Homocysteine, an amino acid, is best known for being a predictor of atherosclerosis (plaque buildup in the arteries), cardiovascular disease, and peripheral arterial disease (PAD).

PAD occurs when blood vessels become narrow due to progression of atherosclerosis, which ultimately impedes blood flow. Approximately eight million Americans are impacted by the negative consequences of PAD. A study tested the effects of folic acid supplementation in the form of 5-MTHF vs. standard folic acid vs. placebo, to determine effects on homocysteine, and subsequently, blood flow in people with PAD. For 16 weeks, patients with PAD took 400 mcgs of one of the two forms of folic acid or placebo. The two groups taking folic acid supplements had significantly lower levels of homocysteine than the placebo group at the end of the study. Another important parameter that was measured was the “pulse wave velocity” (PWV), a test that indicates the stiffness of the blood vessel, which is correlated to increased risk for cardiovascular disease. Whereas 5-MTHF significantly reduced PWV, standard folic acid reduced PWV slightly less effectively and the placebo did not reduce the PWV at all. Inflammatory markers were also measured, but were found to be unchanged in all three of the test groups. Folic acid appears to improve markers that indicate cardiovascular disease risk.

Folic acid is normally converted to 5-MTHF in the body. 5-MTHF is relatively new in supplement form. Research has shown that a subset of individuals do not efficiently convert folic acid from the diet or supplements to this active 5-MTHF due to genetic enzyme deficiencies. Research suggests 5-MTHF is a more efficient form of supplementation than inactive folic acid in these and possibly other individuals.

Br J Surg. 2009 Sep;96(9):990-8.

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