Overview
NMN (β-nicotinamide mononucleotide) is a nucleotide — not a peptide — that sits one step upstream of NAD+ in the salvage pathway. It is included in this library because users overwhelmingly stack NMN alongside peptide regimens for 'longevity,' and because most competitor apps quietly include NAD+/NMN/NR with peptides without disclosing they are not peptides. The bioavailability question is genuinely live: studies suggest much of an oral NMN dose is dephosphorylated to nicotinamide riboside (NR) at the gut wall before reaching systemic circulation, with the SLC12A8 NMN-specific transporter proposed by Yoshida et al. but disputed by Schmidt & Brenner. Several small human RCTs show NMN raises blood NAD+ levels; the leap from 'NAD+ went up' to 'aging slowed' is not established.
Mechanism
NMN is converted to NAD+ by NMNAT enzymes intracellularly. Whether oral NMN is taken up intact (via the proposed Slc12a8 NMN transporter) or whether it is first dephosphorylated to NR at the gut brush border and then re-phosphorylated to NMN inside cells is an active scientific dispute. NAD+ in turn serves as a coenzyme for sirtuins (SIRT1–7), PARPs, and CD38, and is an essential cofactor in glycolysis, the TCA cycle, and oxidative phosphorylation.
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.
Raising blood NAD+ levels
Multiple small human RCTs (Irie et al., Yoshino et al., Liao et al., Pencina/MIB-626 trial) consistently show measurable elevations in whole-blood NAD+ with daily oral dosing. The hormonal/biochemical effect is real. Tier 2 because the indication of 'raising blood NAD+' is biochemical, not a clinical outcome.
Insulin sensitivity / metabolic health
Yoshino et al. (Science 2021, n=25 prediabetic women, 250 mg/day for 10 weeks) reported improved muscle insulin sensitivity. Other studies have been mixed; the MIB-626 trial in overweight middle-aged adults did not show clinically meaningful improvements in insulin sensitivity at the studied doses. Tier 3 by Rule 8 (mixed evidence → conservative).
Aerobic capacity / athletic performance
Liao et al. (J Int Soc Sports Nutr 2021, n=48 amateur runners, 6 weeks) reported modest improvements in aerobic ventilatory thresholds with 300–1200 mg/day. Single small trial; replication outside the original lab is limited.
Generic 'anti-aging' / longevity
Strong preclinical case in mice (Sinclair lab and others). No clinical-outcome data in humans demonstrating slowed aging or extended healthspan. Mechanism-as-evidence is the dominant marketing pattern; resist by Rule 3.
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.
Human RCTs cluster at 100–1200 mg/day oral. Note unit math: 1000 mg = 1,000,000 mcg. This is supplement-scale, very different from microgram-dose peptides.
Compounded SubQ NMN is a smaller market than SubQ NAD+. Doses cluster 50–250 mg per injection. No published RCT validates SubQ bioavailability vs oral.
Contraindications
- Active malignancy (theoretical concern from sirtuin and NAD+ metabolism intersections with cancer biology; consult oncology)
- Pregnancy and breastfeeding (no human safety data)
- Caution with chemotherapy regimens whose mechanism involves NAD+/PARP pathways
- Known hypersensitivity to formulation excipients
Reported side effects
- Oral: generally well tolerated; mild GI upset, headache, occasional flushing
- SubQ: injection-site stinging or redness reported (less commonly than NAD+ SubQ)
- Theoretical: long-term effects of sustained elevated cellular NAD+ on sirtuin activity, immune signaling, and tumor biology are not fully characterized in humans
Reconstitution & storage
Oral NMN is supplied as capsules, powder, or sublingual lozenges — no reconstitution. Compounded SubQ NMN: a 100 mg/mL solution makes a 100 mg dose = 1 mL = 100 units on a U-100 syringe. Concentration varies by compounding pharmacy; verify per batch.
Storage. Oral: room temperature, dry, protect from light. Some manufacturers recommend refrigeration to extend stability. Compounded SubQ: refrigerate 2–8 °C, use within vendor expiration.
Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.
Editorial note
DRAFT — pending Wayne's review. NMN is the cleanest example of mechanism-and-biomarker-as-evidence overshadowing clinical-outcome data. Yes, blood NAD+ goes up. No, there is no Tier 1 evidence that anything important about aging or healthspan changes as a consequence in humans. The bioavailability dispute (Slc12a8 transporter vs gut-wall conversion to NR) is genuinely unresolved — flag, don't paper over. Class field mirrors NAD+'s 'NOT a peptide' framing for the same editorial-honesty reason.
Citations
- [1]Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic womenYoshino M, Yoshino J, Kayser BD, et al. · Science · 2021 · PMID 33888596Anchor Phase 2 RCT showing improved muscle insulin sensitivity with NMN; primary human trial cited for the metabolic indication.View source
- [2]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 the Tier 3 athletic performance claim.View source
- [3]MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and Its Metabolome in Middle-Aged and Older AdultsPencina KM, Lavu S, Dos Santos M, et al. · Journal of Clinical Endocrinology & Metabolism · 2023 · PMID 36702359Larger RCT of pharmaceutical-grade NMN (MIB-626) in middle-aged/older adults; confirms NAD+ elevation but reports limited functional improvement.View source