Steenbock (1919) postulated, and later confirmed, that carotenoid from yellow maize could support growth and prevent ocular lesions by physiological conversion to biologically active vitamin A. Since Isler et al. (1947) discovered a cost-effective way to synthesize vitamin A, cure and prevention are also possible through commercially produced, synthetic vitamin A.
Working at the University of Wisconsin, and later at Johns Hopkins University, McCollum pioneered the use of mice and rats in nutrition experiments. His studies of vitamin A deprived rat colonies—and those of others—were often hampered by early deaths from respiratory and diarrheal illnesses before ocular lesions occurred. These early deaths were partly attributable to loss of epithelial integrity in tissues throughout the bodies of VAD animals, and humans as well (Chytil, 1992; Hayes, 1971; Wolbach, 1937). Similar vitamin-A-deficiency-related morbidity and mortality in human populations were not clearly demonstrated, however, until the seminal community-based studies in the 1980s of Sommer and colleagues in Indonesia (summarized in Sommer and West, 1996). These studies clearly linked increased mortality risk in preschool-age children to vitamin A deficiency, a finding later confirmed among child populations in other countries in Asia and Africa where clinical eye signs occur (Beaton et al., 1993).
Where eye signs are not evident, biochemical deficiency—that is, subclinical deficiency—is also believed to contribute to mortality risk. In free-living populations, however, an unequivocal tie to the incidence of infectious morbidity has not been established. Severity once infection is acquired provides the probable link to mortality (Ghana VAST Study Team, 1993; Underwood and Arthur, 1996). This finding implies a role for vitamin A in immunocompetence, a role suggested by an extensive review of interactions of nutrition and infection published in 1968 (Scrimshaw et al., 1968). That review concluded that VAD showed synergism with almost every known infectious disease. Recent basic studies have been unraveling the complex molecular mechanisms by which vitamin A influences the immune system and alters cellular integrity (Ross and Stephensen, 1996). The combined effect on cellular integrity and immunocompetence is believed to contribute to an annual loss of approximately 1.12 to about 3 million lives of children under 5 years of age that otherwise could be salvaged by normalizing vitamin A status (Gillespie and Mason, 1994; Humphrey et al., 1992).
Severe vitamin A deficiency in animal models is clearly linked to other adverse health effects. These include teratogenic-developmental consequences