Trial reportDiabetes2015
Evidence for a direct effect of the NAD+ precursor acipimox on muscle mitochondrial function in humans.
Trial report in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis.Journal of cachexia, sarcopenia and muscle · 2025Pooled it
- Trial
- NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.The Journal of nutrition · 2021Trial
- Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans.The American journal of clinical nutrition · 2020Trial
- Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NADCell reports · 2019Trial
- Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation.British journal of clinical pharmacology · 2017Trial
- Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals.The Journal of clinical endocrinology and metabolism · 2016Trial
- Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial.The Journal of clinical endocrinology and metabolism · 2016Trial
- Redox Molecules in Aging and Neurodegenerative Disorders.International journal of molecular sciences · 2026Review
- Citric Acid Cycle Genes and Nutrigenetics.International journal of molecular sciences · 2026Review
- Combination therapy of statin and acipimox versus statin monotherapy in acute myocardial infarction with hypertriglyceridemia: a multicenter propensity score-matched analysis.Lipids in health and disease · 2026Article
- Acipimox as a potential antioxidant and neuromodulator mitigates high fat diet induced cognitive dysfunction.Scientific reports · 2025Article
- Research progress on sarcopenia in the musculoskeletal system.Bone research · 2025Review
- A review of the link between the lactate-GPR81 axis and mitochondrial angiopathy in MELAS based on imaging characteristics.Journal of neurology · 2025Review
- Effect of acipimox on skeletal muscle biochemistry, structure and function in older people with probable sarcopenia: an experimental medicine study.GeroScience · 2025Article
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Advances in Management of Mitochondrial Myopathies.International journal of molecular sciences · 2025Review
- Metabolomics in cardiometabolic diseases: Key biomarkers and therapeutic implications for insulin resistance and diabetes.Journal of internal medicine · 2025Review
- Mechanisms of the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans and Mammals and Its Roles in Striated Muscles.Aging and disease · 2024Review
- Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.Signal transduction and targeted therapy · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
Abstract
Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m(2)) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD(+) levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD(+) boosters can also directly affect skeletal muscle mitochondrial function in humans.
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What OpenQuestion holds
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.