Homocysteine, a normal breakdown product of the essential amino acidmethionine, 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,34 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. and a few scientists still have doubts about the importance of elevations in homocysteine for anyone.
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,12 inflammatory bowel disease (Crohn’s disease and ulcerative colitis),13 Alzheimer’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. (See “Nutritional supplements that may be helpful” below.)
What are the symptoms of high homocysteine?
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.
Dietary changes that may be helpful for high homocysteine
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.27 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.28 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.
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.29
Lifestyle changes that may be helpful for high homocysteine
According to a recent study, both cigarette smoking and coffee consumption were associated with increased homocysteine levels.30 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,31 but not others.32
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.33 B vitamin supplements known to reduce blood homocysteine levels were not provided. After only one week in the program, the average homocysteine level fell 13%.
Nutritional supplements that may be helpful for high homocysteine
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,34 35 36 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.37 38 It also effectively lowers homocysteine in people on kidney dialysis.39 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.40 This level of fortification has led to a measurable decrease in homocysteine levels.41 However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,42 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)43 and choline (2 grams per day)44 have each been shown 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.
Niacin, a form of vitamin B3, is sometimes given in large amounts to people with elevated cholesterol levels. A controlled study found that 1,000 mg or more per day of niacin raised homocysteine levels.45 Since other actions of niacin lower heart disease risk,46 47 the importance of this finding is unclear. Nonetheless, large amounts of niacin should never be taken without consulting a doctor.
Are there any side effects or interactions with high homocysteine?
Refer to the individual supplement for information about any side effects or interactions.