NAD+
Also known as: Nicotinamide Adenine Dinucleotide · NAD · Coenzyme I
Contents
MW
663.43 Da
Half-Life
2-4 hours (IV administered)
Route
IV, SubQ, Oral
CAS
53-84-9
Formula
C21H27N7O14P2
Mechanism of Action
NAD+ (Nicotinamide Adenine Dinucleotide) is a critical coenzyme present in every living cell, required for >500 enzymatic reactions.
SIRTUIN ACTIVATION: NAD+ is the essential co-substrate for sirtuins (SIRT1-7) — a family of deacetylases that regulate epigenetic modification, DNA repair, mitochondrial function, inflammation, and metabolism. Sirtuins consume NAD+ to remove acetyl groups from histones and proteins, directly linking cellular NAD+ levels to epigenetic aging.
PARP FUNCTION: PARP enzymes (poly ADP-ribose polymerases) require NAD+ for DNA damage repair. PARP-1 is the major consumer of NAD+ — chronic DNA damage depletes NAD+ pools, creating a vicious cycle of impaired repair capacity.
MITOCHONDRIAL ENERGY: NAD+ is an electron carrier in the mitochondrial electron transport chain (Complex I). Required for oxidative phosphorylation — the primary cellular energy production pathway.
CD38: The enzyme CD38 consumes NAD+ for immune signaling. CD38 expression increases with age, contributing significantly to age-related NAD+ decline.
AGE-RELATED DECLINE: NAD+ levels decline ~50% between ages 40–60. This decline drives age-related dysfunction in sirtuins, PARP, and mitochondria simultaneously. The "NAD+ decline theory of aging" proposes that restoring NAD+ levels can reverse age-related cellular dysfunction.
Dosing Protocol
Low Dose
███ – ███ mcg/day
Standard Dose
███ mcg/day
High Dose
███ – ███ mcg/day
Dosing protocols are for paid members
Get exact dosing ranges, injection frequency, timing rationale, and reconstitution math.
Get Clinical Access — $79/moFrequency
IV: 1–2x/week loading, then monthly maintenance.
Half-Life
2-4 hours (IV administered)
Reconstitution Guide
Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.
Unlock reconstitution guide →Clinical Warnings
IV infusion: chest tightness, nausea, flushing if too fast — MUST be slow drip.
Expensive.
CD38 immune effects possible.
Theoretical cancer concern (cancer cells use NAD+).
Oral NMN/NR may be sufficient — IV necessity debated.
Quality varies widely.
Contraindications
Absolute
Pregnancy
Relative Cautions
Gout (may increase uric acid)
Active cancer
Liver disease
Side Effect Profile
Mild
- ●Flushing
- ●Nausea
- ●Chest tightness (IV)
- ●Abdominal cramping
Moderate
- ●Headache
- ●Fatigue post-infusion
- ●Insomnia
- ●Anxiety
Severe (Rare)
- ●Severe bradycardia (rapid IV)
- ●Liver toxicity (very high doses)
Synergistic Peptides
Common Stacks
SS-31
Epithalon
Research Status
ROBUST MECHANISTIC DATA. PMID 28068316 (Rajman 2018 Cell Metabolism): Comprehensive NAD+ decline and aging review. PMID 38316428 (Iqbal 2024): NAD+ age-related disease therapeutic review. Growing human evidence for oral precursors (NMN, NR). IV NAD+ less studied in RCTs.
Frequently Asked Questions
How does NAD+ work?
NAD+ (Nicotinamide Adenine Dinucleotide) is a critical coenzyme present in every living cell, required for >500 enzymatic reactions. SIRTUIN ACTIVATION: NAD+ is the essential co-substrate for sirtuins (SIRT1-7) — a family of deacetylases that regulate epigenetic modification, DNA repair, mitochondrial function, inflammation, and metabolism. Sirtuins consume NAD+ to remove acetyl groups from histones and proteins, directly linking cellular NAD+ levels to epigenetic aging. PARP FUNCTION: PARP en
What is the standard dose of NAD+?
NAD+ dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: IV: 1–2x/week loading, then monthly maintenance.
What is the half-life of NAD+?
The half-life of NAD+ is 2-4 hours (IV administered). This determines optimal dosing frequency and timing.
Who should not use NAD+?
NAD+ is absolutely contraindicated in: Pregnancy. Use with caution in: Gout (may increase uric acid); Active cancer; Liver disease.
What are the side effects of NAD+?
Common mild side effects include: Flushing, Nausea, Chest tightness (IV), Abdominal cramping. Moderate effects: Headache, Fatigue post-infusion, Insomnia, Anxiety.
What peptides stack well with NAD+?
NAD+ is commonly stacked with: SS-31, Epithalon, 5-Amino-1MQ.
How do you reconstitute NAD+?
NAD+ is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.
How long should you cycle NAD+?
NAD+ cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.
References & Citations
10 PubMed studies · 3 clinical trials
NAD+ Enhanced Mesenchymal Stromal Cells Effect on Muscle Atrophy by Improving SIRT1-Mediated Mitochondrial Function via NAMPT.
Song Jia, Sun Yuting, Zang Nan, Liu Xue et al.. Journal of cachexia, sarcopenia and muscle. 2025
Sarcopenia contributes to all-cause mortality in the elderly; however, there is no specific treatment. Mesenchymal stromal cells (MSCs) ameliorate age-related muscle loss and dysfunction and are poten
Therapeutic Perspectives of SIRT6 Regulation: Computational Analysis of Activation and Inhibition by Bioactive Molecules.
de Carvalho Matias Érika Geicianny, Bezerra Katyanna Sales, Junior Washington Sales Clemente, Oliveira Jonas Ivan Nobre et al.. Journal of molecular recognition : JMR. 2026
Sirtuin 6 (SIRT6) is an enzyme belonging to the class of nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylases. It has been of interest due to its multivariate biological role and as
Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases.
Noreen Saba, Lim Soon Sung, Lee Deokho. International journal of molecular sciences. 2025
Nicotinamide adenine dinucleotide (NAD+) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD+ is linked to the development of pathological retina
Mitochondrial Dynamics in Aging Heart.
Patyal Pankaj, Azhar Gohar, Verma Ambika, Sharma Shakshi et al.. Biomedicines. 2025
Aging is a major risk factor for cardiovascular disease, driving progressive structural and functional decline of the myocardium. Mitochondria, the primary source of ATP through oxidative phosphorylat
Fermented Porcine Placenta and Its Dipeptides Modulate Cellular Senescence in Human Keratinocytes.
Choi Yea Jung, Kang Minseo, Jin Mu Hyun, Kim Jongbae et al.. Current issues in molecular biology. 2025
Skin aging is primarily driven by oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. This study investigated the anti-senescence effects of fermented porcine placenta (FPP) and
Sirtuin Family in Acute Kidney Injury: Insights into Cellular Mechanisms and Potential Targets for Treatment.
Yang Songyuan, Chen Wu, Li Siqi, Zhao Sheng et al.. Biomolecules. 2025
Acute kidney injury (AKI) is a frequent clinical and pathological condition, often resulting from factors like ischemia, toxins, or infections, which cause a sudden and severe decline in renal functio
The Influence of Sirtuin 6 on Chondrocyte Senescence in Osteoarthritis Under Aging: Focusing on Mitochondrial Dysfunction and Oxidative Stress.
Zhao Huiying, Wu Wei. Antioxidants (Basel, Switzerland). 2025
Osteoarthritis (OA) is one of the most common joint diseases worldwide, which is characterized by degenerative changes in articular cartilage and secondary osteophyte formation. Numerous factors influ
Distinctive Gene Expression Profiles and Biological Responses of Skin Fibroblasts to Nicotinamide Mononucleotide: Implications for Longevity Effects on Skin.
Kang Seongsu, Park Jiwon, Cho Eunbyul, Kim Dohyun et al.. Biomedicines. 2025
Background/Objectives: Enhancement of cellular NAD+ mediated by NMN has emerged as a pivotal strategy in modulating the aging process. This study aimed to systematically investigate the anti-aging eff
Registered Clinical Trials
Observation of Non-technical Skills in the Pre-hospital Care in the Czech Republic
A Study of the Effectiveness and Safety of Ramipril in the Treatment of Hypertension in Children and Adolescents
Lactate Kinetics as a Predictor of Survival in ACLF With Septic Shock
Symptom Indications
Full Clinical Access
Complete NAD+ Protocol
Access reconstitution math, cycle guides, drug interaction checker, stack builder with contraindication analysis, symptom checker, and downloadable PDF handouts.
Secure payment powered by Stripe.
This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.