L-Methylfolate:  A Gray-matter Nutrigenomic

                                                                                                by Daniel D. LeLong, M.S., B.S. (psychology), Mensan 

L-methylfolate, or 5-methyltetrahydrofolate (or 5-MTHF), is the fourth-generation molecule for dietetic folate delivery, and has certain unique properties with very strong implications for psychology.  L-methylfolate is an over-the-counter, non-stigmatic vitamin capable of preventing and healing symptoms of many genetically-predisposed brain disorders, including age-related cognitive decline, Alzheimer’s, autism, bipolar disorder, dementia, depression, Parkinson’s, post-traumatic stress disorder (PTSD), schizoid syndromes, vascular dementia, plus other brain diseases and mental illnesses.  According to the science, many cases of military PTSD may be successfully prevented, even healed, at the mess and field-ration (MRE) levels.  Dietary L-methylfolate prevents and heals cerebrocortical emaciation in human beings, such as can be caused by the ubiquitous genetic mutations MTHFR C677T and A1298C.  Those particular mutations express as an intestinal defect which, in turn, predisposes myriad diseases – of the brain as well as of the lower body.  This article primarily focuses on cognitive effects of those commonplace genetic traits:  MTHFR C677T and A1298C.  The A1298C mutation can also, like the C677T, contribute to a methylation problem and its many symptoms.  The C677T single nucleotide polymorphism (SNP or snip) would hamper folate methylation worse than the A1298C snip, but both of those two MTHFR SNPs interfere rather badly with high-order gray-matter neurons and with human healthspans.  It is probably not an exaggeration to say that dietary L-methylfolate, ingested to treat cognitive, vascular, reproductive, or diabetic symptoms of the rampant MTHFR C677T and A1298C methylation-error genetic snips, may be the biggest nutritional discovery of the past one-hundred years!  My nickname for L-methylfolate is ‘the psychological vitamin’ – pun intended – with a psychological vitamin being something that improves morale, but with methylfolate also being activated folic acid, the vitamin B₉ analog that can be very helpful in healing the human brain and its psyche.

Water-soluble folate, also known as vitamin B₉, must be present in the human body for DNA/RNA protein recombination and for cellular mitosis – i.e., for cell division, cell replication, and organ growth.  Methyl ions exist chemically as CH₃^–, and their reactions occur more than one billion times per second in the human body.  Methylation inhibits gene expression of virally-inserted DNA, and prunes tangled neurons.  Folate occurs in green leafy vegetables, and must be present for capillary and circulatory-system health.  Adelle Davis, the renowned 1960s-era nutritionist, wrote that folate deficiency constitutes the worst nutritional problem afflicting the population of the United States.  Physicians recommend folate to pregnant women, to prevent spina bifida- and cleft palate-causing neural-tube defects within their babies.  L-methylfolate is a superior folate supplement to folic acid, for many ladies, to help them conceive and gestate more-consistently healthy babies.  One should take note, however, that chronic overdosage with L-methylfolate can cause temporary, reversible joint pain.  A medical doctor once confided to me that, in her opinion, 15mg/day of methylfolate is the ideal dose.  I wouldn’t very much exceed that, for any great span of time.

The abbreviation ‘MTHFR C677T’ derives from the acronym for the small intestine-produced enzyme ‘methylenetetrahydrofolate reductase’ (MTHFR), plus ‘one cytosine (C) nucleotide base replaced by one thymine (T) nucleotide base, at position 677 of the human MTHFR gene.’  Hence, MTHFR C677T.  Similarly, the A1298C snip’s name derives from the acronym, ‘One adenine (A) nucleotide base replaced by one cytosine (C) nucleotide base, at position 1298 of the human MTHFR gene.’  (The four DNA nucleotide bases are adenine (A), cytosine (C), guanine (G), and thymine (T).)  Those two single nucleotide polymorphisms (SNPs, or snips) effect human folate-methylation abnormalities.  For C677T, the notation CC means ‘no mutation present;’ CT, ‘one chromosome of the two has the snip;’ or, TT, ‘both chromosomes have the trait.’  For A1298C, the corresponding chromosomal notation is AA, ‘no mutation present’; AC, ‘one chromosome is mutated’; or CC, ‘both are mutated.’  L-methylfolate is an odorless, tasteless, white, organic solid at standard temperature and pressure, with a molecular mass of 459.46 g/mol, and a melting point  >  300^oC.  Cells depend upon capillaries; capillaries and cell division are contingent upon folate.  In this relatively-new science, the human genome is estimated to contain between 20,000 to 25,000 genes, with about six-billion nucleotide bases arrayed across man’s 23 chromosomes as nearly three-billion nucleotide-base pairs.

Brain-wise, the ubiquitous MTHFR C677T and A1298C snips are starvation traits, not insanity traits!  Those two MTHFR snips work like lowest common denominators against cognitive health, predisposing a human’s brain to numerous secondary diseases, injuries, and insults, while gradually effecting cerebrospinal emaciation.  The MTHFR C677T and A1298C traits chronically malnourish, across man’s blood-brain barrier (BBB), one specific, crucial bodily organ:  high-order gray-matter nerve cells in the human cerebrocortex and spinal cord.  From young childhood, MTHFR snips starve a man’s 3mm- to 5mm-thick neocortex of the naturally-occurring nutrient L-methylfolate – gradually emaciating his cerebrocortical and spinal-cord gray matter, and predisposing him to myriad diseases.  Those DNA snips cause an intestinal defect which often results in secondary brain disease, apart from dietary L-methylfolate supplementation to ameliorate MTHFR C677T- and A1298C-caused cerebrospinal folate starvation, on a day-by-day basis.

As activated vitamin B₉ and a foodstuff, L-methylfolate is nutrigenomic in action, not pharmaceutic, thus, supplementation with it does not imply medication of a stigmatizing mental defect.  MTHFR mutations (which are determined for life at conception) would be as real and true of a person’s big-toe cells’ DNA as of his brain cells’ DNA, but express as an intestinal defect rather than, directly, as a mental problem.  Eventual neocortical emaciation would thus be a secondary consequence of disorder.  Absorptive cells in the bristle-brush region of man’s small intestine produce the enzyme MTHFR which methylates crude folates into L-methylfolate; but, considerably less so, for folks who have more of an MTHFR snip.  The question becomes, ‘Do the absorptive small intestine cells of any given human body produce enough chemical moles of the enzyme methylenetetrahydrofolate reductase to synthesize sufficient molecular mass of 5-MTHF to anabolize, rather than to starve, that body’s gray-matter neocortex and spinal cord?’  Methylfolate anabolizes neocortical and spinal-cord capillaries and neurons, promoting healthy gray-matter neuron mass, and thus does more lasting good than if it briefly reacted like a rapidly-excreted stimulant, such as caffeine with sugar.  L-methylfolate directly stimulates production, in the brain, of the neurotransmitters serotonin, dopamine, and norepinephrine.  Addressing the same gene expression, many traditional prescription psychiatric drugs methylate genes, as a secondary or tertiary action. 

Absorptive cells of the human small intestine make an enzyme that nourishes high-order neurons and prevents brain disease, but a genetic intestinal defect impedes production of that enzyme and, thus, emaciates gray matter.  Persons’ bodies with the MTHFR C677T or A1298C folic-acid non-methylation genetic errors produce less of this enzyme (MTHFR) and, thus, academically-noncompetitive masses of L-methylfolate, the folate end-product naturally synthesized by the human body from folic acid and other crude folates.  The ubiquitous MTHFR C677T and/or A1298C genetic mutations interfere with synthesis, by bristle-brush absorptive cells of human beings’ small intestines, of the enzyme methylenetetrahydrofolate reductase (MTHFR), instrumental in natural-folate and folic-acid methylation.  Humans’ bodies which have an MTHFR C677T and/or an A1298C snip on one, or both, of their two chromosomes don’t make enough of this enzyme and, thus, don’t make enough L-methylfolate for their cerebrospinal, visuospatial-cognitive needs. 

From the literature, it is clearly evident that less of the enzyme methylenetetrahydrofolate reductase in human beings strongly correlates to more brain diseases – very probably, for instance, due to an MTHFR snip causing deficient L-methylfolate synthesis from crude folates.  Such persons tend to suffer malnourished neocortical gray matter and insufficient cerebrospinal mitosis.  People with this DNA snip (single nucleotide polymorphism) make less MTHFR in their intestines and thus less endogenous L-methylfolate, transport less 5-MTHF across their BBBs, have lower spinal-fluid levels of this vitamin, and thus chronically malnourish their gray matter, emaciating their brains, causing neurasthenia (< Gr., weak nerves), and motivating compensatory overeating. 

This explanation of dietary L-methylfolate’s prevention of MTHFR snip-caused folate starvation in human neocortical and spinal-cord gray matter, by uniquely – amongst folates – crossing our blood-brain barriers (BBBs), is my original line of reasoning, a gradual eureka! of scientific inference and deduction.  I didn’t read it as anybody else’s conclusion, nor was I taught it.  Although there is more to L-methylfolate’s action than that it is the only type of folate able to cross man’s BBB, that particular property of 5-MTHF is true in its simplicity.  My interest piqued via personal experience, then from reading the literature, I reasoned:  that folate is essential to capillary development and cell division; that man’s gray-matter neocortex is on the outside of his BBB; but, that only L-methylfolate, not any crude folate, transports across the human BBB.  Thus, that ubiquitous MTHFR snips specifically starve man’s gray-matter neocortex and spinal cord of crucial folate and of methyl ions, by interference with his body’s enzymatic L-methylfolate synthesis – thereby compromising his cognition.  MTHFR snips’ limitations on small-intestinal methylenetetrahydrofolate reductase production, and on concomitant enzymatic reduction of natural folates into L-methylfolate, inexorably emaciate man’s neocortical and spinal-cord gray matter, endangering his psyche.  Other body parts would have more-or-less normal folate metabolism, but healthspan-crucial cerebrospinal gray matter, outside or behind BBB tissue, would be chronically malnourished – outside of cerebral BBB and behind tubular, spinal BBB.  And, that that is true, lifelong unless dietarily mediated, day-by-day, for about 40% to 60% of the world’s human population.

From conception and through no fault of their own, nearly 60% of the human race has either the MTHFR C677T or A1298C genetic trait, or both – interfering with intestinal MTHFR-enzyme synthesis.  In the case of C677T, that particular snip causes people to underproduce that enzyme, resulting in either approximately 70%-efficient folate methylation (if their chromosomes are heterozygous for the mutation) or about 40%-efficient folate methylation (if they’re homozygous for it).  Heterozygosity (CT) would mean that one chromosome has the C677T mutation and the other chromosome doesn’t.  Homozygosity (TT) for the mutation would mean that both chromosomes have it.  Homozygosity (CC), for not having a C677T snip on either chromosome, would mean abundant MTHFR production, as well as lower risk for genetically-predisposed disorders like vascular dementia, schizoid syndromes, post-traumatic stress disorder (PTSD), Parkinson’s, depression, dementia, bipolar disorder, autism, Alzheimer’s, plus other brain diseases and mental illnesses.  The enzyme in question is methylenetetrahydrofolate reductase (MTHFR) produced by absorptive cells in the bristle-brush region of the human small intestine.  MTHFR is the L-methylfolate-precursor enzyme.  The MTHFR enzyme uniquely methylates crude folates into L-methylfolate, for BBB transit.

All crude folates require reductive (electron-additive) methylation into the water-soluble B-vitamin L-methylfolate, to be capable of crossing the blood-brain barrier (BBB).  Neither oxidized folate (i.e., folic acid) nor any other unmethylated natural folate crosses the human BBB; only reduced folate (L-methylfolate) crosses the BBB.  Folic acid, which was first synthesized in the 1940s, is an artificial form of folate which requires a multi-step enzymatic conversion process in the human body into 5-MTHF, to be able to cross man’s BBB.  L-methylfolate is the trans-BBB-capable form of folate; it’s the bioactive analog of folic acid.  MTHFR snips hamper normal brain-nourishing enzymatic reductive methylation of crude folates, elevate bloodstream levels of artery-scarring homocysteine, cripple L-glutathione’s metabolic excretion of toxic heavy metals, worsen diabetic peripheral neuropathy, and genetically predispose infertility, neural tube defects, and miscarriages.  

Unlike the crude-folate folic acid, L-methylfolate crosses the human blood-brain barrier (BBB) to nutrigenomically nourish man’s gray-matter cerebrocortex on the outside of it.  In every person, only activated folate (methylfolate or 5-MTHF), not synthetic folic acid or any natural folate, crosses the BBB to nutrigenomically nourish cerebrocortical gray matter.  But, about one-half of the world’s population doesn’t competitively methylate folic acid (or other crude folates) into activated L-methylfolate, due to their bodies’ DNA having an MTHFR snip. Their bodies produce sub-optimal masses of methylfolate, to cross their BBBs and develop their gray matter.  The bodies of about one-half of the earth’s human population naturally synthesize academically-competitive masses of methylfolate from raw folates, and the other half’s more-or-less don’t, but all human beings’ gray-matter central nervous systems (CNSs) need active L-methylfolate from either endogenous or exogenous sources.  Each human being has between 3mm and 5mm of gray matter as the outer layer, the neocortex, of his brain, separated from the rest of his brain by his BBB.  One millimeter of high-order gray matter corresponds to much of the difference between a working career as a professional scientist or engineer, and that of a laborer.  Thicker healthier gray matter corresponds to a clearer, truer mind’s eye.  Mammals have gray matter in their brains and spines, with humans and dolphins having the most.  Reptiles and lower life forms have no gray matter.

Much teenage drug abuse may derive from a subconscious desire to self-medicate the symptoms of these two latent MTHFR snips, or to become the life of the party and thereby destigmatize primal dread of dementia.  Many young people with an MTHFR snip despair of intellectual virtuosity, then individuate their developing egos according to collective radicalism instead of to mental objectivity and creative, lucrative scientific knowledge.  Abundant MTHFR supports high-order gray-matter neurons and, thus, strengthens one’s conscious mind (Gr., nous, “nooce”), psyche, and ego.  One duty of conscientious ego is to modulate one’s adult human radicality.  Too often, valuable academic cognitive knowledge becomes compromised by illicit, vitality-sapping carnal knowledge.  Early detection plus dietary 5-MTHF supplementation, to treat MTHFR mutations’ symptoms, will help reverse those problematic trends in our youths!  Provided sufficient nutrition, the human psyche and genome can steadily compensate for past shortcomings. 

Gray-matter methylation can have a holistic effect, startlingly noticeable after prolonged depletion.  Man’s gray matter-to-body mass ratio factors into his appearance and bearing, as revealed to an artist’s eye and to his own body image – something like ( I.Q. / B.M.I. ).  Human neocortical gray matter’s development depends substantially upon methylated folates.  Human gray-matter development is limited in part by methylfolate levels, which are themselves formed by small-intestinal bristle-brush-region MTHFR production, which is, itself, attenuated by any MTHFR C677T or A1298C snip.  Methylfolate synthesis is limited, in about 40% to 60% of the world’s population, by MTHFR mutations (C677T and A1298C).  The entire human spinal cord contains high-order gray matter, protected behind tubular BBB tissue, and plays a vital role in psychological, egoic intelligence.  Gray matter consists mostly of neuronal nuclei and complex dendrites, while white matter consists of elongated axons, encased within insulating myelin sheathing.

Almost from human embryonic conception, any MTHFR mutations hinder natural neuroanabolic methylation of folic acid and raw folates into active L-methylfolate, predispose neocortex-emaciating neurasthenia, and correlate to a wide variety of genetically-predisposed brain disorders, including age-related cognitive decline, Alzheimer’s, autism, bipolar disorder, depression, Parkinson’s, post-traumatic stress disorder (PTSD), schizophrenia-like syndromes, and vascular dementia.  Seventy percent of depressives have the MTHFR C677T genetic error.  Such depressives may eat extra to nourish their neocortical gray-matter intellects, but to limited avail.  Methylfolate has startlingly effective results on depressives with a body-mass index of 30 or greater.  MTHFR genetic errors are not, themselves, a mental illness.  MTHFR C677T and A1298C act like lowest common denominators for multiple brain disorders, effecting gradual-onset cerebrospinal starvation, emaciation, and dementia.  Vascular dementia, for example, results from attenuated folate-dependent capillary development which opposes even exercise-propelled circulatory hyperperfusion.  But, for pennies worth of this activated vitamin B₉  (L-methylfolate) per day, many of those diseases may be delayed in onset, decreased in severity, or prevented altogether, given timely treatment.

The B-vitamin 5-methyltetrahydrofolate provides CH₃^– methyl ions and vitamin-B₉ folate to gray-matter neocortical brain cells and spinal-cord cells situated across man’s BBB, nourishing human gray matter for healthy mitosis and capillary development.  Across the BBB, cerebral neurons and capillaries require folate, and gray-matter genes need methylation. Methylfolate supplies human bodies with both.  Methylfolate dosage should be scaled to protein intake and to growth spurts, but L-methylfolate is a water-soluble B-vitamin that’s normally well tolerated.  Care should be taken, however, to not chronically overdose with L-methylfolate, since that can cause reversible joint pain; if you feel joint discomfort, lower the 5-MTHF dose.  The ideal dose of methylfolate is probably between 5mg/day and 15mg/day, with one medical doctor I talked to recommending the latter.  The most common complaint about L-methylfolate is, ‘Why didn’t I know about this years ago?’  For the three-billion-plus people with MTHFR snips, moderate-dose 5-methyltetrahydrofolate can act like a quality-of-life game changer and help them to think and know via cognitive intelligence, not only emotionally and radically.

L-methylfolate and its significance have fairly recently been discovered, and the vitamin has been synthesized in scale and economically marketed only since about 2012, A.D., but it now enjoys increasing availability over-the-counter from a variety of suppliers in health food stores and over the internet.   The widespread MTHFR C677T genetic error causes worse health troubles for populations of industrialized countries, due to their greater emphases upon intellectual employment.  Nutrigenomic 5-MTHF comprises the cheapest-best nutrient imaginable to improve the quality of life for multiple billions of individuals, mostly for people of European or Oriental descent.  The  MTHFR C677T genetic mutation occurs at a slightly-higher rate among Ashkenazi Jewish than among some Gentile populations.  Some scientists estimate that as many as 60% of the population of the human race has an MTHFR genetic mutation (C677T or A1298C, or both), with a concomitant need for methylfolate supplementation to develop and sustain competitive health, thickness, and robustness of their brains’ gray-matter cerebrocortices.

Soldiers whose genomes contain an MTHFR C677T or A1298C snip would be at worse risk for post-traumatic stress disorder (PTSD).  Methylfolated military rations (MREs) would decrease the frequency and severity of PTSD among our combat troops.  Delicious methylfolated food portions would make perfect additions to school lunches, to military messes and rations (MREs), and to assisted-living, dining-hall, disaster-aid, home food-delivery, hospital, mental-ward, prison, rehab-unit, and other institutional foodstuffs provisions.  Suppliers’ addition of L-methylfolate to flour supplies, in place of currently-added synthetic folic acid, would raise the United States’ average intelligence quotient and lower our brain-related health-care costs.   Methylfolation of flour supplies would not create a utopia on earth, but can make human societies much less dystopic. 

MTHFR gene snips withhold L-methylfolate, a naturally-occurring nutrient, from man’s cerebrocortex across his BBB, thus gradually emaciating his gray matter, proportionate to the rest of his body.  The voluntary remedy, to treat the symptoms, is to add methylfolate to one’s daily diet, scaled to protein intake and to growth spurts.  Only methylfolate (but not folic acid or other crude folate) crosses man’s BBB.  I’d love to read a score of double-blind scientific research studies relating the MTHFR C677T and A1298C single nucleotide polymorphisms, crude folates, L-methylfolate, the human BBB, and gray-matter cerebrocortical functioning to cognitive performance and intellectual function.  For objective evaluation, samples of subjects with and without MTHFR C677T, let’s say, treated or untreated with L-methylfolate over a period of months, can be given before-and-after SPECT magnetic-imaging brain scans, to graphically display cerebral neurons’ metabolic responses, for critical scientific evaluation.  This excellent science is fraught with vast hope, for multiple billions of people!

With L-methylfolate, we can treat symptomatic cerebrospinal gray-matter emaciation but MTHFR single nucleotide polymorphisms (snips), themselves, are determined for any given genome at conception and are deemed irreversible in a biological lifespan.  Other side effects of MTHFR snips include worsened artery-scarring L-homocysteine levels, slower toxic metals excretion, greater risk of infertility, neural tube defects, and miscarriage, and worse propensity for diabetic peripheral neuropathy.  Health science of L-methylfolate to treat MTHFR snips ought to become common knowledge to families, school teachers, academic administrators, and guidance counselors, and intrinsic to scholastic pursuits, with 5-MTHF cheaply available, over-the-counter (OTC), on drugstore, grocery, and convenience-store shelves. 

L-methylfolate, to treat symptoms of MTHFR C677T and A1298C, represents a paradigm leap in cognitive psychology (arguably the purest branch of the science) and in preventative psychiatry, and can greatly enhance cognition, academic performance, and lifelong learning for vast segments of the populace.  Nutrigenomic methylfolate can help students ardently transforming academic mediocrity into prestigious science-technology-engineering-mathematics (STEM) careers, adults maximizing their potential as individuals, senior citizens urgent to prevent dementia and Alzheimer’s, and mental-health clients striving for recovery without relapse. Methylfolated foodstuffs can produce smarter children, raise the national IQ, extend adults’ healthspans, and lower incidences of PTSD, all without adversely affecting people whose biological bodies were conceived as MTHFR C677C or A1298A, free of a mutated MTHFR gene.  For the multiple billions of human beings with a MTHFR DNA snip (a single nucleotide polymorphism), dietary methylfolate supplementation can be a real game changer, with potentially-dramatic benefits to memory, concentration, cognitive stamina, logical reasoning, subject-object dualism, and mental math – and, thus, to mankind’s individual egos!

The B-vitamin methylfolate, ingested to treat MTHFR snips’ deleterious limitations upon human gray matter, proffers sweeping bright pediatric, pedagogic, androgogic, geriatric, and psychiatric hope.  For about half of the human race, methylfolate can help men’s brains to live in health as long as do the rest of their bodies, via a nutrigenomic second wind!  This Nobel Prize-quality science, that of methylfolate to treat the ubiquitous MTHFR C677T and/or A1298C genetic traits’ methylfolate-starvation effect on human gray matter and mental cognition, comprises an interdisciplinary singularity crying out for merciful largescale applications.  The use of dietary L-methylfolate to prevent cerebrospinal symptoms of MTHFR single nucleotide polymorphisms represents an economical, genius solution to many persons’ most-urgent healthspan need.

Curious whether this vitamin would help me, I sampled one small bottle of it bought over-the-counter, across a couple of weeks, at a low dose.  My body and soul liked L-methylfolate, and the vitamin helped my cognition, an effect which I distinctly noticed within that timeframe.  Thus, by inexpensive clinical diagnosis, I learned that my genome has at least one MTHFR snip.  Six months later, I acquired empirical laboratory confirmation by investing in an over-the-counter DNA test kit, then mailed the sample swab back to its lab for chemical analysis.  Since MTHFR C677T was a pre-existing fact of my body since conception, there was virtually no downside to my finding out about it (only that my DNA sequence is on file somewhere).  This knowledge dramatically blesses my ego while helping to extend my healthspan!  If one’s genome does not have C677T (or A1298C), then one’s body may never need 5-MTHF supplementation; but, if one does have one-or-both snips on either chromosome (or both), then he should have dietary L-methylfolate, lifelong, for his brain to persevere in health. 

NutriLogic Formulas, L.L.C., my startup company, with its motto “Helping Families Think!”, purveys hope by producing and selling the delicious granola-protein cognitive-nutrition “Cog Bar” and other L-methylfolated foodstuffs.  Nutrition bars are my present offering, to solve this enormous, global-scale need.  The point is that those two MTHFR genetic snips, C677T and A1298C, run in many, many families – resulting in vast room for growth, via cognitive nutrition, for better learning and for attainment of higher hopes.  Cognitive processing or dystopia – those are the two options facing each family and confronting our civilization.  But, even nutritious healthy NuLoFor Cog Bars pale in importance compared to one’s knowledge of one’s own genome and of the lifelong benefits, to billions of individuals, of dietary L-methylfolate.  Purveying hope, NuLoFor leads the way for billions of human beings to enjoy better cognitive reasoning and quality of life, as well as for equipping children to become better grownups!  “Eat… for strength, and not for drunkenness!” (Ecclesiastes 10:17).  “Cog Bars:  Cognitive Nutrition for Better Living!”

A dilemma I face is that by publishing this science, I invite competition for my company but, if I refrain from publishing it, then I endure very-limited markets, supply lines, and venture capital.  The enormous three-billion-plus servings-per-day, week-in week-out, year-upon-year, global market for methylfolated foodstuffs should bear some competition!  Ambitious venture capitalists and enthusiastic retail associates may start dialog with me, Dan LeLong, via:  ddlelong@hotmail.com.

IMPORTANT!    ALL INFORMATION PRESENTED IN THIS WEBSITE IS INTENDED FOR INFORMATIONAL PURPOSES ONLY, AND NOT FOR THE PURPOSE OF RENDERING MEDICAL ADVICE.  STATEMENTS MADE ON THIS WEBSITE HAVE NOT BEEN EVALUATED BY THE U. S. FOOD AND DRUG ADMINISTRATION.  THE INFORMATION CONTAINED HEREIN IS NOT INTENDED TO DIAGNOSE, TREAT, CURE, OR PREVENT ANY DISEASE – ONLY TO EDUCATE AND STIMULATE DISCUSSION.  CONSULT YOUR HEALTH-CARE PROFESSIONAL BEFORE EMBARKING ON ANY TREATMENT REGIMEN.

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Elena A. Christofides, Virginia Valentine.  (2023).  “L-methylfolate in diabetic peripheral neuropathy:  A narrative review.”  L-Methylfolate in Diabetic Peripheral Neuropathy: A Narrative Review – PubMed (nih.gov)

Suzy Cohen.  (2014).  “Methylation problems lead to 100s of terrible diseases.” http://suzycohen.com/articles/methylation-problems/

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L. L. Huang, J. R. Tong, Y. Huang, Y. N. Wei, H. F. Chen, Y. Chen, J. Y. Su, and L. Deng.  (2023).  “Association of MTHFR gene C677T polymorphism with pregnancy outcome.”  https://pubmed.ncbi.nlm.nih.gov/36647865/    

Lauren LeBano.  (2013).  “L-methylfolate: A promising therapy for treatment-resistant depression?” L-Methylfolate: A Promising Therapy for Treatment-Resistant Depression? | Psych Congress Network | HMP Global (hmpgloballearningnetwork.com)

Carolyn Ledowsky.  (2024).  “MTHFR Fertility:  MTHFR C677T and A1298C can cause miscarriages.”  MTHFR Fertility 

Carolyn Ledowsky. (2017)  “MTHFR Support Australia.”  Scientific precision of the human brain’s folate metabolism.  Folate and Brain | MTHFR Support Australia

M. Levitt, P. Nixon, J. Pincus, J. Bertino.  (1971).  “Transport characteristics of folates in cerebrospinal fluid: A study utilizing double-labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate.”  The Journal of Clinical Investigation, 50, 1301-1308.  JCI71106609.pdf (dm5migu4zj3pb.cloudfront.net)

Lin Wan, Yuhong Li, Zhengrong Zhang, Zuoli Sun, Yi He, and Rena Li.  (2018). “Methylenetetrahydrofolate reductase and psychiatric diseases.”  Translational Psychiatry, 8, 242.  Methylenetetrahydrofolate reductase and psychiatric diseases – PMC (nih.gov)

L-methyfolate overview and synopsis.  (2024).   http://en.wikipedia.org/wiki/Levomefolic_acid

P. L. Rady, S. K. Tyring, S. D. Hudnall, T. Vargas, L. H. Kellner, H. Nitowsky, R. K. Matalon.  (1999).  “Methylenetetrahydrofolate reductase (MTHFR):  the incidence of mutations C677T and A1298C in the Ashkenazi Jewish population.”  American Journal of Medical Genetics, Oct 8; 86(4): 380-4.  Methylenetetrahydrofolate reductase (MTHFR): the incidence of mutations C677T and A1298C in the Ashkenazi Jewish population – PubMed (nih.gov)   

Arthur Strand.  (2015).  “Why So Many People Require the Metabolically Active Form of Folic Acid.” Life Extension Magazine. 5/2015, 56-64. https://www.lifeextension.com/magazine/2015/5/why-so-many-people-require-the-metabolically-active-form-of-folic-acid

Amy Yasko.  (2019).  Nutrigenomics: DNA Methylation Pathway Analysis. Neurological Research Institute. http://www.holistichealth.com  http://www.dramyyasko.com

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A second saliva-swab methylation-pathway DNA laboratory test kit for MTHFR snips, at $129.99 from:  MTHFR Test Kit – MTHFR Doctors

Large-denomination L-methylfolate (5mg tablets – 8.5mg dietary folate equivalent [DFE]) – on sale as cheap as $8.10 for 30 tabs (about $.27 per day, at a 5mg/day dose):  High Potency Optimized Folate, 8500 mcg, 30 vegetarian tablets – Life Extension

Larger-denomination L-methylfolate (15mg capsules – 25.5mg dietary folate equivalent [DFE]) – cheapest-best, as inexpensive as $29.99 for 120 caps (about $.25 per day, at a 15mg/day dose):  Search: 5 results found for “methylfolate” – Carlyle Nutritionals

Washington, DC-area expert on the practice of methylfolate therapy for MTHFR snips:  Andrew H. Heyman, M.D., MHSA; http://www.virginiahealthandwellnesscenter.com ; (703) 327-2434.

Nationwide-prolific American medical doctor and author Daniel G. Amen, M.D., who often recommends L-methylfolate as part of his comprehensive mental-health regimen.  Mental Healthcare Clinic Focusing On Your Brain Health | Dr. Amen (amenclinics.com)    Methylfolate | Folate Supplement & Mood Support (brainmd.com) ; (855) 398-1834.