Homocysteine Metabolism: Nutritional Modulation and Impact on Health and Disease

Interest and research into the causes and treatment of hyperhomocysteinemia has increased dramatically in recent years, as increased plasma homocysteine has joined smoking, dyslipidemia, hypertension, and obesity as an independent risk factor for cardiovascular disease. In addition, elevated homocysteine levels have been implicated in a number of other clinical conditions, including neural tube defects, spontaneous abortion, placental abruption, low birth weight, renal failure, rheumatoid arthritis, alcoholism, osteoporosis, neuropsychiatric disorders, non-insulin-dependent diabetes, and complications of diabetes. Homocysteine is an intermediate metabolite of methionine metabolism and is itself metabolized by two pathways: the re-methylation pathway, which regenerates methionine, and the trans-sulfuration pathway, which degrades homocysteine into cysteine and then taurine. Because homocysteine is located at this metabolic crossroad, it impacts all methyland sulfur-group metabolism occurring in the body. Consequently, elevated levels of homocysteine would be expected to negatively impact the biosynthesis of all of the following: S-adenosylmethionine, carnitine, chondroitin sulfates, coenzyme A, coenzyme Q10, creatine, cysteine, dimethylglycine, epinephrine, glucosamine sulfate, glutathione, glycine, melatonin, pantethine, phosphatidylcholine, phosphatidylserine, serine, and taurine. Nutritional intervention with the cofactors required for optimal metabolism of the methionine-homocysteine pathways offers a new, integrated possibility for primary prevention and treatment. Supplementation with betaine, vitamin B12, folic acid, and vitamin B6 assists in optimizing methyland sulfur-group metabolism, and might play a significant role in the prevention and treatment of a wide array of clinical conditions. (Alt Med Rev 1997;2(4):234-254)