nach oben

Current Nutrition Reports

Erschienen in:

05.06.2023 | REVIEW

NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health

verfasst von: Gabriela Fabiana Soares Alegre, Glaucia Maria Pastore

Erschienen in: Current Nutrition Reports | Ausgabe 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

NAD+ is a vital molecule that takes part as a redox cofactor in several metabolic reactions besides being used as a substrate in important cellular signaling in regulation pathways for energetic, genotoxic, and infectious stress. In stress conditions, NAD+ biosynthesis and levels decrease as well as the activity of consuming enzymes rises. Dietary precursors can promote NAD+ biosynthesis and increase intracellular levels, being a potential strategy for reversing physiological decline and preventing diseases. In this review, we will show the biochemistry and metabolism of NAD+ precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), the latest findings on their beneficial physiological effects, their interplay with gut microbiota, and the future perspectives for research in nutrition and food science fields.

Recent Findings

NMN and NR demonstrated protect against diabetes, Alzheimer disease, endothelial dysfunction, and inflammation. They also reverse gut dysbiosis and promote beneficial effects at intestinal and extraintestinal levels. NR and NMN have been found in vegetables, meat, and milk, and microorganisms in fermented beverages can also produce them.

Summary

NMN and NR can be obtained through the diet either in their free form or as metabolites derivate from the digestion of NAD+. The prospection of NR and NMN to find potential food sources and their dietary contribution in increasing NAD+ levels are still an unexplored field of research. Moreover, it could enable the development of new functional foods and processing strategies to maintain and enhance their physiological benefits, besides the studies of new raw materials for extraction and biotechnological development.

•• Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24(6):795–806. In addition to the anti-aging effect of NMN supplementation in mice preventing age associated gene expression changes and physiological decline, this article showed the first evidence of the natural presence of NMN in food such as fruits, vegetables, and meat.PubMedPubMedCentralCrossRef

Yamaguchi S, Franczyk MP, Chondronikola M, Qi N, Gunawardana SC, Stromsdorfer KL, et al. Adipose tissue NAD⁺ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice. Proc Natl Acad Sci. 2019;116(47):23822–8.PubMedPubMedCentralCrossRef

Abdellatif M, Sedej S, Kroemer G. NAD⁺ Metabolism in cardiac health, aging, and disease. circulation. 2021;144(22):1795–817.

Lautrup S, Sinclair DA, Mattson MP, Fang EF. NAD+ in brain aging and neurodegenerative disorders. Cell Metab. 2019;30(4):630–55.PubMedPubMedCentralCrossRef

Huang Q, Sun M, Li M, Zhang D, Han F, Wu JC, et al. Combination of NAD+ and NADPH offers greater neuroprotection in ischemic stroke models by relieving metabolic stress. Mol Neurobiol. 2018;55(7):6063–75.PubMedCrossRef

Saville KM, Clark J, Wilk A, Rogers GD, Andrews JF, Koczor CA, et al. NAD+-mediated regulation of mammalian base excision repair. DNA Repair (Amst). 2020;93:102930.PubMedCrossRef

Berger F, Ramírez-Hernández MH, Ziegler M. The new life of a centenarian: signalling functions of NAD(P). Trends Biochem Sci. 2004;29(3):111–8.PubMedCrossRef

Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5(1).

Ummarino S, Hausman C, Gaggi G, Rinaldi L, Bassal MA, Zhang Y, et al. NAD modulates dna methylation and cell differentiation. Cells. 2021;10(11):2986.PubMedPubMedCentralCrossRef

10.

Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (80-). 2016;352(6292):1436–43.

11.

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

12.

Seyedsadjadi N, Berg J, Bilgin AA, Braidy N, Salonikas C, Grant R. High protein intake is associated with low plasma NAD+ levels in a healthy human cohort. PLoS One. 2018;13(8).

13.

Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528–36.PubMedPubMedCentralCrossRef

14.

Johnson S, Imai S. NAD+ biosynthesis, aging, and disease [version 1; peer review: 2 approved]. F1000Research [Internet]. 2018;7(132). Available from: http://openr.es/a4e.

15.

Imai S ichiro, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464–71.

16.

Heer CD, Sanderson DJ, Voth LS, Alhammad YMO, Schmidt MS, Trammell SAJ, et al. Coronavirus infection and PARP expression dysregulate the NAD metabolome: an actionable component of innate immunity. J Biol Chem. 2020;295(52):17986–96.PubMedCrossRef

17.

Huizenga R. Dramatic clinical improvement in nine consecutive acutely Ill elderly COVID-19 patients treated with a nicotinamide mononucleotide cocktail: a case series. SSRN Electron J [Internet]. 2020; Available from: https://ssrn.com/abstract=3677428.

18.

Trammell SAJ, Weidemann BJ, Chadda A, Yorek MS, Holmes A, Coppey LJ, et al. Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice. Sci Rep. 2016;6(1).

19.

Hu L, Guo Y, Song L, Wen H, Sun N, Wang Y, et al. Nicotinamide riboside promotes Mfn2-mediated mitochondrial fusion in diabetic hearts through the SIRT1-PGC1α-PPARα pathway. Free Radic Biol Med. 2022;1(183):75–88.CrossRef

20.

Caton PW, Kieswich J, Yaqoob MM, Holness MJ, Sugden MC. Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function. Diabetologia [Internet]. 2011;54(12):3083–92. Available from: https://doi.org/10.1007/s00125-011-2288-0.

21.

Gariani K, Menzies KJ, Ryu D, Wegner CJ, Wang X, Ropelle ER, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology [Internet]. 2016;63(4):1190–204. Available from: https://doi.org/10.1002/hep.28245.

22.

Wang X, Hu X, Yang Y, Takata T, Sakurai T. Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res. 2016;1643:1–9.PubMedCrossRef

23.

Yao Z, Yang W, Gao Z, Jia P. Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neurosci Lett. 2017;647:133–40.PubMedCrossRef

24.

Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E, et al. NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci [Internet]. 2018;115(8):E1876 LP–E1885. Available from: http://www.pnas.org/content/115/8/E1876.abstract.

25.

Ito S, Gotow T, Suetake I, Nagai K. Protective effects of nicotinamide mononucleotide against oxidative stress-induced PC12 cell death via mitochondrial enhancement. PharmaNutrition. 2020;1(11):100175.CrossRef

26.

Chandrasekaran K, Choi J, Arvas MI, Salimian M, Singh S, Xu S, et al. Nicotinamide mononucleotide administration prevents experimental diabetes-induced cognitive impairment and loss of hippocampal neurons. Int J Mol Sci. 2020;21(11).

27.

Gong B, Pan Y, Vempati P, Zhao W, Knable L, Ho L, et al. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol Aging. 2013;34(6):1581–8.PubMedPubMedCentralCrossRef

28.

Guan Y, Wang S-R, Huang X-Z, Xie Q, Xu Y-Y, Shang D, et al. Nicotinamide mononucleotide, an NAD⁺precursor, rescues age-associated susceptibility to AKI in a sirtuin 1–dependent manner. J Am Soc Nephrol [Internet]. 2017;28(8):2337 LP – 2352. Available from: http://jasn.asnjournals.org/content/28/8/2337.abstract.

29.

Elhassan YS, Kluckova K, Fletcher RS, Schmidt MS, Garten A, Doig CL, et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Rep. 2019;28(7):1717–1728.e6.PubMedPubMedCentralCrossRef

30.

Traba J, Kwarteng-Siaw M, Okoli TC, Li J, Huffstutler RD, Bray A, et al. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest. 2015;125(12):4592–600.PubMedPubMedCentralCrossRef

31.

Liu J, Zong Z, Zhang W, Chen Y, Wang X, Shen J, et al. Nicotinamide mononucleotide alleviates lps-induced inflammation and oxidative stress via decreasing COX-2 expression in macrophages. Front Mol Biosci. 2021;6:8.

32.

de Picciotto NE, Gano LB, Johnson LC, Martens CR, Sindler AL, Mills KF, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell [Internet]. 2016;15(3):522–30. Available from: https://doi.org/10.1111/acel.12461.

33.

Yamamoto T, Byun J, Zhai P, Ikeda Y, Oka S, Sadoshima J. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One. 2014;9(6).

34.

Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun [Internet]. 2018;9(1):1286. Available from: https://doi.org/10.1038/s41467-018-03421-7.

35.

Diguet N, Trammell SAJ, Tannous C, Deloux R, Piquereau J, Mougenot N, et al. Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy. Circulation [Internet]. 2018;137(21):2256–73. Available from: https://doi.org/10.1161/CIRCULATIONAHA.116.026099.

36.

Amano H, Chaudhury A, Rodriguez-Aguayo C, Lu L, Akhanov V, Catic A, et al. Telomere dysfunction induces sirtuin repression that drives telomere-dependent disease. Cell Metab [Internet]. 2019;29(6):1274–1290.e9. Available from: https://doi.org/10.1016/j.cmet.2019.03.001.

37.

• Niu K-M, Bao T, Gao L, Ru M, Li Y, Jiang L, et al. The impacts of short-term nmn supplementation on serum metabolism, fecal microbiota, and telomere length in pre-aging phase. Front Nutr. 2021;29:8. In addition to changes in the fecal microbiota and serum metabolite composition related to cofactors/vitamin metabolism in pre-aged mice, oral NMN supplementation for 40 days also resulted in an elongation of telomere length in peripheral blood mononuclear cells (PBMC) in both pre-aging mice and humans.

38.

Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science (80-). 2021;372(6547):1224–9.

39.

Conze D, Brenner C, Kruger CL. Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults. Sci Rep [Internet]. 2019;9(1):9772. Available from: https://doi.org/10.1038/s41598-019-46120-z.

40.

Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020;67(2):153–60.PubMedCrossRef

41.

Trammell SAJ, Y. L, Redpath P, Migaud ME, Brenner C. Nicotinamide riboside is a major NAD+ precursor vitamin in cow milk. J Nutr. 2016;146(5):957–63.

42.

Ummarino S, Mozzon M, Zamporlini F, Amici A, Mazzola F, Orsomando G, et al. Simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and nicotinamide adenine dinucleotide in milk by a novel enzyme-coupled assay. Food Chem. 2017;15(221):161–8.CrossRef

43.

Kim L-J, Chalmers TJ, Smith GC, Das A, Poon EWK, Wang J, et al. Nicotinamide mononucleotide (NMN) deamidation by host-microbiome interactions. bioRxiv [Internet]. 2020;2020.09.10.289561. Available from: http://biorxiv.org/content/early/2020/09/11/2020.09.10.289561.abstract.

44.

Shats I, Williams JG, Liu J, Makarov MV, Wu X, Lih FB, et al. Bacteria boost mammalian host nad metabolism by engaging the deamidated biosynthesis pathway. Cell Metab. 2020;31(3):564–579.e7.PubMedPubMedCentralCrossRef

45.

Huang P, Jiang A, Wang X, Zhou Y, Tang W, Ren C, et al. NMN maintains intestinal homeostasis by regulating the gut microbiota. Front Nutr. 2021;29:8.

46.

Huang P, Wang X, Wang S, Wu Z, Zhou Z, Shao G, et al. Treatment of inflammatory bowel disease: potential effect of NMN on intestinal barrier and gut microbiota. Curr Res Food Sci. 2022;5:1403–11.PubMedPubMedCentralCrossRef

47.

• Lapatto HAK, Kuusela M, Heikkinen A, Muniandy M, van der Kolk BW, Gopalakrishnan S, et al. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv. 2023;9(2). It was the first evidence of gut microbiota modulation in humans mediated by NR. This altered gut microbiota composition was associated with changes in the plasma metabolomic profile, which are related to mitochondrial energy metabolism, lipids, and amino acids. In addition, NR supplementation boosted mitochondrial biogenesis and influenced global DNA methylation in a tissue-specific manner.

48.

Fabrizio G, Scarpa ES, Di Girolamo M. State of the art of protein mono-ADP-ribosylation: biological role and therapeutic potential. Front Biosci - Landmark. 2015;20(3):405–30.CrossRef

49.

Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol [Internet]. 2012;13(4):225–38. Available from: https://doi.org/10.1038/nrm3293.

50.

Vyas S, Matic I, Uchima L, Rood J, Zaja R, Hay RT, et al. Family-wide analysis of poly(ADP-ribose) polymerase activity. Nat Commun. 2014;5(1).

51.

Herceg Z, Wang ZQ. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res - Fundam Mol Mech Mutagen. 2001;477(1–2):97–110.CrossRef

52.

Pittelli M, Felici R, Pitozzi V, Giovannelli L, Bigagli E, Cialdai F, et al. Pharmacological effects of exogenous NAD on mitochondrial bioenergetics, DNA repair, and apoptosis. Mol Pharmacol. 2011;80(6):1136–46.PubMedCrossRef

53.

Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA. NAD+ depletion is necessary and sufficient forpoly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci. 2010;30(8):2967–78.PubMedPubMedCentralCrossRef

54.

Fehr AR, Singh SA, Kerr CM, Mukai S, Higashi H, Aikawa M. The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions. Genes Dev. 2020;34(5–6):341–59.PubMedPubMedCentralCrossRef

55.

Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a preiss-handler independent route to NAD+ in fungi and humans. Cell. 2004;117(4):495–502.PubMedCrossRef

56.

Gazzaniga F, Stebbins R, Chang SZ, McPeek MA, Brenner C. Microbial NAD metabolism: lessons from comparative genomics. Microbiol Mol Biol Rev. 2009;73(3):529–41.PubMedPubMedCentralCrossRef

57.

Rongvaux A, Andris F, Van Gool F, Leo O. Reconstructing eukaryotic NAD metabolism. BioEssays [Internet]. 2003;25(7):683–90. Available from: https://doi.org/10.1002/bies.10297.

58.

Zrenner R, Ashihara H. Nucleotide Metabolism. In: Plant Metabolism and Biotechnology. Chichester, UK: John Wiley & Sons, Ltd; 2011.

59.

Giroud-Gerbetant J, Joffraud M, Giner MP, Cercillieux A, Bartova S, Makarov MV, et al. A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. Mol Metab. 2019;30:192–202.PubMedPubMedCentralCrossRef

60.

Yang Y, Zhang N, Zhang G, Sauve AA. NRH salvage and conversion to NAD+ requires NRH kinase activity by adenosine kinase. Nat Metab. 2020;2(4):364–79.PubMedPubMedCentralCrossRef

61.

Liu Y, Luo C, Li T, Zhang W, Zong Z, Liu X, et al. Reduced nicotinamide mononucleotide (NMNH) potently enhances NAD+ and suppresses glycolysis, the TCA cycle, and cell growth. J Proteome Res [Internet]. 2021;20(5):2596–606. Available from: https://doi.org/10.1021/acs.jproteome.0c01037.

62.

Galeazzi L, Bocci P, Amici A, Brunetti L, Ruggieri S, Romine M, et al. Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine nucleotide cycle reveals a novel broadly conserved amidohydrolase family. J Biol Chem. 2011;286(46):40365–75.PubMedPubMedCentralCrossRef

63.

Trammell SAJ, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7(1).

64.

Yaku K, Palikhe S, Izumi H, Yoshida T, Hikosaka K, Hayat F, et al. BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities. Nat Commun. 2021;12(1):6767.PubMedPubMedCentralCrossRef

65.

Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr [Internet]. 2008;28(1):115–30. Available from: https://doi.org/10.1146/annurev.nutr.28.061807.155443.

66.

Gakière B, Hao J, de Bont L, Pétriacq P, Nunes-Nesi A, Fernie AR. NAD+ biosynthesis and signaling in plants. CRC Crit Rev Plant Sci [Internet]. 2018;37(4):259–307. Available from: https://doi.org/10.1080/07352689.2018.1505591.

67.

Hashida S, Takahashi H, Uchimiya H. The role of NAD biosynthesis in plant development and stress responses. Ann Bot [Internet]. 2009;103(6):819–24. Available from: https://doi.org/10.1093/aob/mcp019.

68.

Smith EN, Schwarzländer M, Ratcliffe RG, Kruger NJ. Shining a light on NAD- and NADP-based metabolism in plants. Trends Plant Sci. 2021;26(10):1072–86.PubMedCrossRef

69.

Decros G, Beauvoit B, Colombié S, Cabasson C, Bernillon S, Arrivault S, et al. Regulation of pyridine nucleotide metabolism during tomato fruit development through transcript and protein profiling. Front Plant Sci [Internet]. 2019;10:1201. Available from: https://www.frontiersin.org/article/10.3389/fpls.2019.01201.

70.

Ashihara H, Stasolla C, Yin Y, Loukanina N, Thorpe TA. De novo and salvage biosynthetic pathways of pyridine nucleotides and nicotinic acid conjugates in cultured plant cells. Plant Sci [Internet]. 2005;169(1):107–14. Available from: https://www.sciencedirect.com/science/article/pii/S0168945205000828.

71.

Katahira R, Ashihara H. Profiles of the biosynthesis and metabolism of pyridine nucleotides in potatoes (Solanum tuberosum L.). Planta [Internet]. 2009;231(1):35–45. Available from: https://doi.org/10.1007/s00425-009-1023-2.

72.

Di Martino C, Pallotta ML. Mitochondria-localized NAD biosynthesis by nicotinamide mononucleotide adenylyltransferase in Jerusalem artichoke (Helianthus tuberosus L.) heterotrophic tissues. Planta [Internet]. 2011;234(4):657. Available from: https://doi.org/10.1007/s00425-011-1428-6.

73.

Medda R, Padiglia A, Lorrai A, Murgia B, Agrò AF, Castagnola M, et al. Purification and properties of a nucleotide pyrophosphatase from lentil seedlings. J Protein Chem [Internet]. 2000;19(3):209–14. Available from: https://doi.org/10.1023/A:1007007803996.

74.

Spanò D, Pintus F, Pes R, Medda R, Floris G. Purification and characterisation of a soluble nucleotide pyrophosphatase/phosphodiesterase from prickly pear (Opuntia ficus indica) fruits. Food Res Int. 2011;44(7):2264–70.CrossRef

75.

Cantó C, Menzies KJ, Auwerx J. NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 2015;22(1):31–53.PubMedPubMedCentralCrossRef

76.

Grozio A, Mills KF, Yoshino J, Bruzzone S, Sociali G, Tokizane K, et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nat Metab [Internet]. 2019;1(1):47–57. Available from: https://doi.org/10.1038/s42255-018-0009-4.

77.

• Garofalo C, Sabbatini R, Zamporlini F, Minazzato G, Ferrocino I, Aquilanti L, et al. Exploratory study on the occurrence and dynamics of yeast-mediated nicotinamide riboside production in craft beers. LWT. 2021;1(147): 111605. In this article, the authors demonstrated the production of NR and NMN in craft beers using yeast-mediated fermentation, and the role of hop in enhancing NR levels during the process. This finding is of great interest to the fields of biotechnology and food science and technology, as it highlights the potential for utilizing fermentation processes to produce NAD+ precursors.CrossRef

78.

Sugiyama K, Iijima K, Yoshino M, Dohra H, Tokimoto Y, Nishikawa K, et al. Nicotinamide mononucleotide production by fructophilic lactic acid bacteria. Sci Rep [Internet]. 2021;11(1):7662. Available from: https://doi.org/10.1038/s41598-021-87361-1.

79.

Xu R, Yuan Z, Lijuan Y, Li L, Li D, Lv C. Inhibition of NAMPT decreases cell growth and enhances susceptibility to oxidative stress. Oncol Rep. 2017;38(3):1767–73.PubMedCrossRef

80.

Grozio A, Sociali G, Sturla L, Caffa I, Soncini D, Salis A, et al. CD73 Protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated Tumor Cells. J Biol Chem. 2013;288(36).

81.

Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S, et al. NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol [Internet]. 2019;21(3):397–407. Available from: https://doi.org/10.1038/s41556-019-0287-4.

82.

Cros C, Cannelle H, Laganier L, Grozio A, Canault M. Safety evaluation after acute and sub-chronic oral administration of high purity nicotinamide mononucleotide (NMN-C®) in Sprague-Dawley rats. Food Chem Toxicol. 2021;1(150):112060.CrossRef

83.

Liu L, Su X, Quinn WJ, Hui S, Krukenberg K, Frederick DW, et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 2018;27(5):1067–1080.e5.PubMedPubMedCentralCrossRef

84.

Okabe K, Yaku K, Uchida Y, Fukamizu Y, Sato T, Sakurai T, et al. Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood nicotinamide adenine dinucleotide levels in healthy subjects. Front Nutr. 2022;11:9.

85.

Huang H. A multicentre, randomised, double blind, parallel design, placebo controlled study to evaluate the efficacy and safety of uthever (NMN supplement), an orally administered supplementation in middle aged and older adults. Front Aging. 2022;5:3.

86.

Nikiforov A, Dölle C, Niere M, Ziegler M. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J Biol Chem. 2011;286(24):21767–78.PubMedPubMedCentralCrossRef

87.

Capuzzi DM, Morgan JM, Brusco OA, Intenzo CM. Niacin dosing: relationship to benefits and adverse effects. Curr Atheroscler Rep [Internet]. 2000;2(1):64–71. Available from: https://doi.org/10.1007/s11883-000-0096-y.

88.

Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1. J Biol Chem. 2002;277(47):45099–107.PubMedCrossRef

89.

Hwang ES, Song SB. Possible adverse effects of high-dose nicotinamide: mechanisms and safety assessment. Biomolecules. 2020;10(5).

90.

Kawamura T, Mori N, Shibata K. β-Nicotinamide mononucleotide, an anti-aging candidate compound, is retained in the body for longer than nicotinamide in rats. J Nutr Sci Vitaminol (Tokyo). 2016;62(4):272–6.PubMedCrossRef

91.

Imai S ichiro. A possibility of nutriceuticals as an anti-aging intervention: activation of sirtuins by promoting mammalian NAD biosynthesis. Pharmacol Res. 2010;62(1):42–7.

92.

Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr [Internet]. 2021;18(1):54. Available from: https://doi.org/10.1186/s12970-021-00442-4.

93.

Mateuszuk Ł, Campagna R, Kutryb-Zając B, Kuś K, Słominska EM, Smolenski RT, et al. Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside. Biochem Pharmacol. 2020;1(178):114019.CrossRef

94.

Zhang R, Shen Y, Zhou L, Sangwung P, Fujioka H, Zhang L, et al. Short-term administration of nicotinamide mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure. J Mol Cell Cardiol. 2017;112:64–73.PubMedPubMedCentralCrossRef

95.

Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, et al. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838–47.PubMedPubMedCentralCrossRef

96.

McReynolds MR, Chellappa K, Chiles E, Jankowski C, Shen Y, Chen L, et al. NAD+ flux is maintained in aged mice despite lower tissue concentrations. Cell Syst [Internet]. 2021;12(12):1160–1172.e4. Available from: https://www.sciencedirect.com/science/article/pii/S2405471221003380.

97.

Zhu X-H, Lu M, Lee B-Y, Ugurbil K, Chen W. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci. 2015;112(9):2876–81.PubMedPubMedCentralCrossRef

98.

Ramsey KM, Mills KF, Satoh A, Imai SI. Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell. 2008;7(1):78–88.PubMedCrossRef

99.

Camacho-Pereira J, Tarragó MG, Chini CCS, Nin V, Escande C, Warner GM, et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab. 2016;23(6):1127–39.PubMedPubMedCentralCrossRef

100.

Takaso Y, Noda M, Hattori T, Roboon J, Hatano M, Sugimoto H, et al. Deletion of CD38 and supplementation of NAD+ attenuate axon degeneration in a mouse facial nerve axotomy model. Sci Rep. 2020;10(1).

101.

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194.PubMedPubMedCentralCrossRef

102.

Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature [Internet]. 2009;458(7241):1056–60. Available from: https://doi.org/10.1038/nature07813.

103.

St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S, et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell [Internet]. 2006;127(2):397–408. Available from: https://www.sciencedirect.com/science/article/pii/S0092867406012281.

104.

Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130(6):1095–107.PubMedPubMedCentralCrossRef

105.

Mueller AL, McNamara MS, Sinclair DA. Why does COVID-19 disproportionately affect older people? Aging (Albany NY) [Internet]. 2020;12(10):9959–81. Available from: https://doi.org/10.18632/aging.103344.

106.

Omran HM, Almaliki MS. Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: a hypothesis. J Infect Public Health. 2020;13(9):1196–201.PubMedPubMedCentralCrossRef

107.

Zheng M, Schultz MB, Sinclair DA. NAD+ in COVID-19 and viral infections. Trends Immunol. 2022;43(4):283–95.PubMedPubMedCentralCrossRef

108.

Kawahara TLA, Michishita E, Adler AS, Damian M, Berber E, Lin M, et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell. 2009;136(1):62–74.PubMedPubMedCentralCrossRef

109.

Altay O, Arif M, Li X, Yang H, Aydın M, Alkurt G, et al. Combined metabolic activators accelerates recovery in mild-to-moderate COVID-19. Adv Sci. 2021;8(17):2101222.CrossRef

110.

Pietrobon AJ, Andrejew R, Custódio RWA, Oliveira L de M, Scholl JN, Teixeira FME, et al. Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients. Front Immunol. 2022;13.

111.

Haskó G, Cronstein B. Regulation of inflammation by adenosine. Front Immunol. 2013;4.

112.

Haag F, Adriouch S, Braß A, Jung C, Möller S, Scheuplein F, et al. Extracellular NAD and ATP: partners in immune cell modulation. Purinergic Signal. 2007;3(1–2):71.PubMedPubMedCentralCrossRef

113.

Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci [Internet]. 2019;26(1):34. Available from: https://doi.org/10.1186/s12929-019-0527-8.

114.

Fan L, Cacicedo JM, Ido Y. Impaired nicotinamide adenine dinucleotide (NAD+) metabolism in diabetes and diabetic tissues: implications for nicotinamide-related compound treatment. J Diabetes Investig [Internet]. 2020;11(6):1403–19. Available from: https://doi.org/10.1111/jdi.13303.

115.

Uddin GM, Youngson NA, Chowdhury SS, Hagan C, Sinclair DA, Morris MJ. Administration of nicotinamide mononucleotide (NMN) reduces metabolic impairment in male mouse offspring from obese mothers. Cells. 2020;9(4).

116.

Yu J, Laybutt DR, Kim L-J, Quek L-E, Wu LE, Morris MJ, et al. Exercise-induced benefits on glucose handling in a model of diet-induced obesity are reduced by concurrent nicotinamide mononucleotide. Am J Physiol Metab [Internet]. 2021;321(1):E176–89. Available from: https://doi.org/10.1152/ajpendo.00446.2020.

117.

Wu J, Jin Z, Zheng H, Yan L-J. Sources and implications of NADH/NAD(+) redox imbalance in diabetes and its complications. Diabetes Metab Syndr Obes [Internet]. 2016;9:145–53. Available from: https://pubmed.ncbi.nlm.nih.gov/27274295.

118.

Blacher E, Bashiardes S, Shapiro H, Rothschild D, Mor U, Dori-Bachash M, et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature [Internet]. 2019;572(7770):474–80. Available from: https://doi.org/10.1038/s41586-019-1443-5.

119.

Sun L-J, Li J-N, Nie Y-Z. Gut hormones in microbiota-gut-brain cross-talk. Chin Med J (Engl). 2020;133(7):826–33.PubMedCrossRef

120.

Mishra AK, Dubey V, Ghosh AR. Obesity: an overview of possible role(s) of gut hormones, lipid sensing and gut microbiota. Metabolism. 2016;65(1):48–65.PubMedCrossRef

121.

Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55–71.PubMedCrossRef

122.

Yang C, Du Y, Ren D, Yang X, Zhao Y. Gut microbiota-dependent catabolites of tryptophan play a predominant role in the protective effects of turmeric polysaccharides against DSS-induced ulcerative colitis. Food Funct. 2021;12(20):9793–807.PubMedCrossRef

123.

Corral-Jara KF, Nuthikattu S, Rutledge J, Villablanca A, Fong R, Heiss C, et al. Structurally related (−)-epicatechin metabolites and gut microbiota derived metabolites exert genomic modifications via VEGF signaling pathways in brain microvascular endothelial cells under lipotoxic conditions: Integrated multi-omic study. J Proteomics. 2022;263:104603.PubMedCrossRef

124.

Marć MA, Jastrząb R, Mytych J. Does the gut microbial metabolome really matter? The connection between GUT metabolome and neurological disorders. Nutrients. 2022;14(19):3967.PubMedPubMedCentralCrossRef

125.

Liu L, Xie Y, Li G, Zhang T, Sui Y, Zhao Z, et al. Gut microbiota‐derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling. Br J Pharmacol. 2022.

126.

Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015;20:6.

127.

Turroni F, Ventura M, Buttó LF, Duranti S, O’Toole PW, Motherway MO, et al. Molecular dialogue between the human gut microbiota and the host: a Lactobacillus and Bifidobacterium perspective. Cell Mol Life Sci. 2014;71(2):183–203.PubMedCrossRef

128.

Wellman AS, Metukuri MR, Kazgan N, Xu X, Xu Q, Ren NSX, et al. Intestinal epithelial sirtuin 1 regulates intestinal inflammation during aging in mice by altering the intestinal microbiota. gastroenterology. 2017;153(3):772–86.

129.

Zhang Y, Wang X, Zhou M, Kang C, Lang H, Chen M, et al. Crosstalk between gut microbiota and sirtuin-3 in colonic inflammation and tumorigenesis. Exp Mol Med. 2018;50(4):1–11.PubMedPubMedCentralCrossRef

130.

Zhang X, Tian B, Deng Q, Cao J, Ding X, Liu Q, et al. Nicotinamide riboside relieves the severity of experimental necrotizing enterocolitis by regulating endothelial function via eNOS deacetylation. Free Radic Biol Med. 2022;184:218–29.PubMedCrossRef

131.

Lozada-Fernández VV, DeLeon O, Kellogg SL, Saravia FL, Hadiono MA, Atkinson SN, et al. Nicotinamide riboside-conditioned microbiota deflects high-fat diet-induced weight gain in mice. mSystems. 2022;7(1).

132.

Stojanov S, Berlec A, Štrukelj B. The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. microorganisms. 2020;8(11):1715.

133.

Fu X, Liu Z, Zhu C, Mou H, Kong Q. Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit Rev Food Sci Nutr. 2019;59(sup1):S130–52.PubMedCrossRef

134.

Ren Z, Xu Y, Li T, Sun W, Tang Z, Wang Y, et al. NAD+ and its possible role in gut microbiota: Insights on the mechanisms by which gut microbes influence host metabolism. Anim Nutr. 2022;10:360–71.PubMedPubMedCentralCrossRef

135.

Jiang Y, Liu Y, Gao M, Xue M, Wang Z, Liang H. Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression. Food Funct. 2020;378–91.

136.

Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux J-J, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci. 2008;105(43):16731–6.PubMedPubMedCentralCrossRef

137.

Munukka E, Rintala A, Toivonen R, Nylund M, Yang B, Takanen A, et al. Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice. ISME J. 2017;11(7):1667–79.PubMedPubMedCentralCrossRef

138.

Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63(8):1275–83.PubMedCrossRef

139.

Wang W, Chen L, Zhou R, Wang X, Song L, Huang S, et al. Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J Clin Microbiol. 2014;52(2):398–406.PubMedPubMedCentralCrossRef

140.

Kiss T, Balasubramanian P, Valcarcel-Ares MN, Tarantini S, Yabluchanskiy A, Csipo T, et al. Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment. GeroScience [Internet]. 2019;41(5):619–30. Available from: https://doi.org/10.1007/s11357-019-00074-2.

141.

Tarantini S, Valcarcel-Ares MN, Toth P, Yabluchanskiy A, Tucsek Z, Kiss T, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2019;1(24):101192.CrossRef

142.

Bertoldo MJ, Listijono DR, Ho WHJ, Riepsamen AH, Goss DM, Richani D, et al. NAD+ repletion rescues female fertility during reproductive aging. Cell Rep. 2020;30(6):1670–1681.e7.PubMedPubMedCentralCrossRef

143.

Wu K, Li B, Lin Q, Xu W, Zuo W, Li J, et al. Nicotinamide mononucleotide attenuates isoproterenol-induced cardiac fibrosis by regulating oxidative stress and Smad3 acetylation. Life Sci. 2021;1(274):119299.CrossRef

144.

Kiss T, Giles CB, Tarantini S, Yabluchanskiy A, Balasubramanian P, Gautam T, et al. Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects. GeroScience [Internet]. 2019;41(4):419–39. Available from: https://doi.org/10.1007/s11357-019-00095-x.

145.

Kiss T, Nyúl-Tóth Á, Balasubramanian P, Tarantini S, Ahire C, Yabluchanskiy A, et al. Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects. GeroScience [Internet]. 2020;42(2):527–46. Available from: https://doi.org/10.1007/s11357-020-00165-5.

146.

Li D-J, Sun S-J, Fu J-T, Ouyang S-X, Zhao Q-J, Su L, et al. NAD(+)-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin. Theranostics [Internet]. 2021;11(9):4381–402. Available from: https://pubmed.ncbi.nlm.nih.gov/33754067.

147.

Wang Z, Bao X, Hu J, Shen S, Xu G, Wu Y. Nicotinamide riboside enhances endothelial precursor cell function to promote refractory wound healing through mediating the Sirt1/AMPK pathway [Internet]. Front Pharmacol. 2021;12:1081. Available from: https://www.frontiersin.org/article/10.3389/fphar.2021.671563.

148.

Park JM, Han YM, Lee HJ, Park YJ, Hahm KB. Nicotinamide riboside vitamin B3 mitigated C26 adenocarcinoma-induced cancer cachexia. Front Pharmacol [Internet]. 2021;12:665493. Available from: https://pubmed.ncbi.nlm.nih.gov/34262449.

149.

Seldeen KL, Shahini A, Thiyagarajan R, Redae Y, Leiker M, Rajabian N, et al. Short-term nicotinamide riboside treatment improves muscle quality and function in mice and increases cellular energetics and differentiating capacity of myogenic progenitors. Nutrition [Internet]. 2021;87–88:111189. Available from: https://www.sciencedirect.com/science/article/pii/S0899900721000514.

Titel: NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health
verfasst von: Gabriela Fabiana Soares Alegre
Glaucia Maria Pastore
Publikationsdatum: 05.06.2023
Verlag: Springer US
Erschienen in: Current Nutrition Reports / Ausgabe 3/2023
Elektronische ISSN: 2161-3311
DOI: https://doi.org/10.1007/s13668-023-00475-y

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Medizinstudium Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Vorhofflimmern bei Jüngeren gefährlicher als gedacht

06.05.2024 Vorhofflimmern Nachrichten

Immer mehr jüngere Menschen leiden unter Vorhofflimmern. Betroffene unter 65 Jahren haben viele Risikofaktoren und ein signifikant erhöhtes Sterberisiko verglichen mit Gleichaltrigen ohne die Erkrankung.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Bildnachweise

Die Leitlinien für Ärztinnen und Ärzte, Digitale Mammographien links in kraniokaudaler Projektion./© Weigel, S. et al. / all rights reserved Springer Medizin Verlag GmbH, Operation bei Blasenkrebs/© anistidesign / Fotolia, Medizinische Fachangestellte sitzt erschöpft auf der Treppe/© Courtney Haas / peopleimages.com /stock.adobe.com (Symbolbild mit Fotomodell), Mann wird von Ärztin untersucht/© Tashi-Delek, Getty Images, iStock (Symbolbild mit Fotomodellen)

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2023

Maternal n-3 PUFA Intake During Pregnancy and Perinatal Mental Health Problems: A Systematic Review of Recent Evidence

Nutrition in the Management of ADHD: A Review of Recent Research

Dairy Foods: Beneficial Effects of Fermented Products on Cardiometabolic Health

The Influence of Grandparents on Children’s Dietary Health: A Narrative Review

Mitochondrial Damage and Hypertension: Another Dark Side of Sodium Excess