Nutrients for prevention: negative trials send researchers back to drawing board.

T he dream of preventing cancer with a vitamin pill is rapidly evaporating. Over the past few months, results from clinical trials and observational studies report no benefit — and in a few cases, possible harm — from supplementation with several micronutrients, including vitamins C, D, and E; selenium; calcium; and folate. The fi ndings have sobered investigators in the fi eld of chemoprevention and led to a wholesale reevaluation of the methods used to assess possible benefi ts of vitamins and minerals and to prioritize them for defi nitive testing. “I think there is a lot of disappointment,” said Peter Gann, M.D., Sc.D., a physician – epidemiologist at the University of Illinois at Chicago who studies nutrition and cancer. “When these expensive trials were being designed, there was a lot of hope. Some pretty heavy bets were being placed on those interventions.” In light of the results, investigators anticipate more laboratory work and smaller, exploratory human studies designed to probe exactly how vitamins and minerals affect tumor formation and growth. They also foresee more research geared toward determining whether certain subpopulations — say, those with a certain genetic profi le — might still benefi t from supplementation. But for preventing cancer in the general population, the prospects look bleaker than ever. “Almost unbelievably, none of the studies has shown a benefi t, and a couple even suggest the potential for harm,” said Philip Taylor, M.D., Sc.D., of the National Cancer Institute’s Genetic Epidemiology Branch. “Given these results, it’s hard to be encouraged about micronutrient trials in well-nourished Western populations.” However, there is one bright spot. As reported in this issue of the Journal, a study led by Taylor and conducted in China found that a supplement containing selenium, vitamin E, and -carotene reduced mortality from gastric cancer. Moreover, the benefi t continued for 10 years after the volunteers stopped taking the supplement. “This represents the longest durability of effi cacy observed ... in any prevention trial, including drug trials,” Taylor said. But he and others point out that the study population, in remote Linxian, China, ate a poor diet and most likely suffered defi ciencies of the nutrients tested. “It may be that with the people of Linxian you tipped them into a relatively normal range” of the target micronutrients, said John Potter , M.D., Ph.D., a senior advisor to the Fred Hutchinson Cancer Research Center in Seattle who studies nutrition and cancer, “whereas in the U.S. populations you’re dealing with people who by and large have adequate amounts of these things.”