Years after they stopped taking high-dose beta-carotene supplements (search), a group of smokers still suffer extra-high rates of lung cancer and death.

The smokers took part in two ill-starred clinical trials testing whether beta-carotene and vitamin A could prevent lung cancer. Nearly everybody thought it would work. And they were wrong. Lung cancer, heart disease, and death from all causes shot up in those who took high-dose beta-carotene.

In the Finnish ATBC study (search) of 29,000 male smokers, 20 mg beta-carotene supplements taken over six years were linked to lung cancer. In the U.S. CARET study of more than 18,000 male and female smokers and male asbestos workers, 30 mg beta-carotene supplements over four years were linked to a 28 percent higher risk of lung cancer and a 17 percent higher risk of deaths from all causes compared with smokers taking a placebo.

Both studies were halted: ATBC in 1994 and CARET in 1996. But study participants are suffering lingering damage, according to a report in the Dec. 1 issue of theJournal of the National Cancer Institute.

Gary E. Goodman, MD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues looked at follow-up data on those who took part in the CARET study. Their finding: In smokers, the higher risk of lung cancer and death continues even after a person stops taking beta-carotene.

"In CARET participants, the relative risk of lung cancer remained elevated (although not statistically significant) four years after the end of the intervention," Goodman and colleagues write.

Most of this risk was seen in female smokers. It's not clear why women have a higher risk. For that matter, it's not clear why beta-carotene supplements hurt smokers. The most likely reason is that damaging free radicals in cigarette smoke may get a boost from megadoses of beta-carotene.

High-dose beta-carotene supplements may give a person too much of a good thing, note Memorial Sloan-Kettering Cancer Center researchers Anna J. Duffield-Lillico, PhD, and Colin B. Begg, PhD. Their JNCI editorial accompanies the Goodman study.

"[The Goodman] findings suggest that the adverse effects of high-dose beta carotene on lung cancer incidence and overall mortality ... may be related to the pharmacologic doses of beta carotene used and the resultant ... concentrations of beta carotene," Duffield-Lillico and Begg write.

In other words, don't stop getting plenty of beta-carotene in your diet, even if you are a smoker. Other studies show that people who get lots of beta-carotene-rich foods have a lower risk of cancer and heart disease.

A lifetime of healthy eating, they say, is far better than a few years of high-dose vitamins during middle age.

These foods are good for smokers, too. Duffield-Lillico and Begg note that low-dose beta-carotene — equivalent to the 6 mg per day a human gets from a diet rich in nuts and vegetables — mildly protects cigarette-smoke-exposed ferrets against cancer.

By Daniel J. DeNoon, reviewed by Brunilda Nazario, MD

SOURCES: Goodman, G.E. Journal of the National Cancer Institute, Dec. 1, 2004; vol 96: pp 1743-1750. Duffield-Lillico, A.J. and Begg, C.B. Journal of the National Cancer Institute, Dec. 1, 2004; vol 96: pp 1729-1731. News release, JNCI.