Role of prostaglandin D2 and the autonomic nervous system in niacin-induced flushing.
BACKGROUND
Although niacin often has beneficial effects on the lipoprotein profile, flushing is an untoward effect associated with its use. Aspirin can only reduce the flushing response by 30-40%. Thus, the aim of the present study was to investigate the mechanisms of niacin-induced flushing, with and without aspirin, in normal, healthy individuals.


METHODS
Niacin-induced flushing was evaluated in 30 healthy individuals after oral administration of 1000 mg niacin alone or with 325 mg aspirin. Neurological, autonomic nervous system, and skin blood flow measurements (using laser Doppler on the glabrous and hairy skin of each participant) were made at various times after drug administration. In addition, the systemic release of 9α,11β-prostaglandin (PG) F(2) was determined. Flushing symptoms of redness, warmth, tingling, itching, and intensity were recorded using the modified Flushing ASsessment Tool (FAST).


RESULTS
After aspirin, the mean flushing scores for all symptoms decreased significantly; however, 36-53% of participants still had some degree of symptoms, even though aspirin completely blocked 11β-PGF(2) synthesis. Maximum skin blood flow (MaxSkBF) in both the glabrous and hairy forearm increased significantly after niacin, but decreased significantly after aspirin only in hairy skin. Regression analysis showed that, in glabrous skin, both PGF(2) and parasympathetic activity were significant predictors of MaxSkBF after niacin, contributing 26% and 14%, respectively (total R(2) = 40%).


CONCLUSIONS
The present study indicates, for the first time, that the parasympathetic nervous system, in addition to PGD(2) , may play an important role in niacin-induced flushing. Changing the sympathetic/parasympathetic balance in favor of parasympathetic activation may be a good therapeutic target to reduce niacin-induced flushing.
Division of Endocrinology and Metabolism, Department of Medicine, Strelitz Diabetes Center for Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, VA, USA.
Henri K
HK
Parson
Hadi
H
Harati
Deona
D
Cooper
Aaron I
AI
Vinik
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001341:Autonomic Nervous System / Q000502:physiology*; D005260:Female; D005483:Flushing / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects*; D015230:Prostaglandin D2 / Q000502:physiology*; D012016:Reference Values
D009525:Niacin; D015230:Prostaglandin D2