NAD+ drops 50% by age 50. Without it, sirtuins and PARP don't function · without sirtuins, no DNA repair or autophagy. NMN and NR are the two precursors with real human evidence. Pillar of modern longevity field (Sinclair · Imai · Brenner).
5NMN / NR appears in 5 protocols personalizable→NAD+ precursors · limiting coenzyme of sirtuins, PARP, CD38 and +500 redox enzymes. Levels drop 50% by age 50 · molecular hallmark of aging.
NAD+ (nicotinamide adenine dinucleotide) is a redox coenzyme present in every cell · participates in over 500 enzymatic reactions. Three critical uses: (1) mitochondrial electron transport chain (ATP production); (2) mandatory cofactor of sirtuins (SIRT1-7) regulating DNA repair, autophagy, mitochondrial biogenesis; (3) PARP substrate for damaged DNA repair.
The problem: tissue NAD+ levels drop 50% between ages 30 and 50. Decline is bidirectional · more consumption (CD38 inflammaging) + less synthesis (NAMPT deficient). Without sufficient NAD+, sirtuins and PARP are functionally silenced · one of the most reproducible molecular hallmarks of aging.
NMN (nicotinamide mononucleotide) is the immediate NAD+ precursor · a single enzymatic reaction (NMNAT) converts it. Sinclair (Harvard) advocates it. NR (nicotinamide riboside) is the other validated precursor · one more reaction (NRK + NMNAT) · ChromaDex holds patent (Tru Niagen brand). Both raise tissue NAD+ in humans per 2020-2024 RCTs.
5 pivotal studies · RCT in prediabetics · postmenopausal women · Parkinson's · long-term safety. Human evidence CONSOLIDATING 2020-2024.
| Study | Finding | Hallmarks |
|---|---|---|
NMN and insulin sensitivity postmenopausal women Yoshino et al · Science 2021 | Double-blind RCT 10 weeks · n=25 prediabetic postmenopausal women · 250 mg NMN/d improved muscle insulin sensitivity (euglycemic clamp) 25% vs placebo. First serious human RCT confirming metabolic effect. | NAD+Metabolic |
NR (Niagen) safety + NAD+ elevation 2 years Conze et al · Nutrients 2019 + Yamaguchi 2022 | RCT n=120 · 100-1000 mg NR/d × 8 weeks · dose-dependent RBC NAD+ elevation (+25% at 100 mg, +90% at 1000 mg). Yamaguchi 2022 2-year follow-up: zero safety red flags, sustained NAD+. | NAD+Safety |
NR in Parkinson · NADPARK trial Brakedal et al · Cell Metab 2022 | RCT n=30 · 1000 mg NR/d × 30 d · brain NAD+ elevation by MRS (magnetic resonance spectroscopy) + UPDRS-III motor function improvement. First NAD+ trial in real neuro-condition. | NeuroParkinson |
NMN safety 12 weeks in older men Yamaguchi et al · Endocr J 2022 | RCT n=30 men 65+ · 250 mg NMN/d × 12 weeks · zero safety red flags + mild walking speed and grip improvement. No clinically relevant adverse effects up to 1200 mg/d in humans. | SafetyAge |
Mills 2016 · NMN reverses age-related changes mice Mills et al · Cell Metab 2016 | Cardinal study · C57BL/6 female mice · 300 mg/kg NMN water · reversed age-related NAD+ decline, improved insulin sensitivity, muscle and lipid mitochondrial function, ocular function. Mechanistic basis of the field. | NAD+Mito |
My Protocol generates 3 personalized plans with exact form, dose and combos based on your profile. No commitment.
López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
NMN sublingual 250-1000 mg/day morning · NR Niagen 300-600 mg/day. Take in morning (mimics endogenous NAD+ circadian cycle).
Start modest dose to evaluate tolerance. Take on waking (endogenous NAD+ has morning peak · supplementing potentiates circadian rhythm). Sublingual better than oral (bypass hepatic first-pass).
Dose of most human RCTs · safety profile confirmed up to 1200 mg/d. If taking NR (Niagen): equivalent ~400 mg NR. Maintain 3-6 months for complete tissue NAD+ repletion.
Sinclair canon dose · 1000 mg NMN morning · add TMG (trimethylglycine · betaine) 500 mg to support methylation (NMN consumes methyls · may deplete SAMe long-term). Optional combo with resveratrol 500 mg + omega-3.
Some authors (Imai) suggest breaks to avoid NAMPT down-regulation (endogenous synthesis). Others (Sinclair) use continuous. Limited human evidence on cycling · pragmatic: cycle if tight budget, continuous if budget covers.
Two distinct compounds (NMN and NR) · each with multiple forms. Stability and bioavailability vary enormously · form + brand are critical.
Market contaminated with low-purity Chinese synthetic NMN · seek HPLC ≥99% + third-party COA. Authentic NMN Uthever® or Niagen® are benchmark.
Dose: 500 mg Uthever® NMN/capsule
Form: Uthever® NMN · HPLC purity 99.7%
Cert.: GMP · third-party COA · Sinclair-endorsed
Fillers: Vegetable DR capsule · zero excipients
Dose: 500 mg NMN/dose (spoon included)
Form: Sublingual NMN powder · stabilized
Cert.: GMP · third-party COA
Fillers: Only NMN · no flavorings
Dose: 300 mg Niagen® NR/day
Form: Niagen® NR · ChromaDex patent
Cert.: GMP · NSF · FDA GRAS
Fillers: Microcrystalline cellulose · Mg stearate
My Protocol recommends form + brand + exact dose based on your age, budget and biomarkers. No commitment · 3 minutes.
Direct biomarker (NAD+) + indirect (insulin sensitivity · walking speed) to confirm real repletion.
NAD+ whole blood. Direct marker · target +50% vs baseline after 8 weeks supplementation. Jinfiniti Biosciences offers home kit (dry drop) ~120 € · Spain courier available. Only real efficacy marker.
Insulin sensitivity (HOMA-IR). Yoshino 2021 showed +25% muscle sensitivity with 250 mg NMN/d × 10 weeks. HOMA-IR baseline vs 12 weeks is indicative. ~15 € general analytic.
Walking speed 4 m (gait speed). Functional indicator · <1 m/s associates with higher mortality. NMN/NR improves speed in elders (Yamaguchi 2022). Self-measurable home · useful monthly follow-up.
Whole blood NAD+ test + insulin sensitivity + HRV + body composition. Pre-post supplementation confirms real repletion. Few clinics offer NAD+ test yet in Spain.
Good safety profile in human RCTs · few contraindications specific to active cancer and pregnancy.
4 combos · NAD+ is upstream of sirtuins · each combo activates a complementary pathway.
Sinclair canon combo · NMN raises NAD+ (sirtuin substrate) + resveratrol activates SIRT1 directly. Mechanistic synergy to activate sirtuins: substrate + activator.
TMG provides methyls · NMN/NR consume methyls to metabolize nicotinamide (byproduct). Long-term combo prevents SAMe depletion. Sinclair pragmatic recommendation.
Apigenin inhibits CD38 (NAD+ degrader) · NMN increases NAD+ production. Combo increases NAD+ pool from two sides: more synthesis + less degradation.
NAD+ is electron donor to respiratory chain · Q10 transports them · combo covers entire mitochondrial ATP production. Complete pro-mitochondrial stack.
8 real questions · 2020-2024 human literature-based answers.
Supplements · treatments · biomarkers for your complete protocol.
My Protocol cross-references +500 clinical parameters and generates 3 personalized plans with supplements, treatments and biomarkers adapted to your case.
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