NAD+

Overview

NAD+ (Nicotinamide Adenine Dinucleotide) is a coenzyme present in all living cells, essential for hundreds of metabolic processes. It plays a critical role in energy production, DNA repair, gene expression, and cellular communication.

NAD+ levels naturally decline with age, and this decline is associated with many hallmarks of aging. Restoring NAD+ levels has become a major focus of longevity research, with various precursors and direct NAD+ supplementation being explored.

Chemical Formula: C21H27N7O14P2

Mechanism of Action

NAD+ functions through multiple critical pathways:

Cellular Energy Production

• Essential cofactor in glycolysis
• Required for mitochondrial electron transport chain
• Enables ATP production (cellular energy currency)
• Supports metabolic flexibility

Sirtuin Activation

• Substrate for sirtuin enzymes (SIRT1-7)
• Sirtuins regulate aging and metabolism
• Influences gene expression and longevity pathways
• Supports mitochondrial biogenesis

DNA Repair

• Consumed by PARP enzymes during DNA repair
• Essential for maintaining genomic stability
• Protects against age-related DNA damage
• Supports cellular health and longevity

Cellular Signaling

• CD38 enzyme uses NAD+ for signaling
• Regulates calcium signaling
• Influences immune function
• Modulates inflammation

Research Summary

Aging and Longevity

NAD+ Decline with Age

• NAD+ levels decrease 50%+ by middle age
• Decline correlates with aging hallmarks
• Restoration improves markers of aging in animals
• Multiple tissues affected by decline

Animal Studies

• Extended lifespan in various models
• Improved metabolic function in aged mice
• Enhanced muscle function and endurance
• Protected against age-related diseases

Cognitive Function

Metabolic Health

Insulin Sensitivity

• Improved glucose tolerance in animal studies
• Enhanced insulin sensitivity
• Supported healthy metabolic function
• Benefits in diabetic models

Mitochondrial Function

• Enhanced mitochondrial biogenesis
• Improved oxidative phosphorylation
• Better cellular energy production
• Reduced oxidative stress

Key Limitations

• Most dramatic results in animal models
• Human clinical trial data still emerging
• Optimal delivery method debated
• Long-term effects not fully characterized
• Direct NAD+ has bioavailability challenges

Pharmacokinetics

Note: Precursors (NMN, NR) often preferred for oral supplementation

Common Protocols

Note: NAD+ therapies are not FDA-approved for anti-aging. The following represents research community protocols.

Direct NAD+ Administration

IV Infusion (Clinical Settings)

• 250-750 mg IV over 2-4 hours
• Series of 4-10 sessions common
• Monthly maintenance sometimes used
• Administered in clinical settings only

Subcutaneous Injection

• 50-100 mg daily
• Self-administered
• Research community protocol
• More practical than IV

NAD+ Precursors (Oral)

NMN (Nicotinamide Mononucleotide)

• 250-1000 mg daily
• Sublingual or oral
• Popular oral option

NR (Nicotinamide Riboside)

• 300-600 mg daily
• Oral capsules
• Well-studied precursor

Timing

• Morning administration typical
• Some report energy effects (avoid evening)
• Consistent daily use for precursors

Side Effects

IV Infusion

• Chest tightness or pressure (during infusion)
• Nausea
• Headache
• Cramping
• Anxiety or restlessness (high doses)
• Flushing

Subcutaneous

• Injection site reactions
• Mild nausea
• Flushing

Oral Precursors

• Generally well-tolerated
• Mild GI upset possible
• Flushing (especially with niacin-based)

Safety Considerations

• IV should only be administered by professionals
• Start with lower doses
• Cancer considerations (NAD+ supports all rapidly dividing cells)
• Long-term safety data still accumulating

Interactions

Potential Interactions

• Chemotherapy (theoretical concern)
• Other NAD+ precursors (additive)
• Alcohol (depletes NAD+)
• Medications metabolized via NAD+-dependent enzymes

Contraindications

• Active cancer (theoretical concern)
• Pregnancy/nursing (insufficient data)
• Severe liver disease
• Children (not studied)

Community Insights

Aggregated from research community reports.

Commonly Reported Experiences

• Increased energy and alertness
• Improved mental clarity
• Better exercise recovery
• Enhanced sleep quality
• Reduced brain fog
• Improved mood

IV vs. Precursors

• IV: More immediate, pronounced effects
• IV: More expensive, requires clinic visits
• Precursors: Convenient, daily option
• Precursors: Effects build over time

Practical Tips

• IV infusion can be intense—start with lower doses
• Hydrate well before and after IV
• Oral precursors: consistency matters more than timing
• Combine with lifestyle factors (exercise, fasting increase NAD+)

Common Stacks

• NAD+ precursors + Resveratrol (sirtuin activation)
• NAD+ + Pterostilbene
• NAD+ + Metformin (longevity protocols)
• Part of comprehensive longevity regimens

References

1. Yoshino J, et al. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513-528.

2. Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-13.

3. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-71.

4. Rajman L, et al. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.

5. Shade C. The Science Behind NMN–A Stable, Reliable NAD+ Activator and Anti-Aging Molecule. Integr Med (Encinitas). 2020;19(1):12-14.

6. Braidy N, et al. Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases. Antioxid Redox Signal. 2019;30(2):251-294.