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Folate deficiency has been associated with vascular disease resulting in heart attack, peripheral vascular disease and stroke. One of the most exciting papers to be published recently, Decreased Rate of Coronary Restenosis After Lowering of Plasma Homocysteine Levels in The New England Journal of Medicine, studied the effect of lowering plasma homocystein levels on restenosis (reblockage) after coronary angioplasty. It revealed that a combination of folate (1 mg), vitamin B12 (400 mcg) and B6 (10 mg) significantly reduces homocystein levels and decreases the rate of restenosis after coronary angioplasty.  B6, while it does not lower homocysteine, may have other beneficial effects and has been shown to alter platelet function. No significant side effects were reported. The mechanism whereby elevated homocysteine mediates these effects is not currently known. It has been shown that traditional methods of measuring folate may be insufficient to detect deficiencies resulting in elevated homocysteine that may be amenable to therapy.

Folate has been recommended as therapy for patients with rheumatoid arthritis on methotrexate and for depressed patients who fail to respond to antidepressant therapy. In patients with non-insulin dependant diabetes on metformin, elevations of homocysteine amenable to therapy by folate have been demonstrated. Also in diabetics elevated homocysteine levels were associated with elevated mean arterial blood pressure. Low serum folate and high homocysteine levels have been associated with an increased risk of colon cancer. Elevated homocysteine and low serum foate levels have been noted in patients with both untreated and treated hypothyroidism. During pregnancy low concentrations of folate are associated with increased risk of preterm delivery, infant low birth weight and fetal growth retardation, and folate supplementation has been shown to decrease incidence of certain birth defects.


Schnyder S et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. NEJM 2001 Nov29;345(22):1593-1600.

Hultberg B et al. Marginal folate deficiency as a possible cause of hyperhomocystinaemia in stroke patients. Eur J Clin Chem Biochem 1997 Jan;35(11):25-8.

Fava M et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997 Mar;154(3);426-8.

Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methyl;enetetrahydrofolate reductase gene. Circulation 1997 Jul 15;96(2):412-7.

Fenech MF et al. Folate. Vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis 1997 Jul;18(7):1329-36.

Woo KS et al. Hyperhomocystenemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997 Oct 21;96(8):2542-4.

Aranow WS et al. Association between plasma homocysteine and coronary artery disease in older persons. Am J Cardiol 1997 Nov 1;80(9):1216-8.

Robinson K et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. Eurpoean cOMAC Group. Circulation 1998 Feb 10;97(5):437-43.

Gupta A et al. High homocysteine, low folate, and low vitamin B6 concentrations: prevalent risk factors for vascular disease in heart transplant recipients. Transplantation 1998 Feb 27;65(4):544-50.

Morgan SL et al. Folic acid supplementation prevents deficient blood folate levels and hyperhomocystenemia during longterm, low dose methotrxate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998 Mar;25(3):441-6.

Moustapha A et al. High plasma homocysteine: a risk factor for vascular disease in the elderly. Coron Artery Dis 1998;9(11):725-30.

Refsum H et al. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31-62.

Stein JH et al. Hyperhomocystenemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment, Arch Intern Med 1998 Jun 22;158(12):1301-6.

Jacob RA et al. Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 1998 Jul;128(7):1204-12.

Aarsand AK et al. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. J Intern Med 1998 Aug;244(2):169-74.

Fiorina P et al. Plasma homocysteine and folate are related to arterial blood pressure in type 2 diabetes mellitus. Am J Hypertens 1998 Sep;11(9):1100-7.

Mansoor MA et al. Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of Vitamin B6 reduces concentrations of serum folate. Scand J Clin Lab Invest 1999 Apr;59(2):139-46.

Brouwer IA et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin nutr 1999 Jan;69(1):99-104.

Moustapha A et al. Homocysteine: an emerging age-related cardiovascular risk factor. Geriatrics 1999 Apr;54(4):41, 44-6, 49-51.

Kato I et al. Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study. Br J Cancer 1999 Apr;79(11-12):1917-22.

De Jong SC et al. Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease, Arterioscler Thromb Vasc Biol 1999 May;19(5):1316-24.

Tokgozoglu SL et al. Methylene tetrahydrofolate reductase genotype and the risk of coronary artery disease on a population with low plasma folate. Heart 1999 May;81(5):518-22.

Catargi B et al. Homocysteine, hypothyroidism, and the effect of thyroid hormone replacement. Thyroid 1999 Dec;9(12):1136-6.

Christensen B et al. Whole blood folate, homocysteine in serum, and risk of first myocardial infarction. Atherosclerosis 1999 Dec;147(2):317-26.

Donnelly JG et al. Occurance of hyerphomocysteinemia in cardiovascular, haematology and nephrology patients: contribution of folate deficiency. Ann Clin Biochem 2000 May;37:304-12.

Scholl To et al. Folic acid: influence in the outcome of pregnancy. Am j Clin Nutr 2000 May;71(5S):1295S303S.

BottiglieriT et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000 Aug;69(2):228-32.







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Last modified: June 04, 2005