NAD+

NAD+ is best known for powering cellular energy production and supporting cellular repair, and because levels naturally decline with age, it's widely studied for aging and metabolism. It's a coenzyme (a cofactor built from two nucleotides) present in every cell, not a peptide, and it's included in this library because it's often used alongside peptide protocols. NAD+ itself is not FDA-approved as a drug; its precursors NMN and NR are sold as dietary supplements (the FDA lifted a 2022 restriction on NMN in 2025, though NMN still needs a formal supplement filing), and IV NAD+ is offered at wellness clinics in a regulatory gray area.

NAD+ (and its precursors NMN and NR) has been studied for aging and metabolism, since cellular NAD+ levels decline with age. Multiple human trials of oral NMN and NR have shown reliable increases in blood NAD+ levels. What is much less clear is whether raising NAD+ translates into meaningful longevity, cognitive, or disease-outcome benefits — that has not been demonstrated in large long-term human trials. The biomarker effect is better supported than any clinical-benefit claim.

NAD+ itself is not FDA approved as a pharmaceutical drug for any indication. NAD+ precursors are widely available as dietary supplements: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are sold as supplements; niacin (nicotinic acid) is FDA-approved as a prescription drug for dyslipidemia and is also available OTC as a vitamin. FDA reversed its 2022 exclusion of NMN in two letters dated September 29, 2025 (reaffirmed in follow-up letters in December 2025), concluding NMN is not excluded from the dietary-supplement definition; NMN nonetheless remains a New Dietary Ingredient (NDI), so each marketer must file an NDI notification. IV NAD+ administration is widely available through wellness clinics in the US and other jurisdictions but operates in a regulatory gray area (compounded by 503A pharmacies for clinical IV use; no FDA approval for IV NAD+ for any indication). Not a peptide — NAD+ is a coenzyme (a nucleotide-derived cofactor) included in the Vialwise library because the library scope explicitly extends to "compounds researchers running peptide protocols use." Not listed in the WADA 2026 Prohibited List — note separately that WADA Method M2.2 prohibits IV infusions and/or injections of more than 100 mL per 12-hour period, a volume some clinic IV NAD+ courses may exceed.

NAD+ is not FDA-approved as a drug; oral precursors are sold as supplements and IV NAD+ operates in a regulatory gray area. NAD+ is not listed by name on the WADA Prohibited List, but WADA Method M2.2 prohibits IV infusions or injections of more than 100 mL per 12-hour period — a volume some clinic IV NAD+ courses may exceed, which matters for tested athletes. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. NAD+ and its precursors (NR, NMN) are not approved by the FDA as pharmaceutical drugs for any indication outside the approved niacin/nicotinic acid use for dyslipidemia. Information in this entry is informational, not medical advice. IV NAD+ administration through wellness clinics is widespread but operates in a regulatory gray area; researchers and clinicians should be aware of the regulatory context.

⚠️ not a peptide — coenzyme/cofactor. NAD+ (nicotinamide adenine dinucleotide) is a small-molecule coenzyme made of two nucleotides joined by phosphate groups. It is not a peptide (no amino acid bonds; not synthesized by ribosomes). Its inclusion in the Vialwise library reflects the library's explicit scope broadening to "compounds researchers running peptide protocols use" — NAD+ is one of the most widely used non-peptide compounds in research-community longevity and recovery protocols.

⚠️ Endogenous coenzyme — supplementation modulates levels of a natively-expressed compound. NAD+ is naturally present in every cell as a cofactor for hundreds of enzymatic reactions, including all redox reactions in cellular respiration, sirtuin enzyme activity, and parp dna-repair activity. Cellular NAD+ levels decline with age, driven in part by accelerated CD38-mediated NAD+ degradation. The supplementation rationale is restoration toward youthful NAD+ levels — not introduction of a foreign compound.

⚠️ Multiple administration routes with substantially different pharmacokinetics and clinical positioning. NAD+ supplementation is delivered through several distinct routes that should not be conflated: (1) Oral NAD+ precursors (NMN, NR) — well-supported by published clinical pharmacokinetic and safety studies showing reliable elevation of blood NAD+ levels;[¹][²] FDA dietary supplement category. (2) IV NAD+ infusion — directly delivers NAD+ to circulation; widely offered at wellness clinics; published clinical evidence is much thinner and predominantly retrospective/observational rather than RCT-grade.[³] (3) Subcutaneous or intramuscular NAD+ injection — research-community use; the published evidence base for this route is essentially absent. (4) Niacin (nicotinic acid) — FDA-approved prescription drug for dyslipidemia at higher doses; precursor to NAD+ via different metabolic pathway than NR/NMN. Researchers should select the route based on the published evidence supporting that specific route, not transfer evidence across routes.

⚠️ The cellular-NAD+-elevation effect is real; the clinical translation to longevity / disease outcomes is uncertain. Multiple human RCTs of oral NMN and NR demonstrate reliable elevation of whole blood NAD+ and metabolite levels.[¹][²] What is much less clear is whether elevating cellular NAD+ levels translates to clinically meaningful longevity, healthspan, cognitive, metabolic, or disease-outcome benefits in humans. Some RCTs of NMN/NR have reported positive secondary endpoints (muscle function in older men, arterial stiffness, inflammatory markers);[²][⁵] the strongest claims (lifespan extension, disease prevention) have not been demonstrated in large-scale long-duration human trials. Researchers should distinguish between "biomarker effect demonstrated" and "clinical benefit demonstrated."

NAD+ (nicotinamide adenine dinucleotide) is a small-molecule coenzyme present in every living cell, where it serves as a substrate for hundreds of enzymatic reactions across cellular metabolism. The compound exists in two forms — oxidized (NAD+) and reduced (NADH) — and the NAD+/NADH ratio is the central currency of cellular redox state. Beyond the canonical role in redox reactions of cellular respiration and metabolism, NAD+ serves as a substrate for several non-redox enzymes including the sirtuin family of NAD+-dependent deacetylases (implicated in aging, metabolism, and stress response), PARP enzymes (DNA damage repair and signaling), and CD38 (an NADase abundantly expressed on immune cells). The interaction between NAD+ availability and these enzymatic systems is the mechanistic basis for the broad research interest in NAD+ supplementation for aging, metabolism, and disease prevention.

The age-related decline. A decline in NAD+ is a recognised feature of ageing and may play a causal role in it.[⁴] The frequently repeated figure of "10–80% reductions across tissues" is not stated in the cited source, and no primary source establishing that range has been located — it is omitted here rather than carried on inherited authority. The decline is driven by multiple factors including increased CD38-mediated NAD+ degradation, decreased NAD+ synthesis capacity, and increased PARP activation in the context of accumulating DNA damage. The age-related NAD+ decline is the primary mechanistic rationale for NAD+ supplementation as a longevity intervention.

NAD+ precursors and pathways. Cellular NAD+ is synthesized via several biosynthetic pathways: - The Preiss-Handler pathway (from nicotinic acid / niacin) — the FDA-approved niacin product feeds this pathway. - The salvage pathway (from nicotinamide → NMN → NAD+) — NMN supplementation feeds this pathway directly. - The NR pathway (nicotinamide riboside → NMN → NAD+) — NR supplementation feeds this pathway one step upstream of NMN. - The de novo pathway (from tryptophan via kynurenine intermediates) — minor contribution under most circumstances.

Different precursors enter the synthesis pathway at different points. NMN and NR are the most-studied precursors for elevating cellular NAD+ in human supplementation contexts; both have demonstrated reliable elevation of blood NAD+ levels in published RCTs.[¹][²] A post-hoc analysis of the same trial cohort as citation [1] examined how those blood NAD+ levels tracked with routine hematologic, lipid and liver laboratory parameters — associations that are hypothesis-generating rather than evidence of clinical benefit.[⁶]

IV NAD+ administration. Direct IV NAD+ delivery bypasses the precursor metabolism and elevates circulating NAD+ acutely. The clinical positioning of IV NAD+ is more controversial than oral precursor supplementation: published clinical evidence is much thinner, predominantly retrospective/observational, and the practice operates in a regulatory gray area in the US (NAD+ for IV use is compounded by 503A pharmacies; no FDA approval exists). Recent retrospective tolerability studies have characterized the IV NAD+ vs IV NR safety profiles in real-world wellness-clinic settings.[³]

Common research interests. NAD+ supplementation use spans: - Longevity / "anti-aging" protocols — the dominant research-community use, driven by the age-related NAD+ decline framing and the sirtuin/PARP mechanism literature. - Cognitive support and brain health — research-community use for cognitive aging, with mixed evidence base. - Metabolic health (insulin sensitivity, fatty liver) — research-community use; some RCT-level evidence supporting NMN and NR for metabolic biomarkers. - Recovery from acute illness, jet lag, post-anesthesia, etc. — clinical wellness IV NAD+ use; not RCT-validated. - Addiction recovery — research-community use of IV NAD+ as adjunct in opioid and alcohol withdrawal; clinical evidence is observational rather than RCT-grade. - Stack with peptides — common as part of longevity, mitochondrial-support, or recovery protocols.

Regulatory status. NAD+ itself is not FDA-approved as a pharmaceutical drug. Niacin (nicotinic acid, an NAD+ precursor via the Preiss-Handler pathway) is FDA-approved at higher doses for dyslipidemia. NMN and NR are sold as dietary supplements under the FDA's DSHEA framework — they are not approved as drugs.

The NMN regulatory reversal (2022 → 2025). In 2022 FDA took the position that NMN was excluded from the dietary-supplement definition on drug-preclusion ("race-to-market") grounds, which pulled NMN listings from several retail channels. In two letters dated September 29, 2025 (announced October 2, 2025), FDA responded to citizen petitions and reversed that position, concluding NMN is not excluded from the dietary-supplement definition; FDA reaffirmed the reversal in follow-up New Dietary Ingredient letters in December 2025. Important nuance: the reversal does not make NMN freely marketable — NMN remains a New Dietary Ingredient (NDI), so each marketer must file an NDI notification (NDIN) with FDA; self-affirmed GRAS status does not substitute for that filing. NR was never subject to the exclusion.

IV NAD+ administration is offered at wellness clinics in the US and other jurisdictions; regulatory enforcement varies. NAD+ is not listed in the WADA 2026 Prohibited List. Separately from substance status, WADA Method M2.2 (a Specified Method, unchanged on the 2026 List) prohibits IV infusions and/or injections of more than 100 mL per 12-hour period except where received in a hospital treatment, surgical procedure, or clinical diagnostic investigation. Typical clinic IV NAD+ courses ( delivered in larger-volume bags over 2–4 hours) can exceed that volume, so a tested athlete could face an anti-doping issue via the infusion method even though the substance itself is not prohibited. Researchers subject to anti-doping testing should evaluate infusion volume, not just substance status.

Commonly reported

• Active cancer concern — NAD+ is required for PARP-mediated DNA repair (which can support cancer cell survival under chemotherapy stress) and for sirtuin activity (which has complex tumor-promoting and tumor-suppressing roles depending on context).
• Long-term safety of supraphysiologic NAD+ elevation — incompletely characterized.
• Pregnancy and lactation safety — limited data; default to caution.

Active malignancy or undiagnosed cancer concern — caution

Pregnancy and lactation — caution; default to manufacturer/clinician guidance

Pediatric use: limited data — should not be used in researchers under 18 in research-community settings

Known hypersensitivity — contraindicated

Regulatory note (US): NAD+ itself is not FDA-approved. NMN/NR are dietary supplements — FDA reversed its 2022 NMN exclusion in September 2025 (reaffirmed December 2025), but NMN remains a New Dietary Ingredient requiring an NDI notification. IV NAD+ operates in a regulatory gray area.

Regulatory note (WADA): NAD+ is not listed in the 2026 WADA Prohibited List. However, WADA Method M2.2 prohibits IV infusions and/or injections of more than 100 mL per 12-hour period (outside hospital treatment, surgical procedures, or clinical diagnostic investigations) — some clinic IV NAD+ infusion volumes may exceed this. Tested athletes should check infusion volume, not just substance status.

Coenzyme

A helper molecule that an enzyme needs in order to carry out a chemical reaction.

Endogenous

Naturally produced by the body, rather than introduced from outside.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Half-life

Roughly how long the body takes to clear half of a dose. A long half-life is why some compounds can be taken only once a week.

Investigational

Still being studied and not yet approved by regulators for general use.

1. Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. (2023). 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, 45(1):29-43. doi: 10.1007/s11357-022-00705-1.(PMID 36482258)
2. Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T, Yamauchi T. (2022). Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging, 8(1):5. doi: 10.1038/s41514-022-00084-z.(PMID 35927255)
3. Reyna K, Heinzen G, Patel N, Ritter M, Siojo A, Legere H, Pojednic R. (2026). Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. Frontiers in Aging, 7:1652582. doi: 10.3389/fragi.2026.1652582.(PMID 41704678)
4. Conlon N, Ford D. (2022). A systems-approach to NAD+ restoration. Biochemical Pharmacology, 198:114946. doi: 10.1016/j.bcp.2022.114946.(PMID 35134387)
5. Han K, Klein RJ, Recupero TC, Russo AC, Sharma R, Gupta AK, Hassanzadeh S, Huffstutler RD, Dagur PK, Fisk B, Redekar NR, Sack MN. (2026). NAD+ augmentation by nicotinamide riboside engages SLIT2/ROBO1 signaling to attenuate Th17 inflammation in psoriasis. JCI Insight, 11(12). doi: 10.1172/jci.insight.203826.(PMID 42048163)
6. Kuerec AH, Wang W, Fokke KDM, Yi L, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V, Maier AB. (2025). Association between blood nicotinamide adenine dinucleotide levels and blood laboratory parameters at baseline and after nicotinamide mononucleotide supplementation in middle-aged healthy individuals: post hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial. GeroScience, 48(3):3305-3313. doi: 10.1007/s11357-025-01968-0.(PMID 41162813)

• Glutathione — same mechanism class
• Cartalax — shared research area
• Cortagen — shared research area
• Epitalon — shared research area
• FOXO4-DRI — shared research area
• Humanin — shared research area