NAD+ Overview
Mechanism of Action
NAD+ (nicotinamide adenine dinucleotide) is a critical coenzyme found in every living cell. It serves as an essential electron carrier in mitochondrial energy production (ATP synthesis) and is required by sirtuins (SIRT1-7), PARPs (DNA repair enzymes), and CD38 (immune signaling). NAD+ levels decline approximately 50% between ages 40–60, contributing to mitochondrial dysfunction, impaired DNA repair, and accelerated aging.
Endogenous NAD+ has a ~1-hour turnover in most tissues. Exogenous SQ administration provides sustained elevation over 4–6 hours.
Timing
Morning preferred (may cause alertness/energy that disrupts sleep if taken late)
Injection Site
Subcutaneous, abdomen or thigh
Food
No restrictions
Common Stacks
- Resveratrol (oral) — SIRT1 activator, amplifies NAD+ effects
- TMG (oral) — Methyl donor to support methylation during NAD+ supplementation
NAD+ Dosing Protocol
Daily SQ Protocol
Ongoing100 mg daily
Steady daily dosing for sustained NAD+ elevation.
Pulse Protocol
Ongoing250 mg 3x/week
Higher doses less frequently. Popular with practitioners.
NAD+ Expected Timeline
Week 1–2
Increased mental clarity and energy levels
Week 3–4
Improved exercise recovery; better sleep quality
Week 4–8
Enhanced cellular energy; improved metabolic markers
Month 2–3
Sustained cognitive benefits; improved resilience to stress
NAD+ Side Effects
Injection site stinging/burning (common, brief)
Flushing or warmth sensation
Nausea at higher doses
Insomnia if dosed too late in the day
NAD+ Research Studies
NAD+ intermediates: the biology and therapeutic potential of NMN and NR
Yoshino J, Baur JA, Imai SI — Cell Metab (2018)
Comprehensive Cell Metabolism review establishing NAD+ decline as a hallmark of aging and demonstrating therapeutic potential of NAD+ restoration across multiple organ systems.
PubMed: 29249689Therapeutic potential of NAD-boosting molecules: the in vivo evidence
Rajman L, Chwalek K, Sinclair DA — Cell Metab (2018)
David Sinclair’s landmark review showing NAD+ supplementation improved mitochondrial function, DNA repair, cognitive function, and lifespan in animal models.
PubMed: 29514064NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice
Zhang H, Ryu D, Wu Y, et al. — Science (2016)
Published in Science, demonstrated NAD+ repletion reversed age-related degeneration in mice by restoring mitochondrial function and adult stem cell pools.
PubMed: 27127236NAD+ FAQ
Why does NAD+ injection sting?
NAD+ is mildly acidic and can cause a brief burning sensation at the injection site. This typically lasts 30–60 seconds and diminishes with consistent use. Injecting slowly and at room temperature helps.
Is subcutaneous NAD+ as effective as IV?
IV NAD+ delivers higher peak concentrations but requires clinical visits and takes 2–4 hours per infusion. Subcutaneous administration provides steady, sustained NAD+ elevation and is far more practical for regular use. Most practitioners now prefer SQ for ongoing protocols.
Should I take TMG with NAD+?
NAD+ metabolism consumes methyl groups. Some experts recommend supplementing with trimethylglycine (TMG) to maintain healthy methylation levels, especially at higher NAD+ doses. This is taken orally, not injected.