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.
Table of Contents
Overview
Vitamin B9 (Folate, folic acid, 5-methylenetetrahydrofolate) is water-soluble, and one of 8 B-Vitamins.
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.
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.
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.
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.
- 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]
- 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.
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) to the rescue
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).
But 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
The 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]
Dosage Notes
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 C
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.
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 is undisguisable from folate deficiency.
Large doses of folate could correct anemia. Without correcting the underlying B12 deficiency. And 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.
Available Forms
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® Whole-Food 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 BioGenesis® 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
We 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 improve energy levels, 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® Whole-Food Multi for men or women.
[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)
Hi David,
One of the best articles written on this topic, great work! Thank you.
Just wondering – in this sub heading – is it supposed to say Folate instead of Folic Acid?
This is taken from your article –
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]
Rose, I included “folic acid” in brackets because that is what was used in the study. I do not recommend using synthetic folic acid in real life. Anyone supplementing with Vitamin B9 should be using methylfolate every day.
Right! Thank you for explaining, that makes sense!
Hello David: Thanks a lot for your valuable information.
I was told that Folic Acid 5mg tablets sold in Europe and Asia for people, who have the family history of colon cancer, to prevent colon cancer. Is this the correct information for taking Folic Acid 5mg once a day? What will be the side effects of 5mg Folic Acid?
Thanks in advance for your reply.
Benyapa, scroll back up this page to the section “Side Effects”. Note that the recommended dosage for “folic acid” is only 500 mcg per day for the reasons detailed in that section.
“Folic acid” is synthetic Vitamin B9. Are far better option, especially if you are considering higher doses like 5 mg is “L-methylfolate”, “5-methyltetrahydrofolate” or “5-MTHF” or the patented versions Quatrefolic® or Metafolin®.
This natural form of folate is what your body expects and recognizes. If you use natural folate like methyl-folate your body does not need to try and convert synthetic “folic acid” into something it can use.
Hello David, I want to ask, if it is better to use methylfolate, methylcobalamin and P-5-P with food or on an empty stomach. Thank you very much.
Josef, it doesn’t really matter because these B-Vitamins are water soluble. And if your system digests them successfully they will get to your cells and do what they’re supposed to do. Regardless if you’re taking with them with food. Or not.
thank you David for all your advice and your work.
Jozef, thank you for your comment. Much appreciated.
Dear David! You should verify your knowledge about B9 and MTHFR mutation. Check this out MTHFR debunked.
Srelus, thank you for sharing that article. But I deleted the URL. Because this is exactly the kind of garbage you’ll find all over the “internet”. Some blogger makes claims with zero science to backup what they say. And often in the dietary supplement space to sell their product.
I stand by my research. When I come across some sound, peer-reviewed clinical studies that show me without a shadow of a doubt that my original research is wrong I’ll update my review.
Hi David,
Can folate be a good alternative to beta blockers, considering its effect on catecholamines?
Thanks,
Aleksandar
Aleksandar, you want something that is more specific to norepinephrine instead of all the catecholamines. This is what I found to be the best natural alternatives to beta blockers: https://nootropicsexpert.com/best-nootropics-for-social-anxiety/#natural-alternatives-to-beta-blockers
I would like to point out that those with depression and the MTHFR mutation may need MUCH HIGHER doses of methylfolate to treat depression. I have an MD who prescribed 15 mg (yes, 15 MG) capsules of methylfolate for me. He suggests that all women of childbearing age take 5 mg daily and carefully avoid folic acid.
I also consulted with a psychiatrist who affirmed that 10-15 mg of methylfolate per day can alleviate treatment resistant depression, but lower doses won’t touch it.
I’m just posting this in case someone is looking for nootropics for depression. Methylfolate is wonderful for everybody, but if you are dealing with moderate to severe depression/ anxiety, 500 mcg to 1 mg might not help much at all.
What are your view on taurine and protein deficiency. Also what to do for adrenaline insufficiency. how to know one have these deficiency.
can you please clarify each of above three.
Mark, sounds like two or three different issues here. This is what happens when you don’t have enough taurine: https://nootropicsexpert.com/taurine/#how-things-go-bad
And do you mean “adrenaline” or “adrenal” insufficiency? Do a general search for “adrenal insufficiency” and see what places like the Mayo Clinic have to say. It’s often attributed to Addison’s Disease. But you can have worn out adrenals from things like inflammation or excess exercise. Which are reversible depending on the original cause.
Hello, in one of the replies above why you told its better to but seperate vitamins than buying a single b complex.
And what can be the cause of Palpitations and fast heart beat along with tiredness and sudden rotation in head.
in the past i have been diagonosed with b12 and d deficiency.
can i have folate or thiamine or other deficiency. what should i do?
James, I can’t imagine why I would recommend separate B-Vitamins vs a B-Complex stack. The key is using a B-Complex with the right dosages and the right form of each vitamin.
Not sure about the palpitations. That’s sometimes caused by excess norepinephrine. Tiredness can be caused by a host of things.
Hi David,
I take SAM-e and vitamin-B complex with Quatrefolic first thing in the morning on an empty stomach for about a year now.
They do make me very sleepy again about 30min later for about an hour.
Is this the metabolic process you talked about and it makes Melatonin that makes me sleepy?
“The methyl donor SAMe is involved in the formation of …coenzyme Q10, carnitine in your brain.
Now I do take those already later in the day: it sounds like I am making them already myself and trow more of them on top of it. Or did I understood that wrong ?
Do B vitamins increase the risk of getting cancer?
“which found that two years of supplementation with 400 mcg of B9 and 500 mcg of B12 changed DNA methylation”
This article worries me a bit.
Do you take other supplements to counter that or maybe what cycling do you recommend here?
Thanks
Wim
Wim, the cancer study that were all over the headlines and that you mentioned fail to read the detail as usual. The study concluded that men who currently smoke and who use these supplements (Vitamin B6 & B12) have three to four times the risk of lung cancer as do men who currently smoke and don’t use these supplements. There is no mention of Vitamin B9 (Folate).
So if you currently smoke the take away from that study is continued high dosage of Vitamin B6 & B12 may increase your chances of lung cancer. If you do not currently smoke then you have nothing to worry about.
Our body requires every single B-Vitamin and SAM-e. Our body does not “cycle” these vitamins. If we lack even one of them we die. If we are low in any one of them we’ll likely get sick.
Many of the vitamins in a B-Complex and SAM-e are required for the synthesis of all major neurotransmitters. It could be your case that for some reason you end up making something in excess for an hour like too much serotonin. It doesn’t sound like you have anything to worry about.
Hi David,
I’ve tried Methylfolate 400mcg on several occasions and it has made me anxious. I tried again yesterday and the anxiety was severe and has persisted into today.
I would like to ask your opinions on why I am reacting like this to Methylfolate? Does it suggest undermethylation or overmethylation?
Thanks
Kenneth, it could be a problem with methylation. You can counter the anxiety affects by taking Vitamin B3 (nicotinic acid or niacinamide) in 50 mg dosages every 30 minutes until you experience relief.
But I suggest you re-read this review starting from “How things go bad”. And see what you should be taking with methylfolate for it to do its job. One easy fix is adding a quality multi like this one: https://nootropicsexpert.com/performance-lab-whole-food-multi-review/
Hi David,
I recently had my homocysteine checked and it is in the lower range of normal which suggests that I would be more likely to be an overmethylator. I am taking niacin 100-200mg daily, zinc, magnesium, Vit C, Probiotic, Rhodiola, Bacopa Monnieri, Curcumin, plus I consume a lot of green juice and fruit. Anything else you would suggest for a suspected overmethylator? Anxiety is the major issue for me. I have tried Ashwagandha for a few months but it didn’t seem to do much. I am living in UAE so some supplements for anxiety are prohibited.
Thanks.
Kenneth, I’d try a quality B-Complex supplement first. And check this page: https://nootropicsexpert.com/top-7-nootropic-adaptogens-to-conquer-anxiety-and-stress/
And this page for more ideas on how to conquer anxiety: https://nootropicsexpert.com/best-nootropics-for-social-anxiety/
Thanks David
Hello David, i discovered after 8 months that i get rushes from the b complex I’m taking, it contains Folate(L5 methyltetrahydrofolate calcium salt), thiamine hlc, riboflavin, niacin, b6, b12 (methylcobalamin), biotin, pantothenic acid, calcium, inositol, paba.
Ones i started to take it i didn’t feel a big difference in the mood cognition or nothing, but i did feel like it could be goving me what i call bad mood…
I didn’t understand why so i searched and i found that if you have sings of OCD you shouldn’t take it because of the methylation chain… i don’t understand that very well as i am an ordinary person… but maybe be that my chemistry in the body doesn’t like it…
Then i started to have rushes in both of my ring fingers… then after 8 months i took it of and immediately the rush disappeared…
I don’t know what component is doing that if it can be folate and how to replace that b complex… is very important for me because I’m vegan… and I’m not sure if take iron or how to suplement myself!!
I will use some advice!
Thank you so much!
Shelita, the only obvious thing in that supplement to cause a “rush” would be niacin. Everything else looks like it’s the same type of vitamins your body would get from food and should recognize it as such.
Check out the reviews on Nootropics Expert for the rest of the vitamins and minerals your body needs including magnesium and zinc. This post is a good place to start: https://nootropicsexpert.com/13-vitamins-essential-for-the-optimized-brain/ and https://nootropicsexpert.com/13-minerals-essential-for-the-optimized-brain/
Thank you, but is it true that people with ocd shouldn’t take folate suplements?
Shelita, 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.
You would die without folate in your body. So to say that someone with OCD shouldn’t use a folate supplement does not make sense to me. If you have excess folic acid plugging up receptors in your body and brain, or are low in natural folate, then you should take a folate supplement. No matter what condition you are suffering from.
Hi David
Is “Quatrefolic” enough to attest the quality of a product? I ordered this one …
and then read a bad review about the brand. Do you have an idea, should I buy another one? Thanks for your expertise 🙂
Catherine, Quatrefolic is a patented version of Vitamin B9 (folate). If the manufacturer of the supplement shows on the bottle or package that they are using Quatrefolic then I’d assume that they are really using this ingredient.
To be sure, you can do a search of the brand on a site like Amazon and see what verified buyers are saying. Then do a regular “google” search and find out if there are any lawsuits, actions by the FDA or anything else that turns up that looks suspicious or negative.
I personally usually choose manufacturers I know and trust to buy supplements like this. Big brands like Doctor’s Best, Swanson, Life Extension, etc. And stay away from brands I’ve never heard of.
Dear David.
Thank you very much for the good article! I mainly refer to your site to make up my stack to overcome depression. There are 20 different supplements in my stack.
What do you think about choice of ‘Jarrow formulas B-Right’ over ‘Life Extension BioActive complete B-complex’? Because Jarrow fomulas contains ‘Quatrefolic’ 400mcg. You said ‘which are branded forms of folate ensuring their purity and effectiveness.’ But Jarrow has less amount of other things than Life Extension. but also contains Choline and Pantethine.
This is Jarrow’s
Vitamin B1 (as Thiamin Mononitrate) 25 mg ,Vitamin B2 (as Riboflavin) 25 mg, Niacin (as Nicotinic Acid ) 25 mg ,Vitamin B6 (as Pyridoxine HCI) 25 mg ,Vitamin b6 (as Pyridoxal 5-Phosphate) 10 mg ,Folate (as Quatrefolic (6S)-5-Methyltetrahydrofolic Acid Glucosamine Salt) 400 mcg ,Vitamin B12 (as Methylcobalamin) 100 mcg ,Biotin 300 mcg ,Vitamin B5 (as calcium D-Pantothenate) 100 mg,Choline (as Choline Bitartrate) 50 mg ,Pantethine (Vitamin B5 Derivative) 25 mg, Inositol 50mg
Jay, looks like Jarrow has a good quality B-Complex supplement with all the right ingredients.
Can you explain what’s wrong with “folic acid” other than being synthetic?
John, a critically important question.
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.
Tetrahydrofolate (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.
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.
And then there’s the issue of problems with the MTHFR gene explained in detail in this section of the post: https://nootropicsexpert.com/vitamin-b9-folate/#problems-with-mthfr
High doses of synthetic folic acid may increase your risk of cancer, immune system damage and other health problems. (links to these studies are in the “REFERENCES” pulldown menu below this post).
This is somewhat worrisome due to the recommendation that pregnancy women supplement with “folic acid” and the problems that may cause, and also the problems that might occur if they do NOT supplement with any B9.
Dear David,
After doing some research into choline sources I came to the conclusion that supplementing with raw egg yolks could be a good alternative for ( 1 large yolk) folate,(24.8mcg) vitamin D (18.2IU), choline (116mg) along with the other elements found in a bioavailable form. The egg source is certainly important (free range). My nootropic stack is already extensive and to combine several of those individual items into food based source would be a good move for me; plus eggs are cheap. 2 to 3 egg yolks twice a day would suffice for me. I assume that this would qualify a fat from a beneficial source an a good source cholesterol ( is cholesterol a nootropic?) for hormone production. Plus it would fit into a ketogenic diet which is suppose to enhance cognition.
Your Dedication and persistence is Admirable. You inspire me!
Barry
Barry, according to several sources including Harvard (https://www.health.harvard.edu/newsletter_article/cholesterol-the-mind-and-the-brain) the human brain contains about 25% of the body’s total cholesterol. But since it’s made in your liver rather than from your diet we couldn’t technically call it a nootropic. But it’s certainly critical for brain function. And one of the reasons why statins can be so deadly for the brain.
Hello!! Very nice blog, I am currently soaking up all the information here!
I have a question concerning my stack, especially my folate dosage.
My Stack currently includes the following: ALCAR (3x 500mg), AlphaGPC (2x 250mg), Omega 3 (1000mg), L-Theanine (2x 200mg), L-Tyrosin (2x 3g), L-Tryptophan(3 x 500mg), Vitamin D3 4.000 IE, Vitamin K2 (200μg), Zink (25mg), Creatine (5g), a low dosage Multivitamin and soon Noopept (Did not yet arrive will; will start with 2x 10mg a day).
I ordered a B-Vitamin package to boost the effects of the Stack. It includes a Vitamin B Complex (Thiamine: 125mg; Riboflavin: 125mg; Niacin: 125mg NE; Panthothenic Acid: 125mg; B6: 125 mg; B12: 125μg; Folic Acid: 800μg; Inositol: 125mg; PABA: 125 mg; and Biotin: 125μg) The dosage is high, however for some of the B-Vitamines not as high as you recommend for nootropic use.
Therefore I ordered along with it high dosages for Vitamin B3 (500mg), Panthothenic Acid (500mg), Inositol (750mg) and L-Methylfolate (1000 μg). Do you think it is save to supplement them all together at the same time? The folic acid of the Vitamin B Complex is probably not folate, thats why I ordered additional L-Methylfolate. However I think the toal dosage for the folates will be too high (Folic Acid 800 μg form the complex and L-Methylfolate 1000μg =1800μg total folate intake). What are your thoughts on that? Should I just not take the L-Methylfolate?
Moreover, do you think the stack above is alright for a beginner in nootropics or do you have any recommendations?!
My aim is too increase my cognitive function, my memory, my focus, and my motivation/mood at work.
Cheers!
Leo, you are right in being concerned about folic acid and folate. The problem as you know is your body needs to convert folic acid to folate before it can be used. There are several problems with that. First, many people cannot do that conversion efficiently. Second, the overload of folic acid blocks the receptors that folate needs to do its job. And you get folic acid added to many processed foods to make matters worse.
I know you don’t want to here this but I would discard the B-Complex supplement you’ve got. And use the individual B-Vitamins you have coming instead. Down the road you could save some money and get a better B-Complex stack like the one produced by Life Extension called “Bio-Active Complete”.
The rest of your stack looks great. I recommended adding magnesium for several reasons. Including your body cannot use Vitamin D very well without magnesium. https://www.sciencedaily.com/releases/2018/02/180226122548.htm
Wow thank you for the quick reply, David!
I do have magnesium in my stack, forgot to metion it. Well I guess I will ditch the complex. I will then have to order thiamin, B6 and B12 in seperate dosages to complete my Vitamin Bs, right? 🙂
I have three other questions: (I hope its okay to ask them here on the Folate page)
1) Would it be better to switch the L-Tyrosine for the N-Actyl-L-Tyrosine, next time I restock? You seem to prefer this type of tyrosine…
2) I also have a bottle of Q10 (200mg) here. I read on this blog that it has nootropics effects, too. However I’m still 22 years old. Does it make sense for me to supplement Q10 at my age or does my body still produce enough of it on its own? Would it benefit me, if i added it to my stack?
Last question: 3) Have you heard of supplementing Pregnenolone? I heard it has nootropic effects, elevating the mood of many people and enhancing their cognitive function.
Cheers!
Leo, some respond better to L-Tyrosine and some better to NALT. Only way to truly find out is try each separately and see how you feel.
If you can, it’s less expensive finding a B-Complex with the right bioavailable B-Vitamins than getting them separately. I’m aware of Life Extension’s version. But there must be one or two others out there.
Doesn’t hurt to use CoQ10 at any age especially in our modern world. Try it and see if you feel a difference. If not, then resume CoQ10 in about 10 years.
I have not done a review nor tried pregnenolone. But intend to write a post on hormones and brain optimization sometime this year. My doctor has me using progesterone and I find that helps somewhat in the cognition department.
Hello,
I want to try the Mind Lab stack but have MTHFR 1298 variant. My doctor has me taking Ortho Molecular Products Methyl B12 which has Folate as Quatrefolic® 1000mg and Methylcobalamin 5,000mg. Should I continue to take this along with the Mind Lab?
Thanks, I am new to this and also want to get my son who is 26 to try the Mind Lab as well.
Randie, yes you can continue to take both with Mind Lab Pro. The dosages in MLP for the B-Vitamins are low enough that you are not in danger of over-dosing. And I like your doctor for recommending these products. Wish there were more like him in the medical profession.
Wow! I’m really really impressed about the importance of the Vitamin B9.
I’m the guy with ADHD of 17 years and going to try your advised stack and i have some questions. I’m trying the Lab pro but don’t make an impressive effect (I’m more mentally resilient but nothing more -> 3x day) but this don’t resolve the problem of 4 years to the root.
I want start taking stack parts to see how feels and i was thinking to this:
First 3 days:
ALCAR
Vinpocetine
DHA
6th day
sulbutiamine
1 tablespoon Coconut Oil
aniracetam
9th day
NALT
Ritalin 1x10mg
methylcobalamin (1000mcg?)
methyl-folate (some advice of where to buy?
Vitamin B2, Vitamin B3, Vitamin B6, trimethyl glycine, and Vitamin C (in a row or gradually and what’s theyre effects?)
i really appreciate your patience and attention
thanks David 🙂
Giulio, it may take 2 – 4 weeks to realize the effects of Mind Lab Pro. This stack does not have a ‘stimulant’ in it like some manufacturers use to give you the impression it’s working. One day you may realize recalling something that you weren’t able to before. Or your mood is lighter and you’re more sociable around other people. The benefits will sneak up on you until one day you notice the difference.
As for the rest of your proposed stack, please follow the dosage instructions. For example, to get the benefits of Aniracetam, you need to stack it with Alpha GPC or CDP-Choline.
I can’t recall what country you’re in to recommend a seller for folate. Here in the USA, folate is available from Amazon and at the Vitamin Shop.
You should be using the B-Vitamins everyday because the rest of your stack will not work well if you don’t have enough of each of the B-Vitamins. As for effects? Your memory will gradually improve. Your mood should be better. Less irritability. More motivation and you’ll simply feel better.