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The Peptide Effect
phase 2Longevity & Cellular Health

NAD+

Also known as: Nicotinamide Adenine Dinucleotide, NAD, Coenzyme I, Diphosphopyridine nucleotide, DPN

NAD+ (Nicotinamide Adenine Dinucleotide) is an essential coenzyme found in every living cell, involved in over 500 enzymatic reactions. While not technically a peptide, it is widely discussed alongside peptides in the longevity and anti-aging space. NAD+ levels decline approximately 50% by age 60, and this decline is implicated in mitochondrial dysfunction, DNA damage accumulation, and metabolic deterioration. NAD+ can be boosted through precursors (NMN, NR, niacin) or direct IV infusion.

Key Facts

Mechanism
NAD+ serves as a critical coenzyme in cellular metabolism, functioning as an electron carrier in redox reactions (glycolysis, TCA cycle, oxidative phosphorylation). Beyond energy metabolism, NAD+ is consumed as a substrate by three major enzyme families: Sirtuins (SIRT1–7), which deacetylate proteins to regulate gene expression, mitochondrial function, and DNA repair; PARPs (Poly-ADP-ribose polymerases), which detect and repair DNA damage; and CD38/CD157, ectoenzymes involved in calcium signaling and immune function. CD38 activity increases with age and is considered a major driver of age-related NAD+ depletion. Restoring NAD+ levels reactivates sirtuins and PARPs, theoretically reversing aspects of cellular aging.
Research Status
phase 2
Half-Life
~30 minutes (NAD+ in blood); NMN ~2–3 hours; NR ~3–4 hours
Molecular Formula
C₂₁H₂₇N₇O₁₄P₂
Primary Use
Longevity & Cellular Health

Benefits

  • Activates PARPs for enhanced DNA repair, protecting against genomic instabilitystrong
  • Activates sirtuins (SIRT1–7) for cellular maintenance, stress resistance, and longevity pathwaysstrong
  • Improves mitochondrial function and biogenesis through SIRT1/PGC-1α signalingmoderate
  • Potential anti-aging effects — reverses age-related decline in NAD+ dependent processesmoderate
  • Improved metabolic health — enhances insulin sensitivity and glucose metabolismmoderate
  • Neuroprotective — supports neuronal health and may protect against neurodegenerationpreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Oral (NMN)250–1000 mgOnce daily, typically morningSublingual NMN may improve bioavailability; take with food to reduce GI effects
Oral (NR / Niagen)300–1000 mgOnce or twice dailyNR (Nicotinamide Riboside) is the most clinically studied NAD+ precursor
Intravenous infusion (NAD+)250–750 mgSingle session over 2–4 hours; series of 4–8 sessionsInfusion rate should be slow to minimize chest tightness; clinic-administered only

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • GI upset (nausea, bloating, diarrhea) with oral NMN/NR precursorscommon
  • Flushing, warmth, and itching with niacin (vitamin B3) pathwaycommon
  • Chest tightness and anxiety during IV NAD+ infusion (dose-rate dependent)common
  • Headache and fatigue during initial supplementationrare
  • Theoretical concern: NAD+ fuels cancer cell metabolism — may promote growth of existing tumorsserious

Frequently Asked Questions

What is the difference between NMN, NR, and niacin for boosting NAD+?
All three are NAD+ precursors but enter the biosynthesis pathway at different points. NMN (Nicotinamide Mononucleotide) is one step away from NAD+ and requires the transporter SLC12A8 for cellular uptake. NR (Nicotinamide Riboside) enters cells via nucleoside transporters and is converted to NMN then NAD+. Niacin (vitamin B3) uses the Preiss-Handler pathway but causes flushing at effective doses. NR has the most published human clinical trial data. NMN has growing evidence and is favored by some researchers. Cost, bioavailability, and side effect profiles differ between them.
Is IV NAD+ better than oral NMN or NR?
IV NAD+ infusion bypasses the digestive system and delivers NAD+ directly to the bloodstream, producing immediate and dramatic increases in blood NAD+ levels. However, NAD+ in the blood has a very short half-life (~30 minutes) and the extent to which IV NAD+ enters cells is debated. Oral precursors (NMN, NR) are converted to NAD+ inside cells where it is actually needed. The "best" approach likely depends on the goal: IV NAD+ is popular for acute applications (detox, energy boost), while oral precursors are more practical for sustained daily NAD+ elevation.
What does David Sinclair say about NAD+ and aging?
Dr. David Sinclair, a Harvard genetics professor, has been a prominent advocate for NAD+ supplementation as an anti-aging strategy. His lab's research demonstrated that NMN can reverse aspects of aging in mice, including improved blood vessel growth, exercise endurance, and muscle function. Sinclair has publicly stated he takes NMN daily as part of his personal longevity regimen. While his research is respected, it is important to note that animal results do not always translate to humans, and large-scale human longevity trials with NMN are still ongoing.
What is the optimal dose and timing for NAD+ supplementation?
There is no universally agreed-upon optimal dose. Human trials have used NR at 300–2000 mg/day and NMN at 250–1200 mg/day, generally showing safety and NAD+ elevation across this range. Many researchers and clinicians recommend starting at 250–500 mg NMN or 300 mg NR daily and adjusting based on response. Morning dosing is preferred as NAD+ is involved in circadian rhythm regulation. Taking precursors with food may reduce GI side effects. Some practitioners cycle NAD+ supplementation (5 days on, 2 days off) to prevent potential downregulation of salvage pathway enzymes.
Is it too late to start NAD+ supplementation at age 60 or older?
No. In fact, the greatest NAD+ decline occurs between ages 40 and 70, making this the period where supplementation may have the most impact. Animal studies have shown benefits even when NAD+ boosting is initiated in old age — including improved mitochondrial function, reduced inflammation, and better metabolic markers. Some researchers argue that older individuals may benefit more because they have a larger NAD+ deficit to correct. The key concern is the theoretical cancer risk, which should be discussed with a physician, particularly for older individuals who have a higher baseline cancer risk.

References

  1. 1
    NAD+ metabolism and its roles in cellular processes during ageing(2018)PubMed ↗
  2. 2
    Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults(2021)PubMed ↗
  3. 3
    Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging(2013)PubMed ↗
  4. 4
    Effect of oral nicotinamide mononucleotide (NMN) on plasma NMN concentration and safety in healthy Japanese men(2020)PubMed ↗

Last updated: 2026-02-14