News Release

Can a vitamin a day help keep heart disease away?

Peer-Reviewed Publication

Michigan Medicine - University of Michigan

U-M study predicts benefit from boosting nutrients to lower homocysteine

ANN ARBOR, MI - 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 University of Michigan 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 B12 in middle age and beyond from inexpensive multivitamins. The benefit would be most cost-effective if the increased vitamins go to 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, backs up recent calls for middle-aged Americans to get more of both nutrients. It's 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 percent 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, for instance if clinical trial results show that lowering homocysteine levels cuts homocysteine-related heart risk by 40 percent. It looked at costs and benefits for making sure that all at-risk people, or just those known to have high homocysteine, get enough folic acid and B12. Even if it turns out that lowering only cuts men's homocysteine-related risk 11 percent, and women's risk 23 percent, the study says the effort to lower levels would be worthwhile.

Among the authors is noted preventive medicine expert and U-M Health System head Gilbert S. Omenn, M.D., Ph.D., U-M 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 B12 through diet or supplements," says Omenn, who was on a recent national folic acid panel and co-authored a major study on homocysteine.

"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, M.D., M.P.H., a cardiology fellow who began the study as a resident.

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

"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 they 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 micromol per liter. An estimated 40 percent of men over 40 years of age and 32 percent of women over 50 years of age 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 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 B12 and B6 can also help. Much higher doses may be needed in people with end-stage kidney disease.

Coincidentally, 400 mcg is also the Food & Drug Administration's 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 B12, the U-M group and others have recommended that B12 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 costs of saving life-years under three scenarios: no change in the population's folic acid/B12 intake; an increase to 400 mcg of folic acid and 500 mcg of B12 per day for all at risk of heart disease; or 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 homocysteine-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 at those who could most benefit from reducing homocysteine levels.

###

The paper's authors also include Sanjay Saint, M.D., MPH, Melvyn Rubenfire, M.D., and Rajesh Bandekar, Ph.D.


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.