Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Seeing red: flushing out instigators of niacin-associated skin toxicity
Richard L. Dunbar, Joel M. Gelfand
Richard L. Dunbar, Joel M. Gelfand
Published July 26, 2010
Citation Information: J Clin Invest. 2010;120(8):2651-2655. https://doi.org/10.1172/JCI44098.
View: Text | PDF
Commentary

Seeing red: flushing out instigators of niacin-associated skin toxicity

  • Text
  • PDF
Abstract

The use of niacin to improve plasma lipid levels and reduce risk of myocardial infarction is limited by noxious skin effects that result from stimulation of G protein–coupled receptor 109A (GPR109A) in skin immune cells. Niacin causes vasodilation, manifest as rubor (redness) of the head and neck, providing a visible sign associated with other, more bothersome skin complaints. The working theory is that niacin provokes Langerhans cells to produce prostaglandin D2 (PGD2), stimulating vascular DP1 receptors to cause vasodilation. In this issue of the JCI, Hanson and colleagues raise a serious challenge to this paradigm in showing that the major player in vasodilation is the keratinocyte, which produces PGE2, stimulating EP2/4 receptors, shifting the role of the Langerhans/PGD2/DP1 pathway to that of an accomplice. They also show that the antipsoriasis drug monomethyl fumarate, itself a GPR109A agonist, provokes vasodilation through the same cells. These efforts bring us one step closer to solving a key limitation of an important cardioprotective drug and reveal that the skin response to niacin is much more complicated than previously thought.

Authors

Richard L. Dunbar, Joel M. Gelfand

×

Figure 1

Overlap of clinical effects of niacin and fumarates.

Options: View larger image (or click on image) Download as PowerPoint
Overlap of clinical effects of niacin and fumarates.
This Venn diagram d...
This Venn diagram depicts the known similarities and differences between the clinical effects of niacin (nicotinic acid) and fumarates (fumaric acid). Notably, both are small carboxylic acids (middle). The carboxyl group is an important feature of GPR109A activation and is shared by the known GPR109A agonists. This receptor is responsible for many of the effects of niacin, and its role in psoriasis is now beginning to attract attention. The overlapping symptoms are probably mediated by stimulation of GPR109A, although this has only been shown for rubor. GI, gastrointestinal.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts