Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.