Top

Published in:

Open Access 01-06-2019 | Nicotinic Acid | Review

NAD⁺ metabolism as a target for metabolic health: have we found the silver bullet?

Authors: Niels J. Connell, Riekelt H. Houtkooper, Patrick Schrauwen

Published in: Diabetologia | Issue 6/2019

Abstract

NAD⁺ has gone in and out of fashion within the scientific community a number of times since its discovery in the early 1900s. Over the last decade, NAD⁺ has emerged as a potential target for combatting metabolic disturbances and the mitochondrial dysfunction that is mediated through sirtuin (SIRT) enzymes. The beneficial metabolic effects of the NAD⁺/SIRT axis have triggered an increased interest in NAD⁺ as an enhancer of energy metabolism. As a result, a myriad of publications have focused on NAD⁺ metabolism, with the majority of the work having been performed using in vitro models, and in vivo work largely consisting of interventions in Caenorhabditis elegans and rodents. Human intervention trials, on the other hand, are scarce. The aim of this review is to provide an overview of the state-of-the-art on influencing NAD⁺ metabolism in humans and to set the stage for what the future of this exciting field may hold.

Available only for authorised users

Frederick DW, Loro E, Liu L et al (2016) Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab 24(2):269–282. https://doi.org/10.1016/j.cmet.2016.07.005 CrossRefPubMedPubMedCentral

Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384–387. https://doi.org/10.1126/science.1104343 CrossRefPubMed

Hesselink MK, Schrauwen-Hinderling V, Schrauwen P (2016) Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus. Nat Rev Endocrinol 12(11):633–645. https://doi.org/10.1038/nrendo.2016.104 CrossRefPubMed

Milne JC, Lambert PD, Schenk S et al (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450(7170):712–716. https://doi.org/10.1038/nature06261 CrossRefPubMedPubMedCentral

Houtkooper RH, Auwerx J (2012) Exploring the therapeutic space around NAD⁺. J Cell Biol 199(2):205–209. https://doi.org/10.1083/jcb.201207019 CrossRefPubMedPubMedCentral

Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13(4):225–238. https://doi.org/10.1038/nrm3293 CrossRefPubMedPubMedCentral

Banks AS, Kon N, Knight C et al (2008) SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab 8(4):333–341. https://doi.org/10.1016/j.cmet.2008.08.014 CrossRefPubMedPubMedCentral

Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH (2008) Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci U S A 105(28):9793–9798. https://doi.org/10.1073/pnas.0802917105 CrossRefPubMedPubMedCentral

Minor RK, Baur JA, Gomes AP et al (2011) SRT1720 improves survival and healthspan of obese mice. Sci Rep 1(1):70. https://doi.org/10.1038/srep00070 CrossRefPubMedPubMedCentral

10.

Smith JJ, Kenney RD, Gagne DJ et al (2009) Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo. BMC Syst Biol 3(1):31. https://doi.org/10.1186/1752-0509-3-31 CrossRefPubMedPubMedCentral

11.

de Ligt M, Bruls YMH, Hansen J et al (2018) Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes. Mol Metab 12:39–47. https://doi.org/10.1016/j.molmet.2018.04.004 CrossRefPubMedPubMedCentral

12.

Timmers S, de Ligt M, Phielix E et al (2016) Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care 39(12):2211–2217. https://doi.org/10.2337/dc16-0499 CrossRefPubMed

13.

Imai S (2010) “Clocks” in the NAD world: NAD as a metabolic oscillator for the regulation of metabolism and aging. Biochim Biophys Acta 1804(8):1584–1590. https://doi.org/10.1016/j.bbapap.2009.10.024 CrossRefPubMed

14.

Jukarainen S, Heinonen S, Ramo JT et al (2016) Obesity is associated with low NAD⁺/SIRT pathway expression in adipose tissue of BMI-discordant monozygotic twins. J Clin Endocrinol Metab 101(1):275–283. https://doi.org/10.1210/jc.2015-3095 CrossRefPubMed

15.

Camacho-Pereira J, Tarrago MG, Chini CCS et al (2016) CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab 23(6):1127–1139. https://doi.org/10.1016/j.cmet.2016.05.006 CrossRefPubMedPubMedCentral

16.

Yoshino J, Mills KF, Yoon MJ, Imai S (2011) Nicotinamide mononucleotide, a key NAD⁺ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab 14(4):528–536. https://doi.org/10.1016/j.cmet.2011.08.014 CrossRefPubMedPubMedCentral

17.

Zhu XH, Lu M, Lee BY, Ugurbil K, Chen W (2015) In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A 112(9):2876–2881. https://doi.org/10.1073/pnas.1417921112 CrossRefPubMedPubMedCentral

18.

Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ (2012) Age-associated changes in oxidative stress and NAD⁺ metabolism in human tissue. PLoS One 7(7):e42357. https://doi.org/10.1371/journal.pone.0042357 CrossRefPubMedPubMedCentral

19.

Mouchiroud L, Houtkooper RH, Auwerx J (2013) NAD⁺ metabolism: a therapeutic target for age-related metabolic disease. Crit Rev Biochem Mol Biol 48(4):397–408. https://doi.org/10.3109/10409238.2013.789479 CrossRefPubMed

20.

Houtkooper RH, Canto C, Wanders RJ, Auwerx J (2010) The secret life of NAD⁺: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31(2):194–223. https://doi.org/10.1210/er.2009-0026 CrossRefPubMed

21.

Canto C, Menzies KJ, Auwerx J (2015) NAD⁺ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab 22(1):31–53. https://doi.org/10.1016/j.cmet.2015.05.023 CrossRefPubMedPubMedCentral

22.

Feige JN, Lagouge M, Canto C et al (2008) Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab 8(5):347–358. https://doi.org/10.1016/j.cmet.2008.08.017 CrossRefPubMed

23.

Ratajczak J, Joffraud M, Trammell SA et al (2016) NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nat Commun 7(1):13103. https://doi.org/10.1038/ncomms13103 CrossRefPubMedPubMedCentral

24.

Schenk S, McCurdy CE, Philp A et al (2011) Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J Clin Invest 121(11):4281–4288. https://doi.org/10.1172/JCI58554 CrossRefPubMedPubMedCentral

25.

Wang RH, Kim HS, Xiao C, Xu X, Gavrilova O, Deng CX (2011) Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Invest 121(11):4477–4490. https://doi.org/10.1172/JCI46243 CrossRefPubMedPubMedCentral

26.

Canto C, Houtkooper RH, Pirinen E et al (2012) The NAD⁺ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab 15(6):838–847. https://doi.org/10.1016/j.cmet.2012.04.022 CrossRefPubMedPubMedCentral

27.

Bai P, Canto C, Oudart H et al (2011) PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab 13(4):461–468. https://doi.org/10.1016/j.cmet.2011.03.004 CrossRefPubMedPubMedCentral

28.

Canto C, Gerhart-Hines Z, Feige JN et al (2009) AMPK regulates energy expenditure by modulating NAD⁺ metabolism and SIRT1 activity. Nature 458(7241):1056–1060. https://doi.org/10.1038/nature07813 CrossRefPubMedPubMedCentral

29.

Revollo JR, Grimm AA, Imai S (2004) The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem 279(49):50754–50763. https://doi.org/10.1074/jbc.M408388200 CrossRefPubMed

30.

Frederick DW, Davis JG, Davila A Jr et al (2015) Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism. J Biol Chem 290(3):1546–1558. https://doi.org/10.1074/jbc.M114.579565 CrossRefPubMed

31.

Costford SR, Brouwers B, Hopf ME et al (2018) Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance. Mol Metab 7:1–11. https://doi.org/10.1016/j.molmet.2017.10.012 CrossRefPubMed

32.

Fulco M, Cen Y, Zhao P et al (2008) Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell 14(5):661–673. https://doi.org/10.1016/j.devcel.2008.02.004 CrossRefPubMedPubMedCentral

33.

Canto C, Jiang LQ, Deshmukh AS et al (2010) Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11(3):213–219. https://doi.org/10.1016/j.cmet.2010.02.006 CrossRefPubMedPubMedCentral

34.

Brandauer J, Vienberg SG, Andersen MA et al (2013) AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle. J Physiol 591(20):5207–5220. https://doi.org/10.1113/jphysiol.2013.259515 CrossRefPubMedPubMedCentral

35.

Ito Y, Yonekura R, Maruta K et al (2003) Tryptophan metabolism was accelerated by exercise in rat. Adv Exp Med Biol 527:531–535CrossRefPubMed

36.

Mills KF, Yoshida S, Stein LR et al (2016) Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab 24(6):795–806. https://doi.org/10.1016/j.cmet.2016.09.013 CrossRefPubMedPubMedCentral

37.

de Picciotto NE, Gano LB, Johnson LC et al (2016) Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15(3):522–530. https://doi.org/10.1111/acel.12461 CrossRefPubMedPubMedCentral

38.

Yang SJ, Choi JM, Kim L et al (2014) Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes. J Nutr Biochem 25(1):66–72. https://doi.org/10.1016/j.jnutbio.2013.09.004 CrossRefPubMed

39.

van de Weijer T, Phielix E, Bilet L et al (2015) Evidence for a direct effect of the NAD⁺ precursor acipimox on muscle mitochondrial function in humans. Diabetes 64(4):1193–1201. https://doi.org/10.2337/db14-0667 CrossRefPubMed

40.

Haffner CD, Becherer JD, Boros EE et al (2015) Discovery, synthesis, and biological evaluation of thiazoloquin(az)olin(on)es as potent CD38 inhibitors. J Med Chem 58(8):3548–3571. https://doi.org/10.1021/jm502009h CrossRefPubMed

41.

Fang Evandro F, Scheibye-Knudsen M, Brace Lear E et al (2014) Defective mitophagy in XPA via PARP-1 hyperactivation and NAD⁺/SIRT1 reduction. Cell 157(4):882–896. https://doi.org/10.1016/j.cell.2014.03.026 CrossRefPubMedPubMedCentral

42.

Pirinen E, Canto C, Jo YS et al (2014) Pharmacological inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab 19(6):1034–1041. https://doi.org/10.1016/j.cmet.2014.04.002 CrossRefPubMedPubMedCentral

43.

Zha S, Li Z, Cao Q, Wang F, Liu F (2018) PARP1 inhibitor (PJ34) improves the function of aging-induced endothelial progenitor cells by preserving intracellular NAD⁺ levels and increasing SIRT1 activity. Stem Cell Res Ther 9(1):224. https://doi.org/10.1186/s13287-018-0961-7 CrossRefPubMedPubMedCentral

44.

Chiang SH, Harrington WW, Luo G et al (2015) Genetic ablation of CD38 protects against western diet-induced exercise intolerance and metabolic inflexibility. PLoS One 10(8):e0134927. https://doi.org/10.1371/journal.pone.0134927 CrossRefPubMedPubMedCentral

45.

Escande C, Nin V, Price NL et al (2013) Flavonoid apigenin is an inhibitor of the NAD⁺ ase CD38: implications for cellular NAD⁺ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes 62(4):1084–1093. https://doi.org/10.2337/db12-1139 CrossRefPubMedPubMedCentral

46.

Tarrago MG, Chini CCS, Kanamori KS et al (2018) A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD⁺ decline. Cell Metab 27(5):1081–1095. e1010. https://doi.org/10.1016/j.cmet.2018.03.016 CrossRefPubMedPubMedCentral

47.

Smith RL, Soeters MR, Wust RCI, Houtkooper RH (2018) Metabolic flexibility as an adaptation to energy resources and requirements in health and disease. Endocr Rev 39(4):489–517. https://doi.org/10.1210/er.2017-00211 CrossRefPubMedPubMedCentral

48.

Costford SR, Bajpeyi S, Pasarica M et al (2010) Skeletal muscle NAMPT is induced by exercise in humans. Am J Phys Endocrinol Metab 298(1):E117–E126. https://doi.org/10.1152/ajpendo.00318.2009 CrossRef

49.

Vargas-Ortiz K, Perez-Vazquez V, Figueroa A, Diaz FJ, Montano-Ascencio PG, Macias-Cervantes MH (2018) Aerobic training but no resistance training increases SIRT3 in skeletal muscle of sedentary obese male adolescents. Eur J Sport Sci 18(2):226–234. https://doi.org/10.1080/17461391.2017.1406007 CrossRefPubMed

50.

Rappou E, Jukarainen S, Rinnankoski-Tuikka R et al (2016) Weight loss is associated with increased NAD⁺/SIRT1 expression but reduced PARP activity in white adipose tissue. J Clin Endocrinol Metab 101(3):1263–1273. https://doi.org/10.1210/jc.2015-3054 CrossRefPubMed

51.

Seyssel K, Alligier M, Meugnier E et al (2014) Regulation of energy metabolism and mitochondrial function in skeletal muscle during lipid overfeeding in healthy men. J Clin Endocrinol Metab 99(7):E1254–E1262. https://doi.org/10.1210/jc.2013-4379 CrossRefPubMed

52.

Mendola G, Casamitjana R, Gomis R (1989) Effect of nicotinamide therapy upon B-cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia 32(3):160–162. https://doi.org/10.1007/BF00265087 CrossRefPubMed

53.

Pozzilli P, Visalli N, Ghirlanda G, Manna R, Andreani D (1989) Nicotinamide increases C-peptide secretion in patients with recent onset type 1 diabetes. Diabet Med 6(7):568–572. https://doi.org/10.1111/j.1464-5491.1989.tb01229.x CrossRefPubMed

54.

Vague P, Picq R, Bernal M, Lassmann-Vague V, Vialettes B (1989) Effect of nicotinamide treatment on the residual insulin secretion in type 1 (insulin-dependent) diabetic patients. Diabetologia 32(5):316–321. https://doi.org/10.1007/BF00265549 CrossRefPubMed

55.

Pozzilli P, Visalli N, Signore A et al (1995) Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study). Diabetologia 38(7):848–852. https://doi.org/10.1007/s001250050362 CrossRefPubMed

56.

Visalli N, Cavallo MG, Signore A et al (1999) A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (the IMDIAB VI). Diabetes Metab Res Rev 15(3):181–185. https://doi.org/10.1002/(SICI)1520-7560(199905/06)15:3<181::AID-DMRR31>3.0.CO;2-H CrossRefPubMed

57.

Stratford MR, Rojas A, Hall DW et al (1992) Pharmacokinetics of nicotinamide and its effect on blood pressure, pulse and body temperature in normal human volunteers. Radiother Oncol 25(1):37–42. https://doi.org/10.1016/0167-8140(92)90193-X CrossRefPubMed

58.

Dragovic J, Kim SH, Brown SL, Kim JH (1995) Nicotinamide pharmacokinetics in patients. Radiother Oncol 36(3):225–228. https://doi.org/10.1016/0167-8140(95)01581-Z CrossRefPubMed

59.

Petley A, Macklin B, Renwick AG, Wilkin TJ (1995) The pharmacokinetics of nicotinamide in humans and rodents. Diabetes 44(2):152–155. https://doi.org/10.2337/diab.44.2.152 CrossRefPubMed

60.

Winter SL, Boyer JL (1973) Hepatic toxicity from large doses of vitamin B3 (nicotinamide). N Engl J Med 289(22):1180–1182. https://doi.org/10.1056/NEJM197311292892208 CrossRefPubMed

61.

Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES (2005) Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 45(2):185–197. https://doi.org/10.1016/j.jacc.2004.10.031 CrossRefPubMed

62.

Poynten AM, Gan SK, Kriketos AD et al (2003) Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content. Metabolism 52(6):699–704. https://doi.org/10.1016/S0026-0495(03)00030-1 CrossRefPubMed

63.

Capuzzi DM, Guyton JR, Morgan JM et al (1998) Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol 82(12):74U–81U. https://doi.org/10.1016/S0002-9149(98)00731-0 CrossRefPubMed

64.

Ranchoff RE, Tomecki KJ (1986) Niacin or niacinamide? Nicotinic acid or nicotinamide? What is the difference? J Am Acad Dermatol 15(1):116–117. https://doi.org/10.1016/S0190-9622(86)80149-9 CrossRefPubMed

65.

Benyo Z, Gille A, Bennett CL, Clausen BE, Offermanns S (2006) Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells. Mol Pharmacol 70(6):1844–1849. https://doi.org/10.1124/mol.106.030833 CrossRefPubMed

66.

Santomauro AT, Boden G, Silva ME et al (1999) Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes 48(9):1836–1841. https://doi.org/10.2337/diabetes.48.9.1836 CrossRefPubMed

67.

Cusi K, Kashyap S, Gastaldelli A, Bajaj M, Cersosimo E (2007) Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with Acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes. Am J Phys Endocrinol Metab 292(6):E1775–E1781. https://doi.org/10.1152/ajpendo.00624.2006 CrossRef

68.

Castro-Marrero J, Cordero MD, Segundo MJ et al (2015) Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal 22(8):679–685. https://doi.org/10.1089/ars.2014.6181 CrossRefPubMedPubMedCentral

69.

Castro-Marrero J, Saez-Francas N, Segundo MJ et al (2016) Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - a randomized, controlled, double-blind trial. Clin Nutr 35(4):826–834. https://doi.org/10.1016/j.clnu.2015.07.010 CrossRefPubMed

70.

Bogan KL, Brenner C (2008) Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr 28(1):115–130. https://doi.org/10.1146/annurev.nutr.28.061807.155443 CrossRefPubMed

71.

Martens CR, Denman BA, Mazzo MR et al (2018) Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD⁺ in healthy middle-aged and older adults. Nat Commun 9(1):1286. https://doi.org/10.1038/s41467-018-03421-7 CrossRefPubMedPubMedCentral

72.

Trammell SA, Schmidt MS, Weidemann BJ et al (2016) Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun 7(1):12948. https://doi.org/10.1038/ncomms12948 CrossRefPubMedPubMedCentral

73.

Airhart SE, Shireman LM, Risler LJ et al (2017) An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD⁺ levels in healthy volunteers. PLoS One 12(12):e0186459. https://doi.org/10.1371/journal.pone.0186459 CrossRefPubMedPubMedCentral

74.

Dellinger RW, Santos SR, Morris M et al (2017) Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD⁺ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis 3(1):17. https://doi.org/10.1038/s41514-017-0016-9 CrossRefPubMedPubMedCentral

75.

Dollerup OL, Christensen B, Svart M et al (2018) A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr 108(2):343–353. https://doi.org/10.1093/ajcn/nqy132 CrossRefPubMed

76.

Zhou CC, Yang X, Hua X et al (2016) Hepatic NAD⁺ deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol 173(15):2352–2368. https://doi.org/10.1111/bph.13513 CrossRefPubMedPubMedCentral

77.

Gariani K, Menzies KJ, Ryu D et al (2016) Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology 63(4):1190–1204. https://doi.org/10.1002/hep.28245 CrossRefPubMed

78.

Fukuwatari T, Shibata K (2013) Nutritional aspect of tryptophan metabolism. Int J Tryptophan Res 6(Suppl 1):3–8. https://doi.org/10.4137/IJTR.S11588 CrossRefPubMedPubMedCentral

79.

Fernstrom JD (2012) Effects and side effects associated with the non-nutritional use of tryptophan by humans. J Nutr 142(12):2236S–2244S. https://doi.org/10.3945/jn.111.157065 CrossRefPubMed

80.

Chen T, Zheng X, Ma X et al (2016) Tryptophan predicts the risk for future type 2 diabetes. PLoS One 11(9):e0162192. https://doi.org/10.1371/journal.pone.0162192 CrossRefPubMedPubMedCentral

81.

Fong PC, Boss DS, Yap TA et al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361(2):123–134. https://doi.org/10.1056/NEJMoa0900212 CrossRefPubMed

82.

McKeage K (2016) Daratumumab: first global approval. Drugs 76(2):275–281. https://doi.org/10.1007/s40265-015-0536-1 CrossRefPubMed

Title: NAD+ metabolism as a target for metabolic health: have we found the silver bullet?
Authors: Niels J. Connell
Riekelt H. Houtkooper
Patrick Schrauwen
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Keywords: Nicotinic Acid
Insulins
Insulins
Published in: Diabetologia / Issue 6/2019
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-019-4831-3

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

NAD⁺ metabolism as a target for metabolic health: have we found the silver bullet?

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2019

Pre-diagnostic plasma enterolactone concentrations are associated with lower mortality among individuals with type 2 diabetes: a case-cohort study in the Danish Diet, Cancer and Health cohort

Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study

Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis

Large enteroviral vaccination studies to prevent type 1 diabetes should be well founded and rely on scientific evidence. Reply to Skog O, Klingel K, Roivainen M et al [letter]

Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study

Apolipoprotein C-III and its defined lipoprotein subspecies in relation to incident diabetes: the Multi-Ethnic Study of Atherosclerosis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page