Methyltetrahydrofolate is More Effective than Folic Acid

Elevated levels of homocysteine, an amino acid byproduct of essential metabolic reactions, are well-known to be related to cardiovascular diseases. High concentrations of homocysteine are an important predictor of mortality in patients with coronary heart disease. They have also been linked to diseases such as vascular dementia and mental cognitive dysfunction, and have been suggested to be a risk factor for cancer.

The body eliminates homocysteine by converting it into useful products such as methionine and cysteine. This process requires B vitamins and folate. High levels of homocysteine are frequently associated with folate deficiency. Folate supplements generally use folic acid, a synthetic form that is not found in nature. All dietary folate is transformed inside the liver to L-5-methyltetrahydrofolate (MTHF), which is the biologically active form that is used to convert homocysteine to methionine.

A double-blind, placebo-controlled study recently published in the European Journal of Clinical Nutrition observed the effects of MTHF compared to folic acid or placebo on elevated homocysteine levels in liver transplant recipients. These patients generally have increased levels of homocysteine which, along with a high incidence of obesity, arterial hypertension, and diabetes mellitus put them at an increased risk for cardiovascular disease. Secondary organ loss is often caused by vascular diseases and their complications. In one study, cardiovascular events caused 19% of mortality in liver transplant patients 5 or more years after transplantation.

48 patients were given 1 mg MTHF/day, 1 mg folic acid/day, or placebo for 8 weeks. At the end of the supplementation period, there was a significant 37% decrease in total plasma levels of homocysteine in the MTHF group. This decrease was still present after 2 weeks of follow-up. The decrease in homocysteine levels was not significant in the group supplemented with folic acid (24%) or placebo.

The study concluded that the effects of MTHF are more potent than folic acid itself.
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Akoglu B, Schrott M, Bolouri H, Jaffari A, Kutschera E, Caspary WF and Faust D. The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study. EJCN 2008;62:796-801.