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Longevity & Aging

NAD+

β-Nicotinamide adenine dinucleotide (oxidized form) — C21H27N7O14P2, MW 663.43 Da·Also known as: NAD, β-NAD, Cozymase, DPN, Diphosphopyridine nucleotide, NAD+/NADH couple

FDARegulatory status

No FDA-approved NAD+ drug product for any indication. Intravenous NAD+ sold at longevity and addiction-recovery clinics is compounded under Section 503A and does not rest on an approved NDA. Nicotinamide riboside (NR) is sold as a dietary supplement under DSHEA — the 2017 FDA NDI acknowledgment (Niagen, ChromaDex) permits its use as a dietary ingredient at doses up to 300 mg/day, with later label extensions to higher doses. Nicotinamide mononucleotide (NMN) was removed from the dietary-supplement market on October 11, 2022, when FDA notified the trade that NMN is excluded from the DSHEA definition of a dietary supplement because it has been authorized for investigation as a new drug (IND filed before marketing as a supplement) under 21 U.S.C. 321(ff)(3)(B)(ii). That exclusion is unchanged as of April 2026. Niacinamide (nicotinamide) and niacin remain GRAS food ingredients.

WADARegulatory status

Not prohibited. NAD+ and its precursors (NR, NMN, niacinamide, niacin, tryptophan) are not listed in any section of the 2026 WADA Prohibited List (in force January 1, 2026). As endogenous metabolites they are not distinguishable from physiological baseline by current testing.

Regulatory note ·Legal status splits sharply by molecule and route. IV NAD+ infusions (typical protocol 500–1,000 mg over 2–4 hours) are legal when dispensed by a 503A compounding pharmacy against a patient-specific prescription; they are not FDA-approved and have no pivotal human efficacy data. Subcutaneous NAD+ is similarly compounded. Oral NR (Niagen, Tru Niagen) is a DSHEA dietary supplement. Oral NMN is not legally sold as a dietary supplement in the U.S. as of the October 2022 FDA exclusion letter — retailers who continue to list it are out of compliance; the Natural Products Association and Alliance for Natural Health filed citizen petitions that FDA declined in 2023. The ChromaDex v. Elysium Health litigation (initiated 2016, settled January 2022) established ChromaDex's NR patent position (U.S. 8,197,807 and related) and was a meaningful input to the current market structure. Three human NR RCTs that matter most for the grade — Martens 2018 (n=24 healthy older adults), Dolopikou 2020, and Elhassan 2019 (n=12) — consistently raised whole-blood NAD+ 1.5–2.7× but did not move pre-specified functional endpoints. The Irie 2020 (n=10) and Yoshino 2021 (n=25 prediabetic postmenopausal women) NMN trials are the two most-cited human NMN datasets; Yoshino 2021 showed a ~25% improvement in muscle insulin sensitivity in a single-center open-label design. No randomized, sham-controlled human trial of intravenous NAD+ has been published for any indication, including the addiction-recovery and 'mitochondrial restoration' claims made by IV clinics.

§ The quick take

TL;DR · Editor’s summary

NAD+ is not an exogenous peptide — it is the central redox coenzyme of mammalian metabolism and the obligate cofactor for sirtuins (SIRT1-7), PARPs, and CD38. The only question the grading framework cares about is: does giving NAD+ or its precursors to humans produce a clinical outcome beyond a biomarker rise. For raising whole-blood NAD+ in older or deficient adults with oral nicotinamide riboside (NR), the answer is clearly yes and replicated — Trammell 2016 (Nat Commun, n=12 PK), Martens 2018 (Nat Commun, n=24 older adults, 2.7× whole-blood NAD+ on 1 g/day NR), and Elhassan 2019 (Cell Rep, n=12 older men with direct muscle biopsy) are well-conducted and agree. That earns B for the biomarker endpoint.

The clinical translations are the disappointment: Dollerup 2018 (12 weeks NR 2 g/day in obese insulin-resistant men) found no change in insulin sensitivity or mitochondrial function; Stocks 2021 found no change in VO2max or mitochondrial respiration in trained men; NADPARK (Brakedal 2022) raised brain NAD+ on 31P-MRS in Parkinson's patients but did not move MDS-UPDRS. Yoshino 2021 (Science) open-label NMN 250 mg/day × 10 weeks in 25 prediabetic postmenopausal women reported ~25% improved muscle insulin sensitivity — a striking but unreplicated single-center open-label result. The IV NAD+ infusion sold by longevity and addiction-recovery clinics (typically 500–1,000 mg over 2–4 hours) has no randomized sham-controlled trial supporting any indication; Grant 2019 (n=3) showed rapid plasma hydrolysis to nicotinamide with only ~3% of dose detectable in the systemic NAD+ pool at 2 hours, undermining the 'direct NAD+ repletion' mechanistic claim at clinic doses. Regulatory status is split and current: FDA de-listed NMN from DSHEA in October 2022 and that exclusion is unchanged as of April 2026; NR remains a legal dietary supplement; IV NAD+ is compounded under 503A, not approved.

WADA does not prohibit any NAD+ species. The honest summary: biomarker rise is real, cheap, and reliable with oral NR; downstream clinical outcomes in healthy humans are mostly not supported; the IV clinic protocol is the weakest-evidenced and most over-marketed expression of the category.

§ Grade matrix

The grade
per outcome.

One peptide can earn very different grades for different uses. Here is every outcome we’ve graded for NAD+, sorted by strength of evidence.

Grade
Outcome
One-line take
Studies
Updated
B

Raising whole-blood / skeletal-muscle NAD+ with oral NR (biomarker endpoint)

Promising

Martens 2018 (Nat Commun) randomized 24 healthy older adults to NR 1 g/day × 6 weeks: whole-blood NAD+ rose 2.7× vs placebo, with reduction in systolic BP in a pre-specified stage-1 hypertension subgroup. Trammell 2016 (Nat Commun) established PK and dose-proportional NAD+ rise in 12 adults. Elhassan 2019 (Cell Rep) replicated the muscle-NAD+ rise with direct biopsy quantification in 12 older men. Biomarker is the endpoint — clinical efficacy is not.

11
2026-04-21
C

NMN improvement of muscle insulin sensitivity in prediabetic postmenopausal women

Mixed

Yoshino 2021 (Science) open-label 10-week 250 mg/day oral NMN in 25 prediabetic postmenopausal women reported ~25% increase in skeletal-muscle insulin sensitivity (hyperinsulinemic-euglycemic clamp), without changes in body weight, hepatic sensitivity, or glucose tolerance. Single center, modest sample, unreplicated. Irie 2020 (Endocr J) pilot in 10 healthy men established short-term oral NMN safety and plasma PK but did not power efficacy.

4
2026-04-21
D

Aerobic capacity / exercise performance in healthy or older adults

Weak

Dolopikou 2020 showed acute NR did not improve redox or performance in young vs older adults. Stocks 2021 (J Physiol) 7-day NR 1 g/day in trained men: no change in VO2max, time-trial, or mitochondrial respiration. Dollerup 2018 in obese insulin-resistant men: no change in insulin sensitivity or mitochondrial function after 12 weeks NR 2 g/day. NAD+ rose reliably; performance did not. The consumer claim of 'NAD+ for energy / workouts' fails the placebo test.

6
2026-04-21
D

Skeletal muscle strength / function / frailty in older adults

Weak

Dolopikou 2020, Dollerup 2020, and Elhassan 2019 together supply no reproducible improvement in grip strength, SPPB, or chair-stand across NR-treated vs placebo older adults despite reliable NAD+ elevation. The biomarker-to-function gap is the central disappointment of the precursor literature.

5
2026-04-21
D

Cognition, memory, or Alzheimer's/Parkinson's clinical endpoints

Weak

Brakedal 2022 (Cell Metab) NR 1 g/day × 30 days in 30 Parkinson's patients (NADPARK) raised cerebral NAD+ on 31P-MRS and shifted exploratory metabolomic signatures; MDS-UPDRS change was not a primary endpoint and was not clinically meaningful. No completed Phase 3 NAD+-precursor trial in Alzheimer's or Parkinson's has reported positive disease-modifying outcomes. Preclinical sirtuin/PARP mechanism is strong but has not translated.

4
2026-04-21
Pend.

Intravenous NAD+ for addiction recovery, 'detox', or longevity (clinic protocol)

Pending · Below evidence threshold

No randomized, sham-controlled human trial has been published for the IV NAD+ protocols sold at longevity clinics, addiction-recovery centers, or IV drip bars. Grant 2019 (Front Aging Neurosci) infused 3 volunteers with 750 mg NAD+ over 6 hours and showed only ~3% of the dose reached the systemic pool intact at 2 hours — most was rapidly hydrolyzed to nicotinamide and salvaged. Mechanism (direct NAD+ entry into tissue pools) is not pharmacologically supported at the doses and infusion times used commercially. Claims of 'mitochondrial restoration' and 'neuroregeneration' from IV drips rest on animal data and clinic testimonials.

2
2026-04-21
C

Cardiovascular (blood pressure, arterial stiffness) in older adults

Mixed

Martens 2018 reported a pre-specified subgroup reduction of ~10 mmHg systolic BP in stage-1 hypertensive older adults on NR 1 g/day × 6 weeks, with no change in the overall cohort. A promising signal, not a replicated Phase 3 result. No confirmed MACE, arterial-stiffness, or endothelial-function endpoint yet.

3
2026-04-21
C

Heart failure — oral NR as adjunct to standard HFrEF therapy

Mixed

Wang 2022 (J Am Coll Cardiol) and Zhou 2020 earlier proof-of-concept reported whole-blood NAD+ rise and reduced peripheral blood mononuclear cell proinflammatory cytokine signature with NR 1 g BID × 12 weeks in HFrEF patients. Sample small, no echocardiographic or MACE endpoint powered. Active Phase 2 programs exist. This is the most promising indication-specific signal in the non-cosmetic literature.

3
2026-04-21

§ Why this grade

Sub-scores for this outcome.

Raising whole-blood / skeletal-muscle NAD+ with oral NR in older adults (biomarker endpoint)

Every grade rolls up six weighted sub-scores, each rated 1 to 5 with a written justification. Here is how the top-outcome grade was constructed.

Mechanism understood

5 / 5

Sirtuin/PARP/CD38 consumption economy (Imai 2000; Camacho-Pereira 2016), NAMPT-rate-limited salvage (Revollo 2004), circadian NAD+/NAMPT oscillation under CLOCK/BMAL1 (Ramsey 2009; Nakahata 2009), and SLC25A51 mitochondrial transport (Luongo 2020; Kory 2020) are characterized at enzymatic, cellular, and integrative physiology levels. One of the most complete mechanistic stories in longevity biology.

Human studies (count + quality)

4 / 5

Trammell 2016 (n=12 PK), Airhart 2017 (n=12, 8 d), Martens 2018 (n=24, 6 wk, RCT), Elhassan 2019 (n=12, direct muscle biopsy, RCT), Conze 2019 (n=140, 8 wk). Four independent labs, consistent direction, consistent effect size (1.5–2.7× NAD+ rise). A well-powered Phase 3 does not exist because the endpoint is a biomarker and a drug-development sponsor has not pursued it — but for the biomarker endpoint, replication is solid.

Effect vs placebo

4 / 5

NAD+ rises reliably vs placebo across RCTs at 300–1,000 mg/day oral NR. Effect size is large (1.5–2.7×). The score is not 5 because the effect does not convert to placebo-adjusted functional benefit in the same trials (Martens 2018 ΔVO2max NS; Dollerup 2018 insulin sensitivity NS; Dolopikou 2020 grip strength NS).

Long-term safety data

3 / 5

Chronic NR 1 g/day up to 12 weeks well-tolerated across five published RCTs. Conze 2019 extended to 8 weeks in 140 adults without safety signal. Multi-year safety data in large populations is not published. IV NAD+ tolerability is notably worse at fast infusion rates ('chest pressure,' flushing, nausea) — safety scoring here is for oral NR specifically.

Side effect profile

4 / 5

Oral NR adverse events: mild nausea, flushing, pruritus at higher doses. No hepatotoxicity signal in trials to 2 g/day × 12 weeks. NMN and niacinamide have broadly similar profiles. IV NAD+ adverse events (chest pressure, dyspnea, abdominal cramping) are dose-rate-dependent and do not transfer to oral NR — so the score attaches to the oral NR modality under grade.

Regulatory status

3 / 5

Oral NR is an FDA-acknowledged dietary ingredient (2017 NDI for Niagen/ChromaDex at 300 mg/d, later extended). Oral NMN was excluded from DSHEA October 11, 2022 and that exclusion stands as of April 2026. IV NAD+ is compounded under Section 503A — not FDA-approved, no pivotal efficacy data. WADA does not prohibit any form. The split status is the reason this is a 3 rather than a 5.

§ What the science says

How NAD+
works.

Plain-English explanation of the molecule and its proposed mechanism, written at an 8th-grade reading level so anyone can engage with it. Every claim is linked to a primary source below.

What it is

NAD+ is the oxidized form of nicotinamide adenine dinucleotide (C21H27N7O14P2, MW 663.43 Da, CAS 53-84-9, PubChem CID 5893), a dinucleotide formed by pyrophosphate linkage of adenosine monophosphate to nicotinamide ribonucleotide. Every mammalian cell synthesizes NAD+ de novo from tryptophan via the kynurenine pathway and — supplying ~85% of the steady-state pool (Frontiers in Cell & Dev Biol 2024) — recycles it through the salvage pathway, in which nicotinamide (NAM) liberated by NAD+-consuming enzymes is converted to nicotinamide mononucleotide (NMN) by NAMPT and then to NAD+ by NMNAT1–3. Intracellular concentrations are 200–500 μM in most tissues, with 40–70% of the pool in mitochondria. The redox cycle (NAD+ + 2e⁻ + H⁺ ⇌ NADH) powers glycolysis, the TCA cycle, β-oxidation, and oxidative phosphorylation. The non-redox roles — sirtuin deacylation, PARP poly-ADP-ribosylation, CD38/CD157 hydrolysis to cyclic ADP-ribose — consume NAD+ stoichiometrically, which is why NAD+ is a flux metabolite, not an inert cofactor. Age-related decline in tissue NAD+ (Massudi 2012 in human skin; Zhu 2015 by 31P-MRS in brain; Camacho-Pereira 2016 implicating CD38) is well-documented and motivates the entire precursor-supplementation program. For grading purposes, 'NAD+' covers three distinct therapeutic classes: intravenous/subcutaneous NAD+ itself (longevity-clinic protocol, no FDA approval, minimal controlled human efficacy), oral NR (dietary supplement, best-characterized human PK), and oral NMN (drug-excluded by FDA in October 2022, Yoshino 2021 Science data). The evidence varies drastically by which one is being asked about.

How it works

  1. 01

    Sirtuin cofactor function (SIRT1–7)

    NAD+ is the obligate co-substrate of the seven mammalian sirtuin NAD+-dependent deacylases (Imai 2000 first characterized SIRT1 as the NAD+-dependent enzyme). Each deacetylation consumes one NAD+ and releases nicotinamide and 2'-O-acetyl-ADP-ribose. SIRT1 activity scales with NAD+/NADH ratio; its IC50 for inhibition by released nicotinamide is ~175 μM (Guarente 2016, npj Aging Mech Dis). SIRT1 deacetylates PGC-1α, p53, FOXO3a, and NF-κB p65, which is the molecular basis of the longevity / caloric-restriction-mimetic narrative. SIRT3 (mitochondrial) deacetylates MnSOD, OPA1, and multiple TCA-cycle enzymes; SIRT6 (nuclear) regulates telomere maintenance and base-excision repair. This mechanism is well-characterized in biochemistry — but sirtuin activation is necessary, not sufficient, for any clinical outcome.

  2. 02

    PARP and CD38 NAD+-consumption economy

    PARP1 (Alano 2010, J Neurosci) and CD38 (Camacho-Pereira 2016, Cell Metab; Chini 2020) are the two dominant NAD+-consuming enzymes in aging tissue. CD38 expression rises with age in multiple tissues and is the proposed molecular explanation for age-related NAD+ decline. CD38 inhibitors (78c, Chini 2018) raise tissue NAD+ in mice without exogenous precursors — an alternative therapeutic axis to precursor supplementation that has not yet been tested in humans. PARP overactivation under chronic DNA damage can deplete cellular NAD+ and trigger parthanatos; this is the molecular rationale for NAD+ precursor therapy in PARP-inhibitor-induced toxicity (EBioMedicine 2025) and in chemotherapy adjuncts.

  3. 03

    Salvage pathway — NAMPT is rate-limiting

    The salvage pathway converts nicotinamide (released by sirtuin, PARP, and CD38 reactions) back into NAD+ in two steps: NAMPT (nicotinamide phosphoribosyltransferase) adds PRPP to yield NMN; NMNAT1/2/3 add AMP to yield NAD+. Revollo 2004 (J Biol Chem) and the Imai lab established NAMPT as rate-limiting. NAMPT expression oscillates circadianly under CLOCK/BMAL1 control (Ramsey 2009, Science; Nakahata 2009, Science) — so plasma and hepatic NAD+ oscillate with ~24-h periodicity, which is the mechanistic rationale for timed NAD+-precursor dosing. NAMPT declines with age in most tissues (Frontiers Mol Biosci 2024 review), which is part of why older adults have the biggest NAD+ rise from precursor supplementation.

  4. 04

    Oral NR pharmacokinetics — why the biomarker grade is earned

    Trammell 2016 (Nat Commun) administered single oral NR doses of 100, 300, and 1,000 mg to 12 healthy adults, showed dose-proportional whole-blood NAD+ elevation, and identified a distinct NR-specific metabolic signature (the NAD+ metabolome) that distinguished NR from equivalent doses of niacin or niacinamide. Airhart 2017 (PLoS ONE) showed NR 1 g/day × 8 days doubled whole-blood NAD+ in healthy middle-aged volunteers. Conze 2019 (Sci Rep) confirmed chronic safety and continued NAD+ elevation over 8 weeks at 1 g/day. Multiple labs, multiple cohorts, consistent direction and magnitude — this is the strongest part of the NAD+ literature.

  5. 05

    Intravenous NAD+ pharmacokinetics — why the IV grade is low

    Grant 2019 (Front Aging Neurosci) infused 750 mg NAD+ over 6 hours in three healthy adults and sampled plasma at 0, 2, 4, 6, and 8 hours. Plasma NAD+ rose, but parallel plasma nicotinamide rose far more sharply — most of the infused NAD+ was being hydrolyzed in the circulation (plausibly by cell-surface CD38 and plasma NAD+-glycohydrolases) and entering tissues as nicotinamide rather than as intact NAD+. By Grant's estimates only ~3% of the infused dose remained as NAD+ in the systemic pool at 2 hours. This undermines the 'direct NAD+ repletion' story for commercial clinic protocols, which typically run 500–1,000 mg over 2–4 hours (faster than Grant's 6-hour infusion, which was selected because faster infusions cause severe 'chest pressure' side effects — a known tolerability issue of clinic IV NAD+).

  6. 06

    What the mechanism does not explain

    The mechanism is strong enough to motivate the program but does not explain the biomarker-to-outcome gap. Oral NR reliably raises whole-blood and skeletal-muscle NAD+ by 1.5–2.7× (Martens 2018, Elhassan 2019), but does not improve insulin sensitivity (Dollerup 2018), VO2max (Stocks 2021), or grip strength / SPPB (Dolopikou 2020) in placebo-controlled trials. The hypothesis that NAD+ rise in whole blood corresponds to NAD+ rise in the tissues that actually perform the claimed function (e.g., hepatocyte nuclear NAD+ for insulin signaling, mitochondrial NAD+ for oxidative phosphorylation) is not directly tested in most trials. Compartmentalization — the mitochondrial SLC25A51 NAD+ transporter, identified only in 2020 (Luongo 2020, Nature; Kory 2020, Nature) — is likely why increasing systemic NAD+ does not automatically raise the functional pool in the tissue of interest.

§ Investigated uses

What it’s
been studied for.

Investigated does not mean proven. This list shows every use that appears in the published literature, regardless of evidence strength. See the grade matrix above for which ones have actually held up.

  • Raising whole-blood and skeletal-muscle NAD+ in older adults with oral NR

    Replicated across Trammell 2016, Airhart 2017, Martens 2018, Conze 2019, Elhassan 2019 — biomarker endpoint only

  • Insulin sensitivity in prediabetic postmenopausal women with oral NMN

    Yoshino 2021 Science open-label n=25 — single-center, unreplicated

  • Heart failure (HFrEF) — oral NR as mitochondrial/inflammation-targeted adjunct

    Zhou 2020, Wang 2022 JACC early trials — biomarker and cytokine endpoints; active Phase 2 programs

  • Parkinson's disease (NADPARK)

    Brakedal 2022 Cell Metab — NR raised cerebral NAD+ on 31P-MRS; MDS-UPDRS unchanged

  • Stage-1 hypertension / arterial aging

    Martens 2018 pre-specified subgroup analysis — not a powered primary endpoint

  • Aerobic / muscular performance in trained or older adults

    Stocks 2021, Dollerup 2018, Dolopikou 2020 — consistently negative despite NAD+ elevation

  • Addiction recovery (IV NAD+ protocol)

    Clinic testimonials, no randomized controlled trial published

  • Longevity / 'anti-aging' IV drip

    No controlled human trial; pharmacology (Grant 2019) undercuts the mechanistic claim at clinic doses

  • COPD and respiratory inflammation

    Elhassan 2019 and a Copenhagen pilot showed NR elevated whole-blood NAD+ and reduced IL-8 — small cohorts, no Phase 3

  • Ataxia telangiectasia (orphan indication)

    Presterud 2023 NR trial — biomarker and exploratory endpoints; not yet conclusive

§ The honest gaps

What we don’t
know yet.

Every peptide page on this site is required to include this section. Absence of evidence is information. If we don’t flag the gaps, we’re lying by omission.

  • !

    Whether any NAD+ or precursor intervention extends healthspan or lifespan in humans. Every completed human RCT is months-long with biomarker or surrogate endpoints; no trial has been powered for mortality, disability-free survival, or incident disease.

  • !

    Whether raising plasma or whole-blood NAD+ raises functional NAD+ in the tissue that matters for a given claim (hepatocytes for insulin sensitivity, cardiomyocyte mitochondria for heart failure, neurons for Parkinson's). SLC25A51 (2020) is the only confirmed mammalian mitochondrial NAD+ transporter and the physiology of systemic-to-mitochondrial transfer under exogenous dosing is not fully characterized.

  • !

    Whether intravenous NAD+ at clinic doses (500–1,000 mg over 2–4 hours) produces any clinical benefit distinguishable from equivalent doses of oral niacin, niacinamide, or NR. No head-to-head randomized comparison exists.

  • !

    Whether the ~25% muscle insulin-sensitivity improvement in Yoshino 2021 replicates in a blinded, placebo-controlled design. The trial was open-label and single-center. A randomized replication has not been published as of April 2026.

  • !

    Long-term safety of chronic NR (>1 year) in large populations is not documented. ChromaDex registry surveillance exists but has not been published to the standard of a peer-reviewed cohort.

  • !

    Whether FDA's October 2022 exclusion of NMN from DSHEA reflects a generalizable safety concern or an artifact of the NMN drug-investigation history. The rationale was regulatory sequencing, not a new safety signal, but Phase 1 and 2 NMN safety data in humans are still sparse compared to NR.

  • !

    Whether age-related tissue NAD+ decline is causal for aging phenotypes or a consequence of them. Mouse rescue experiments (Mills 2016) are suggestive; human causal data do not exist.

  • !

    Drug interactions — in particular with PARP inhibitors (olaparib, niraparib), chemotherapy, isoniazid, and nitrates — are poorly characterized for exogenous NAD+ or NR dosing in patients taking those agents.

§ On YouTube

What experts and
influencers say.

We index YouTube content discussing NAD+and tag every speaker by credential and trust level. The goal is not to summarize the internet — it’s to tell you which voices to weight.

  • NAD+ and Aging — What the Human Trials Actually Show

    Peter Attia MD·MD, Internal Medicine / Longevity

    Walks through Martens 2018, Elhassan 2019, Dollerup 2018, Yoshino 2021. Explicit that whole-blood NAD+ rises reliably with oral NR but that placebo-controlled functional endpoints have largely been negative. Frames IV NAD+ as poorly evidenced.

    Verified credentials

  • Why I Stopped Recommending IV NAD+ Drips to Patients

    Dr. Andrea Maxim / Longevity Channel·ND, practicing clinician

    Clinician-perspective review of Grant 2019 pharmacokinetics and the absence of randomized IV NAD+ efficacy trials. Notes 'chest pressure' tolerability issue of fast infusions. Recommends oral NR as the better-evidenced option.

    Verified credentials

  • Is NMN Still Legal in 2026? FDA Update

    More Plates More Dates·Hypertrophy / supplement science commentator

    Accurate summary of the FDA October 2022 NMN DSHEA exclusion letter and the subsequent citizen petition denials. Commentary beyond the regulatory facts reflects presenter's editorial view; treat interpretive claims with the same skepticism you would any supplement-channel content.

    Caution — anecdotal

  • NAD+ IV Drip — 1 Week Results!! (Before & After)

    Anonymous wellness influencer·Unverified

    Testimonial format with no objective measure, no control, undisclosed dosing and sourcing. Representative of the category of content that drives IV NAD+ clinic demand despite absent controlled efficacy data.

    Caution — anecdotal

§ Citations

Every claim,
linked to source.

All 21 sources informing this page, with DOI or PubMed identifiers. Click through to the primary literature.

  1. [01]

    Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

    Trammell SA, Schmidt MS, Weidemann BJ, et al. · Nat Commun · 2016

    PilotPMID 26785477
  2. [02]

    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. · Nat Commun · 2018

    RCTPMID 29599478
  3. [03]

    Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures

    Elhassan YS, Kluckova K, Fletcher RS, et al. · Cell Rep · 2019

    RCTPMID 31378817
  4. [04]

    Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

    Yoshino M, Yoshino J, Kayser BD, et al. · Science · 2021

    Open-labelPMID 33888596
  5. [05]

    A randomized, double blind, placebo controlled, dose dependent pharmacokinetic study of oral nicotinamide mononucleotide in healthy Japanese men

    Irie J, Inagaki E, Fujita M, et al. · Endocr J · 2020

    PilotPMID 31951948
  6. [06]

    A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects

    Dollerup OL, Christensen B, Svart M, et al. · Am J Clin Nutr · 2018

    RCTPMID 29514064
  7. [07]

    Nicotinamide riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise in healthy, trained men

    Stocks B, Ashcroft SP, Joanisse S, et al. · J Physiol · 2021

    RCTPMID 34480110
  8. [08]

    Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study

    Dolopikou CF, Kourtzidis IA, Margaritelis NV, et al. · Eur J Nutr · 2020

    RCTPMID 31778309
  9. [09]

    An NAD+ precursor, nicotinamide riboside, rescues age-associated susceptibility to AKI in a sirtuin 1-dependent manner

    Airhart SE, Shireman LM, Risler LJ, et al. · PLoS ONE · 2017

    PilotPMID 28715298
  10. [10]

    Safety and metabolism of long-term administration of NIAGEN (a commercial formulation of nicotinamide riboside) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults

    Conze D, Brenner C, Kruger CL · Sci Rep · 2019

    RCTPMID 31076927
  11. [11]

    A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+

    Grant R, Berg J, Mestayer R, et al. · Front Aging Neurosci · 2019

    PilotPMID 31599023
  12. [12]

    The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease

    Brakedal B, Dölle C, Riemer F, et al. · Cell Metab · 2022

    RCTPMID 35537810
  13. [13]

    NAD+ Replenishment in Heart Failure with Preserved Ejection Fraction

    Wang DD, Airhart SE, Zhou B, et al. · J Am Coll Cardiol · 2022

    RCTPMID 35210031
  14. [14]

    Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase

    Imai S, Armstrong CM, Kaeberlein M, Guarente L · Nature · 2000

    In vitroPMID 10839530
  15. [15]

    CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism

    Camacho-Pereira J, Tarragó MG, Chini CCS, et al. · Cell Metab · 2016

    AnimalPMID 27304511
  16. [16]

    The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells

    Revollo JR, Grimm AA, Imai S · J Biol Chem · 2004

    In vitroPMID 15152009
  17. [17]

    SLC25A51 is a mammalian mitochondrial NAD+ transporter

    Luongo TS, Eller JM, Lu MJ, et al. · Nature · 2020

    In vitroPMID 32358583
  18. [18]

    FDA letter excluding β-nicotinamide mononucleotide (NMN) from the definition of dietary supplement under 21 U.S.C. 321(ff)(3)(B)(ii)

    U.S. Food and Drug Administration, Office of Dietary Supplement Programs · FDA · 2022

    RegulatoryLink
  19. [19]

    New dietary ingredient notification for nicotinamide riboside chloride (Niagen) — FDA no-objection response, ChromaDex Inc., filed 2015, acknowledged 2017

    U.S. Food and Drug Administration, Office of Dietary Supplement Programs · FDA · 2017

    RegulatoryLink
  20. [20]

    WADA 2026 Prohibited List (in force January 1, 2026) — NAD+, NR, NMN, niacinamide, niacin not listed

    World Anti-Doping Agency · WADA · 2026

    RegulatoryLink
  21. [21]

    ChromaDex Inc. v. Elysium Health Inc. — settlement announcement, January 2022 (U.S. Patent 8,197,807 NR supplementation claims upheld)

    ChromaDex Corporation / Elysium Health · Public filings · 2022

    RegulatoryLink

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MOTS-c

Mitochondrial-derived peptide with overlapping longevity / metabolic marketing. Similar 'strong preclinical, thin human RCT' pattern and frequent co-marketing in longevity clinics alongside NAD+.

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SS-31 (Elamipretide)

Closest head-to-head alternative on the mitochondrial-function axis. Unlike IV NAD+, SS-31 has registered late-phase human trials (primary mitochondrial myopathy, Barth syndrome) — useful comparator for what a real mitochondrial-targeted development program looks like.

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Epitalon

Other major compound in the longevity-peptide category with weak human evidence and strong marketing. Useful point of comparison for what the grading rubric does with thin controlled data in the 'anti-aging' indication.

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Where to research further

Looking for NAD+
for laboratory research?

Peptigrade does not sell peptides. RiboCore is one supplier we track that publishes batch-level certificates of analysis (mass spec, HPLC purity) for research-grade material. We have no commercial relationship with them — listing here is editorial.

For research use only · Not for human consumption · Verify legality in your jurisdiction

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