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Editor's Correspondence
September 11, 2000

Betaine Supplementation and Plasma Homocysteine in Healthy Volunteers

Arch Intern Med. 2000;160(16):2546. doi:

Elevated plasma total homocysteine concentrations are considered a risk factor for giving birth to a child with a neural tube defect1,2 and for cardiovascular disease.3 Epidemiological studies suggest that elevated homocysteine concentrations are an independent and graded risk factor for vascular disease, with no apparent threshold.3-6 Therefore, it appears that a decrease in plasma total homocysteine concentration in the lower range is still relevant. Homocysteine can be transsulfurated to cysteine using vitamin B6 as a cofactor. It can also be remethylated to methionine. This reaction either uses 5-methyltetrahydrofolate as a substrate in a vitamin B12–dependent reaction or it uses betaine. In humans, the folate-dependent remethylation takes place in all cells, whereas the betaine-dependent remethylation reaction is mainly confined to the liver.7 Supplementation with folic acid has been shown to decrease total plasma homocysteine concentrations in healthy volunteers.8,9 As supplementation with betaine decreases plasma total homocysteine concentrations substantially in patients with homocystinuria,10,11 it might be expected to decrease homocysteine concentrations in healthy subjects as well. However, to our knowledge, no studies that investigated this matter have been reported. Therefore, the question remains whether intake of betaine indeed decreases plasma total homocysteine concentrations in healthy subjects.