Beginning in the late 1990s, medical researchers began to suspect that high levels of homocysteine (a substance produced when the body breaks down the amino acid methionine) may accelerate
Most of the supporting evidence for a homocysteine–atherosclerosis connection comes from
Several massive studies of this type were initiated in response to the observational data. The results of 5 such trials have now been reported, involving a total of more than 18,000 men and women.
A smaller study failed to find that these same homocysteine-lowering vitamins preserved mental function in people with loss of mental function caused by atherosclerosis in the brain.
Besides atherosclerosis, correlations have also been found between high homocysteine levels and numerous other diseases, including
On a positive note, a double-blind, placebo-controlled study of 728 Danish seniors with high homocysteine and relatively low folate intake found that use of folate supplements slowed the progression of age-related hearing loss.
Another study found that in people who had already had a stroke and were partially paralyzed, supplementation with vitamin B
and folate reduced the risk of falls leading to hip fractures.
Principal Proposed Natural Treatments
Three nutrients act together to help the body reduce homocysteine levels: vitamin B 6
Nonetheless, as noted above, studies utilizing high doses of these vitamins for lowering homocysteine and therefore preventing cardiovascular disease have generally failed to find benefit. For more information on these nutrients, including dosage and safety issues, see the full
Other Proposed Natural Treatments
Some people develop extraordinarily high levels of homocysteine due to a genetic defect. The supplement trimethylglycine (TMG)
2. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998;98:204-210.
4. Cattaneo M, Vecchi M, Zighetti ML, et al. High prevalence of hyperhomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications? Thromb Haemost. 1998;80:542-545.
12. den Heijer M, Brouwer IA, Bos GMJ, et al. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol. 1998;18:356-361.
17. National Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington DC: National Academy Press; 1998.
19. Venn BJ, Mann JI, Williams SM, et al. Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial. Eur J Clin Nutr. 2002;56:748-754.
23. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291:565-575.
24. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. New England Journal of Medicine website. Available at: http://www.nejm.org . Accessed March 12, 2006.
25. Bønaa K, Njølstad I, Ueland M, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. New England Journal of Medicine website. Available at: http://www.nejm.org . Accessed March 12, 2006.
27. Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA. 2002;288:973-979.
32. Schwab U, Torronen A, Meririnne E, et al. Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. J Nutr. 2005;136:34-38.
34. Olthof MR, Brink EJ, Katan MB, et al. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005;82:111-117.
35. Reimann M, Dierkes J, Carlsohn A, et al. Consumption of soy isoflavones does not affect plasma total homocysteine or asymmetric dimethylarginine concentrations in healthy postmenopausal women. J Nutr. 2005;136:100-105.
37. den Heijer M, Willems HP, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep-vein thrombosis and pulmonary embolism. A randomized, placebo-controlled, double blind trial. Blood. 2006 Sep 7. [Epub ahead of print]
40. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369:208-216.
41. Green TJ, McMahon JA, Skeaff CM, et al. Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial. Am J Clin Nutr. 2007;85:460-464.
44. Herrmann M, Umanskaya N, Traber L, et al. The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial. Clin Chem Lab Med. 2007 Nov 18. [Epub ahead of print]
45. Green TJ, McMahon JA, Skeaff CM, et al. Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-year randomized controlled trial. Am J Clin Nutr. 2007;85:460-464.
47. Sun Y, Lu CJ, Chien KL, et al. Efficacy of multivitamin supplementation containing vitamins b(6) and b(12) and folic Acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in taiwanese patients. Clin Ther. 2007;29:2204-2214
48. van Uffelen JG, Chin A Paw MJ, Hopman-Rock M, et al. The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial. Qual Life Res. 2007 Jul 7. [Epub ahead of print]
49. Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008;299:2027-2036.
50. Ebbing M, Bleie O, Ueland PM, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008;300:795-804.
Last reviewed April 2009 by EBSCO CAM Review Board
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