygous for C677T with normal A1298C. I have had 6 miscarriages since having my two boys earlier in life.

    My son’s results came back as Heterozygous for Factor V Leiden (R506Q) and Compound Heterozygous for one copy each of C677T and A1298C. (I assume one copy from me (C677T) and one copy from Dad? (A1298C)

    Shayne was born without his left main feeder artery and had to have open heart surgery at 3 months old to make a new artery out of the pericardium that surrounds the heart.

    Shayne’s symptoms are extreme fatigue, headaches, low testosterone, muscle cramps, and major ADD.

    I need help to get him on track and feeling better with diet and exercise. We are now all taking VitaMed MD plus Rx which has been great because it is only 5 dollars per month and comes directly to the house. We are also taking a baby aspirin a day.

    My father was just tested and we are waiting for the results. His homocystine levels came back as 15.6 which is high.

    Please give me any advise as to how to help our family.

  212. Carrie October 14, 2014 at 9:08 pm # Reply

    Dr B. I am positive for 2 copies of the a1298C.
    Results ” is homozygous for th e a1298c and negative for the c677t…..

    What does 2 copies mean? And what should I be doing????

  213. Jodi Goering October 17, 2014 at 10:56 pm # Reply

    I have hetro A1298C mutation. My integrative doctor is having me take O.N.E. Multivitamin with metafolin L-5 MTHF, probiotics and rhodiola. I had a healthy baby boy in February 2012, a miscarriage in December 2013, I have had symptoms for years of fatigue, mood swings, irritability, insomnia, stressed, depression, anxiety, breast cancer 2010, my mother, both grandmothers breast cancer ( I have tested negative for the BRCA 1 & 2 ) My vitamin D levels have measured in the teens for a few years now most recent test 7/25/14 was 21, vitamin B12 is 362 and vitamin A is 36, thyroid T4 is 1.07, iron 40, TIBC 321 and the iron % saturation 12. Is there other blood work I should have done?

  214. Aly October 22, 2014 at 5:22 pm # Reply

    I was diagnosed with this mutation in July 2014. I’ve had 2 miscarriages. They put me on one 325mg asprin a day and have said nothing else about it. Is there vitamin supplements I should be taking as well? Also, I’ve been on antidepressants for years. Is depression associated with this mutation? I need info!

    • Jodi October 30, 2014 at 10:17 pm # Reply

      Have you seen an integrative doctor? I would if I were you and seeking supplements – I was on anti depressants every one you can think of as well as anti anxiety meds. I now see an integrative health doctor. Good luck! Jodi

  215. Sep October 27, 2014 at 4:56 pm # Reply

    Hi Dr Ben,
    My was diagnosed with infantile spasm when she was 8 months old and she almost failed all frontline meds. Now after 8 months we have just found out that she positive for A1298C hetero. We have also done kryptopyrrole test and it wasn’t normal either. We had pest control one month before clinical symptoms. Do you think these are related? My baby has developmental delay too. Any recommendation?
    Thank you so much.

  216. Rhona November 3, 2014 at 8:38 pm # Reply

    Dr. Ben,
    Lab results show me as Homozygous for A1298CC and normal for C677T. I could go on for some time about all my health issues. But I am concerned for my 38 year old son.
    He has not been tested, but wouldn’t it be likely that he would have some of the same mutation as myself? He is being treated with Xeralto for blood clots that traveled to his lungs following an injury to his knee.
    I would like to ask if he is likely a candidate to take the methylated folic acid and would that be safe while taking Xeralto?
    Some of his other problems include the following:
    Hand tremors (since childhood)
    Disturbed Vision
    Irregular heartbeat

    Thank you for your time!

  217. Joni Friberg November 7, 2014 at 12:15 am # Reply

    I’m confused. This article is about A1298C MTHFR, which I have. I’m currently going through my third miscarriage, with no other explanation of why from the doctors. I truly believe it has to do with MTHFR.

    But you state, in the 3rd to last paragraph says “Again, a single copy of A1298C MTHFR does not appear to be harmful unless it is combined with the C677T MTHFR snp – known as compound heterozygous.”

    Should I be concerned with my single copy of A1298C or not?

    • Dr Lynch November 8, 2014 at 7:49 am # Reply

      Joni –

      I would not be concerned about a single MTHFR A1298C SNP. I may have some information that is contradictory as my education increases as does my clinical experience. I recommend further genetic testing through 23andMe or your doctor. Factor V Leiden is very important to evaluate.

      • Joni Friberg November 11, 2014 at 10:41 pm # Reply

        Lab results for Factor V Leiden is negative.

        I am now going through my 3rd miscarriage. Any other ideas?

        • Heather November 11, 2014 at 11:46 pm # Reply

          Hi Joni,
          Have you looked into the PCOS ?
          Just a thought.

          I don’t want to say to much about it as far as medical facts because I’m going off memory but while trying to find a dr for MTHFR I found a doctor who had done research on MTHFR so I went and saw him. Turned out he didn’t know to much, if any about MTHFR but treats PCOS .. Helped many women with pregnancy. While waiting in the waiting area, I read letter after letter after letter.. women had written him thanking him for the treatment of PCOS which in turn stopped the miscarriages and infertility issues they were having.
          Just a suggestion. Don’t know if you have explored this route but thought I’d throw it out there just in case.
          Hope it helps you.

  218. laura November 7, 2014 at 10:28 pm # Reply

    I have homogeneous A1298C mutuation. I’ve been experiencing severe hypoglycemia symptoms. Does anyone know if there is a correlation? My doctors can not find anything.

  219. Nan November 8, 2014 at 3:59 pm # Reply

    Hello Dr Ben,

    My son is 28 months and was dx with autism. After being on gfcfsf diet he has no sensory or autistic issues exept being nonverbal and some minor GI issues which we are treating. We started him on mb12 injections and are seeing overall focus but not speech. He lost speech after his 15 month mmr.

    Here are the 23and me results-
    1. MTHFR a1298c +/-
    2. COMT v158m and h62h +/-
    3. VDR taq and bsm +/-
    4. MTRR a66g and a664a +/-
    5. BHMT 02 and 08 +\-
    6. CBS a360a and c699t +/-
    I have been very concerned about his speech. He gains some words but is never consistent. Please provide your suggestions Dr Ben. Will methyl folate or dealing help with speech on top of methylb12?
    Thank you

    • Dr Lynch November 8, 2014 at 10:37 pm # Reply

      Nan –

      I would consider putting some Optimal Creatine in his bottle about 1 scoop – and a little of Optimal Electrolyte (1/4 scoop) and can do both a couple times a day – spread out by about 4 hours or so.

      Creatine is known to be deficient in those with autism and speech delay.

      Make sure he drinks adequate water to stay hydrated as creatine absorbs a lot of water.

      His SNPs do not look that bad to me – the ones you included.

      Need to check his GAMT, PEMT, PON1, BCMO1 and Methylation status.

      Check those genes by running the MTHFR Support report

      Have your doctor order the Methylation Profile by Doctors Data. If they cannot or won’t, you may order it here: Methylation Profile by Doctors Data.

  220. Sophie November 10, 2014 at 12:07 am # Reply

    Hello Dr. Ben,

    just read about the boy above and maybe you could give us also some advice
    Our daughter is 5 years old and has an ataxia and speech delay.
    The speech is the major topic because it’s very difficult for other to understand her and
    she cannot speak long sentences just 2-4 words and she says not “I…” but her “name” instead of “I…”.
    Could you see a link to the sympthoms based on below results?

    The MTHFRSupport Results are:
    ACE Del16 +/+
    ADD1 G460W +/+
    MAO A R297R +/+
    MTHFR A1298C +/+
    MTHFR rs1476413 +/+
    MTHFR rs4846049 +/+

    In Addition we got following Organix Comprehensive profile results
    High a-Ketoglurate 40.3 (Citric acid cycle)
    High Succinate 38.8 (ATP production)
    High a-Keto-ß-Methylvalerate 0.45 (Impaired Isoleucine metabolism)
    High ß-hydroxyisovalerate14.9 (Impaired Isoleucine metabolism)
    High 8-Hydroxy-2-deoxyguanosine 8.1 (DNA oxidation product)’
    Very High Glucarate 18.2 (Hepatic Phase 1 and 2 detox)
    High Pyroglutamate 112 (Glutathione wasting)
    Normal Methylmalonate 1
    Normal Forminioglutamate 1.9

    and +/- for
    AGT M235T/C4072T
    CBS A13637G
    CBS A360A
    CBS C19150T
    CBS C699T
    COMT H62H
    COMT V158M
    DAO rs3741775
    GAD1 rs12185692
    GAD1 rs3828275
    GAD1 rs701492
    GIF (TCN3)
    MTHFD1 C105T
    MTHFD1 G1958A
    MTHFR 03 P39P
    MTHFR A1572G
    MTHFR G1793A (R594Q)
    MTHFR rs3737964, rs4846048
    MTRR A66G
    MTRR rs3776467
    NOS2 rs2297518
    NOS3 rs1800783, rs1800779, rs3918188
    PEMT rs4244593, rs4646406, rs7946
    SHMT2 rs34095989
    TCN2 C766G
    VDR Bsm

    Thank you

  221. Greg November 12, 2014 at 11:46 pm # Reply

    What should I do for heterozygous mthfr 1298a>c ac? Any supplements?

  222. Heather November 13, 2014 at 4:40 am # Reply

    Dr. Lynch,

    How can I possibly deal with doctors who won’t listen to me or give me the time of day to even pass along information that would help them, help me ?
    I have looked high and low for a doctor. I have been to three family doctors, hematologist, endocrinologist, gynecologist, neurologist, DO, can’t find a naturopath in my area.

    How many classes do doctors take when they take your training ? Are there levels of this training ?

    So another one bites the dust……..
    The last appointment with a very well known hematologist did me in, so to speak. I have almost lost all faith in the medical world.
    I made so many phone calls and I point blank asked if the doctor knew about MTHFR, how to work with it if it needed to be worked with, will they run proper blood testing … Etc.
    I asked because I am tired of going and then asking and they look at me like I’m crazy. I thought that approach would gain some sympathy from one of the doctors and they would decide to want to learn [with me ] and get me healthy. As time keeps passing the worse I am getting. So, I go to the blood doctor with very high hopes, so excited,,, telling my family and friends how excited I was and I just couldn’t wait to meet him.
    When I arrived I was the only patient there and all other staff had gone home. I was the last patient.. Victim. That’s how I felt. Victimized.
    He tells me he can’t help me because those are my genes and that would be like me asking him to ” change the color of my eyes from blue to brown ” he said.. it’s just your genes and nothing you can do about it.
    Furthermore , he says, that my compound heterozygous mutation isn’t anything to be concerned about. He states that my two abnormal copies is like a mathematic equation where two negatives equal positive so – he says – I’m actually normally anyways.
    I was crying at this point in pure defeat and knowing better from learning from Dr. Lynch research and videos.. And what about ALL my symptoms ? I am 37 years old and I have been disabled for 3 years now.. Disabled at 34 and no one knows why ? I want to be a functioning, normal, living adult. My gosh if someone would help me. This is ridiculous because I know in my heart of hearts that it can be fixed, I can be fixed.
    This doctor ended up asking me to leave because I was crying. He never ran blood test, never looked at my blood work I brought with me that is over two years old, he didn’t even look at me other then a easy pay check..
    What he did was bill my insurance for 600.00 and I was there for approximately 7 minutes.
    I didn’t know he couldn’t change the color of my eyes.. What a shame and a disservice.

    I’m sorry for the rant but we really need more Drs like Dr. Lynch.

    All I can do is keep self educating, I guess. Seems like the only option, unless someone has any ideas they would care to share ? Any categories of doctors I’m missing ?

    • Dr Lynch November 14, 2014 at 7:43 am # Reply

      Heather –

      It is so sad to read of these experiences with doctors. Sorry that you keep experiencing this.

      There are plenty of good doctors – but sadly they are indeed hard to find.

      The list of ‘Find a Doctor’ here on MTHFR.Net is pretty good and so is the Physician Directory at

      Good doctors:
      – Orthomolecular
      – Naturopathic Physicians
      – Functional Medicine
      – Environmental Medicine
      – ACAM

      Look for a doctor that belongs to one of those organizations and you should be in much better hands than that dingbat.

      He has absolutely no clue. He likely has no clue what ‘epigenetics’ is and that is what governs our genes.