NAD+ Dosing Guide: Protocols & Timing (2026)

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme present in every living cell, essential for mitochondrial energy production, DNA repair, sirtuin activation, and hundreds of enzymatic reactions. NAD+ levels decline approximately 50% between ages 40 and 60 (Massudi et al., 2012), driving interest in direct supplementation and precursor strategies to restore youthful concentrations.

NAD+ is not FDA-approved as an anti-aging therapy. The protocols below reflect published research, clinical practice patterns, and community experience. This is not medical advice.

Quick Reference: NAD+ Dosing by Route

Most common starting protocol: 50 mg subcutaneous injection 3x per week, titrating to 100-200 mg based on tolerance. For non-injectable approaches, 500 mg NMN daily is the most widely used protocol.

For NAD+ vendor pricing and product comparisons, see our NAD+ page.

Subcutaneous Injection Protocol

Subcutaneous NAD+ injection delivers the molecule directly into tissue, bypassing first-pass metabolism. This is the most common injectable route for self-administration.

Standard Protocol

Titration Schedule

• Weeks 1-2: 50 mg per injection, 3x per week
• Weeks 3-4: 100 mg per injection, 3x per week
• Weeks 5-12: 150-200 mg per injection, 3x per week (based on tolerance)

Injection site note: NAD+ injections can cause a stinging or burning sensation at the injection site lasting 5-15 minutes. Injecting slowly and rotating sites helps manage discomfort. Some users ice the area beforehand.

Timing

• Morning dosing is preferred by most users due to potential energizing effects
• Avoid evening injections if sleep disruption occurs
• No fasting requirement, though some users prefer dosing on an empty stomach

IV Infusion Protocol

IV NAD+ delivers the highest peak plasma concentrations and is typically administered in clinical settings. It is the most studied route for acute NAD+ replenishment.

Standard Protocol

Loading Protocol

Some clinics use a loading phase for initial NAD+ replenishment:

• Days 1-3: 250 mg IV daily (over 2-3 hours each)
• Days 4-5: 500 mg IV daily (over 3-4 hours each) if tolerated
• Maintenance: 250-500 mg IV every 2-4 weeks

Side Effects of IV NAD+

IV infusion commonly produces side effects that are rate-dependent:

• Flushing and warmth — caused by GPR109A receptor activation and prostaglandin release
• Nausea and abdominal cramping — more common at faster infusion rates
• Chest tightness or pressure — typically resolves by slowing the drip
• Headache — occasional, usually mild

These effects are managed by reducing the infusion rate. Most side effects resolve within 30 minutes of completing the infusion. A 250 mg dose over 3-4 hours is generally well-tolerated even in sensitive individuals.

Research context: A pharmacokinetic study by Grant et al. demonstrated that a single 3-hour IV infusion of 750 mg NAD+ increased blood NAD+ levels approximately 398% above baseline in healthy adults (Grant et al., 2019).

Sublingual Protocol

Sublingual NAD+ bypasses gastrointestinal degradation by absorbing through the mucous membranes under the tongue.

Sublingual delivery offers better bioavailability than oral NAD+ capsules since the molecule partially avoids hepatic first-pass metabolism. However, absorption is variable and less predictable than injection.

Nasal Spray Protocol

Intranasal NAD+ delivers the molecule across the nasal mucosa, offering a needle-free alternative with moderate bioavailability.

Nasal delivery may provide preferential access to the central nervous system via the olfactory pathway, making it a route of interest for cognitive applications. However, human pharmacokinetic data for intranasal NAD+ remains limited.

Oral Precursors: NMN and NR

Rather than supplementing NAD+ directly, oral precursors provide the building blocks for endogenous NAD+ synthesis. Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are the two most studied precursors.

NMN Protocol

NMN is converted to NAD+ via nicotinamide mononucleotide adenylyltransferase (NMNAT). A 12-week randomized controlled trial in healthy middle-aged adults demonstrated that 250 mg/day NMN significantly increased blood NAD+ metabolite concentrations and improved physical performance measures (Yoshino et al., 2021).

NR Protocol

NR enters cells via equilibrative nucleoside transporters and is phosphorylated to NMN by nicotinamide riboside kinases (NRK1/2). A randomized, double-blind trial showed 1000 mg/day NR increased whole-blood NAD+ by approximately 60% over 6 weeks in healthy overweight adults (Martens et al., 2018).

NMN vs NR Comparison

Both precursors reliably increase circulating NAD+ levels. The choice between them is largely one of preference and availability.

Reconstitution Guide for Injectable NAD+

NAD+ is typically supplied as a lyophilized (freeze-dried) powder that must be reconstituted with bacteriostatic water before injection.

Reconstitution Table

Reconstitution Steps

1. Wipe the vial stopper and BAC water vial with alcohol swabs
2. Draw the appropriate volume of bacteriostatic water into a syringe
3. Inject the water slowly into the lyophilized NAD+ vial, directing the stream against the glass wall
4. Swirl gently until fully dissolved — do not shake
5. Solution should be clear and colorless; discard if cloudy or particulate
6. Store reconstituted vial refrigerated at 2-8 degrees C
7. Use within 28 days of reconstitution

Storage note: Unreconstituted NAD+ powder should be stored frozen (-20 degrees C) or refrigerated for maximum stability. NAD+ is less stable in solution than many peptides, so prompt refrigeration after reconstitution is important.

Cycling Recommendations

Injectable NAD+ Cycling

Cycling injectable NAD+ allows assessment of sustained effects and prevents potential receptor or pathway adaptation. During off-cycle periods, many users maintain NAD+ support with oral NMN or NR.

Oral Precursor Cycling

Oral NMN and NR are commonly used continuously based on published trial protocols lasting 6-12 weeks without cycling. For those who prefer cycling:

• Standard: 3 months on, 1 month off
• Conservative: 8 weeks on, 4 weeks off

Combined Protocol

A practical approach many users follow:

1. Weeks 1-10: Subcutaneous NAD+ 100-200 mg 3x/week + NMN 250 mg daily
2. Weeks 11-14 (off cycle): NMN 500 mg daily (bridge with oral precursor)
3. Repeat

Who Uses NAD+ Protocols

NAD+ replenishment targets several interconnected aging and performance pathways:

Longevity and anti-aging: NAD+ is required for sirtuin activation (SIRT1-7), a family of deacetylases that regulate DNA repair, mitochondrial biogenesis, inflammation, and stress resistance. Age-related NAD+ decline impairs sirtuin function (Imai & Guarente, 2014).

Cellular energy and mitochondrial function: NAD+ is a critical electron carrier in the mitochondrial electron transport chain. Declining NAD+ directly impairs oxidative phosphorylation and ATP production. Restoring NAD+ levels improves mitochondrial membrane potential and energy output (Stein & Imai, 2012).

Cognitive function: NAD+ supports neuronal health through SIRT1-mediated neuroprotection, PARP-dependent DNA repair in neurons, and maintenance of axonal integrity. Preclinical models demonstrate that boosting NAD+ protects against neurodegeneration (Lautrup et al., 2019).

DNA repair: PARP enzymes consume NAD+ during DNA repair. As DNA damage accumulates with age and NAD+ levels fall, repair capacity is compromised. Supplementation restores PARP function and genomic stability (Fang et al., 2017).

Exercise performance and recovery: NAD+ supports metabolic flexibility and mitochondrial adaptation to exercise. NMN supplementation has been shown to improve aerobic capacity in amateur runners (Liao et al., 2021).

Side Effects and Safety

Injectable NAD+ (SC)

• Injection site stinging/burning: Very common, lasting 5-15 minutes. The most frequently reported side effect.
• Mild flushing: Occasional, less intense than IV route
• Nausea: Rare at subcutaneous doses

IV NAD+

• Flushing, warmth, chest tightness: Common, rate-dependent. Managed by slowing infusion.
• Nausea and cramping: Common at higher doses or faster rates
• Headache: Occasional
• Muscle cramping: Occasional

Oral Precursors (NMN/NR)

• GI discomfort: Mild and infrequent at standard doses
• Flushing: Rare (NMN/NR do not directly activate the niacin flush receptor at typical doses)
• Insomnia: Occasional if taken late in the day

Safety Considerations

NAD+ precursors have favorable safety profiles in published human trials. NR at 1000 mg/day for 6 weeks showed no serious adverse events (Martens et al., 2018). NMN at 250 mg/day for 12 weeks was well-tolerated (Yoshino et al., 2021).

For injectable NAD+, long-term safety data from controlled trials is limited. Users should monitor for injection site reactions and systemic effects, and consult a healthcare provider before starting any injectable protocol.

Stacking NAD+ with Longevity Peptides

NAD+ replenishment addresses one pillar of mitochondrial aging. Combining it with peptides that target complementary pathways creates a broader anti-aging approach:

NAD+ + SS-31

SS-31 stabilizes cardiolipin in the inner mitochondrial membrane while NAD+ fuels the electron transport chain that cardiolipin organizes. SS-31 optimizes the machinery; NAD+ provides the fuel.

NAD+ + MOTS-c

MOTS-c activates AMPK to improve metabolic signaling, while NAD+ directly restores coenzyme levels. MOTS-c enhances how cells use energy; NAD+ ensures there is energy to use.

NAD+ + Epitalon

Epitalon activates telomerase to maintain telomere length. NAD+ supports the PARP and sirtuin enzymes that maintain genomic integrity alongside telomere function. Together they address two distinct aspects of cellular aging.

Frequently Asked Questions

What is the best route of administration for NAD+?

It depends on your goals. Subcutaneous injection offers the best balance of bioavailability and convenience. IV infusion delivers the highest peak NAD+ levels but requires clinical supervision. Sublingual and nasal routes are non-invasive alternatives with moderate bioavailability. Oral NMN/NR precursors are the most accessible but rely on indirect NAD+ synthesis.

How much NAD+ should I inject subcutaneously?

Community protocols typically use 50-200 mg per injection, 2-3 times per week. Most users start at 50 mg to assess tolerance (injection site stinging is common) and titrate up to 100-200 mg over several weeks.

Why does IV NAD+ cause flushing and nausea?

NAD+ activates the GPR109A receptor (the same niacin flush receptor), triggering prostaglandin release that causes vasodilation, warmth, flushing, and sometimes nausea. Slower infusion rates (2-4 hours for 250-500 mg) significantly reduce these effects.

How do I reconstitute NAD+ for injection?

Add bacteriostatic water to the lyophilized vial. For a 250 mg vial, add 2.5 mL BAC water for a 100 mg/mL concentration. Draw 50 units on an insulin syringe for a 50 mg dose. Store refrigerated at 2-8 degrees C, use within 28 days.

Should I take NMN or NR instead of injecting NAD+?

Oral NMN (250-1000 mg daily) and NR (300-1000 mg daily) are convenient and well-studied precursors that raise NAD+ levels over days to weeks. Direct NAD+ injection provides faster, higher peak levels. Many users combine low-dose oral precursors with periodic injections.

How long does it take to feel effects from NAD+?

IV infusion effects (energy, mental clarity) are often noticed within hours. Subcutaneous injection effects typically emerge over 1-2 weeks of consistent dosing. Oral precursors may take 2-4 weeks of daily use to produce noticeable changes.

Do I need to cycle NAD+?

Cycling is recommended for injectable NAD+ (8-12 weeks on, 4 weeks off) to prevent receptor adaptation. Oral NMN/NR precursors are commonly used continuously without cycling, though some users cycle 3 months on, 1 month off.

Can I combine NAD+ with other longevity peptides?

Yes. NAD+ is commonly stacked with SS-31 (mitochondrial membrane stabilization), MOTS-c (AMPK activation), or Epitalon (telomerase activation). These target different aging pathways and complement NAD+ replenishment.

Related Guides

• SS-31 Dosing Guide — Mitochondrial peptide for cardiolipin stabilization
• Epitalon Dosing Guide — Telomerase activation for cellular longevity
• MOTS-c Dosing Guide — Mitochondrial-derived metabolic peptide
• Humanin Dosing Guide — Neuroprotective mitochondrial peptide
• Peptide Stacking Guide — How to combine longevity peptides effectively

References

For educational and research purposes only — no clinical use is approved. This is not medical advice. NAD+ supplementation is not FDA-approved for any anti-aging indication.