The University Record, December 11, 2000

Can a vitamin a day help keep heart disease away? Study predicts benefit from boosting nutrients

By Kara Gavin
Health System Public Relations

The jury is still out on exactly how much benefit our hearts can get from lowering the level of homocysteine in our blood. But that doesn’t mean people at risk for heart disease should wait for a verdict from big clinical trials before having their levels tested and getting more homocysteine-lowering nutrients, a new U-M study finds.

In fact, the researchers report, Americans could live longer lives if more of us got the recommended daily level of folic acid and vitamin B-12 in middle age and beyond from inexpensive multivitamins. The benefit would be most cost-effective for those whose blood tests show an elevated level of homocysteine, a harmful amino acid.

The finding, published in the Dec. 11 Archives of Internal Medicine, supports recent calls for middle-aged Americans to get more of both nutrients. The study is based on a computer model that takes into account what’s known about homocysteine’s harmful effects, folic acid’s ability to lower levels of homocysteine in the blood and observations that people with lower homocysteine tend to have lower heart risk. High homocysteine levels may be associated with up to 6 to 10 percent of all heart deaths in the United States.

The study looked at the hypothetical balance between costs and benefits under several different scenarios:

  • Whether clinical trial results show that lowering homocysteine levels cut homocysteine-related heart risk by 40 percent.

  • The costs and benefits for making sure that all at-risk people, or just those known to have high homocysteine, get enough folic acid and B-12.

    Even if it turns out that lowering homocysteine only cuts men’s homocysteine-related risk 11 percent, and women’s risk 23 percent, the study says the effort would be worthwhile.

    Among the authors is preventive medicine expert and Health System head Gilbert S. Omenn, executive vice president for medical affairs. “It will take years for current clinical trials to tell us how much we can reduce heart disease risk by reducing elevated homocysteine levels. This analysis suggests we should go ahead and encourage blood testing and increased intake of folic acid and B-12 through diet or supplements,” Omenn says.

    “In addition to helping patients, physicians and policy-makers decide a course of action, we also hope our finding will help those designing the next wave of homocysteine clinical trials,” says Brahmajee Nallamothu, a cardiology fellow who began the study as a resident.

    The research model used in the study is called decision analysis. It’s especially good in situations in which physicians have a lot of information about a substance’s potential risk or benefit, but no conclusive proof, says co-author Mark Fendrick, of the U-M’s Consortium for Health Outcomes, Innovation and Cost-Effectiveness Studies.

    “Homocysteine is a notable case of a known medical risk where we strongly suspect a possible benefit from an inexpensive intervention. This conservatively designed study suggests that the benefit doesn’t need to be very large to make the intervention worthwhile,” Fendrick says.

    Homocysteine is found everywhere in the body and, along with related compounds, is known as homocyst[e]ine. Laboratory studies show it can harm the lining of blood vessels, encourage more smooth muscle cells to grow in vessel walls, and create an environment in which blood clots more easily—all risk factors for clogged arteries and heart disease.

    Some—but not all—studies have found that people whose homocysteine levels are even mildly high are more likely to have heart disease, and that risk rises with levels above 11 micromolecules per liter. An estimated 40 percent of men 40 years and older and 32 percent of women 50 years and older fall into this group.

    Fortunately, scientists have found that folic acid can lower homocysteine levels by helping in its breakdown. They’ve determined that the most effective dose for this effect is 400 micrograms (mcg) a day; higher doses don’t seem to lower homocysteine levels much further. It takes about six weeks for folic acid to bring levels down. Vitamins B-12 and B-6 also can help. Much higher doses may be needed in people with end-stage kidney disease.

    Coincidentally, 400 mcg also is the Food and Drug Administration’s (FDA) new recommended daily allowance for folic acid, based on its proven ability to prevent neural tube defects in babies if their mothers get enough of the nutrient. In 1997, the FDA mandated a moderate level of folic acid fortification of grain products. Still, most people don’t get enough folic acid.

    Because there’s evidence that high folic acid can mask a deficiency of vitamin B-12, the U-M group and others have recommended that B-12 be taken along with any folic acid supplements. Most multivitamins contain both nutrients, as do whole grains, oranges and green vegetables.

    The U-M study was funded in part by the Agency for Healthcare Research and Quality. It estimated the cost of saving life-years under three scenarios: no change in the population’s folic acid/B-12 intake, an increase to 400 mcg of folic acid and 500 mcg of B-12 per day for all at risk of heart disease, and screening all at-risk people and giving vitamins to those with high levels.

    The study first looked at the effect on life expectancy and costs under the assumption that reducing homocysteine levels could reduce related heart disease risk 40 percent. The team found that about eight life-years could be saved per 1,000 men, and almost four life-years per 1,000 women, no matter whether the vitamins were given to all at-risk people or just those whose blood test showed they had elevated homocysteine.

    Looking at the cost of the two approaches, however, the team found that despite the up-front blood test cost, the screening approach would cost up to 60 percent less in the long run, since vitamins would be targeted to those who could most benefit from reducing homocysteine levels.

    The paper’s authors also include Sanjay Saint, assistant professor of internal medicine, Melvyn Rubenfire, professor of internal medicine, and Rajesh Bandekar, visiting assistant professor of biostatistics.