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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Mini-Review Article

N1-Methylnicotinamide: Is it Time to Consider it as a Dietary Supplement for Athletes?

Author(s): Hamid Reza Nejabati*, Mahsa Ghaffari-Novin, Nazila Fathi-Maroufi, Yousef Faridvand, Hans-Christer Holmberg, Ola Hansson, Saba Nikanfar and Mohammad Nouri*

Volume 28, Issue 10, 2022

Published on: 05 April, 2022

Page: [800 - 805] Pages: 6

DOI: 10.2174/1381612828666220211151204

Price: $65

Open Access Journals Promotions 2
Abstract

Exercise is considered to be a “medicine” due to its modulatory roles in metabolic disorders, such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduces serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeogenesis and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1). It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the activity of NNMT in the adipose tissue and acts as an inhibitor of its activity. NNMT-MNAM axis is more activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption of MNAM during training, especially endurance training, could boost exercise capacity and improve performance. Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports medicine.

Keywords: MNAM, exercise, sports medicine, dietary supplement, myokine, vitamin B3.

[1]
Moghetti P, Bacchi E, Brangani C, Donà S, Negri C. Metabolic effects of exerciseSports Endocrinology. Karger Publishers 2016; pp. 44-57.
[2]
Plowman SA, Smith DL. Exercise physiology for health fitness and performance. Lippincott Williams & Wilkins 2013.
[3]
Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 2013; 17(2): 162-84.
[http://dx.doi.org/10.1016/j.cmet.2012.12.012] [PMID: 23395166]
[4]
Mougios V. Exercise biochemistry. Human Kinetics Publishers 2019.
[5]
Tiidus PM, Tupling AR, Houston ME. Biochemistry primer for exercise science. Human Kinetics 2012.
[6]
McArdle WD, Katch FI, Katch VL. Exercise physiology: energy, nutrition, and human performance. LWW 1991.
[7]
Stryer L. Fatty acid metabolism. Biochemistry 1995; 3: 469-93.
[8]
Spiegelman BM. Transcriptional control of energy homeostasis through the PGC1 coactivators. Novartis Found Symp 2007; 286: 3-6.
[http://dx.doi.org/10.1002/9780470985571.ch2]
[9]
Hardie DG, Sakamoto K. AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 2006; 21(1): 48-60.
[http://dx.doi.org/10.1152/physiol.00044.2005] [PMID: 16443822]
[10]
Kvorning T, Kadi F, Schjerling P, et al. The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels. Acta Physiol (Oxf) 2015; 213(3): 676-87.
[http://dx.doi.org/10.1111/apha.12404] [PMID: 25294097]
[11]
Cleasby ME, Reinten TA, Cooney GJ, James DE, Kraegen EW. Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression. Mol Endocrinol 2007; 21(1): 215-28.
[http://dx.doi.org/10.1210/me.2006-0154] [PMID: 17021050]
[12]
Kimball SR, Jefferson LS. Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise. J Biol Chem 2010; 285(38): 29027-32.
[http://dx.doi.org/10.1074/jbc.R110.137208] [PMID: 20576612]
[13]
Champagne CD, Crocker DE, Fowler MA, Houser DS. Fasting physiology of the pinnipeds: the challenges of fasting while maintaining high energy expenditure and nutrient delivery for lactation Comparative physiology of fasting, starvation, and food limitation. Springer 2012; pp. 309-36.
[14]
Secor SM, Carey HV. Integrative physiology of fasting. Compr Physiol 2016; 6(2): 773-825.
[http://dx.doi.org/10.1002/cphy.c150013] [PMID: 27065168]
[15]
Arnould JP, Green JA, Rawlins DR. Fasting metabolism in Antarctic fur seal (Arctocephalus gazella) pups. Comp Biochem Physiol A Mol Integr Physiol 2001; 129(4): 829-41.
[http://dx.doi.org/10.1016/S1095-6433(01)00339-7] [PMID: 11440869]
[16]
Pinheiro EC, Taddei VA, Migliorini RH, Kettelhut IC. Effect of fasting on carbohydrate metabolism in frugivorous bats (Artibeus lituratus and Artibeus jamaicensis). Comp Biochem Physiol B Biochem Mol Biol 2006; 143(3): 279-84.
[http://dx.doi.org/10.1016/j.cbpb.2005.11.013] [PMID: 16455278]
[17]
Cherel Y, Charrassin J-B, Challet E. Energy and protein requirements for molt in the king penguin Aptenodytes patagonicus. Am J Physiol 1994; 266(4 Pt 2): R1182-8.
[PMID: 8184961]
[18]
David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505(7484): 559-63.
[http://dx.doi.org/10.1038/nature12820] [PMID: 24336217]
[19]
Farley SD, Robbins CT. Lactation, hibernation, and mass dynamics of American black bears and grizzly bears. Can J Zool 1995; 73(12): 2216-22.
[http://dx.doi.org/10.1139/z95-262]
[20]
Pernia SD, Hill A, Ortiz CL. Urea turnover during prolonged fasting in the northern elephant seal. Comp Biochem Physiol B 1980; 65(4): 731-4.
[http://dx.doi.org/10.1016/0305-0491(80)90188-1]
[21]
Nordøy ES, Stijfhoorn DE, Råheim A, Blix AS. Water flux and early signs of entrance into phase III of fasting in grey seal pups. Acta Physiol Scand 1992; 144(4): 477-82.
[http://dx.doi.org/10.1111/j.1748-1716.1992.tb09324.x] [PMID: 1318637]
[22]
Robin J-P, Frain M, Sardet C, Groscolas R, Le Maho Y. Protein and lipid utilization during long-term fasting in emperor penguins. Am J Physiol 1988; 254(1 Pt 2): R61-8.
[PMID: 3337270]
[23]
Edenfield KM. Sports supplements: Pearls and pitfalls. Primary Care: Clinics in Office Practice 2020; 47(1): 37-48.
[http://dx.doi.org/10.1016/j.pop.2019.10.002] [PMID: 32014135]
[24]
Marriott BM, Nesheim RO, Rosemont C. Fluid replacement and heat stress: A report of the proceedings of a workshop.
[25]
Maughan RJ, Burke LM, Dvorak J, et al. IOC consensus statement: dietary supplements and the high-performance athlete. Int J Sport Nutr Exerc Metab 2018; 28(2): 104-25.
[http://dx.doi.org/10.1123/ijsnem.2018-0020] [PMID: 29589768]
[26]
Kerksick CM, Wilborn CD, Roberts MD, et al. ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr 2018; 15(1): 38.
[http://dx.doi.org/10.1186/s12970-018-0242-y] [PMID: 30068354]
[27]
Gleeson M, Bishop NC, Oliveira M, Tauler P. Daily probiotic’s (Lactobacillus casei Shirota) reduction of infection incidence in athletes. Int J Sport Nutr Exerc Metab 2011; 21(1): 55-64.
[http://dx.doi.org/10.1123/ijsnem.21.1.55] [PMID: 21411836]
[28]
Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev 2015; (2): : CD006895.
[http://dx.doi.org/10.1002/14651858.CD006895.pub3] [PMID: 25927096]
[29]
Institute of medicine committee on military nutrition R Fluid Replacement and Heat Stress Marriott BM, Stress H. Eds. Washington, DC: National Academies Press (US). 1994.
[30]
Owens DJ, Allison R, Close GL. Vitamin D and the athlete: current perspectives and new challenges. Sports Med 2018; 48(S1): 3-16.
[http://dx.doi.org/10.1007/s40279-017-0841-9] [PMID: 29368183]
[31]
Shuler FD, Wingate MK, Moore GH, Giangarra C. Sports health benefits of vitamin D. Sports Health 2012; 4(6): 496-501.
[http://dx.doi.org/10.1177/1941738112461621] [PMID: 24179588]
[32]
DellaValle DM, Haas JD. Iron supplementation improves energetic efficiency in iron-depleted female rowers. Med Sci Sports Exerc 2014; 46(6): 1204-15.
[http://dx.doi.org/10.1249/MSS.0000000000000208] [PMID: 24195864]
[33]
Rubeor A, Goojha C, Manning J, White J. Does iron supplementation improve performance in iron-deficient nonanemic athletes? Sports Health 2018; 10(5): 400-5.
[http://dx.doi.org/10.1177/1941738118777488] [PMID: 29792778]
[34]
Burke LM. Caffeine and sports performance. Appl Physiol Nutr Metab 2008; 33(6): 1319-34.
[http://dx.doi.org/10.1139/H08-130] [PMID: 19088794]
[35]
Ganio MS, Klau JF, Casa DJ, Armstrong LE, Maresh CM. Effect of caffeine on sport-specific endurance performance: a systematic review. J Strength Cond Res 2009; 23(1): 315-24.
[http://dx.doi.org/10.1519/JSC.0b013e31818b979a] [PMID: 19077738]
[36]
Talanian JL, Spriet LL. Low and moderate doses of caffeine late in exercise improve performance in trained cyclists. Appl Physiol Nutr Metab 2016; 41(8): 850-5.
[http://dx.doi.org/10.1139/apnm-2016-0053] [PMID: 27426699]
[37]
Wellington BM, Leveritt MD, Kelly VG. The effect of caffeine on repeat-high-intensity-effort performance in rugby league players. Int J Sports Physiol Perform 2017; 12(2): 206-10.
[http://dx.doi.org/10.1123/ijspp.2015-0689] [PMID: 27197120]
[38]
Wiles JD, Coleman D, Tegerdine M, Swaine IL. The effects of caffeine ingestion on performance time, speed and power during a laboratory-based 1 km cycling time-trial. J Sports Sci 2006; 24(11): 1165-71.
[http://dx.doi.org/10.1080/02640410500457687] [PMID: 17035165]
[39]
Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab 2003; 13(2): 198-226.
[http://dx.doi.org/10.1123/ijsnem.13.2.198] [PMID: 12945830]
[40]
Buford TW, Kreider RB, Stout JR, et al. International society of sports nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr 2007; 4(1): 6.
[http://dx.doi.org/10.1186/1550-2783-4-6] [PMID: 17908288]
[41]
Lanhers C, Pereira B, Naughton G, Trousselard M, Lesage F-X, Dutheil F. Creatine supplementation and upper limb strength performance: A systematic review and meta-analysis. Sports Med 2017; 47(1): 163-73.
[http://dx.doi.org/10.1007/s40279-016-0571-4] [PMID: 27328852]
[42]
Peeling P, Binnie MJ, Goods PSR, Sim M, Burke LM. Evidence-based supplements for the enhancement of athletic performance. Int J Sport Nutr Exerc Metab 2018; 28(2): 178-87.
[http://dx.doi.org/10.1123/ijsnem.2017-0343] [PMID: 29465269]
[43]
Chung W, Shaw G, Anderson ME, et al. Effect of 10 week beta-alanine supplementation on competition and training performance in elite swimmers. Nutrients 2012; 4(10): 1441-53.
[http://dx.doi.org/10.3390/nu4101441] [PMID: 23201763]
[44]
Lancha Junior AH, Painelli VS, Saunders B, Artioli GG. Nutritional strategies to modulate intracellular and extracellular buffering capacity during high-intensity exercise. Sports Med 2015; 45(S1): S71-81.
[http://dx.doi.org/10.1007/s40279-015-0397-5] [PMID: 26553493]
[45]
Bailey SJ, Varnham RL, DiMenna FJ, Breese BC, Wylie LJ, Jones AM. Inorganic nitrate supplementation improves muscle oxygenation, O₂ uptake kinetics, and exercise tolerance at high but not low pedal rates. J Appl Physiol 2015; 118(11): 1396-405.
[http://dx.doi.org/10.1152/japplphysiol.01141.2014] [PMID: 25858494]
[46]
Thompson C, Wylie LJ, Fulford J, et al. Dietary nitrate improves sprint performance and cognitive function during prolonged intermittent exercise. Eur J Appl Physiol 2015; 115(9): 1825-34.
[http://dx.doi.org/10.1007/s00421-015-3166-0] [PMID: 25846114]
[47]
Wylie LJ, Bailey SJ, Kelly J, Blackwell JR, Vanhatalo A, Jones AM. Influence of beetroot juice supplementation on intermittent exercise performance. Eur J Appl Physiol 2016; 116(2): 415-25.
[http://dx.doi.org/10.1007/s00421-015-3296-4] [PMID: 26614506]
[48]
Wylie LJ, Ortiz de Zevallos J, Isidore T, et al. Dose-dependent effects of dietary nitrate on the oxygen cost of moderate-intensity exercise: Acute vs. chronic supplementation. Nitric oxide. Biology and Chemistry 2016; 57: 30-9.
[49]
Cantoni G. Methylation of nicotinamide with a soluble enzyme system from rat liver. Waberly Press 1951.
[http://dx.doi.org/10.1016/S0021-9258(18)56110-X]
[50]
Cantoni G. The nature of the active methyl donor formed enzymatically from l-methionine and adenosinetriphosphate1, 2. J Am Chem Soc 1952; 74(11): 2942-3.
[http://dx.doi.org/10.1021/ja01131a519]
[51]
Nejabati HR, Mihanfar A, Pezeshkian M, et al. N1-methylnicotinamide (MNAM) as a guardian of cardiovascular system. J Cell Physiol 2018; 233(10): 6386-94.
[http://dx.doi.org/10.1002/jcp.26636] [PMID: 29741779]
[52]
Nejabati HR, Samadi N, Roshangar L, Nouri M. N1-methylnicotinamide as a possible modulator of cardiovascular risk markers in polycystic ovary syndrome. Life Sci 2019; 235: 116843.
[http://dx.doi.org/10.1016/j.lfs.2019.116843] [PMID: 31494172]
[53]
Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends Endocrinol Metab 2017; 28(5): 340-53.
[http://dx.doi.org/10.1016/j.tem.2017.02.004] [PMID: 28291578]
[54]
Aksoy S, Szumlanski CL, Weinshilboum RM. Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. J Biol Chem 1994; 269(20): 14835-40.
[http://dx.doi.org/10.1016/S0021-9258(17)36700-5] [PMID: 8182091]
[55]
Hong S, Moreno-Navarrete JM, Wei X, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med 2015; 21(8): 887-94.
[http://dx.doi.org/10.1038/nm.3882] [PMID: 26168293]
[56]
Peng L, Yuan Z, Li Y, et al. Ubiquitinated sirtuin 1 (SIRT1) function is modulated during DNA damage-induced cell death and survival. J Biol Chem 2015; 290(14): 8904-12.
[http://dx.doi.org/10.1074/jbc.M114.612796] [PMID: 25670865]
[57]
Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature 2014; 508(7495): 258-62.
[http://dx.doi.org/10.1038/nature13198] [PMID: 24717514]
[58]
Kannt A, Pfenninger A, Teichert L, et al. Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance. Diabetologia 2015; 58(4): 799-808.
[http://dx.doi.org/10.1007/s00125-014-3490-7] [PMID: 25596852]
[59]
Liu M, Li L, Chu J, et al. Serum N 1-methylnicotinamide is associated with obesity and diabetes in Chinese. J Clin Endocrinol Metab 2015; 100(8): 3112-7.
[http://dx.doi.org/10.1210/jc.2015-1732] [PMID: 26066674]
[60]
Riederer M, Erwa W, Zimmermann R, Frank S, Zechner R. Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteine. Atherosclerosis 2009; 204(2): 412-7.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.09.015] [PMID: 18996527]
[61]
Jell J, Merali S, Hensen ML, et al. Genetically altered expression of spermidine/spermine N1-acetyltransferase affects fat metabolism in mice via acetyl-CoA. J Biol Chem 2007; 282(11): 8404-13.
[http://dx.doi.org/10.1074/jbc.M610265200] [PMID: 17189273]
[62]
Koponen T, Cerrada-Gimenez M, Pirinen E, et al. The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis. Amino Acids 2012; 42(2-3): 427-40.
[http://dx.doi.org/10.1007/s00726-011-1013-0] [PMID: 21814795]
[63]
Pirinen E, Kuulasmaa T, Pietilä M, et al. Enhanced polyamine catabolism alters homeostatic control of white adipose tissue mass, energy expenditure, and glucose metabolism. Mol Cell Biol 2007; 27(13): 4953-67.
[http://dx.doi.org/10.1128/MCB.02034-06] [PMID: 17485446]
[64]
Li J-H, Qiu L-Q, Zhu X-J, Cai C-X. Influence of exercises using different energy metabolism systems on NNMT expression in different types of skeletal muscle fibers. Sci Sports 2017; 32(1): 27-32.
[http://dx.doi.org/10.1016/j.scispo.2016.06.004]
[65]
Ström K, Morales-Alamo D, Ottosson F, et al. N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism. Sci Rep 2018; 8(1): 3016.
[http://dx.doi.org/10.1038/s41598-018-21099-1] [PMID: 29445118]
[66]
Gall WE, Beebe K, Lawton KA, et al. α-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One 2010; 5(5): e10883.
[http://dx.doi.org/10.1371/journal.pone.0010883] [PMID: 20526369]
[67]
Lord RS, Bralley JA. Clinical applications of urinary organic acids. Part I: Detoxification markers. Altern Med Rev 2008; 13(3): 205-15.
[PMID: 18950247]
[68]
Schmeisser K, Mansfeld J, Kuhlow D, et al. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol 2013; 9(11): 693-700.
[http://dx.doi.org/10.1038/nchembio.1352] [PMID: 24077178]
[69]
Osęka F-G. Application for the approval of 1-methylnicotinamide chloride (1-MNA) as a novel food ingredient for use in the manufacture of food supplements pursuant to eu novel foods regulation (EC) 258/97. 2013.
[70]
Przyborowski K, Wojewoda M, Sitek B, et al. Effects of 1-methylnicotinamide (MNA) on exercise capacity and endothelial response in diabetic mice. PLoS One 2015; 10(6): e0130908.
[http://dx.doi.org/10.1371/journal.pone.0130908] [PMID: 26115505]
[71]
Brown BG, Zhao X-Q, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345(22): 1583-92.
[http://dx.doi.org/10.1056/NEJMoa011090] [PMID: 11757504]
[72]
Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007; 298(3): 299-308.
[http://dx.doi.org/10.1001/jama.298.3.299] [PMID: 17635890]

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