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Pellagra is generally characterized as a niacin deficiency disease. Symptoms include the four “D's” - dermatitis, diarrhea, dementia, and death. Historically, it has been linked to high maize and low protein diets. The “plague of com” was rampant in southern Europe for centuries and prevalent among U.S. Southerners in the early 1900s. Pellagra's social history is extensive and stands as a classic in the study of vitamins and nutrient deficiencies. However, to date none of this work has focused on the fact that mortality rates for women have been double that of men. This paper calls for a biocultural perspective that investigates the clear difference in both morbidity and mortality rates related to sex and gender. To do so, one must discuss diet and digestion by integrating the role of estrogen during the female lifecycle (from menarche to menopause) with differential gender-based food consumption patterns.