Overmethylation and Undermethylation: Case Study

downloadI am going to share with you a classic situation which happens all the time.

I hear it a few times a week while working with clients and guiding various doctors.

This case study shows how fast methylation can become imbalanced – and how fast it can be rebalanced.

It also shows how sensitive methylation is – and how careful one must be with it.

I encourage you to not alter your physician’s treatment plan without discussing with them first – and obtaining approval.

Here is a short case study demonstrating the speed and sensitivity of methylation:
A gentleman with MTHFR homozygous C677T, in his 60’s, is experiencing symptoms of depression and fatigue.

Yesterday, I consulted with him for the first time.

His physician prescribed Wellbutrin, Armour Thyroid and Arimidex.

Then, his physician prescribed methylfolate without tapering down the medications.

As expected, the methylfolate definitely began working – too well.

Here is some of our dialogue via email:

Dr Lynch – June 25, 2:46 PM:  I think you are going to have to taper down on your thyroid, Arimidex and Wellbutrin once you begin methylation. You’ll have to have your physician monitor and help you with this.

Client – June 26, 2:55 PM: I stopped the methylfolate and B12 yesterday afternoon and took 500 mg niacin and I feel pretty down and foggy today – and nauseous.

Dr Lynch – June 26, 2:55 PM: 500 mg of niacin is quite a bit – I typically suggest people start with 1/10th of that – 50 mg. Get back on the methylfolate and B12 and stop the niacin – appears you are undermethylated.

Client – June 27, 4:03 PM: Well if I wasn’t a believer before I am now! I felt better almost immediately after restarting the methylfolate at 400 mcg. This morning I felt a bit anxious so I took 50 mg niacin and felt calmer within the hour.

I spoke with my psychiatrist this morning and he said that the methylfolate will boost the effectiveness of the Wellbutrin, but I suspect that it’s reacting more with the Armour and making me hyperthyroid. That’s easy to test though so if it persists I’ll do a lab to see.

What is going on here?
This is a classic balancing act between how much methylation is ideal.

You can see exactly how fast the balance can shift.

First, the client is obviously undermethylated due to his symptoms so his doctor appropriately addressed it through prescribing methylfolate and methylcobalamin.

The only issue is the doctor did not realize how effective methylation is at supporting neurotransmitters and thyroid hormone production.

So what happened is the gentleman decided to skip his methylfolate and methylcobalamin dose, take a lot of niacin (which is a methyl ‘sponge’) and he immediately tanked his methyl groups which caused symptoms of undermethylation.

Then, upon restarting the methylfolate and methylcobalamin, and maintaining his current dosage of medications, he felt great for a few hours.

Then anxiety hit due to excessive neurotransmitter production and likely thyroid hormone production.

So – in order to quiet those symptoms, I told him about how niacin works and how to take it and his anxiety decreased almost immediately.

My point:
There is no set MTHFR protocol for anyone.

Genetics, lifestyle, diet, medications all play a role in how much methylfolate and methylcobalamin are needed – and these amount can change daily as well.

Finding a doctor that understands this is critical – or you will have a difficult time regaining health – and maintaining it.

Why Niacin??!
You’re likely wondering why niacin was so effective at reducing this gentleman’s anxiety.

I’ll let you in on the secret and wonderful actions of biochemistry.

Niacin restored his mood in two ways – at least the two three ways that I am familiar with:

  1. Nicotinic acid (Niacin USP) requires SAMe to be metabolized. SAMe is a major methyl donor. Thus, when one consumes niacin, SAMe gets used up and methyl donors drop. Thereby excessive methylation goes away.
  2. Nicotinic acid also supports the elimination of glutamate. Many with elevated levels of glutamate do not do well with methylfolate or any type of folate until the levels of glutamate are balanced.
  3. Niacin supports the feedback inhibition of the IDO1 gene which feeds into the kyurenine pathway. This pathway can deplete one’s tryptophan levels which makes them low in serotonin. The niacin slows the loss of tryptophan by pushing it towards serotonin formation.

Comments welcomed below.

Share your stories and experiences of undermethylation and overmethylation.

Did it happen to you in the same day as well?

89 Responses to “Overmethylation and Undermethylation: Case Study”

  1. Kayla June 28, 2012 at 1:11 am # Reply

    I sure appreciate your research and your generous sharing of information! My brain power has been severely limited due to health issues, so please forgive me if I’m misunderstanding or slow to understand.

    I have both copies of MTHFR with the same C677T mutation. This was discovered just a few weeks ago, but we felt it explained a good number of my lifelong health issues. (I am a 51yo female.)

    So my new MD-turned-alternative/natural practitioner started me on her own compounded mixture as an injection that my husband gives me. I don’t know all the details about it, but it has methylfolate and methylB12 and amino acids as well as some other natural ingredients, at a dose of 2ml each week.

    I had my 6th shot Friday evening but didn’t sleep well that night (I have struggled with sleep problems for a few years now) and Saturday I felt weaker and more fatigued than I had in a long time, even cancelling plans because of it. And I’m experiencing bouts of anxiety. I’m a little better each day, but I feel that I’ve slid back to how I was before the shots – and this was just after my very best week in years.

    I was blaming this sudden regression on eating pork – I haven’t had any in a very long time, and recent testing indicated that I’m allergic to it (IgG). I’m also experiencing hot flashes and other menopause-related trouble, so I thought maybe my hormones did a major shift. But if I’m reading this article correctly, could it be that I’ve already pulled up my B12 and folate levels and this most recent injection was too much? Could taking niacin relieve this feeling and return the newly gained energy and higher mood I was experiencing last week? Any insight would be greatly appreciated.

    • Dr Ben June 28, 2012 at 7:41 am # Reply

      Kayla –

      Exactly.

      I believe you may be yet another example of someone who is now overmethylated and using 50 mg of Niacin may really help bring ‘you back’.

      Do talk with your doctor that you believe you are overmethylated, give your symptoms and talk with them about taking 50 mg of niacin.

      You may need to take the 50 mg twice in a day – depends on how much methylation is going on along with how much the COMT enzyme needs niacin to help break down the anxiety-causing neurotransmitters.

      I also caution about ‘mixtures’ especially right out of the gate. I feel that people need to start methylation one nutrient at a time – beginning with vitamin B12. Once that goes well for a week, then introduce methylfolate – and then B6, then TMG, then B2, etc

      This way one knows which nutrient is working well – and which is not – and it also speeds up the methionine cycle slowly – not all at once.

      • Kayla June 28, 2012 at 10:53 pm # Reply

        I so appreciate your feedback! I left a message for my doctor today and got a message back. Wish I could have talked with her. She didn’t feel I was overmethylated (not completely sure I agree, but this is all new territory for me), but she did say the niacin would be good for me. At the health food store the gal said she’d not heard of such a tiny niacin dose as 50 mg. All I could find was a 250 mg niacin in a 2-stage time release – half fast-acting and the rest time-released over 8 hours. Is this dose and the 2-stage situation going to cause problems for me? (I’m due for my shot tomorrow and plan to drop the dose from 2 ml to 1.75 or even 1.5.)

  2. MJ June 28, 2012 at 5:26 am # Reply

    I can relate to this story as I’ve been on antidepressants for years. It wasn’t until this past spring that I found out that I’m homogeneous with A1298C mutation gene. My naturopath started me on 1mg 5-MTHF and eventually up to 2 mg. However, I was still on Wellbutrin. After a couple months, I felt like I was going to jump out of my skin. I was so anxious that it wasn’t until my husband noticed that the Wellbutrin side effects was what I was experiencing. In other words, my neurotransmitters were kicking in with being methylated that Wellbutrin put me into overdrive.

    Since I was on a very low dose of Wellbutrin, i stopped taking it for a few days and I felt fine. No more stiff neck pain or wanting to jump out of my skin. I felt relaxed. I did visit my doc after those few days and she agreed that I no longer needed the Wellbutrin.

    I did have a bit of a lull/sleepiness from coming off the Wellbutrin, but with help of Rhodiola, I’ve regained some of the get up and go energy/neurotransmitter that the Wellbutrin provided and that the methylation might not be providing.

    This does make me wonder if adding a bit more 5-MTHF would assist with.

    • Dr Ben June 28, 2012 at 7:44 am # Reply

      MJ –

      Thanks for sharing.

      Of all the articles I’ve shared, I think this one may be the most helpful so far as it really brings to light the side effects which are so commonly caused by methylfolate.

      I think trying more methylfolate along with vitamin B12 as methylcobalamin – may prove useful for you.

      Start low and work up.

      Vitamin B12 is needed to bring in the methyl group from the methylfolate. Without cobalamin, the methylfolate is worthless in the methionine cycle.

  3. diane June 28, 2012 at 3:54 pm # Reply

    wow! I have a loved one that has mthfr compound heterozygous 6677 and 1298 along with comt+/+ and finding this methylation balance to be very complex in trying to achieve. Im very grateful that the doc at least knew to test for it but Im not sure he is fully educated on exactly what to do. Thanks 4 sharing info.!

  4. Tracy June 28, 2012 at 4:00 pm # Reply

    Wow, I wonder if this is what is what is wrong with me? My doctor gave me deplin 15 mg after tests showed I am homozygous for a1298, 2 copies. Initially, I felt great, with a reduction in my depression and anxiety. Now I suffer from fatigue constantly, although I’m not depressed.

    After reading these forums and doing some research on my own, I’ve added in methyl b12, and b2 supplements, but it sounds like I may need niacin as well?

    • Dr Ben June 28, 2012 at 5:12 pm # Reply

      Tracy –

      You may – it is hard to say without more information.

      Please do share with your doctor how you are feeling and have your protocol adjusted. 15 mg is a LOT for someone with homozygous A1298C – or any MTHFR mutation in my opinion.

      • Tracy June 29, 2012 at 8:51 pm # Reply

        Thanks Dr. Ben, I appreciate the advice and will consult my doctor. I’m going to refer him copy some information from your site and take it to him as I have a feeling much of this is new to him as well, and he’s not considering other nutritional support. I’m going to try cutting the methylfolate in half for the time being. Thank you!

  5. SA June 29, 2012 at 12:56 pm # Reply

    Dr. Lynch

    I am a 41 yr old wife and mother to 6 and 9 yr old boys. 9 yr old has been a mystery since birth. Virtually meeting every major developmental milestone, except for language and cognition was slower to come. Since he was 3 and 1/2 it has been my quest to heal him. Some experts say he is not autistic others say they think he is somewhere on the spectrum, but they can’t quite say where he would fall on the spectrum. Where am I going with this? After relocating recently and a horrific experience in third grade we had yet another psych test done. He has a normal IQ, including non-verbal! We found an MD that does nutritional evaluations, but her practice is closed to new patients. By the Grace of God I was able to get him in to see her. Found he had too much bad bacteria and yeast. She suspected “leaky gut” and we began a whole foods diet. With pro-biotoics and supplements I saw almost and immediate improvement in many ways. She tested us both for MTHFR. We are both compound heterozygous A1298C and C677T. We are both now on 5-MTHFR 1mg. 2 capsules twice daily. I am now having high blood pressure episodes after taking 60 mg of vyvanse. It was as high as 143/ 99 yesterday. This morning it was 123 /72. I was diagnosed with ADD two years ago and have been on 2 capsules 2 times daily of 5-MTHFR 1mg for about a month now. I was just in my doctors office and no problems with BP. Now I am noticing a difference. I also take 40mg of Celexa that I would like to taper down and eventually stop. I have been on an antidepressent for anxiety and depression since the birth of our first child. I already have gone from 70 mg Vyvanse to 60mg. I am concerned for my risk of stroke or heart attack. High risk on my paternal grandparents and their siblings who all died of heart attacks in their early 50s and 60s and all were female. Please advise. I will be in touch with my MD also. I also let her know about your website. Thank you.

  6. Terri June 30, 2012 at 1:11 pm # Reply

    What about Hashimotos? I take armour thyroid and liothyronine. If I begin methylation could this turn around the functioning of my thyroid? Having gone through menopause at age 43 after surgery at age 33 due to endometriosis, I have been guided by doctors to take a number of supplements. I also have osteoporosis. Supplements include: cal assimilate plus, magnesium glycinate and multi vitamin complex from Klaire Labs; super d3, super vitamin b complex (not methylated) and esterol from Allergy Research Group; basic minerals from Douglas Labs; L Lysine from Solgar; and iodoral. I would like to begin using your optimal multivitamin. Do I start as directed- 4 twice a day? Should I continue any of my current supplements – in particlular iodoral, L Lysine? Thank you for all you do!

  7. Terri July 1, 2012 at 1:08 am # Reply

    I realized that in my earlier post I forgot to say I am heterozygous for C6771T.

  8. Robin July 20, 2012 at 5:36 pm # Reply

    Hi, I am currently going through a meth crash and very unpleasant it is too. I took 400 micro grammes of 5 mthf to boost my escitalopram and cymbalta, 60 mg and 10 respectively. After just two days I had more energy, my mood lifted a bit, but I felt very anxious. I took 25 mg niacin, then 50 mg four hours later. The anxiety dropped, but so did my mood. The next day I took 100 mg 5mthf and hope to improve on that dose.
    My questions are:
    1. I am confused about dosage. How come deplin starts at 7 mg but other formulas come in doses about 400 mcg, ie about fifteen times less? 400 mcg was too much for me, so surely 7mg would be dangerous?
    2. Is there a best time of day to take mthf?
    Thanks for the informative site
    Robin

    • Dr Ben July 25, 2012 at 7:27 am # Reply

      Hi Robin –

      It is all a balance and you are a perfect example – yet another one ;) – that demonstrates how fast the balance can tip.

      Deplin is a very high and potent amount of methylfolate. I do not ever recommend it but I know many docs do. I always start low and work up.

      The best time to take MTHF is upon rising, when you feel down/fatigued and some also find they do well taking it before bed – again – depends on which neurotransmitter imbalances you have.

      You will find out how much methylfolate to take and how much niacin. Ideally, you’ll just take the methylfolate when your mood is down or your thinking is slow. If you wake up alert, happy and ready to go, then I don’t recommend taking additional methylfolate. It may ramp you up too much.

      This is how I personally take methylfolate and I find it very useful listening to how I feel before I pop it in my mouth.

      We all need to understand that supplementation does not have to be done daily. The name itself – supplement – means that one uses additional nutrients when needed – not daily.

  9. Kathy Stocker July 21, 2012 at 4:01 am # Reply

    i have c677t one copy and of course doc put me on deplin15mg. After 2 weeks or so I was in bed feeling like I had bone cancer and extremely tired. Found your website and actually stopped taking deplin for a few days then tried again with half the dose and found myself in bed again. I also have stomach problems and read on your site if your gut isn’t right then work on that first then try again. Went to my family doctor and told her of this MTHFR results and she ran tests and my B6 was 110* normal range 5-50. Does this mean that the folic is just sitting there not able to be converted to folate? I have been so sick for 3 years now with diverticulitis, colon resection, arthritis, skeletal problems, fibro, knee replacements, adhesions in small intestines, blockages, and know of course depression from pain. Whole family has c677t. Each time I tried to start deplin, I find myself not being able to get out of bed. Now i started cutting the 15mg into 1/5 so roughly taken 3mg with 30mg of cymbalta. Im suppose to take 60mg but raises blood pressure and heart rate and makes me crabby! Psych Doc tests you for MTHFR doesn’t explain much and forget about getting a hold of them. You have to wait two mo, and don’t know what to do besides lay in bed and pray for a better day tomorrow. My Mom passed away at 61 with stomach cancer, i just had an upper and lower scope done yesterday and I am a big believer in probiotics. I trust you as I have researched your info and I will do any protocol you tell me. I feel like Im dying, I have totally lost myself in the past 3 yrs. I am currently 51, No ambition to do anything. I was fine 3 yrs ago taking care of my husband, kids, worked part time, cooked, cleaned, ect… now after total hyster 09 colon resection 10 and TKR 2011, depression fatigue stomach blockage’s and now C677t. B12 was 590 normal range >180 I also have hypothyroid and glaucoma diagnosed about 15 yrs ago. HELP!

    • Dr Ben July 25, 2012 at 7:19 am # Reply

      Hi Kathy –

      Sorry to hear that you are not feeling well and not receiving adequate guidance.

      You are right – gut first.

      Given the complexity, there is no way I can safely make any recommendations without a consult. I wish I could – well – in fact I can make one:
      – use castor oil packs over your entire abdomen and do daily –

      I do also recommend locating an integrative doctor that is near your home. I can help you via phone consults but you do need a great medical team that you can confide in locally. There are great docs out there – they are just not always easy to find ;)

      Should you like to discuss with me about where to start and how to start, I am available via consults. You may call 800-547-9812 or you may RSVP online as well. Given your complexity, an hour consult is highly recommended along with the pre-consult questionnaire. Lab testing is not needed if it is older than 6 months. There is also a lot to go on without lab testing results.

  10. p July 22, 2012 at 5:07 pm # Reply

    Does niacinamide interact with folate in the same ways as nicotinic acid ?

    • Dr Ben July 25, 2012 at 6:38 am # Reply

      I believe it does – yes – however, I do use pure nicotinic acid personally with my clients and that is what I get results with over and over again. Amazingly, the results are fast and dramatic. This single recommendation has literally changed the lives of many many people. I highly recommended it during the appropriate times.

  11. anne marie July 31, 2012 at 1:21 pm # Reply

    My son is 6 years old and diagnosed with ASD. At age two his bloodwork showed very evelated levels of B12. His DAN dr at the time noted a MHTFR mutation ( not sure how he came to that conclusion) . We used B12 injections for about 8 months and he did make good progress during that time but we didn’t know what to attribute it to b/c we were trying so many things at once. Looking back now his progress has slowed through the years. Perhaps the injections were doing more than I assumed. Recently, after listening to your podcasts and reading your work I started using a good quality multi vitamin which which has folate as well as b12 methylcobalamin (klaire labs vitaspectrum). What does an elevated level mean Do we still supplement with B12? Is the supplemental version as good as injection. It was so diffivult to inject him, one of the main reasons we stopped.

    anne marie

  12. melvin August 1, 2012 at 6:25 am # Reply

    I have MTHFR C677T++ and COMT V158M++ plus 3 other homozygous and 5 hetero snps. Will the niacin help with the overmethyllation and anxiety since all of my comps are homozygous.

    Since my comp is slow at breaking down and you said niacin is used to make the enzyme that is used by these snps…….is this something that can be part of the protocol that would help these defective snps.

    • Lynn_M August 1, 2012 at 5:26 pm # Reply

      C677T++ causes low methylation, whereas with COMT V158M ++ the metabolism of methyl groups is downregulated, and lots of free methyl groups are hanging around. What happpens when you put those two mutations together – does each offset the other or does one predominate? And how do the other mutated snps play into this? I suppose symptoms could be an indicator. You mention anxiety. Have you ever had your homocysteine, folate, or MMA levels tested?

      Niacin doesn’t work as you say. Rather, as niacin gets metabolized, it uses up methyl groups. So that would help with the COMT V158M++ excess methyl problem, but it works against the lack of sufficient methyl groups from the 677T++ mutation, if you look at the two pieces separately.

      It seems to me that trying to figure out theoretically what each genetic piece is doing is fruitless, particularly because you don’t know which genes are expressed. I think you’d be better off doing a functional test such as the Methylation Pathways Panel by Vitamin Diagnostics (now called Health Research and Diagnostics Institute). That test gives you the total picture of how well your methylation pathways are actually working. Dr. Ben offers it at http://www.seekinghealth.com/methylation-pathway-panel-vitamin-diagnostics.html.

      • Dr Ben August 1, 2012 at 5:59 pm # Reply

        I want to add to Lynn’s great response:

        Niacin is also a cofactor for the COMT enzyme so it appears to help speed up the COMT enzyme despite the mutation that is present.

        One may look at dealing with MTHFR and COMT mutations together as ‘driving with one foot on the gas and one on the brake.’

        It is common for those with COMT mutations to suffer anxiety, irritability while on methylfolate and/or methylcobalamin. These signs of irritability can be reduced by taking niacin, using less methylfolate and using less methylcobalamin – while at the same time supporting your liver via nutrients, diet and lifestyle changes.

        • melvin August 1, 2012 at 7:41 pm # Reply

          Thank you Dr. Ben for all you do….you do make a difference in peoples life..

          i’ll try the niacin….besides i always felt better when on b complex…trying to figure things out is so hard…for every study theres another study with opposing finds even vit d now my doctor says it can cause pancreatic cancer

        • S.G. August 10, 2012 at 9:10 pm # Reply

          A few q’s-
          So, if you take 50mg of Niacin you may feel relief from overmethylation, but if you take let’s say 250mg then you can feel depressed because you’ve eatin up too much methyls and this halted Nuerotransmitter production?
          I read in several places that Serotonin can be raised by Niacin. So, would the depression be more from dampening the Catecholamines?
          That being said. If someone were “Bipolar” or had high Cats and low Serotonin. Could they take Niacin with 5htp or similar and maybe get some relief without triggering “mania”?

      • melvin August 1, 2012 at 7:33 pm # Reply

        Thank You Lynn for your response…..Does the test reveal anything different than Dr. Yasko’s ?
        Dr.Ben had said that niacin helped the enzyme that is used in the comp snp and yes it also used up methyls. I’ve researched for 35 yrs trying to find that something that was missing or I needed. Vitamins, herbs, amino acids and all test were dead end. Tested different diets, foods, single amino acids and on and on. Finally my Dr. tested b12 and it was slightly low she said and started me on you guessed it cyanocabolamin….made some difference but wasn’t the magical cure.

        Started following Fredd and Richvank on Phoenix rising and learned about methyl b12,methylfolate and all co-factors. Had hyc checked and it was 53..wow…added in tmg and other things and got it under control. Also folate test was way high but little did I know then about unmetabolized folic acid. Following them is what led me to be tested at Dr.Amy Yasko’s site and found out that I have 2 comt homozygous 1 comt hetero vdr fok missing mao a missing mthfr c677t homozygous mtrr a66g hetero mtrr 11 hetero cbs a360a hetero shmt c1420t hetero nos d298e homozygous

        Read and researched everthing that I found and been following Dr.Ben for awhile now also.
        I had gotten so bad that I was bed bound for2 years and couldn’t even lift my arms to wash off and wheel chair to go to doctors……….methylb12 the life vitamin that helped when all neuro, gastro and hemo docs couldn’t..the cyano shots never got my b12 to stay up or fix my problems just like Fredd talks about.
        Added in metafolin methylfolate and got even better but short lived like Dr.Ben said I had reactions after 3 months after I thought I had found the secret ingredient….back of head hurt so bad and anxiety something I’d never had….if only I’d heard of Dr. Ben’s remedy and the cause overmethyllation wouldn’t have had such a setback
        Rambled too much……thank you again and I’ll look into that test
        Best of life to you melv

        • Lynn_M August 2, 2012 at 6:25 am # Reply

          Melvin, the methylation pathways panel is not a genome test, so nothing like Dr. Yasko’s methylation panel. Go to the link I gave and click on the blue Methylation Pathways Panel Sample Report.on the left side of the page. It lists everything that gets tested.

          Richvank says this is the often times the only lab test that will turn up anything amiss in people with CFS/ME. He has recommended it many times on Phoenix Rising. He discusses it on one of his sticky pages on PR. Do a search on the “methylation pathways panel” and richvank as the author.

          I’m not as familiar with the COMT mutation as MTHFR, so wasn’t aware of niacin’s role in that snp. I was half right, half wrong there. Good to learn more.

          I think you may have found the secret ingredient for your situation, it’s just that you went from one extreme to the other. Now you just need to learn what doses you need to achieve a happy balance between the COMT and MTHFR mutations and who knows what all the other mutations are doing. Since your hcy was so high to start with, maybe that will be a good marrker for you down the road as a measure of how well your methylation is doing. If you do the methylation pathways panel, I would do a hcy at the same time, to see how well it correlates with your methylation test results.

          Your struggle sounds a bit like Freddd’s (note it’s ddd). I hope you’re familiar with his story, because his near-normal outcome should be an inspiration for someone like you that battled a mystery illness for 35 years and became wheelchair bound, as he also was. Sounds like you’ll be joining him as an inspiration story yourself.

          • pat November 3, 2012 at 3:48 am #

            HI lynn, could you please forward me a link about Fredd’s story, I cant seem to find anything about his story anywhere.Thanks.Pat.

  13. jane gilman August 6, 2012 at 1:21 am # Reply

    I am compound heterozgous mutation.

    Because of bad arthritis in my knee I have been taking SAMe (1200mgs) daily for past few months which has really helped. But I see SAMe may not be a good supplement for my mutation.

    My question is: if I take metafolin, methyl B12 and Niacin will that allow me to safely supplement with SAMe. I am a vegetarian for decades now and quite healthy otherwise with no chronic health problems. I am 54 years old.

    May be good to have a phone consult if you’re still doing that.

    • Dr Ben August 6, 2012 at 8:38 am # Reply

      Hi Jane –

      You may be benefiting from SAMe – it may be just fine for you.

      If you take metafolin, methylB12 and niacin – it may help – or it may be too much for you. Since you are a vegetarian, the methylB12 may be the first place to start.

      I am still doing consults – this week is very busy but I may have some space available. Please call 800-547-9812 to schedule.

      • Barry September 26, 2012 at 5:31 pm # Reply

        First off, Thank you Dr. Ben for all you information here.
        A few things I’m so confused by and I hope you can shed some light regarding methylation and niacin.
        This is from a friend of mine who is one of your clients-
        “If people take way too much Niacin and have adverse reaction then they take an anti-histamine because they’ve likely created to much Histamine. Is that implying that if you take high doses of a co-factor, you speed up that enzyme?
        If that’s the case then why is Niacin said to eat up Glutamate when it’s one of only two cofactors in the enzyme that CREATES Glutamate from Glutamine. why doesn’t it hold true in this pathway and create more Glutamate? Niacin is not involved in any other enzymes in Glutamate metabolism. (to my knowledge). I’ll have to look into this more.
        And Niacin “sops up” or “uses up” methyls because it requires SAMe to be methylated and metabolized, but so does precursors like Tyrosine/5htp..it uses methionine and methyl b12 in the methyl-transferase enzyme. So if one takes high doses of 5htp….could they have a reaction due to using up too much methyls?
        I’d like to find some studies on how intake of and levels of cofactors actually effect the various enzymes.
        On a side note-I just read they’re now believing that it’s not the Serotonin/Dopamine etc… but the metabolites that the COMT/MAO enzymes breakdown that are the true Nuerotransmitters. Didn’t mention Histamine and Glutamate tho.”

        Can you clarify on any of this? I was asking her about Niacin/Methylation because I have some similar issues as her and she knows a lot. But I’m all over the place with my reactions to both Methyls sometimes and Niacin sometimes. I’d like to order your Methylation test.

        • Kimberly September 28, 2012 at 3:54 pm # Reply

          Barry,
          I also stated that Niacin plays a role in Glutamate oxidation but I didn’t know much about it. I will look into it more.
          As for the Nuerotransmitter/metabolites.I’ve came to understand this after researching hormones and Estrogen metabolism.I found that it is NOT the circulating levels of hormones that determines your true working levels but HOW they’re metabolized. For example, If your COMT pathway is blocked in the liver then estrogen is not metabolizes from it’s less harmful to a more water soluble form. Same with other liver pathways. This leaves you with more circulating estrogen but unmetabolized does not give you the benefits. It actually puts you at risk for cancers.
          This got me thinking about Nueros and whether or not the circulating levels matter or if it’s how they’re metabolized. I’m only guessing that if you had MTHFR , your excess folate would spill back down the pathway resulting in things like higher Glutamate and Histamine. So, I figure same thing with Serotonin. If you cannot methylate it into Melatonin, then it will spill down back pathways like MAO (which doesn’t require methyls) to 5HIAA, and Kynurenine pathway if your hydroxylase isn’t operating well, etc…
          These are just my thoughts so, don’t take it to the bank!

  14. Cindy September 10, 2012 at 3:18 am # Reply

    My son is homozygote to MTHFR gene mutation C677T and hetero for two COMT genes. He also has CBS, MAO A and NOS homozygote mutations. VDR Taq hetero.

    He’s on methyl folate 1 mg a day, hydroxy B12 1mg/day and methylb12 1 injection each 3 days. Also mlolibdenium, yucca everyday.
    Some days he is hyper. Other days he acts better.
    I wonder if the days he is hyper i should add a little of niacin to help. or it will be worse?

    Thank you

    • Dr Ben September 10, 2012 at 5:44 pm # Reply

      Hi Cindy –

      On the days he is hyper, I would consider some niacin – and use less methylfolate and less methylB12.

    • Lynn_M September 10, 2012 at 6:34 pm # Reply

      Cindy,
      Does your son get hyper on the days he gets the methylb 12 injection? Is there any pattern to when his hyper state occurs?

      If he gets hyper on the days he gets the methylb!2 injection, you might want to skip the hydroxy B12 that day or the day before, or reduce the methyl b12 injection dose.

      • Hannah S-Q September 29, 2012 at 1:41 am # Reply

        I thought I’d chime in on this one.

        My daughter is also compound heterozygous and I’ve had some trouble with the methyl b-12 shots. On the one hand, we’ve seen tremendous cognitive surges, but her mood and behavior suffers terribly when she gets the MB-12 shots.

        The first time we did them (last year) she was extremely hyper/cranky, etc. At that time I didn’t know anything about MTHFR, and we were doing it because of her seizure disorder (which has been in remission/seizure-free for 2.5 years now!) and her low lab levels of B6, B12, through the ONE diagonistic test.

        Our doctor recommended she be tested for MTHFR this year and she was positive (compound hetero) but I find it hard to find the proper balance methylation wise. I don’t have any of the other genetic mutation testing (can’t afford it at this time) so I don’t know if there’s something else going on.

        My story (if it helps Cindy) is that when we started this we were on higher doses of the P5P, methyl-folate. I feel that once we lowered the dose of those we saw less mood/behavior issues. It’s a nerve-racking thing for me because I worry that if I don’t provide enough of these active b’s for her then she may regress or, worse yet, begin having grand mal seizures again.

        A few months ago we began the B-12 injections again. Within a few days I saw the intense moodiness and problems. This is when I halved the folate (which was about 1mg, I believe, that we worked up to), and a small amount of P5P+, when we began the MB12 shots the second time around she did a lot better. Still some mood responses but not as bad as the last time.

        Unfortunately, I find myself in a similar position as I was a while back in that my daughter is getting incredibly cranky, weepy and obstinate. Something is off but I have no idea what and I have no way of testing it. She has been on the MB12 injections (along with the other nutrients I mentioned, plus probiotics, fish oil, vitamin D, etc and so forth) for more than two months now and so I wondered if it took that long for her to become overmethylated. This is all speculation.

        Today I felt really worn out from the constant moodiness, and concerned about my daughter, so I purchased some niacin and gave my daughter about 30mg. I will see what happens. I’m going back to sublingual b-12, and now I’m wondering if I should try hydroxycobalamin instead, as I haven’t had the greatest luck with the MB12, though I find the sublingual more tolerable mood-wise than the injections.

        I really wish I had a doctor to consult with 24/7 on this (for free-hehe) but that is unrealistic, obviously. These things are definitely not so much instinctual as they are experimental. I try to remember that when things are going badly.

        Excuse the ramble…

        Hugs,
        Hannah

      • Jessie January 5, 2014 at 2:37 am # Reply

        Cindy,

        I have a 10yr old, and I’m wondering how much niacin is safe to use. Have you figured this out yet? I’ve got the Seeking Health 500mg Niacin, so I’m sure I’ll need to split the tablet several times in order to give him the recommended pediatric dose. Thanks!

        • Dr Lynch January 5, 2014 at 10:21 pm # Reply

          Hi Jessie –

          yes – you will need to split this tablet of niacin into smaller pieces. The dose is dependent on what your doctor suggests and how your son does with it.

          BTW – I am currently making a 50 mg Niacin lozenge that will be easy for a child to swallow or suck on – along with a 50 mg niacin capsule – very small. Will be available at http://www.SeekingHealth.com around March 2014.

  15. Marlene October 6, 2012 at 3:59 pm # Reply

    I hardly tolerate any B12 supplements at all although my tests reveal I’m very deficient in methylB12, folate, B6, serotonin, etc.

    Before I injected cyanocobalamin but it was unbearable. My lab results showed I don’t break down cyanide. For over a year I tried hydroxyB12, it lifted my brainfod but it only worked for 24-36 jours.

    About 4 months ago, I started 1/10 of 5 mg methylfolate and 400 mcg metafolin as well as vit E, fish oil, 100 mcg selenium, 50 mg zinc, lecithin, 10 mg biotin, DL-phenylalaline, … I take 100 mg of niacin at bedtime because they are too painful and I have tendency to have a vasovagal response.

    My first reactions were limbs being paralised. After a few weeks and adding up the dose, I had tremor/parkinson like reactions for 3 days. After 3 months I finally reached 5 mg of methylB12 every 2-3 days but it makes me feel down, very down for 48 hours. I’m very upset, irritable, I feel suicidal and it makes me sick as well. Every part of my body hurts. I can hardly leave my bed.

    When it is passed, I feel much better but is there a way to avoid this?

    • llawrence April 27, 2014 at 11:43 am # Reply

      phenylalaline – stop it. too stimulatory. use tyrosine instead. monitor and adjust as neccecary… as you FEEL. not ___mg per day, every day.

      Niacin. firstly, dont take any since it blocks methylation. 100mg is too much! especially since you feel like fainting!. only take it if you feel anxious. 50mg max only.

      1/10th of 5mg is 500mcg. too much folate. plus you add 400 metafolin!
      get a 400mcg methylfolate TABLET(you can cut with a pill cutter from the pharmacy) and start with a half or quarter. forget about the metafolin.
      monitor and adjust as neccecary… as you FEEL. not ___mg per day, every day.

      5 mg of methylB12 is ridiculous. thats 5000mcg. get a 1000 or 500mcg sublingual tablet and start with half daily.

      use sublingual P5P B6 also. but start LOW. can make you feel anxious. get a 25mg tab and start with half or quarter daily.

      with everything- LISTEN TO YOUR BODY! —BEATS any test, anyday. tells you what you need. might take time to get the hang of it because there are many variables but it is worth it. you may need to “asses” each supplement individually to get the right dose that feels right.
      monitor and adjust as neccecary… as you FEEL. not ___mg per day, every day.

    • Michael (NW) May 19, 2014 at 10:34 pm # Reply

      Hi Marlene,

      Do you have an update? What is working what is not?

      I got more to share, but wanted to see where you were at with your health and what products you are now taking.

      Thanks.

      Michael

  16. Rosa October 18, 2012 at 2:16 am # Reply

    I have at least one copy of C677T (test only looked for “carrier status” so it didn’t look for two copies, but did check 35 SNPs associated with MTHFR).

    Just received my 5-methyltet…folate (Thorne Labs 1000mcg/cap) today and took one. Within 30 minutes I felt the entire left side of my body get very warm. Head, into mouth, down torso, down left leg was significantly warm as if warm water were being poured over just the left side of my body. Lasted about 10 min. Wasn’t painful, just strange.

    People in a MTHFR support group online said it was a detox response due to opening up the methylation pathways — I have Lyme disease poorly treated due to conflicts with the treatment drugs.

    I was advised by group members to use a lower dose. And taper up slowly. I thought I WAS beginning low. I haven’t read this reaction in your list of side-effects or on any other website with good MTHFR info.

    Not sure what detox products to use, either as I had a very bad painful reaction to low dose one time of chlorella. Figured it was metal toxicity being released. Not sure, obviously. But I don’t want to add this kind of pain to the one-sided warmth reaction.

  17. Amee October 30, 2012 at 7:25 pm # Reply

    Hello: I have suffered from both depression and anxiety for years and was recently found to have homozygous C677T mutation. However, upon taking methylfolate my anxiety symptoms seemed to have worsened. I stopped any methylfolate and tried niacin, starting at 100 mg and up to 300 mg of niacin at one time, but did not notice any improvement in my anxiety. For now I am not taking any methylfolate.

  18. janis bell February 27, 2013 at 10:43 pm # Reply

    I read in a book today that overmethylation can contribute to MCS. I’m not sure how this would work. If you can address this is another blog, I’d much appreciate the effort.

    • janis bell February 27, 2013 at 10:51 pm # Reply

      Hi, I want to add that I have been taking 800 mcg methylfolate (as Quatrefolic or metafolin) and 2000 mcg hydroxycobalamin for over a year, did not do well on higher doses, but am growing increasingly sensitive. My genetics are COMT ++. CBS+-. MAO+-, MTHFR C677 +-, MTR A196+-, MTRR K350A +-, NOS+-, ACE+-. I tend to have high or high normal MCV and MCH.

      Janis

  19. Bec March 1, 2013 at 9:21 pm # Reply

    Thankyou Dr Ben for this information.

    I am NOW – after many awful years of debilitating symptoms, beginning to realise i have methylation problems. Currently awaiting genetic test results.

    I have taken a silly high dose of niacin (flush form) and flushed like crazy for 2 hrs! Hives and nausea, i felt so sunburnt – but the next day – NO ANXIETY – for the first time in 3 yrs! I was amazed and at the time had no idea why niacin worked in that way for me.

    Another time i tried 400mg SAMe for depression/anxiety/ and to improve liver function – and had the most awful day – was very agitated and depressed and could have thrown myself in front of a bus – it was so awful. I believe this reaction is due to methylation issues too. Am currently researching more.

    Your site has helped me better understand this complex subject in simple explanations! Thank you so much for all your educational efforts Dr Ben – i’m healing bit by bit and now feel i’m finally on the right road to function fully once again.

  20. Gabriela March 18, 2013 at 10:06 pm # Reply

    Let me see If I am getting it. If I take niacin and I feel better that means that I was overmethylated in the first place? Because I went to the orthomolecular stuff way before I got the mtfhr test done. I did the niacin and it usually calmed me down, but never enough. A few months later (after being put on xanax and celexa to stop panic attacks) I went to a naturopathic doctor and she was the one who told me about my genetic mutations (heterozygous for MTHFR C677T and MTHFR A1298C). I am more confused than ever. I am taking luvox, no more xanax, but when I take methylfolate some days I am great some days the anxiety is too much. When I take methylcobalamin I feel totally drugged up and anxious like crazy. My naturopathic doctor has NO idea what else she needs to do and my psychiatrist just told me basically, that I am on my own if I drop the meds.

    • Robin March 19, 2013 at 1:18 am # Reply

      Likely too much. What dose were you on?

      • janis bell March 19, 2013 at 5:28 am # Reply

        Gabriela,
        Not all docs believe you have to use the methyl forms to get methylation going. (I’m thinking of Vinitsky and Yasko.) If the methyl forms rev you up and create anxiety, take hydroxy B12 and natural folates (for example, Innate Response has a B vitamin without artificial folic acid in it and folates as they occur in vegetables). Your COMT status could be making it hard for you to tolerate methyl groups, if like those of us who are COMT++, we are slow to break down dopamine and serotonin. Also, if your VDR is +, you will have even more difficulty with methyl groups because you’ll be using Vit D to make dopamine. Check out the information at heartfixer.com for each of the genetic variations you know you have.
        In my case, I could never tolerate antidepressants of any kind without getting horrid anxiety. Similarly get anxiety and palpitations from too many methyl groups. Yasko’s forum is another great source of information.

  21. birgitte rodh July 3, 2013 at 7:50 am # Reply

    Hi, I have experienced anxiety on/off for many years and also too early meno pause (at 39). During the last 2 years I have also developed a severe food intolerances (histamine, salicylate, grain, milk, sorbitol..). This started slowly but increased very quickly after exposure to mold, vaccines, penicillin and NSAIDs. Now I have taken the 23 and me gene test and I’m trying to figure out how to support methylation. I haven’t got the MTHFR mutations (luckily), but I do have 2 x COMT ++ and some +- : CBS, 2xVDR, MAO and several MTR and MTRR. I have had some good results already from adding GABA (Holistic Heal test showed I was low). It took away ear ringing and heart palpations, when I added 1/4 of a capsule – but 1 capsule a day gives me added ear ringing and heart palpation. But I believe GABA is not really a methyl donor, so will this qualify as an example of the switch between under/over methylation? I am trying to adress my COMT ++ but not sure how to approach this as my few trials have ended up with bad reactions, that I believe is sign of over- or under-methylation – but I’m not sure which one! Should I now add in niacin or other supplements for the slow COMT++ function to lower methylation and lower norepinephrine, epinephrine (and estrogen) and thus lower anxiety? But then I am actually not sure I am over-methylating as my Holistic Heal tests show I have high methyl histidine and low methionine, and this is supposed to be a sign of low methylation? And I have histamine intolerance, that is also a sign of low methylation. And niacin is also supposed to give a histamine rush – not exactly, what you need, when you are high histamine in the first place… So in this case, I believe methylation is very tricky – as if a mix of high and low methylation is already occurring before even adding methyl donors…. Could early meno pause (and ongoing hot flashes) be connected to the COMT++ and this unstable situation too, and so regulating this would help on those issues? – And could food intolerances be connected in any way? I am rather confused, but willing to do what is necessary, if I only know, what direction to take..

    • Janis Bell July 4, 2013 at 1:00 am # Reply

      Birgiite, I hope Dr. Ben answers your question as I have almost identical genetics and have had almost identical symptoms. I can’t take a lot of methyl donors due to my COMT++ and yet my tests show inadequate methylation and a need for methylation supplements, although serum B12 and serum folic acid and other forms of folate (except RBC folate) are normal.

      One thing I’ve discovered over the past two years is that my inflammatory reaction to mold and mycotoxins seems to interfere with methylation and it raises something (stress hormones? glutamate? histamine? all three?) that leaves me wired. When I get into the desert and there is no humidity, and a lot less mold outdoors, almost all of my symptoms disappear, a miracle after suffering with a diagnosis of ME-CFS for over 20 years.

      Before that I tried Yasko, Vinitsky, and Rich VanK’s approaches to methylation and nothing made a difference.

  22. Michael July 10, 2013 at 9:10 pm # Reply

    Hi, I’m also from Oregon. Grew up going to Sunriver. Love Central Oregon! Anyway, I have symptoms of under methlyation, and over methlyation. But, I think I fit more in the under methlyation. I had some blood work done over the past 2 years. More recently my himstaine level was high/normal. My homocystiene was high/normal. I have very high B12 in my blood, was up to 1700, now I think it’s 1500. I broke out with severe Anxiety 2 years ago, non stop, felt awful, then had panic, severe insomnia due to the start of adrenaline surges, then depression, now adrenal fatigue etc….Nothing really helped, although Ativan brought some temporary relief, but I rarely used it due to issues with Benzos. Anyway, had bad reactions to SSRi’s, Zoloft made me feel severely hopeless, high anxiety, impending doom, etc…Lexapro made me feel stimulated at first then numbed my emotions making me feel more depressed. About 6 months ago I went on a Amino Acid Treatment through a ND. It contained 5-htp, Tyrosine, Choline, Pantethine, MSM, Mucuna Puriens (l-dopa), SAM-e, with the addition of 5-MTHF and Methly B12. I’m assuming I was under methlyated, but I heard that Choline can cause OCD to be worse. But, my ND said if you are supporting Dopamine which we were with tyrosine and L-dopa then it shouldn’t be a problem. And I’ve read that Folate can cause under methlyators depression to worsen. So, I was worried about taking Folate although it’s an important factor to the methlyation process. Is it possible that folate is only an issue for a under methlyator if they have the gene defect that doesn’t allow the conversion of folate to 5-MTHF? I had the mutated gene test done and it can back negative. But, my blood tests showed I had which seemed elevated folate levels which worried me, but maybe because my methlyation cycle was stuck, and the reason for all this B12 not methlyating…(I did have magnsium/B shots for a few months and that might be how I accumulated a bunch of it, but for some reason I wasn’t methlyating or urinating it out). I also had the NutraEval test done by Genova Labs and it showed my body had a high need for B12, so maybe it was hanging on to it for some reason.

    Anyway, I’ve been on this amino acid therapy for about 6 months, slowly increasing the dose until I was taking HIGH doses of 5-htp and Tyrosine. I got marginally better, mood slightly improved so I had more interest in doing things, my anxiety/panic was lower but I still didn’t feel normal…I’m still concerned whether or not this mix is helping, or making me worse. I think the high doses of the aminos were over stimulating me, so I backed down to what they call a maintenance dose. That helped. Didn’t get anxious or sweaty after taking a dose…I recently decided to drop the SAM-e, too expensive, too many fillers, etc….I decided to use Methionine and DMG (didn’t have any TMG on hand) so my body can make it’s own SAM-e. And I hear that TMG and hopefully DMG can help kick start the methlyation process..So, I’ve been doing the DMG and Methionine for about a week, and I noticed an improvement in mood stability. So, maybe this is what I needed…I’m hoping for continued improvement….

    I’m still concerned about taking folate for 5-MTHF form of Folate, and how much methly-B12 I should take when I have an over abundance of unmethlyated B12 in my blood. I know MethlyB12 is really good for the methlyation process, so I’d like to take more of it, but I’d also like my body to use up the B12 it already has. Do I need more 5-MTH to do this? Is it safe to take for an under methlyator who doesn’t have the mutated gene? How much do I take? I know so many questions, but I don’t get a lot of answers from my ND’s… So I do my own research….

    I also had a test done recently, where I had to take a steroid pill (5mg) at midnight, then have my blood drawn in the morning to test cortisol. We were checking to see if I had overproduction of cortisol or something….I have an adrenal nodular on my left adrenal gland. Apparently it doesn’t seem to be producing excess hormones. I have to wonder though, that taking blood samples only one day if it will catch excess hormone production. I happened to feel pretty good that day I had the blood drawn. Anyway, my cortisol level was VERY low. So, I’m taking Isocort in the morning to bring that up. I think that has helped a little with brain fog/lethargy. My testosterone levels are also lower than they should be. I just had more blood drawn after 2 weeks of Cortisol treatment to see if my levels go up. If not, then I might have to take some “T” for a while. Could be why I’m still feeling a bit depressed, but not sure if it would cause my anxiety…

    When I first got really ill two years ago with anxiety, panic, etc…, nothing helped but ativan… Herbs either didn’t touch it, or made me worse. It seemed most things made me feel worse. Now, I can handle more herbs and things. Kava root REALLY helps. Kavinace helps some. Taurine really helps. I thought Magnesium would help, but it seems to stimulate me….strange…

    Sorry, I gave a lot of info, but if you have any questions, comments, suggestions that might help me, I’d appreciate it.

    Thank you…..

    • emma August 24, 2013 at 7:14 am # Reply

      Hi Micheal

      I just read your comment and sounds like what my partner is going through he has been diagnosed with pyrrole disorder but also has severe undermethylation levels,

      he is anxious, depressed, fatigued and is an insomniac and has to take medication to sleep.

      can i ask how you are doing and what has helped you?

      my partner is all so taking sam-e he has only been on it for about 3-4 months along with other medication he has been prescribed to take from his naturapath. he would be able to tell you more about what he is taking as i am not 100% sure.

      i am looking for any information or something that can help him or any one that has these conditions also,

      i would really appreciate any information you can give me also.

      you can email me at ecurn@y7mail.com

      Thank you
      Emma

  23. Jenny August 15, 2013 at 7:25 pm # Reply

    WHat would you recommend for someone who is compound homozygous COMT (+/+) then with severe anxiety. I also have several MTHFR (+/-) mutations, 2 CBS (+/-) mutations, and a SHMT (+/-) mutation. I have been advised AGAINST niacin in the past – wondering what the logic there would be if it works to help with anxiety (which I am on pharma meds for).

  24. Sara August 23, 2013 at 12:09 am # Reply

    Hi Dr Ben!
    I have been experiencing something pretty crazy for the past several weeks. I have one copy each of MTHFR C677T and MTHFR A1298C. I have been so freakn’ wound up and I can’t stop shaking parts of my body…it seems that I’m going to explode if I don’t move! I’m taking one capsule a day of methyl guard plus, ester C,D,E, curcumin,alphalipoic acid, beta carotene, Quercatin, CoQ10 and milk thistle…oh and mega dose of probiotics and fish oil. The weird thing is too, I just ran out of my methyl guard plus three days ago and that has not changed anything. Can you give me a clue as to what you think might be going on?
    I know you’re super busy so if you get the opportunity to answer, it would be much appreciated :)

    • Lynn_M August 23, 2013 at 6:10 am # Reply

      I would be suspicious of the alpha lipoic acid, especially if you have amalgam fillings. It is used to chelate mercury, but if not taken in small, very frequent doses, ALA will redistribute mercury around the body and across the blood brain barrier. You may have mercury toxicity symptoms.

    • Dr Lynch August 24, 2013 at 1:16 am # Reply

      Sara –

      Curcumin is a MAO Inhibiter so it may be causing you to be a bit more amped than usual.

      Consider Niacin to knock down that effect along with GABA.

      • Mary January 11, 2014 at 12:35 am # Reply

        Dear Dr. Ben,
        I have a 37 year old son that has gouty arthritis, Raynauds, fibromyalgia, chronic fatigue, depression………That’s just off the top of my head… He has been sick since he was a small boy. His fingernails turned white when he was a teenager and he was tested for all kinds of things. They found nothing. He has been going to a regular MD for the last several years. He is an arthritis specialist. He put him on Methotrexate, Cymbalta and Hydrocodone. The only thing my son has taken faithfully is the Hydrocodone. He is now addicted to them and struggles with this on top of everything else. He only took the Methotrexate for a short while then stopped thank God. I took him to the hospital this summer after watching him lay in bed with his legs so swollen he could not walk. I had to talk him in to going and it took me several days to convince him something was wrong. This happened after starting the Cymbalta. He was also on Nifedipine for the Raynauds. He got off of them both and the swelling went down. He is so sick and addicted that it is hard for me get through to him. However after his body swelled up twice its size he was willing to go see someone else. I was able to get him to a ND and she did bloodwork and had him do the 23andMe testing. It came back positive for the Mthfr mutation. I think he is compound heterozygous from looking at the paperwork.The dr was 20 min going over his bloodwork and genetic test so she only had 20 min to explain his results. She rushed through everything so fast that my son and I had no idea what she was even talking about. She didn’t even explain what Mthfr is or what the results were. She sped through the diet and supplements in 15 min and then said she had another client. The protocol she put him on he us unable to do. It is so complicated I cant even understand it and I worked in a Nutritional Therapists office for 5 years. My husband says he cant understand it either. After reading what you have to say I don’t think it is something he should do anyway. She has him on a rotation diet of low sulfate foods as follows. 1. Rotate for 3 days of sulfite containing foods and days of low sulfite containing foods. 2 supplements: for the 3 days of sulfite containing foods follow the MTHFR cycle supplements:example (help with Methylation and transufation) Methylfolate L-5-MTHF 60 caps take 1 per day. Sam-e 200 mg 30 tabs. Yucca 500 mg 100 caps sprinkle on meat. B. for the 2 days of low sulfite foods follow the CBS supplements (to slow down transulfation). Grapefruit 4 oz. 2 times a day (slows down phase 1 in the liver to allow phase 2 to catch up to help remove toxins in the bowels and urine. Molybdenum (Glycinate) 250 mcg (required for Suox to function, decrease sulfites) Vitamin E 400 IU take 3 a day.(decrease sulfites) Everyday: Probiotic ( to support immune and neurological function) 1 capsule a day HMF Intensive. Fish Oil 1000 mg 3 per day. Jarrow Methyl B 12 1000 mcg 5 per day. CoQ10 UBQH 3 twice a day.(for energy production) Vitamin D3 10000IU 1 per day. C (rotating in general: Add in Gaba if you feel anxious or need to even out your mood or shaky any time of day between 2 to 500 mg at a dose and this can be done 2 to 3xs a day. Creatine powder to support same drained with CBS upregulation and support production of ATP (energy) fuel for muscle contraction. 1 scoop in water 2xs a day. Taking B6 and zinc for Pyrulouria? (she didn’t finish this question because she ran out of time. My son was absolutely mute looking at all of this and said there was no way he would take all those supplements and no way he could remember all this or remember to take them on a rotation of food plus supplemnents as he can barely function. I said I would help him but it was very complicated for me to understand and we were out of money since it took all I had to pay for the appointments and bloodwork and genetic testing. She said if he was serious about getting well he would have to do what she has written. We both left the office totally overwhelmed and discouraged. I am hopeless. I am waiting for my results for the 23andMe myself and suspect I have similar issues. I have insurance and can see another Dr. but my son has no money and no insurance. Is there a simple way to start this process? I can help him with food and a few supplements but if he gets his Methylfolate through leafy green but they are full of sulfites I don’t even know what foods he can eat according to what I see in her instructions. I called her office and asked about the B6 and Zinc and was told I needed to make another appointment or email to get my questions answered. I am so depressed from all of this I don’t think I can continue but I am afraid if I don’t figure this out my whole family is going to continue to suffer and die. My mother died last year at the age of 86 from Ideopathic Pulmonary Fibrosis. I saw on another webside this is a condition of MTHFR. Is this true?

        • Mary March 16, 2014 at 8:01 pm # Reply

          Dear Dr. Ben,
          I have a 37 year old son that has gouty arthritis, Raynauds, fibromyalgia, chronic fatigue, depression………That’s just off the top of my head… He has been sick since he was a small boy. His fingernails turned white when he was a teenager and he was tested for all kinds of things. They found nothing. He has been going to a regular MD for the last several years. He is an arthritis specialist. He put him on Methotrexate, Cymbalta and Hydrocodone. The only thing my son has taken faithfully is the Hydrocodone. He is now addicted to them and struggles with this on top of everything else. He only took the Methotrexate for a short while then stopped thank God. I took him to the hospital this summer after watching him lay in bed with his legs so swollen he could not walk. I had to talk him in to going and it took me several days to convince him something was wrong. This happened after starting the Cymbalta. He was also on Nifedipine for the Raynauds. He got off of them both and the swelling went down. He is so sick and addicted that it is hard for me get through to him. However after his body swelled up twice its size he was willing to go see someone else. I was able to get him to a ND and she did bloodwork and had him do the 23andMe testing. It came back positive for the Mthfr mutation. I think he is compound heterozygous from looking at the paperwork.The dr was 20 min going over his bloodwork and genetic test so she only had 20 min to explain his results. She rushed through everything so fast that my son and I had no idea what she was even talking about. She didn’t even explain what Mthfr is or what the results were. She sped through the diet and supplements in 15 min and then said she had another client. The protocol she put him on he us unable to do. It is so complicated I cant even understand it and I worked in a Nutritional Therapists office for 5 years. My husband says he cant understand it either. After reading what you have to say I don’t think it is something he should do anyway. She has him on a rotation diet of low sulfate foods as follows. 1. Rotate for 3 days of sulfite containing foods and days of low sulfite containing foods. 2 supplements: for the 3 days of sulfite containing foods follow the MTHFR cycle supplements:example (help with Methylation and transufation) Methylfolate L-5-MTHF 60 caps take 1 per day. Sam-e 200 mg 30 tabs. Yucca 500 mg 100 caps sprinkle on meat. B. for the 2 days of low sulfite foods follow the CBS supplements (to slow down transulfation). Grapefruit 4 oz. 2 times a day (slows down phase 1 in the liver to allow phase 2 to catch up to help remove toxins in the bowels and urine. Molybdenum (Glycinate) 250 mcg (required for Suox to function, decrease sulfites) Vitamin E 400 IU take 3 a day.(decrease sulfites) Everyday: Probiotic ( to support immune and neurological function) 1 capsule a day HMF Intensive. Fish Oil 1000 mg 3 per day. Jarrow Methyl B 12 1000 mcg 5 per day. CoQ10 UBQH 3 twice a day.(for energy production) Vitamin D3 10000IU 1 per day. C (rotating in general: Add in Gaba if you feel anxious or need to even out your mood or shaky any time of day between 2 to 500 mg at a dose and this can be done 2 to 3xs a day. Creatine powder to support same drained with CBS upregulation and support production of ATP (energy) fuel for muscle contraction. 1 scoop in water 2xs a day. Taking B6 and zinc for Pyrulouria? (she didn’t finish this question because she ran out of time. My son was absolutely mute looking at all of this and said there was no way he would take all those supplements and no way he could remember all this or remember to take them on a rotation of food plus supplemnents as he can barely function. I said I would help him but it was very complicated for me to understand and we were out of money since it took all I had to pay for the appointments and bloodwork and genetic testing. She said if he was serious about getting well he would have to do what she has written. We both left the office totally overwhelmed and discouraged. I am hopeless. I am waiting for my results for the 23andMe myself and suspect I have similar issues. I have insurance and can see another Dr. but my son has no money and no insurance. Is there a simple way to start this process? I can help him with food and a few supplements but if he gets his Methylfolate through leafy green but they are full of sulfites I don’t even know what foods he can eat according to what I see in her instructions. I called her office and asked about the B6 and Zinc and was told I needed to make another appointment or email to get my questions answered. I am so depressed from all of this I don’t think I can continue but I am afraid if I don’t figure this out my whole family is going to continue to suffer and die. My mother died last year at the age of 86 from Ideopathic Pulmonary Fibrosis. I saw on another webside this is a condition of MTHFR. Is this true?

          • Amee March 16, 2014 at 11:47 pm #

            Dear Mary: I hope Dr. Ben writes back because it sounds like your son is having a very tough time. It sounds like that doctor was not very helpful, which is very disappointing. I can understand why you are depressed. I wouldn’t be able to follow those recommendations either. Personally, I would demand more attention –without additional payment–from this doctor.
            If you haven’t read these posts, maybe they will be helpful to you:
            http://mthfr.net/read-this-first/2012/01/25/
            http://mthfr.net/mthfr-c677t-mutation-basic-protocol/2012/02/24/

            Good luck , I hope your son finds some good help from a better doctor soon.

        • Kelly April 13, 2014 at 10:08 pm # Reply

          Mary, I noticed you mentioned both sulfate and sulfite containing foods. Sulfate is completely different from sulfite, and shouldn’t be a problem. Sulfites should be avoided.

          Also, you might look into mycotoxins. They are in tons of foods, and Dr. Joseph Brewer M.D. has found his patients who have been sick for 20-30 years are improving using an antifungal protocol. His paper was published in December.

          I encourage Dr. Lynch to look at this paper as well, as it shows a link between mycotoxins (in the environment, in foods, etc.,) and mitochondrial dysfunction.

          • Lisa November 25, 2014 at 12:02 am #

            Okay Danny, thanks.

  25. emma August 24, 2013 at 6:59 am # Reply

    HI
    My partner is 24 and suffers severe under-methylation and also has been diagnosed with pyrrole disorder.

    is there any one in this forum that has either one of these? or both?

    has any one been cured or have there disorder under control and is working and living a happy life?

    please any insight or information would be greatly appropriated.

  26. Brenda August 25, 2013 at 6:07 pm # Reply

    Hello Dr. Lynch,
    I am compound heterozygous for c677t and a1298c, my doctor put me on 15mg of Deplin which I’ve been taking everyday for approximately 2 years, along with 5000mcg of methylcobalamin, which I’m just realizing also has 400 mcg of folic acid in it. First question, Is this enough B12 for 15mg of Deplin? Also, just sent off for 23andme to find out if there are more mutations.
    Also, I have hashimoto’s and I started the iodine protocol, I started taking ATP cofactors which contains inositol hexanicotinate and riboflavin, I do feel like it has increased my energy, which is great! However, I’m concerned about this form of niacin, does it act like nicotinic acid, and reduce methylation? Any comment would be appreciated.

  27. josh January 1, 2014 at 12:09 am # Reply

    Hi Doctor Ben, I have a heterozygous mutation for the C677t and A1298, I started on 200mcg of 5mthf, then after a week moved up to 400 mcg and stayed on that for a week or so. I then added 1 mg of methylb12 and had some adverse reactions. I had severe chest pain around my heart as well as in the center of my chest. Increased heart rate, when I would lie down I could feel my heart beat in all parts of my body. Sharp pain in the muscles of my arms shoulders and neck(as if I was being stabbed by tiny needles). Depression, fatigue, and feeling incredibly sick like I was going to vomit for a few hours after ingesting the methylb12. It took about a week and a half for those symptoms to diminish. How could methylb12 cause those symptoms? Overmethylation? Detox? These symptoms struck me as being quite severe for overmethylation. I felt like I was doing pretty damn well on the 400 mcg 5 mthf. Any help would be much appreciated.

  28. Sherry January 26, 2014 at 9:51 pm # Reply

    I have the MTHFR mutation C677T, hashimotos , and anxiety. When I showed my chiropractor my results she said it was an easy fix and told me to take several methylated B vitamins.I felt horrible. Depressed,slow,tired,nauseous. I stopped taking them and most days feel my normal which is anxious,active,brain fog, memory issues, trouble finding words, insomnia but functioning. This weekend I have been very depressed,in bed all day which is not me at all. I am on cymbalta, alprazolam,tirocint 88, and cytomel.I excersie,eat clean, and I’m gluten free. These bouts of depression have been pretty severe and uncharacteristic.I have thought that I would prefer not to live at all then to live like this. Today I took fish oil, mentholated B complete, magnesium, and niacin. Feel nauseous.Also have chronic constipation. Any feedback would be greatly appreciated.Docs have been no help at all.

    • Amee January 27, 2014 at 7:32 pm # Reply

      Sherry: Since you have thyroid issues, you may find some helpful information here: http://www.stopthethyroidmadness.com/
      I am still trying to learn myself how the thyroid and adrenals related to the MTHFR issues and this website has helped me a lot.
      Good luck. I hope you feel better soon.

  29. Jessie January 30, 2014 at 2:34 pm # Reply

    My son is compound heterozygous. He takes zinc and magnesium, and I’ve just introduced B6. When he takes B6, he seems to overmethylate (i.e., he acts the same way he did on Deplin, b12, hydroxy b12, and 5MTHF ). HIs integrative doc wants him on B6 to help with the magnesium, and he wants me to start L-thiamine. Any tips on why he can’t tolerate B6 and whether I’ll see a similar rejection with L-thiamine?

    Thank you!

  30. pat January 30, 2014 at 7:52 pm # Reply

    I will soon be starting to treat as I am homozygous A-gene (very slow methylation). My doctor has prescribed 5-MTHF – take 1 mg per day for 4 weeks then up it to 5 mg per day, pyridoxal-5-phosphate – take 50-75 mg per day and methyl B12 take 2,000-5,000 per day.

    I am concerned this may be too much to start with. If it is what should it be? If I do overdose what besides niacin can I take? I read there is something else butndidnt make a note ofthe that.

    I should also say that I used to take 150mcg synthroid, have reduced that and am now taking 12.5 cytomel & 25 mcg synthroid. This is causing heart palps. I believe I am now undermedicated thyroid wise.

  31. Michael (NW) February 19, 2014 at 5:10 pm # Reply

    Hi, does anyone know where to get these additional methyl defects tested?

    GSTM1 – major detoxifier
    HNMT – processes histamine (primary is DAO)
    GAD – glutamate to gaba
    QDPR – recycles BH4

    Thanks.

  32. Julie March 16, 2014 at 2:59 am # Reply

    Hi Ben, quick question that I can’t make sense of- Niacin turns down methylation. So, why is it suggested by many to supplement it (sometimes at considerably high dosages) for depression and Lyme disease? I have also read about using it against Candida. How would this work??
    Grateful for your help in my healing : )

    • Dr Lynch March 16, 2014 at 4:18 am # Reply

      Niacin helps reduce nitric oxide, also helps increase serotonin levels and also supports Complex 1 of the mitochondria. Not sure why good against candida.

  33. Julie March 16, 2014 at 2:08 pm # Reply

    Thank you!! I am struggling with lyme-related low immunity problems. I want to up my niacin intake for this reason, but was concerned to do so because I know that methylation is also important.
    It can be hard at times to gauge where you’re standing with methylation. I think, I’m still overmethylating from some methylfolate that I probably over did it with last month. Hard to say.

  34. Mary March 16, 2014 at 8:03 pm # Reply

    Dear Dr. Ben,
    I have a 37 year old son that has gouty arthritis, Raynauds, fibromyalgia, chronic fatigue, depression………That’s just off the top of my head… He has been sick since he was a small boy. His fingernails turned white when he was a teenager and he was tested for all kinds of things. They found nothing. He has been going to a regular MD for the last several years. He is an arthritis specialist. He put him on Methotrexate, Cymbalta and Hydrocodone. The only thing my son has taken faithfully is the Hydrocodone. He is now addicted to them and struggles with this on top of everything else. He only took the Methotrexate for a short while then stopped thank God. I took him to the hospital this summer after watching him lay in bed with his legs so swollen he could not walk. I had to talk him in to going and it took me several days to convince him something was wrong. This happened after starting the Cymbalta. He was also on Nifedipine for the Raynauds. He got off of them both and the swelling went down. He is so sick and addicted that it is hard for me get through to him. However after his body swelled up twice its size he was willing to go see someone else. I was able to get him to a ND and she did bloodwork and had him do the 23andMe testing. It came back positive for the Mthfr mutation. I think he is compound heterozygous from looking at the paperwork.The dr was 20 min going over his bloodwork and genetic test so she only had 20 min to explain his results. She rushed through everything so fast that my son and I had no idea what she was even talking about. She didn’t even explain what Mthfr is or what the results were. She sped through the diet and supplements in 15 min and then said she had another client. The protocol she put him on he us unable to do. It is so complicated I cant even understand it and I worked in a Nutritional Therapists office for 5 years. My husband says he cant understand it either. After reading what you have to say I don’t think it is something he should do anyway. She has him on a rotation diet of low sulfate foods as follows. 1. Rotate for 3 days of sulfite containing foods and days of low sulfite containing foods. 2 supplements: for the 3 days of sulfite containing foods follow the MTHFR cycle supplements:example (help with Methylation and transufation) Methylfolate L-5-MTHF 60 caps take 1 per day. Sam-e 200 mg 30 tabs. Yucca 500 mg 100 caps sprinkle on meat. B. for the 2 days of low sulfite foods follow the CBS supplements (to slow down transulfation). Grapefruit 4 oz. 2 times a day (slows down phase 1 in the liver to allow phase 2 to catch up to help remove toxins in the bowels and urine. Molybdenum (Glycinate) 250 mcg (required for Suox to function, decrease sulfites) Vitamin E 400 IU take 3 a day.(decrease sulfites) Everyday: Probiotic ( to support immune and neurological function) 1 capsule a day HMF Intensive. Fish Oil 1000 mg 3 per day. Jarrow Methyl B 12 1000 mcg 5 per day. CoQ10 UBQH 3 twice a day.(for energy production) Vitamin D3 10000IU 1 per day. C (rotating in general: Add in Gaba if you feel anxious or need to even out your mood or shaky any time of day between 2 to 500 mg at a dose and this can be done 2 to 3xs a day. Creatine powder to support same drained with CBS upregulation and support production of ATP (energy) fuel for muscle contraction. 1 scoop in water 2xs a day. Taking B6 and zinc for Pyrulouria? (she didn’t finish this question because she ran out of time. My son was absolutely mute looking at all of this and said there was no way he would take all those supplements and no way he could remember all this or remember to take them on a rotation of food plus supplemnents as he can barely function. I said I would help him but it was very complicated for me to understand and we were out of money since it took all I had to pay for the appointments and bloodwork and genetic testing. She said if he was serious about getting well he would have to do what she has written. We both left the office totally overwhelmed and discouraged. I am hopeless. I am waiting for my results for the 23andMe myself and suspect I have similar issues. I have insurance and can see another Dr. but my son has no money and no insurance. Is there a simple way to start this process? I can help him with food and a few supplements but if he gets his Methylfolate through leafy green but they are full of sulfites I don’t even know what foods he can eat according to what I see in her instructions. I called her office and asked about the B6 and Zinc and was told I needed to make another appointment or email to get my questions answered. I am so depressed from all of this I don’t think I can continue but I am afraid if I don’t figure this out my whole family is going to continue to suffer and die. My mother died last year at the age of 86 from Ideopathic Pulmonary Fibrosis. I saw on another webside this is a condition of MTHFR. Is this true?

  35. Summer April 8, 2014 at 9:34 am # Reply

    I took one dose of deplin (about 5-6mg, I opened the capsule and poured some out) and within about 3 hours I was very awake and agitated. Unfortunately it was evening, needless to say I got no sleep, had panic attack symptoms, stomach ache, felt hot in the face and ears. Is it possible to have this strong of a reaction after one pill?its 2am now and looks like I won’t be sleeping. I’m worried this might indicate bipolar,I haven’t had any issue in the past except extreme fatigue and brain fog. I haven’t taken any other supplements or medication. Does this sound like a normal reaction or should I be worried?

  36. Michele May 6, 2014 at 4:59 pm # Reply

    Hi, thank you in advance for getting back to me on this!

    I am MTHFR 1298 (+/-) and I also have ACAT1 rs3741049 A AG +/-
    Plus here is my COMT results:
    MIR4761 (COMT -61 P199P) rs769224 A GG -/-
    MIR4761 (COMT H62H) rs4633 T CC -/-
    MIR4761 (COMT V158M) rs4680 A GG -/-
    MIR4761 (COMT) rs6269 G GG +/+

    Here is a link to see my livewello report..you’ll have to create a username and login to see my report but all that is free.
    https://livewello.com/c/gene-app/coralashley

    Anyways, I have hypothyroidism and am on t3 and Armour to help with that.. However even before that I was finding that my temps go up after noon.. But I find that when I take Nicain 50-75 it goes back down. Then a friend sent me this link about the methyl connection to why niacin helps.

    So here is what I need help understanding: Should I be taking the methly forms of Folate and B12? I am not taking those right now.
    A friend of mine says I should be on hydroxo B12 instead because of my ACAT/COMT issue.

    I am lost on all this and really need help understanding if Niacin works because I have too much methly and if I should be taking the Niacin 2x a day. Also what forms of B should i be taking and should I take folate? if so, how much of each should I be taking?
    If not what b’s should I be on and how many.

    I do also need help on my hubby and kids, my hubby has 1298 and 677 and 1 of my sons has only 677 and I’m waiting for the results to get back to me from 23andme for my other sons test.. but I’m sure whatever you post about them it’ll will help me with his.
    My son doesn’t have ACAT but his COMT is different then mine:
    MIR4761 (COMT -61 P199P) rs769224 A GG -/-
    MIR4761 (COMT H62H) rs4633 T CT +/-
    MIR4761 (COMT V158M) rs4680 A AG +/-
    MIR4761 (COMT) rs6269 G AG +/-

    My husband doesn’t have ACAT but his COMT is also different:
    MIR4761 (COMT -61 P199P) rs769224 A GG -/-
    MIR4761 (COMT H62H) rs4633 T TT +/+
    MIR4761 (COMT V158M) rs4680 A AA +/+
    MIR4761 (COMT) rs6269 G AA -/-

    Please advise me on if my son and hubby should be taking different forms of b12 ten me, etc.
    :-) Thank you for your help!
    Thanks!

  37. Kathy T. May 30, 2014 at 11:33 pm # Reply

    Dr. Lynch, thank you for all of this useful information. I have a question: if Niacin cancels out methyfolate’s ability to do what it’s supposed to do, does that mean that the multivitamin line you sell (which contains niacin as well as methylfolate) might not work as well? If it contains the niacin, does that have any limiting effect on the methylfolate? Basically, if I take one or your multivitamins that have both of those supplements, does that not mean the methylfolate won’t work as well since there’s niacin right along with it? Thank you so much for an answer to this!

  38. Kim June 23, 2014 at 3:57 pm # Reply

    All this talk of Niacin makes me wonder about my doc recommendation of 500 mg of Niacin per day for lowering LP(a). I am MTHFR C677T (Heterozygous) and have been doing fairly well on the vitamin protocol she gave me including 800 mcg of Folate and B12 per day until I added Curcumin and Niacin. Now I am having crazy panic attacks.

  39. JimE June 26, 2014 at 4:34 pm # Reply

    I am very frightened of taking Nisan, even a small amount in a B-complex vitamin makes me psychotic. I have fits of “sudden uncontrollable rage” at the slightest provocation. Embarrassing and dangerous. I have recently found out that I have low vitamin B12 which has caused other mild psychotic problems. Could this be a methylation problem? Sorry this my first visit to this blog, but not the last. I have research I need to do. Any comments and help would be appreciated.

  40. Bibsi June 28, 2014 at 7:25 am # Reply

    this is not a sign of over-methylation – this is a sign of a need of methyl donors – that’s the opposite

  41. Joy July 2, 2014 at 11:19 am # Reply

    My doctor recently found that I have copper overload and undermethylation.
    Now I’m really confused. I am homozygous MTHFR A1298 and heterozygous Prothrombin II. Previously I was taking B Complex with Methylfolate and also NAC. My doctor recently found that I have copper overload and undermethylation. The new protocol is Vitamin C 1000mg, Vitamin B6 300 mg, Vitamin E 400 iu, P5P 50 mg, Cal/Mag 500/250, Zinc starting with 15-30 mg and working up to 75 mg, and SAMe 200-400 mg.
    I’m assuming that this should replace what I was on before and not include any methofolate? I’m confused with the B6 and the P5P because I understand that to be an active form of B6. Should I not be taking any methylfolate? Any input or suggestions about the copper overload?

  42. Michael (NW) July 29, 2014 at 7:37 pm # Reply

    I’m trying to figure out if I’m over methylating, or my hormones are too high…

    Very quick history…I was hit with MAJOR anxiety, panic, then severe depression, all along with insomnia, then adrenal fatigue. I’ve tried so many differen things. Meds made me much worse. I tried an amino acid protocol with the b vitamins and other co-factors. Got some help, but I think I was dealing wtih adrenal fatigue at the time. Started doing some St. John’s Wort while getting off the aminos and eventually my anxiety/panic became a lot less. But my mood, energy, etc… still low. I started adding back some 5-htp and Tyrosine or Mucuna. I started to feel some mood elevations. But if I took 5-htp alone, I would eventually feel worse. So, I’d add some Mucuna (for dopamine) and feel a bit better. tyrosine seems to stimaluting so I can’t take much.

    I found out based on testing that I was very low in Manganese, Magnesium, B12 and Zinc. So, I started supplementing those. (I was already taking methyl-b12). This started to help even more.

    So, now, I’m taking SJW, Magnesium, B12, Manganese, Zinc, 5-htp, Mucuna, l-phenylalanine (instead of tyrosine), a little maca, etc… This has really helped. I also take B6 (P-5-P). 5-MTHF (Folate) seems to make me feel worse, so I don’t typically use that. I don’t have 5-MTHF defect, but do have MTR. And I have CBS, yet my sulfur and ammonia levels are normal.

    I started taking some Theanine, Hops, Taurine for sleep. Taurine seems to really help, and I feel more calm during the day. (I’m hoping the Taurine doesn’t cause a problem with my CBS).

    I also take a litlte Methionine now and then.

    Lately, I increased my B6 to 100mg. Still taking 5-htp, mucuna, l-phenylalanine, etc..I started having feelings of agitation/agression. The come and go really quick. Very uncomfortable. I had these when I went off trials of two SSRI’s (only on for a couple of weeks) then went on/off a SJW mix and also stopped a higher dose of Maca. Anyway, the feelings were really intense then. Not sure if a certain hormone had gone way up, or if a particular neurotransmitter was elevated.

    So, I’m trying to figure out if I’m over methylating. Too many methyl-donors, (Thenaine, mucuna, B12, B6, methionine (I take now and then), etc…?

    If high norepinephrine could cause these scary feelings, or high testosterone, or… I’ve read where one PhD said that low Serotonin can, but I’m taking plenty of 5-htp, unless I’m taking too many dopamine precursors and caused my serotonin levels to drop…. There was a little extra feelings of OCD also, which had been pretty much gone.

    What neuro or hormone could cause these intermittent feelings of agression/agitation?

    Is it over methylation?

    I’m feeling better than I have in a long time overall, but these new feelings are scary and uncomfortable and haven’t felt them in a long time.

  43. Kelly August 30, 2014 at 3:16 am # Reply

    Dr. Lynch,

    Does niacin affect all methyl donors, for example, would it affect methylcobalamin levels too?

    Thank you in advance,

    Kelly

  44. BRO November 15, 2014 at 6:40 pm # Reply

    Hi Dr. Lynch,
    Can you advice me perhaps? I have histamine intolerance – but I am also overmethylated – I react to even small drops of methyl donors on thin skin. Why can this be? I had neurotransmitters tested, and serotonin is very low, GABA low if I don’t supplement this (many GAB 1 mutations). The others are in balance. Oestrogen is low, the rest of the sex hormones are sort of OK. Adrenals sort of OK, but DHEA low. Thyroid free T3 low if I don’t supplement. I have 3 full COMT mutations. Several CYP450 mutations etc (1A2, 2C9, 2D6, SOD2). 3 full FUT2 mutations. No MTHFR-mutations. B12 and Folate levels are OK. SIgA is immune defect level (low low). Anything I can do to lower my sensitivity to methyl donors? Not sure niacin is good when you have histamine intolerance. Btw I have salicylate sensitivity and MCS too. Can’t take herbs and most meds. Minerals, bacteria, animal hormones etc are OK.

    • Marcia November 16, 2014 at 8:29 pm # Reply

      Hopefully Dr. Lynch will find a moment to answer the question about salicylate/phenol intolerance as quite a few of his products are not sal-free, and many people (including myself) suffer from it, and it’s very common in the autism community.

      But I don’t think he can answer your overall question as that would be asking him to give medical advice for free.

      I’m not a doctor, but I’m not sure you can say you’re ‘overmethylated’ because you reacted to small amounts of methyl donors on your skin. Methylation should help with histamine intolerance, so you could be reacting to something else in the products?

      It’s my understanding that niacin is not good for histamine intolerance.

      Again, hopefully Dr. Lynch will comment about salicylate/phenol intolerance in general. I’d be very interested to hear his thoughts on it.

  45. pea November 21, 2014 at 2:41 pm # Reply

    It is 3am and I can’t sleep because I am over methylated :( where can i get niacin at this hour?
    Everytime I try these things (SAMe, something COMT related) I over methylate. Tell me that finding the balance makes it all worthwhile!

  46. Tanya November 26, 2014 at 10:55 am # Reply

    For anyone knowledgeable in this area;
    Other than the standard behaviours/feelings (we know there not good) of overmethylation is there any other harm to ones health?
    I have had 6 miscarriages (no medical reason could be given), through following your protocol and adding progesterone (first 12 weeks) and low dose aspirin I was able to conceive my little miracle man. I’m older, I wld like to give my bubba a sibling (so he won’t feel alone in the world when he’s older). My bubba was born with a tongue tie and a sacral dimple (benign but related to spina bifida) – good indications of a lack of folate. I have increased my methylfolate and at times feel the effect of overmethylation. I don’t want to take Niacin as I don’t want to use up the vital methylation I may need (I also have a lot of BHMT so possible lack of shortcut) – so I look for the signs and I’m aware of my emotions, I decrease stresses and snap out of it. Other than feeling annoyed ect. is there any other health issues of overmethylation?
    I have a few mutations that havn’t helped; COMT +/+ GAD, MAO, and other mutations that would benefit from Niacin. It would be good to help break down the oestrogen. But I don’t want to risk undermethylation if I fall pregnant. Is my thinking correct?

Trackbacks/Pingbacks

  1. My Meth • MTHFR Living - August 22, 2013

    […] with the methylated vitamin supplements, mostly because I hadn’t yet seen this item on methylation dosing or the comments. I didn’t start with the methylcobalamin first. And despite going slowly when […]

  2. Methylation problems and MTHFR gene defects - a potential cause of diseases - EczeMag - July 6, 2014

    […] To help clarify and emphasize the importance of this point, and the need for niacin take a moment to read this article on how Dr. Lynch balanced out a gentleman who became ‘overmethylated.’ […]

  3. Undermethylation Diet | We Get Healthy - August 30, 2014

    […] Overmethylation and Undermethylation: Case Study – … – I am going to share with you a classic situation which happens all the time. I hear it a few times a week while working with clients and guiding various doctors. This …… […]

Leave a Reply

Read previous post:
MTHFR Mutation? So What.

Have you, or someone you love, been recently diagnosed with the MTHFR mutation? Is this the final piece of the...

Close