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Niacin: another look at an underutilized lipid-lowering medication

Nature Reviews Endocrinology volume 8, pages 517–528 (2012)Cite this article

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Abstract

Niacin, or water-soluble vitamin B3, when given at pharmacologic doses, is a powerful lipid-altering agent. This drug, which lowers the levels of atherogenic, apolipoprotein-B-containing lipoproteins, is one of few medications that can raise the levels of atheroprotective HDL cholesterol. Niacin also has beneficial effects on other cardiovascular risk factors, including lipoprotein(a), C-reactive protein, platelet-activating factor acetylhydrolase, plasminogen activator inhibitor 1 and fibrinogen. Many clinical trials have confirmed the lipid effects of niacin treatment; however, its effects on cardiovascular outcomes have been called into question owing to the AIM-HIGH trial, which showed no benefit of niacin therapy on cardiovascular endpoints. Furthermore, use of niacin has historically been limited by tolerability issues. In addition to flushing, worsened hyperglycaemia among patients with diabetes mellitus has also been a concern with niacin therapy. This article reviews the utility of niacin including its mechanism of action, clinical trial data regarding cardiovascular outcomes, adverse effect profile and strategies to address these effects and improve compliance.

Key Points

  • Niacin exerts several beneficial lipid-altering effects, including lowering the levels of all atherogenic particles that contain apolipoprotein B, such as LDL, VLDL, IDL and lipoprotein(a), and raising HDL cholesterol levels

  • Niacin should be used in the immediate-release or extended-release forms only, as the sustained-release preparations have been associated with hepatotoxicity

  • Compliance with niacin can be hindered by flushing, gastrointestinal and metabolic effects; of these, flushing is the most common reason for discontinuation of niacin therapy

  • Symptoms of flushing can be alleviated if the possibility of flushing is discussed in advance and advice is given to take a low-fat snack and a nonsteroidal anti-inflammatory drug and to avoid hot or spicy foods at the time of niacin ingestion

  • Use of niacin in patients with diabetes mellitus is often constrained by concern over provoking hyperglycaemia, but evidence would suggest that increases in plasma glucose levels are modest and transient

  • Despite the disappointing results of the AIM-HIGH trial, the relation between niacin therapy and cardiovascular disease endpoints remains yet to be fully defined by larger and more definitive clinical trials

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Figure 1: Mechanisms of action of niacin on lipoprotein parameters.
Figure 2: Approach to initiating and monitoring niacin therapy.

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  1. Robarts Research Institute and Schulich School of Medicine and Dentistry, University of the Western Ontario, 100 Perth Drive, Ontario, N6A 5K8, London, Canada

    Julia C. Creider, Robert A. Hegele & Tisha R. Joy

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  1. Julia C. Creider
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Contributions

J. C. Creider and T. R. Joy researched the data for the article. All authors provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Tisha R. Joy.

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Competing interests

J. C. Creider declares no competing interests. R. A. Hegele declares associations with the following companies: Abbott (consultant; speakers bureau [honoraria]), AstraZeneca (consultant; speakers bureau [honoraria]; grant/research support), Merck (consultant; speakers bureau [honoraria]; grant/research support), Pfizer (grant/research support), Sepracor (consultant; speakers bureau [honoraria]). T. R. Joy declares associations with the following companies: Eli Lilly (speakers bureau [honoraria]), GlaxoSmithKline (speakers bureau [honoraria]), Merck (consultant; speakers bureau [honoraria]), Novo Nordisk (consultant; speakers bureau [honoraria]), Sanofi (consultant), Sepracor (consultant; speakers bureau [honoraria]).

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Creider, J., Hegele, R. & Joy, T. Niacin: another look at an underutilized lipid-lowering medication. Nat Rev Endocrinol 8, 517–528 (2012). https://doi.org/10.1038/nrendo.2012.22

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