J.D. Moyer

sci-fi writer, beat maker, self-experimenter

B-Vitamins, Mood, and Methylation — It’s Complicated

B-vitamins, building blocks of mental health?  Or B.S.?

There’s a great deal of misinformation on the internet regarding B-vitamins and health.  I know this because I’ve read most of it.  During the 5 years or so when I was researching how to cure my own asthma, I devoured every text I could find regarding the physiological effects of specific vitamins and minerals — especially the B-vitamins.  Large doses of B-complex or individual B-vitamins are recommended to improve mood, reduce PMS, reduce asthma symptoms, reduce the risk of various cancers, reduce the risk of heart disease, fight yeast infections, ward off mosquitoes, and prevent or cure numerous other ailments.

Which of these claims are based on reputable clinical research, and which are bullshit?

A quick overview — B-vitamins are water-soluble nutrients found in whole foods, and less so in refined/processed foods (unless they are added back in, as is the case with most white flour and breakfast cereals).  They are needed for various metabolic processes, are generally non-toxic, and deficiencies can result in serious illness and death.  The B-vitamins [wikipedia] include:

  • B1 (thiamine) — deficiency results in beriberi
  • B2 (riboflavin) — deficiency results in ariboflavinosis
  • B3 (niacin or niacinamide) — deficiency results in pellagra
  • B5 (pantothenic acid) — deficiency can contribute to acne
  • B6 (pyridoxine and other forms) — deficiency can lead to microcytic anemia or depression
  • B7 (biotin) — deficiency may cause growth problems in children
  • B9 (folic acid) — deficiency results in macrocytic anemia and can cause birth defects
  • B12 (cyanocobalamin and other forms) — deficiency results in macrocytic anemia, memory loss and other cognitive problems

Unless your diet is terrible or you’re a raging alcoholic, you’re unlikely to develop beriberi or pellegra.  However, many people can benefit from careful, controlled supplementation of one or more of B-vitamins. Clinical research supports supplemental doses of various B vitamins being effective in the following ways:

Mosquitoes — B1 won’t protect you.

In no way is the above list meant to be comprehensive — there are hundreds of clinical studies demonstrating positive effects from supplemental and dietary B-vitamin intake.  Other claims, such as the idea that B-6 can cure carpal tunnel, or that B-1 can repel mosquitoes, haven’t held up under clinical scrutiny.

Less frequently noted are the side effects of taking very large doses of various B-vitamins, which can include:

  • rapid and/or irregular heartbeat (B1)
  • poor circulation/cold hands (B6)
  • irritability, hostility (B6)
  • numb hands/feet, neuropathy (B6)
  • inability to fall asleep, interrupted sleep (almost all)
  • increased histamine levels, worsened asthma symptoms (B3, B12)
  • neon yellow pee (B2)
  • loose stools/diarrhea/nausea (niacin)
  • facial/skin flushing (niacin)
  • liver damage (high doses of niacin, niacinamide)
  • worsen acne (biotin)

I’ll share what I’ve learned and experienced — but consult your doctor before taking or stopping any supplements or medications.  I don’t have any medical training — I’m just an interested blogger.

Methylation, Health, and B-Vitamins

The same B-vitamins can affect different people in different (and even opposite) ways.  These differences may have to do with a genetic predisposition to being a “fast methylator” or a “slow methylator.” Methylation is a process by which a molecule donates or accepts a methyl group (CH3).  In biological systems DNA can be methylated, as well as proteins (lysine and arginine).  One type of protein methylation — the transfer of methyl groups from SAMe to histones — affects epigenetic expression (the degree to which certain genes are turned on or off).

The degree of protein and DNA methylation in an organism profoundly affects numerous aspects of physiology, including prenatal development, growth, metabolic levels, ATP (energy) production, neurotransmitter levels, metabolism of heavy metals, and susceptibility to cancer.  Problems with the methylation cycle may also be related to autism, mental illness, food allergies, asthma, and the development of heart disease.

So what influences rates of methylation?  Four factors, as far as I can tell:

  1. Genetic factors, especially variants in the MTHFR and COMT genes
  2. Psychological/emotional/physical stress
  3. Smoking and other environmental toxins
  4. Diet and nutrition (including supplements), especially B-vitamin and methionine intake

The effects of vitamins, even plain-old-regular multivitamins, are not trivial.  This study found that regular multivitamin intake reduced lung-cancer risk in former and current smokers by 43%, and that that risk reduction was associated with the methylated state of eight different genes (p16, MGMT, DAPK, RASSF1A, GATA4, GATA5, PAX5α, and PAX5β) involved in tumor suppression (adequate folate prevents these genes from becoming hypermethylated/turned off).  Eating green leafy vegetables and/or other highly pigmented fruits and vegetables also provided a more modest protective effect.  This study also found associations between folate and methionine levels and hypermethylation of the RASSF1A and MTHFR genes (also related to cancer suppression).  This study (PDF) found that hypermethylation of the MGMT gene was implicated in prostate cancer and was strongly associated with meat-eating and smoking, and less so with alcohol consumption.

Regarding the MGMT study, why would meat-eating be associated with gene hypermethylation?  One possibility is the higher availability of the essential amino acid methionine (a methyl donor) in meat diets (although vegetarian diets can still be high in methionine if they include eggs, soy, brazil nuts, and/or sesame).  There is some evidence that methionine restricted diets are associated with longevity, with effects similar to caloric restriction.  Another possibility is the (presumed) increased availability of folate (from green leafy vegetables and other vegetable sources) in the diets of the vegetarians in the study.  A third possibility is that the study didn’t control for other lifestyle factors associated with meat-eating that could have influenced MGMT methylation levels.

Edit: This study found that higher B6 and methionine levels protected against lung cancer.  Increased dietary methionine may in fact be protective against many forms of cancer.

One reason to take up smoking — multivitamins will have more of a protective health effect. Wait …

The Biochemistry of Mental Illness

So, can we say that folic acid and folate are good, and methionine is bad, and leave it at that?  Not so fast.  Carl Pfeiffer was a pharmacologist who studied schizophrenia, manic-depression, and other forms of mental illness.  Along with Abram Hoffer, he co-founded the field of orthomolecular psychiatry.  He hypothesized that most people suffering from mental illness could be categorized into one of the following three groups:

“Histapenic” (low-histamine) individuals exhibited the following:

  • low blood histamine
  • high (toxic) copper levels
  • low levels of zinc and manganese
  • low levels of folate and/or B12
  • high levels of homocysteine
  • slower metabolic rates (higher body fat)

These patients tended to suffer from paranoid schizophrenia, bipolar disorder, psychosis, anxiety/panic attacks, hallucinations, hyperactivity, and depression (the latter especially in older patients).  Pfeiffer found that these people often benefited from large doses of folic acid, B12, B3, B6, zinc, and manganese.

“Histadelic” (high histamine) individuals exhibited the following:

  • high blood histamine and basophil counts
  • normal or low copper levels
  • low levels of homocysteine
  • higher metabolic rates (lower body fat)

These patients tended to suffer from depression, compulsions (like OCD), addictions (gambling/shopping/sex/alcohol, etc.), eating disorders (anorexia/bulimia), and phobias.  They reacted badly to folate — even dietary folate in fresh vegetables could worsen their depression (dubbed “salad bowl depression” by Pfeiffer).  They responded well to methionine and calcium supplements.

“Pyroluric” (pyroluria) individuals exhibited the following:

  • excrete large quantities of kryptopyrrole in urine
  • low levels of zinc and B6
  • “sweet/fruity” body odor/breath
  • pale skin, inability to tan

This condition, which could overlap with either of the other two or exist on its own, was associated with anxiety, depression, food sensitivities/celiac disease, social withdrawal, learning disabilities/ADHD, and autism.  More severe cases resulted in mental retardation and delayed growth and puberty.  In some cases psychological symptoms could be alleviated within just a few days with supplemental B6 and zinc.

Carl Pfeiffer

This paper from Pfeiffer goes into more detail, especially in regards to zinc and manganese supplementation and reactions to folic acid supplements.

Continued research in this field, carried out primarily by researchers at the Pfeiffer Treatment Center, has revealed that the first two types have methylation problemsThis paper from William Walsh goes into the details, but can be summarized as follows:

  1. “Histapenic” (low histamine) types are “over-methylators.”  They tend to have higher methyl to folate ratios, which can result in the overproduction of dopamine, norepinephrine, and serotonin (via the BH4 rate-controlling process in catecholamine synthesis).  These types can benefit greatly from increased dietary and supplemental folate, B12, and other nutrients.  Here’s Dr. Walsh describing over-methylators on youtube.
  2. “Histadelic” (high histamine) types are “under-methylators.” They have low methyl to folate ratios, which can result in lower levels of dopamine, norepinephrine, and serotonin.  These types can benefit from supplemental methionine, SAMe, and inositol (methyl donors).  Here’s Dr. Walsh describing under-methylators.
  3. The third type, “Pyroluria”, is a genetic disorder which increases B6 and zinc urinary excretion, resulting in deficiencies of both nutrients and increased oxidative stress.  Here’s Dr. Walsh describing pyroluria.

While mainstream psychiatry has generally rejected the field of orthomolecular psychiatry in its entirety, some reputable papers (such as this one, published in The Lancet, and this one) allow that there may be relationships between folate levels, methylation processes, and mental illness.  While serious cases of schizophrenia are usually not treatable with vitamins alone (as is suggested by this study), that doesn’t mean that medical professionals should entirely discount the affects of vitamins on methylation processes when designing treatment protocols.  Schizophrenics may benefit from low methionine diets and the addition of B12, folic acid, niacin, zinc, manganese, and B6, but should avoid excess copper.  Patients with obsessive-compulsive disorders or intense phobias should probably avoid folic acid and manganese supplements, but may benefits from SAMe, methionine, inositol, and other methyl donors, as well as calcium and magnesium.  Depressed or anxious patients who don’t respond to SSRI’s might be pyroluric, and could benefit from B6 and zinc supplementation, as well as evening primrose oil (a source of GLA).  Numerous clinical case studies, like these, make me think there is probably some relationship between methylation processes and mental health.

So, if both cancer and schizophrenia are related to abnormalities in various methylation processes, is there any link between the two diseases?  There is; schizophrenics are less likely to get cancer.  Variations in the genes NRG1, AKT1, PIK3, COMT, PRODH and ErbB4 are implicated in cancer (when these genes trigger rapid, out-of-control cell replication) and schizophrenia (when the same genes slow down various cellular processes).  However, this study found that death rates from cancer were higher in schizophrenics than in the general population.  It may be significant that the latter study took place in France, where rates of either MTHFR polymorphism are extremely low (around 2%).

All Vitamins Are Not Created Equal

There is a difference between folate (absorbed from food) and folic acid (the synthesized form).  The former is methylated, the latter requires a methylation process to become biologically active (metafolin).  In terms of vitamin B12, the cheaper and more common cobalamin is non-methylated, while the more expensive hydroxycobalamin or methylcobalamin are methylated.

Could non-methylated folic acid, B12, and niacin supplements be helpful to  “over-methylators” because they “use up” methyl groups when they are metabolized in excess, thus normalizing the methyl to folate ratio?

Or is the truth more complex?  People with one of two common (about 50% in North America) polymorphisms in the MTHFR gene can’t effectively convert to (and/or use) active folate.  These types have low folate and high homocysteine, but can react badly to folic acid supplements (which can actually reduce blood levels active metafolin in people with the MTHFR gene variants), and do better getting folate from green leafy vegetables and other food sources (and/or supplementing with a methylated form, like l-methylfolate).

Edit: This study found that supplementing with methylfolate improved recovery for patients diagnosed with major depression or schizophrenia.

Nutritional Supplements and Medical DIY

Trying to understand methylation processes and how they relate to vitamin supplements and nutrition can tie your brain in a knot.  Most medical professionals are no help at all — they’ll get that “you’re one of those” look if you suggest that vitamin supplements have significant psychological effects.  Probably more than anyone else, parents of bipolar, schizophrenic, and autistic children have pushed the field of orthomolecular psychiatry forward — they are desperate to help their kids thrive and will go to great lengths to understand and experiment with whatever works, including nutritional supplements.

Karen DeFelice’s site is one example.  The It’s Not Mental site and DetoxPuzzle.com are two more.  There are dozens of others.  Many of these parents have effectively cured their children with aggressive nutritional interventions.  Common themes seem to be avoidance of gluten and casein, adding supplements to either slow down or speed up methylation processes (depending on the condition), balancing copper/zinc levels, and troubleshooting bottlenecks in various detoxification processes (phenols, sulfur metabolism, etc.).

My Own Self Diagnosis Process

I began this investigation of B-vitamins and methylation process in an attempt to cure my asthma.  Ultimately I discovered that a more-or-less paleo diet resolved most of my asthma symptoms, with some supplements being helpful as well (notably vitamin D, magnesium, fish oil, evening primrose oil, and vitamin C).  None of the B-vitamins proved to be helpful for asthma, and multivitamins often aggravated my symptoms.

I suspect I have one or both polymorphisms of the MTHFR gene, but if I do, that’s probably not related to asthma.

I do exhibit most of the less severe signs of being an “under-methylator,” including seasonal allergies, hypomania/overconfidence alternating with melancholy/demoralization, calm demeanor but high internal stress/anxiety, stong-willed/stubborn, low tolerance for stress, high libido, high motivation/ambition, perfectionism, a high desire for order/organization, addictive/compulsive tendencies, etc.

I experience a significant energy boost from B6 + zinc, which can quickly escalate into hostility/irritability/agitated depression.  I’m guessing somehow that nutrient combination spikes norepinephrine and lowers serotonin (I have no idea how), but it could be something else (maybe some kind of “detox” reaction, or homocysteine converting too quickly to cysteine).

I experience a calming, mood-boosting effect from taking niacinamide (higher serotonin?).  But too much niacinamide interrupts my sleep cycle and aggravates my breathing.

Taking B12 can improve my sleep, but only if I take it early in the day.

I seem to do well on a high protein, high methionine diet, but if I cut carbs too low I feel agitated and irritable (probably from low serotonin).

I’ve only tried taking SAMe (a methyl donor) a few times and I can’t remember the effects.  People I’m close to have found it to be extremely effective for carpal tunnel and fighting “the blues.”

Designing Your Own Supplement Program

Short of genetic testing (which is now a realistic and affordable option), looking at your family history from a health perspective is probably a good place to start when considering your own supplement program.  For example:

If Alzhemier’s runs in your family, consider supplementing with niacinamide.  Niacinamide may also be effective in reducing anxiety, including severe social anxiety.

If there are cases of cancer in your family, consider increasing folate levels from food sources and vitamins.  B6 may provide additional protection against colon cancer.

If you fall somewhere along the autism spectrum, considering supplementing with zinc + manganese, and restricting copper.

If you have asthma, you might try experimenting with a paleo or gluten-free diet, and supplementing with fish oil, evening primrose oil, magnesium, and C.  Some people have experienced relief from asthma symptoms by increasing vitamins B5 and B6.

If you think you might be experiencing negative side effects from a multivitamin, go cold turkey and see how you feel.  For people with either or both polymorphisms of the MTHFR gene, supplemental folic acid may actually be harmful.  Take methyfolate instead, or just eat more leafy greens and nutritious food and don’t take a multi.

Feel free to share your own experiences with B-vitamin and other supplements in the comments.  Hope you enjoyed this post — if you did please tweet it.


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  1. Incredibly well-researched! Thank you!

    I developed asthma around 40yo. I’d always been “an allergic person” since childhood. After the asthma, I started getting hives. At first it was just intermittently ans to a couple food chemicals. Then followed years of severe chronic hives barely contained with multiple medications.
    It was only after finding my own children’s underlying issues with their supposed “mental illness” that I delved into my own biology.

    I, too, have a problem with methylation. I am on both methylated folate and methylated B12, and several other B vitamins. The SpectraCell test can determine if we are getting enough of these and other nutrients inside our cells, as there can be other issues, such as a vitamin D cell-receptor issue necessitating taking higher levels of vitamin D3.

    Some doctors use testing from Genova Diagnostics, such as one called the NutrEval, possibly in conjunction with others to get a better picture of what is going on and how your methylation is going, and general health. The solution to the methylation may be a matter of not just supplementing, but healing your gut, addressing sleep issues, hormone issues, and generally taking a look at general health.

    In the meantime, the best cure to my own asthma was the same as for getting rid of my hives. I got off foods I didn’t even know were contributing to my problems – gluten, dairy, soy, eggs… I am still and “allergic person.” But at least I am on many less medications, feeling better, and no longer carrying around an emergency inhaler. I no longer “have asthma.”

  2. Jeanie — thanks for your comment and for sharing your own experience. I wonder what exactly the link is (if any), between MTHFR variants, methylation, folic acid utilization, and allergic diseases. The Danish study I linked in this post couldn’t find a link to the C677T polymorphism, but I wonder about the A1298C variant (which is related to the use of active folate in BH4 production). I’m curious to know which form of MTHFR I have — I think I’ll get tested.

    • Michelle

      Well documented indeed!
      J.D. I have been struggling with toxicity and OCD for many years, and I read pretty much everything there is out there trying to find a solution to my problems. MetablociTyping test from Healthexcel will help you truely determine if you are an over/under methylator and what is your individual nutritional plan. You can also do the OAT/ORGANICACIDTEST to find out that and many many important parameters about your metabolism. And the 23andme test to see if you present any gene variations.
      Nevertheless, it is extremely important to take into account that the expression of the genes that you mentioned MTHFR, COMT, CBS and others may be altered by unknown, undiscovered, latent viral infections and bacteria! They can change your gene code as they are so pervasive and enter your cell and modify your DNA. So you may in fact not be undeor or over methylator, but to have a virus that does that!
      Also, you should do a heavy metal testing, to check your heavy metal toxicity! Vitamins alone won’t cure schizophrenia, ocd, bipolar. But detoxification and correcting nutritional deficiencies according to your metabolic type will surely do so cause I sincerely believe that 98% of mental illness equals toxicity (in its various forms: heavy metals, radiation, ddt, phtalates, pesticides, viral load, bacteria etc) and nutritional deficiencies!
      So no one with mental illness should focus on just one of these two elements. Detox and nourish.

  3. Sara

    This is incredibly interesting and may provoke me into a little more detective work. I’ve had problems with mood disorders for years, mostly SAD syndrome, low energy and seasonal allergies, eczema etc.. I’ve always thought that I have a tendency to an addictive personality and over the past couple of years have been unwell having developed CFS/M.E. I’ve experimented a lot with diet, and the only thing I know for sure is that I feel generally better on a high protein, low carb diet, but this is far harder to keep up in winter. I also eat lots of green but haven’t noticed a problem. So maybe I’m also an under methylator? I do take a good general vitamin supplement, and extra magnesium but perhaps I’ll investigate SAMe and see whether that’s a useful consideration.

    I sometimes feel as though I’m shooting in the dark, so thanks for researching all of this. Maybe testing is the way forward for many of us?

  4. JD! This is amazing. I’m always impressed when people have time for a blog but I’m grateful as hell when the blog is as useful and informative as yours are. I have developed asthma too (it’s minor and I mostly ignore it. But…). I know that I might need to deal with it at some point. The tips for cancer prevention are helpful too. My mom has had more cancer than you can imagine. She has nine lives apparently and manages to remain spunky and involved. Thanks again for generously and articulately sharing your research.

  5. This study is interesting — folic acid supplements in mice increased asthma risk in offspring (via epigenetic inheritance/DNA methylation).


    I wonder if folic acid supplementation is behind skyrocketing asthma rates in developed countries … and maybe autism too.

    Here’s the full paper:

  6. elise brewin

    Hi J.D.
    Awesome and timely. I need vitamin help!
    I’ve noticed Rose’s temperment is effected by nutriets, but haven’t been able to figure it all out, as I have been in a drastically low Vit. D brainfog, and maybe messed myself up w/ too much vit. C, thyroid problems, and ???
    Anyhow, I’d love to help Rose (and myself), and the answer is somewhere in this blog, but I think I need to talk to you…
    Thanks, as ever, for diving right into the science. And the description of what doctors do when people like us show up.
    (Oh, Rose is the 6 year old formerly known as Hazel Rose – Rose only has 4 letters, compared to 9 in Hazel Rose, a fact she noticed and acted on just before Kindergarten last year)
    🙂 elise

  7. Ellen

    You need to contact Dr. David Brownstein, Dr. Stephen Smith http://www.nwhealthcare.net (Explaination of MTHFR, Grids showing treatment and disaeses it causes as well as a video lecture that Dr. Rawlins does around the country on Deplin) and Dr. Neil Rawlins-OBGYN Both Dr. Stephen Smith and Dr. Rawlins have the a variant of the MTHFR Genes and are based out of Richland WA. They have an MTHFR protocol that works as well as Pam Labs has Deplin, Metanx and Cerefolin NAC that all help with MTHFR.

  8. Ellen

    I have tested positive for the MTHFR Gene A12098/T677C as well both of my children. My sister and her 2 children have also tested positive for the same. My first cousin recently was tested and she has the double T677C!

  9. Thanks for the information Ellen. I believe this is the chart you are referring to:

  10. I have a friend with undiagnosed mood disorders (depression, aggressiveness, peaks of childish joy). I taught her how to look at herself in a critical light to properly diagnose “symptoms”, and she eventually managed to accumulate a ton of B-related vitamin deficiency symptoms over 6 months.

    Seeing as how she was already on a multi that I had recommended her (very high dosages) and did not see an improvement, I posited that MTHFR was a possible culprit. We tried MethylGuard PLUS from Thorne Research for her and it was miraculous. I hadn’t seen her for two weeks after giving her the bottle, and I thought it had been a gradual process, but no. She says the change happened on the very first day (which makes sense considering we’re talking about water-soluble vitamins), although a morning dose was better for her.

    We’re in the process of getting her tested for the mutation and figuring out if low to medium dosages of methyltetrahydrofolate could be more economical. Bottom line: the impact this can have is real and massive.

    • Interesting. I also recently switched to a Thorne multi (Basic Nutrients V) after learning which MTHFR variant I have from my 23andMe test. I have the AG variant of MTHFR 677 [Rs1801133], which according to some sources means I convert folate to methylfolate somewhat less efficiently than those with the GG or “normal” variant. Since the change to methylated forms of folate and B12, my sleep pattern has changed (I’m sleeping more deeply and continuously). Could be the vitamin change, could be winter, could be something else … but worth noting.

    • One of my MTHFR kids actually took the precription product, Metanx for a while since she needed both methylated folate and B12. I later found out I, too am deficient and take two products. There IS a test that can be done to monitor levels inside our cells – using lymphocytes – via SpectraCell laboratory. (Obviously, with this condition, serum levels are fairly useless).

  11. Kelly

    If you have the MTHFR 677 mutation, you also need more b2 — riboflavin. Riboflavin is SO important, very underrated, misunderstood — it helps your body convert all the other b’s, and is critical especially for b6 and folate utilization. If you were having trouble supplementing w/b6 as above, then b2 should help with that.

    • Mary

      THANK YOU I have always had low b2 and b6. I have the COMT gene alteration (double) so methylation is important but in that test (DetoxiGenomics) they didn’t do the MTHFR… If I am always low b2 and b6 is that an indication?

  12. Annie

    Hi, a couple of years ago, I thought I had a B12 deficiency because I had pretty much all of its symptoms listed on line. I took about 83,000% of my daily B12 in the form of sublingual methycobalin. After taking it for a few months, my grades went up, but i felt like I was no longer in love with my boyfriend and felt cynical about life, people, marriage, and having children. I know methylation helps you see the consequences of your behavior better, and I was wondering if you could tell me if there’s a connection. I definitely feel less needy.
    Also, since I took those vitamins, I have had two episodes of psychosis, including auditory hallucinations, delusions and paranoia. They were set off by medications, but I’d never had these episodes before. I’m 22, and I was 19 when I started taking B12. I was wondering if there could be a connection with all of this, like maybe I threw my myelin sheath out of whack or caused other vitamins to be depleted by taking such a large dose of B12 for a total of 6 months. I’ve asked my doctors, and they have no idea and seem to think it’s just in my head. i
    I don’t know if this helps, but before taking the vitamins, I was already diagnosed with ADD inattention, depression, and significant anxiety issues, including social anxiety. Do you think there is a connection between any of this? Thank you for any help you can give. Your piece was very informative and interesting.

    • Hello Annie,

      First of all, no, it’s not in your head.

      Medications lower your cellular levels of vitamins, and sometimes even minerals. On top of that, your B-Vitamins are almost all antagonists towards each other. That means you can deplete your own levels just by dosing yourself too high. You will feel great for a while because you’ll be compensating for the deficiency, but you’ll most likely overshoot.

      Let me know if you want a step-by-step for fixing this situation.

      Take care,

      William C.

      • Annie

        Hey, William, thanks so much for acknowledging my issues. I would absolutely love a step-by-step for solving this situation!!! I thought I might have overdosed too, but I have not found anything on the internet about what to do about it. Everywhere just says it’s non-toxic so you’ll be fine, ha. You can email me at [email protected]

    • Hi Annie. Extremely high doses of vitamin B-6 for prolonged periods can have neurotoxic effects, but I’ve never heard of permanent damage from B12. In general, I think it’s a good idea to find the minimum effective dose for vitamin supplements, and not exceed that dose. Even non-toxic water-soluble vitamins like vitamin C can have side effects for some people.

      Some people have had good results taking niacinamide (a form of B3 — different than niacin) for social anxiety, and there’s some clinical research to support this.

      • Mary

        Hey JD I have COMT mutations; don’t know about the MTHFR mutation. I am low in B2 and B^ always ( which always puzzles me) Everytime I took them I would be totally insomniac. Like a half a B6 would make me insomniac for 2 nights!! And tired all day. I was doing Methylcobalamin shots on my own for years and they were AMAZING. MOst importantly helped my sex performance, my droopy eyelid and god a dozen other things. Shots are so expensive that I really want that Guard product to work…. I was mainly scared to buy it because I DON’T WANT TO BE INSOMNIAC AGAIN and it has B6 in ti which is the culprit. Can you tell me if the B6 being ‘methylated’ makes a difference? Am I better to use shots? I also do organic raw barley grass JUICE powder for B’s as I was told that is the best natural source of Bs …. but no B12 and I’ve been vegetarian for 25 years. Whew!
        Can you help me out on this from your experience?

    • Debbie Hawkings

      Hi, as someone who has b12 deficiency, along with my five daughters, I just wanted to mention that if you did have that deficiency then taking oral or sublingual supplementation is not going to help you long term. The can raise the serum blood level and have a small effect, but the long term repair and healing will need b12 injections. The level in your blood is of little consequence compared to your symptoms. Having supplemented for so long you may find it difficult to get a diagnosed of B12d from your doctor. Try looking up the condition so you can understand it well. Those symptoms are very much to do with b12d, but your treatment is not effective.

  13. Annie

    Thank you for your reply. I might try niacinamide.

  14. Annie, You might want to find an Integrative Medical doctor and have him/her find out your levels withIN cells via SpectraCell Laboratories.
    Also, you say things happened while on medications. Sometimes after fixing a problem, the same medications you used before may no longer be appropriate. Lastly – the body can change. Some people can start becoming paranoid and psychotic on medications used for that same thing (called a paradoxical reaction) or react that way even to asthma and allergy medication!
    Best bet – see a doctor really knowledgeable in this area.

    • Annie

      I’d never heard of that before. Very intriguing. I’ll talk to my parents about it. I know some other B vitamins and calcium are important for schizophrenia. The medications I took that caused psychosis were prednisone and ciprofloxacin. I didn’t release how much some medicines can deplete you of nutrients. Have you or someone you’ve known had their nutrient levels tested before with that kind of technology? Thanks for your help!

  15. Annie

    Hi, JD and Jeanie. First of all, thanks for all the help! I told my mom about the nutritional testing, and we are going to look at it together the next weekend I come home from college.
    I had been eating sweetened yogurt, so I am going to get unsweetened next time I go to the grocery store. I’ve tried Kefir first and liked it, so may get some more of that as well. I actually have raw sauerkraut, so that’s convenient. Do either of y’all recommend a brand of yogurt?

    I also read the cipro can deplete calcium and iron, so I am taking good supplements for those as well. I’ve read that calcium can affect schizophrenia too. Thanks again 🙂

    • I just noticed that Clover Organic kefir contains L. rhamnonsus, which is the same general strain that reduced anxiety in mice (via influencing GABA levels in the brain, mediated through the vagus nerve). This kind of research is still in very early stages — there’s no evidence yet that the same effect would work in humans. But as long as you don’t have a negative reaction to dairy products, it probably can’t hurt.

      Here’s another article on that same study:

      • Annie

        Thanks, J.D. Right now I am drinking green tea because the l-theanine makes me feel calm. I believe it effects Gaba as well. I didn’t see Kefir in Whole Foods when I went to buy my groceries, but i’ll keep a look out. I am definitely into things that can’t hurt, haha.

  16. Just a correction. I didn’t mean to type vitamin D2. I meant vitamin D3. That is a very important distinction. The daughter who used to have “schizoaffective” not only needed extra vitamin D3 because of the polymorphism, but she also had low intestinal absorption of calcium and required a highly absorbable liquid form of it she got from the doctor’s office (although it is sold without a prescription).

  17. acdoland

    Ahh ok, D3 makes more sense. Hopefully I’ll get my nutrient levels tested and figured out. The medicine I’m staying on to prevent hallucinations is pretty expensive, so I am definitely into alternative therapies. Did she doing anything else to treat (not hide) her schizoaffective symptoms? Thanks!

  18. hazeraze

    Please look into this…I have been battling systemic candida for years, many conventional doctors do not research the correlation between chronic inflammation and parasites. The connection between parasites and asthma is astounding, along with the prevelance of toxic heavy metals, and lowered immunity, which in turn makes one susceptible to all forms of infestation. We are, after all, just organisms, and oftentimes people feign ignorance to the fact that with the plethora of enviromental toxins we are faced with daily, decreased nutrients in our food supply, and exposure to thousands of species of parasites via water sources, pets, etc. This is not just a “third world country” disease, parasites and worms are very prevalent today in America….however big pharma does not wish do shed light on this because to suggest so would mean the key to fighting many chronic and debilitating diseases. They would rather prescribe costly drugs that mask symptoms, not eradicate the root cause of the disease.


    By Michael Biamonte, C.C.N.

    The subject of intestinal worms is probably very frowned upon or avoided by most people, including doctors. The truth of the matter is, based on my current research, one out of six Americans has actual living worms inside his body.
    There are many types of worms. There are tapeworms which are long, opaque, thin, ribbon-like sort of noodle-shaped things, which live in the intestines, can grow well over fifteen feet long, and specialize in consuming your food. This can cause you to be chronically hungry but not able to gain weight.

    There are round worms that can grow sometimes up to a foot long and just look literally like a worm out of the garden. There are pinworms which are smaller worms which actually resemble a pin in shape and size. These are usually very close to the anal area and cause a lot of itching. There are even worms which live in your bladder which many times look like a fish with a head or a tail and can be expelled through the colon when taking the right medicine.

    There are worms that live in the liver and actually can migrate to other parts of the body and take up residence there.

    The typical symptoms of worms include all types of gastrointestinal stress, rectal itching, itching on the skin and throughout the body, all manner of digestive discomfort which could include constipation and diarrhea. A crawling feeling is very commonly reported by people who have worms.

    There are other symptoms but the main ones would be: anemia, chronic fatigue, inability to gain or lose weight, insatiable appetite (hungry all the time but never satisfied), any general gastrointestinal distress such as bloating, burping and belching. Key signs are rectal itching, especially when it seems to be worse between one and three a.m.. Some patients also report a worsening of these symptoms that we’ve already mentioned when the moon is full! It seems that worms living in the body become more active when there’s a full moon. I guess if a wolf or dog howls, worms can be more active!

    These are some of the key signs of worms. There are many others, but these tend to be the most outstanding.

    How do I know that one out of six people have worms? In my practice we see many people who have chronic fatigue (which can be caused by a host of different viruses) and also chronic candida (a yeast infection in the intestines, vaginal, or genital area in men). Recently, we gave all the patients that we have with these conditions–which number in the hundreds–herbs which would expel worms if indeed these patients had them. To my amazement, 50% of those who took the herbs called up to tell us that they were seeing strange things in their feces. Very commonly, the scenario went like this: The patient took the herbs, then began to feel an increased amount of rectal itching or itching on the skin, increased amount of burning upon having a bowel movement, or an increase in some type of wet or moist feeling in the rectal area. This was then followed by abdominal cramps and pain upon which the person had to have an urgent bowel movement. Having the bowel movement, the patient reported seeing worms in their stool or in the toilet water. Some only saw a few, but one patient actually saw an entire handful! Luckily for these patients the worms were dead, as the herbs had killed them.

    Statistically, after going over all the records, I found that it was just about half the patients. This tells me that 50% of all the people with chronic fatigue and candida have worms.

    Loosely figuring, if one out of three people in this country has an overgrowth of candida or one of the viruses that are known to cause chronic fatigue, and if we conclude that half of all our patients with those conditions had worms, then we can compute that one out of six Americans probably has worms.

    We can only guess how many people with gastrointestinal complaints, chronic fatigue, anemia, and the other symptoms I’ve mentioned, have worms–and it’s being completely overlooked by their doctors! In America, most physicians and health practitioners would consider that we’re too hygienically clean to ever have such a thing. Maybe in third world countries, but not here. Well, I’ve got news for all those practitioners and doctors. If they take a good walk down the streets in Manhattan and take a look at who’s handling the food we buy, they’ll find that it is mainly people from third world countries who are ignorant to our hygienic standards. So, it’s no wonder that American could be getting worms without having to travel to third world countries!

    If we examine the common causes of why one would have worms, we find this: 1) eating sushi or improperly cooked meats will cause worms; 2) eating vegetables or fruits not properly washed could also cause worms if they are exposed to fecal matter, even in tiny amounts. 3) sexual practices which involve the rectal area and involve contacting feces can also pass worms.

    Exactly how one would get worms is pretty simple. Someone eating improperly or raw cooked meat, fish, chicken or some other food that has had some contact with feces. The next step is that the food comes into your stomach and if your stomach does not make enough acid to destroy harmful bacteria in the food, worms or eggs which might already be present in the food will pass into the digestive tract where they begin to grow. Bacteria, mixing with improperly cooked flesh, will actually give rise to eggs of different types of worms. Beef, poultry, pork, fish, all individually have their own unique types of worms that will grow from them. Once these worms begin growing in the intestinal tract many of them will start to reproduce and lay eggs. Worms generally are male and female, so they literally reproduce and the female drops her eggs into the intestinal tract where they hatch. The next thing you know, you have a living colony of these things in your intestines. Then the symptoms begin.

    Several factors have to be present for the person to be susceptible to worms. The stomach would be low in acid, the digestive juices that the body makes from the pancreas would be low, or the bile from the liver would be deficient. Normally, these juices aid in destroying organisms before they’re able to grow and mature. A weakened immune response also would be involved. Many times people with candida and other microscopic parasites already have the perfect home in their intestinal tract for worms to grow. (For our purposes in this article, parasites refer to organisms seen only with a microscope while worms can be seen with the naked eye.) The worms settle in and nest and multiply and soon they’re all living together in harmony, much to your dismay.

    In order to properly eliminate worms from your system, one must first eliminate the other infections, whether they’re bacterial, fungal, yeast, viral or parasitic. Then you would take herbs that would literally purge the worms out. Fasting for at least a 24-hour period before taking the worm expellers is ideal. Veterinarians have done this for years, but many doctors don’t seem to utilize this. Once the worms are eliminated, herbs that would be able to destroy the eggs they leave behind should be taken for at least a month to make sure the worms don’t come back.

    The worm purging should also be done every few weeks to kill any eggs that have grown into mature adults. Then we normalize the intestinal tract and digestive system to prevent the situation from ever reoccurring. You would need to take certain natural substances which can absorb any harmful toxins in the intestines and clean it and make it germ and poison free. The next step is taking natural substances to strengthen the digestive system and make sure you’re producing enough digestive juices so any future organisms that are ingested can be killed. Substances like FOS, which feed the friendly bacteria, need to be taken to build up the friendly bacteria and increase your own immune response. There are natural substances we now know of which do increase the immune response in addition to the friendly bacteria.

    All these things need to be done to ensure the person has eliminated the worms and they won’t come back. When this is done we can start to correct vitamin deficiencies and boost the person’s overall immune system so that the problem doesn’t return.

    A person who has had worms once in the past is definitely more susceptible to getting them again. The reason for that is most people who have had worms and eliminated them have not gone through these other steps after initially killing the worms.

    Most of our patients who have expelled worms have reported the greatest increase in energy and well-being after the worms were eliminated; even more so than when their viruses or candida were eliminated, or any other infection! One by one, man or woman, they all reported the greatest improvements in their overall energy after they expelled worms. That really makes you wonder!

    Michael Biamonte holds a Doctorate of Nutripathy, and is a New York State certified Clinical Nutritionist. He is a professional member of the International and American Association of Clinical Nutritionists,The American College of Nutrition and is a member of the Scientific Advisory Board for the Clinical Nutrition Certification Board. He is listed in “The Directory of Distinguished Americans” for his research in Nutrition and Physiology.

    For an appointment, contact our office at:

    Michael Biamonte, C.C.N.
    139 Fulton St.
    Suite 507
    New York, NY 10038
    (877) 223-3066

    ©1997 – Current Year: MTB Management, Inc.
    ©1997 – Current Year: MTB Management, Inc.

    Back Top of Page
    Check out these websites!!!! EYE OPENING!!!!
    The different ways that bacteria can affect the human body are:

    An infection which weakens the immune system and allows other biocontaminants which would normally be under control to affect the human host.
    An infection to a healthy immune system that has been transmitted by airborne inhalation. (Tuberculosis and Legionnaires Disease)
    A contagious bacterial infection that can be found on any surface where an organism might grow or attach.
    By being transmitted from the excrements of rats, squirrels, and birds. Often these bacteria will become airborne by attaching to tiny particles and moisture.
    By causing or contributing to hypersensitivity pneumonitis, chronic fatigue, irritability, depression, dermatitis, respiratory infections, asthma, sinus infections, ear infections, skin infections, Legionnaire?s Disease, meningitis, tuberculosis (TB), pneumonia, allergic rhinitis, chronic bronchitis, humidifier fever, cold and flu-like symptoms, and many other conditions of compromised health.
    By releasing endotoxins that are also infectious agents.

  19. I’m just wondering whether anybody here would like some live kefir? For the past couple of months I have been culturing my own kefir from actual live grains, (not a starter powder) and because they grow at a steady rate I often have some extra grains which I dry. I live in the UK but have sent a small packet of my dried grains to my daughter in the USA and they’ve been very successful. Kefir is just about the best probiotic you can get which is why I’m now supplementing my diet in this way. I’ve also written a leaflet with instructions for culturing which I can include. So if anybody is interested I’d be happy to supply some for free if you’d be willing to make just a small contribution for postage and packing?

    Please email me if you’re interested.

  20. Also – not sure why because I’m rubbish with all this gravatar stuff – I appear to have logged in as Saraji10, but I’m also Sara who commented above, way back in September!

  21. Andrea

    manganese what is the dose?

  22. SB


    Prednisone and cipro both deplete folate, as does b12. Perhaps that is why after high doses of b12 those meds induced adverse effects, whereas before they didn’t. High levels of B12 are also known to be antagonistic to iron.

    Not sure about the link re folate during pregnancy causing asthma, there are other studies/claims that refute that (though who knows whether impartial or what have you). Though it is interesting to consider the timeline for rise in asthma vs folate supplementation, I’m mindful that correlation does not equal causation. It’s also interesting to consider the apparently not insignificant number of alpha-1-anti-trypsin deficiency cases that are mistakenly diagnosed as asthma.

    Good article and interesting discussion in the comments. Testing in my country is archaic and I wouldn’t know where to start.

    • Thanks for the comment. For those that want to check their gene for alpha-1-anti-trypsin deficiency, it’s one of many traits you can view on your 23andMe profile.

      • SB

        Is the MTHFR mutation available on the 23andMe results as well? Couldn’t see it on their list.

        • You have to search the raw data.

          MTHFR 677 is at Rs1801133 (GG/CC is “normal”, AA/TT is 30% of regular activity). When people talk about a “MTHFR mutation”, they usually mean AA at Rs1801133.

          MTHFR 1298 is at Rs1801131, but I don’t know how to interpret the results. Here’s a post on the topic:

          MTHFR 1793 is at Rs22749746, but isn’t included in the 23andMe data (so far).

          You can either enter the SNP in the search, or use a link like this once you’re logged in:


          Some other SNPs in the raw data that are interesting (to me at least) include:

          COMT (how fast dopamine is broken down) rs4680

          DRD2 (dopamine, error avoidance) rs1800497

          OXTR (oxytocin) Rs53576, Rs1042778, Rs2268490, Rs237887

          5-HTTLPR (stress resilience) rs25531

          MAOA (how fast multiple neurotransmitters are broken down) rs6323

        • As I understand it, they look at SNPs in MTHFR in two separate tests:
          1- The test done for “Neural Tube Defects” uses the MTHFR gene. 23andMe does SNPs and so lists many items as such rather than by the gene the SNP is in. Here is what it said they were looking at in my report: “copies of rs1801133 (also known as C677T) in the MTHFR gene”
          2- The other is “High Blood Pressure (Hypertension)” saying,
          “[Researchers] found that each copy of a G at rs17367504 in the MTHFR gene was associated with 0.89 times the odds of high blood pressure.

          When the daughter I talk about in my book was genetically tested, it was not via 23andMe, although I have been tested that way since I was in a research study and got the 23andMe for free. If I recall correctly, I think she first was tested from Kimball genetics. It was some years ago.

      • SB

        Sorry, replied to this post because your one below does not have a reply link.

        Yes, the following would also be of interest to me, especially considering the amount of foods that contain phenols/flavones/whatever that affect/inhibit MAO A and or B, tyrosinase, etc etc.

        On the whole, have you found the 23 and Me report useful? Have you been able to effectively/consistently improve mood/health?

        I have not been able to tolerate any B-vitamins without adverse effects, it doesn’t matter which one it is or which brand, combo, individual, etc, nor any supplement for that matter (e.g. chelated minerals). One of the possibilities I looked at is the fact that vitamins/minerals etc are manufactured via fermentation using Aspergillus, but mentioning stuff like that is when you start to get strange looks so I keep it to myself. I coughed up a fungus ball at one stage, and suspected Aspergillosis (living in a place in which I found black mould, Aspergillus Niger, also the same mould used in citric acid production).

        COMT (how fast dopamine is broken down) rs4680

        DRD2 (dopamine, error avoidance) rs1800497

        OXTR (oxytocin) Rs53576, Rs1042778, Rs2268490, Rs237887

        5-HTTLPR (stress resilience) rs25531

        MAOA (how fast multiple neurotransmitters are broken down) rs6323

        • I think it’s extremely useful. Part of the benefit is psychological … I learned I was actually low risk for several diseases that I assumed I had a higher risk for (based on family history). I’ve also made dietary changes, like consuming less dietary iron, and changing to a methylated form of B-vitamins. Here’s my post on the service, highlighting both benefits and potential concerns:


          • SB

            Thanks for reply. Re consuming less dietary iron, is that due to iron storage issues?

            • One mutation for hemachromatosis … not expressed but iron levels have always been within normal range but on the high side when I give blood. And in general it’s a good idea for men to limit iron intake unless there is potential anemia.

              • SB

                I gather you were able to see the hemochromatosis mutation on 23andMe.

                In the results, are you able to clearly see these details? I understand what you mentioned in an above post re MTHFR, but am presuming as this is one of the things tested for that it’s more obvious rather than having to read screeds of data? I haven’t seen an example of the results.

                Apologies for the many questions, your responses have been helpful 🙂

  23. Yes … you can drill down on the details for each SNP that is related to a particular disease or trait (I think there are at least four related to hemachromatosis). Here’s an example page with the overview:

  24. And, to be clear, I’m not an investor, they’re not paying me, and I don’t know anybody who works there. I just think it’s a great service.

    • SB

      “And, to be clear, I’m not an investor, they’re not paying me, and I don’t know anybody who works there. I just think it’s a great service.”

      That didn’t cross my mind, however now that you mention it *suspicious face*

      Joking. Personally, I don’t think anyone who has posted what you have would be.

  25. David Baldwin

    I have been completely lost for 3 years. I’m 32 now had a stressful life but now I’m unemployed, socially anxious, low sex drive, pale skin, wheat intolerant and lost completely, I was tested and found to be low In B2, B6, B12, selenium and vitamin D along with an exhausted nervous system and adrenal glands. I’m not sure if I have Pyroluria or Low histamine? My doctor gave me anti depressants which do nothing. 5HTP helps a little. Someone help me I’m begging xx

  26. Jim

    Interesting post. I’ve actually been going through a very similar process. Unwittingly and despite being treated for vitamin deficiency by my doctor, I’ve been ill to the point of severe malnutrition. I’ve managed to pull myself back from the brink with high doses of folic acid, L5-methyltetrahydrofolate, B12, fish oils and other vitamins and minerals. Prior to that I was diagnosed with ADHD as an adult, not realising that I had a severe folate deficiency and while being treated for B12 deficiency.

    I think that folate deficiency is actually the main problem very many people have. It results in B12 deficiency, problems with the digestive tract and hence absorption of other vitamins and minerals and leads to, essentially, malnutrition. Obviously, folate and B12 deficiency result in macrocytic anaemia which should be straightforward for a doctor to diagnose. Unfortunately, however, diagnosis is often made difficult by the fact that folate and B12 deficiency often coincide with iron deficiency(or microcytic anaemia). Many doctors are unable to diagnose this either from blood tests(high MCH in a full blood count) or symptoms. Normalisation of the full blood count by reducing MCV, MCH and increasing RBC(conversely increasing MCV and MCH for those with just iron deficiency) will give the best platform for determining further intervention and supplementation.

    I feel that the fundamental issue of anaemia is what must be addressed by people who are either borderline or completely anaemic. Once this is resolved by supplementing with folate, B12 and iron, they should ensure that their digestive tract is functioning normally and that their gut flora hasn’t been damaged by prescription antibiotic use. After that, they should ensure that their inflammation levels are reduced by measuring homocysteine and cholesterol. Levels can be reduced by omega 3/6 supplementation.

    If you’re interested in my approach to improving full blood count parameters as a measure of progress, feel free to email.

    • Amanda

      Your comment sounds very similar to what I am going through now. I am also stressed to the max with two surviving triplet boys that are 2 years old now, so any shortcuts to research I can make would be so helpful. You offer your approach through email. I just stumbled on this blog so I would appreciate having your email to communicate through. Thanks so much.

  27. Laura

    Hi JD!!! Thank you for sharing all your research! SO many people are suffering out there, like me, and are in meds. I’ve been on
    antidepressants since 1994, tried to wean off many times and literally cannot do it. I’ve been to at least 15 different Dr.’s. I’ve been miserable pretty much my whole life-I’m almost 40. I can’t tell you how many times I’ve wanted to die. I still wouldn’t mind going…but I have 4 kids-that was always the dream.
    I am very sure I have Pyroluria:
    I had a test run by a Naturopath back in 2005, I had elevated pyrrols. 47 to be exact.
    I’ve had tingling/numbness in extremities for over 11 years. I’ve had countless rage episodes, impatience, a huge need to have my life go very specifically.
    I’ve even had somewhat psychotic episodes.

    I tried to tell my new Dr. about Pyroluria, which she never heard of and didn’t look into. I showed her my labs. She hardly listened to me, because she was convinced that I had a MTHFR polymorphism, so I went with it. She ordered a Genova Dx NutraEval, which cost us $800 we didn’t have. (Husband lost job 17 months ago)… The test showed no MTHFR polymorphism, so now she thinks I have comt defect. She said to go in her methyl B’s, methyl Folate, vesselcare and fish oil. I’ve been a raging, psychotic bitch!! I told her the methyl B’s made me worse and she told me to restart them. She also put me on NAC because she said the tests revealed severe glutathione depletion and amino acid metabolism disorder, high oxidative stress and very low antioxidants. Please, please help me. I can’t go on. I see it hurting my kids when they see me freak out. I also have adrenal fatigue/issues. Part of the vesselcare is inositol. We can’t afford to go to anyone else…we’ll have to put our house up for sale
    this May. Sorry this is so long, I’ve been suffering since I can remember-age 9.
    Thanks, Laura

    • Laura

      Couple more things… I’ve had ferritin tested many times and the docs always say it’s very low. I think my last count was 5.
      I’ve been told by past docs that I have B 12 deficiency. Our whole family just went Gluten free, we eat organic chicken, and red meat. We make smoothies with kale, fruit, carrot juice, spirulina.
      I think that’s it. I’m on 10-20 mg of Lexapro, depending on time of month. I have severe Pms too, in addition to the rest.

    • Hi Laura — sorry to hear you are having a rough time. I’m not medically trained, so I can only speculate and not give advice. Have you tried high doses of B6 and zinc+manganese? That would be the treatment for pyroluria, according to Pfeiffer.

      In terms of medical tests, I am very happy with the service 23andMe provides (genome analysis), and the price just went down to $100. You can find out which COMT variants you have, as well as everything else you ever wanted to know about your genome.

    • rose

      Hi Laura – I’m no MD or anything either and only share this in case it helps prompt your own thinking. You sound very similar to me in terms of stage of life, reactions to things etc etc. I’m a similar age – I recently turned 41.

      From what you describe it sounds like:
      High manganese (perhaps due to excess storage in liver)
      Low copper
      Low iron

      (Normal manganese with low iron is ultimately the same as excess manganese. Low iron can be caused by low copper – see copper deficiency anemia).

      Do you have frequent menstrual cycles or infrequent ones?
      (e.g. cycles of normal length or shorter/longer?)
      Do you have issues with low blood sugar?

      I have similar responses to fish oil and methyl folate. I can’t touch fish oil because I get full on rage when I take it, and it seems most other things that are supposed to help people do not help me AT ALL. I have my own theories re me and the fish oil etc but won’t go there.

      I (have tried but) avoid supplemental manganese like the plague – it makes PMT worse as it’s VERY estrogenic. Great it you are low estrogen (e.g. post menopause). Terrible if you have excess estrogen!

      High intakes of zinc are terrible for thyroid. So please be careful if you go down the pyroluria path.

      I find I might get a brief reprieve from ONE dose of NAC but I can’t continue to take it. Sulfur opposes copper – NAC is a sulfur amino. In my case, the info re detox reactions does not apply to NAC or anything else I’ve tried. Are any of your meds in sulfate form?

      I personally avoid any b-vits and most supplements to be honest, including zinc (iron antagonist and copper antagonist – iron/ferritin needs copper). I actually find copper helps but only specific forms of it (e.g. not glycinate nor sebacate).

      I find things that oppose manganese have helped at times (e.g. potassium, calcium, iodine), but some manganese antagonists have the downside of opposing iron (e.g. calcium) or copper (B6, vit C). If copper is depleted you might find you get a very brief holiday then deteriorate quickly.

      I’ve found potassium bicarbonate to be the most beneficial so far because potassium is a copper synergist and it doesn’t seem to antagonise iron (I also tried potassium chloride and gluconate without success). I think carbonates/bicarbonates are beneficial because I read (on Wikipedia, yes, I know, shoot me) that:

      “For the iron ion to bind, an anion is required, preferably carbonate (CO2−3).”

      I’ve found most supplemental forms of iron do not help. I recently found a different, specific type which seems to be better than others but won’t post it for now as I don’t want anyone to think the reason I’m typing this is to promote it. Previously I’d tried everything from iron sulfate to ferritin to freeze-dried liver to eating raw liver.

      The reason this other iron apparently works (backed by peer reviewed studies etc), is because it does not break down until it reaches a more alkaline environment in the intestine where iron is absorbed. Also of benefit is the fact that the absorption of this form of iron is not reduced by food (or some meds). However, I find I can’t take too much without adversely affecting copper.

      Anyway – hang in there Laura 🙂
      Hope some of this helps.

    • rose

      Re: “I can’t tell you how many times I’ve wanted to die. I still wouldn’t mind going”

      P.S. This is something I would think/say, DO think/say, e.g. I wish there were euthanasia centre’s you could go to and opt out, “I’ve had enough now, I gave it a fair attempt, please just let me off the planet”. Or something like that. Maybe a lethal overdose in a packet. Take one and don’t call in the morning etc 🙂

      I’ve also “been miserable pretty much my whole life”. Anti-depressants don’t work for me. You can guarantee that if a side-effect is that it might worsen depression, then it does. And it stays worse. Or I am left super-glued to the floor, unable to move/need to sleep 48 hours a day. It certainly seems as if the medical profession still thinks the only neurotransmitter that needs fixing is serotonin. Heh. Sad face.

      I don’t know if you are aware there is a thing called Manganism? (Aka “Manganese Madness”). Excessive storage of manganese is known to cause mental illness. They treat it with L-Dopa. “High levels of manganese can produce violence and other mental changes, including a psychiatric disorder resembling schizophrenia.”

      Hope you get the help you need Laura. If your GP or doc isn’t listening, please find another one. I know that’s easier said than done. I’m tired of explaining the same shit over and over to doctors who can’t even tell you the side effects of the medications you’re on or the ones that they’re trying to prescribe you, and accuse you of “being difficult” or “knowing too much” if you dare to be informed yourself.

      • Interesting idea re: manganese toxicity. There are definitely documented cases, but there is usually an environmental source (welding, or even manganese blue paint before modern pigments). Here’s one article:

        • rose

          I’m talking more about instances of excess due to liver damage/medication/drugs/other supplements/physiological reasons etc. Quite a few cases of people (women) developing mental illness later in life etc, after manganese (and/or iron or anything else) has had time to build up. Probably not on Pubmed though 🙂

          As I noted in my post, normal manganese with low iron/low copper is essentially the same as high/excess manganese.

          Hair analysis would be the way to go if you don’t want to spend time/money via process of elimination. Many advocate hair analysis as a better tool/indicator of hormone imbalance as well.

        • rose

          The other thing to watch out for is B12 opposes iron. If iron is low then B12 will antagonise.

          B12 also opposes potassium. Low potassium is also associated with neuropathy issues. Folic acid antagonises potassium.

          Many people look to things like B6 for peripheral neuropathy etc. Personally I’d start with electrolytes before mega dosing on anything else.

    • James Herd

      Hi Laura,

      There must be a reason why your doctor wanted to test you for MTHFR. I would suggest that this is probably an avenue worth exploring. Folate deficiency is a major problem for a lot of people and it was actually the cause of my illness which I have now resolved. It also leads to B12 deficiency which is often what is picked up first by doctors. Unfortunately, many of them fail to recognise folate deficiency and treat the B12 which leads to very severe problems down the line. I also believe that folate deficiency is a factor in much so-called mental illness and can cause psychosis.

      Do you suffer from diarrhea? That is a symptom of folate deficiency. Also, if you have had a full blood count recently, what was you MCH? MCH is the same as MCV: if either are high, you have anaemia, i.e folate/B12/iron deficiency. HIgh MCH particularly implies deficiency in all three.

      If you are anaemic then this is the first thing that you need to resolve.

  28. Michelle

    I am hetero mthfr and I also have low b12 which I take injections for. I recently Noticed in the last six months have been experiencing extreme depression and uncontrollable rage. I did get the copper iud 2 years ago and I started thinking I was becoming toxic. The last week I have started taking zinc supplements and extra b6. Huge improvement.

    • Copper levels can be tested for. I think mine were done to see intracellular levels, via SpectraCell Labs. For too high copper levels, I was given Moly-B (molybdenum). We get all kinds of toxicities – not just elemental ones. Glad to hear you figured out what you lneeded. I wish we did not require any supplements. I always worry about balance. Taking one nutrient can interfere with others. I have read that getting them in *real* foods allows our body to use them or not as needed. Unfortunately, our food supply, (and often what I have chosen to eat in the past) has inadequate nutrition.

  29. SeReNa Lytle

    Kudos !! Wanted to say Awesome and most Informative Independent Research Information I have Ever read on this Topic Issue. I Myself have been Devouring and Researching these findings an trial and error workings on myself.

    Tired of self medicating and ready to Pursue Whole hardedly a career as a Physicians Assistant.

    Need more like you. R u in the medical field ?

  30. Adam

    FYI, the following is a great site to use for analysing your genetic Methylation data from 23andme:


    & Dr. Amy Yasko is one of the Pioneers on this topic.

  31. mark

    I have anxiety and sometimes insomnia. Got 23andme done, turns out I have really shitty methylation pathyways, particularly by the the way my body uses b12 (MTRR). This made sense, as I was glutathione deficient.
    I am going to try SAM-E tommorow and see if that helps. Methylcobalamin helps.

    • Jim

      MTRR A66G? If so, I have that too and I’ve found by far the best treatment is injected hydroxocobalamin(B12). AFAIK his gene means that methylcobalamin is used too quickly. I think that hydroxocobalamin is relatively slowly methylated and drip feeds methylcobalamin into your system allowing better uptake.

      You need to inject hydroxocobalamin but it’s easy to learn subcutaneous injection techniques. Ask your doctor for help.

      • mark

        I inject cyanocobalamin as is, does that not do much? Yea I am homozygous recessive for MTRR A66G

  32. mark

    I inject cyanocobalamin as is, does that not do much? Yea it is homozygous recessive for MTRR A66G

    • Jim

      Cyano may not be the best choice: http://www.ncbi.nlm.nih.gov/m/pubmed/9192785/?i=1&from=cyanocobalamin%20(c-lactam)%20inhibits

      I would switch to hydroxocobalamin if I were you. Have you had a full blood count lately? What’s your MCH?

      • mark

        Ill talk to my doctor about it. I take methylcobalamin sublingually now. Is MCH a blood test I should get done?
        I started SAM-e this morning, maybe to help with the methyulation process.

        • Jim

          Methylcobalamin is a methyl donor as is SAMe. I didn’t notice any additional benefit from SAMe myself perhaps because I was injecting methylcobalamin.

          MCH is one of the parameters of the full blood count. It can point to macrocytic/microcytic anaemia even if MCV is normal. If it’s high, as mine was, this can indicate combined macro/microcytic anaemia. In my case, daily folic acid and hydroxocobalamin every other day brought it down into the normal range. I think the microcytic anaemia was caused by a candida infection, acquired as a result of antibiotic use, which actively destroys red blood cells to get at the iron.

          I’m still learning and experimenting. NHS in the UK hasn’t a clue about any of this stuff. Keep reading and hopefully you’ll find what works for you.

          • mark

            How frequently do you inject hydroxycobalamin. Also, is it much more expensive?

            • Jim

              I’m trying to inject every other day. I’d prefer to do it every day but the injections cost around £1(UK sterling) per jab and I have to buy them from Germany. No idea about US prices.

  33. mark

    How frequently do you inject hydroxycobalamin. Also, is it much more expensive?

  34. A wonderful detailed piece of scientific account about biomolecules. As a science teacher in third world part of this earth, i was looking for some information on the relationship between methylation and libido. Am so concerned because the school going children are “fed” with methyl-rich meals to lower their libido. Does this have any longterm effect on them?? Kindly reply. Disturbed teacher.

  35. firebird

    It would be nice to see updates to some of your commentary. In particular, as it happens I do not consume any alcohol, yet there was a period of time unexplained vomiting resulted in an extreme B1 deficiency.

    Such a deficiency can result within a period as short as 10 days to 2 wks and most certainly can lead to sign & symptoms of both dry and wet Beriberi manifestations. FWIW, it was not even a blip on multiple doctor’s radar.

    Thank you for making note of this detail; because although reports may relay it is rarely seen these days in the western hemisphere unless one is an alcoholic, that is not necessarily the case.

  36. Shane

    Am I likely an over-methylator? Whenever I have taken Methylcobalamin I get the following symptoms: depression, hoplessness, roid-rage-like-irritability, heavy head, & dry burning eyes.

  37. Christy May

    Maybe you can help? I am bi polar and was trying to supplement my body to stay/get healthy. It seems every time I take a multi vitamin I get rageful and aggressive and super scatter brained. Can’t focus or even sit still. What could be causing this particular reaction? Anything I might try to avoid from your knowledge? Thanks

    • It sounds like avoiding multivitamins altogether is your best bet. If you eat a nutrient rich diet you’re unlikely to develop any deficiencies.

    • Jim

      I disagree. I suspect that you might be extremely vitamin deficient and the reaction is due to your body having nutrients all of a sudden. This happened to me many years ago. I just stopped taking the vitamins because I didn’t know any better and it was several years before I was diagnosed.

      Investigate you methylation defects at a genetic level with the help of a good naturopath ASAP. Read about things like the MTHFR gene, mutations of which cause problems absorbing folate which is vital for DNA synthesis and creating neurotransmitters.

      • Michelle

        I would look into doing 23andme only 99$,!genetic testing it looks at several other snps that are involved in methylation. I am heterozygous for Moa-a which can cause aggressive, OCD and personality disorders when combined with a comt mutation.

        • Jim

          Yes, that’s what I’ve done. I’d still recommend trying to find a naturopath with deep knowledge of methylation defects to help though. It’s not easy to do it for yourself. Both routes are expensive but a good naturopath might save you cash in the long run.

          • Even if deficiencies are the problem, multivitamins might not be the best approach. Some forms of non-methylated vitamins (folic acid, B12) can actually reduce physiological usage of bioactive forms (folonic acid, P5P B6, methyl B-12). On the other hand megadosing with with bioactive forms may ramp up neurotransmitter production to the extent that you feel overstimulated or aggravated. Trust your body on this one; if a supplement makes you feel bad, don’t take it.

            Agreed that knowing your genetic profile may be helpful, especially in regards to MTHFR.

            • Jim

              Sorry, I should’ve been clearer in my reply. I was really objecting to your statement that if she ate a nutrient rich diet she wouldn’t have any deficiencies. I think most people have a range of deficiencies and would be well advised to supplement.

              As I said, I had a similar reaction to a multivitamin which was actually a warning sign of severe deficiencies. It would probably be wise to stop taking the multi for the moment while she is tested for her deficiencies by a competent doctor, e.g. a naturopath with knowledge of genetic issues with methylation. However, I am certain that she needs a very comprehensive supplement regime as soon as possible.

    • Jim

      Hardly what I’d call weighing in. 23andMe seems to be being extremely cautious on this which is fair enough. They don’t want to go out on a limb when the research is in its infancy.

      However, there are many very sick people today who simply can’t afford to wait for a scientific consensus which may take decades if, indeed, it ever arrives.

      Pregnancy is certainly a situation that puts increased demands on a person’s folate. Other, equally important, situations include: childhood growth spurts, adolescence, stress, illness, alcohol consumption, drug taking(pharmaceutical or otherwise), dieting and exercise. These situations can be demanding for those without an MTHFR mutation, never mind those with.

      Contrary to 23andMe, in excess of half the population have diets deficient in folate. It’s hardly surprising that folate deficiency is considered such a serious public health issue that in the US, flour is fortified with it.

      I think that anyone with health issues should be screened for this SNP and others including MTRR A66G which is implicated in vitamin B12 deficiency. It’s cheap now and it’s better to be safe than sorry.

  38. David

    Just stopped by for the first time and have something to share. For those interested in getting more out of their 23andme results, check out geneticgenie.org. It will analyze the raw data and cross reference against the works of a well known methylation specialist. It’s free and well worth the effort.

  39. glen

    I was diagnosed hetero A1298C and a normal C677T. I have very high RBC folate and b12 with moderately high to high homocysteine of “16” (depending on whose scale you believe). My doc sees this as a failure to convert the folate and b12 into active forms. Podiapn was prescribed (5mg of methyl folate), and when I took only 1/2 capsule to start i literally thought i was going to die. i hope i’m not in homocysteine “checkmate” since i don’t tolerate supplemental b’s.

  40. Adam Bliss

    @ Glen- How is your BHMT pathway? Supplementing with Trimethyglycine should help to lower the high homocysteine levels… Also- what happened when you took 1/2 (2.5 mgs) capsule of methylfolate? Maybe start with a much lower dose like 400 mcg’s and see how that effects you…

  41. glen

    @ Adam-yes my recent switch to TMG seems to be a VERY good fit right now along with a product called Flavay and intermittent liposomal vitamin C. I believe all these to be great and effective products. For the record, I have no financial interest in any of the products. Dr. Lawrence Wilson has a great IP article about TMG, Flavay has been around a very long time, and if you google “New Zealand swine flu cure with vitamin C”, you will link to a 60 Minutes documentary on youtube that is so amazing it will seem incredible. Also, and this is a long story, i may have gallbladder issues in the mix, even though testing shows nothing wrong…i understand this is not an unusual scenario. I have tried very small doses of the M-folate, etc. and it was intolerable. A local Dr./personal friend said people with impaired gallbladder function will not tolerate supplemental B vitamins, but she could not recall the source of the information.

  42. rebecca brown

    Supplimentation is more complicated than a particular one being good for you or not. It’s also about what the suppliment is made from and how it is absorbed. An example of this is B12, which often cannot be absorbed by some, especially older people who lack the cofactor in their stomach so need a suppliment in sublingual form. Also most B suppliments are made from yeast so, as I’m allergic to yeast, make me feel very ill. So alternatives have to be found. I recently took B2 to help with allergies and asthma. Later relised that it had been made from yeast even though the container stated yeast free. I realised something was wrong when my asthma suddenly got worse on the secord day. Your article is very helpful but you could try other suppliments to help with your asthma / allergies. Always buy the most pure form and where impurities have been filtered out. I find powdered MSM helps with detox, Pura EPA fish oils helps lower inflammation and depression, powdered dried milk thistle herb helps cleanse liver and detox and buffered Vit C. powder improves adrenal function and lowers inflammation.

  43. Susun

    Vitamin D3 supplements, taken in mega quantities, have increase my Vit D levels from 17 ng/mL to 80 ng/mL, I now take 10k IUs of D3 daily as maintenance and my Seasonal Affective Disorder symptoms are gone, which was the goal, I did this after reading a John Hopkins University Study where they found 100,000 IUs of D3 in an on/off dose (1x dose) to be more effective than light therapy… but as an added bonus, I also no longer need my asthma inhaler! No more asthma symptoms, wheezing, whatsoever! Note: when taking mega doses of D3 you should also take k2 supplements to facilitate calcium moving from your arteries to your bones & teeth. Google that for verification. When I miss several days of D3 (I can be forgetful,) Iknow to get back on track when wheezing returns.

  44. Adam Bliss

    @ Glenn- Lithium orotate will help usher B12 into the cells. You said after taking that much methylfolate you felt like you were going to die. What does that mean? What were the symptoms? Sounds like maybe you were having a reaction downstream in the methylation cycle when you jumpstarted it by adding the methylfolate. Not turning B12 into the active form could be problem in the MTR or MTRR Gene, or Lithium deficiency as lithium is required to get B12 inside the cell along with a carrier from the gut.Methy B12 is the active form of B12, have you tried that? Can you handle Methyl Donors ok? But the reaction leads me to believe you were deficient in Methylfolate and thus not methylating correctly and when you added the methylfolate it jumpstarted your methylation cycle and you either have a SNP later in the Cycle prolly COMT or MAO, as CBS would tend to drain the Homocysteine. Have you done your genetic profile?

  45. PC

    I’m pretty sure I am low in B vitamins but all this MTHFR stuff is very confusing to me. I suffer from depression and anxiety, not sure where to start. Can anyone recommend any supplements? I can’t really afford tests. I’ve tried Niacinamide before and it did have a calming effect. But I think I’m probably deficient in the main B’s since I cut grains and lots of other foods from my diet due to intolerances. I probably get some B12 from red meat.

  46. CJ

    I just came across your site. I’m just coming down from what felt like a psychotic reaction to 7.5mg Deplin. Does this sound at all possible? After stopping taking it for one day, my symptoms seem to have declined. Very scary.

    • Adam Bliss

      CJ- Yes a very common occurance with so much methylfolate. Nicotenic acid can help sponge up extra methyl donors. Sounds like u are having a reaction downstream probably to do with COMT…

  47. Nuno

    Thank you for your post, I found it when researching vitamin B can cause depression, because in my case, it does create a similar feeling has do depressed people have. Is it possible to test this? It has happend to me in several different occasions, when takin multivitamins, or hair supplements, but my confirmation that it could be vitamin B the reason, was when I took a B complex vitamins and felt even worse than before. I’ve been trying to find medical journals or articles that adress this issue only to find research done that claims the exact opposite. I would really appreciate If you or any other person reading this post could point me in the right direction.

    Best regards.

  48. Jan

    I’m thrilled to find your blog. To net it out, my mental illness is on my mother’s side of the family. My mother has been in a nursing home since she was 62 years old due to psychotic depression. She’s now almost 90. I’ve also suffered with anxiety since very young childhood. I’m currently taking Effexor, but would like to get off the drug. I’ve only recently heard of MTHFR mutation. Not clear on what it means, but think it likely has something to do with my family history. My brother has been diagnosed with schizophrenia. My question for now is: Will it negatively affect me to take nutritional yeast for restless legs syndrome? Thanks so much. Will read more on your blog. Great info!!

    • Hi Jan — I’m not a doctor so please don’t accept my advice without consulting a medical professional, but in my opinion nutritional yeast is a safe bet. You might also consider a chelated form of magnesium (like magnesium glycinate) for restless leg syndrome. Good health to you!

  49. julie

    good blog.My relative was a research subject at NIH and n carolina university.
    they had homocysteine was too high,also has dysautonomia and pots.NC discovered a gene for too low choline and choline transporter issue.their serotonin is too high mine too low.Im also low in sam e and phostyltilserine and choline.They treated homocysteine w/ b6.They experimented w/pharmacetical phostytlcholine and betaine w/ mixed results.I am also too high in histamine.methyl b12 (without xylitol) will actually stop my asthma.I also was diagnosed w/ fibro (years ago) and suffer from arthritis symptoms.Iknow too high serotonin can make you angry too low depressed.I was looking for supplement to give my dobiemixed breed to lower her serotonin.she’s a rescue and very dog agressive.I think prozac is making her worse and am stopping it.Maybe you could suggest the right b vitamins to try to help her calm down.She was starved and abandoned when I found her in New orleans.I have very bad joints probably from the low choline and its hard to walk her when she sees another dog.I”m also looking into sjorgensen for my own symptoms.I have very dry eyes eyelash loss joint pain,severe tmj and daily migraines.And the fatigue.I have had high white blood cells,and swollen glands over the years.I was diagnosed w/ an cmv infection after a severe illness lasting two years.I think I’ve had relapses.If anyone has any info.I take lysine sometimes to suppress it.Good luck to everyone.Julie

    • Hi Julie — it might be worth trying strict paleo (no grains or legumes or packaged foods) to see if it improves your health (and same for your dog). Marksdailyapple.com is a good resource. Good health to you!

  50. julie

    Thanks.I added me in there as an afterthought.I think I just give up some times trying to feel healthy.I am going to give the gluten free thing a real try.I always fell off the wagon.Despite not coming up w/ a positive for gluten sensitivity,i”ve always suspected I am.Apparently the test can be inconclusive.I know I am allergic to rye and chemically wheat is very similiar.I’ll have to modify the paleo thing.I am allergic to shellfish(very)fish(somewhat)beef(taste good but makes me swollen the next day).Peanuts(somewhat)walnut family,almond/peach(can have alternate days)kiwi (an odd one),coconut,palm,sunflower/safflower.I’ve heard avoiding the nightshade family(potato/tomato) is good for arthritis.Is soy permitted?

    The one thing I learned about the methylation cycle from my relatives trials,is that when one amino/molecule is too high it usually a sign that something else is too low.I am trying to figure out which b vitamin mite be too lowto cause the sam-e molecule to be too high.I’m pretty sure methly B12 is the necessary precursor to having enough sam-e,which is why I take it.I found one study on serotonin in dogs at the U of Pa.,but they don’t offer a test to the public.It’s hard enough to find testing and research on humans let alone canines
    .If in your studies you find anything on a study involving too high Sam-e, human please let me know..

    • A grain-free, legume-free, high-organ meat diet might be helpful for your dog. Organs meats are extremely high in B-vitamins (including B12), and removing grains and legumes will remove anti-nutrients (phytates, lectins) which could be blocking nutrient absorption.

  51. julie

    human or animal study

  52. This was fascinating and helpful. Thanks!! Soooo complicated…it makes my head spin. But at least you narrowed it down to simple points for those of us who can’t do the primary research.

    About your asthma…have you heard about the Buteyko method? Look it up online. I searched it out recently when someone mentioned it, and it’s really, really interesting. I don’t have asthma but if I did, that would be my first thing to try.

  53. Oops, sorry…this was the only page I had read because someone sent me here. Now I’ve seen your “How I cured my asthma” page and you definitely did try Buteyko. I’ll be reading and referencing your page for my friend with asthma, thanks!!

    • Thanks for your comment and welcome! I don’t mind helpful suggestions … I don’t expect everyone to read my entire blog on their first visit. 😉

  54. Emily

    Thank you for all the information! (Sorry for any improper terms or mistakes) I have a double Mthfr defect, suffer from extreme anxiety and agoraphobia and have not responded well to any ssri treatment. I was prescribed deplin (a metabolized form of folate). In an attempt to finally feel better I have started to adjust my supplements and diet. I was on a high dose of deplin, with terrible side effects. I went to the lower dose and still anger issues, couldn’t get out of bed…I just started using niacin (nicotinic acid) to stop the overmethylation and within 30 minute panic attacks are shut down. Add b-12 supplement and I’m in terrible shape. I could take a video and show how extreme overmethylation is and how quickly it can affect your mental state! I’m glad that this is something that’s getting attention and I appreciate your info and advice!

    • Hi Emily — thanks for your comment and for sharing your experience. Do you respond well to folate rich foods?

  55. Julie Hill

    Thanks for all the information put together in one spot! I’ve been living with problems for so long, like a lot of people here. I really empathize with Laura and wonder if she’s found anything that helps yet. I tried methylfolate and methylb12 briefly but got very agitated. All the things that are supposed to help me make me feel worse, including the GAPS diet – broth, raw eggs, yogurt, saurkraut, kefir, etc. I kept restricting foods and then reacting to the few foods I was eating, it was a nine month nightmare and couldn’t overcome the weakness (got down to 91 pounds). I had my stool tested and don’t have any parasites, or candida overgrowth, just a low amount of the good bacteria and an overgrowth of staph and strept. I wish I could have made the GAPS diet work, I would love to populate my gut with good bacteria, but ingesting probiotics and even fermented cod liver oil gives me horrible depression, and I need to be able to take care of my two year old daughter who I’m trying to recover from autistic symptoms. I had the testing done and know that I am double positive for COMT V158M and COMT H62H which I guess is why I can’t tolerate the methyl donors. Next step is hair mineral analysis but I suspect I won’t be able to take the very minerals I’m deficient in. Does anyone know how to overcome the COMT mutations and get well? I’m really intrigued with Dr. Abram Hoffer’s niacin therapy – it seems to work for so many who obviously also have genetic mutations, but when I start to build my dose of Niacin I get really sick. Reading people’s comments it seems that taking one supplement depletes another one, and people still can’t figure it out. It seems so hopeless.

    • Hang in there Julie! I don’t know much about the GAPS diet but I’m not sure why any diet would recommend raw eggs. Raw egg white destroys biotin, which is important for encouraging the growth of beneficial gut bacteria. Also note that niacin and niacinamide have distinct effects — many people have had success alleviating anxiety with the latter.

      If you are AA at COMT V158M and TT at COMT H62H you may have slower than average breakdown of dopamine and higher than average dopamine fluctuation (which could result in mood swings). VDR (vitamin D receptor) stimulation can regulate COMT activity — how are your vitamin D levels?

  56. Oh wow – I didn’t think anyone would actually reply to my comment, thanks! Yes, the raw egg issues seem to be controversial – whether or not to eat them raw, and if so is it ok to eat the whites raw. It seems that raw yolks are the way to go because they are so easily digested (Dr. Natasha Campbell McBride compares them to breast milk). Also, yolks will provide you with most essential amino acids, many vitamins (B1,B2, B6, B12, A, D, biotin), essential fatty acids, a lot of zinc, magnesium, etc. They are also rich in cholin which is essential for the nervous system and liver to function. And cooking them destroys a lot of the nutrients. The debate about raw whites rages on but I’ve been siding with the people (like Dr. Mercola) who say the egg is a whole food that is balanced when eaten together, even balancing biotin, even raw. But maybe I will try just eating the yolks raw and see if I notice a difference. I’ve gone back to taking niacin (small doses) and that helps more than anything I’ve tried lately, especially with food intolerances, but still can’t tolerate probiotic foods. I don’t know about my vitamin D levels, but I was getting good sun a few times a week until recently and didn’t notice any improvement from that. But from what you said that may be important for me so I will look into supplementing. I’m sick of testing – I just paid out of pocket to get testing done at my doctor’s office and I look extremely healthy on paper, except for an elevated TSH but my t3 and t4 are in range so I don’t understand that. (And of course, I couldn’t tolerate Synthroid or Armour thyroid.) I’ve seen people chatting about serum level testing being innacurate anyways because it doesn’t show what’s being absorbed into the cells, so maybe I’ll look into other methods of testing. Anyways, sorry to ramble on, it’s just complicated! Thanks so much for your suggestions!

    • Libby

      Please go to stopthethyroidmadness.com and read everything on that site. You need to get labs of your Free T3 and Free T4 to determine if your thyroid levels are ok. You also need to get your thyroid antibodies checked. TSH is not a good marker for thyroid. It is a pituitary marker only. You might also want to get Dr. David Brownstein’s books: Iodine, “Why You Need It, Why You Can’t Live Without It” and “Salt Your Way To Health”.

  57. Libby

    For carpal tunnel, you need to take a b-complex (100mg 2x daily) along with a high potency methyl form of b12 (1,000-5,000mcg) twice daily. I developed nerve pain along my thumb joint and wrist from spending too much time playing games on a handheld DS. The pain had become constant to the point I wore a stabilzation brace for my thumb and wrist to ease the pain. I took 100mg B complex and 5,000mcg of methylcobalmine twice a day and by the end of the week, the throbbing pain was so much better that I was able to leave the brace off most of the time. By the end of the 2nd week, the pain was about 90% gone.

    A coworker had carpel tunnel so bad that she had to wear a brace and the doctor was talking about surgery. I told her to go get a bottle of b-complex 100mg and take 2 twice daily. She did and her carpel tunnel healed.

  58. Sharon

    I have been looking all over the internet for something like this for two weeks! My methylation page from genetic genie looks like a primary color rainbow (ok, not quite). Only eight are green, several are white (no call – whatever that means), most are yellow, and three are red. I have two full mutations of the COMT, including the 4680 (met/met). As I read the research on COMT, it suddenly explained a whole lot of my life. The depression and anxiety, focusing on negatives, etc.

    After a physical and emotional crash a couple years ago, my naturopath put me on methylated B5, 6, and 12, just to give my system a jump start. About a year later, she told me that they weren’t for long term and to go back to a B complex. After three days, I knew it wasn’t working. After five, I wanted to crawl out of my skin. Thankfully, I had saved some of the methylated ones. After two days back on them, I was totally normal again. She then suggested MTHFR and 23andme.

    After trial and error, the supplements I cannot live without are a very high quality liquid fish oil, evening primrose oil, methylated B5, 6, 12, Vitamin D3 in high doses (northern climate and VDR heterozygous mutation), and an herb blend to balance hormones.

    I am currently doing a paper for college on the COMT mutations. I have hunted high and low for info, but have only been able to find out about the brain. I’m assuming that’s because people are willing to pay for research about schizophrenia or cancer, but not about what vitamins help who. Sigh.

    My question is this. Why do I need the methylated Bs? Obviously my body is not capable of doing enough methylation. But WHERE does that happen? The liver? I know COMT works in the liver (soluable type). But I have been unable to find any kind of explanation of how in the scholarly journals and encyclopedias. Honestly, I’m fine with a “non-approved” study, but I can’t use those for school.

    My best guess from what I have managed to find is that digestion has something to do with it, and the liver does the rest. But when the COMT isn’t working right, then it can’t process the Bs. And stress probably makes the COMT work less and less which would explain how I used to sort of manage life, but couldn’t after some major stressors. Anybody have any ideas?

  59. Margarita

    I confess that this is very confusing to me, because I have both bipolar and bulimia, which you listed in two different methylation categories. I am ordering a genetic test to see if I have one of the genetic mutations, but I wonder if the results will help at all or confuse me further. I take medication for bipolar and bulimia, which seem to help with my mood and to stop the urge to vomit. However, I have very low energy, which my psychiatrist said may be linked to a problem with B vitamin metabolism, especially with methylfolate and methycobalamin. I’m supplementing with both, in addition to a low-potency B-complex vitamin with B-6 in it. So far it has really energized me, but I am experiencing some small headaches. I’ve had stress headaches (and dehydration/electrolyte imbalance headaches) before. I wonder if my headaches could be associated with electrolyte imbalance caused by these supplements? Does anyone have a similar experience? Because I believe that having bipolar and bulimia are common combinations, just based on some research that I’ve read.

    • Hi Margarita — thanks for your comment. I’m not a doctor so I can’t advise you directly, but this case study is interesting … a woman with a similar condition who responded extremely well to Ritalin:


      The low energy could be simply because you’re not getting enough food. Definitely the headaches could be related to the supplements … I would suggest experimenting on/off the various supplements and see if the headaches subside.

      Best wishes in your healing journey and good health to you!

      • Margarita

        Hi J.D., yes I take methylphenidate (ritalin). It is next to impossible to find an MD who will prescribe some, because they usually insist I either do not have ADD (not hyperactive type) or think I would abuse it (despite the fact that I have never abused any drug, not even alcohol). Ritalin has been very effective for me, but the combination of methylated B vitamins seems to be the most helpful so far. I have contacted my MD to see if I can lower the dose of the vitamins, and how best to do that.

        I was given Ritalin for a few months in 2009, followed by a month on the slow-release patch, and never felt better, with few side effects. Then I moved, and no one would give it to me again. So I went into a 7-year slump until now, when I’ve again been given ritalin.

        I don’t know if you’ve experienced this, but I hate it when doctors give you something automatically for a condition because that is what everyone else does. For instance, Prozac for bulimics. It never helped for me, but Cymbalta does.

        I actually stopped purging except for holidays (when huge amounts of food available and stress with too much family), and now mostly I binge and feel terrible after. Which is not technically bulimia, but either EDNOS or COE. I think of it as bulimia, though, because I still feel ashamed of eating, and would really prefer to get rid of the food discretely, despite understanding it doesn’t work and is harmful to the body. Actually, bulimia is integral to bipolar and vice versa (for the women I’ve met with that co-morbidity), because the mania/depression cycle is linked to the bulimic starvation/binge and purge cycle. I personally think bulimia is a coping mechanism for untreated or poorly treated bipolar…at least for me. Anyway thanks for the article! I’ll check it out.

      • Margarita

        OMG J.D. I scanned this…and her story is nearly the same as mine! It’s scary how similar our life stories are! This is so surreal…

        • Keep searching for an MD that will pay attention to your history, and bring a print-out of the study so they will at least have one other case history on which to base the prescription. Good luck!

          You might find that B-vitamin rich foods are a better fit than supplements (liver, greens, etc.). ALL food vitamins are in the methylated form.

  60. I am a little confused about the amino acid methionine. I do best on a higher
    protein/ low carb diet that includes animal protein. Recently, I went on a ketogenic diet staying in ketosis for about 6 months. However, my cancer markers started to increase. After researching diets I decided that I could eat
    a diet low in methionine. I have had one or 2 panic attacks in the last 20 years. I am fearful that this type of diet might cause me to be prone to panic attacks. I could get my protein from pea plant protein and gelatin. Any thoughts on this subject (or this type of diet). You seem knowledgeable in this
    area and information is hard to come by. Thanks for any information you
    can give me.

    • I don’t feel qualified to give individualized dietary advice (I’m not a doctor) but I have heard that long-term ketosis can deplete selenium. Good health to you!

  61. Dr. Patrick has created a great free product which you can download here:

    She is one of the most knowledgeable people I know of in terms of nutrition, genetics, mental health, etc. The PDF is an EXCELLENT resource for analyzing your nutritional needs based on your 23andMe data.

  62. Am 60 yr old female, am new to the methylation issues. I read the whole blog and am looking for answers to an amine problem. I cannot tolerate b vitamins, anything fermented. Besides extreme arthritis I get gout attacks from vitamins, etc. Except for calcium/magnesium. I have high iron levels. Can’t tolerate Dr.s anymore looking at me like I’m an idiot. Help!

    • Birgit — are you donating blood? Reducing iron can help with a number of health conditions. You might also be an excellent candidate for cryotherapy:

      Good health to you!

      • I have been a donator in the past, and I should get on that again, I was especially curious if anyone had similar problems with Amines or mold. And the connection to gout. I have an amazing intolerance to vitamins or anything that is healthy, fish oil, olive oil, antioxidants. Pretty much if it’s healthy Stay away from it! I recently have been doing a lot of Paleo foods and can now walk in the evenings and dress myself without assistance. I feel that the foods that I can tolerate are becoming less and less till there won’t be much left to eat.

  63. Pauline Price

    wow, what a great attempt to get a handle on this complex stuff – thanks for sharing it!

  64. joely cruz

    I have the 677 from one parent and 1298 from the other parent. As much reading as I do it just seems to overwhelm me to a point I’m not sure what to take!! I do have other issues such as adrenal fatigue, hypothyroid but I truly believe many of these issues were brought about by years of not knowing about the mutations and lack of methylation. I guess my question would be where do I start? I have a very expensive methylated multi but it really does not make me feel well when I take it. I would say my worst symptoms are low energy, mild depression, moodiness, body pain that comes and goes, brain fog, diminished joy. Not sure if I’m an over or under methylator …ANY help would be so appreciated. Thank you in advance

  65. can over/undermethylation or pyroluria be mistaken for bipolar? Especially if one has been diagnosed due to anxiety, ADHD symptoms, generally high energy with periods of depression? I don’t want to put $ into testing if isn’t likely. Many people in my family have such symptoms and severe.

  66. Shelley

    I never saw that you mentioned histamines. There are certain methylation mutations that cause a person to be more sensitive to them (allergens in the air, compounded by histamine foods and histamine liberating foods). Vitamin C helps with histamines, so I wonder if this as well as other things you did that tweaked your methylation helped the asthma (common for histamine intolerance) to go away. Start here: http://chriskresser.com/what-you-should-know-about-histamine-intolerance/

  67. Shelley

    Of course you mentioned histamines, but not in the way I described. Sorry to not clarify in the beginning…

  68. Tauni

    Hi JD. Great research! I have been going to a new doctor to figure out what is going on with my body. I have been asthmatic since I was a baby, food allergies, environmental allergies, GERD and the list goes on. I’ve been on a restrictive food plan for the past two years and realized I didn’t feel great. She has done some initial testing (Genova) and told me about methylation, the gene and a few other issues I am experiencing. She has me on all B vitamins, B12 shots, Iodine and am taking my zinc-carnosine for my GERD. I have done more tests on food allergies and my thyroid. I will get my results soon. I am so happy to find you and the people who have posted here because I don’t feel alone AND all of you have done some further research. I have been reading the medical papers and good gracious – way over my head. 🙂 My new doctor is an internist and she leans towards natural supplements vice medication – big reason I went to her. I’ve also done the LEAP program (Genova did the testing) – it helped me to determine which foods were causing inflammation. Anyway – again, thank you for the research you did and am sure it will help me as I learn more about me.

  69. Peter

    This is a fantastic page, both for the post and the excellent comments already posted.

    I found it while researching B12, which I’ve just started taking as I’ve got shingles. I’m taking 1000mcg of Methylcobalamin sublingually, but as soon as the tablet dissolves my stomach heaves, and shortly after I get loos stools/diarrhoea. This is listed as a common side effect of B12 but what I can’t determine is whether it’s a positive (though unpleasant) side effect, or a signal that my body doesn’t want it. Thoughts?

    • That doesn’t sound positive to me. Clams, liver, and caviar are the highest food sources … maybe go in that direction instead?

  70. Susan F.

    I could not read through all of this so I apologize if I have missed something. I have the MTHFR c677t homozygous snp as well as many other bad snps. I’ve been on methylated B’s for quite some time, but during that time developed some sort of sero-negative arthritis (but moderately high sed rates). I still have high homocysteine and I think something wrong with the SAMe ratio (some test I did can’t exactly recall). I want to take low dose niacinamide every few hours because I read it would help arthritis and even know of a friend of a friend who was helped by this. But would this not squash the methylation that I am supposing fixing with the methylated B’s ?
    Anyone have experience with this? Thanks

    • Hi Susan — it seems reasonable to proceed with low dose niacinamide (perhaps once a day) and see how you feel.

    • Robin

      Susan, I had the same question about niacin, and so I tried taking TMG with it. Still if I take too much niacin it will case hay fever-like symptoms. TMG and DMG are methyl-donors attached to glycine (which is good for the liver, too.)
      Oh and to JD, I really like your blog. I would look into iodine therapy if I were suffering with asthma. I take it daily and hate to think about ever being on a deserted island without it. But Sara is right, you need guidance. When you first start it, there is a bromide detox that can be brutal. I suspect it is also chlorine and fluoride that come out too. It hurts, but it’s worth it.

  71. Melissa

    Hi, I was wondering if anyone had similar reaction as myself. I was give a b12 shot even though I knew I had issues with supplements. And since had fast heart rate and insomnia, it has been over two mnths and hr has gotten lil better but not insomnia. My b12 level wasn’t very low 300s one test 450 one test, should have never got the shot. The whole reason even had gotten into looking into vitamin levels was a bad reaction from antibiotic flagyl. Thought vitamin would clear up depression and brain fog, now more depressed cause can’t sleep and I feel to bright too much adrenaline. No drs have been any help. Can one b12 shot give you permanent insomnia? Or trigger something else cause insomnia? Thyroid tests come up negative and b12 level lower then before shot soo weird.

    • Melissa,

      Not everyone can efficiently convert cyanocobalamin (the type of B12 that is commonly injected) into a bioavailable form. I would recommend food-based sources of B12 (meat, cheese, clams, liver) and see if you feel better. If you take any supplements, try taking them in the morning instead of with dinner, and possibly taking a supplement break or reducing the dose — especially anything containing B vitamins.

      I would also recommend a chelated magnesium (glycinate or malate) supplement to help you sleep (take with any meal). Fish oil and vitamin D will help with brain fog and depression. Please read my posts in the Mental Health category for more detail. I also have a few posts on sleep.

      Good health to you!

      • J. A. Fenn

        I am compound heyerozygous for both methylation genes (C677T and A1298C) and had to do a lot of digging about this subject. Yes, it is complicated, and doctors with training are few and far between. But there are doctors who are trying to get up to speed on what we have relatively recently learned. Most have holistic, naturopathic, or functional medicine leanings. If you want to learn more, the best information I’ve found so far is on four sites: mthfr.net (Ben Lynch), Suzy Cohen’s methylation articles, Jill Carnahan, and Any Yasko. Your genetic tests can be interpreted at genetic genie or mthfr support, to name two. Read, educate yourself, and find a doctor who is knowledgable in treating this so you don’t have the reactions people are posting here, or at least know what to do if one occurs. Otherwise, find an open minded doctor and learn together. Ben Lynch has training modules for both patients and practioners. Amy Yasko and Ben Lynch have written books. It may ultimately improve or save your life. None of us has the time to wait for conventional medicine to grind through 20 year double-blind studies to prove something that accomplished naturopaths, doctors of functional medicine, and others have been successfully using for years. We need to become educated medical consumers who can make informed decisions about how best to improve and maintain our health.

  72. My 14 year old son (who has autism) needs L-methylfolate, and this was prescribed, along with methyl B12 and NAC (N-acetyl cysteine) added to the formula. After a month of use, his mood is slowly improving. Smiling more, less irritable, fewer aggressive outbursts (less than 5 per week, way down from over 40). His psychiatrist discovered the folate deficiency from a cheek swab, and as there is sound evidence for methylated folate use for autism and aggression, he prescribed it (after Abilify and Depakote failed, both resulted in increased irritability, aggression, hyperactivity, and mania). The cheek swab results also suggested that SAM-e might be a good add-on, but we had to stop after 6 days. Although his mood was fabulous, he quickly became overly hyperactive, escalated, restless (like he was on speed!) and was having trouble sleeping, reminding me very much of when he was on Abilify. He only took 200 mgs. Using at supposed “therapeutic levels” (400 -800 mgs) was out of the question. My guess is he falls into the “low histamine” category, with high levels of homocysteine. I’m hoping with continued use, that the L-methylfolate formula he is taking will continue to stabilize his homocysteine levels. Do you know if adding another methyl group, like B6, will help support the current supplementation, or is what he on likely enough to keep his methylation system working normally to promote a healthy mood? Will adding another methyl group cause his body to produce too much SAM-e, resulting in a similar reaction?? Having a hard time finding zinc and manganese together except with other trace minerals (like copper which you said should be avoided), these also sound like good add-ons. My goal is promote a healthy mood and energy, without the excessive hyperactivity, borderline mania, and insomnia that seems to accompany things like SAM-e and 5-HTP.

  73. No way my son will eat oysters but almonds sound good. Thanks. My son has a very sensitive system and typical and atypical antipsychotics tend to introduce more irritability than they treat. He does take Risperdal but only a low dose, as more increases irritability and aggression. He also takes Intuniv, but again low dose. More increases irritability. The folic acid deficiency was the closest thing we’ve had to an answer to all his issues with aggression, which began at age 9. I’m glad we’re getting to the root cause and treating what’s wrong. I’d be interested in having his homocysteine levels checked, even if just to get a baseline. I’ll see if his zinc, b6, and manganese levels can be checked. BTW, is there a methyl b6 or does this not need to be converted to be usable?

  74. Thank you! This is very helpful, and just what I was looking for! I’ll bounce off his psychiatrist as an add-on to his methyl formula, which has really been helping and he’s taking beautifully. Hopefully he can determine the dose that he needs, or if he even needs it. Yes, I had heard of B6 deficiency’s link to autism years ago on NPR but it’s all coming full circle now as I research how all these enzymes and vitamins fit together in the human body. Makes sense why so many autistic kids crave carbs and chicken nuggets. Their bodies are starving for those B vitamins and folate!

  75. I have another question. The L-methylfolate/methyl B12 complex he takes comes in capsules, 2 per day. There were no instructions, except to take with 8 oz food and water. We get them mail-order through Bellevue Pharmacy, by prescription. Initially I was giving both to once in the morning. But he seemed irritable within an hour of taking, so I’ve been giving in divided doses, one capsule with breakfast and one with dinner. Does it matter if I split the dose?

    • That should be fine, as long as the evening dose doesn’t disturb his sleep.

      BUT, respectfully, that should be a question for the doctor that prescribed the vitamins, not some random music producer on the internet who writes about vitamins in his spare time (me). The irritability after the full AM dose may be useful feedback for the doctor; he may reduce the prescribed dose based on that information.

      • Thanks, and I totally agree! His dr. isn’t the easiest to nail down, so thought I’d get your educated “lay” opinion.

  76. No, the evening dose doesn’t disturb his sleep, he’s been sleeping great while on this supplement. It’s not so much irritability…it’s more a look…the same Iook he gets after he gets his Intuniv and his Risperdal…it’s a look that says, “I’m feeling something and not sure if I like it.” He’s a nonverbal child so I only have his reactions to guide me. After I started splitting the dose, that look went away, at least for the supplement. But yeah, I’ll mention these things at our next appt. I appreciate the advice, even from a “random music producer who writes about vitamins”! 🙂

  77. racerbiker

    This is interesting.
    I have severe anxiety, panic attacks and phobias for the last 10 years.
    – homocysteine and histamine levels are high
    – copper, folic acid zinc levels are normal
    – low Vitamin B12

    So with the above data do I fall in the over or under methylator?

    • It doesn’t sound like you fit neatly into either category. It might be worth getting a 23andMe test if you are interested in investigating what is going on genetically (in terms of how quickly various neurotransmitters are produced and broken down in your brain, or special nutritional needs). For example your results of SNPs rs1801133 and rs1801131 might indicate reduced function in the MTHFR gene and a corresponding need for additional dietary folate. Other “SNPs of interest” might include rs4680 (COMT gene), rs1800497 (DRD2 … related to dopamine), rs25531 (5-HTTLPR), and rs6323 (MAOA). In the last few years we’ve moved beyond the need for crude diagnostic categories … it’s easy and cheap to investigate your genotype directly.

      • RE: COMT gene. Our test revealed that the enzyme that breaks down folic acid was rated as “low activity” and he needed L-methylfolate, which he is taking, per doctor’s prescription. Also said that COMT enzyme registered as “low activity.” Do you know what this might be telling us?? The test suggested SAM-e could be used therapeutically. Said SAM-e is a “co-substrate” for COMT, whatever that means! Do you know what this is referring to?

        • COMT is involved in the breakdown of dopamine, so slow COMT activity corresponds to higher dopamine levels in the brain (“worrier” type vs. “warrior” type). I am GG/Val-Val at rs4680 (fast activity). That potentially means I have a bit more trouble concentrating, but perform well under pressure (“warrior” type). The “worrier” type does less well under pressure but otherwise can concentrate easily for long periods. Of course other genes, conditions, habits, environment, etc. will also influence real world results. This article gets into some more details:


          • Thank you! Interesting article! So sounds like high or low COMT activity is not necessarily bad or good, just more gives us info about who we are. Is this correct?? Makes sense why his doctor is treating the MTHFR problem, and kind of blew off the low COMT issue. He was just like, “well you have to take these tests with a grain of salt.” BTW, we did try SAM-e for a short time, but given that only 200 mgs made him hyper, and that he’s deficient for folate and B12, I’m inclined to think my son is an overmethylator, not an undermethylator like I originally thought. Might be worth having him tested to know for sure. Thanks for your info, we have an appointment in a couple of weeks and learning what I can about the test results will help me understand them better and ask intelligent questions at our appointment! 🙂

  78. Scott

    I became interested in B vitamins after reading about their usefulness in reducing cravings for alcohol.
    I began taking coenzyme B complex multiple times a day. I was skeptical but within a week my cravings went from an 8 down to around a 4. In addition, my energy levels and mood were the highest they’d been in years. Normally, I’d get anxious and even lethargic when I wouldn’t drink.
    I added in some extra niacin and the cravings all but completely diminished. It was nothing short of remarkable. Things were great until this happened: The pollen count here got extremely high and my allergies kicked in. My energy levels and mood completely plummeted. My eyes burned, throat was incredibly sore, terrible nasal drip, and a constant cough and difficulty breathing. I was miserable – couldn’t sleep.
    Here’s the funny thing. I’ve lived here for 12 years and I’ve never had allergies. I never would have put two and two together if it weren’t for reading this blogpost a while back. I discontinued the extra niacin and the allergy symptoms went away, even with a higher pollen count.

    Granted, this is just an anecdotal account of my experience but it’s both interesting and exciting to know that we can alter our experience of and physical reaction to the world with the nutrients that we choose to put into our bodies. Great post!

  79. According to this study, excess nicotinamide can raise plasma serotonin and histamine (not good for someone like myself, vulnerable to asthma and allergies). This is too bad, considering the potential benefits of nicotinamide in raising NAD+, improving neurocognitive function, etc. But for slow methylator/high-histamine types, megadosing niacinamide will probably come with negative side effects.


  80. JE

    I am an undermethylator (high histamine) and my copper is on the high side too. The ratio between my copper and zinc (zinc normal) are not too bad. My doc is Walsh trained. I have been taking B6, P5P (B6 diff kind),B12, Calcium, Mag, Vit E, Vit D, Moly, Selenium. Was asked to take L-Serine but felt worse after taking it and stopped. My homocysteine was at 11.9 when I started and 4 weeks later it was 11.4. That isn’t fast at all!! Since my doc has been too busy I researched and I found TMG might help my homocysteine decrease. I have been taking that for 3 weeks (1.5 g) and will have a blood draw tomorrow. I also found on my own http://www.lifeextention.com offers blood tests that are very very reasonable rate as compared to DHA costs. My copper was 144 when I began and it has dropped to 136 in 4 wks. I am concerned the TMG might slow or stop the copper detox but I should find out after tomorrow’s blood draw. Rather than sitting around and feeling sorry and depressed I have been researching and applying things myself. I’m sure my doc won’t like it but I dislike her unavailability (and my deep depressions.. at least this way I feel more in control) I have read numerous conflicting things about copper, zinc, and undermethy so I am sure it is a challenge to get the right combo.

  81. I have found tremendous help from a new product called Enlyte which is L methylfolate plus B vitamins. It is a prescription but it deals with both forms of the MTHFR polymorphism. I can’t believe how the fog has lifted and my memory has returned with a vigor, amazing!!

  82. Aisha Tejani

    Great article!

    If I have pyroluria and am an undermethylator, what are good b’s to take to make sure the b6 I am taking doesn’t deplete me of other bs?

    I’ve tried multi bs with methyl folate and methyl b12 and niacin but they make me too wired, so I think I will have to take other bs individually so that I can avoid methyl b12, niacin and methylfolate.

    Also, do undermethylators need even a little bit of methyl b12, niacin, or methylfolate? Or none at all?

    Thanks so much!

  83. Anonymous

    Thank you for this article—- However, I’m still confused as to whether I’m over or under methylated…. I apologize if you’ve already addressed a lot of this in your article, however, my brain feels like ‘mush’ lately and it’s difficult to remember and integrate information like I used to.

    My tendency is toward depression, isolation, inner anxiety (outwardly I appear very calm usually), ocd-ness, tiredness, lack of libido, lack of motivaton, hair loss (this has gotten worse over the last few months), food sensitivities, ….. Would taking Methyl B12 be more helpful– or harmful in this kind of situation?

  84. If you want to sure your asthma, reach out to me. I have 30 years in this space and have cured asthma and many other things. If you decide to use my work to cure your asthma, we should talk about you writing for me. I only work with people who have the experience of my work for obvious reasons. I like your ethics, integrity, passion and discernment. http://www.AliciaKali.com

  85. Hi J.D., we do like this post about methylation, and notice some methylation products mentioned here. Please also have a look at our new methylation product: https://www.vitacure.me/products/methyl-plus

  86. Great content!

  87. Thank you so very much for maintaining this page. I have spent years trying to find an explanation for aggressive feelings after taking B supplements, and becoming “thick as two short planks” if I did not, with a real fear that if the slide in mental performance continued, I would lose my livelihood. This is the best researched and most eloquent and understandable explanation in more then 20 years of looking. Bravo to you, better then the professionals, and an oasis of common spence and understanding in a really difficult and misunderstood subject.

  88. Jolene W (Kirkland, WA)

    A warm thank you for this mindful and wise content. It’s comforting, well-informed and gave me a hope after many years of depression and auto-immune challenges.

  89. Kellie

    Both my daughter and I are positive for the c677t polymorphism and have been taking an activated complex B Vitamin and are vegans. We noticed great improvement in health and over all well being. However, she still suffers terribly from acne. I’ve heard B12 can cause acne, as well as biotin. I’ve heard pantothenic acid could help. Our focus has always been methylfolate. I thought she needed b12 for folate absorption, but now I wonder if it’s doing more harm than good. Maybe I need to switch her to strictly folate and add B5? You’re right, dr’s are of little help. I’m at a loss. As usual. I want to help her so much. She has greatly restricted her diet with no improvement at all.
    I thank you for your article- it was very helpful! The acne thing has me as perplexed as ever though……….

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