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Expert Commentary: Niacin Safety

  • B. Greg Brown
    Correspondence
    Address for reprints: B. Greg Brown, MD, PhD, University of Washington, Department of Cardiology, A509 HSB, 1959 Pacific Street, Seattle, Washington 98195.
    Affiliations
    Department of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
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Published:November 29, 2006DOI:https://doi.org/10.1016/j.amjcard.2006.11.019
      Nicotinic acid, or niacin, has been recognized for >50 years as therapy for the vitamin B3 deficiency disorder pellagra and as a cholesterol-lowering agent.
      • Altschul R.
      • Hoffer A.
      • Stephen J.D.
      Influence of nicotinic acid on serum cholesterol in man.
      During its long-term use in the latter capacity, its favorable effects on lipid profile and on cardiovascular risk, as well as its spectrum of side effects, have been well documented. Although niacin has shown no severe toxicities, as documented in clear and well-supported detail in the report by Guyton and Bays
      • Guyton J.R.
      • Bays H.E.
      Safety considerations with niacin therapy.
      in this supplement, its side effects have tended to discourage widespread use. The dominant side effect is cutaneous flushing, with variable severity among patients; in addition, infrequent hepatic toxicity, hyperglycemia, gout, and rare retinal macular edema have been reported. All these effects are niacin dose dependent and fully reversible given timely discontinuation. Much of the lore on niacin stems from studies of the immediate-release (IR) and the very-slow-release preparations.
      • Knopp R.H.
      • Ginsberg J.
      • Albers J.J.
      • Hoff C.
      • Ogilvie J.T.
      • Warnick G.R.
      • Burrows E.
      • Retzlaff B.
      • Poole M.
      Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin.
      Hepatic toxicity and flushing have been favorably affected by recent preparations that attempt to strike a beneficial balance between the duration and the peak levels of plasma drug exposure. During this long period of niacin observation and investigation, we have come to better understand the dosing requirements for its effective use in cardiovascular prevention. When prescribing niacin, physicians can improve outcomes if they (1) use daily doses of no more than about 2 g of prolonged-release niacin, and 4 g of IR niacin, as tolerated; (2) avoid high or prolonged plasma levels; and (3) gradually increase the daily dose over a 1- to 4-month period to reach the target dose. New prescription preparations designed around these principles compare favorably with older preparations.
      • Guyton J.R.
      • Goldberg A.C.
      • Kreisberg R.A.
      • Sprecher D.L.
      • Superko H.R.
      • O’Connor C.M.
      Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia.
      • Knopp R.H.
      • Alagona P.
      • Davidson M.
      • Goldberg A.C.
      • Kafonek S.D.
      • Kashyap M.
      • Sprecher D.
      • Superko H.R.
      • Jenkins S.
      • Marcovina S.
      Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.
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