Vitamin a deficiency and clinical disease: an historical overview.

Vitamin A deficiency has a plethora of clinical manifestations, ranging from xerophthalmia (practically pathognomonic) to disturbances in growth and susceptibility to severe infection (far more protean). Like other classical vitamin deficiency states (scurvy, rickets), some of the signs and symptoms of xerophthalmia were recognized long ago. Reports related to vitamin A and/or manifestations of deficiency might conveniently be divided into "ancient" accounts; eighteenth to nineteenth century clinical descriptions (and their purported etiologic associations); early twentieth century laboratory animal experiments and clinical and epidemiologic observations that identified the existence of this unique nutrient and manifestations of its deficiency; and, most recently, a flowering of carefully conducted clinical studies and field-based randomized trials that documented the full extent and impact of deficiency among the poor of low- and middle-income countries, which in turn changed global health policy.