Folate and vitamin B12 are involved in hundreds of biological processes in the human body. However, both folate and cobalamin can be affected by intestinal disorders and mutations that play important roles in their uptake and usage[16].

Combining methylfolate and methylcobalamin can have numerous benefits for the body and mind. 

Methylated nutrients are at their most important during fetal development and can improve the chance of pregnancy success.

Lack of methyl-donor nutrients in the developing fetus has been linked to a higher risk of complications in pregnancy and congenital abnormalities. Supplementing with L-methylfolate[6] rather than folic acid can prevent folate-related complications and health issues during pregnancy. Vitamin B12 works alongside folate in red blood cell formation and the development of the brain during childhood. Methylcobalamin is one of three naturally-occurring forms of B12 shown to be superior in absorption to cyanocobalamin. 

Supplementation with L-methylfolate has been shown to improve response to antidepressants in people with treatment-resistant depression, with many patients showing improvement within 2-4 weeks.

Sufficient vitamin B12 is required for the production of serotonin as well as other monoamine neurotransmitters and catecholamines.

Naturally occurring methylfolate is shown to be superior to synthetic folic acid[20] because it is well absorbed in the body, even when gastrointestinal pH is insufficient for proper digestion. The bioavailability of methylfolate is not affected by metabolic defects or genetic mutations.

Clinical studies show that methylcobalamin is successful in restoring B12 in the body and lacks the cyanide molecule which is present in cynacobalamin. It is also worth noting that cyanocobalamin is a synthetic form of vitamin B12 used most often in supplements, while methylcobalamin is the natural form of B12.

Homocysteine is converted to methionine via the remethylation pathway in which both folate and vitamin B12 are required as cofactors. Both methylfolate and methylated B12 are required to initiate the methylation pathway and provide the necessary methyl groups for this reaction.

Deficiency in either folate or vitamin B12 can lead to elevated homocysteine and subsequent cardiovascular health issues. 

Both methylfolate and methyl B12 are essential for bypassing the malfunctioning conversion process and ensuring the methylation cycle functions optimally. The bioavailability of methylfolate is not affected by metabolic defects[20], and it eliminates the risk of harmful unconverted folic acid[20] in the peripheral circulation. In addition, methylfolate does not mask symptoms of vitamin B12 deficiency, nor does it interact with medications that inhibit dihydrofolate reductase (the enzyme required for reducing dihydrofolic acid to tetrahydrofolic acid). This is especially important for people with MTHFR mutations.

Synthetic folic acid cannot be fully processed in those with MTHFR mutations. As a result, it may accumulate as unmetabolized folic acid, which can be hazardous. In addition, the build-up of homocysteine may damage blood vessels and increase the risk of complications in pregnancy[17].

Vitamin B12 deficiency is shown to be more prevalent in those with MTHFR mutations[18].

A lack of methylcobalamin is believed to impair cell multiplication and may also lead to accumulated homocysteine[19].

Those with MTHFR mutations are urged to take methylated forms of folate in order to bypass the MTHFR insufficiency. Taking methyl B12 alongside methylfolate ensures optimal uptake and utilization in the body.

As with any nutritional supplement, it is important to first consult your health professional about the appropriate dosage for you.

If you have an MTHFR mutation, it is also advisable to read our dosage guidelines on taking methylfolate and also our guidelines on taking vitamin B12.