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Medicine NAD

A Swiss-grid reading of the NAD+ literature — the coenzyme, its oral precursors (NMN and NR), and the metabolic and muscle endpoints the human trials actually measured, set on a precise editorial grid.

Section 07 · Where’s the paper behind the claim?

Which papers let you check a NAD+ finding?

Pill researchers wanted to learn whether replacing NAD+ could improve health during aging. These papers describe what the tests found. Your doctor can check who was studied before judging a claim.

Return to the results in peopleChoose a question for your doctor

How can you find the paper that goes with a number?

Pill researchers tried the ingredients NR and NMN with hopes of restoring an aging body's NAD+ supply. Those pill ingredients undergo changes inside cells before becoming NAD+. A 2025 review considered the human results and the questions left unanswered. I'd check what people received before treating a blood rise as evidence of better health.

The numbers beside claims match the papers listed below. Links lead to a paper or a short published summary. Some experiments used mice; others tested cells grown in a dish, with no people receiving treatment. You can bring the relevant paper to your doctor with the question you want answered.

Which papers studied people, and which used animals or dishes?

Yoshino's 2021 Science paper tested women's muscles taking sugar from blood [1]. Yi's 2023 paper compared NMN amounts [3]. Conze's 2019 trial measured blood NAD+ after NR [4].

Those studies didn't test years of better health. Liao's 2021 paper studied exercise tests in runners [7]. Kim's 2022 paper examined older adults' leg tests [6].

Covarrubias's 2021 review explained NAD+ during aging [5]. Camacho-Pereira's 2016 experiment examined a protein breaking down NAD+ [2]. Fouquerel's 2014 review examined proteins using NAD+ to repair DNA [13].

Mills's 2016 paper and Yoshino's 2011 paper tested mice, whose results can't predict yours. Other experiments involved immune cells, which help the body fight germs [11][14][15]. A 2025 review assessed how little was established about lasting health benefits in people [12].

The study details below help your doctor find the right paper. DOI identifies a paper's permanent link; PubMed provides a short published summary. Chemical names needn't prevent you asking which changes the study participants experienced. If a claim links to the wrong paper, send the claim and link through the contact form.

  1. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. ↗
  2. Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016;23(6):1127-1139. ↗
  3. Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29-43. ↗
  4. Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019;9(1):9772. ↗
  5. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. ↗
  6. Kim M, Seol J, Sato T, et al. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Nutrients. 2022;14(4):755. ↗
  7. Liao B, Zhao Y, Wang D, et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021;18(1):54. ↗
  8. Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795-806. ↗
  9. de Guia RM, Agerholm M, Nielsen TS, et al. Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiol Rep. 2019;7(12):e14139. ↗
  10. Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536. ↗
  11. Shim DW, Cho HJ, Hwang I, et al. Intracellular NAD+ Depletion Confers a Priming Signal for NLRP3 Inflammasome Activation. Front Immunol. 2021;12:765477. ↗
  12. Vinten KT, Trętowicz MM, Coskun E, et al. NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Nat Metab. 2025. ↗
  13. Fouquerel E, Sobol RW. ARTD1 (PARP1) activation and NAD+ in DNA repair and cell death. DNA Repair (Amst). 2014;23:27-32. ↗
  14. Cameron AM, Castoldi A, Sanin DE, et al. Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species-mediated DNA damage. Nat Immunol. 2019;20(4):420-432. ↗
  15. Wang C, Chen Q, Chen S, et al. Serine synthesis sustains macrophage IL-1β production via NAD+-dependent protein acetylation. Mol Cell. 2024;84(4):744-759. ↗