Atherosclerosis, the hardening and narrowing of arteries, is often associated with heart disease, but can occur in any artery in the body. When arteries in the brain are affected, it’s called cerebral vascular disease; in the legs, peripheral vascular disease ; and in the heart, coronary artery disease . By limiting blood flow, vascular disease can lead to stroke , heart attack , and death. Several studies have linked elevated levels of the amino acid homocysteine to a greater risk of cardiovascular disease and its most serious complications. A trio of B vitamins—folic acid, B6, and B12—can lower homocysteine levels. What has yet to be proven, though, is if the homocysteine-lowering effects of these vitamins will result in a lower risk of heart attack, stroke, and death. This is the question the HOPE 2 researchers set out to answer.

The HOPE 2 findings, published in the March 12, 2006 online version of the New England Journal of Medicine , show that supplements combining folic acid and vitamins B6 and B12 do not reduce the risk of heart attack, stroke, or death in patients with cardiovascular disease.

About the Study

The 5,522 volunteers in the HOPE 2 trial were age 55 or older, drawn from 13 countries, and considered at risk for heart attack, stroke, or death due to a history of cardiovascular disease or diabetes. The volunteers were instructed to take one pill daily for five years. In the treatment group, the pill contained 2.5 milligrams (mg) folic acid, 50 mg vitamin B6, and 1 mg vitamin B12. The placebo group received a sugar pill. Patients were evaluated every six months and blood samples were taken three times to measure homocysteine. The investigators compared the number of heart attacks, strokes, and deaths between the two groups.

Homocysteine levels dropped significantly in the treatment group and rose slightly in the placebo group. The differences ended there. The rates of heart attack, stroke, and death due to cardiovascular causes were the same in both groups; the supplements had no effect.

A possible limitation of this study is that 70% of the volunteers live in countries where foods are fortified with folic acid. These people likely consume more folic acid and have lower homocysteine levels than people from countries that do not fortify. The result is fewer people with very high levels of homocysteine, which is precisely the subgroup that would benefit most from supplementation. However, NORVIT, The Norwegian Vitamin Trial, published in the same issue of the New England Journal of Medicine , studied 3,749 patients in Norway, a country that does not fortify food with folic acid. This study also found no vascular benefit to folic acid, B6, and B12 supplements.

How Does This Affect You?

Should you stop taking a daily multivitamin with folic acid, B6, and B12? If you’re taking them exclusively for the purpose of lowering your risk of cardiovascular disease, this large study suggests the answer is “yes”. However, if you choose to continue taking supplements for other reasons, be sure your pill provides no more than 100% of the RDA. The amounts given in HOPE 2 were substantially higher than the RDAs (e.g., 2,500 micrograms of folic acid vs. the RDA of 400 micrograms). In addition, the NORVIT study detected a possible harmful effect of supplementation with the three B vitamins; their levels also exceeded the RDAs.

Despite the supplements’ lack of effect, its important to emphasize that food sources of folic acid, B6, and B12 are essential to a healthful, balanced diet. These include fruits, vegetables, legumes, fortified grains, lean meats (B6 & B12), and low-fat dairy products (B12). In addition, every woman who is or may become pregnant should take a multivitamin with 400 micrograms of folic acid to protect against birth defects.

Since lowering homocysteine apparently has little or no benefit, it appears to be a marker, rather than a cause, of cardiovascular disease. However, other factors are more strongly linked to cardiovascular disease, and therefore, have a more direct protective role. These include:

  • Regular exercise
  • Reduced intake of saturated and trans fats
  • Increased intake of fresh fruits and vegetables
  • Not smoking
  • Keeping blood sugar under control, if you have diabetes
  • Keeping blood pressure under control, if you have hypertension