The Importance of 5-MTHF: Methylation and Your Body

Methylation is a hot topic lately, but it’s not necessarily an easy one to understand.

To simplify: methylation is a biochemical process that involves the transfer of four atoms—one carbon and three hydrogen atoms (CH3)—from one substance to another. In practice, this seemingly simple process plays a crucial role in DNA and neurotransmitter production, detoxification, histamine, and estrogen metabolism, energy production, and more.

5-MTHF is the most active form of folate, or vitamin B9. Folic acid is the synthetic form of B9, also known as pterolymonoglutamic acid, which must be converted to 5-MTHF by several key enzymes. A vast majority of people cannot convert folic acid into 5-MTHF effectively, and unmetabolized folic acid is linked to serious health problems.

For pregnant and breastfeeding women, those experiencing high levels of stress, and those interested in longevity and normalizing inflammatory pathways, supplementing with 5-MTHF is worth considering and discussing with your practitioner.*

what is methylation?

You can think of methylation as the continuing evolution of how we understand longevity long-term health and wellness in the body. It is essential for the proper function of almost all body systems, including the cardiovascular, reproductive, neurological, hormonal, and detoxification systems. This complex biochemical process can be considered the on or off switch for a myriad of crucial functions.

For methylation to function effectively and efficiently, it requires optimal levels of certain nutrients and compounds, including B vitamins. The body is provided CH3 via a universal methyl donor called SAMe (S-adenosylmethionine). The system responsible for producing SAMe relies on 5-MTHF, and without it, methylation can go awry.

Without sufficient SAMe and effective methylation, a domino effect occurs: the body is unable to produce sufficient amounts of vital molecules like glutathione, melatonin, serotonin, coenzyme Q10, norepinephrine, epinephrine, taurine, L-Carnitine, and cysteine.

what role does 5-mthf play in methylation?

Since the production of SAMe directly relies on 5-MTHF, methylation depends on sufficient levels of active folate to carry out its many functions. In conjunction with vitamin B12, 5-MTHF functions as a methyl group donor, facilitating the conversion of the amino acid homocysteine to methionine. Elevated homocysteine is a risk factor for several health complications.^[1]

5-MTHF is particularly well-known and important for the developing fetus, as it allows the spinal cord and brain to develop more rapidly and efficiently.* Women with inadequate levels of 5-MTHF have been shown to birth children with a higher risk for attention or behavioral issues, gastrointestinal problems, and other complications.

Many people have trouble converting folic acid to folate, leading to low levels of 5-MTHF. This insufficiency can be due to an ill-functioning liver, intestinal issues, or a genetic problem that inhibits the conversion of folic acid to 5-MTHF.

5-mthfr gene

The 5-MTHFR gene regulates methylation and can cause the body to either over- or under-methylate. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that works as a catalyst for various biochemical reactions, including the conversion of folate into 5-MTHF. The MTHFR gene itself can be considered an instruction manual for the production of the MTHFR enzyme.

Four different mutations or variations commonly occur in the MTHFR gene. They are referred to as SNPs, or single nucleotide polymorphisms. Each SNP is essentially a variation of a building block of DNA. Some have no ill effect on human health, while others can impact a gene’s function for the worse.

MTHFR SNPs are quite common, and their different variations impact how effectively the MTHFR enzyme and the body’s methylation function. Signs of possible MTHFR gene mutations vary widely and include cardiovascular problems, mood imbalances, fatigue, and more.

Genetic testing to evaluate potential gene variations is the first step, followed by metabolic testing and an organic acid panel to understand possible signs of poor methylation. With this information, you can determine whether or not supplementation with 5-MTHF is appropriate and what dosage will work best.

who should supplement with 5-mthf?

Certain people are highly likely to benefit from 5-MTHF supplementation after speaking with their integrative doctor. In particular, pregnant and breastfeeding women who want to avoid a folate deficiency during pregnancy, those with various medical issues, those dealing with high levels of stress, and anyone interested in longevity might find 5-MTHF supplementation advantageous.*

Supplementing with 5-MTHF to support DNA methylation might also support a healthy gut microbiome and neurological health, particularly after antibiotic use.^[2]

five ways to support methylation

Along with testing and possible supplementation with 5-MTHF, here are five other strategies to naturally support optimal methylation.

eat methylation-supporting foods

Strive for at least one cup per day of foods that support methylation, such as kale, Swiss chard and other dark leafy greens, broccoli, and dandelion.

reduce your exposure to toxins

Avoid or omit toxins whenever possible, including toxins in home cleaning products, hygiene products, makeup, and non-organic foods.

limit alcohol and tobacco

Smoking tobacco deactivates vitamin B6, which also plays an essential role in methylation. More than three drinks per week can deplete the body’s B vitamin levels.^[3]

support gut health

Proper gut health allows you to absorb the vitamins and other nutrients that support methylation.

Related content: the four best supplements for gut health

promote normal homocysteine levels

Foods high in antioxidants and supplements like magnesium and zinc can help promote healthy homocysteine levels.

conclusion

Methylation plays a vital role in almost every body system, relying on 5-MTHF to function correctly. If you or your doctor suspect poor methylation, it can be helpful to undergo genetic and metabolic testing and supplement with 5-MTHF, the active form of folate.

[1] Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008 Jun;29(2 Suppl):S101-11; discussion S112-5. doi: 10.1177/15648265080292S114. PMID: 18709885.

[2] https://www.cell.com/iscience/fulltext/S2589-0042(21)00765-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004221007653%3Fshowall%3Dtrue

[3] Laufer EM, Hartman TJ, Baer DJ, Gunter EW, Dorgan JF, Campbell WS, Clevidence BA, Brown ED, Albanes D, Judd JT, Taylor PR. Effects of moderate alcohol consumption on folate and vitamin B(12) status in postmenopausal women. Eur J Clin Nutr. 2004 Nov;58(11):1518-24. doi: 10.1038/sj.ejcn.1602002. PMID: 15138463.