High Dietary Niacin May Increase Prostaglandin Formation but Does Not Increase Tumor Formation in Apc Min/+ Mice

Abstract

High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D2 (PGD2). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD2, niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E2 (PGE2) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8–3.9). PGE2 promotes tumors in the intestines, whereas PGD2 may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc Min/+ mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc Min/+ mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc Min/+ mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.