NAD+ molecular structure
NAD+ molecular structure
Approved
Longevity

NAD+

Also known as: Nicotinamide Adenine Dinucleotide, NAD, Coenzyme NAD

Routes

6 routes

NAD+ (nicotinamide adenine dinucleotide) is a critical coenzyme present in every living cell, involved in over 500 enzymatic reactions. It plays a central role in energy metabolism, DNA repair, gene expression, and cellular signaling. NAD+ levels decline by approximately 50% between ages 40 and 60, contributing to mitochondrial dysfunction, impaired DNA repair, and metabolic decline. NAD+ can be administered directly via intravenous (IV) infusion or as an oral/sublingual powder. IV delivery provides 100% bioavailability, while oral NAD+ has limited absorption due to its large molecular structure. NAD+ is not a peptide but is widely included in longevity research alongside peptide bioregulators.

Research Use OnlyFor educational and research purposes only

Research Applications

Aging and Longevity

• Direct NAD+ restoration has been shown to extend lifespan in animal models • IV NAD+ infusions rapidly increase blood and tissue NAD+ levels with 100% bioavailability • Supports DNA repair, mitochondrial function, and sirtuin activation — key longevity pathways

Metabolic Health

• Enhances mitochondrial energy production and ATP synthesis • Improves insulin sensitivity and supports healthy glucose metabolism • Reduces chronic low-grade inflammation linked to metabolic syndrome

Neurodegeneration

• NAD+ depletion is closely linked to Alzheimer’s and Parkinson’s disease progression • IV NAD+ therapy is being studied for neuroprotective effects in neurodegenerative conditions • Supports neuronal energy supply and DNA damage repair in brain cells

Cardiovascular Health

• Promotes healthy endothelial function and blood vessel elasticity • Helps reduce arterial stiffness associated with aging • Supports cardiac energy metabolism and heart muscle contractility

Addiction and Recovery

• IV NAD+ therapy is being researched for substance abuse recovery support • May help reduce withdrawal symptoms and cravings • Supports neurochemical balance restoration

Mechanism of Action

NAD+ functions as a coenzyme in redox reactions, carrying electrons between metabolic enzymes. It activates three key enzyme families: sirtuins (SIRT1-7, deacetylases regulating gene expression, metabolism, and stress responses), PARPs (poly-ADP-ribose polymerases for DNA repair), and CD38/CD157 (immune signaling). SIRT1 activation deacetylates PGC-1α (mitochondrial biogenesis), FOXO (stress resistance), and NF-κB (inflammation reduction). NAD+ is also essential for the electron transport chain in mitochondria, directly powering ATP production.

Biological Pathways

NAD+/SIRT1/PGC-1α for mitochondrial biogenesis. NAD+/PARP for DNA repair. NAD+/SIRT1/FOXO for stress resistance. NAD+/SIRT3 for mitochondrial protein deacetylation. CD38/NAD+ for immune function.

Dosage Information

Typical dosage ranges for research applications. Always verify with current literature.
Typical Dose
500 mg
Dose Range
100 - 1,000 mg
Frequency
1-4 sessions per week in clinical settings

Reconstitution Notes

Administered as slow IV drip over 2-4 hours in a clinical setting. Dosage depends on the treatment goal.

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Calculation Results

Concentration
2.5 mg/ml
Dose Volume
0.1 ml0.100 ml
Insulin Syringe
10 units
Doses per Vial
2020 doses @ 250 mcg

Syringe Fill Level (100u syringe)

05010010.0uunits
0u10.0 / 100 units (10%)100u

Protocols

Comprehensive Longevity Stack
Advanced
Anti-Aging
3-6 months

Multi-peptide anti-aging protocol combining telomerase activation, mitochondrial support, and GH optimization.

Dosage
Epithalon: 1mg daily, MOTS-c: 10mg 2x/week, NAD+: 500mg daily, CJC/Ipa: 200mcg each daily
Frequency
Daily or as specified per peptide
Cycle
Epithalon: 50-day course yearly. MOTS-c: Ongoing 2x/week. NAD+: Daily. CJC/Ipa: 5 on/2 off.
Stacking Notes
Comprehensive approach targeting multiple aging pathways. Requires significant commitment and cost.

Warning: Very advanced protocol. Consider blood work monitoring.

NAD+ Restoration Protocol
Beginner
Anti-Aging
Ongoing — NAD+ levels return to baseline within 2-4 weeks after discontinuation. Most users supplement continuously as part of a longevity regimen.

Protocol for restoring cellular NAD+ levels using one of three interchangeable approaches: direct NAD+ administration, NMN supplementation, or Nicotinamide Riboside (NR). Choose ONE approach based on your budget, preferred route, and goals. NAD+, NMN, and NR all raise NAD+ levels — they are alternatives, not a stack. NAD+ levels decline ~50% between ages 40-60, contributing to aging, cognitive decline, and metabolic dysfunction. Restoring NAD+ supports DNA repair, mitochondrial function, sirtuin activation, and cellular energy production.

Dosage
Option A (NMN oral — most popular): 250-500 mg daily in the morning. Option B (NR oral — best researched): 250-500 mg daily with food. Option C (NAD+ injection — most potent): 50-100 mg subcutaneous 1-2x/week. Option D (NAD+ IV — clinical setting): 250-500 mg infusion 1x/week.
Frequency
Daily for oral supplements (NMN/NR), 1-3x per week for injections (NAD+)
Cycle
No cycling required for oral NMN/NR. For NAD+ injections: some practitioners recommend 4 weeks on, 1 week off. Loading phase option: higher doses for 7-10 days initially, then maintenance.
Stacking Notes
Recommended additions: Resveratrol (500-1000 mg) — activates sirtuins that depend on NAD+. TMG / Trimethylglycine (500-1000 mg) — replenishes methyl donors depleted by NAD+ metabolism. Do NOT combine multiple NAD+ precursors (e.g. NMN + NR) — choose one. Can be combined with other longevity peptides (Epithalon, MOTS-c) in broader anti-aging protocols.

Warning: Consult a physician before starting, especially with cancer history (NAD+ may theoretically support cancer cell proliferation). Avoid during pregnancy/breastfeeding. NAD+ IV infusion may cause temporary flushing, nausea, or headache — slow infusion rate helps. Start with lower doses to assess individual tolerance.

Stability & Storage

NMN and NR are relatively stable as dry powders. Store at room temperature in cool, dry conditions (some products recommend refrigeration). NMN is more stable than NR. Both are orally bioavailable. Enteric coating may improve delivery.

Side Effects & Precautions

Well-tolerated in clinical trials at standard doses. Mild GI discomfort (nausea, bloating) at higher doses. Flushing with high-dose niacin (not with NMN/NR). Theoretical concern about cancer cell NAD+ metabolism, though not observed in human studies.

Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.

Regulatory Status

Approved

NR is FDA GRAS and available as a dietary supplement (Tru Niagen, Niagen). NMN regulatory status varies by country — available as supplement in US, recently restricted in some interpretations of FDA classification. Not WADA-prohibited.

Research Studies

NAD+ Metabolism in Health and Disease

Verdin E.

Science
2015
View Source

Chronic NMN Supplementation Elevates Blood NAD+ in Healthy Adults

Yi L, Maier AB, Tao R, et al.

GeroScience
2023
View Source

NR Supplementation Increases NAD+ Metabolism in Humans

Martens CR, Denman BA, Mazzo MR, et al.

Nature Communications
2018
View Source
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