High Homocysteine

Also indexed as: Hyperhomocysteinaemia

What you need to know

The lower the better when it comes to homocysteine levels. According to research or other evidence, the following self-care steps may help you avoid higher levels that have been linked to heart disease:

Seek support from supplements
Lower homocysteine levels in the blood by taking a daily supplement of over-the-counter folic acid, vitamin B6, and vitamin B12

Back up the B
When B-vitamin supplements do not sufficiently lower your levels, take 1,500 mg of betaine or 2,000 mg of choline each day

Diet right
Help lower homocysteine levels by eating plenty of fruits and vegetables

These recommendations are not comprehensive and are not intended to replace the advice of your doctor or chemist. Continue reading the full high homocysteine article for more in-depth, fully-referenced information on medicines, vitamins, herbs, and dietary and lifestyle changes that may be helpful.

About high homocysteine

Homocysteine, a normal breakdown product of the essential amino acid methionine, is believed to exert a few 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,¹² Crohn’s disease, 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.

Product ratings for high homocysteine

Rating	Nutritional Supplements	Herbs
	Folic acid, vitamin B6, and vitamin B12 (in combination)
	Betaine (trimethylglycine) Choline Vitamin B2 (riboflavin) (for people with a specific genetic make-up)
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

What are the 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.

Dietary changes that may be helpful

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 pulse 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

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 programme 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 programme, the average homocysteine level fell 13%.

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.

Vitamins that may be helpful

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. A few 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 programme.

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).⁴³ 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.

Betaine (trimethylglycine) (6 grams per day) and choline (2 grams per day) have each been shown to lower homocysteine levels.⁴⁴ ⁴⁵ Choline in the amount of 2.6 grams per day (provided as 34 grams per day of soya lecithin) has also been shown to lower homocysteine levels in a double-blind trial.⁴⁶ 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.⁴⁷ 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, beetroot, and other plant foods).

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.⁴⁸ Since other actions of niacin lower heart disease risk,⁴⁹ ⁵⁰ 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?
Refer to the individual supplement for information about any side effects or interactions.

References

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The information presented in 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. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or chemist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires September 2008.

2007-09-01