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Pellagra is a disease caused by severe vitamin B3 deficiency. Its manifestations can include sun-sensitive dermatitis, diarrhea and neurological changes, including dementia. These familiar “three Ds” summarize possible effects; they are not a requirement that every affected person show all three. Vitamin B3 supplies precursors of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, so adequate dietary energy alone does not guarantee adequate support for metabolism.^[ref]

In 1915, Joseph Goldberger and G. A. Wheeler tested a restricted, cereal-heavy diet at a Mississippi prison farm. At least six of eleven remaining volunteers developed signs judged to be pellagra within five months; none were observed among the comparison prisoners. The reported menu supplied about 2,952 calories per man per day, making the contrast between calories and dietary composition especially revealing. Prisoners were offered pardons for participation; allocation was not described as randomized.^[ref]

The experiment supported a dietary cause under its conditions. It did not identify the missing molecule chemically: demonstrating that a restricted diet produces a disease and identifying the specific vitamin are different experimental achievements.