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.