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Health Condition

High Homocysteine

About This Condition

Homocysteine, a normal breakdown product of the essential amino acid methionine, is believed to exert several toxic effects.

A growing body of evidence suggests that an elevated homocysteine level is a risk factor for heart disease, independent of other known risk factors, such as elevated serum cholesterol and hypertension.1,2 The evidence is not all one-sided, however. In some research the link has appeared only in women,3 and a few scientists still have doubts about the importance of elevations in homocysteine for anyone.4 The clear association between elevated homocysteine levels and heart disease reported in most studies5 does not conclusively prove that homocysteine causes heart disease. It might only be a marker for something else that is the real culprit.6 Nonetheless, many cardiologists take seriously the association between elevations in homocysteine and increased risk of heart disease.

Anger and hostility correlate with the risk of heart disease.7,8 A preliminary study found a link between high homocysteine levels and hostility and repressed anger.9 While anger, hostility, high homocysteine, and heart disease all appear to be tied together, which of these is cause and which is effect remains somewhat unclear.

Increased homocysteine levels may also be a risk factor for the development of many other conditions, including stroke,10 thromboembolism11 (blood clots that can dislodge and cause stroke, heart attack, and other complications), osteoporosis,12Crohn’s disease, ulcerative colitis,13Alzheimer’s disease,14 death from diabetes,15 miscarriage,16,17,18,19,20 other complications of pregnancy,21,22,23,24,25 and hypothyroidism.26

Scientists have yet to prove that elevated homocysteine levels cause any of these diseases. However, most doctors believe that high homocysteine increases the risk of at least heart disease. Fortunately, homocysteine levels can easily be reduced with safe and inexpensive B vitamin supplementation.

Symptoms

Extremely high homocysteine can cause blood clots, rapid bone loss, and, in children, mental retardation. But in general, high homocysteine does not cause symptoms until and unless one of the diseases with which it is associated, appears.

Other Therapies

People with high homocysteine are typically advised to eat less processed food, meat, and saturated fat to lower the risk of heart disease.

References

1. Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877-81.

2. Bostom AG, Silbershatz H, Rosenberg IH, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiobascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077-80.

3. 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. Circulation 1998;98:204-10.

4. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196-9 [editorial/review].

5. Christen WG, Ajani UA, Glynn RJ, Hennekens CH. Blood levels of homocysteine and increased risks of cardiovascular disease. Arch Intern Med 2000;160:422-34.

6. Meleady R, Graham I. Plasma homocysteine as a cardiovascular risk factor: causal, consequential, or of no consequence? Nutr Rev 1999;57:299-305 [review].

7. Williams JE, Paton CC, Siegler IC, et al. Anger proneness predicts coronary heart disease risk: prospective analysis from the atherosclerosis risk in communities (ARIC) study. Circulation 2000;101:2034-9.

8. Kawachi I, Sparrow D, Spiro A 3rd, et al. A prospective study of anger and coronary heart disease. The Normative Aging Study. Circulation 1996;94:2090-5.

9. Stoney CM, Engebretson TO. Plasma homocysteine concentrations are positively associated with hostility and anger. Life Sci 2000;66:2267-75.

10. Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995;346:1395-8.

11. Langman LJ, Ray JG, Evrovski J, et al. Hyperhomocyst(e)inemia and the increased risk of venous thromboembolism: more evidence from a case-control study. Arch Intern Med 2000;160:961-4.

12. Brattstrom LE, Hultberg BL, Hardebo JE. Folic acid responsive postmenopausal homocysteinemia. Metabolism 1985;34:1073-7.

13. 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;80:542-5.

14. Clarke R, Smith D, Jobst KA, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449-55.

15. Hoogeveen EK, Kostense PJ, Jakobs C, et al. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes : 5-year follow-up of the Hoorn Study. Circulation 2000;101:1506-11.

16. Sutterlin M, Bussen S, Ruppert D, Steck T. Serum levels of folate and cobalamin in women with recurrent spontaneous abortion. Hum Reprod 1997;12:2292-6.

17. Wouters MG, Boers GH, Blom HJ, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993;60:820-5.

18. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet 1992;339:1122-3 [letter].

19. Quere I, Bellet H, Hoffet M, et al. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril 1998;69:152-4.

20. Nelen WL, Blom HJ, Steegers EA, et al. Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obstet Gynecol 2000;95:519-24.

21. de Vries JI, Dekker GA, Huijgens PC, et al. Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies. Br J Obstet Gynaecol 1997;104:1248-54.

22. Goddijn-Wessel TA, Wouters MG, van de Molen EF, et al. Hyperhomocysteinemia: a risk factor for placental abruption or infarction. Eur J Obstet Gynecol Reprod Biol 1996;66:23-9.

23. Leeda M, Riyazi N, de Vries JI, et al. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 1998;179:135-9.

24. Dekker GA, de Vries JI, Doelitzsch PM, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995;173:1042-8.

25. Rajkovic A, Catalano PM, Malinow MR. Elevated homocyst(e)ine levels with preeclampsia. Obstet Gynecol 1997;90:168-71.

26. Catargi B, Parrot-Roulaud F, Cochet C, et al. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid 1999;9:1163-6.

27. Glueck CJ, Shaw P, Land JE, et al. Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients. Am J Cardiol 1995;75:132-6.

28. Ubbink JB, Vermaak WJH, van der Merwe A, Becker PJ. Vitamin B12, vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993;57:47-53.

29. Ubbink JB, Vermaak WJH, ven der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.

30. Dierkes J, Kroesen M, Pietrzik K. Folic acid and vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women. Int J Vitam Nutr Res 1998;68:98-103.

31. Stein JH, McBride PE. Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. Arch Intern Med 1998;158:1301-6.

32. McGregor D, Shand B, Lynn K. A controlled trial of the effect of folate supplements on homocysteine, lipids and hemorheology in end-stage renal disease. Nephron 2000;85:215-20.

33. Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Fed Regist 1996;61:8781-97.

34. Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340:1449-54.

35. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998;338:1009-15.

36. Wilcken DEL, Wilcken B, Dudman NP, Tyrrell PA. Homocystinuria—the effects of betaine in the treatment of patients not responsive to pyridoxine. N Engl J Med 1983;309:448-53.

37. Jancin B. Amino acid defect causes 20% of atherosclerosis in CHD. Fam Pract News 1994(Oct 15):7.

38. Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 2005;82:111-7.

39. Olthof MR, van Vliet T, Boelsma E, Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr 2003;133:4135-8.

40. Wilcken DEL, Wilcken B, Dudman NP, Tyrrell PA. Homocystinuria—the effects of betaine in the treatment of patients not responsive to pyridoxine. N Engl J Med 1983;309:448-53.

41. Jancin B. Amino acid defect causes 20% of atherosclerosis in CHD. Fam Pract News 1994(Oct 15):7.

42. Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 2005;82:111-7.

43. Olthof MR, van Vliet T, Boelsma E, Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr 2003;133:4135-8.

44. McNulty H, Dowey LR, Strain JJ, et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677Cà T polymorphism. Circulation2006;113:74-80.

45. Jang Y, Lee JH, Kim OY, et al. Consumption of whole grain and legume powder reduces insulin demand, lipid peroxidation, and plasma homocysteine concentrations in patients with coronary artery disease: randomized controlled clinical trial. Arterioscler Thromb Vasc Biol2001;21:2065-71.

46. Broekmans WM, Klopping-Ketelaars IA, Schuurman CR, et al. Fruits and vegetables increase plasma carotenoids and vitamins and decrease homocysteine in humans. J Nutr 2000;130:1578-83.

47. Boers GHJ, Smals AGH, Trijbels FJM, et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N Engl J Med 1985;313:709-15.

48. Nygård O, Refsum H, Ueland PM, Vollset SE. Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study. Am J Clin Nutr 1998;67:263-70.

49. Stolzen berg-Solomon RZ, Miller ER III, Maguire MG, et al. Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am J Clin Nutr 1999;69:467-75.

50. Nieto FJ, Comstock GW, Chambless LE, Malinow RM. Coffee consumption and plasma homocyst(e)ine: results from the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 1997;66:1475-85 [letter].

51. DeRose DJ, Charles-Marcel ZL, Jamison JM, et al. Vegan diet-based lifestyle program rapidly lowers homocysteine levels. Prev Med 2000;30:225-33.

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The information presented by Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2018.

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