MTHFR polymorphism and methylation (supplement marketing)
Marketing concept: commercial labs test MTHFR C677T and A1298C polymorphisms and sell «personalised packs» of methylfolate, methylcobalamin and pyridoxal-5-phosphate with promises of resolving anxiety, depression, fatigue and infertility. In most people with heterozygous or even homozygous MTHFR polymorphism, folate metabolism compensates and there are no clinical consequences. EFSA 2014 and Cochrane do not confirm any advantage of active B-vitamin forms over regular forms in people without confirmed functional deficiency.
Also known as: MTHFR mutation supplements, Methylation panel
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- DLevomefolate (L-methylfolate, 5-MTHF)Not recommended · Active form of vitamin B9, ready for methylation reactionsLevomefolate (L-methylfolate, 5-MTHF) is an active form of folate. Supplement brands market it for people with the MTHFR gene polymorphism, claiming it supports "methylation" better than ordinary folic acid. There is no convincing evidence that methylfolate gives carriers of this polymorphism an advantage over folic acid on clinical outcomes. For documented folate deficiency and pregnancy planning, folate supplementation at recommended doses is what has proven value, and matching the "methyl form" to a genotype does not meaningfully change outcomes. The compound itself is safe in this use, but do not take it instead of therapy with proven benefit, since that risks missing the treatment you actually need.
- DMethylcobalaminNot recommended · Active coenzyme form of vitamin B12Methylcobalamin has become the favoured form in the biohacking segment: marketed as «the only correct B12 form» promising relief of fatigue, anxiety, depression and cognitive decline in MTHFR-polymorphism carriers. In most people with MTHFR polymorphism without confirmed B12 deficiency, it offers no benefit over placebo or regular cyanocobalamin. NICE 2024 and BSH 2014 do not single out methylcobalamin as preferred. If it was prescribed after MTHFR testing with normal B12 and homocysteine, consider seeking a second opinion.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit