What is Homocysteine?
Homocysteine is produced by the demethylation of dietary methionine which comes from protein containing foods. Homocysteine is then recycled back into methionine through a pathway that involves Vitamin B12 in the form of methylcobalamin and folate as a natural folate rather than synthetic folic acid.
Homocysteine is simply an intermediate in a very important biochemical pathway. Plasma homocysteine can also travel another route which involves passing of sulfur groups. This is vitamin B6 dependent and results in the production of cysteine which can convert into the most important antioxidant in the body, glutathione.
What does an elevated homocysteine level mean in simple language?
Excess homocysteine in the circulation can damage the lining of arterial walls making them narrow and inelastic. Research suggests that a raised homocysteine level is an independent risk factor for :
- hardening of the arteries,
- coronary heart disease,
- peripheral vascular disease and other conditions associated with abnormal blood clotting.
Elevated homocysteine is also linked with a number of other serious medical conditions including :
- Alzheimer's disease,
- multiple sclerosis,
- rheumatoid arthritis,
- spontaneous abortion,
- placental abruption,
- neural tube defects (spina bifida, cleft palate, etc)
- renal failure,
- and type II diabetes.
When homocysteine is elevated it reduces nitric oxide (NO) production which can increase risk of hypertension and erectile dysfunction.
What causes Homocysteine to become elevated?
Any road block in this pathway can cause homocysteine to elevate. When we intricately study the biochemistry of the homocysteine pathway we can see that it involves a series of conversions that require enzymes. Several nutrients, especially B vitamins, are needed for these conversions to occur. Stress can deplete B vitamins, as can many medications.
What are ideal homocysteine levels for individuals?
Initially, levels between 8 and 15 micromol/L were considered ideal. Latest research suggests maintaining even tighter control as homocysteine levels above 6.9 micromol/L may be harmful for long-term health. A rise in serum homocysteine of 5 micromol/ L may increase cardiovascular risk by 20% to 30%. Homocysteine levels tend to rise with age.
Folic acid in a specific form, not the synthetic version in many vitamin formulas and B12 also in an absorbable form absorption decline as we age, so as we get older we may require higher doses of these nutrients to lower homocysteine levels effectively. Also, medications commonly taken by these individuals deplete folic acid such as Ibuprofen and other NSAIDS.
How and how often should we test homocysteine levels? Individuals with a personal or family history of coronary heart disease, or other CHD risk factors, or who have the MTHFR gene variation should test every 6 months.
Homocysteine Level Risk Level
- 4.0 - 6.9 micromol/L Optimum (low risk)
- 7 - 9.9 micromol/L Mild risk
- 10. - 12.9 micromol/L Moderate Risk
- 13 - 20 micromol/L High risk
- Over 20 micromol/L Very high risk
- Verhoef P et al. Plasma total homocysteine, B vitamins and risk of coronary atherosclerosis. Arterioscler Thromb Vasc Biol 1997;17:989-95
- Refsum H et al. Homocysteine and cardiovascular disease Ann Rev Med 1998;49:31-62
- Boushey CJ et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probably benefits of increasing folic acid intakes. JAMA 1995;274:1049-57
- Voutilainen S et al. Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels. Arterioscler Thromb Vasc Biol 1999;19:1263-6
- Tsai JC et al. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci USA 1994;91:6369-73
- Nappo F et al. Impairment of endothelial function by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 1999;281:2113-18
- Toprak A, Erenus M, Ilhan AH, Haklar G, Fak AS, Oktay A.The effect of postmenopausal hormone therapy with or without folic acid supplementation on serum homocysteine level. Climacteric. 2005 Sep;8(3):279-86.
- Malinow MR et al. Homocysteine, diet and cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99:178-82.
- Ueland PM et al. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000;72:324-32.
- Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr. 2005 Oct;82(4):806-12.
- Richter B, Stegmann K, Roper B, Boddeker I, Ngo ET, Koch MC. Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population. J Hum Genet. 2001;46(3):105-9.
- Hackam DG et al. What level of plasma homocysteine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocysteine levels above and below 14 micromol/L. Am J Hypertens. 2000;13:105-10.
- Laboratory Evaluations in Molecular Medicine?J. Alexander Brally, PhD, CCN and Richard Lord, PhD (Metametrix Biochemistry Textbook).
- Stern LL, Bagley PJ, Rosenberg IH, Selhub J. Conversion of 5-formyltetrahydrofolic acid to 5-methyltetrahydrofolic acid is unimpaired in folate-adequate persons homozygous for the C677T mutation in the methylenetetrahydrofolate reductase gene. J Nutr. 2000 Sep;130(9):2238-42.
- Berlin H BR, and Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinisic factor. Acta Med Scand. 1968; 184:247-248
- Kelly GS. Folates: supplemental forms and therapeutic applications. Altern Med Rev. 1998 Jun;3(3):208-20.
- Bayes B, Pastor MC, Bonal J, Junca J, Romero R. Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E. Nephrol Dial Transplant. 2001 Nov;16(11):2172-5.
- Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, Friedman JM. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006 Mar 14;113(10):1335-43
- Evers S et al. Features, symptoms and neurophysiological findings in stroke associated with hyperhomocysteinemia. Arch
- Neurol 1997;54:1276-82
- Catargi B, Parrot-Roulaud F, Cochet C, Ducassou D, Roger P, Tabarin A. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid. 1999 Dec;9(12):1163-6.