Pellagra Pre-Goldberger: Rupert Blue, Fleming Sandwith, and The "Vitamine Hypothesis".

The conquest of pellagra is commonly associated with one name: Joseph Goldberger of the US Public Health Service, who in 1914 went south, concluded within 4 months that the cause was inadequate diet, spent the rest of his life researching the disease, and--before his death from cancer in 1929--found that brewer's yeast could prevent and treat it at nominal cost. It does Goldberger no discredit to emphasize that between 1907 and 1914 a patchwork coalition of asylum superintendents, practicing physicians, local health officials, and others established for the first time an English-language competence in pellagra, sifted through competing hypotheses, and narrowed the choices down to two: an insect-borne infection hypothesis, championed by the flamboyant European Louis Westerna Sambon, and the new "vitamine hypothesis," proffered by Casimir Funk in early 1912 and articulated later that year by two members of the American Clinical and Climatological Association, Fleming Mant Sandwith and Rupert Blue. Those who resisted Goldberger's inconvenient truth that the root cause was southern poverty drew their arguments largely from the Thompson-McFadden Pellagra Commission, which traces back to Sambon's unfortunate influence on American researchers. Thousands died as a result.

Niacin.

Nicotinic acid and nicotinamide, collectively referred to as niacin, are nutritional precursors of the bioactive molecules nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are important cofactors for most cellular redox reactions, and as such are essential to maintain cellular metabolism and respiration. NAD also serves as a cosubstrate for a large number of ADP-ribosylation enzymes with varied functions. Among the NAD-consuming enzymes identified to date are important genetic and epigenetic regulators, e.g., poly(ADP-ribose)polymerases and sirtuins. There is rapidly growing knowledge of the close connection between dietary niacin intake, NAD(P) availability, and the activity of NAD(P)-dependent epigenetic regulator enzymes. It points to an exciting role of dietary niacin intake as a central regulator of physiological processes, e.g., maintenance of genetic stability, and of epigenetic control mechanisms modulating metabolism and aging. Insight into the role of niacin and various NAD-related diseases ranging from cancer, aging, and metabolic diseases to cardiovascular problems has shifted our view of niacin as a vitamin to current views that explore its potential as a therapeutic.

Nicotinamide: a double edged sword.

Enrichment of diet with Nicotinamide in the West was introduced in the 1940s to prevent the dietary deficiency disorder Pellagra. Pellagra was caused by a particular form of poor vegetarian diet leading to Nicotinamide and Tryptophan deficiency. Arguably Pellagra would have disappeared if dietary measures suggested at the time had been implemented before Nicotinamide was even discovered. Diets may sometimes now be too high in selected pyridines and inadvertently we have exchanged one neurodegenerative disease for another. Parkinson's disease triggered in contrast to Pellagra by a particular form of rich omnivorous diet. Moderation of Nicotinamide intake would be easy to begin with compared with other dietary manipulations as there is no behavior change necessary for individuals. A substantial amount of Nicotinamide can be removed when and where there is too much that has been introduced artificially and inserted where there is too little because meat is unaffordable.

Tryptophan deficiency and picolinic acid: effect on zinc metabolism and clinical manifestations of pellagra.

In five experiments, rats were fed tryptophan (Tryp)-deficient diets with 6-12 micrograms/g zinc (Zn) and, in one experiment, a Zn-deficient diet to test the effect on clinical manifestations, plasma and bone Zn, and ability of picolinic acid (PA) or extra (12 micrograms/g) Zn to compensate. Tryp deficiency caused classical manifestations of pellagra although niacin intake was in excess of normal requirements. At marginal Zn intakes, oral PA caused a significant increase of plasma Zn and, compared with Tryp-adequate controls, Tryp deficiency resulted in lower plasma Zn and plasma:bone Zn ratios. Extra Zn (total 24 micrograms/g) was ineffective. Subcutaneous PA showed a tendency to lower plasma Zn. PA had no effect on clinical manifestations. We conclude that a Tryp metabolite other than nicotinic acid is necessary in the prevention of pellagra. Our hypothesis links this finding with the observed Tryp and PA effect on Zn metabolism.

Should calcium and vitamin D be added to the current enrichment program for cereal-grain products?

Mean dietary intakes of calcium and vitamin D in the US adult population are far below the adequate intake (AI) values recommended by the Food and Nutrition Board, Institute of Medicine of the National Academy of Sciences, and thus substantial segments of the American population have inadequate intakes and elevated risks of osteoporosis and colon cancer. The current Code of Federal Regulations, Title 21, sets standards for the optional addition of moderate amounts of calcium and vitamin D in the enrichment of cereal-grain products, a provision that is essentially not used. We propose that the addition of calcium and vitamin D to currently enriched cereal-grain products be mandated in the United States: this would result in an increase in mean daily dietary intakes in the United States of approximately 400 mg Ca and > or =50 IU (or possibly >200 IU) vitamin D. The benefits would be a significant reduction in the incidences of osteoporosis and colon cancer over time and overall improvement in health, with little risk and a modest financial cost because of the ability to capitalize on existing technology. We suggest a full scientific review of cereal-grain enrichment with calcium and vitamin D.

Synthesis and availability of niacin in roasted coffee.

The coffee bean contains about 1% of trigonelline that is demethylated at temperatures approaching 200 degrees C; it is partially converted into nicotinic acid. This operation is mainly proportional to the severity of dry heat treatment; various other physico-chemical factors also influence the synthesis of niacin during the roasting. The niacin content of weakly roasted commercial coffee is about 10 mg/100 g (American coffee) and it reaches 40 mg in heavy roasted coffees, i.e. Italian coffee. Caffeine-free coffee is lower in niacin than the corresponding raw coffee. The drinking retains 85% of the niacin formed during roasting; it is totally available for the organism and can constitute a noticeable part of the daily supply in niacin.