Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin‐resistant men

Dollerup, Ole L.; Chubanava, Sabina; Agerholm, Marianne; Søndergård, Stine D.; Altıntaş, Ali; Møller, Andreas B.; Høyer, Kasper F.; Ringgaard, Steffen; Stødkilde‐Jørgensen, Hans; Lavery, Gareth G.; Barrès, Romain; Larsen, Steen; Prats, Clara; Jessen, Niels; Treebak, Jonas T.

doi:10.1113/jp278752

Cited by 145Sirtuins and Resveratrol in MedicineAdipose Tissue and MetabolismMitochondrial Function and Pathology

Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin‐resistant men

Dollerup, Ole L., Chubanava, Sabina, Agerholm, Marianne, Søndergård, Stine D., Altıntaş, Ali, Møller, Andreas B., Høyer, Kasper F., Ringgaard, Steffen +7 more·2020·The Journal of Physiology

DOI 10.1113/jp278752

Open this paper in CoChat — free account

Abstract

Key points: This is the first long‐term human clinical trial to report on effects of nicotinamide riboside (NR) on skeletal muscle mitochondrial function, content and morphology. NR supplementation decreases nicotinamide phosphoribosyltransferase (NAMPT) protein abundance in skeletal muscle. NR supplementation does not affect NAD metabolite concentrations in skeletal muscle. Respiration, distribution and quantity of muscle mitochondria are unaffected by NR. NAMPT in skeletal muscle correlates positively with oxidative phosphorylation Complex I, sirtuin 3 and succinate dehydrogenase. Preclinical evidence suggests that the nicotinamide adenine dinucleotide (NAD + ) precursor nicotinamide riboside (NR) boosts NAD + levels and improves diseases associated with mitochondrial dysfunction. We aimed to determine if dietary NR supplementation in middle‐aged, obese, insulin‐resistant men affects mitochondrial respiration, content and morphology in skeletal muscle. In a randomized, placebo‐controlled clinical trial, 40 participants received 1000 mg NR or placebo twice daily for 12 weeks. Skeletal muscle biopsies were collected before and after the intervention. Mitochondrial respiratory capacity was determined by high‐resolution respirometry on single muscle fibres. Protein abundance and mRNA expression were measured by Western blot and quantitative PCR analyses, respectively, and in a subset of the participants (placebo n = 8; NR n = 8) we quantified mitochondrial fractional area and mitochondrial morphology by laser scanning confocal microscopy. Protein levels of nicotinamide phosphoribosyltransferase (NAMPT), an essential NAD + biosynthetic enzyme in skeletal muscle, decreased by 14% with NR. However, steady‐state NAD + levels as well as gene expression and protein abundance of other NAD + biosynthetic enzymes remained unchanged. Neither respiratory capacity of skeletal muscle mitochondria nor abundance of mitochondrial associated proteins were affected by NR. Moreover, no changes in mitochondrial fractional area or network morphology were observed. Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin‐resistant men. Future studies on the effects of NR on human skeletal muscle may include both sexes and potentially provide comparisons between young and older people.

Integrity signals

Registry

Crossref · 10.1113/jp278752

Cites

77 of 77 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

NR and NMN supplementation exhibited minimal or no efficacy against aging and age-associated diseases in several clinical trials.
“However, NR and NMN supplementation exhibited minimal or no efficacy against aging and age-associated diseases in several clinical trials, suggesting that further investigation of NAD+ metabolism is necessary (20, 21).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD + synthesis via enterohepatic circulation (2025) · cites this paper as [20]
Human studies of exogenous NAD+ precursors such as nicotinamide riboside have not shown improved muscle function nor increased muscle NAD+.
“these approaches have not shown improved muscle function [179], nor have they shown increased muscle NAD+ [180, 181].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [180]

Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Silhouettes: A graphical aid to the interpretation and validation of cluster analysis
Rousseeuw, P. J. (1987) · Journal of Computational and Applied Mathematics · doi:10.1016/0377-0427(87)90125-7 · Cited by 21,392 · see citing works
The Hallmarks of Aging
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Missing Value Estimation Methods for DNA Microarrays
Troyanskaya, O., Cantor, M., Sherlock, G., Brown, P., Hastie, T., Tibshirani, R., Botstein, D., & Altman, R. B. (2001) · Bioinformatics · doi:10.1093/bioinformatics/17.6.520 · Cited by 4,230 · see citing works
Ward’s Hierarchical Agglomerative Clustering Method: Which Algorithms Implement Ward’s Criterion?
Murtagh, F. D., & Legendre, P. (2014) · Journal of Classification · doi:10.1007/s00357-014-9161-z · Cited by 3,939 · see citing works
Estimation of metabolite concentrations from localized in vivo proton NMR spectra
Provencher, S. W. (1993) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910300604 · Cited by 3,659 · see citing works
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300 · see citing works
Fiber Types in Mammalian Skeletal Muscles
Schiaffino, S., & Reggiani, C. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2010 · Cited by 3,022 · see citing works
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321 · see citing works
Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · see citing works
Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340 · see citing works
Ward's Hierarchical Clustering Method: Clustering Criterion and Agglomerative Algorithm
(2011) · doi:10.48550/arxiv.1111.6285 · Cited by 1,313 · see citing works
NAD + repletion improves mitochondrial and stem cell function and enhances life span in mice
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., et al. (2016) · Science · doi:10.1126/science.aaf2693 · Cited by 1,255 · cited 4× · see citing works
“Moreover, in aged mice, NR was demonstrated to rejuvenate muscle stem cells by improving mitochondrial function in a SIRT1-dependent manner (Zhang et al. 2016).”
BackgroundInfluential
The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238 · see citing works
Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects
Larsen, S., Nielsen, J., Hansen, C. N., Nielsen, L. B., Wibrand, F., Stride, N., Schroder, H. D., Boushel, R., Helge, J. W., Dela, F., et al. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.230185 · Cited by 1,180 · cited 2× · see citing works
“CS activity has been previously shown to correlate well with mitochondrial abundance assessed by transmission electron microscopy (TEM) (Larsen et al. 2012).”
BackgroundSelf-citation
NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061 · see citing works
High-Resolution Respirometry: OXPHOS Protocols for Human Cells and Permeabilized Fibers from Small Biopsies of Human Muscle
Pesta, D. H., & Gnaiger, E. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-382-0_3 · Cited by 1,005 · see citing works
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930 · see citing works
Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle
Cantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · see citing works
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865 · see citing works
PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation
Bai, P., Cantó, C., Oudart, H., Brunyánszki, A., Cen, Y., Thomas, C., Yamamoto, H., Huber, A., Kiss, B., Houtkooper, R. H., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.004 · Cited by 837 · see citing works
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · see citing works
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans
Trammell, S. A. J., Schmidt, M. S., Weidemann, B. J., Redpath, P., Jaksch, F., Dellinger, R. W., Li, Z., Abel, E. D., Migaud, M. E., & Brenner, C. (2016) · Nature Communications · doi:10.1038/ncomms12948 · Cited by 697 · see citing works
Bioenergetic role of mitochondrial fusion and fission
Westermann, B. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.02.033 · Cited by 687 · see citing works
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018) · Nature Communications · doi:10.1038/s41467-018-03421-7 · Cited by 588 · see citing works
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes
Liu, L., Su, X., Quinn, W. J., Hui, S., Krukenberg, K., Frederick, D. W., Redpath, P., Zhan, L., Chellappa, K., White, E., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.018 · Cited by 564 · see citing works
Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue
Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., & Guillemin, G. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042357 · Cited by 545 · cited 2× · see citing works
“Progressive deterioration of mitochondrial function (López-Otı́n et al. 2013) and NAD+ metabolism are hallmarks of ageing of mouse (Yoshino et al. 2011; Gomes et al. 2013; Frederick et al. 2016; Zhou et al. 2016) and human tissues (Massudi et al. 2012; Zhu et al. 2015; Zhou et al. 2016).”
Background
Mitochondrial dysfunction and insulin resistance: an update
Montgomery, M. K., & Turner, N. A. (2014) · Endocrine Connections · doi:10.1530/ec-14-0092 · Cited by 530 · see citing works
NAD(+) in aging: molecular mechanisms and translational implications
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.001 · Cited by 501 · see citing works
NAD + metabolism: Bioenergetics, signaling and manipulation for therapy
Yang, Y. J., & Sauve, A. A. (2016) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2016.06.014 · Cited by 488 · see citing works
In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences
Zhu, X.-H., Lu, M., Lee, B.-Y., Ugurbil, K., & Chen, W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417921112 · Cited by 468 · see citing works
Mechanism of Sirtuin Inhibition by Nicotinamide: Altering the NAD+ Cosubstrate Specificity of a Sir2 Enzyme
Avalos‬, J. L., Bever, K. M., & Wolberger, C. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.022 · Cited by 462 · see citing works
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures
Elhassan, Y. S., Kluckova, K., Fletcher, R. S., Schmidt, M. S., Garten, A., Doig, C. L., Cartwright, D. M., Oakey, L., Burley, C. V., Jenkinson, N., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.043 · Cited by 448 · see citing works
Self-citation
Activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenase in muscle from vertebrates and invertebrates
Alp, P. R., Newsholme, E. A., & Zammit, V. A. (1976) · Biochemical Journal · doi:10.1042/bj1540689 · Cited by 404 · see citing works
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201403943 · Cited by 385 · see citing works
Pharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · see citing works
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Ratajczak, J., Joffraud, M., Trammell, S. A. J., Ras, R., Canela, N., Boutant, M., Kulkarni, S. S., Rodrigues, M., Redpath, P., Migaud, M. E., et al. (2016) · Nature Communications · doi:10.1038/ncomms13103 · Cited by 378 · cited 1× · see citing works
“The Journal of Physiology C© 2019 The Physiological Society NAD+ levels in skeletal muscle (Ratajczak et al. 2016; Fletcher et al. 2017).”
Background
Stain-Free technology as a normalization tool in Western blot analysis
Gürtler, A., Kunz, N., Gomolka, M., Hornhardt, S., Friedl, A. A., McDonald, K., Kohn, J. E., & Posch, A. (2012) · Analytical Biochemistry · doi:10.1016/j.ab.2012.10.010 · Cited by 369 · see citing works
Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice
Gariani, K., Menzies, K. J., Ryu, D., Wegner, C. J., Wang, X., Ropelle, E. R., Moullan, N., Zhang, H., Perino, A., Lemos, V., et al. (2016) · Hepatology · doi:10.1002/hep.28245 · Cited by 368 · see citing works
Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle
Frederick, D. W., Loro, E., Liu, L., Davila, A., Chellappa, K., Silverman, I. M., Quinn, W. J., Gosai, S. J., Tichy, E. D., Davis, J. G., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.005 · Cited by 367 · cited 7× · see citing works
“Recent studies in mice employing stable isotope-labelled NR tracers have demonstrated that orally consumed NR is extensively metabolized to NAM and only very limited amounts of NAD+ in skeletal muscle are generated directly from NR (Frederick et al. 2016; Liu et al. 2018).”
BackgroundInfluential
A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in Cockayne syndrome
Scheibye-Knudsen, M., Mitchell, S. J., Fang, E. F., Iyama, T., Ward, T., Wang, J., Dunn, C. A., Singh, N., Veith, S., Hasan-Olive, M. M., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.005 · Cited by 352 · see citing works
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
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre, M., Ono, K., Sauve, A. A., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.005 · Cited by 345 · see citing works
NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease
Cerutti, R., Pirinen, E., Lamperti, C., Marchet, S., Sauve, A. A., Li, W., Leoni, V., Schon, E. A., Dantzer, F., Auwerx, J., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.001 · Cited by 343 · cited 4× · see citing works
“In addition, NR showed promising effects in two different transgenic mouse models of mitochondrial myopathy (Cerutti et al. 2014; Khan et al. 2014).”
BackgroundInfluential
Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice
Mitchell, S. J., Bernier, M., Aon, M. A., Cortassa, S., Kim, E. Y., Fang, E. F., Palacios, H. H., Ali, A., Navas-Enamorado, I., Di Francesco, A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.001 · Cited by 338 · see citing works
Skeletal muscle NAMPT is induced by exercise in humans
Costford, S. R., Bajpeyi, S., Pasarica, M., Albarado, D. C., Thomas, S. C., Xie, H., Church, T. S., Jubrias, S. A., Conley, K. E., & Smith, S. R. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00318.2009 · Cited by 297 · see citing works
Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats
Koltai, E., Szabo, Z., Atalay, M., Boldogh, I., Naito, H., Goto, S., Nyakas, C., & Radak, Z. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.11.002 · Cited by 283 · see citing works
A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
Dollerup, O. L., Christensen, B., Svart, M., Schmidt, M. S., Sulek, K., Ringgaard, S., Stødkilde-Jørgensen, H., Møller, N., Brenner, C., Treebak, J. T., et al. (2018) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy132 · Cited by 282 · see citing works
Self-citation
Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart
Xu, W., Barrientos, T., Mao, L., Rockman, H. A., Sauve, A. A., & Andrews, N. C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.023 · Cited by 274 · see citing works
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
Airhart, S. E., Shireman, L. M., Risler, L. J., Anderson, G. D., Gowda, G. A. N., Raftery, D., Tian, R., Shen, D. D., & O’Brien, K. D. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186459 · Cited by 260 · see citing works
NAD + repletion improves muscle function in muscular dystrophy and counters global PARylation
Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A. G., Mouchiroud, L., Marshall, P. L., Campbell, M. D., Ali, A. S., Knowels, G. M., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf5504 · Cited by 256 · see citing works
Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle
Pirinen, E., Cantó, C., Jo, Y. S., Morato, L., Zhang, H., Menzies, K. J., Williams, E. G., Mouchiroud, L., Moullan, N., Hagberg, C., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.002 · Cited by 254 · cited 1× · see citing works
“…of boosting NAD+ metabolism, including NMN supplementation and pharmacological inhibition of the NAD+-consuming PARP1 enzyme (Bai et al. 2011; Pirinen et al. 2014), ameliorate mitochondrial dysfunction in the skeletal muscle of mice (Gomes et al. 2013; Mills et al. 2016; Uddin et al. 2016).”
Background
Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
Hesselink, M. K. C., Schrauwen-Hinderling, V., & Schrauwen, P. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.104 · Cited by 242 · see citing works
The human NAD metabolome: Functions, metabolism and compartmentalization
Nikiforov, A. A., Kulikova, V., & Ziegler, M. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1028612 · Cited by 214 · see citing works
Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing
Zhou, C., Yang, X., Hua, X., Liu, J., Fan, M.-B., Li, G., Song, J., Xu, T., Li, Z., Guan, Y., et al. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13513 · Cited by 198 · see citing works
A novel cycling assay for cellular cADP-ribose with nanomolar sensitivity
Graeff, R. M., & Lee, H. C. (2002) · Biochemical Journal · doi:10.1042/bj3610379 · Cited by 193 · see citing works
Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects
Traba, J., Kwarteng-Siaw, M., Okoli, T. C., Li, J., Huffstutler, R. D., Bray, A., Waclawiw, M. A., Han, K., Pelletier, M., Sauve, A. A., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83260 · Cited by 180 · see citing works
Mitochondrial Involvement and Impact in Aging Skeletal Muscle
Hepple, R. T. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00211 · Cited by 155 · see citing works
SIRT3 is crucial for maintaining skeletal muscle insulin action and protects against severe insulin resistance in high-fat-fed mice
Lantier, L., Williams, A. S., Williams, I. M., Yang, K. K., Bracy, D. P., Goelzer, M., James, F. D., Gius, D., & Wasserman, D. H. (2015) · Diabetes · doi:10.2337/db14-1810 · Cited by 151 · see citing works
Evidence for a Direct Effect of the NAD+ Precursor Acipimox on Muscle Mitochondrial Function in Humans
van de Weijer, T., Phielix, E., Bilet, L., Williams, E. G., Ropelle, E. R., Bierwagen, A., Livingstone, R., Nowotny, P., Sparks, L. M., Paglialunga, S., et al. (2015) · Diabetes · doi:10.2337/db14-0667 · Cited by 139 · see citing works
Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells
Fletcher, R. S., Ratajczak, J., Doig, C. L., Oakey, L. A., Callingham, R., Xavier, G. D. S., Garten, A., Elhassan, Y., Redpath, P., Migaud, M. E., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.05.011 · Cited by 121 · see citing works
Self-citation
Three‐dimensional reconstruction of the human skeletal muscle mitochondrial network as a tool to assess mitochondrial content and structural organization
Dahl, R., Larsen, S., Dohlmann, T. L., Qvortrup, K., Helge, J. W., Dela, F., & Prats, C. (2015) · Acta Physiologica · doi:10.1111/apha.12289 · Cited by 111 · see citing works
Self-citation
AMP‐activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle
Brandauer, J., Vienberg, S. G., Agerholm, M., Ringholm, S., Risis, S., Larsen, P. S., Kristensen, J. M., Frøsig, C., Leick, L., Fentz, J., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.259515 · Cited by 105 · see citing works
Self-citation
Aerobic and resistance exercise training reverses age‐dependent decline in NAD+salvage capacity in human skeletal muscle
de Guia, R. M., Agerholm, M., Nielsen, T. S., Consitt, L. A., Søgaard, D., Helge, J. W., Larsen, S., Brandauer, J., Houmard, J. A., & Treebak, J. T. (2019) · Physiological Reports · doi:10.14814/phy2.14139 · Cited by 99 · see citing works
Self-citation
Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice
Uddin, G. M., Youngson, N. A., Sinclair, D. A., & Morris, M. J. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00258 · Cited by 95 · cited 1× · see citing works
“…of boosting NAD+ metabolism, including NMN supplementation and pharmacological inhibition of the NAD+-consuming PARP1 enzyme (Bai et al. 2011; Pirinen et al. 2014), ameliorate mitochondrial dysfunction in the skeletal muscle of mice (Gomes et al. 2013; Mills et al. 2016; Uddin et al. 2016).”
Background
Chronic Reduction of Plasma Free Fatty Acid Improves Mitochondrial Function and Whole-Body Insulin Sensitivity in Obese and Type 2 Diabetic Individuals
Daniele, G., Eldor, R., Merovci, A., Clarke, G. D., Xiong, J., Tripathy, D., Taranova, A. G., Abdul-Ghani, M. A., & DeFronzo, R. A. (2013) · Diabetes · doi:10.2337/db13-1130 · Cited by 83 · see citing works
Nicotinamide Phosphoribosyltransferase Is Required for the Calorie Restriction-Mediated Improvements in Oxidative Stress, Mitochondrial Biogenesis, and Metabolic Adaptation
Song, J., Ke, S.-F., Zhou, C.-C., Zhang, S.-L., Guan, Y.-F., Xu, T.-Y., Sheng, C., Wang, P., & Miao, C. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt122 · Cited by 79 · see citing works
Weight Loss Is Associated With Increased NAD+/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue
Rappou, E., Jukarainen, S., Rinnankoski‐Tuikka, R., Kaye, S. M., Heinonen, S., Hakkarainen, A., Lundbom, J., Lundbom, N. M. I., Saunavaara, V., Rissanen, A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3054 · Cited by 78 · see citing works
Effects of Nicotinamide Riboside on Endocrine Pancreatic Function and Incretin Hormones in Nondiabetic Men With Obesity
Dollerup, O. L., Trammell, S. A. J., Hartmann, B., Holst, J. J., Christensen, B., Møller, N., Gillum, M. P., Treebak, J. T., & Jessen, N. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-01081 · Cited by 77 · see citing works
Self-citation
A need for NAD+ in muscle development, homeostasis, and aging
Goody, M. F., & Henry, C. A. (2018) · Skeletal Muscle · doi:10.1186/s13395-018-0154-1 · Cited by 75 · see citing works
Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape mammalian cell physiology under varying biological cues
Ruggieri, S., Orsomando, G., Sorci, L., & Raffaelli, N. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2015.02.021 · Cited by 71 · see citing works
Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes
Lee, H. J., Hong, Y., Jun, W., & Yang, S. J. (2015) · Journal of Medicinal Food · doi:10.1089/jmf.2015.3439 · Cited by 62 · see citing works
Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet
Shi, W., Hegeman, M. A., van Dartel, D. A. M., Tang, J., Suarez, M., Swarts, H., van der Hee, B., Arola, L., & Keijer, J. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600878 · Cited by 62 · see citing works
Perturbations of NAD+salvage systems impact mitochondrial function and energy homeostasis in mouse myoblasts and intact skeletal muscle
Agerholm, M., Dall, M., Jensen, B. A. H., Prats, C., Madsen, S., Basse, A. L., Graae, A.-S., Risis, S., Goldenbaum, J., Quistorff, B., et al. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00213.2017 · Cited by 43 · see citing works
Self-citation
The emergence of the nicotinamide riboside kinases in the regulation of NAD+ metabolism
Fletcher, R. S., & Lavery, G. G. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0085 · Cited by 39 · see citing works
Self-citation
Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial
Makimura, H., Stanley, T. L., Suresh, C., Sousa‐Coelho, A. L. D., Frontera, W. R., Syu, S., Braun, L. R., Looby, S. E. D., Feldpausch, M. N., Torriani, M., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3696 · Cited by 29 · see citing works
Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I–Mutant Fibroblasts
Felici, R., Lapucci, A., Cavone, L., Pratesi, S., Palmini, R. B., & Chiarugi, A. (2015) · Molecular Pharmacology · doi:10.1124/mol.114.097204 · Cited by 28 · see citing works

Flagged first, then by citations

Sorted by citations

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments
Guo, J., Huang, X., Dou, L., Yan, M., Shen, T., Tang, W., & Li, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01251-0 · Cited by 1,834 · see citing works
The sirtuin family in health and disease
Wu, Q., Zhang, T., Chen, H., Yu, X., Lv, J.-L., Liu, Y., Liu, Y., Zheng, G., Zhao, J.-Q., Wei, Y., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01257-8 · Cited by 891 · see citing works
Epigenetic regulation of aging: implications for interventions of aging and diseases
Kang, W., Liu, H., Hu, Q., Wang, L., Liu, J., Zheng, Z., Zhang, W., Ren, J., Zhu, F., & Liu, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01211-8 · Cited by 694 · see citing works
Mitophagy in human health, ageing and disease
Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00930-8 · Cited by 635 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Evolving concepts in NAD+ metabolism
Chini, C. C. S., Zeidler, J. D., Kashyap, S., Warner, G. M., & Chini, E. N. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.04.003 · Cited by 294 · see citing works
Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults
Singh, A., D'Amico, D. F., Andreux, P. A., Fouassier, A. M., Blanco-Bose, W. E., Evans, M., Aebischer, P., Auwerx, J. H., & Rinsch, C. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100633 · Cited by 276 · see citing works
NAD + Metabolism in Cardiac Health, Aging, and Disease
Abdellatif, M., Sedej, S., & Kroemer, G. (2021) · Circulation · doi:10.1161/circulationaha.121.056589 · Cited by 262 · see citing works
NAD+ homeostasis in human health and disease
Perez, R. Z., Wanders, R. J. A., van Karnebeek, C., & Houtkooper, R. H. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202113943 · Cited by 238 · see citing works
Sarcopenia and Muscle Aging: A Brief Overview
Dao, T., Green, A. E., Kim, Y.-A., Bae, S., Ha, K., Gariani, K., Lee, M.-R., Menzies, K. J., & Ryu, D. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.405 · Cited by 228 · see citing works
Age-related NAD+ decline
McReynolds, M. R., Chellappa, K., & Baur, J. A. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110888 · Cited by 169 · see citing works
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
Remie, C. M., Roumans, K. H., Moonen, M. P., Connell, N. J., Havekes, B., Mevenkamp, J., Lindeboom, L., de Wit, V. H., van de Weijer, T., Aarts, S. A., et al. (2020) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa072 · Cited by 160 · see citing works
The role of NAD+ metabolism and its modulation of mitochondria in aging and disease
Yusri, K., Jose, S., Vermeulen, K. S., Tan, T. C. M., & Sorrentino, V. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-025-00067-0 · Cited by 171 · see citing works
NAD metabolism: Role in senescence regulation and aging
Chini, C. C. S., Cordeiro, H. S., Tran, N. L. K., & Chini, E. N. (2023) · Aging Cell · doi:10.1111/acel.13920 · Cited by 138 · see citing works
Regulation of and challenges in targeting NAD+ metabolism
Migaud, M. E., Ziegler, M., & Baur, J. A. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00752-w · Cited by 134 · see citing works
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study
Lapatto, H. A. K., Kuusela, M., Heikkinen, A., Muniandy, M., van der Kolk, B. W., Gopalakrishnan, S., Sandvik, M., Schmidt, M. S., Heinonen, S., Saari, S., et al. (2023) · Science Advances · doi:10.1126/sciadv.add5163 · Cited by 128 · see citing works
The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update
Song, Q., Zhou, X., Xu, K., Liu, S., Zhu, X., & Yang, J. J. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.08.008 · Cited by 122 · see citing works
Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men
Igarashi, M., Nakagawa-Nagahama, Y., Miura, M., Kashiwabara, K., Yaku, K., Sawada, M., Sekine, R., Fukamizu, Y., Sato, T., Sakurai, T., et al. (2022) · npj Aging · doi:10.1038/s41514-022-00084-z · Cited by 125 · see citing works
The autophagy–NAD axis in longevity and disease
Wilson, N., Kataura, T., Korsgen, M. E., Sun, C., Sarkar, S., & Korolchuk, V. I. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.02.004 · Cited by 107 · see citing works
Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects
Okabe, K., Yaku, K., Uchida, Y., Fukamizu, Y., Sato, T., Sakurai, T., Tobe, K., & Nakagawa, T. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.868640 · Cited by 105 · see citing works
Regulation of NAD+ metabolism in aging and disease
Chu, X., & Raju, R. P. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154923 · Cited by 106 · see citing works
What is really known about the effects of nicotinamide riboside supplementation in humans
Damgaard, M. V., & Treebak, J. T. (2023) · Science Advances · doi:10.1126/sciadv.adi4862 · Cited by 99 · see citing works
Self-citation
Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study
Liao, B., Zhao, Y., Wang, D., Zhang, X., Xuan-ming, H., & Hu, M. (2021) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-021-00442-4 · Cited by 96 · see citing works
Impaired nicotinamide adenine dinucleotide (NAD + ) metabolism in diabetes and diabetic tissues: Implications for nicotinamide‐related compound treatment
Fan, L., Cacicedo, J. M., & Ido, Y. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13303 · Cited by 86 · see citing works
BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities
Yaku, K., Palikhe, S., Izumi, H., Yoshida, T., Hikosaka, K., Hayat, F., Karim, M., Iqbal, T., Nitta, Y., Sato, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27080-3 · Cited by 76 · see citing works
NAD+ repletion with niacin counteracts cancer cachexia
Beltrà, M., Pöllänen, N., Fornelli, C., Tonttila, K., Hsu, M. Y., Zampieri, S., Moletta, L., Corrà, S., Porporato, P. E., Kivelä, R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37595-6 · Cited by 71 · see citing works
NAD+ regulates nucleotide metabolism and genomic DNA replication
Munk, S. H. N., Merchut‐Maya, J. M., Adelantado-Rubio, A., Hall, A., Pappas, G. D., Milletti, G., Lee, M., Johnsen, L. G., Guldberg, P., Bártek, J., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01280-z · Cited by 71 · see citing works
Resistance training increases muscle NAD(+) and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals
Lamb, D. A., Moore, J. H., Mesquita, P. H. C., Smith, M. A., Vann, C. G., Osburn, S. C., Fox, C. D., Lopez, H. L., Ziegenfuss, T. N., Huggins, K. W., et al. (2020) · Aging · doi:10.18632/aging.103218 · Cited by 62 · see citing works
Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity
Basse, A. L., Agerholm, M., Farup, J., Dalbram, E., Nielsen, J., Ørtenblad, N., Altıntaş, A., Ehrlich, A. M., Krag, T. O. B., Bruzzone, S., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101271 · Cited by 62 · see citing works
Self-citation
The therapeutic perspective of NAD+ precursors in age-related diseases
Iqbal, T., & Nakagawa, T. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149590 · Cited by 65 · see citing works
Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions
Freeberg, K. A., Udovich, C. C., Martens, C. R., Seals, D. R., & Craighead, D. H. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad106 · Cited by 68 · see citing works
NAD+ and NAFLD – caution, causality and careful optimism
Dall, M., Hassing, A. S., & Treebak, J. T. (2021) · The Journal of Physiology · doi:10.1113/jp280908 · Cited by 57 · see citing works
Self-citation
Impact of NAD+ metabolism on ovarian aging
Liang, J., Huang, F., Song, Z., Tang, R., Zhang, P., & Chen, R. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00398-w · Cited by 56 · see citing works
Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities
Sun, X., & Feinberg, M. W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.693067 · Cited by 55 · see citing works
Clinical Trials Targeting Aging
Nielsen, J. L., Bakula, D., & Scheibye‐Knudsen, M. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.820215 · Cited by 51 · see citing works
The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation
Poljšak, B., Kovač, V., Špalj, S., & Milisav, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032959 · Cited by 58 · see citing works
Emerging strategies, applications and challenges of targeting NAD+ in the clinic
Zhang, J., Wang, H., Lautrup, S., Nilsen, H. L., Treebak, J. T., Watne, L. O., Selbæk, G., Wu, L. E., Omland, T., Pirinen, E., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00947-6 · Cited by 58 · see citing works
Self-citation
Targeting mitochondrial fitness as a strategy for healthy vascular aging
Rossman, M. J., Gioscia‐Ryan, R. A., Clayton, Z. S., Murphy, M. P., & Seals, D. R. (2020) · Clinical Science · doi:10.1042/cs20190559 · Cited by 50 · see citing works
The crosstalk of NAD, ROS and autophagy in cellular health and ageing
Sedlackova, L., & Korolchuk, V. I. (2020) · Biogerontology · doi:10.1007/s10522-020-09864-0 · Cited by 47 · see citing works
Nicotinamide riboside supplementation does not alter whole‐body or skeletal muscle metabolic responses to a single bout of endurance exercise
Stocks, B., Ashcroft, S. P., Joanisse, S., Dansereau, L. C., Koay, Y. C., Elhassan, Y., Lavery, G. G., Quek, L., O’Sullivan, J., Philp, A. M., et al. (2021) · The Journal of Physiology · doi:10.1113/jp280825 · Cited by 43 · see citing works
Self-citation
Impact of nutraceuticals and dietary supplements on mitochondria modifications in healthy aging: a systematic review of randomized controlled trials
Lippi, L., Uberti, F., Folli, A., Turco, A., Curci, C., D’Abrosca, F., Alessandro de, S. I. R. E., & Invernizzi, M. (2022) · Aging Clinical and Experimental Research · doi:10.1007/s40520-022-02203-y · Cited by 43 · see citing works
Targeting NAD+ in translational research to relieve diseases and conditions of metabolic stress and ageing
Gilmour, B. C., Gudmundsrud, R., Frank, J., Hov, A., Lautrup, S., Aman, Y., Røsjø, H. R., Brenner, C., Ziegler, M., Tysnes, O., et al. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111208 · Cited by 43 · see citing works
Nicotinamide, Nicotinamide Riboside and Nicotinic Acid—Emerging Roles in Replicative and Chronological Aging in Yeast
Orlandi, I., Alberghina, L., & Vai, M. (2020) · Biomolecules · doi:10.3390/biom10040604 · Cited by 40 · see citing works
Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives
Biţă, A., Scorei, I. R., Ciocîlteu, M. V., Nicolaescu, O. E., Pîrvu, A. S., Bejenaru, L. E., Rău, G., Bejenaru, C., Radu, A., Neamţu, J., et al. (2023) · Molecules · doi:10.3390/molecules28166078 · Cited by 41 · see citing works
Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations
Cercillieux, A., Ciarlo, E., & Cantó, C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04499-5 · Cited by 41 · see citing works
Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD + synthesis via enterohepatic circulation
Yaku, K., Palikhe, S., Iqbal, T., Hayat, F., Watanabe, Y., Fujisaka, S., Izumi, H., Yoshida, T., Karim, M., Uchida, H., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr1538 · Cited by 40 · see citing works
“However, the increase of NAD + levels in the skeletal muscle after NR and NMN administration is not as efficient as that in the liver ( 17 , 18 , 20 , 39 – 42 ).”
A systems-approach to NAD+ restoration
Conlon, N. J., & Ford, D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114946 · Cited by 40 · see citing works
Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise
Ji, L. L., & Yeo, D. (2022) · Cells · doi:10.3390/cells11040710 · Cited by 43 · see citing works
Impact of Aging and Lifelong Exercise Training on Mitochondrial Function and Network Connectivity in Human Skeletal Muscle
Ringholm, S., Gudiksen, A., Halling, J. F., Qoqaj, A., Rasmussen, P. M., Prats, C., Plomgaard, P., & Pilegaard, H. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac164 · Cited by 42 · see citing works
Self-citation
A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals
Jensen, J. B., Dollerup, O. L., Møller, A. B., Billeskov, T. B., Dalbram, E., Chubanava, S., Damgaard, M. V., Dellinger, R. W., Trošt, K., Moritz, T., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.158314 · Cited by 39 · see citing works
Self-citation
NAD+-consuming enzymes in immune defense against viral infection
Shang, J., Smith, M. R., Anmangandla, A., & Lin, H. (2021) · Biochemical Journal · doi:10.1042/bcj20210181 · Cited by 38 · see citing works
NAD+ centric mechanisms and molecular determinants of skeletal muscle disease and aging
Wagner, S., Manickam, R., Brotto, M. A. P., & Tipparaju, S. M. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04408-1 · Cited by 39 · see citing works
Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial
McDermott, M. M., Martens, C. R., Domanchuk, K. J., Zhang, D., Peek, C. B., Criqui, M. H., Ferrucci, L., Greenland, P., Guralnik, J. M., Ho, K. J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49092-5 · Cited by 37 · see citing works
Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing
Broome, S. C., Whitfield, J., Karagounis, L. G., & Hawley, J. A. (2024) · Sports Medicine · doi:10.1007/s40279-024-02072-7 · Cited by 39 · see citing works
Treating age-related multimorbidity: the drug discovery challenge
Ermogenous, C., Green, C., Jackson, T., Ferguson, M. A. J., & Lord, J. M. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.06.016 · Cited by 33 · see citing works
NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults
Connell, N., Grevendonk, L., Fealy, C., Moonen-Kornips, E., Bruls, Y., Schrauwen-Hinderling, V., de Vogel, J., Hageman, R., Geurts, J., Zapata-Perez, R., et al. (2021) · The Journal of Nutrition · doi:10.1093/jn/nxab193 · Cited by 33 · see citing works
What is bipolar disorder? A disease model of dysregulated energy expenditure
Mansur, R. B., Lee, Y. L., McIntyre, R. S., & Brietzke, E. M. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.006 · Cited by 33 · see citing works
NAD + Precursors in Human Health and Disease: Current Status and Future Prospects
Yaku, K., & Nakagawa, T. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0354 · Cited by 31 · see citing works
Strategies to protect against age-related mitochondrial decay: Do natural products and their derivatives help?
Visioli, F., Ingram, A., Beckman, J. S., Magnusson, K. R., & Hagen, T. M. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.12.008 · Cited by 31 · see citing works
A reduced form of nicotinamide riboside protects the cochlea against aminoglycoside-induced ototoxicity by SIRT1 activation
Fang, J., Wu, H., Zhang, J., Mao, S., Shi, H., Yu, D., Chen, Z., Su, K., Xing, Y., Dong, H., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113071 · Cited by 31 · see citing works
NAD+ precursor supplementation in human ageing: clinical evidence and challenges
Vinten, K. T., Trętowicz, M. M., Coskun, E., van Weeghel, M., Cantó, C., Perez, R. Z., Janssens, G. E., & Houtkooper, R. H. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01387-7 · Cited by 32 · see citing works
Hypothalamic NAD+-Sirtuin Axis: Function and Regulation
Roh, E., & Kim, M. (2020) · Biomolecules · doi:10.3390/biom10030396 · Cited by 29 · see citing works
Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans
Nascimento, E. B. M., Moonen, M. P. B., Remie, C. M. E., Gariani, K., Jörgensen, J. A., Schaart, G., Hoeks, J., Auwerx, J. H., Lichtenbelt, W. D. V. M., & Schrauwen, P. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa960 · Cited by 27 · see citing works
Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin‐mediated deacetylation
Mishra, S., Welch, N., Karthikeyan, M., Bellar, A., Musich, R. J., Singh, S. S., Zhang, D., Sekar, J., Attaway, A. H., Chelluboyina, A. K., et al. (2023) · Aging Cell · doi:10.1111/acel.13852 · Cited by 26 · see citing works
NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
Chubanava, S., Karavaeva, I. E., Ehrlich, A. M., Justicia, R. M., Basse, A. L., Kulik, I., Dalbram, E., Ahwazi, D., Heaselgrave, S. R., Trôst, K., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.04.002 · Cited by 28 · see citing works
Self-citation
Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD+ without impacting respiratory capacity or insulin sensitivity
Damgaard, M. V., Nielsen, T. S., Basse, A. L., Chubanava, S., Trôst, K., Möritz, T., Dellinger, R. W., Larsen, S., & Treebak, J. T. (2022) · iScience · doi:10.1016/j.isci.2022.103863 · Cited by 25 · see citing works
Self-citation
Exercise-induced benefits on glucose handling in a model of diet-induced obesity are reduced by concurrent nicotinamide mononucleotide
Yu, J., Laybutt, D. R., Kim, L.-J., Quek, L.-E., Wu, L. E., Morris, M. J., & Youngson, N. A. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00446.2020 · Cited by 24 · see citing works
A new clinical age of aging research
Zhang, Z., Yang, R., Zi, Z., & Liu, B. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.08.004 · Cited by 25 · see citing works
Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications
Benjamin, C., & Crews, R. (2024) · Metabolites · doi:10.3390/metabo14060341 · Cited by 23 · see citing works
Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans
Peluso, A. A., Lundgaard, A. T., Babaei, P., Mousovich‐Neto, F., Rocha, A. L. S., Damgaard, M. V., Bak, E. G., Gnanasekaran, T., Dollerup, O. L., Trammell, S. A. J., et al. (2023) · npj Aging · doi:10.1038/s41514-023-00106-4 · Cited by 24 · see citing works
Self-citation
Nicotinamide riboside has minimal impact on energy metabolism in mouse models of mild obesity
Cartwright, D. M., Oakey, L. A., Fletcher, R. S., Doig, C. L., Heising, S., Larner, D. P., Nasteska, D., Berry, C. E., Heaselgrave, S. R., Ludwig, C., et al. (2021) · Journal of Endocrinology · doi:10.1530/joe-21-0123 · Cited by 22 · see citing works
Self-citation
The use of a systems approach to increase NAD+ in human participants
Henderson, J. D., Quigley, S. N. Z., Chachra, S. S., Conlon, N. J., & Ford, D. (2024) · npj Aging · doi:10.1038/s41514-023-00134-0 · Cited by 21 · see citing works
Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells
Kolotyeva, N. A., Groshkov, A. A., Rozanova, N. A., Berdnikov, A. K., Novikova, S. V., Komleva, Y. K., Salmina, A. B., Illarioshkin, S. N., & Пирадов, М. А. (2024) · Biomolecules · doi:10.3390/biom14121556 · Cited by 22 · see citing works
Nicotinamide riboside—A missing piece in the puzzle of exercise therapy for older adults?
Custodero, C., Saini, S. K., Shin, M., Jeon, Y. K., Christou, D. D., McDermott, M. M., Leeuwenburgh, C., Anton, S. D., & Mankowski, R. T. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110972 · Cited by 21 · see citing works
Complementary NAD+ replacement strategies fail to functionally protect dystrophin-deficient muscle
Frederick, D. W., McDougal, A. V., Semenas, M., Vappiani, J., Nuzzo, A., Ulrich, J. C., Becherer, J. D., Preugschat, F., Stewart, E. L., Sévin, D. C., et al. (2020) · Skeletal Muscle · doi:10.1186/s13395-020-00249-y · Cited by 21 · see citing works
NAD+: An old but promising therapeutic agent for skeletal muscle ageing
Xu, Y., & Xiao, W. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102106 · Cited by 19 · see citing works
Effects of NAD+ supplementation with oral nicotinamide riboside on vascular health and cognitive function in older adults with peripheral artery disease: Results from a pilot 4-week open-label clinical trial
Szarvas, Z., Reyff, Z., Péterfi, A., Pinto, C. B., Owens, C. D., Kaposzta, Z., Mukli, P., Pinaffi‐Langley, A. C. D. C., Adams, C., Muranyi, M., et al. (2025) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103607 · Cited by 19 · see citing works
Nicotinamide riboside supplementation confers marginal metabolic benefits in obese mice without remodeling the muscle acetyl-proteome
Williams, A. S., Koves, T. R., Pettway, Y. D., Draper, J. A., Slentz, D. H., Grimsrud, P. A., Ilkayeva, O., & Muoio, D. M. (2021) · iScience · doi:10.1016/j.isci.2021.103635 · Cited by 17 · see citing works
Targeting Intramyocellular Lipids to Improve Aging Muscle Function
Russ, D. W., Manickam, R., & Tipparaju, S. M. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02622-6 · Cited by 15 · see citing works
“However, these approaches have not shown improved muscle function [179], nor have they shown increased muscle NAD+ [180, 181].”
NAD+-Increasing Strategies to Improve Cardiometabolic Health?
Blanco‐Vaca, F., Rotllán, N., Canyelles, M., Mauricio, D., Escolá‐Gil, J. C., & Julve, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.815565 · Cited by 15 · see citing works
NAD+ Therapeutics and Skeletal Muscle Adaptation to Exercise in Humans
Campelj, D. G., & Philp, A. (2022) · Sports Medicine · doi:10.1007/s40279-022-01772-2 · Cited by 15 · see citing works
Pharmacological interventions in human aging
Petr, M. A., Matiyevskaya, F., Osborne, B., Berglind, M., Reves, S., Zhang, B., Ezra, M. B., Carmona-Marin, L. M., Syadzha, M. F., Mediavilla, M. C., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102213 · Cited by 16 · see citing works
Long COVID as a disease of accelerated biological aging: An opportunity to translate geroscience interventions
Shafqat, A., Masters, M. C., Tripathi, U., Tchkonia, T., Kirkland, J. L., & Hashmi, S. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102400 · Cited by 15 · see citing works
NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence
Gallagher, C., & Emmanuel, O. O. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103057 · Cited by 17 · see citing works
Improving Mitochondrial Function in Skeletal Muscle Contributes to the Amelioration of Insulin Resistance by Nicotinamide Riboside
Li, Q., Jiang, X., Zhou, Y., Gu, Y., Ding, Y., Luo, J., Pang, N., Sun, Y., Pei, L., Pan, J., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241210015 · Cited by 13 · see citing works
Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway
Li, P., Feng, X., Ma, Z., Yuan, Y., Jiang, H., Xu, G., Zhu, Y., Yang, X., Wang, Y., Zhu, C., et al. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01244-2 · Cited by 13 · see citing works
Regular exercise effectively protects against the aging-associated decline in skeletal muscle NAD content
Chubanava, S., & Treebak, J. T. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112109 · Cited by 13 · see citing works
Self-citation
Nutritional approaches targeting mitochondria for the prevention of sarcopenia
Hahm, J., Nirmala, F. S., Ha, T. Y., & Ahn, J. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad084 · Cited by 12 · see citing works
An Updated Review on the Mechanisms, Pre‐Clinical and Clinical Comparisons of Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR)
Xu, Y., Lu, A., Guan, X., Ying, T., Pan, J., Tan, M., & Lu, J. (2024) · Food Frontiers · doi:10.1002/fft2.511 · Cited by 11 · see citing works
Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging
Carpenter, B. J., & Dierickx, P. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00239.2022 · Cited by 11 · see citing works
The potential of aging rejuvenation
O’Loghlen, A. (2022) · Cell Cycle · doi:10.1080/15384101.2021.2013612 · Cited by 11 · see citing works
Exercise training upregulates intracellular nicotinamide phosphoribosyltransferase expression in humans: a systematic review with meta-analysis
Sun, X., Su, L., Bu, T., & Zhang, Y. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1287421 · Cited by 10 · see citing works
RTB101 and immune function in the elderly: Interpreting an unsuccessful clinical trial
Kaeberlein, M. R. (2020) · Translational Medicine of Aging · doi:10.1016/j.tma.2020.01.002 · Cited by 10 · see citing works
NAD in pathological cardiac remodeling: Metabolic regulation and beyond
Norambuena‐Soto, I., Deng, Y., Brenner, C., Lavandero, S., & Wang, Z. V. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167038 · Cited by 9 · see citing works
Synthesis of Mixed Dinucleotides by Mechanochemistry
Hayat, F., Makarov, M. V., Belfleur, L., & Migaud, M. E. (2022) · Molecules · doi:10.3390/molecules27103229 · Cited by 9 · see citing works
Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials
Chen, F., Zhou, D., Kong, A. P.-S., Yim, N. T., Dai, S., Chen, Y., & Hui, L. L. (2024) · Current Diabetes Reports · doi:10.1007/s11892-024-01557-z · Cited by 8 · see citing works
Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole‐body glucose homeostasis: does it actually work in humans?
Leduc‐Gaudet, J., Dulac, M., Reynaud, O., Ayoub, M., & Gouspillou, G. (2019) · The Journal of Physiology · doi:10.1113/jp279280 · Cited by 8 · see citing works
Program with last minute abstracts of the Padua Days on Muscle and Mobility Medicine, 27 February – 2 March, 2024 (2024Pdm3)
Zampieri, S., Bersch, I., Smeriglio, P., Barbieri, E., Boncompagni, S., Maccarone, M. C., & Carraro, U. (2024) · European Journal of Translational Myology · doi:10.4081/ejtm.2024.12346 · Cited by 8 · see citing works
Harmonization of experimental procedures to assess mitochondrial respiration in human permeabilized skeletal muscle fibers
Doerrier, C., Gama-Pérez, P., Pesta, D. H., Distéfano, G., Soendergaard, S. D., Chrøis, K. M., González-Franquesa, A., Goodpaster, B. H., Prats, C., Sales‐Pardo, M., et al. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.07.039 · Cited by 7 · see citing works
Self-citation
Mitochondrial quality control in human ageing and longevity
Picca, A., & Ferrucci, L. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01563-3 · Cited by 9 · see citing works

Impact of nicotinamide riboside supplementation on skeletal muscle mitochondria and whole‐body glucose homeostasis: challenging the current hypothesis
Moore, M. P., & Mucinski, J. M. (2020) · The Journal of Physiology · doi:10.1113/jp279749 · Cited by 4 · see citing works
Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD+ without impacting respiratory capacity or insulin sensitivity
Damgaard, M. V., Nielsen, T. S., Basse, A. L., Chubanava, S., Trôst, K., Möritz, T., Dellinger, R. W., Larsen, S., & Treebak, J. T. (2022) · iScience · doi:10.1016/j.isci.2022.103863 · Cited by 25 · see citing works
Self-citation
Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole‐body glucose homeostasis: does it actually work in humans?
Leduc‐Gaudet, J., Dulac, M., Reynaud, O., Ayoub, M., & Gouspillou, G. (2019) · The Journal of Physiology · doi:10.1113/jp279280 · Cited by 8 · see citing works
Nicotinamide riboside supplementation does not alter whole‐body or skeletal muscle metabolic responses to a single bout of endurance exercise
Stocks, B., Ashcroft, S. P., Joanisse, S., Dansereau, L. C., Koay, Y. C., Elhassan, Y., Lavery, G. G., Quek, L., O’Sullivan, J., Philp, A. M., et al. (2021) · The Journal of Physiology · doi:10.1113/jp280825 · Cited by 43 · see citing works
Self-citation
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
Remie, C. M., Roumans, K. H., Moonen, M. P., Connell, N. J., Havekes, B., Mevenkamp, J., Lindeboom, L., de Wit, V. H., van de Weijer, T., Aarts, S. A., et al. (2020) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa072 · Cited by 160 · see citing works

Authors: Dollerup, O. L., Chubanava, S., Agerholm, M., Søndergård, S. D., Altıntaş, A., Møller, A. B., Høyer, K. F., Ringgaard, S., Stødkilde‐Jørgensen, H., Lavery, G. G., Barrès, R., Larsen, S., Prats, C., Jessen, N., & Treebak, J. T.
Affiliations: University of Copenhagen (DK)
Aarhus University (DK)
Aarhus University Hospital (DK)
University of Birmingham (GB)
Corresponding author: Treebak, Jonas T.
ORCID: Dollerup, Ole L.
Chubanava, Sabina
Agerholm, Marianne
Altıntaş, Ali
Møller, Andreas B.
Høyer, Kasper F.
Ringgaard, Steffen
Stødkilde‐Jørgensen, Hans
Lavery, Gareth G.
Barrès, Romain
Larsen, Steen
Prats, Clara
Jessen, Niels
Treebak, Jonas T.
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2019-12-26
Volume: 598
Issue: 4
Pages: 731-754
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jp278752
OpenAlex: W2984413344
Cited by: 145
References: 76
Citations by year: 2026: 13 · 2025: 14 · 2024: 20 · 2023: 25 · 2022: 26 · 2021: 28 · 2020: 18 · 2019: 1
FWCI: 9.62
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: Novo Nordisk Fonden (NNF14OC0009315, NNF13OC0003882)
Det Frie Forskningsråd (DFF 4004‐00235)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: nicotinamide riboside, NAD+ precursors, skeletal muscle mitochondria, mitochondrial respiration, mitochondrial morphology, mitochondrial content, visfatin, NAD biosynthesis, obesity, insulin resistance, oxidative phosphorylation, SIRT3, succinate dehydrogenase
MeSH terms: Humans, Insulin Resistance, Male, Middle Aged, Mitochondria, Muscle, NAD, Niacinamide, Obesity, Pyridinium Compounds, Muscle, Skeletal, Nicotinamide Phosphoribosyltransferase

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin‐resistant men

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks