Vitamin B9 - Folate dosage

Vitamin B9 (Folate)

David Tomen
Author:
David Tomen
15 minute read
Vitamin B9 is known to improve mood, energy, initiative, alertness, concentration, psychomotor speed, and social activity

Vitamin B9 (Folate, folic acid, 5-methylenetetrahydrofolate) is water-soluble, and one of 8 B-Vitamins.

Folate functions as a coenzyme in single-carbon transfers in the synthesis of DNA and RNA. And converts homocysteine to methionine which is used in the synthesis of S-Adenosyl-methionine (SAMe).[i]

As a nootropic, folate is also involved in gene expression, amino acid synthesis, myelin synthesis, and is required for the synthesis of the neurotransmitters dopamine, epinephrine, norepinephrine and serotonin.

Many neurohackers, including doctors and other health professionals confuse folate with folic acid. They are NOT the same.

In this article, we’ll explore the differences between folate and folic acid. And how Vitamin B9 (folate) is critical for the fully optimized brain.

Vitamin B9 (Folate) helps:

  • Brain Optimization: Folate is involved in DNA and RNA synthesis, gene expression, amino acid synthesis and metabolism, and myelin synthesis and repair.
  • Neurotransmitters: Folate is required for the synthesis of dopamine, epinephrine and serotonin.
  • Mood: It is thought within research circles that folate’s involvement in neurotransmitter synthesis is most responsible for mood and cognition. Even increasing the effect of SSRI’s in those being treated for depression.

Overview

Vitamin B9 (Folate, folic acid, 5-methylenetetrahydrofolate) is water-soluble, and one of 8 B-Vitamins.

l-methyl-folate
L-Methyl-Folate (L-5-MTHF, L-methylfolate)

Folate is a critical component of DNA and RNA synthesis, gene expression, amino acid synthesis, and myelin synthesis and repair. Folate is required as part of the cycle that produces most of your major neurotransmitters including dopamine, epinephrine, norepinephrine and serotonin.

Folate is used in red blood cell production, helps break down and use proteins, and just about every other process in your body.

Folate deficiency is found in at least a third of those suffering from depression. Folate touches nearly everything happening in your brain. And the reason why we’re investigating it here. Folate should be part of your nootropic stack.

Green leafy vegetables, or ‘foliage’ are rich sources of folate. And how ‘folate’ got its name. You can also get folate from citrus fruit juice, legumes, fortified foods and liver.L-Methyl-Folate = foliage

When you eat vegetables containing folate, or eat flour-enriched with folic acid, an enzyme called MTHFR (5,10-methylenetetrahydrofolate reductase) converts folic acid and food folate into 5-methylenetetrahydrofolate (methyl-folate or 5-MTHF).

Folate is a general term for a group of various tetrahydrofolate (THF) derivatives naturally found in food.  Folic acid refers to an oxidized synthetic compound used in dietary supplements and food fortification.

THF can enter the main and natural folate metabolic cycle which starts out in the mucosa of your small intestine. Synthetic Folic acid on the other hand undergoes initial reduction and methylation in your liver, where conversion to the THF form requires the enzyme dihydrofolate reductase.

One of the problems with choosing the unnatural folic acid version is if there is low activity of the dihydrofolate reductase enzyme, combined with high intake of folic acid, you end up with unnatural levels of unmetabolized folic acid entering your circulation.

Several studies have reported the presence of this unmetabolized folic acid in blood following consumption of folic acid supplements, or folic acid-fortified food.[ii]

We have growing evidence in Western society that we generally test for excess levels of unnatural folic acid. Due mainly to eating processed foods and folic acid-enriched flour. And still suffer from a folate deficiency.

High doses of synthetic folic acid may increase your risk of cancer, immune system damage and other health problems.[iii]

Problems with MTHFR

Another major problem affecting folate deficiency is problems with the MTHFR gene. Remember that this enzyme called MTHFR (5,10-methylenetetrahydrofolate reductase) is needed to convert folic acid and food folate into 5-methylenetetrahydrofolate.Mthfr gene mutation results in folate deficiency

There are two common variants in this gene that affects the functioning of MTHFR. They are called C677T and A1298C. Both variants are genetically inherited. And depending on their presence in your system, can reduce the effectiveness of MTHFR from 30 – 70%. Another cause for folate deficiency.

Estimates of the prevalence of these mutations in our general population are up to 60%. Some doctors report that nearly every patient in their practice have one or both MTHFR mutations.[iv]

And we have clinical evidence of the association between both MTHFR mutations in depression, bipolar disorder, and schizophrenia.[v]

Folate is one busy molecule in your body:

  • Donates a methyl group to homocysteine to make SAMe. The methyl donor SAMe is involved in the formation of phospholipids, glutathione, myelin, coenzyme Q10, carnitine and creatine in your brain
  • Synthesizes the enzyme cofactor biopterin (BH4) which is critical for the synthesis of major neurotransmitters including dopamine, epinephrine, norepinephrine and serotonin
  • Synthesizes DNA and tRNA
  • Recycles and reduces the inflammatory amino acid homocysteine
  • Builds red and white blood cells and platelets.

l-methyl-folate-increases-energy

How does Vitamin B9 (Folate) work in the Brain?

Vitamin B9 (Folate) boosts brain health and function in several ways. But two in particular stand out.

  1. Folate influences neuroplasticity and neurotransmitters. Folate is required for the synthesis of the neurotransmitters dopamine, epinephrine, and serotonin.

The active metabolite of folate, 5-methyltetrahydrofolate (5-MTHF, L-methylfolate), participates in re-methylation of the amino acid homocysteine, creating methionine. S-adenosylmethionine (SAMe), the downstream metabolite of methionine, is involved in numerous biochemical methyl donation reactions, including reactions forming the above-mentioned neurotransmitters.

Without the participation of 5-MTHF in this process, SAMe and neurotransmitter levels decrease in the cerebrospinal fluid, contributing to the disease process of depression.

Studies have shown that those being treated for depression with SSRI antidepressants, and not responding to these drugs, can get a much better response by taking folate with their antidepressants.[vi]

  1. Folate helps reduce depression. Folate is involved in one-carbon metabolism in the brain. This folate cycle is responsible for the synthesis of methyl groups, which are utilized by SAMe in several methylation reactions involving nucleoproteins, proteins, phospholipids, neurotransmitters and monoamines.

Deficiency of both folate and Vitamin B12 will impair methylation processes. Causing the accumulation of homocysteine. Low concentrations of folate in your blood, red blood cells and cerebrospinal fluid are associated with depression and dementia.

Research shows that cognitive function is related to methylation processes in your brain.[vii] This depression hypothesis is supported by the similar effect of SAMe on monoamine neurotransmitter metabolism, which is also implicated in depression.[viii]

The lowest concentrations of folate and SAMe in cerebrospinal fluid are found in dementia, including Alzheimer’s Disease.[ix]

How things go bad

Methyl-folate (5-MTHF) works with Vitamins B2, B6 and B12 as well as cofactors like magnesium in this methylation cycle in every cell in your body and brain.l-methyl-folate-reduces-anxiety

The metabolic process called methylation occurs when one molecule provides a methyl group, which is a carbon atom linked to three hydrogen atoms, to another molecule. And makes things like creatine, carnitine, CoQ10, phosphatidylcholine (PC), melatonin and a bunch of other crucial neurotransmitters and substances in your body.

Methylation is involved in cognition, repairing DNA, turning genes on and off, fighting infections and inflammation, getting rid of toxins and much, much more.

Problems with methylation (which can be caused by not enough folate) can contribute to addictions, Alzheimer’s, anxiety, ADD and ADHD, bipolar and manic depression, chronic fatigue syndrome, dementia, diabetes, fibromyalgia, schizophrenia, and hypothyroidism.

Methylation is not only involved in the synthesis of neurotransmitters, but breaking them down as well. This critical step, when broken, causes a buildup of neurotransmitters that can lead to seizures, insomnia, panic attacks, fits of rage, and more. Much more.

A deficiency of methyl-folate (5-MTHF) in your body caused by problems with this methylation pathway leads to a deficiency of glutathione, your major antioxidant. This can take shape as fibromyalgia, chronic fatigue, increased immune activation, chemical sensitivities and even diseases like ALS, MS, and Parkinson’s.

Not enough folate and you can experience:

Mitochondrial dysfunction[x]

↓ Depression, mood and social function decline

↓ Cognitive function declines

Concentration, cognition and memory decline

↑ Risk of Alzheimer’s and dementia increase

↑ Risk of anemia increases

↑ Irritability, forgetfulness, and mental sluggishness increase

Vitamin B9 supplementation can help increase the density of serotonin and dopamine neurotransmitters in your brain. And improve neurotransmitter signaling. Helping you to cope with stress, lessen depression and improve memory.

Vitamin B9 (Folate) benefits

Depression affects about a quarter of the US population who will have at least one depressive episode in their lifetime. (My apologies to our readers from other countries. I only have statistics for the USA).

L-Methyl-Folate-improves-cognitionBut world-wide, folate deficiency is found in at least a third of those suffering from depression. And research shows that folate levels even in the “normal range” might be inadequate for methyl donation and neurotransmitter synthesis.

By adding folate, or methyl-folate to your nootropic stack, you’re adding a necessary ingredient for the synthesis of the neurotransmitters dopamine, epinephrine, norepinephrine and serotonin.

The active metabolite of folate (5-MTHF, L-methyl-folate) participates in the re-methylation of the amino acid homocysteine creating methionine. SAMe, the downstream metabolite of methionine, is involved in several methyl donor reactions, including forming most of your major neurotransmitters.

Methyl-folate also seems to save the day by stepping in, and substituting for tetrahydrobiopterin (BH4), an essential cofactor in neurotransmitter synthesis (when BH4 is low).

The bottom-line: folate helps boost alertness, attention, cognition, memory, and mood. And helps alleviate brain fog, anxiety and depression.

How does Vitamin B9 (Folate) feel?

Up to 60% of us do not produce enough of the enzyme needed to break down the synthetic folic acid found in supplements and fortified foods like breakfast cereal and bread. And the simple presence of this impostor in our diet is likely contributing to many of our modern diseases.

Neurohackers report that dosing with methyl-folate:

  • Boosts alertness and energy levels
  • Relief from chronic pain
  • Tolerance for heat increases
  • Sociability increases
  • Relief from depression, fatigue and paranoia
  • Fewer headaches
  • Mental clarity increases
  • Much happier, calmer, more energetic
  • Gingivitis and gum inflammation decreases

l-methyl-folate-reduces-depression

Vitamin B9 (Folate) Clinical Research

Folate as an Antidepressant

Many who use antidepressants experience little to no relief in depressive symptoms. And researchers set out to find out why antidepressant meds were not working.

Dr. Jerome Sarris of the University of Melbourne decided to do a meta-analysis of clinical trials using ‘nutrients’ along with antidepressants in PubMed, CINAHL, Cochrane Library, and Web of Science up to 2015.

The research team found that Omega-3’s combined with antidepressants boosted the success of using these meds for depression. The team also found strong evidence for methyl folate, Vitamin D, and SAMe.

The research showed that using folic acid or inositol provided no benefit. The team concluded there was strong evidence for using methyl folate, Omega-3, Vitamin D and SAMe with antidepressants to reduce depression.[xi]

Another study in Milan compared using methyl-folate with the antidepressant Trazadone. 96 patients with dementia received either 50 mg of methyl-folate per day, or 100 mg of Trazadone.

After 4 weeks of treatment, depression scores for the methyl-folate patients decreased more than for the Trazadone patients.[xii]

Folate Reduces Risk for Dementia

Folate deficiency is associated with a tripling in the risk of developing dementia among elderly people. Researchers tracked 518 people over the age of 65 for 2 years for dementia development. The study found that the onset of dementia was much more likely in those whose folate levels fell over 2 years.[xiii]

Another study published in the British Medical Journal looked at the neurological status of 24 folate-deficient patients compared with a control group of 21 normal folate-level patients.

The study showed a significant increase in organic brain syndrome in the folate-deficient group.[xiv] Organic brain syndrome is a general term used to describe decreased mental function caused by something other than psychiatric illness.

Vitamin B9 (Folic Acid) Improves Memory

A study published in the Journal of the American Medical Association evaluated nutritional status and cognitive function in 260 men and women older than 60 years. The study showed there was a significant relation between impaired abstract thinking ability and memory, and lower folate levels and intake.[xv]

In another open study of 38 folate deficient subjects with depression, lethargy, and memory impairment, 50 mg of folinic acid per week for 120 days significantly improved visuomotor performance, visuospatial memory, logical reasoning, associative memory, and activities for daily living.[xvi]

Vitamin B9 (Folate) Recommended Dosage

Recommended dosage for Vitamin B9 (Folate) is 500 mcg.

If you decide to add folate to your nootropic stack, start with B12 in the form of methylcobalamin. And then introduce your dose of methyl-folate and cofactors such as Vitamin B2, Vitamin B3, Vitamin B6, trimethyl glycine, and Vitamin CVitamin B9 - Folate dosage

If you have an adverse reaction to methyl-folate (agitation, increased anxiety, headache), you can take Vitamin B3 (nicotinic acid or niacinamide) in 50 mg dosages every 30 minutes until you experience relief.

Note that Vitamin B3 (niacin) requires SAMe for its metabolism. And can contribute to a drop in methylation if you’re low in SAMe.  It is also a cofactor for the enzyme COMT that breaks down norepinephrine, epinephrine, and estrogen, which are all potentially elevated if you are experiencing anxiety.

Vitamin B9 (Folate) Side Effects

Vitamin B9 (Folate) is non-toxic. So is considered well-tolerated and safe.

But note that higher doses of Vitamin B9 like those used in clinical trials nearly always use synthetic folic acid. If you are deficient in Vitamin B12, and many people are, can manifest as anemia. And looks just like folate deficiency.

Large doses of folate could correct anemia. But without correcting an underlying B12 deficiency can leave you at risk for irreversible brain damage.

This is why the US Institute of Medicine advises that all adults limit their intake of folic acid supplements to 1 mg daily.

Note that it is unlikely that you’ll encounter this problem by using folate or methyl-folate instead of folic acid. But we don’t have the science yet to back this claim up.

High concentrations of unmetabolized folic acid in your blood, especially if you’re low in Vitamin B12, could result in a compromised immune system.  And problems with cognition.

Other side effects of using folic acid, particularly in high doses include stomach problems, insomnia, skin reactions, confusion, loss of appetite, nausea and seizures.

Many medications interfere with folic acid absorption including antibiotics, Dilantin, Daraprim, chemo meds, antacids, proton pump inhibitors, anti-seizure medications, NSAIDS (ibuprofen and naproxen), Azulfidine, and Methotrexate.

Vitamin B9 (Folate) types to buy

Vitamin B9 (Folate) is available in capsules, softgels, and in powder form.

Studies have shown that the active form of folate, methyl-folate, which is more easily absorbed, and easily crosses the blood-brain barrier, may be effective in the prevention and treatment of depression and dementia.[xvii]

Look for a folate supplement that says “L-methylfolate”, “5-methyltetrahydrofolate” or “5-MTHF” on the label. Even better, with the word Quatrefolic® or Metafolin® which are branded forms of folate ensuring their purity and effectiveness.

One great option to ensure you are getting all the vitamins and cofactors you need for the methylation cycle is to use a multivitamin.

And all multivitamins include some form of Vitamin B9 (folate) in their formula. But many of these multis don’t contain enough for optimum health. And the majority use the folic acid version of this nutrient.

The Performance Lab® NutriGenesis Multi offers a nature-identical form of Vitamin B9 (folate) and is now my favorite daily multivitamin/mineral supplement.

I prefer the Performance Lab® multi because it’s more potent, it’s biologically active and I’ve found to be a far more effective multi compared to every other multivitamin supplement I’ve ever used.

Performance Lab® uses their own priority NutriGenesis® vitamins and minerals which are grown on probiotic, plant and yeast cultures in a state-of-the-art lab.

Avoid any product, including multivitamins, which list “folic acid” on the label.

 Nootropics Expert Recommendation

Vitamin B9 (Folate) up to 500 mcg

Nootropics Expert Tested and ApprovedI recommend using Vitamin B9 (Folate) as a nootropic supplement.

Your body does not make Vitamin B9 on its own. So you must get folate from food or a supplement.

Vitamin B9 (Folate) is especially helpful for those suffering from anxiety, depression, panic attacks, or OCD. Folate can help reduce insomnia, and help increase energy levels.

Experience shows Vitamin B9 helps stop and reverse the symptoms associated with high homocysteine levels.

Vitamin B9 is also particularly helpful to quell anxiety caused by social situations.

Vitamin B9 can help you get a good night’s sleep. You may find it as effective as sleep meds and other nootropics used for sleep. You’ll awaken feeling refreshed and calm. Ready to start your day.

The recommended dosage of Vitamin B9 (Folate) is up to 1,000 mcg per day. Start low at 500 mcg and see how your body reacts.

Please refer to Dosage Notes in this article for adding the other B-Vitamins to your stack for an optimal methylation cycle. Your neurotransmitters are counting on it.

At the very minimum every neurohacker should be using a multivitamin every day that includes Vitamin B9 (folate but NOT folic acid!). The best multi I’ve found and use every day is the Performance Lab® NutriGenesis Multi for men or women.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] Selhub J. “Folate, vitamin B12 and vitamin B6 and one carbon metabolism.” Journal of Nutrition, Health and Aging. 2002;6(1):39-42. (source)

[ii] Powers H.J. “Folic acid under scrutiny.” British Journal of Nutrition 2007 Oct;98(4):665-6 (source)

[iii] Troen A.M. et. Al. “Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women” The Journal of Nutrition January 2006 vol. 136 no. 1 189-194 (source)

[iv] Miller A.L. “The Methylation, Neurotransmitter, and Antioxidant Connections Between Folate and Depression” Alternative Medicine Review Volume 13, Number 3 2008 (source)

[v] Gilbody S., Lewis S., Lightfoot T.  “Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review.” American Journal of Epidemiology. 2007 Jan 1;165(1):1-13 (source)

[vi] Miller A.L. “The methylation, neurotransmitter, and antioxidant connections between folate and depression.” Alternative Medicine Review. 2008 Sep;13(3):216-26. (source)

[vii] Reynolds E.H., Carney M.W., Toone B.K. “Methylation and mood.” Lancet. 1984 Jul 28;2(8396):196-8. (source)

[viii] Bottiglieri T., Crellin R., Reynolds E.H. ‘Folate and neuropsychiatry’. In: Bailey LB, editor. Folate in health and disease. New York: Marcel Dekker; 1995. pp. 435–462

[ix] Bottiglieri T., Godfrey P., Flynn T., Carney M.W., Toone B.K., Reynolds E.H. “Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine.” Journal of Neurology and Neurosurgery Psychiatry. 1990 Dec;53(12):1096-8. (source)

[x] Nikkanen J., et. Al. “Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism” Cell Metabolism Volume 23, Issue 4, p635–648 (source)

[xi] Sarris J., Murphy J., Mischoulon D. Papakostas G.I., Fava M., Berk M. Ng C.H. “Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses” The American Journal of Psychiatry Volume 173, Issue 6, June 01, 2016, pp. 575-587 (source)

[xii] Passeri M., Cucinotta D., Abate G., Senin U., Ventura A., Stramba Badiale M., Diana R., La Greca P., Le Grazie C. “Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.” Aging (Milano). 1993 Feb;5(1):63-71. (source)

[xiii] “Folate Deficiency Associated With Tripling Of Dementia Risk, Study Shows” Science Daily February 5, 2008 retrieved November 15, 2016 (source)

[xiv] Reynolds E.H., Rothfeld P., Pincus J.H. “Neurological disease associated with folate deficiency.” British Medical Journal. 1973 May 19;2(5863):398-400 (source)

[xv] Goodwin J.S., Goodwin J.M., Garry P.J. “Association between nutritional status and cognitive functioning in a healthy elderly population.” JAMA. 1983 Jun 3;249(21):2917-21. (source)

[xvi] Rapin J.R., Le Poncin M., Grebyl J. “Blood folate deficiencies and cognitive functions in aging.” Trends in Biomedical and Gerontology. 1988;1:221–223.

[xvii] Mischoulon D., Raab M.F. “The role of folate in depression and dementia.” Journal of Clinical Psychiatry. 2007;68 Suppl 10:28-33. (source)

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Join The Discussion - 100 comments

salem
February 12, 2024

hi david

is L-5-Methylfolate, glucosamine salt good form ?

    David Tomen
    February 13, 2024

    Salem that form of folate is patented and called Quatrefolic® and is one of the most bioavailable forms of methylfolate available. You system uses it as soon as it gets into your digestive tract and does not require any type of conversion.

Andrew
January 27, 2024

I brought this brand Natural Factors, BioCoenzymated, Active B Complex

i have tried many other active forms of B vitamin and they always made me feel awful but not this though I think taking every second day as i geta good kick of energy from it

are some active B vitamin made synthetically including MTHFR ones?

This was seem to be made from more Natural Processed Plant Extracts so more organic

    David Tomen
    January 27, 2024

    Andrew, that is a good, bioactive B-Complex. The quickest way to judge if something is synthetic or bioactive is if Vitamin B9 says “folic acid” it is synthetic. If it says “methylfolate” it is bioactive. B12 “cyanocobalamin” is synthetic (including a cyanide molecule) but methylcobalamin is bioactive. And B6 “Pyridoxine” is synthetic. But P-5-P is bioactive.

    I has been my experience that with a Multivitamin, if anyone of those B-Vitamins is synthetic then the rest of the formula is synthetic also. Including using ground up rock for the minerals. Ones that come to mind include One-a-Day and Centrum.

      Andrew
      January 27, 2024

      I must also ask about B3 Niacin because its 100, from thing i read on some website it says that slow release can be harmful to the liver at higher dosages what is your opinion on this ? since i’m only taking the B-complex every second day that would be more like 50Mg because its 100 spanning 2 days in a sense but just curious on your thought about its harm on the liver

        David Tomen
        January 28, 2024

        Andrew, it is the amount of these supplements that can become toxic if you dose too high. It has nothing to do with extended release vs. instant release. “Some website” does not count here. Go with the science and my dosage recommendations and you’ll be fine. And BTW, the days you do not use any of these B-Vitamins are the days you are not getting their benefit. They are water soluble and what your system does not use ends up in the toilet.

        Andrew
        January 28, 2024

        Just wanted to make sure taking this every second day long term isn’t going to be an issue that was all . i’m sure you have been on b-vitamins for a long time that’s is all!

        David Tomen
        January 30, 2024

        At the dose you suggested, you can use it for the rest of your life without a problem. Unless you have liver and/or kidney problems.

Jozef
October 10, 2022

Hi David, please can you advise me how my uncle could improve his memory? He is very forgetful, he doesn’t often remember things that happened five minutes ago. Well thank you.

Jozef
September 27, 2022

Hi David, is this good choice? Life Extension BioActive B-Complex

    David Tomen
    September 27, 2022

    Jozef, yes and I recommend this B-Complex all the time.

Ragnar
September 10, 2022

Good evening! I’m curious why mind lab pro or Qualia mind does not content Folate that much.Is there any Interaction with Nootropics or something! Many stacks seems to avoid it or put just 25% of daily need but why?

Thanks David wish you best!

    David Tomen
    September 13, 2022

    Ragnar, not sure about Qualia but Mind Lab Pro contains enough methylfolate to support the use of N-Acetyl L-Tyrosine as a precursor to the synthesis of dopamine. Because B9 is a cofactor in the synthesis of dopamine. It is not meant to restore an overall folate deficiency.

    If that is what you need I highly recommend the best Multi on the planet. The Performance Lab NutriGenesis Multi for men (https://bit.ly/347dm5M) contains 668 mg of methylfolate which is 167% of the RDA.

Mel
August 31, 2022

Hi David,

My son has the MTHFR C677T gene (homozygous). He also suffers from OCD, tics and ADHD (thus low serotonin). Dr. William Walsh states that those undermethylated and have low serotonin cannot tolerate a folate supplement because it can worsen their condition. Is this true?

Here is a quote from his website:

“Although most undermethylated patients thrive on folates, supplements of folates must be avoided for patients whose problems are dominated by low activity at serotonin receptors. Folic acid, folinic acid, and methylfolate all reduce serotonin/dopamine neurotransmission by an epigenetic mechanism, and this effect overwhelms the folate benefits of improved methylation and serotonin synthesis.”

    David Tomen
    September 1, 2022

    Mel, those with the MTHFR C677T mutation have a reduced ability to convert folic acid into its active form, L-methylfolate. So the key is to use natural L-methylfolate but keep the dose under 400 mcg.

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