Why do vitamins keep on failing in clinical trials?

Hopes that vitamin supplements can fend off cancer, cognitive decline, and other health problems keep on getting dashed. The arc is pretty familiar. Epidemiologic studies, often with animal experiments and lab-based research thrown in, suggest protective effects. But results from randomized clinical trials show no effect. The bubble of optimism pops, and the public attitude toward nutrition science and advice sours.

There are several explanations for why this happens. People inclined to take vitamins often have good health habits, and those health habits, rather than the vitamins, may be responsible for the positive effects seen in epidemiologic studies, despite good-faith efforts (and fancy statistical techniques) used by researchers to separate them out. Vitamins in food may be one thing, vitamins in pill form, another. Short trials may not last long enough for vitamins to have a pronounced effect on some of the diseases being studied. And in longer ones, compliance with taking a test nutrient often falls off, diminishing the contrast with the control group and increasing the chances that the results won't show any difference between those who took the nutrient and those who didn't.