Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
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BACKGROUND: Nicotinamide riboside (NR) is an NAD+ precursor that boosts cellular NAD+ concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. OBJECTIVES: We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers. METHODS: A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism. RESULTS: Markers of increased NAD+ synthesis-nicotinic acid adenine dinucleotide and methyl nicotinamide-were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% ± 2.49% compared with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 ± 749 compared with 3025 ± 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 ± 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 ± 0.30 compared with 2.40 ± 0.33 mmol/kg wet weight; change: 0.53 ± 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism. CONCLUSIONS: NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed.This trial was registered at clinicaltrials.gov as NCT02835664.
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Participants in neither study showed any signs of weight loss, increased insulin sensitivity or enhanced mitochondrial function, among other metabolic parameters studied.
“Unfortunately, while NR could effectively increase NAD+ levels in these individuals94, participants in neither study showed any signs of weight loss, increased insulin sensitivity or enhanced mitochondrial function, among other metabolic parameters studied.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [94]
NR could effectively increase NAD+ levels in these individuals.
“Unfortunately, while NR could effectively increase NAD+ levels in these individuals94, participants in neither study showed any signs of weight loss, increased insulin sensitivity or enhanced mitochondrial function, among other metabolic parameters studied.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [94]
Two recent randomized and double-blind studies treated patients with overweight and obesity with NR for 6 weeks and 12 weeks.
“However, two recent randomized and double-blind studies treated patients with over-weight and obesity with NR for 6 weeks and 12 weeks93,94.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [94]
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- Authors
- 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., Lutgens, E., Schomakers, B. V., Elfrink, H. L., Zapata-Pérez, R., Houtkooper, R. H., Auwerx, J., Hoeks, J., Schrauwen-Hinderling, V. B., Phielix, E., & Schrauwen, P.
- Affiliations
- Maastricht University (NL)
- Maastricht University Medical Centre (NL)
- Amsterdam University Medical Centers (NL)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Schrauwen, Patrick
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 112
- Issue
- 2
- Pages
- 413-426
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC7398770
- OpenAlex
- W3016629372
- Cited by
- 160
- References
- 54
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 23 · 2023: 30 · 2022: 32 · 2021: 27 · 2020: 6
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by-nc)
- Pure Amsterdam UMC (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Research Publications (Maastricht University) (submittedVersion, cc-by-nc)
- Funders
- Dutch Heart Foundation
- CVON Energise (CVON2014-02)
- European Union's Horizon 2020
- Marie Sklodowska-Curie (840110)
- ERC (759161)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- nicotinamide riboside, NAD+ precursors, obesity, overweight, body composition, fat-free mass, skeletal muscle, acetyl-L-carnitine, mitochondrial function, insulin sensitivity, sleeping metabolic rate, energy metabolism, NAD+ metabolism, metabolic health, mitochondrial uncoupling, inflammation, lipid accumulation, cardiac ejection
- MeSH terms
- Acetylcarnitine, Aged, Body Composition, Female, Humans, Male, Middle Aged, NAD, Niacinamide, Obesity, Pyridinium Compounds, Muscle, Skeletal, Dietary Supplements, Overweight
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