The flavonoid luteolin inhibits niacin‐induced flush

Background and purpose: Sustained release niacin effectively lowers serum cholesterol, LDL and triglycerides, while raising HDL. However, 75% of patients experience cutaneous warmth and itching known as flush, leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this flush only by about 30%, presumably through decreasing prostaglandin D 2 (PGD 2 ). We investigated whether niacin‐induced flush in a rat model involves PGD 2 and 5‐HT, and the effect of certain flavonoids. Experimental approach: Three skin temperature measurements from each ear were recorded with an infrared pyrometer for each time point immediately before i.p. injection with either niacin or a flavonoid. The temperature was then measured every 10 min for 60 min. Key results: Niacin (7.5 mg per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally increased ear temperature to 1.9±0.2 o C at 45 min. Quercetin and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45 min prior to niacin, inhibited the niacin effect by 96 and 88%, respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the niacin effect by only 30%. Niacin almost doubled plasma PGD 2 and 5‐HT, but aspirin reduced only PGD 2 by 86%. In contrast, luteolin inhibited both plasma PGD 2 and 5‐HT levels by 100 and 67%, respectively. Conclusions and implications. Niacin‐induced skin temperature increase is associated with PGD 2 and 5‐HT elevations in rats; luteolin may be a better inhibitor of niacin‐induced flush because it blocks the rise in both mediators. British Journal of Pharmacology (2008) 153 , 1382–1387; doi: 10.1038/sj.bjp.0707668 ; published online 28 January 2008