Evidence map›Paper›PMID 34191033›Full record

Trial reportThe Journal of nutrition2021

NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.

N J Connell, L Grevendonk, C E Fealy, E Moonen-Kornips, Y M H Bruls, V B Schrauwen-Hinderling, J de Vogel, R Hageman, J Geurts, R Zapata-Perez and 4 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of nutrition, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03310034 (The Effects of NAD+-Precursor Supplementation on Energy Metabolism in Physically Compromised Elderly), which is not on this map. Cited by 22 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03310034 naterminatednot on this map

The Effects of NAD+-Precursor Supplementation on Energy Metabolism in Physically Compromised Elderly

TypeinterventionalSponsorMaastricht UniversityRan2017 to 2020Enrolled14ConditionsAging, Mitochondrial FunctionArmsNAD-precursors, Control
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Restoring NADFrontiers in nutrition · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. The role of NADnpj metabolic health and disease · 2025
    Review
  11. Review
  12. Protein Acetylation and NAD+ Homeostasis in Aging Muscle.Advances in experimental medicine and biology · 2025
    Review
  13. Regulation of and challenges in targeting NADNature reviews. Molecular cell biology · 2024
    Review
  14. Review
  15. Review
  16. Impact of NAD+ metabolism on ovarian aging.Immunity & ageing : I & A · 2023
    Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

N J ConnellDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
L GrevendonkDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
C E FealyDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
E Moonen-KornipsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
Y M H BrulsDepartment of Radiology and Nuclear Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
V B Schrauwen-HinderlingDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
J de VogelDanone Nutricia Research, Utrecht, The Netherlands.
R HagemanDanone Nutricia Research, Utrecht, The Netherlands.
J GeurtsFriesland Campina, Amersfoort, The Netherlands.
R Zapata-PerezLaboratory Genetic Metabolic Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
R H HoutkooperLaboratory Genetic Metabolic Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
B HavekesDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
J HoeksDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
P SchrauwenDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.ORCID 0000-0002-0973-847X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBoosting 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.

objectivesWe investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults.

methodsA 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.

resultsFollowing 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].

conclusionsOur 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.

Indexed as

NiacinAgedDietary SupplementsFemaleHumansMaleMitochondriaMuscle, SkeletalNADNiacinamideTryptophanNADNiacinNiacinamideTryptophanmetabolismmitochondrial functionmuscle healthNAD+-precursorsolder adultsskeletal muscle

Identifiers

PMID34191033
PMCPMC8485915

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.