Nicotinamide: A cardioprotective form of Vitamin B3
Abstract
Nicotinamide, a form of vitamin B3, has emerged as a potential cardioprotective agent against ischemia-reperfusion (I/R) injury, a critical factor in the pathogenesis of myocardial infarction, heart failure, and other cardiovascular diseases. This compound plays a significant role in energy metabolism, DNA repair, and cell survival by participating in the biosynthesis of NAD+, a coenzyme essential in redox reactions. The underlying mechanism of cardioprotection afforded by nicotinamide involves enhancing NAD+ biosynthesis, which in turn regulates SUR2A to modulate ATP-sensitive K+ (KATP) channels, influences sirtuin activity, and affects poly(ADP-ribose) polymerases (PARPs) activity to conserve NAD+ levels. Additionally, nicotinamide exhibits anti-inflammatory properties, regulates autophagy, and exerts antioxidant effects, collectively contributing to its potential to mitigate the impact of I/R injury on the myocardium. Despite its wide range of therapeutic applications and safety profile, distinctions between nicotinamide and another form of vitamin B3 nicotinic acid (niacin) are crucial, especially regarding their effects on lipid profiles and vascular functions. Unlike niacin, nicotinamide does not affect lipid levels or pose a risk of increasing cardiovascular events, highlighting its safety for clinical use at recommended doses. However, so far, no clinical study of nicotinamide in the context of cardioprotection has been done. Randomized controlled trials are clearly needed to examine nicotinamide's possible role in clinical practice, define optimal dosing strategies, and understand its long-term effects. However, considering the history of nicotinamide use, this is a compound that could be quickly introduced in clinical practice for cardioprotection.
References
Jovanović A. Cardioprotective signalling: Past, present and future. Eur J Pharmacol. 2018;833:314-319.
Freese R, Lysne V. Niacin - a scoping review for Nordic Nutrition Recommendations. Food Nutr Res. 2023;12:67.
Tannous C, Booz GW, Altara R, Muhieddine DH, Mericskay M, Refaat MM, Zouein FA. Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases. Acta Physiol (Oxf). 2021;231:e13551.
Zhang T, Xu L, Guo X, Tao H, Liu Y, Liu X, et al. The potential of herbal drugs to treat heart failure: The roles of Sirt1/AMPK. J Pharm Anal. 2024;14:157-176.
Zapata-Pérez R, Wanders RJA, van Karnebeek CDM, Houtkooper RH. NAD+ homeostasis in human health and disease. EMBO Mol Med. 2021;13:e13943.
Blanco-Vaca F, Rotllan N, Canyelles M, Mauricio D, Escolà-Gil JC, Julve J. NAD+-increasing strategies to improve cardiometabolic health? Front Endocrinol (Lausanne). 2022;12:815565.
Tosti G, Pepe F, Gnagnarella P, Silvestri F, Gaeta A, Queirolo P, Gandini S. The role of nicotinamide as chemo-preventive agent in NMSCs: A systematic review and meta-analysis. Nutrients. 2023;16:100.
Joshi M, Hiremath P, John J, Ranadive N, Nandakumar K, Mudgal J. Modulatory role of vitamins A, B3, C, D, and E on skin health, immunity, microbiome, and diseases. Pharmacol Rep. 2023;75:1096-1114.
Wu W, Yuan S, Tang Y, Meng X, Peng M, Hu Z, Liu W. Effect of exercise and oral niacinamide mononucleotide on improving mitochondrial autophagy in Alzheimer's Disease. Nutrients. 2023;15:2851.
Iqbal T, Nakagawa T. The therapeutic perspective of NAD+ precursors in age-related diseases. Biochem Biophys Res Commun. 2024;702:149590.
Crawford RM, Jovanović S, Budas GR, Davies AM, Lad H, Wenger RH, et al. Chronic mild hypoxia protects heart-derived H9c2 cells against acute hypoxia/reoxygenation by regulating expression of the SUR2A subunit of the ATP-sensitive K+ channel. J Biol Chem. 2003;278:31444-31455.
Du Q, Jovanović S, Sukhodub A, Jovanović A. Infection with AV-SUR2A protects H9C2 cells against metabolic stress: a mechanism of SUR2A-mediated cytoprotection independent from the K(ATP) channel activity. Biochim Biophys Acta. 2010;1803:405-415.
Mahdi H, Jovanović A. SUR2A as a base for cardioprotective therapeutic strategies. Mol Biol Rep. 2022;49:6717-6723.
Sukhodub A, Du Q, Jovanović S, Jovanović A. Nicotinamide-rich diet protects the heart against ischaemia-reperfusion in mice: a crucial role for cardiac SUR2A. Pharmacol Res. 2010;61:564-570.
Sukhodub A, Sudhir R, Du Q, Jovanović S, Reyes S, Jovanović A. Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart. J Cell Mol Med. 2011;15:1703-1712.
Henning RJ, Bourgeois M, Harbison RD. Poly(ADP-ribose) Polymerase (PARP) and PARP inhibitors: Mechanisms of action and role in cardiovascular disorders. Cardiovasc Toxicol. 2018;18:493-506.
Meng Y, Song C, Ren Z, Li X, Yang X, Ai N, et al. Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells. Cell Death Dis. 2021;12:1119.
Li D, Wang X, Huang Q, Li S, Zhou Y, Li Z. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitro. Redox Biol. 2018;15:62-73.
Wang ZK, Chen RR, Li JH, Chen JY, Li W, Niu XL, et al. Puerarin protects against myocardial ischemia/reperfusion injury by inhibiting inflammation and the NLRP3 inflammasome: The role of the SIRT1/NF-κB pathway. Int Immunopharmacol. 2020;89:107086.
Ding X, Zhu C, Wang W, Li M, Ma C, Gao B. SIRT1 is a regulator of autophagy: Implications for the progression and treatment of myocardial ischemia-reperfusion. Pharmacol Res. 2024;199:106957.
Zhang T, Xu L, Guo X, Tao H, Liu Y, Liu X, et al. The potential of herbal drugs to treat heart failure: The roles of Sirt1/AMPK. J Pharm Anal. 2024;14:157-176.
Condori LDM, Vivas CV, Barreto YB, Gomes LF, Alencar AM, Bloise AC. Effects of Hypoxia and Reoxygenation on Metabolic Profiles of Cardiomyocytes. Cell Biochem Biophys. 2024. doi: 10.1007/s12013-024-01249-1. Epub ahead of print. PMID: 38498099.
Gille A, Bodor ET, Ahmed K, Offermanns S. Nicotinic acid: Pharmacological effects and mechanism of action. Ann Rev Pharmacol Toxicol. 2008;48:79-106.
AIM-HIGH Investigators; Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255-2267. Erratum in: N Engl J Med. 2012;367:189.
Nikas IP, Paschou SA, Ryu HS. The role of nicotinamide in cancer chemoprevention and therapy. Biomolecules. 2020;10:477.
Crinò A, Schiaffini R, Manfrini S, Mesturino C, Visalli N, Beretta Anguissola G, et al. A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX). Eur J Endocrinol. 2004;150:719-724.
Maise K, Chong ZZ, Hou J, Shang YC. The vitamin nicotinamide: translating nutrition into clinical care. Molecules. 2009;14:3446-3485.
Niacin-Health Professional Fact Sheet [Internet] [cited 2024 Oct 10]. Available from: https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/.
Hwang ES, Song SB. Possible adverse effects of high-dose Nicotinamide: Mechanisms and safety assessment. Biomolecules. 2020;10:687.
Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659-661.
Cosmetic Ingredient Review Expert Panel. Final report of the safety assessment of niacinamide and niacin. Int J Toxicol. 2005;24 Suppl 5:1-31.
Huber R, Wong A. Nicotinamide: An update and review of safety & differences from niacin. Skin Therapy Lett. 2020;25:7-11.
Kaanders JH, Bussink J, van der Kogel AJ. ARCON: a novel biology-based approach in radiotherapy. Lancet Oncol. 2002;3:728-737.
Duncan KO, Stock EO, Damian DL, Miller SJ. Nicotinamide for high-risk skin cancer patients: An update. J Am Acad Dermatol. 2024;19:S0190-9622(24)02737-3.
Olmos PR, Hodgson MI, Maiz A, Manrique M, De Valdés MD, Foncea R, et al. Nicotinamide protected first-phase insulin response (FPIR) and prevented clinical disease in first-degree relatives of type-1 diabetics. Diabetes Res Clin Pract. 2006;71:320-333.
Crinó A, Schiaffini R, Ciampalini P, Suraci MC, Manfrini S, Visalli N, et al. A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2005;18:749-754.
Overview on tolerable upper intake levels as derived by the Scientific Committee on Food (SCF) and the EFSA Panel on dietetic products, nutrition and allergies (NDA) [Internet] [cited 2024 Oct 10]. Available from: https://www.efsa.europa.eu/sites/default/files/2024-05/ul-summary-report.pdf.
B-3 Nicotinamide 500 mg 100 Vcaps [Internet] [cited 2024 Oct 10]. Available from: https://www.amazon.com/Nicotinamide-500-100-Vegetarian-Capsules/dp/B01M2CA564.
Vitamin B3 Nicotinamide 500mg 180 Capsules (Flush Free Niacin) Niacinamide [Internet] [cited 2024 Oct 10]. Available from: https://www.ebay.co.uk/itm/153088095839.
