NAD+

From Retapedia, the free peptide encyclopedia
"NAD+" redirects here. For other uses, see NAD+ (disambiguation).
Medical disclaimer. This article is for informational purposes only and does not constitute medical advice. Consult a qualified clinician before considering any compound discussed below. See Retapedia : Medical disclaimer.

NAD+ (also known as NAD+ or Nicotinamide Adenine Dinucleotide) is a therapeutically researched peptide studied for its effects on anti-aging, recovery, metabolic health. Essential cellular coenzyme for energy, DNA repair, and aging. Precursors (NMN/NR) or IV boost NAD+ levels. Cellular benefits proven, longevity unproven.

NAD+ (Nicotinamide Adenine Dinucleotide) is a critical coenzyme found in all living cells that plays essential roles in cellular metabolism, energy production, DNA repair, and aging processes. NAD+ levels naturally decline with age (up to 50% by middle age), contributing to mitochondrial dysfunction, reduced cellular repair capacity, and various age-related conditions. NAD+ serves as a crucial substrate for sirtuins (SIRT1-7) and poly(ADP-ribose) polymerase (PARP) enzymes that regulate cellular longevity, stress adaptation, and DNA repair mechanisms.

Natty status
NAD+ is generally regarded as compatible with natural bodybuilding, though competitive federations may differ. See § Natty status.
Contents [hide]
  1. 1 Overview
  2. 2 Mechanism of action
  3. 3 Reported effects
  4. 4 Dosage and administration
  5. 5 Natty status
  6. 6 Research
  7. 7 Related compounds
  8. 8 References
  9. 9 External links

Overview

While NAD+ itself is poorly absorbed orally, precursor compounds including Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) effectively increase NAD+ levels via salvage pathways.

Clinical trials demonstrate NR/NMN supplementation (250-1000mg daily) safely elevates blood NAD+ levels, with observed improvements in mitochondrial function, insulin sensitivity, muscle performance, and cardiovascular markers.

However, experts emphasize there is no conclusive evidence that NAD+ supplementation extends human lifespan despite cellular benefits.

Common administration methods include oral supplementation (NR/NMN), IV infusions (500-1500mg, 2-4 hours), and subcutaneous injections (50-100mg weekly).

Side effects are generally mild and transient, including nausea, flushing, headache, and GI discomfort.

Potential concerns include unknown long-term safety profile, theoretical tumorigenesis risk (unproven in humans), and significant cost ($1000+ for IV sessions).

NAD+ restoration represents a promising but still investigational approach to cellular regenerative medicine, requiring more robust long-term human clinical trials to establish definitive therapeutic applications and longevity benefits.

Mechanism of action

Boosts cellular energy production and DNA repair. Activates longevity enzymes. Improves metabolism and mitochondrial health. Cellular benefits proven, human longevity unproven.

Reported effects

Effects reported in the literature and from preclinical models include:

  • In older adults, NAD+ precursor supplementation shows potential benefits for mitochondrial efficiency, cellular stress responses, and cognitive performance, though human findings vary across populations and dosing strategies [9] Phase II
  • Oral nicotinamide reduces the incidence of new non-melanoma skin cancers and actinic keratoses in high-risk patients, while topical nicotinamide consistently improves wrinkles, texture, pigmentation, and skin barrier function via the NAD+ salvage pathway [11] Phase II
  • NAD+ and nicotinamide support neuroprotection by enhancing mitochondrial function and cognitive resilience in Alzheimer's models (countering PARP1-driven NAD+/ATP depletion), protecting retinal ganglion cells in glaucoma by sustaining NAD levels, and linking autophagy failure to neuronal death; inherited NAD biosynthesis (NMNAT1) defects cause an ocular-predominant neurologic disorder [3][4][6][13] Preclinical
  • The NAD+/SIRT1 axis links energy metabolism to epigenetic and circadian regulation of the liver, positioning NAD+ restoration as an experimental strategy for age-related liver metabolic dysfunction and steatotic liver disease [5][8] Preclinical
  • Depletion of NAD+ and NAD+-dependent enzyme activity is implicated as a driver of mitochondrial dysfunction, impaired autophagy, and cellular senescence across cancer, chronic kidney disease, inflammatory bowel disease, rheumatoid arthritis, and reproductive and gestational aging [2][7][10][12][14][15][18][19][1] Preclinical
  • By sustaining mitochondrial quality control and acting as an NAD+-dependent metabolic checkpoint in stem-cell aging, NAD+ restoration is proposed as a gerotherapeutic strategy to improve metabolic resilience and immune function during human ageing [16][17][20][21] Preclinical

Evidence grades: FDA approved Phase III Phase II Phase I Preclinical Anecdotal

Dosage and administration

⚠
Dosage information is included for encyclopedic purposes only. Retapedia does not provide medical advice. See Retapedia : Medical disclaimer.

Oral NMN

  • Beginner: 250mg daily on empty stomach
  • Intermediate: 500-600mg daily, split into 2 doses
  • Advanced: 900-1200mg daily for intensive protocols

Oral NR

  • Beginner: 100-300mg daily
  • Standard: 500mg daily (most studied dose)
  • Advanced: 1000-2000mg daily for therapeutic goals

IV Infusion

  • Standard: 500-750mg per session over 2-4 hours
  • Intensive: 1000-1500mg per session

Subcutaneous Injection

  • Start: 50mg (0.5mL) once weekly for 4 weeks
  • Maintenance: 100mg (1mL) 1-3x weekly

Timing

  • Take oral forms morning/early afternoon (may affect sleep if taken late)

Frequency

  • Oral daily, IV weekly to monthly, injections 1-3x weekly

Natty status

See also: Peptide § Natty status

NAD+ is generally regarded as compatible with the natty designation, particularly when used for therapeutic healing purposes. Opinions vary across natural bodybuilding federations, and athletes who compete should consult the rulebook of their respective sanctioning body.[22]

Research

137 active clinical trials on record — highest phase: Phase 4
View on ClinicalTrials.gov · fetched Jul 17, 2026

The peptide has been the subject of 33 studies and reference works collected on this site. The full bibliography is in § External links below.

Other peptides in this catalogue with overlapping mechanisms or status:

5-Amino-1MQ Not natty
Oral small-molecule NNMT inhibitor that raises NAD+ and S-adenosyl methionine to boost fat-cell energy expenditure. Studied only in rodents for fat loss; no human trials exist.
mots-c Not natty
Mitochondrial-derived peptide that activates AMPK to improve insulin sensitivity and reproduce exercise-like metabolic adaptations in preclinical models. Investigational and WADA-banned; no approved human use.
Glutathione Natty
The body's master intracellular antioxidant. Scavenges free radicals and supports liver phase-II detoxification. Regenerates vitamins C and E. Used for liver health, skin brightening, and anti-aging.
Ozempic Natty
Reduces appetite and slows digestion for 15-21% weight loss. Improves blood sugar control. Lowers heart attack and stroke risk by 20%.

References

  1. ^ Insights into SIRT2 inhibition from machine learning-assisted multi-level screening of the NCI database.
  2. ^ Repurposing Syrosingopine for Cancer Therapy: Lactate Trapping and ISR Sensitization as Metabolic Vulnerabilities. Recent review
  3. ^ From DNA repair to neurodegeneration: PARP1 mechanisms and inhibitor strategies in Alzheimer's disease. Recent review
  4. ^ Clinical and biochemical footprints of inherited cofactor disorders. Recent review
  5. ^ Epigenetic Information Loss and Chronosenescence in Liver Aging: From Molecular Mechanisms to Therapeutic Interventions. Recent review
  6. ^ From autophagy-lysosomal deficits to neurodegeneration in Niemann-Pick type C1 disease: implications for age-related neurodegenerative disorders. Recent review
  7. ^ Nicotinamide N-methyltransferase in Inflammatory bowel disease: Multidimensional Regulation, Mechanistic Insights, and Therapeutic Potential. Recent review
  8. ^ MicroRNA-SIRT1 crosstalk in liver diseases: molecular regulation of metabolism, inflammation, and cell survival. Recent review
  9. ^ Targeted Supplementation and Nutritional Strategies for Healthy Aging: A Review of Physiological and Molecular Benefits. Recent review
  10. ^ Nutritional Regulation of Ovarian Bioenergetics: Implications for Reproductive Aging and Female Infertility. Recent review
  11. ^ Skin Cancer Prevention and Antiaging: Role of Nicotinamide. Recent review
  12. ^ The SIRT1/STAT3 axis as a central regulator of immune, inflammatory, and lipid metabolic dysregulation in rheumatoid arthritis: therapeutic implications. Recent review
  13. ^ Prospects for Neuroprotective Therapies in Glaucoma: Drug Targets and Emerging Clinical Strategies. Recent review
  14. ^ Nicotinamide N-methyltransferase as a stress-responsive metabolic-epigenetic regulator of tubular senescence in chronic kidney disease. Recent review
  15. ^ Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics. Recent review
  16. ^ Mitochondrial quality control in human ageing and longevity. Recent review
  17. ^ Cell-Type-Specific Calibration of Mitochondrial Ubiquitination in Stem Cell Fate Decisions. Recent review
  18. ^ Mitochondrial dysfunction and cellular senescence drive accelerated gestational aging in spontaneous preterm birth: a narrative review. Recent review
  19. ^ SIRT5/7 desuccinylation in cancer: linking metabolism, immunity, and drug resistance. Recent review
  20. ^ Network Destabilization in Aging: Mitochondrial Dysfunction, Nutrient Sensing, and Chronic Inflammation as Interconnected Drivers. Recent review
  21. ^ The mitochondrial logic of inflammaging: how energy imbalance drives fibroblast SASP and tissue-specific aging. Recent review
  22. a b World Anti-Doping Agency. (2026). Prohibited List 2026.

External links

Categories: Peptides | Therapeutic peptides | Anti-aging | Recovery | Metabolic health | Oral

This page was last updated on July 17, 2026, at 16:23 (UTC).

Research last reviewed on July 17, 2026.

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