Prof. PeptideProf. Peptide

NAD+

Longevity

Last reviewed: May 26, 2026

Also Known As: Nicotinamide adenine dinucleotide, NAD, Coenzyme I. Precursors: NMN (nicotinamide mononucleotide), NR (nicotinamide riboside)

Supplement Class: Essential pyridine nucleotide coenzyme / oral NAD+ precursor (NMN, NR) / sirtuin substrate / electron carrier in cellular respiration

Evidence Tier: Moderate — Strong for blood NAD+ elevation across NR and NMN trials (Martens et al. 2018, Igarashi et al. 2022, Conze et al. 2019, Yi et al. 2023); Moderate for functional/clinical outcomes (Yoshino et al. 2021 insulin sensitivity, Igarashi et al. 2022 muscle function, Liao et al. 2021 aerobic capacity); human lifespan evidence does not exist; FDA regulatory notification on NMN issued November 2022.

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What is NAD+ supplementation?

NAD+ (nicotinamide adenine dinucleotide) is an essential pyridine nucleotide coenzyme present in every living cell — central to energy metabolism (electron carrier in cellular respiration), longevity biology (substrate for sirtuin enzymes SIRT1–SIRT7), and DNA repair (substrate for PARP enzymes). NAD+ levels are reported to decline measurably with age, to roughly half of youthful baseline by midlife. Direct oral NAD+ supplementation has poor bioavailability, so practical supplementation uses precursor strategies: NMN (nicotinamide mononucleotide), one biochemical step from NAD+, with recent positive trial evidence (Yoshino et al. 2021, Igarashi et al. 2022, Yi et al. 2023); or NR (nicotinamide riboside), with the longer trial track record and cleaner regulatory status (Martens et al. 2018, Conze et al. 2019). Both reliably elevate blood NAD+ per the trials cited. The most direct alternative route is the NAD+ peptide (injectable / subcutaneous), which delivers NAD+ directly and bypasses oral bioavailability entirely. NAD+ supplementation is discussed alongside Epitalon for the pineal-axis arm of longevity protocols. NMN carries an FDA regulatory notification (November 2022, excluding it from dietary-supplement classification) — see Limitations below.

Reported benefits:

  • Reliable blood NAD+ elevation (Martens et al. 2018 NR ~60%; Igarashi et al. 2022 NMN ~38%)
  • Improved muscle insulin sensitivity in prediabetic populations (Yoshino et al. 2021 in Science, hyperinsulinemic-euglycemic clamp)
  • Improved gait speed and grip strength in older adults (Igarashi et al. 2022)
  • Increased oxygen uptake and ventilatory-threshold power in amateur runners (Liao et al. 2021)
  • Epigenetic age (DNAm Age) biomarker improvement (Yi et al. 2023 dose-response)
  • Sirtuin pathway activation via NAD+ substrate availability
  • PARP DNA-repair enzyme support via NAD+ substrate

Common dose: NR 300–1,000 mg/day, commonly split AM and midday. NMN 250 mg/day in the trials establishing its core effects; 600–900 mg/day in Yi et al. 2023's dose-ranging arms showing larger biomarker changes. Morning dosing is the common label pattern, aligned with NAD+'s reported circadian peak.

Product-quality notes: For NR, the NIAGEN ingredient form has the longest published trial record among branded formulations. For NMN, purity (β-NMN, the bioactive isomer, vs. α-NMN, inactive) is the relevant quality marker. Review the quality-markers checklist in the Product-quality considerations section below.

On this page
  1. 1.How does NAD+ supplementation work?
  2. 2.What does the evidence say NAD+ supplementation does?
  3. 3.How is NAD+ supplementation dosed in trials and on labels?
  4. 4.How NAD+ supplements are taken
  5. 5.What does NAD+ supplementation stack with?
  6. 6.Side effects and interactions
  7. 7.What isn't established about NAD+ supplementation
  8. 8.Product-quality considerations
  9. 9.NAD+ Supplement FAQ
  10. 10.References
  11. 11.Published Studies

How does NAD+ supplementation work?

Oral NAD+ supplementation works almost entirely through precursors — NMN and NR — that absorb intact, then convert to NAD+ in tissues via the salvage pathway. The intact NAD+ molecule itself is poorly absorbed; non-oral routes (sublingual, liposomal, IV, subcutaneous peptide) are the reported ways around this limitation.

  1. NAD+ in cellular metabolism. NAD+ is an essential coenzyme present in every living cell, functioning as an electron carrier in cellular respiration (shuttling electrons during ATP synthesis), a substrate for sirtuins (the SIRT1–SIRT7 enzyme family), and a substrate for PARP enzymes that detect and repair DNA strand breaks. NAD+ levels are reported to decline measurably with age — by midlife, levels may be roughly half of youthful baseline.
  2. The salvage pathway and precursor strategy. Cells synthesize NAD+ from precursors via the NAD+ salvage pathway: NR → NMN → NAD+ (or via longer pathways from tryptophan/niacin). Supplementing the precursors is reported as more efficient than supplementing NAD+ itself, because the precursor molecules are smaller, more bioavailable, and use the cell's native synthesis machinery.
  3. Oral bioavailability limitation for NAD+ itself. Intact NAD+ is poorly absorbed across the gut wall — most is degraded to nicotinamide before crossing into circulation. This is reported as the reason NMN and NR are the dominant oral routes, and why direct NAD+ delivery requires injectable or sublingual formulations to bypass first-pass metabolism.
  4. NR absorption and conversion. Nicotinamide riboside is reported to absorb intact via the gut Slc12a8 transporter, convert to NMN intracellularly via NRK1/NRK2 kinases, then to NAD+ via NMNAT enzymes. Martens et al. 2018 and Conze et al. 2019 documented roughly 60% blood NAD+ elevation at 500 mg twice-daily NR.
  5. NMN absorption — partial intact + partial hydrolyzed. NMN absorption is reported as partly intact (via Slc12a8) and partly hydrolyzed to NR in the gut, then reassembled to NMN inside cells. Igarashi et al. 2022 documented roughly 38% blood NAD+ elevation at 250 mg/day NMN; Yi et al. 2023's dose-ranging trial extends this to higher doses.
  6. Sirtuin activation. NAD+ is the obligate substrate for SIRT1–SIRT7 enzymes, which regulate gene expression, mitochondrial biogenesis, DNA repair, and stress responses. Elevating NAD+ availability is the mechanism underlying the "sirtuin activation" framing of longevity protocols.
  7. PARP and DNA repair. NAD+ also serves as substrate for PARP enzymes that detect DNA damage and initiate repair. Age-related NAD+ decline is reported to correlate with reduced DNA-repair capacity.

What does the evidence say NAD+ supplementation does?

Oral NAD+ precursor supplementation reliably elevates blood NAD+ levels — the most-replicated finding across the trials cited on this page. Functional and clinical outcome data is mid-stage: insulin sensitivity (Yoshino et al. 2021), muscle function (Igarashi et al. 2022), aerobic capacity (Liao et al. 2021), and biological-age biomarkers (Yi et al. 2023) show reported improvements. Human lifespan evidence doesn't exist.

  1. Blood NAD+ elevation (Strong). Multiple RCTs (Martens et al. 2018 NR, Igarashi et al. 2022 NMN, Conze et al. 2019 NR, Yi et al. 2023 NMN dose-ranging) consistently report significant blood NAD+ elevation with oral precursor supplementation — the most-replicated biomarker effect in this literature.
  2. Insulin sensitivity (Moderate-Strong). Yoshino et al. 2021 in Science used hyperinsulinemic-euglycemic clamp (the gold-standard methodology) to report significant muscle insulin sensitivity improvements with NMN in prediabetic postmenopausal women. Replication across subsequent trials is partial.
  3. Muscle function in older adults (Moderate). Igarashi et al. 2022 reports improved gait speed and grip strength with NMN in older men.
  4. Aerobic capacity and exercise performance (Moderate). Liao et al. 2021 (NMN dose-ranging in amateur runners) reports increased oxygen uptake and ventilatory-threshold power in the medium and high-dose groups relative to control, though peak VO2max itself did not differ significantly from baseline across groups.
  5. Biological-age biomarkers (Emerging). Yi et al. 2023 reports DNAm Age (epigenetic age clock) improvements at 600–900 mg/day NMN over 60 days. Whether epigenetic-age improvement translates to clinical longevity outcomes is not established.
  6. Cognitive function (Mixed). Trial results in the broader literature are mixed — the cognitive case is reported as less robust than the metabolic and physical-function case.
  7. Cardiovascular biomarkers (Emerging). Some evidence reports improved arterial stiffness and modest blood-pressure reduction with chronic NR supplementation; hard cardiovascular outcomes data is limited.
  8. Lifespan (Unknown). Animal-model lifespan extension is reported as dramatic and replicated across species; human lifespan trials don't exist.

How is NAD+ supplementation dosed in trials and on labels?

NAD+ supplement dosing reported across trials and labels is precursor- and goal-dependent. For NR: 300–1,000 mg/day, typically split AM and midday in the cited trials. For NMN: 250–900 mg/day, typically dosed in the morning. For oral NAD+ directly: 250–1,000 mg/day, with lower reported tissue delivery than precursors given the bioavailability limitation described above.

Prof. Peptide reports what trials established and what research communities practice, labelled separately. Neither is a recommendation.

  1. NR (nicotinamide riboside). Martens et al. 2018 used 1,000 mg/day (500 mg twice daily); Conze et al. 2019's dose-ranging trial tested 100–300 mg twice daily. Labels commonly range 300–1,000 mg/day.
  2. NMN. Yoshino et al. 2021 and Igarashi et al. 2022 used 250 mg/day; Yi et al. 2023's dose-ranging trial tested 300, 600, and 900 mg/day, with the 600–900 mg arms showing the larger reported biomarker changes. FDA regulatory status is discussed in the Limitations section below.
  3. Combined oral protocols. Some products and protocols combine NR and NMN (e.g., NR in the morning, NMN later in the day). This combination is mechanistically discussed in the literature but is not itself the subject of a published RCT.
  4. Oral NAD+ molecule itself. Labeled in the 250–1,000 mg/day range; reported tissue delivery is lower than precursor forms given the bioavailability limitation above.
  5. Sublingual NMN or NAD+. Marketed to bypass first-pass hepatic metabolism when held under the tongue before swallowing. Head-to-head bioavailability data versus oral capsules is limited in the trials reviewed for this page.

Reported timeline: blood NAD+ levels rise within days in the cited trials; functional/clinical effects were measured at 8–12 weeks. Trial endpoints are predominantly biomarker-based rather than subjective.

Label math. A "NAD+ booster 500 mg" product may combine 250 mg NMN with 250 mg of other ingredients, while "NMN 500 mg" is expected to mean 500 mg of the actual compound. Labels vary in whether they specify the precursor (NR, NMN, or intact NAD+) and its elemental mg content per serving.

How NAD+ supplements are taken

NAD+ precursors are taken orally as capsules, sublingual tablets, or powder. The table below reports what the cited trials and labels describe for precursor choice, timing, and route.

AspectReported
FrequencyOnce daily in the morning for lower doses in the cited trials; split AM/midday for higher doses (600+ mg), a pattern reported to maintain steadier NAD+ levels through the day.
Time of dayMorning is the common labeling pattern; NAD+ levels follow a circadian rhythm peaking in early morning per the mechanism discussed above. Some users report evening dosing interferes with sleep.
FoodAbsorption is not reported as strongly food-dependent in the cited trials.
FormNR or NMN as capsule/powder are the standard oral forms in the cited trials; sublingual products are marketed as an absorption-route alternative; the intact NAD+ molecule is the least bioavailable oral route per the mechanism above. The NAD+ peptide (injectable) bypasses oral bioavailability entirely.
Standardization markerProducts vary in whether they disclose which NMN stereoisomer they contain — only β-NMN is reported as bioactive, while α-NMN is an inactive byproduct found in some lower-purity products. Third-party (HPLC) purity testing is the relevant verification.
CyclingNo cycling protocol appears in the cited trials — chronic daily use is the trial-validated pattern.

What does NAD+ supplementation stack with?

Oral NAD+ precursors appear in the literature alongside the broader longevity/NAD+/autophagy stack. The shared theme is NAD+ substrate supply, which is discussed as complementary to direct NAD+ delivery via peptide injection, sirtuin activators, autophagy inducers, and senolytics.

With peptides

Oral NAD+ precursor supplements are discussed alongside the longevity peptide cluster. NAD+ peptide (injectable/subcutaneous) delivers NAD+ directly into circulation, bypassing the salvage pathway. Oral precursors (NMN, NR) feed the salvage pathway continuously through the day — different kinetics, the same overall direction of effect. Epitalon is discussed as adding the pineal-axis longevity arm — telomere maintenance and circadian regulation through a separate pathway. A protocol described in this literature combines a daily oral NMN or NR baseline, periodic NAD+ peptide injections, and Epitalon courses — three different layers of longevity biology (salvage-pathway substrate, direct tissue delivery, pineal regulation) with no documented negative interaction between them.

With supplements

  1. NMN (dedicated profile) — the most proximal NAD+ precursor, with the more recent positive trial evidence cited above; see the dedicated profile for NMN-specific dosing and regulatory detail.
  2. Resveratrol — a sirtuin activator; discussed in the Sinclair-protocol pairing as NAD+ precursor supplying the substrate that resveratrol-activated sirtuins consume.
  3. Spermidine — an autophagy activator via EP300 inhibition, a separate aging-biology mechanism discussed as complementary to NAD+ supply.
  4. Quercetin — a senolytic (often paired with fisetin), a separate aging-biology mechanism and common co-occupant in longevity-stack products.
  5. Apigenin — a CD38 inhibitor; CD38 consumes NAD+, so reducing CD38 activity is discussed as complementary to precursor supplementation, though this specific combination is not itself RCT-validated.
  6. CoQ10 — supports mitochondrial electron transport; NAD+ feeds Complex I of the electron transport chain, and CoQ10 carries electrons forward from there.

With lifestyle factors

  1. Intermittent fasting / time-restricted eating. Fasting is reported to independently elevate NAD+ levels via SIRT1 activation, mechanistically additive to precursor supplementation.
  2. Endurance exercise. Exercise is reported to raise NAD+ via NAMPT upregulation in muscle, a separate route to the same pathway precursor supplementation targets.
  3. Caloric restriction. CR is one of the more validated longevity interventions in animal models, partly attributed to NAD+/sirtuin pathway activation — mechanistically overlapping with precursor supplementation.
  4. Circadian alignment. NAD+ levels are reported to follow a circadian rhythm peaking in early morning, which labels commonly cite as the rationale for morning precursor dosing.
  5. Biomarker tracking. Trial-measured effects are biomarker-based (DEXA, HbA1c, biological-age clocks, lipid panels) rather than subjective, per the Research section above.

Side effects and interactions

Oral NAD+ precursors show a favorable safety profile in the published trials cited on this page at supplemental doses. The main considerations reported are mild GI effects, niacin-flush interaction at very high combined doses, and an open question about the cancer context given NAD+'s dual role in DNA repair and cellular metabolism.

Common (mostly transient)

  1. Mild GI discomfort — reported occasionally, particularly with NR at higher doses or on an empty stomach.
  2. Mild flushing — reported as uncommon with NMN/NR alone (neither carries the niacin-flush mechanism); more likely reported when combined with high-dose niacin.
  3. Headache or dizziness — reported occasionally, generally mild and dose-related.
  4. No serious adverse events are documented at standard supplemental doses across the human RCT base cited above.

Less common (watch-list)

  1. Active cancer — a context-dependent open question. NAD+ supports DNA repair (potentially protective) and PARP activity, but also supports cancer-cell metabolism; oncology coordination is standard guidance in this context.
  2. Long-term safety beyond 12 months — most cited trial data extends to 8–12 weeks; multi-year safety has not been directly characterized by RCT.
  3. Insomnia with evening dosing — reported by some users; morning dosing is the common label pattern.

Drug and supplement interactions

  1. Chemotherapy — NAD+ precursors are reported to potentially affect both DNA-repair pathways and cancer-cell metabolism; specialist input is standard guidance before combining with active oncology treatment.
  2. PARP inhibitors (olaparib, niraparib, rucaparib) — NAD+ precursors are reported to potentially interact with PARP inhibitor activity; oncologist guidance is standard before coadministration.
  3. Niacin / nicotinic acid — high-dose niacin causes flushing via a different pathway; combining at high doses may amplify the flush reaction. Typical NR/NMN doses alone don't produce this effect.
  4. Other longevity supplements (resveratrol, spermidine, quercetin, fisetin) — no negative interaction is documented; see the Stacks section above.
  5. Pregnancy and breastfeeding — data are insufficient; NAD+ biology in pregnancy is not well characterized.

What isn't established about NAD+ supplementation

NAD+ supplementation is a widely used longevity intervention with reliable biomarker effects but considerable open questions about translation to clinical outcomes.

Blood NAD+ vs tissue NAD+ vs clinical outcomes. Trials reliably show oral precursors raise blood NAD+ levels. Whether blood NAD+ elevation translates to meaningful tissue NAD+ elevation across relevant tissues (brain, heart, kidney, muscle) is less directly characterized — each step in the chain from blood biomarker to tissue level to cellular function to clinical outcome carries its own uncertainty.

Human lifespan evidence. Doesn't exist and won't for decades. Animal-model lifespan extension is striking; human extrapolation remains unproven.

NMN regulatory uncertainty. The FDA's November 2022 notification that NMN is excluded from dietary-supplement classification creates ongoing legal ambiguity. Enforcement has been minimal and sales continue; whether the situation resolves via legislation or a formal FDA reversal isn't established.

NMN vs NR head-to-head outcomes. Both precursors reliably raise blood NAD+ in the trials cited above. Which produces larger functional/clinical effects per dose has not been rigorously tested head-to-head at scale. NR has the longer trial track record; NMN has the more recent positive trials.

Dose-response ceiling. Trial data (Yi et al. 2023) suggests benefit plateaus somewhere in the 600–900 mg/day range for the biomarkers measured. Whether doses above 1 g/day produce additional benefit isn't well-characterized.

Cancer context dual role. NAD+ supports DNA repair and PARP activity (generally protective roles) but also fuels cancer-cell metabolism. Clinical implications for people with a cancer history or active oncology treatment aren't well defined by the current literature.

CD38 axis and apigenin pairing. CD38 activity, which consumes NAD+, is reported to increase with age and inflammation. Apigenin (a CD38 inhibitor) is discussed as potentially complementary to precursor supplementation by reducing NAD+ consumption — mechanistically plausible but not RCT-validated as a combination.

Product-quality considerations

Oral NAD+ precursors are widely available from supplement retailers. Quality is reported to vary, particularly around NMN purity (the β-NMN vs α-NMN stereoisomer question) and NR sourcing. The markers below are reported across sources as relevant to product quality.

Quality markers reported in the category

  • For NR: the NIAGEN ingredient form — the specific nicotinamide riboside chloride formulation used in the Martens et al. 2018 and Conze et al. 2019 trials cited above, with the longest published trial record for this precursor.
  • For NMN: explicitly labeled β-NMN — purity matters because only the β-isomer is reported as bioactive; α-NMN is an inactive contaminant reported in some lower-purity products.
  • Precursor mg per serving explicitly disclosed — rather than an undifferentiated "NAD+ complex" mass figure.
  • Third-party tested for purity — HPLC verification of NMN stereoisomer purity is the relevant test; USP, NSF, or ConsumerLab certifications signal broader independent verification.
  • cGMP-certified manufacturing facility.
  • No proprietary "longevity blends" that obscure the actual precursor dose behind fillers.
  • Sublingual options — marketed as bypassing first-pass hepatic metabolism, for the absorption-route alternative discussed above.
  • Manufacture-date freshness — NMN and NR are reported to degrade with prolonged exposure to heat and humidity.
  • NMN regulatory status — the FDA's 2022 notification discussed above is relevant context for any NMN purchase.
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NAD+ Supplement FAQ

NMN vs NR vs oral NAD+ — how do the three precursor routes compare?

The three routes have reported trade-offs. NMN (nicotinamide mononucleotide) is one biochemical step from NAD+ and has more recent positive trial evidence (Yoshino et al. 2021 insulin sensitivity, Igarashi et al. 2022 muscle function, Yi et al. 2023 dose-response) — but the FDA notified sellers in November 2022 that NMN is excluded from the dietary-supplement definition, though enforcement has been minimal. NR (nicotinamide riboside) has the longer trial track record and a cleaner regulatory status; the trials cited below (Martens et al. 2018, Conze et al. 2019) reliably document NAD+ elevation. Oral NAD+ itself (the intact molecule, not a precursor) has poor bioavailability and is reported as the least efficient of the three oral routes. The NAD+ peptide (injectable) delivers NAD+ directly and bypasses the oral-bioavailability limitation entirely.

Why is oral NAD+ itself less used than a precursor?

Intact NAD+ is reported as poorly absorbed across the gut wall — most of an ingested dose is broken down to nicotinamide and other components before crossing into circulation, meaning the actual NAD+ molecule reaching tissue is a small fraction of the label dose. NMN and NR are smaller, more bioavailable precursors that absorb intact (NR via the gut Slc12a8 transporter; NMN partly via the same route and partly hydrolyzed to NR before absorption), then convert to NAD+ in tissues via the salvage pathway, per the mechanism section above. Products marketed as "oral NAD+" are sold at a lower per-mg cost than precursor products, but the bioavailability difference affects tissue NAD+ delivered per dollar.

What is NMN's regulatory status as a supplement?

The FDA notified NMN sellers in November 2022 that NMN is excluded from the definition of a dietary supplement under FD&C Act §201(ff)(3)(B) — its stated basis is that pharmaceutical company Metro International Biotech filed an Investigational New Drug application for NMN before NMN was marketed as a supplement. The Natural Products Association and Council for Responsible Nutrition have pushed back through legal and legislative channels. As of this page's last review, NMN remains widely available from major US supplement retailers; enforcement of the FDA notification has been minimal and the agency's position has not been formally reversed.

How quickly do NAD+ supplement effects appear?

Not quickly, and not subjectively for most users in the trials cited. NAD+ is not reported as a stimulant or fast-acting compound; the cited trials measure biological-age biomarkers, muscle function, and insulin sensitivity over 8–12 weeks rather than subjective effects in the first weeks. Some trial participants and users report mild energy or cognitive changes after several weeks of consistent use; the primary trial endpoints are biomarker-based rather than subjective.

Can oral NAD+ precursors be combined with NAD+ peptide injections?

The two routes are described in longevity-protocol literature as complementary rather than redundant. NAD+ peptide (injectable/subcutaneous) delivers NAD+ directly into circulation, bypassing the salvage pathway. Oral NMN or NR feeds the salvage pathway continuously through the day — different kinetics, same overall direction of effect. A protocol described in this literature combines daily oral NMN or NR with periodic (weekly or bi-weekly) NAD+ peptide injections, sometimes alongside Epitalon for the pineal-axis longevity arm.

Does the evidence show NAD+ supplementation extends lifespan?

Not on current human data. Animal-model evidence is described as striking — NAD+ precursor supplementation extends lifespan and healthspan in aged mice. Human lifespan trials don't exist and are unlikely to exist for decades, since lifespan endpoints require multi-decade follow-up. Current human evidence measures intermediate biomarkers: blood NAD+ levels (reliably elevated by NMN and NR per the trials below), insulin sensitivity (Yoshino et al. 2021), muscle function (Igarashi et al. 2022), aerobic capacity (Liao et al. 2021), and epigenetic age markers (Yi et al. 2023). These are reported as meaningful intermediate signals rather than direct lifespan evidence.

How do NAD+ IV infusions compare to oral supplementation?

IV infusions (typically 500–1,000 mg over 2–4 hours) bypass oral bioavailability and are reported to produce dramatic acute NAD+ elevation, with subjective effects (energy, mental clarity) commonly reported during and after infusion in clinical settings such as addiction recovery clinics and longevity medicine practices. Costs are reported in the $200–$1,000+ per infusion range, with the sessions running multiple hours, and the durability of the acute elevation's benefit is not well characterized. The injectable NAD+ peptide is positioned in this literature as an intermediate option — self-administered subcutaneously, faster-acting than oral precursors, lower-cost than IV.

Is combining NAD+ precursors with resveratrol (the Sinclair protocol) mechanistically supported?

The mechanistic rationale connecting the two is described as coherent. Sirtuins are NAD+-dependent enzymes; resveratrol is reported to activate sirtuins; NAD+ precursors supply the substrate those enzymes require. The two act on the same pathway at different points. Trial evidence for the combination specifically — rather than for each compound alone — is thinner. Spermidine is discussed in the same literature as adding an autophagy-activation arm via a separate mechanism (EP300 inhibition); a four-supplement combination (NAD+ precursor, resveratrol, spermidine, and a senolytic such as fisetin or quercetin) is a commonly discussed longevity stack, with combination-specific trial evidence thinner than for the individual compounds.

References

  1. Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. https://pubmed.ncbi.nlm.nih.gov/29599478/
  2. Igarashi M, Nakagawa-Nagahama Y, Miura M, et al. Chronic nicotinamide mononucleotide supplementation elevates blood NAD+ levels and alters muscle function in healthy older men. NPJ Aging. 2022;8(1):5. https://pubmed.ncbi.nlm.nih.gov/35927255/
  3. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. https://pubmed.ncbi.nlm.nih.gov/33888596/
  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. https://pubmed.ncbi.nlm.nih.gov/31278280/
  5. Yi L, Maier AB, Tao R, et al. 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. https://pubmed.ncbi.nlm.nih.gov/36482258/
  6. Yoshino J, Baur JA, Imai SI. NAD+ intermediates: the biology and therapeutic potential of NMN and NR. Cell Metab. 2018;27(3):513-528. https://pubmed.ncbi.nlm.nih.gov/29249689/
  7. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021;18(1):54. https://pubmed.ncbi.nlm.nih.gov/34238308/

Published Studies

Plain-English summaries of the peer-reviewed studies behind the claims above. Click any title to read the source paper.

Nature Communications · 2018Open Access
Chronic Nicotinamide Riboside Supplementation Is Well-Tolerated and Elevates NAD+ in Healthy Middle-Aged and Older Adults →

Martens CR, Denman BA, Mazzo MR, et al.

A 6-week randomized double-blind placebo-controlled crossover trial of 500 mg nicotinamide riboside twice daily in 24 healthy middle-aged and older adults. Reports NR significantly elevated whole-blood NAD+ metabolism (~60% increase) and was well-tolerated.

NPJ Aging · 2022Open Access
Chronic Nicotinamide Mononucleotide Supplementation Elevates Blood NAD+ Levels and Alters Muscle Function in Healthy Older Men →

Igarashi M, Nakagawa-Nagahama Y, Miura M, et al.

A 12-week randomized double-blind placebo-controlled trial of 250 mg/day NMN in 42 healthy older men (average age 65). Reports NMN significantly elevated blood NAD+ levels by ~38% and improved muscle function metrics including gait speed and grip strength, with no serious adverse events.

Science · 2021Paywalled
Nicotinamide Mononucleotide Increases Muscle Insulin Sensitivity in Prediabetic Women →

Yoshino M, Yoshino J, Kayser BD, et al.

A 10-week randomized double-blind placebo-controlled trial of 250 mg/day NMN in 25 postmenopausal women with prediabetes. Reports NMN significantly increased muscle insulin sensitivity by hyperinsulinemic-euglycemic clamp without changing body weight, body composition, blood pressure, or plasma lipids.

Scientific Reports · 2019Open Access
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 →

Conze D, Brenner C, Kruger CL

An 8-week randomized double-blind placebo-controlled trial of NIAGEN-brand nicotinamide riboside chloride (100–300 mg twice daily) in 132 healthy overweight adults. Reports NR significantly elevated whole-blood NAD+ in a dose-dependent manner and was well-tolerated across all doses.

GeroScience · 2023Open Access
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 →

Yi L, Maier AB, Tao R, et al.

A 60-day randomized double-blind placebo-controlled dose-ranging trial of 300, 600, and 900 mg/day NMN in 80 healthy middle-aged adults. Reports all three doses significantly raised blood NAD+ versus placebo, dose-dependently; SF-36 physical performance and DNAm Age (biological age) markers improved in the 600 mg and 900 mg arms.

Journal of the International Society of Sports Nutrition · 2021Open Access
Nicotinamide Mononucleotide Supplementation Enhances Aerobic Capacity in Amateur Runners: A Randomized, Double-Blind Study →

Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M

A 6-week randomized, double-blind, placebo-controlled, four-arm trial (300/600/1,200 mg/day NMN vs. placebo) in 48 amateur runners training 5–6×/week. Reports oxygen uptake, percentage of VO2max, and ventilatory-threshold power increased more in the medium and high-dose groups than in the control group; peak VO2max itself did not differ significantly from baseline across groups.

NAD+ PrecursorNMNNRSirtuinsMitochondrialLongevity

Related Supplements

NMN (dedicated profile)ResveratrolSpermidineQuercetinApigeninCoQ10

Comparisons

NAD+ vs NMN vs NREpitalon vs NAD+

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