The Niacin Rebirth: Revisiting the Potential of Nicotinic Acid Therapy for Cardiovascular Disease and Niacin Supplementation for Healthy Aging
Main Article Content
Abstract
The aging of the global population and the associated increase in chronic disease burden requires a paradigm shift in how we care for older adults, one that could benefit from exploring a return to nicotinic acid (NA) therapy for dyslipidemia management and niacin supplementation to support healthy aging. Despite the exceptional benefits NA demonstrated in the Coronary Drug Project for improving dyslipidemia, reducing cardiovascular disease (CVD), and enhancing longevity, it has since experienced a significant decline in usage. Several factors have contributed to this decline, including poor dosing and side effect management by providers; poor outcomes of subsequent trials that combined NA with statin drugs that, in retrospect, have been attributed to poor study design; and, a faulty meta-analysis that concluded NA did not significantly reduce CVD. In addition, recent research reveals statins increase the risk of dementia in older persons, and providers are urged to look for alternative ways to manage dyslipidemia. One alternative is NA. This review explains the factors that led to the decline in NA use, provides an overview of the lipid and non-lipid effects of niacin (as NA or nicotinamide) for treating dyslipidemia and other age-related diseases, describes clinical protocols that promote efficacy and patient compliance, and identifies other factors that may contribute to a revival of niacin usage, or a “Niacin Rebirth.”
Keywords:
niacin formulations, nicotinic acid, niacinamide, cardiovascular disease, glaucoma, chronic kidney disease, stroke, dyslipidemia, healthy aging
Article Details
How to Cite
KEENAN, Joseph.
The Niacin Rebirth: Revisiting the Potential of Nicotinic Acid Therapy for Cardiovascular Disease and Niacin Supplementation for Healthy Aging.
Medical Research Archives, [S.l.], v. 12, n. 7, july 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5521>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i7.5521.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. . Lukasova M, Hanson J, Tunaru S, Offermanns S. Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potentials. Trends Pharmacol Sci. 2011;32(12):700-707. Doi:10.1016/j.tips.2011.08.002
4. . Rahilly-Tierney CR, Spiro A, 3rd, Vokonas P, Gaziano J.M. Relation between high-density lipoprotein cholesterol and survival to age 85 years in men (from the VA Normative Aging Study). Am J Cardiol. 2011;107:1173–1177. Doi: 10.1016/j.amjcard.2010.12.015.
5. . Jellinger PS. American Association of Clinical Endocrinologists/American College of Endocrinology management of dyslipidemia and prevention of cardiovascular disease clinical practice guidelines. Diabetes Spectr. 2018;31(3):234-245. Doi:10.2337/ds18-0009
6. . Sahebkar A, Reiner Ž, Simental-Mendía LE, Ferretti G, Cicero AF. Effect of extended-release niacin on plasma lipoprotein(a) levels: a systematic review and meta-analysis of randomized placebo-controlled trials. Metabolism. 2016;65(11):1664-1678. Doi:10.1016/j.metabol.2016.08.007
7. . Prasanna P, Liu S, Silverman D. Lipophilic statins in subjects with early mild cognitive impairment: associations with conversion to dementia and decline in posterior cingulate brain metabolism in a long-term prospective longitudinal multi-center study. J Nucl Med. 2021;62(supp 1). Abstract 102.
8. . Berge KG, Canner PL. Coronary drug project: experience with niacin. Coronary Drug Project Research Group. Eur J Clin Pharmacol. 1991;40 Suppl 1:S49-S51. Doi.org/10.1007/BF03216290.
9. . Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245-1255. Doi:10.1016/s0735-1097(86)80293-5.
10. . Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment effect of Niaspan, a controlled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial. J Cardiovasc Pharmacol Ther. 1996;1(3):195-202. Doi:10.1177/107424849600100302.
11. . Knopp RH, Alagona P, Davidson M, et al. Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism. 1998;47:1097-1104. Doi:10.1016/s0026-0495(98)90284-0.
12. . Keenan JM, Fontaine PL, Wenz JB, Myers S, Huang ZQ. Niacin revisited: a randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia. Arch Intern Med. 1991;151(7):1424-1432. Doi:10.1001/archinte.151.7.1424.
13. . Keenan JM. Wax-matrix extended-release niacin vs inositol hexanicotinate: a comparison of wax-matrix, extended-release niacin to inositol hexanicotinate "no-flush" niacin in persons with mild to moderate dyslipidemia. J Clin Lipidol. 2013;7(1):14-23. Doi:10.1016/j.jacl.2012.10.004.
14. . Shin D, Kongpakpaisarn K, Bohra C. Trends in the prevalence of metabolic syndrome and its components in the United States 2007-2014. Int J Cardiol. 2018;259:216-219. Doi:10.1016/j.ijcard.2018.01.139.
15. . Canner PL, Furberg CD, McGovern ME. Benefits of niacin in patients with versus without the metabolic syndrome and healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2006;97(4):477-479. Doi:10.1016/j.amjcard.2005.08.070.
16. . Keenan JM, Bae CY, Fontaine PL, et al. Treatment of hypercholesterolemia: comparison of younger versus older patients using wax-matrix sustained-release niacin. J Am Geriatr Soc. 1992;40(1):12-18. Doi:10.1111/j.1532-5415.1992.tb01822.x.
17. . Li Y, Yang G, Yang X, et al. Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway. J Nutr Biochem. 2015;26(11):1338-1347. Doi:10.1016/j.jnutbio.2015.07.006.
18. . Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B-26B. Doi:10.1016/j.amjcard.2008.02.029.
19. . Bale BF, Doneen AL, Vigerust DJ. High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis. Postgrad Med J. 2017;93(1098):215-220. Doi:10.1136/postgradmedj-2016-134279.
20. . Shehadah A, Chen J, Zacharek A, et al. Niaspan treatment induces neuroprotection after stroke. Neurobiol Dis. 2010;40(1):277-283. Doi:10.1016/j.nbd.2010.05.034.
21. . McConnell S, Penberthy WT. Reversing chronic kidney disease with niacin and sodium bicarbonate [press release]. Wichita, KS: Orthomolecular Medicine News Service; October 14, 2021. http://orthomolecular.org/resources/omns/v17n22.shtml. Accessed May 29, 2024.
22. . Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210(2):353-361. Doi:10.1016/j.atherosclerosis.2009.12.023.
23. . Tribble JR, Otmani A, Sun S, et al. Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biol. 2021;43:101988. Doi:10.1016/j.redox.2021.101988.
24. . McReynolds MR, Chellappa K, Baur JA. Age-related NAD+ decline. Exp Gerontol. 2020;134:110888. Doi: 10.1016/j.exger.2020.110888.
25. . AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J. 2011;161(3):471-477.e2. Doi:10.1016/j.ahj.2010.11.017.
26. . Teo KK, Goldstein LB, Chaitman BR, et al. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic syndrome with low HDL/High Triglycerides: Impact on Global Health outcome (AIM-HIGH) trial. Stroke. 2013;44(10):2688-2693. Doi:10.1161/STROKEAHA.113.001529.
27. . Guyton JR, Slee AE, Anderson T, et al. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013;62(17):1580-1584. Doi:10.1016/j.jacc.2013.07.023.
28. . Toth PP, Jones SR, Slee A, et al. Relationship between lipoprotein subfraction cholesterol and residual risk for cardiovascular outcomes: a post hoc analysis of the AIM-HIGH trial. J Clin Lipidol. 2018;12(3):741-747.e11. Doi:10.1016/j.jacl.2018.03.077.
29. . HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-212. Doi:10.1056/NEJMoa1300955.
30. . HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34(17):1279-1291. Doi:10.1093/eurheartj/eht055.
31. . Superko HR, Zhao XQ, Hodis HN, Guyton JR. Niacin and heart disease prevention: engraving its tombstone is a mistake. J Clin Lipidol. 2017;11(6):1309-1317. Doi:10.1016/j.jacl.2017.08.005.
32. . D'Andrea E, Hey SP, Ramirez CL, Kesselheim AS. Assessment of the role of niacin in managing cardiovascular disease outcomes: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(4):e192224. Doi:10.1001/jamanetworkopen.2019.2224.
33. . Saxon DR, Eckel RH. Statin Intolerance: a literature review and management strategies. Prog Cardiovasc Dis. 2016;59(2):153-164. Doi:10.1016/j.pcad.2016.07.009.
34. . Arrieta A, Page TF, Veledar E, Nasir K Economic evaluation of PCSK9 inhibitors in reducing cardiovascular risk from health system and private payer perspectives. PLoS One. 2017;12(1):e0169761. Doi:10.1371/journal.pone.0169761.
35. . Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367(9524):1747-1757. Doi:10.1016/S0140-6736(06)68770-9.
36. . Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69-81. Doi:10.1016/j.jep.2014.09.049
37. . Zhang P, Ma D, Wang Y, et al. Berberine protects liver from ethanol-induced oxidative stress and steatosis in mice. Food Chem Toxicol. 2014;74:225-232. Doi:10.1016/j.fct.2014.10.005
38. . Warowicka A, Nawrot R, Goździcka-Józefiak A. Antiviral activity of berberine. Arch Virol. 2020;165(9):1935-1945. Doi:10.1007/s00705-020-04706-3
39. . Imenshahidi M, Hosseinzadeh H. Berberine and barberry (Berberis vulgaris): A clinical review. Phytother Res. 2019;33(3):504-523. Doi:10.1002/ptr.6252
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