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Home > Living Well > Health Library > High Homocysteine (Holistic)
Lower homocysteine levels in the blood by taking a daily supplement of over-the-counter folic acid, vitamin B6, and vitamin B12
When B-vitamin supplements do not sufficiently lower your levels, take 1,500 mg of betaine or 2,000 mg of choline each day
Help lower homocysteine levels by eating plenty of fruits and vegetables
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
disease,14 death from diabetes,15 miscarriage,16, 17, 18, 19, 20 other
complications of pregnancy,21, 22, 23, 24, 25 and
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.
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.
According to a recent study, both cigarette smoking and coffee consumption were associated with increased homocysteine levels.27 These findings are consistent with studies that have found both smoking and caffeine consumption to be associated with an increased risk of both cardiovascular disease and osteoporosis. The link between coffee and increased homocysteine has been confirmed by some researchers,28 but not others.29
In one study, a diverse group of people participated in a week-long program that included a strict vegan diet, stress management and spirituality enhancement sessions, group support, and exclusion of tobacco, alcohol, and caffeine.30B vitamin supplements known to reduce blood homocysteine levels were not provided. After only one week in the program, the average homocysteine level fell 13%.
Another study of men with heart disease demonstrated that consumption of whole-grain and legume powder at breakfast, instead of their usual breakfast of
refined rice, resulted in a significant reduction in homocysteine levels.
Since homocysteine is produced from methionine, intake of large amounts of methionine would presumably increase homocysteine levels. Indeed, ingestion of supplemental methionine is used experimentally as a way to increase homocysteine levels. Foods high in methionine that have also been linked with an increased risk of heart disease include meat and eggs. The extent to which consumption of these foods affects the risk of heart disease as a result of their methionine content remains unknown.
A controlled trial showed that eating a diet high in fruits and vegetables containing folic acid, beta-carotene and vitamin C effectively lowered homocysteine levels. Healthy people were assigned to either a diet containing a pound of fruits and vegetables per day, or to a diet containing three and a half ounces of fruits and vegetables per day. After four weeks, those eating the higher amount of fruits and vegetables had an 11% lower homocysteine level compared with those eating the lower amount of fruits and vegetables.
Our proprietary "Star-Rating" system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by some in the medical community, and whether studies have found them to be effective for other people.
For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.
3 StarsReliable and relatively consistent scientific data showing a substantial health benefit.
2 StarsContradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1 StarFor an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.
Vitamin B6, folic acid, and vitamin B12 all play a role in converting homocysteine to other substances within the body. By so doing, they consistently lower homocysteine levels in research trials, a finding that is now well accepted. Several studies have used (and some doctors recommend) 400–1,000 mcg of folic acid per day, 10–50 mg of vitamin B6 per day, and 50–300 mcg of vitamin B12 per day.
Of these three vitamins, folic acid supplementation lowers homocysteine levels the most for the average person. It also effectively lowers homocysteine in people on kidney dialysis. In 1996, the FDA required that all enriched flour, rice, pasta, cornmeal, and other grain products contain 140 mcg of folic acid per 3½ ounces. This level of fortification has led to a measurable decrease in homocysteine levels. However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine, suggesting that the FDA-mandated supplementation is inadequate to optimally protect people against high homocysteine levels. Therefore, people wishing to lower their homocysteine levels should continue to take folic acid supplements despite the FDA-mandated fortification program.
Betaine (trimethylglycine) (6 grams per day) and choline (2 grams per day) have each been shown to lower homocysteine levels. Choline in the amount of 2.6 grams per day (provided as 34 grams per day of soy lecithin) has also been shown to lower homocysteine levels in a double-blind trial. More recently, 1.5 grams of betaine per day, an amount similar to that in a typical diet, also has been found to lower homocysteine levels. Doctors usually consider supplementation with these nutrients only when supplementation with folic acid, vitamin B6, and vitamin B12 do not reduce homocysteine levels sufficiently. The results of this study, however, point to the potential benefit of increasing one's intake of foods rich in betaine (such as whole wheat, spinach, beets, and other plant foods).
In a preliminary trial, 20 patients with sickle cell anemia were given either 1 mg of folic acid per day or folic acid plus 6 grams of aged garlic extract, 6 grams of vitamin C, and 1,200 mg of vitamin E per day for six months. Patients taking the combination had a significant improvement in their hematocrit (an index of anemia) and less painful crises than those taking just folic acid.
Preliminary research has found that patients with sickle cell anemia are more likely to have elevated blood levels of homocysteine compared to healthy people. Elevated homocysteine is recognized as a risk factor for cardiovascular disease. In particular, high levels of homocysteine in sickle cell anemia patients have been associated with a higher incidence of stroke. Deficiencies of vitamin B6, vitamin B12, and folic acid occur more frequently in people with sickle cell anemia than in others and are a cause of high homocysteine levels. A controlled trial found homocysteine levels were reduced 53% in children with sickle cell anemia receiving a 2–4 mg supplement of folic acid per day, depending on age, but vitamin B6 or B12 had no effect on homocysteine levels. A double-blind trial of children with sickle cell anemia found that children given 5 mg of folic acid per day had less painful swelling of the hands and feet compared with those receiving placebo, but blood abnormalities and impaired growth rate associated with sickle cell anemia were not improved. In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily. Anyone taking this amount of folic acid should have vitamin B12 status assessed by a healthcare professional.
Vitamin B2 (riboflavin) supplementation (1.6 mg per day) has been shown to lower homocysteine levels by 22 to 40% in a subset of the population that has a certain genetic variant of an enzyme involved in folic acid metabolism (the 677Cà T polymorphism for the methylenetetrahydrofolate reductase gene). Approximately 15 to 20% of the population carries this gene and could benefic from taking riboflavin. Since genetic testing is expensive and not readily available, it would seem reasonable for all people trying to lower their homocysteine levels to include riboflavin in their regimen of B vitamin supplementation.
Elevated blood levels of homocysteine, a toxic amino acid byproduct, have been linked to risk of stroke in most studies. Supplementation with folic acid, vitamin B6, and vitamin B12 generally lowers homocysteine levels in humans. In a pooled analysis (meta-analysis) of eight randomized trials, folic acid supplementation in varying amounts (usually 0.5 mg to 5 mg per day) reduced stroke risk by 18%.
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. 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.
28. 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.
29. 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].
30. DeRose DJ, Charles-Marcel ZL, Jamison JM, et al. Vegan diet-based lifestyle program rapidly lowers homocysteine levels. Prev Med 2000;30:225-33.
Last Review: 06-08-2015
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