Overview
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme — not a peptide — present in every cell and central to redox reactions, sirtuin and PARP signaling, and mitochondrial energy metabolism. It is included in this peptide companion library because users overwhelmingly stack NAD+ (or its precursors NMN and NR) alongside peptide regimens, and because most competitors lump NAD+ in with peptides without disclosing it isn't one. Cellular NAD+ declines with age, and that observation has driven a large supplement and IV-clinic market. The clinical evidence behind raising NAD+ is weaker than the marketing, and the bioavailability question — whether oral, IV, or subcutaneous NAD+/NMN/NR meaningfully raises tissue NAD+ in ways that translate to clinical outcomes — remains genuinely contested.
Mechanism
Acts as an electron carrier in core metabolic pathways (glycolysis, TCA cycle, oxidative phosphorylation), and as a cosubstrate for sirtuins (SIRT1–7), PARPs, and CD38. Cellular NAD+ pools decline with age and in metabolic stress; the question of whether boosting them therapeutically reverses age-related dysfunction is the crux of the field. Notably, NAD+ itself is a large polar molecule with poor membrane permeability — most of the supplementation effect is thought to come via precursor uptake (NMN, NR, niacin) followed by intracellular synthesis, not direct NAD+ entry into cells.
Evidence by indication
We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.
Age-related cellular / metabolic decline
Strong preclinical and mechanistic story. Small human RCTs of oral NR and NMN show measurable increases in blood NAD+ levels but inconsistent or null effects on functional endpoints (insulin sensitivity, walking distance, cardiovascular markers). The link from 'blood NAD+ went up' to 'aging slowed' is not established in humans.
Energy / fatigue / 'hangover recovery' (IV clinic use)
Marketed widely as an IV 'energy boost.' No published RCT supports this indication. Subjective reports are heavily confounded by saline volume, B-vitamin co-infusions, and clinic placebo effect.
No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.
Cognitive performance
Mechanistic plausibility from sirtuin and mitochondrial roles in neurons. A handful of small human studies of NR or NMN report mixed effects on cognitive endpoints. No replicated RCTs supporting cognitive enhancement in healthy adults.
Athletic performance / exercise capacity
A few small human RCTs of NMN in amateur runners and middle-aged men report modest improvements in aerobic capacity. Effect sizes are small; methodological quality is mixed; replication outside the original lab groups is limited.
Addiction recovery / withdrawal management (IV NAD+)
Specialty IV-NAD+ addiction-recovery clinics market this indication aggressively. Published evidence is limited to case series and small uncontrolled observational reports. No RCT.
No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.
Studied dose ranges
The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.
Oral NR / NMN human studies typically test 100–1000 mg/day. Note the unit math: 1000 mg = 1,000,000 mcg. Very different scale from injectable peptides — this is a supplement, not a microgram-dose peptide.
Clinic IV NAD+ infusions are typically 100–1000 mg per session, infused over 1–4 hours. Faster infusion is poorly tolerated (nausea, chest pressure, anxiety). No standardized clinical protocol; vendor-specific.
Compounded SubQ NAD+ is increasingly common as a 'painless' alternative to IV. Doses cluster at 50–250 mg per injection. No published RCT validates SubQ bioavailability or efficacy.
Contraindications
- Active malignancy — sirtuin and NAD+ metabolism intersect with cancer biology in complex, dose- and tumor-type-dependent ways; consult oncology before use
- Pregnancy and breastfeeding (no human safety data for high-dose IV/SubQ administration)
- Severe cardiac arrhythmia (rapid IV infusion has caused chest pressure, tachycardia, anxiety)
- Known hypersensitivity to NAD+ or compounding excipients
- Caution with chemotherapy regimens whose mechanism involves NAD+/PARP signaling — discuss with oncologist
Reported side effects
- IV: nausea, chest pressure, abdominal cramping, flushing, anxiety during rapid infusion (rate-dependent — slowing the infusion typically resolves)
- SubQ: injection-site stinging, redness; some users describe more discomfort than typical peptide injections
- Oral NR / NMN: generally well tolerated; mild GI upset, headache
- Flushing (from niacin metabolites)
- Theoretical: long-term effects of sustained high cellular NAD+ on sirtuin activity, cancer biology, and immune signaling are not fully characterized in humans
Reconstitution & storage
NAD+ for IV / SubQ use is supplied by compounding pharmacies as either a sterile solution (e.g., 100 mg/mL) or a lyophilized powder. Not the typical sub-mg microgram-dose peptide reconstitution math: a 100 mg SubQ dose at 100 mg/mL = 1 mL = 100 units on a U-100 syringe (a full syringe). Many clinics and users prefer divided dosing or smaller volumes due to injection discomfort. NMN and NR are oral capsules / powders — no reconstitution.
Storage. Compounded sterile solutions: refrigerate 2–8 °C, follow vendor expiration. Lyophilized: refrigerate; reconstituted within 30 days typical. Oral NR / NMN: room temperature, dry, protect from light.
Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.
Editorial note
DRAFT — pending Wayne's review. Included in the 'peptide companion' library as a deliberate stretch — it's a coenzyme commonly stacked with peptides, and most competitor apps quietly lump it in with peptides without disclosure. The class field literally says 'Coenzyme — NOT a peptide' so the badge prevents user confusion. Editorial posture: respect the biology, name the bioavailability question, and don't oversell the IV market — the energy/hangover/addiction-recovery indications are Tier 4 and that needs to land. Vendor_class is 'mixed' (the spec asked for 'compound' but the type doesn't allow that value — closest honest mapping is mixed since NAD+ exists across compounded IV/SubQ and OTC supplement channels).
Citations
- [1]Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adultsMartens CR, Denman BA, Mazzo MR, et al. · Nature Communications · 2018 · PMID 29467442Human RCT showing NR raises blood NAD+; null on most functional endpoints. Anchor for Tier 3 metabolic indication.View source
- [2]Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic womenYoshino M, Yoshino J, Kayser BD, et al. · Science · 2021 · PMID 33888596Small Phase 2 RCT showing improved muscle insulin sensitivity with NMN in prediabetic women; primary human trial cited for the metabolic indication.View source
- [3]Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind studyLiao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M · Journal of the International Society of Sports Nutrition · 2021 · PMID 34238308Small RCT of oral NMN and aerobic capacity; anchor for Tier 3 athletic-performance indication.View source