A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
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Background Animal studies suggest a positive role for nicotinamide riboside (NR) on insulin sensitivity and hepatic steatosis in models of obesity and type 2 diabetes. NR, an NAD+ precursor, is a member of the vitamin B-3 family now available as an over-the-counter supplement. Although data from preclinical trials appear consistent, potential effects and safety need to be evaluated in human clinical trials.Objective The aim of this study was to test the safety of dietary NR supplementation over a 12-wk period and potential to improve insulin sensitivity and other metabolic parameters in obese, insulin-resistant men.Design In an investigator-initiated randomized, placebo-controlled, double-blinded, and parallel-group designed clinical trial, forty healthy, sedentary men with a body mass index (BMI) > 30 kg/m2, age-range 40-70 y were randomly assigned to 12 wk of NR (1000 mg twice daily) or placebo. We determined the effects of NR supplementation on insulin sensitivity by a hyperinsulinemic euglycemic clamp and substrate metabolism by indirect calorimetry and labeled substrates of tritiated glucose and palmitate. Body composition and fat mass distribution were determined by whole-body dual-energy X-ray absorptiometry (DXA) and MRI scans, and measurements of intrahepatic lipid content were obtained by MR spectroscopy.Results Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved by NR supplementation. Similarly, NR supplementation had no effect on resting energy expenditure, lipolysis, oxidation of lipids, or body composition. No serious adverse events due to NR supplementation were observed and safety blood tests were normal.Conclusion 12 wk of NR supplementation in doses of 2000 mg/d appears safe, but does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men. This trial was registered at clinicaltrials.gov as NCT02303483.
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NR is orally bioavailable, well tolerated, and raises NAD+ in healthy middle-aged and older adults and in older diabetic males.
“NR is orally bioavailable, and it is well tolerated and elevates NAD+ in healthy middle-aged and older adults as well as in old diabetic males.”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Dollerup et al., 2018
NR is safe in diabetic men even at 2,000 mg/day taken twice daily for 12 weeks.
“NR was safe even at 2,000 mg/day (twice a day) for 12 weeks”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Dollerup et al., 2018
NR has shown little to no effect in aged men with obesity.
“NR has shown little to no effect in aged men with obesity93,186,188”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [186]
One trial showed short-term NR administration has some beneficial effects in healthy elderly individuals, and another showed positive results in patients with ALS.
“One trial showed that short-term NR administration has some beneficial effects in healthy elderly individuals185, and another showed positive results in patients with ALS93,186,187.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [186]
Human studies of nicotinamide riboside at 2,000 mg per day show it is safe but does not improve insulin sensitivity or whole-body glucose metabolism in patients with obesity and insulin resistance.
“However, results from human studies testing nicotinamide riboside supplementation at 2,000 mg per day showed that although safe, nicotinamide riboside does not improve insulin sensitivity and whole-body glucose metabolism in patients with obesity and insulin resistance259.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [259]
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- Authors
- Dollerup, O. L., Christensen, B., Svart, M., Schmidt, M. S., Sulek, K., Ringgaard, S., Stødkilde-Jørgensen, H., Møller, N., Brenner, C., Treebak, J. T., & Jessen, N.
- Affiliations
- University of Copenhagen (DK)
- University of Iowa (US)
- Aarhus University (DK)
- Corresponding author
- Treebak, Jonas T
- Jessen, Niels
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 108
- Issue
- 2
- Pages
- 343-353
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2827617026
- Cited by
- 282
- References
- 52
- Citations by year
- 2026: 28 · 2025: 26 · 2024: 31 · 2023: 34 · 2022: 44 · 2021: 50 · 2020: 37 · 2019: 29 · 2018: 2
- FWCI
- 16.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Novo Nordisk Foundation (NNF14OC0009315, NNF13OC0003882)
- Danish Council for Independent Research (DFF 4004-00235)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- nicotinamide riboside, obesity, insulin resistance, insulin sensitivity, NAD+ precursors, dietary supplementation, hyperinsulinemic-euglycemic clamp, glucose metabolism, lipolysis, lipid oxidation, resting energy expenditure, intrahepatic lipid, hepatic steatosis, body composition, body fat distribution, drug safety
- MeSH terms
- Adult, Aged, Body Composition, Double-Blind Method, Glucose, Humans, Insulin Resistance, Male, Middle Aged, Niacinamide, Obesity, Pyridinium Compounds, Dietary Supplements, Lipid Metabolism
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.
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