Two new studies question the conventional wisdom that folic acid and B vitamin supplements cut cardiovascular risk. Healthcare practitioners have often prescribed these supplements in an attempt to reduce blood levels of homocysteine, a protein that has been linked to heart attack and stroke. However, the new research suggests that lowering homocysteine by supplementation has no effect on preventing heart attacks-and that these supplements may even trigger a slight rise in heart attack risk.
"Combination vitamin therapies, which do lower homocysteine, have no effect on cardiovascular events, even though the homocysteine level is lowered," says Dr. Joseph Loscalzo, head of the department of medicine at Brigham and Women's Hospital in Boston.
The First Study
In the first study, called the Norwegian Vitamin (NORVIT) trial, Norwegian researchers randomly assigned 3,749 men and women who had had heart attacks to receive either folic acid along with vitamins B-6 and B-12, or a placebo.
During the three years of the trial, the researchers found that while homocysteine levels dropped an average of 27% among the people taking folic acid and vitamin B-12, this decline had no significant effect on whether they had or died from another heart attack. In fact, the people who were taking all three supplements actually had a slightly increased risk of having another heart attack, the researchers report.
"Doctors should not advise patients who have cardiovascular disease to take B vitamins in order to prevent heart disease or stroke," says lead author Dr. Kaare Harald Bonaa, a professor of medicine and consultant cardiologist at the Institute of Community Medicine at the University of Tromso in Norway. "B vitamins do not prevent heart disease."
The Second Study
In the Heart Outcomes Prevention Evaluation (HOPE) 2 study, researchers gave more than 5,500 patients who had diabetes or vascular disease supplements of folic acid and vitamins B-6 and B-12, or a placebo.
During the five years of the study, homocysteine levels dropped significantly among those receiving the supplements, but this did not translate into a significantly reduced risk of death from heart disease or heart attack.
There did, however, appear to be a slight reduction in the number of people who had a stroke among those taking the supplements, the researchers report.
Overall, the researchers say that, "combined daily administration of 2.5 milligrams [mg] of folic acid, 50 mg of vitamin B-6 and 1 mg of vitamin B-12 for five years had no beneficial effects on major vascular events in a high-risk population with vascular disease." They conclude, "Our results do not support the use of folic acid and B vitamin supplements as a preventive treatment."
However, Anne Dickinson, a consultant and past president of the Council for Responsible Nutrition, a group that represents the supplements industry, says that because the two studies involved individuals who had a history of heart attack, heart disease, diabetes and other problems, the findings may not apply to relatively healthy Americans.
"These studies did not test whether B vitamins used by healthy people can help keep them healthy," Dickinson says. "Instead, they looked at whether B vitamins can treat or reverse heart disease in people who already have it. Vitamins should not be expected to perform like drugs their greatest purpose is in prevention."
Alice H. Lichtenstein, director of the Cardiovascular Nutrition Lab at the US Department of Agriculture's (USDA) Human Nutrition Research Center at Tufts University, disagrees. She notes that even outwardly "healthy" Americans develop some level of atherosclerosis (hardening of the arteries) as they age, and therefore, the findings would probably apply to the average person, as well.
Analyzing The Findings
Loscalzo believes that at the dosages used in the study, folic acid and B vitamins somehow counteract their beneficial effect of reducing homocysteine levels. "Some of those adverse effects may have to do with the complex metabolism of the vitamins," he speculates. "These vitamins are important for cell growth. It may be that the doses used might have stimulated the growth of cell and atherosclerotic plaque."
Vitamin therapy may not be the best way to lower homocysteine levels, he suggests. "These high doses of folic acid don't provide any benefit and shouldn't be used," Loscalzo says. Or perhaps lower doses are the key. "Lower doses are safe and may provide benefit, but we don't know that yet."
Lichtenstein agrees that high doses of vitamins may not be as beneficial as some experts had thought. "This is one of those cases where you see an association between a reduced risk of heart disease and levels of vitamins that would normally be consumed [through diet]. But when we go to considerably higher levels than people could consume from diet, we get disappointing results," she says.