Niacin-induced "flush" involves release of prostaglandin D ₂ from mast cells and serotonin from platelets: Evidence from human cells in vitro and an animal model

Niacin lowers serum cholesterol, low-density lipoprotein, and triglycerides, and it raises high-density lipoprotein. However, most patients experience cutaneous warmth and vasodilation (flush). Acetylsalicylic acid (ASA) can reduce this flush, presumably by decreasing prostaglandin D₂ (PGD₂) release from macrophages. Here, we show that methylnicotinate induces significant PGD₂ release from human mast cells and serotonin from human platelets. Intradermal injection of methylnicotinate induces rat skin vasodilation and vascular permeability. Niacin increases plasma PGD₂ and serotonin in a rat model of flush. The phenothiazine prochlorperazine, the H₁, serotonin receptor antagonist cyproheptadine, and the specific serotonin receptor-2A antagonist ketanserin inhibit niacin-induced temperature increase by 90% (n = 5, p < 0.05), 90 and 50% (n = 3, p < 0.05), and 85% (n = 6, p = 0.0008), respectively, in this animal model. These results indicate that niacin-induced flush involves both PGD₂ and serotonin, suggesting that drugs other than ASA are required to effectively inhibit niacin-induced flush.