NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults
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BACKGROUND: Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. OBJECTIVES: We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults. METHODS: A randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly. RESULTS: Following supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342]. CONCLUSIONS: Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.
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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 [179]
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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].”
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- Authors
- Connell, N., Grevendonk, L., Fealy, C., Moonen-Kornips, E., Bruls, Y., Schrauwen-Hinderling, V., de Vogel, J., Hageman, R., Geurts, J., Zapata-Perez, R., Houtkooper, R., Havekes, B., Hoeks, J., & Schrauwen, P.
- Affiliations
- Maastricht University (NL)
- Nutricia Research (Netherlands) (NL)
- FrieslandCampina (Netherlands) (NL)
- Maastricht University Medical Centre (NL)
- Corresponding author
- Schrauwen, P
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 151
- Issue
- 10
- Pages
- 2917-2931
- ISSN
- 0022-3166 (ISSN-L)
- PMC
- PMC8485915
- OpenAlex
- W3176196950
- Cited by
- 33
- References
- 58
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 1
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, cc-by-nc)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Top Institute Food and Nutrition (16NH01)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- NAD+ precursors, tryptophan, nicotinic acid, nicotinamide, skeletal muscle mitochondrial function, mitochondrial oxidative capacity, exercise efficiency, older adults, physical impairment, NAD+ metabolism, healthy aging, mitochondrial respiration, sarcopenia, mitochondrial uncoupling, ADP-stimulated respiration
- MeSH terms
- Aged, Female, Humans, Male, Mitochondria, NAD, Niacin, Niacinamide, Tryptophan, Muscle, Skeletal, Dietary Supplements
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