The mechanism and mitigation of niacin-induced flushing
- Author(s): Kamanna, VS
- Ganji, SH
- Kashyap, ML
- et al.
Published Web Locationhttps://doi.org/10.1111/j.1742-1241.2009.02099.x
Aims: To summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research. Methods and results: This comprehensive review of the mechanism of action of niacin-induced flushing critically evaluates research regarding flushing mitigating formulations and agents. Niacin induces flushing through dermal Langerhans cells where the activation of G protein-coupled receptor 109A (GPR109A) increases arachidonic acid and prostaglandins, such as prostaglandin D2(PGD2) and prostaglandin E2(PGE2), subsequently activating prostaglandin D2receptor (DP1), prostaglandin E2receptor (EP2) and prostaglandin E receptor 4 (EP4) in capillaries and causing cutaneous vasodilatation. Controlling niacin absorption rates, inhibiting prostaglandin production, or blocking DP1, EP2and EP4receptors can inhibit flushing. Niacin extended-release (NER) formulations have reduced flushing incidence, duration and severity relative to crystalline immediate-release niacin with similar lipid efficacy. Non-steroidal anti-inflammatory drugs (NSAIDs), notably aspirin given 30 min before NER at bedtime, further reduce flushing. An antagonist to the DP1receptor (laropiprant) combined with an ER niacin formulation can reduce flushing; however, significant residual flushing occurs with clinically-relevant dosages. Conclusions: Niacin is an attractive option for treating dyslipidemic patients, and tolerance to niacin-induced flushing develops rapidly. Healthcare professionals should particularly address flushing during niacin dose titration. © 2009 Blackwell Publishing Ltd.
Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.