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Nutrition Notes Topics

Homocysteine, Cardiovascular Disease, stroke prevention

Folic Acid and Cardiovascular Disease

Homocysteine (HCY) is derived from the intracellular metabolism of the amino acid, methionine and is exported into the blood where it circulates mostly in oxidized forms, bound to proteins. Concentrations of HCY are increased in 15-40% of patients with coronary, cerebral and peripheral arterial diseases. The increased concentrations of HCY are corrected by supplementation of the diet with folic acid, pyridoxine, and vitamin B12.

The role of homocysteine in causing arterial disease was originally suggested by Dr. Kilmer McCully in the late 60's. McCully was a pathologist at the Massachusetts General Hospital. Apparently, his theory was not well-received by his colleagues and he was eventually asked to leave Mass. General. McCully observed that high cysteine levels were associated with early deaths from arterial disease in patients with homocysteinuria. Homocysteinuria is a rare autosomal recessive disease complicated by early and aggressive occlusive arterial disease associated with high levels of blood homocysteine. Milder hyperhomocysteinemia appears to be common and may be a risk factor for coronary artery disease. Homocysteine undergoes metabolism either by remethylation or transsulfuration, and deficiency or dysfunction of any of the substances that regulate these reactions may lead to hyperhomocysteinemia. Homocysteine may have adverse effects on platelets, clotting factors and endothelial cells. Studies have demonstrated significantly higher plasma homocysteine levels in patients with occlusive arterial disease than in controls.

There is a confusing array of studies in the medical literature that both support and deny benefits of folic acid supplementation. A Chinese review, for example concluded:" Our analysis indicated that folic acid supplementation is effective in stroke prevention in populations with no or partial folic acid fortification. In addition, a greater beneficial effect was observed among trials with a lower percent use of statins. Our findings underscore the importance of identifying target populations that can particularly benefit from folic acid therapy."(Int J Clin Pract. 2012 Jun;66(6):544-51

Another study concluded: "Our meta-analysis indicates that folic acid supplementation may be effective for CVD prevention in patients with kidney disease, particularly in trials among patients without a history of grain fortification with folic acid, with lower percent baseline diabetes, and in patients with end-stage renal disease (ESRD) or advanced chronic kidney disease (ACKD. (Clin Nutr. 2013 Oct;32(5):722-7).

The best role for folate might be in early prevention of CV Disease. People with established coronary artery disease do not reduce the risk of heart attacks by taking folic acid supplements.

Some Folic Acid Topics from Nutrition Notes