Vitamin A as "anti-infective" therapy, 1920-1940

In the last fifteen years, a large series of controlled clinical trials showed that vitamin A supplementation reduces morbidity and mortality of children in developing countries. It is less well known that vitamin A underwent two decades of intense clinical investigation prior to World War II. In the 1920s, a theory emerged that vitamin A could be used in "anti-infective" therapy. This idea, largely championed by Edward Mellanby, led to a series of at least 30 trials to determine whether vitamin A--usually supplied in the form of cod-liver oil--could reduce the morbidity and mortality of respiratory disease, measles, puerperal sepsis, and other infections. The early studies generally lacked such innovations known to the modern controlled clinical trial such as randomization, masking, sample size and power calculations, and placebo controls. Results of the early trials were mixed, but the pharmaceutical industry emphasized the positive results in their advertising to the public. With the advent of the sulfa antibiotics for treatment of infections, scientific interest in vitamin A as "anti-infective" therapy waned. Recent controlled clinical trials of vitamin A from the last 15 y follow a tradition of investigation that began largely in the 1920s.