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?

114 Responses to “Overmethylation and Undermethylation: Case Study”

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

    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.

    • Cathy Thomas July 20, 2017 at 2:28 pm #

      I am hypothyroid as well as hetero and found myself having severe chest pains when taking methyl b-12 shots. Dr says it’s not possible.

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

    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 #

      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.

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

    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!

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

    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.

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

    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.

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

    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 #

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

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

    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.

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

    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?

    • Chris July 20, 2017 at 12:57 am #

      My heart goes out to you. I have serious issues with an adult son and we are both homozyMTHFR. Look at Nancy Mullans site. She has certain protocol she all written out and a special night for questions. She is a psychiatrist that specializes in MYHFR

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

    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?

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

    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!

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

    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!

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

    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.

    • Dave November 24, 2015 at 9:18 pm #

      I am also using Niacin for high Lp(a), it’s helping, but I thinks i am in heavy undermethylation now … perhaps supplement with methyl donors (Niacin is a methyl ‘sponge’).I don’t won’t to give up the positive aspects of Niacin, but I don’t want high homocysteine and anxiety, etc.

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

    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.

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

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

    • Ninka March 10, 2017 at 11:11 pm #

      Yes it is a sign of over methylation

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

    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?

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

    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.

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

    Dr. Lynch,

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

    Thank you in advance,

    Kelly

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

    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 #

      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.

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

    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!

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

    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?

  21. Ken December 18, 2014 at 11:02 am #

    What about the flushing effects of niacin and the potential to worsen gout? Will 50 mg taken regularly do that.. What combination is best for person with anxiety?

  22. Jessica Karns December 18, 2014 at 4:14 pm #

    Exactly what I need this morning!!! My husband is bipolar (only diagnosed by myself) and we have done really well lately controlling it with with amino acids and herbs, but when that switch is flipped to manic then I feel completely helpless. Definitely going to have Niacin in my pocket for these situations!!! Really don’t have a ton of issues with under methylation except following a manic period, but I have methyl folate and need to get the b12. I’m so excited to try this out!! It seems he’ll go manic at the most inconvenient time and if I could balance him out right away that would be great!!

    • Aisling Fitzgibbon February 7, 2017 at 9:43 pm #

      Jessica have you ever researched the role of magnesium in bi polar illness?

  23. spiralgal December 18, 2014 at 4:22 pm #

    Thanks for the post. That patient was lucky that you (and his doc) understood what to do for him. I am heterozygous for both SNPs and have a heck of a time balancing methylation, especially because I have other SNPs that I am sure interfere with how my body is reacting. When my doc first prescribed methyl folate and methylcobalamin, he gave me too large of a dose and I experienced intense anxiety and racing thoughts AND depression. He tapered it down and that helped. The problem is my B12, folate levels AND homocysteine are now high, so he doesn’t know what to do with that. I also get days where I am sure I am overmethylating. It is hard to find someone who understands the intricacies of these SNPs to help balance them effectively.

  24. Lori December 18, 2014 at 5:16 pm #

    Dr. Ben,

    You speak of undermethylation as well as overmethylation, the language of Carl Pfeiffer, MD and William Walsh, PhD.

    What are your thoughts on their methods to evaluate methylation (whole blood histamine determination) to measure histamine excess or depletion as a means to evaluate appropriate use of specific methyl donors? Blood testing provides a clear path to ‘balance’ and a method to test dosing rather than a functional experimentation with methyl donors you mentioned above.

    I am curious if you believe this method is valid, and if so, are you utilizing this method with your patients? If you are not, why not?

  25. Thomas December 19, 2014 at 9:16 am #

    Hello Dr. Lynch,

    Am I also over/under-methylating? :
    I suffer from brain fog and strong fluctuating energy and mood (doctors would call it bipolar II ultra rapid cycling). At the same time my digestion is fluctuating between normal and constipated, even if I always eat the same. (Also take probiotic long time)

    A ketogenic diet lead to more stability of mood but I still have too less energy, too often brain fog and either depressive or irritability/anxiety.

    I tried your multi with b12+methylfol.
    Just took one and a few hours later I felt like having social anxiety (which I totally lost through ketogenic diet)

    So I stopped taking it.

    What I also found: 1 week ago I started drinking bulletproof coffee. It lifted my brain fog and my energy and mood levels for three days so that I felt great (totally normal with significant better energy and no brain fog)

    On the fourth day I got constipated again and as always parallel with this my energy levels get worse, my mood get either irritated or depressive…

    I feel Know of food or drink having impact on my body and mind but I knew this since 3 years and I experiment.

    Even if I Do the same thing everyday I cannot control it enough. Something needs to be adressed to get a constant level of higher energy…

    Kind regards

  26. Emma January 2, 2015 at 2:07 am #

    Hi

    So the reason I have contacted you is because my partner suffers from
    sever anxiety and drepeession along with OCD and is an insomniac. He Can not sleep without taking anything.
    In the past he has been on medication I’m not 100% sure of all that he has taken but when I met him 4 years ago he was on seroquel and has was on a fairly high dose of it for 5 or 6 years.
    For the last 3 years he has been seeing a nutrient therapist and that has put him on to high doses of vitamins and nutrients he is lacking. As he been diagnosed as undermethylated and pyroluria (not sure if you are aware of these or not) he feels he is bi-polar but has not been diagnosed.
    He has also been seeing a naturopath
    who is focusing more on his gut health.

    I have read up about cbd oil, I read about it and believe it could help.
    I feel like we have exhausted all our options and he needs help with sleep amoung other things, he has not been able to work for the last 4
    years.
    He currently takes melatonin calcium magnesium and inositol to sleep.

    Also do you know if this will effect anything he is taking?
    I have also read it can work by using it externally rather thank consuming it.

    I appriciate any information or advise you may have.

    Thankyou

  27. Karla January 14, 2015 at 7:42 pm #

    how exactly do I know If I am an “under pr Over methylator’? I am confused, my symptoms are: feeling sleepy (no matter if I sleep 10 -8 or 6 hours) lethargic, no desire to anything fun ( i rather stay home and do nothing), body aches ( mostly, shoulders, baack hips and knees ) i feel weak ( lost strength and muscle mass), sometimes a bit sad ( not so often) and i wake up at night 2 times.
    I have read that over methylators feel anxious, moody, can be upset very easly, shaky, nervous, wired, like hyper feelings and have insomnia….
    maybe I am wrong in my observations.

    is there any way I can be sure what is my case?

  28. Ken January 15, 2015 at 11:22 am #

    Does Dr Lynch or anybody answer any of these questions. It all seems to confusing to me and I know of no doctor who understands this treatment. It sounds if a person that know what they are doing you can make yourself worst. My problem is chronic anxiety and now insomnia from being on Klonopin seven years.

  29. Aleisha January 17, 2015 at 3:26 am #

    Hi Dr. Ben and or Dr. Lynch,

    I am having some issues with oxalate and leaky gut. Also have lots of cysts on my ovaries. I have been taking a B50 complex to help with the oxalate and then I started to become hyper alert to the environment. Shadows bugged me and for a few seconds once I actually thought a person in the car in front of me was trying to give me an evil message! I got a hold of myself but it was scary. I stopped the B suppliments and things are very slowly lessening but still have a lot of anxiety and racing thoughts. I can’t take any hormonal form or birth control as it makes me go off the deep end. Any thoughts on what is going wrong?

    Thanks a million zillion.

  30. Caroline Herman January 30, 2015 at 9:21 pm #

    Hi. I am 18 years old and I am not entirely sure but I think I am homozygous c677t. My doctor before didn’t really know what it meant at the time and then we moved. Before we moved though, he started me on 15mg of Deplin. At first I felt great like you said, but then every now and again I have relapses of panic attacks and severe anxiety. Usually I can just stop taking the Deplin and three or four days later start it again and be fine. But for the last month or two, the panic is back and I tried reducing the Deplin to 7.5mg daily. It has been about a week since then and still nothing. I am having such bad anxiety that I can’t even leave the house. Any suggestions for what to do? I don’t have a doctor for this problem and my GP has no clue about any of it either. Thanks so much.

    • Dr Lynch January 31, 2015 at 7:33 pm #

      Hi Caroline –

      There are many reasons for this – and sorry to hear about it.

      I would stop the methylfolate with permission from your doctor.

      Then, I’d start taking some liposomal glutathione to reduce oxidative stress – which goes way up in some people who take too much methylfolate. Reducing the oxidative stress helps your brain make the right chemicals again and calm you down. Glutathione is a big quencher of oxidative stress.

      I would also consider niacin – 50 mg – every 30 minutes until you feel better.

      And one more – electrolytes – if cells are not communicating well, you will not feel well.

      – Optimal Liposomal Glutathione is a non-GMO, non-soy liposomal glutathione that I’ve designed. Start low – 1/4 tsp – and work up to 1 tsp twice daily – away from food ideally.
      – Optimal Electrolyte is a blend of electrolytes with mitochondrial support – which is needed to get the electrolytes into the cell
      – Niacin 50 mg every 30 min until feeling better – then STOP
      – possibly additional choline – as Optimal PC – 1 capsule with food – twice daily – possibly.

      Doing one at a time is recommended – so you can feel what works – and what makes you worse.

      My experience though is pretty good and the above are pretty good typically – but we’re ALL different.

      All these may be found at http://www.seekinghealth.com – my company.

      I also invite you to read this:
      http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

      Talk with your docs –

      Also tell your doctors that they can get training on this difficult topic by viewing some online courses – and they also get CE credits – available at
      http://www.seekinghealth.org

      Best to you
      These

  31. Diana Howell February 1, 2015 at 12:51 am #

    Hello, Dr. Lynch,

    Thank you for taking the time to read this.

    I’m very confused about this methylation topic. I am homozygous A1298C, and my naturopath has me on MethylAssist – (1 pill daily -1,000 mcg), Methylcobalamin Vitamin B12 Liquid (1mg – 3 droppers day) and PhytoMulti w/iron, 2 tablets day (B12 as Methylcobalamin 400 mcg). I’ve felt absolutely miserable for days. I’m reading about something called “over-methylating” as possibly being my problem. Do you think this might be a concern for me? I’ve been on for 15 days now, and each day I feel worse than the last, not better like I’d hoped.

    Thank you for reading this.

  32. Diana Hartwell February 1, 2015 at 12:54 am #

    Hello, Dr. Lynch,

    Thank you for taking the time to read this.

    I’m very confused about this methylation topic. I am homozygous A1298C, and my naturopath has me on MethylAssist – (1 pill daily -1,000 mcg), Methylcobalamin Vitamin B12 Liquid (1mg – 3 droppers day) and PhytoMulti w/iron, 2 tablets day (B12 as Methylcobalamin 400 mcg). I’ve felt absolutely miserable for days. I’m reading about something called “over-methylating” as possibly being my problem. Do you think this might be a concern for me? I’ve been on for 15 days now, and each day I feel worse than the last, not better like I’d hoped.

    Thank you for reading this.

  33. Michael (NW) February 20, 2015 at 5:12 pm #

    Hi,

    I’ve been doing a range of things to treat all my symptoms. I wont go into a lot of detail here, but my mood was improving, my anxiety/panic gone, insomnia still bad, but I was starting to feel more normal, but I was also on St. John’s Wort at 900mg. I started to taper to 600mg for 6 weeks which seemed to feel okay, then I dropped it to 300mg for one week and started not feeling very good, some of the bad feelings started to come back, so I went back to 600mg, and have felt up/down ever since. It’s been a week or so back at 600mg. Not sure if I need to go back to 900mg or not.

    Anyway, I’ve been on SJW for almost 2 years. Not sure why it’s taking SOOOO long to feel better. I also take trysoine (off/on), mucuna, and tryptophan. Tryptophan felt really good and seemed to really help. Then I started taking some niacin (nicotinic acid) with tryptophan to help it convert more to Serotonin. I thought it helped, but then I started feeling more depressed/flat and unmotivated. Made me think if I was burning up methlydonors and my dopamine levels were dropping? Not sure how to tell.

    So, I guess my niacin question would be….does Niacinamide burn up methly-donors? If not, then I would think that would be a better form for those needing more Serotonin and don’t want to deplete methly donors and disrupt dopamine prodution. I’m MTRR MTR postiive. CBS Postive. COMT–, VDR positive. So it would seem I need more methly-donors to keep my dopamine levels up.

    Another question…I don’t seem to be MTHFR postiive. Not with the common ones. My ND suggested taking MUCH higher doses of MTHFR (methyl-folate) to help. Would that be helpful or make things worse?

    Thank you!!!

  34. Matina April 25, 2015 at 5:43 pm #

    I started up on the methylfolate and methylcabolamin again today. 1000 mcg’s of each; two hours after my 10 mgs. of Escitalopram and .25 of clonazopram. Within 20 minutes I began having severe soreness in my shoulder blades and pressure in my chest, along with mild left arm pain. I did not take any B6 or niacin with it, after or during the episode. I still have the pain and soreness. In my notes I see this has happened to me before even on a lower dose of 400 to 400 mcgs.’s of each. What are your thoughts on this?

    • Kelly April 25, 2015 at 8:12 pm #

      Start with much smaller doses, and also I would start with the b12 first, for a week or so, then start with smaller doses of the folate, so you can tell which is causing the problem.

      • Matina April 26, 2015 at 5:15 pm #

        Thanks Kelly. I am still in pain today so I took neither. This has been a nightmare for years trying to get the right balance. I have written so many times here with questions about the anti depressant and other medicine combinations and got SOME responses in the past. But now I am only on the two medicines with hope of finding whether I will ever get off of them or have to augment with these nutrients or another medicine. Any way you suggested to just begin again with the B12. and then add in the folate again in another week or so. I wonder if I only need a small amount of the folate anyway. It seems to me that I read somewhere that Dr. Lynch said compound heterogouz’ don’t need as much folate as the other mutations. It baffled me. Do you ever recall reading such?

        • Kelly April 30, 2015 at 10:38 pm #

          I think I read that as well. I do know that Dr. Lynch says to skip the methylfolate if you’re feeling better. In other words, if you take some, say twice a day and start to feel better, then there’s no need to keep taking it twice a day as it could overdrive methylation. But if you start to sense that you’re going downhill again, then it may be time to take another dose.

          You may not need the folate at all — at least not from supplements. B12 is shown to help w/depression all by itself.

          • Matina May 1, 2015 at 12:56 am #

            Hi. I don’t remember him saying skip the methylfolate if you are feeling well. He may have meant that though when I read a piece where he said some may have to take a certain dose every day and some may only have to take that dose every day. I guess the important piece is to find the dose that is a good fit for me and other too should; and realize that the dose will vary according to other factors and also whether we take an anti depressant or not. I do know that he did say in one of his posts that as you titrate up with the methylfolate some will need to wean down on the anti depressant if you are one.
            I made an an appointment with one of the resource doctors he recommends on his site. Both my daughter and I went. She and I are both compound heteregouz. Funny too because she was adopted! Anyway, he told me that ‘I’ should not take the B12 right now with the folate. He suggested that judging from my lab results it was not so low that I should need to supplement. BUT that I did need to take the folate but at a very low dose to start. He suggested the 400 mcg. range. Instead of using the niacin for for methylation he suggested SAME. I wonder if anyone else has used this. He did also suggest that we both do the 123ME labs to get a better picture of what is happening in my system. The problem is that even if it is only $100 / $200 for the both of us; I just don’t have the funds for it until I get well enough to get back to work. Hopeful I will make some progress in the next several weeks and be able get a part time job of some sort and get the labs done.
            He did recommend fish oil, vitamin C, more vitamin D and what seemed like large doses of iodine. He added in some different supplements to begin one at a time also. Many of which I had been on and stopped out of confusion of what was helpful or not.
            NOW my daughter who is also on a low dose anti depressant; he has suggested she CONTINUE the methylcabolamin B12 due to her levels being much lower than mine and her sluggishness; along with beginning the 400 mcg.of methlyfolate. He may be right in my not using the B12 I have taken that dose of methlyfoloate alone and not felt hat pain in my arm and chest.
            Plus I get very energetic and have a hard time stopping at he end of the day. What I appreciated about him is that he did not try to get me off of the antidepressants. In fact he told me that though he is not pro anti depressants for many; he felt it was apparent I did need to be on them at this time; and may need to switch in the future. but first want to start with the nutrients again. Time will tell.

  35. Michael (NW) September 2, 2015 at 8:40 pm #

    How does Over-Methylation cause depression? I know that in under-methylation Serotonin levels typically would be low, maybe other neuros as well like dopamine? But, I’ve read that over-methylators could be high in dopmaine, and maybe high in other neurotransmitters as well. So, what causes crying and hopeless feelings in someone who is over-methylated? Does high Serotonin and Dopamine cause this? Or, can you have high dopamine but low serotonin in a over-methylator? In this case, the patient is MTHFR +-, MTRR and MTR +-, and VDR +- and COMT ++. Their main symptoms are crying and hopeless type depression and boughts of anxiety.

    Folate (and I’m assuming this includes Methly-Folate) is not good for under-methylators but good for over-methylators? How is that? Shouldn’t someone who is undermethylated require Methylfolate to help with the whole methylation cycle? I’m assuming that if you are MTHFR ++ you would require it, but wouln’t these people be under-methylated? Or does the under/over methlyators depend on the COMT status? What if someone is COMT ++ yet are also MTHFR +- and MTRR/MTR +- and VDR +-?

    How does methylfolate help with an over methylator? Yet if the person is COMT — and is an under methylator, methylfolate is supposed to be bad for them but…?

    I understand some of the picture, but the folate piece is a bit confusing, and how someone is maybe overmethlyated would have cyring/hopeless depression. etc…

    • Lynn_M September 2, 2015 at 11:46 pm #

      Michael (NW),

      Maybe this video “The Role of Methylation and Epigenetics in Brain Disorders” presented by William J. Walsh, PhD” will answer some of your questions. It’s a long one, 2 hr. 17 minutes, but he does talk abut depression, overmethylation, and undermethylation, among other subjects. You can find it at https://www.youtube.com/watch?v=W14kkO61Ano.

      • Dan September 3, 2015 at 1:40 am #

        Keep in mind that Walsh thinks folic acid is fine to use, and dismisses methylfolate — the opposite of what Dr. Lynch recommends.

        It would be helpful if Dr. Lynch could comment on Walsh’s video, but it’s my understanding he’s swamped preparing for an upcoming seminar.

        • Lynn_M September 3, 2015 at 4:06 am #

          Dan,

          After listening to Dr. Walsh’s 2014 video that I linked to in my post to Michael (NW), I disagree with your comment that Dr. Walsh dismisses methylfolate.

          Starting at 1:28:56 into the video, Dr. Walsh begins talking about folates. He says folic acid, folinic acid, and methylfolate are all effective methylating agents, but L-methylfolate is the most effective. However, he says folates also increase gene expression of SERT transport proteins, resulting in reduced serotonin neurotransmission. Most undermethylated depressives with low serotonin activity are intolerant to folates, because it worsens their depression.

          At the question and answer period at the end, at 1:58:38, he addresses the question of how to enhance the methylation cycle in people who shouldn’t take folate. He emphasizes here that when he talks about the negative effects of folate, he is only talking about people with brain disorders that have low serotonin or dopamine activity. He says methylfolate is one of the best ways to help everyone else.

          For people with low serotonin or dopamine activity whom he recommends against taking folate, he says methylB12 and TMG can enhance methylation, as is ensuring sufficient methyl groups and methionine.

          • Dan September 3, 2015 at 7:20 am #

            Hi Lynn,

            And thanks so much for your detailed response — much appreciated, especially noting where he mentions the forms of folate, etc. My brain fog is terrible. I had made notes six months ago, but tossed them I guess, and didn’t have the ‘energy’ to find exactly where he made certain statements.

            I guess I became a little skeptical back then when he said things like ‘methylfolate…can cause histamine to be methylated and go back to methionine’. Histamine and methionine are two completely different compounds…that didn’t make sense to me.

            Then he says this (paraphrasing in parts): “(Methylfolate) is a suicidal nutrient — it reacts only once…and then becomes garden variety THF, tetrahydrofolate. It does it’s job once and becomes just like all the rest of the folate forms.”

            I don’t understand that. If it’s a limited or ‘suicidal’ version of folate because it only does it’s job once, suggesting the other forms are better, then how can that be if it eventually becomes just like al the rest of the folate forms”?

            And if he says that folate (via increased gene expression of sert proteins) results in reduced serotonin (and dopamine?) neurotransmission, then how does that explain the use of high — super-high dose methyltolate (Deplin) used to augment SSRI therapy?

            Thanks in advance for your help on this issue.

  36. Michael (NW) September 2, 2015 at 8:46 pm #

    oh, here is the other question I had. If someone is over-methylated, has COMT ++, and needs Hydroxy B12 (MTR and MTRR) and Methly-Folate (MTHFR +-), how does that lower over-methyation and get that cycle working better? Or, better yet, how do you lower over-methyation and keep COMT ++ under control, etc….? I know this is complex and all the different SNP’s play into the proper treatment, but in general how do you treat over-methylation? Thanks.

  37. Cynthia September 30, 2015 at 4:30 am #

    I’m confused! I do terribly on folic acid (insomnia, anxiety, panic attacks, nervousness). I also do terribly with methylated forms of vitamins. I get the exact same reaction when I take methylcobalamin. Is this because I’m an undermethylator and that means that methyl groups are just piling up? So should I avoid methylated forms of vitamins? I already do because I feel horrible when I take them.
    How does the folic acid and pregnancy work when you don’t react well to it?
    Thanks!

  38. Michael (NW) October 14, 2015 at 6:15 pm #

    Hi,

    I keep reading how “nicotinic acid” is used to use up methly-donors, etc… What about “niacinamide”? Does it have the same effect in that regards? It seems that the last two times I’ve taken “nicotinic acid” 50mg to 100mg, my mood dropped. maybe just a coincidence but…

    I’m a undermethlyator, and am COMT – – , and MTRR ++, etc… I’m keeping my dopamine levels up with Mucuna, and L-phenylalanine(Tryosine precursor).

    I’ve taken 250mg niacinamide and that didn’t seem to effect my mood.

    Thank you,

  39. Mary October 16, 2015 at 5:50 am #

    Brain or no Brain Fog this is all so confusing! I had so many different snps that the doctor I had didn’t know what kind of a diet I could be on. By the time she eliminated everything I wasn’t supposed to eat there was nothing much left that I could eat. She consulted another doctor and they decided for now I should just try to eat healthy and not worry about it. I was told to take each supplement separately and watch for any adverse reactions. Does anyone know what that is like for a person with Panic Anxiety Disorder and that that is exactly what triggers my Panic Attacks? How does the “average” person figure this all out? Several thousand dollars later I’m still right back where I started from.

    • Dan October 16, 2015 at 3:19 pm #

      First of all, I’d get a new doctor. Or join a forum like Phoenix Rising, where many have figured out their snps and are improving. The fact that your doctor thought that your snps would influence what type of diet you should eat says a lot about his or her ignorance on the subject.

      Many of us do have to take for example the b vitamins separately, as some will have a reaction to say, b6, or some of the different forms of folate. Some say to start with B12 (which indeed seems to be pretty side-effect free) and then wait a week before starting with small amounts of folate.

      And as Dr. Lynch and others have said, just because one has a bunch of snps, doesn’t necessarily mean they’re being expressed or causing problems. There are other factors like gut bacteria and integrity, mitochondrial function, and yes, diet that may be more important to deal with before tackling methylation.

  40. MIchael (NW) December 12, 2015 at 5:59 am #

    Hi,

    I was an under-methylator. I have been taking TMG 600mg-1200mg daily in the mornings, and 5000mcg of Active B12, etc….Is it possible to start over-methylating? I was feeling REALLY good for a while, but now I’m feeling over stimluated, like I’ve had too much caffeine. I don’t feel any anxiety/panic, but just feel stimulated. And I also have some excess nervousness, and/or butterfly feelings in my stomach, but again, I don’t have any anxiety/panic. I might get nervous easy going into a meeting or a party, but I look forward to going and usually have a good time although I’m feeling really uncomfortable with this stimluation feeling. My heart rate is normal, I’m not sweating like a pig, just this uncomfortable stimulation feeling. And it has caused severe insomnia as I’m just very alert/wired.

    I thought I had some adrenal fatigue. And there’s warning about taking B12 as you could feel good for a while then crash your adrenals. Yet, I’ve heard you need B12 to keep your energy going so that your adrenals don’t have to compensate.

    I am MTRR++, so I require Methly-B12.

    I did have some extra stressors that seemed to kind of trigger some of this, but I have to wonder how much of this is due to being over methlyated and being suspectable to being easily stressed?

    I’m also on 300mg of St. John’s Wort, so it’s possible I’m making too much of a particular neurotransmitter. But….

    I could try 500mg Niacin and see if this feeling shuts off. If it does, then maybe I need to lower my dose of B12 and/or TMG….

    Any thoughts? Thank you!!!

    • Lynn_M December 12, 2015 at 7:49 am #

      Michael (NW),

      Maybe you’ll find something in the comments at http://180degreehealth.com/glutathione/ that explains what’s happening with you. The article is about glutathione, but they get into methylation issues in the comments.

      • Mitchell December 12, 2015 at 8:05 am #

        Actually I have to disagree strongly with Lynn regarding finding something helpful re methylation and glutathione at the 180degree site. The article is written by Joel Brind, who sells a glycine supplement, hence his bias. But mainly he doesn’t have the knowledge that Dr. Lynch does, as evidenced by this sentence:

        “So the bottom line is that the liver makes more GSH as a response to excess levels of methionine and its unstable derivative, SAMe, so that toxic downstream products of SAMe can be detoxified.”

        Naturally, since he’s selling glycine, then of course glycine is the answer. But note the comments by some who have found that glycine increases oxalates and other nasty compounds, sending some into severe pain and worse problems.

        There are much better sources of info than 180degreehealth and “Dr.” Joel Brind.

  41. Chuck January 14, 2016 at 10:24 pm #

    Dr. Ben, Thank you for your Posts . The info you provide is helping many.

    I have been fighting High BP and High Heart Rate.
    The med doc has ruled out liver and kidney he says from blood test, so the assumption is that my problem must lie in restricted arteries. I was given Beta blockers and it seem to work for a while, though at best could only reduce from 150/100 to 140/90.
    Doc said that if my heart ever really started going hard to take up to 4 of the Atenolol and that should bring it down. Well, I did take the 4 Atenolol and the result was nothing more than the usual 140/90. That got me to thinking that this med that I am thinking is helping me is really doing nothing.
    So I am a 766T/1298C Poly (one copy of each). So, I know that there will be mountains to climb.
    Some time ago I was having trouble sleeping and a friend said that 5HTP helped them sleep. I tried it and it really did not help me sleep. But, what it did do was to raise my heart rate up quite a bit and drive my bp up. I tried tryptophan and that gives me a headache.
    I do not take those any more.
    So, recently I read that one can have tooo much Serotonin and I got to thinking that perhaps that is what could be pushing me into hypertension state. I do not feel stressed, but I am very talkative and up beat .
    To make things more confusing I have mild symptoms of CF… thick mucous in lungs and trouble digesting carbohydrates some times. I take Methionine , A-L-Carnitine and N-A-Cysteine and these relax my lungs and thin the mucous so I can breath mostly normal except for an occasional clog.

    My question is , Could I be an Over-methylator and be driving my Serotonin up so high that it is causing my hypertension ?
    If this is possible , would you have any ideas on how to bring it down some other than niacin ?
    Are there any tests I could take to quantitate Serotonin levels ?

    I do feel better taking niacin but the most I can do is 100mg about 2 times a day , otherwise the flushing is overwhelming.

    (I have had classified allergic reactions to an SSRI and to Tramadol )

  42. Kali February 3, 2016 at 12:28 am #

    Ben, I have had every test under the sun it feels like and they come back normal. I have read about menthylation. Feeling like I might be over I asked my doctor about it. He doesn’t think so because one gene came back normal. I have Many symptons though and its been such a struggle. My question is my lab test show my b12 normal and one gene normal but my C677T is heterozygous. Can that be a result of whats happening with me.

  43. Mary February 12, 2016 at 9:11 pm #

    Hi there,
    I’m experiencing some of the same symptoms. For the past month, I’ve been on methylcobalamin, methylfolate, and p5p and I’ve felt amazing. The past few days I have kind of crashed (anxiety has skyrocketed) and I’m not sure why. Could I be overmethylated? Should I take niacin?

    • Dr Lynch March 8, 2016 at 7:13 am #

      Yes this is a sign you may be taking too much.

      It’s best to take these nutrients on and off – not all the time. Once you do this – you will find what works best for you – it may be 2 days on and 3 off or 3 on and 1 off – or 5 on and 2 off –

      Simply tune in to how you’re feeling.

      When you’ve taken too much – yes – niacin can help a lot.

      Also read this –
      http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

  44. Katie May 14, 2016 at 7:06 pm #

    Stopped taking Deplin 15 mg – don’t know what to do – was I over mythelated or is it Lyme infection. I was diagnosed homozygous C677T. I started taking Deplin 15 mg per my doctors instruction in September. I was going through withdrawal from Cymbalta and Xanax at the time, so I’m not sure how the Deplin effected me. I did start having body pain with tender points like fibromyalgia in October and it continued to get worse. I had to go back on an anti-depressant in January. I was seeing a wholistic doctor who told me that she was familiar with MTHFR, but she didn’t have me on anything except the Deplin and amino acids to try to raise my nuerotransmitters. I did take B shots. I think they were B12. The body pain went away once I started back on the anti-depressant – I’m taking Viibryd. But I started having cycles of not feeling well. I would feel good and then start to feel bad – anxious or irritable, body pain, feeling like my body was throbbing at this point I would loose my appetite and not eat much for a few days and then feel better and then a week or so later the cycle would start again. I went to a natropathic doctor a few weeks ago that discovered I have Lyme with co-infections. I have started taking silver to fight the infections and I’m taking other supplements and probiotics now. I stopped the Deplin and started taking B-Suprem by designs for health 3 weeks ago. I am feeling more anxious and depressed now so I don’t feel like the B-Supreme is enough methylated folate. I don’t know if my issues are from being over methylated or from the Lyme and co-infections. I don’t know what to do. I wish I had started with your protocol from the beginning, but not sure what to do now. I don’t even know if the infections are even causing the problems. After reading a lot of your articles I am not sure if it is the infections causing my problem or being overmethylated. Do you think these problems are over mythelation?

  45. Kenna June 16, 2016 at 9:11 pm #

    Dr. Lynch, I take 2 antidepressants. They have been lifesavers for me. But I’m wondering if the short term memory issues I’ve been having lately could be a reaction similar to what was happening in the e-mail exchange you shared. Could methylfolate/hydroxocobalamin be speeding up my methylation and therefore causing an overmedicating effect? Thanks in advance.

  46. Cherrie June 16, 2016 at 10:05 pm #

    I’m kinda newish to all this. I am taking methylcobolimin (5,000 mcg) and methyl folate (400 mcg)…my thyroid is showing low function…wondering if I treat that traditionally (well as traditional as I get seeing a naturopath…armoured thyroid) or do something else with the methylation treatment first? The only times in my life I have ever taken a niacin supplement…it want WAY beyond “flush” I itched all over and felt truly unwell. So I feel hesitant about that…but I have no idea what that dose was and it’s been YEARS. I’ve been taking the two above-mentioned supplements for 2-3 months now. Also working to balance hormones that have been resistant to anything resembling balance since a radical hysterectomy 22 years ago. (I’m 55 btw).

  47. Casey June 17, 2016 at 1:58 am #

    Thank you for this info! I can totally relate to this article. I tried the lowest dose of Niacin (25mg) which made me flushed. The 2nd dose the following week made me super flushed and very itchy on my hands and feet, so now I am afraid to try it again even though I also became totally overmethylated.

    What do you recommend for hypothyroid + general anxiety (I have been on Celexa for 15 years and am worried it has triggered the hypothyroid condition)? My naturopath is a bit stuck and is recommending PheniTropic. Thank you very much!

  48. Claudia June 17, 2016 at 2:02 pm #

    Dr. Lynch,
    I think your post may be timely for me.
    I began treatment with my ND for severe SIBO 6 weeks ago, using antimicrobials, Iberogast and silver hydrosol Argentyn. The past two weeks I’ve been taking my B12 Plus(Douglas Labs) and B Complex (Metabolic Maintenance) about every other day, as she had prescribed. Also, my thyroid is still in flux, adding liothyronine and adjusting, and she just prescribed a big change in compounded hormones, from an estrogen, progest, DHEA Combo to 500 mg. progesterone only after saliva hormone tests came back. I also take and need adrenal support, as I’m in stage three adrenal exhaustion.
    I’m feeling heavy, can’t think we’ll, sinuses feel swollen, my stomach FEELS AWFUL, and I’m having all kinds of weird pain in my legs and abdomen.
    I’m 61, and I’ve head health problems since I was 22 years old. I learn everything I can, my finances are nearly exhausted, and I’m getting tired of fighting. I tested homozygous for C677T, as suggested by my ND, but curiously, she now says MTHFR is not as big a deal as “they ” say it is…what ????
    Frustrated and very low functioning, I need help.

    • Kelly June 17, 2016 at 7:38 pm #

      Hi Claudia,

      Note that Dr. Lynch posted this article four years ago. He doesn’t usually have time to answer questions anymore, but does have a list of doctors that have taken his courses.

      Having said that, I’m no doctor, but it just sounds to me like two things may be happening. Your doctor may have overprescribed too many things at once. That’s a guess. And also maybe changed too many things at once, so it would be hard to tell what is causing what.

      But your stomach feeling awful and having pains, etc., sounds like a die-off reaction. Maybe ask your doc about cutting back on some of the antimicrobials.

      As for MTHFR not being as big of a deal as ‘they’ say, yes, there are other docs who feel this way. That if you fix other things, like your SIBO and gut issues, then there will be less issues with MTHFR expressing itself.

      And even Dr. Lynch says fix the gut and the mitochondria first, especially if one has problems with methylfolate and other methyl supplements.

      • Claudia June 19, 2016 at 1:48 pm #

        Thank you, Kelly. I’ve come to that conclusion as well. It’s hard with thyroid suddenly becoming unstable, sudden weight gain around the middle, sleep issues…but I’m backing off and giving myself a “pause” in treatment, focusing on the SIBO protocol, easing up on that too.

        • Leigh April 29, 2017 at 8:17 pm #

          The sudden weight gain (middle) and probably also in your face (side, cheeks) and maybe some joint discomfort–is adipose fat. If you wait 4 hours between meals and stick to protein and veggies, that will begin to rapidly turn around. If possible, wait more than 4 hours–even better. Good luck!

  49. Amy June 18, 2016 at 2:34 am #

    Dr. Claudia,

    One thing I have learned from decades of trial and error is that every individual is unique and I have to listen to my body. Some examples:

    I am homozygous MTHFR, but my folate levels and homocysteine n bloodwork are normal and I felt worse on Methylfolate. B12 makes me anxious.

    I went to an MD who used saliva testing and prescribed estrogen/progesterone cream, which made me feel worse. She also tried thyroid, which also made me worse. I now discount saliva testing, at least for me.

    I finally went to a traditional gynecologist for perimenopausal symptoms, mostly depression and insomnia, and I take 100 mg of progesterone per night, the smallest dose for prescription pills, ( I take it with .5 estrogen, the lowest dose). I feel better. I would like more of the beneficial aspects, but when I take more, i get more negative side effects.

    You don’t say how many of your symptoms are new vs. old, and I am no health expert but personally I would suggest listning closely to your body, stop taking anything if it makes things worse, and find a new doctor if this one isn’t helping you.

    What is the weird pain? I had pain due to a mold sensitivity. The day after mold remediation in my house, the pain went away. But that’s just me. I hope you find some relief. You deserve it.

    • Claudia June 19, 2016 at 2:00 pm #

      Thank you, Amy. I’m 61, 7 yrs post menopausal. Poor detoxification history goes way back, with all the diagnoses to prove it. Digestion became intolerable this past year, SIBO was diagnosed as severe, and treatment wasn’t optional. Anytime I treat microbes or viruses, die off is very hard for me to clear. Because of upside down cortisol levels, high during the night, baseline from noon on, sleep has been big problem. Progesterone helped for about two weeks, now waking during the night again. As with Kelly’s suggestion, I’m taking yours to heart. How did you detect the mold in your home? I did a home test kit, and it came back negative, yet I smell it in my basement.

  50. Sarah June 21, 2016 at 5:22 am #

    Good evening Dr.,

    I am 28 years old and have been sick most of my life. I can’t seem to tolerate any food that I eat and have severe chronic fatigue. I have had genetic testing done and it turns out I am COMT++ and MTHFR heterozygous (C677T+- and A1298C+-). I have no idea what to supplement with to balance out the polymorphisms. I know I am overmethylating with COMT++ but are the MTHFR mutations causing me to over or undermethylate? Any advice on foods to steer clear of or supplements to take would be extremely appreciated as I am ready to end this vicious illness.

    Thank you;
    Sarah

  51. Leah Fielding June 23, 2016 at 8:05 am #

    Hi, how do you know if you are an over or under methylater? I have been diagnosed with Pyroluria and c677t homozygous, and I was told in that case I must over methylate. So it leaves me a little confused with what vitamins I’m meant to take ..

    • Dr Lynch June 23, 2016 at 8:45 pm #

      Leah –

      I must admit I’m tired of people throwing words out there which are causing confusion.

      Sorry you’re at the receiving end of it.

      The information you received is wrong.

      It’s not that cut and dry.

      Please read this and follow the lifestyle, diet, environmental recommendations first – then apply the nutrients – one at a time as needed and as recommended by your healthcare professional.

      http://mthfr.net/mthfr-c677t-mutation-basic-protocol/2012/02/24/

  52. Beth L. August 25, 2016 at 4:43 pm #

    I was recently diagnosed with hetero C677, Pernicious Anemia, possible candida, possible adrenal issue with high coritsol and have been treating for hypothyroid for years. I have started taking B12 shots and continue on my NDT meds for hypo. My dr. said no trmt necessary for MTHFR. Is that correct? How do I know if I am over or under methylating?

  53. Ky September 1, 2016 at 9:05 pm #

    I am 27 and have struggled with bouts of anxiety, depression, weight loss/gain, IBS, GI problems, and yeast issues for years. After trying many SSRIs, and birth controls to no avail my psychologist ordered a genetic screen.

    Mutations are as follows:

    Serotonin Transporter
    (SLC6A4)
    L(A)/S

    Calcium Channel
    (CACNA1C)
    A/A

    Methylenetetrahydrofolate
    Reductase
    (MTHFR)
    C677T:
    C/T
    A1298C:
    A/C

    Brain-derived
    Neurotrophic Factor
    (BDNF)
    Val/Met

    I was started on Enlyte for the MTHFR and am taking omega 3’s for the calcium channel mutation… With that said I noticed an improvement in my mood lability and anxiety/depression upon starting the Enlyte which was alleviated for about a month. Now I am feeling worse than before… I have zero motivation, tons of anxiety, have gained at least 10 lbs. I am feeling my worst… is it possible I am overmethylating or maybe there is a piece of this gene puzzle I am missing? I recently saw that there can be gene mutation that causes problems specifically with the metabolism of cerebral folate. Anyway, just looking to feel better. You can give me specifics… I am a Ph.D. chemist who has been lately working more on finding the answer to my mental health issues than my current research project :-(.

    Thank you

    • Dr Lynch September 2, 2016 at 7:37 am #

      Classic sign of taking too much. These nutrients are powerful. I highly recommend talking with your doctor and stopping this supplement for a bit. Niacin may be needed to rebalance you a bit. Consider 50 mg of niacin every 30 minutes (max three times) until your anxiety lifts. One or two doses of 50 mg niacin usually does the trick for most – along with stopping the supplement which contributed to the anxiety / issues such as Enlyte in this case.

      This is why I recommend the ‘pulse method’ which is where you take the nutrients when you feel you need them – and don’t take them when you feel you don’t – like on vacation possibly.

  54. Michael (NW) September 29, 2016 at 6:07 pm #

    I’m MTRR ++. I take anywhere from 1000mcg to 10,000mcg of Methyl-B12. I also take Methionine and some liquid SAMe. I’m an Undermethylator. I might have Pyroluria. My doctor thinks so, I have many of the symptoms, just haven’t had a positive test yet. Anyway, is it possible to become overmethylated at least temporarily by taking too many methyl-donors?

  55. Michael (NW) October 3, 2016 at 11:02 pm #

    Hi,

    I’m reading more about how folate is bad for undermethylators. Why is this? I’m assuming for someone who has MTHFR ++ they need folate. But what about undermethylators who aren’t MTHFR++? I do have MTRR++, does this require some 5-MTHF (folate) to function properly?

    Cheers

  56. Chuck October 4, 2016 at 2:34 am #

    Folate has been a mystery to me .
    my doctor did some extensive bloodwork including genetics testing . because of my 677 and 1298 polymorphisms and because of my high homocysteine level and because of my very small particle very oxidized LDLcholesterol, he was very pointed saying that I needed to take Folate and lots of it.
    The problem is that every time I took Folate I would develop joint pain and eventually become super tired. I would take a little bit every once in a while just to appease my doctor.
    Recently he started me on COQ10 400 mg spaced through the day. A week went by and I took my normal little dose of folate and I had no negative response. I took more and more trying to invoke the joint pain that I used to experience. I got up to 10 mg a day for a few days with no pain and no loss of energy. I’ve back down to a milligram a day. And as long as they take the CoQ10 I seem to be fine.
    I’ve wondering if anybody else has reactivity to Folate like this but has been able to mediate the issue with CoQ10.

    • Dr Lynch October 5, 2016 at 4:43 am #

      That’s a great observation. Thank you for sharing. I wonder if by adding folates – which are also used by the mitochondria – and one is lacking CoQ10, the mitochondria end up burning out and causing oxidative stress vs ATP.

      I wonder if this is also why niacin helps reduce side effects. Niacin is the precursor to NAD which is also transformed and used by the mitochondria as NADH.

      So – the combination use of NADH + CoQ10 may be very useful for those experiencing side effects from folates.

      Not all people – but a number -especially if related to increased pain and fatigue.

      Brilliant observation, Chuck!

  57. melvin October 5, 2016 at 3:12 pm #

    Folate in mitochondria? NADH and Coq10 in the electron transport chain for sure.
    Could you please specify where a folate chemical reaction or redox would occur in the kreb cycle or the etc.

    thanks

  58. Mr Tam November 30, 2016 at 2:51 pm #

    how much should i take methioine and same, Methyfolate,methy-b12, b6 per day?

  59. Michael (NW) December 9, 2016 at 8:08 pm #

    Niacin as “Nicotinic Acid” is supposed to help with lowering cholesterol (does Niacinamide have the same effect?) Anyway, Niacin is supposed to help with overmethylation symptoms (nicotinic acid is recommended for this but does Niacinamide help also?) and is not really recommended for those who are undermethylated. Niacin is suggested for those with Pyroluria. So, how much Niacin can one take to help lower cholesterol, help with Pyroluria, yet not burn up methylation donors?

  60. Kay March 5, 2017 at 6:49 pm #

    6 weeks ago I had a rare reaction to increased dosage of gabapentin that has caused a burning sensation in many parts of my body. It was a nightmare!! I titrated off within 3 week, but still have mild burning and tingling; however 3 days stopping the med, I developed mouth burning. I have found relief with b12, but my doctor had done tests around this same time and found I have the MTHFR mutation and wanted me to take L-methylfolate. My problem, I have taken the methylfolate 3 days, and each day it seems to make the mouth burning flare up again for a while. Any suggests? I am starting slower than my doctor wanted & taking 2.5mg (rather than 10mg) of L-methylfolate and am taking 1000IU methylcobalamin 3 or 4 times a day.

  61. Ashley July 17, 2017 at 4:48 am #

    I have been experiencing an estrogen rebound or gynecomastia reaction of sorts after a few days of methylation (really sore nipples and instant fat in my upper arms, upper back, and waistline), and I am a thin 36 year old female. I have been trying to back off to small doses every three or four days and even moved to hydroxo B12 but have had this happen three or four times now. Any ideas off the top of your head? I feel so amazing until this happens!

Trackbacks/Pingbacks

  1. 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.’ […]

  2. 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 …… […]

  3. Why Your Prenatal Folic Acid Might Not Be Enough… - January 5, 2015

    […] http://mthfr.net/overmethylation-and-undermethylation-case-study/2012/06/27/ […]

  4. Expanded Explanation of My Homozygous, “MTHFR” Genetic Mutations. – Erin Marie McDowell - May 24, 2016

    […] 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 […]

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