Longevity and MitochondriaWell researchedNot technically a peptidemitochondrialcoenzymesirtuinsenergyaging

NAD+

Also known as Nicotinamide adenine dinucleotide, NAD, beta-NAD, Coenzyme 1

NAD+ is a coenzyme found in every living cell, not a peptide. It is central to energy metabolism and DNA repair, declines with age, and is injected or infused by people hoping to restore energy, cognition, and cellular resilience.

Reviewed by the amino101 editorial team. , first published .

Status
Unapproved as a drug; sold as a compounded injectable, IV infusion, and supplement
Typical dose
50 to 100 mg
daily or a few times per week for injections; IV infusions weekly to monthly
Route
Subcutaneous, Intramuscular, Intravenous, Oral
Subcutaneous, belly or thigh, is gentler; intramuscular is faster and more likely to cause a flush; IV only in a clinic
Cycle
ongoing or blocks of several weeks
Break: no established break; many run 4 to 8 weeks then reassess
Storage
Fridge 2 to 8 C
fridge 2 to 8 C once mixed, use within 2 to 4 weeks; discard if the solution turns yellow or cloudy

Quick start

What people commonly do. Not a prescription.
Typical dose
50 to 100 mg per injection
How often
daily or a few times per week for injections; IV infusions weekly to monthly
Where
Subcutaneous, belly or thigh, is gentler; intramuscular is faster and more likely to cause a flush; IV only in a clinic
Timing
morning, since the post injection dip or flush is easier to deal with early in the day
Effects timeline
flush or fatigue 20 to 60 minutes after injection, energy later that day for some; anything cumulative takes 2 to 4 weeks and is subjective
Storage
fridge 2 to 8 C once mixed, use within 2 to 4 weeks; discard if the solution turns yellow or cloudy
Cycle length
ongoing or blocks of several weeks
Break between
no established break; many run 4 to 8 weeks then reassess

Overview

NAD+ is not a peptide. It is a small molecule made of two nucleotides joined by their phosphate groups, one containing adenine and the other nicotinamide. It shows up in peptide databases because it is sold as a lyophilized powder in vials, reconstituted with bacteriostatic water, and injected subcutaneously or intramuscularly by the same people who use peptides. It is a coenzyme, meaning it shuttles electrons in hundreds of metabolic reactions and serves as a substrate for sirtuins, PARPs, and CD38.

The aging story is real at the biological level. NAD+ levels fall in many tissues with age, and restoring them in old mice improves mitochondrial function, muscle performance, and some measures of healthspan. Most of that research used precursors such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), which cells can absorb and convert, rather than NAD+ itself. Human trials of those precursors reliably raise blood NAD+ but have shown modest or inconsistent functional benefits so far.

Direct NAD+ administration has much less data. A small Australian pharmacokinetic study of a six-hour intravenous infusion found plasma NAD+ did not rise until about two hours in, suggesting rapid uptake or breakdown, and that the infusion mainly raised nicotinamide and other metabolites. Oral NAD+ is largely broken down in the gut into precursors before absorption. Injected NAD+ probably works, if it works, by being converted to nicotinamide and rebuilt inside cells. The widespread IV clinic and injection use for fatigue, addiction recovery, and anti-aging rests on that plausible but unproven chain.

How it works

NAD+ accepts and donates electrons in glycolysis, the citric acid cycle, and fatty acid oxidation, cycling between NAD+ and NADH to keep the mitochondrial electron transport chain running. Separately from that redox role it is consumed as a substrate by sirtuins, which deacetylate proteins involved in stress resistance and mitochondrial biogenesis, by PARP enzymes that repair DNA, and by CD38, an enzyme that rises with inflammation and age and is a major cause of NAD+ decline. Raising NAD+ availability is thought to restore sirtuin and PARP activity and improve mitochondrial efficiency. Injected NAD+ is not transported intact into most cells; it is likely broken down outside cells into nicotinamide and nicotinamide riboside, which cells take up and rebuild into NAD+.

Molecular weight
663.4 Da
Length
not a peptide; two nucleotides (adenine and nicotinamide) joined through a pyrophosphate bridge
Type
Coenzyme

Where the research stands

Human trials
Small pilots only
Animal data
Extensive
Safety data
Limited
Regulatory
Not approved as a drug anywhere; sold as a compounded injectable, IV infusion, and dietary supplement
WADA
Not listed
Age related NAD+ decline and mitochondrial functionModerate evidence
  • Raising blood NAD+. Human RCTs of oral NR and NMN reliably raise blood NAD+; injected NAD+ has only a small pharmacokinetic study.
  • Muscle and mitochondrial function in old mice. Rodent; restoring NAD+ improved mitochondrial function, muscle performance, and some healthspan measures.
  • Functional outcomes in people. Precursor RCTs show modest or inconsistent effects on strength, metabolism, and cognition despite the NAD+ increase.
NeurodegenerationEmerging
  • Parkinson disease. Small human trials of oral NR raised brain NAD+ and showed early clinical signals; nothing with injected NAD+.
  • Mouse models of neurodegeneration. Rodent; NAD+ precursors improved outcomes in several models.
Fatigue and energyEmerging
  • Chronic fatigue and low energy. Community reports and clinic use are widespread, but no controlled trial of injected or IV NAD+ for fatigue has been done.
Addiction recovery and withdrawalWeak or mixed
  • IV NAD+ in detox clinics. Uncontrolled case series only; no placebo controlled data.
Key findings
  • rodentNAD+ levels decline with age in multiple human and mouse tissues, and restoring them in old mice improves mitochondrial function and muscle performance.
  • human RCTOral NR and NMN reliably raise blood NAD+ in humans in randomized trials, with modest or inconsistent functional benefits.
  • human pilotA six-hour intravenous NAD+ infusion in healthy volunteers did not raise plasma NAD+ until about two hours in, with rapid metabolism to nicotinamide and other products.
  • rodentCD38 upregulation is a primary driver of age-related NAD+ decline in mice.
  • rodentNAD+ precursors improved outcomes in mouse models of neurodegeneration and metabolic disease.

Rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.

Levels over time

Modeled from the half-life. Illustrative, not measured.
Peak
not clearly established; a six hour IV infusion did not raise plasma NAD+ until about 2 hours in, and no subcutaneous injection data exists
Half-life
minutes in plasma; rapidly broken down to nicotinamide and other metabolites
Cleared
within about an hour from plasma; metabolites such as nicotinamide persist for hours
Repeated dosing every 24 hDose
100%50%dose 114m27m41m54mnext dose at 24h, long after clearance
What this means for dosing

A half-life of 6 min against dosing every 24 h means each dose has cleared before the next. Nothing stacks; you start from zero every time, and the tissue effect is what carries over.

Injected NAD+ probably does not enter cells intact and instead supplies precursors that cells rebuild, so what matters is the cumulative daily supply rather than plasma NAD+, which is why daily or several times weekly dosing is used.

NAD+ dosage and protocols

No established cycle. People either run daily injections for a few weeks and reassess, or use a few injections per week indefinitely. IV clinics space infusions weekly to monthly. Start at the low end to gauge the flush.

GoalDoseFrequencyRoute
Daily subcutaneous50 mgonce dailySubcutaneous, morning
Higher subcutaneous100 mgonce daily or every other daySubcutaneous, morning
Intramuscular50 to 100 mg2 to 3 times weeklyIntramuscular
Clinic infusion250 to 1000 mgweekly to monthlyIntravenous over 2 to 6 hours
Oral precursor alternative250 to 1000 mg NR or NMNonce dailyOral, with or without food
Timing

Morning, and not right before training or driving because of the possible fatigue wave. Injecting slowly reduces the flush. Food does not matter for injection; oral precursors work with or without food.

Per injection, subcutaneous or intramuscular. IV clinics infuse 250 to 1000 mg over several hours. Oral NAD+ is mostly broken down before absorption; oral precursors like NR and NMN are used at 250 to 1000 mg daily.

Dose calculator

U-100 insulin syringe
Draw
- units
- mL at -
- doses per vial. - per unit.

Units are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.

Common vial sizes and reconstitution
VialSuggested waterConcentrationLow dose draw
500 mg5 mL100 mg/mL50 units
1000 mg10 mL100 mg/mL50 units

How to reconstitute NAD+

  1. 1

    Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.

  2. 2

    Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.

  3. 3

    Draw the bacteriostatic water into a mixing syringe.

  4. 4

    Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.

  5. 5

    Swirl gently or leave it to dissolve. Do not shake.

  6. 6

    Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.

  7. 7

    Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.

  8. Full walkthrough with syringe reading and site rotation: reconstitution guide.
Quality check
  • ✓
    White, fluffy cake

    Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.

  • ✓
    Clear after mixing

    Once dissolved the solution should be water-clear with nothing floating in it.

  • !
    Slight clumping

    Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.

  • ✕
    Collapsed or melted

    Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.

  • ✕
    Cloudy or particles

    Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.

What to expect
  1. First injection

    Stinging at the site, then a flush, mild nausea, or a wave of fatigue lasting 20 to 60 minutes; slower subcutaneous injection makes this milder.

  2. Week 1 to 2

    Some people report better afternoon energy and sleep; many report nothing beyond the injection reaction.

  3. Week 2 to 4

    Whatever benefit there is has usually shown up by now; there is no home measurable marker to track.

  4. Ongoing

    Injection tolerance improves; long term effects on aging in people are unproven.

Interactions and stacking

MOTS-ccompatible

MOTS-c signals through AMPK and mitochondrial pathways that depend on NAD+ availability; no combined data.

SS-31compatible

SS-31 stabilizes the electron transport chain that NAD+ feeds; no overlap in side effects and no combined data.

Glutathionecompatible

Often infused together in clinics as a general antioxidant and energy combination without controlled evidence.

Epithaloncompatible

Common longevity pairing with no interaction expected and no data either way.

5-Amino-1MQcompatible

NNMT inhibition spares nicotinamide, which in theory keeps more available for NAD+ synthesis; untested in combination.

Methyl donors (TMG, B12, folate)compatible

Large NAD+ doses produce a lot of nicotinamide that is cleared by methylation; some people add methyl donors, though the practical need is debated.

Active cancer or chemotherapycaution

NAD+ supports proliferating cells as much as healthy ones; the concern is theoretical but there is no safety data in this setting.

Safety

Side effects and cautions
  • ▲Stinging, redness, or swelling at the injection site
  • ▲Flush, chest tightness, cramping, and nausea, mainly with fast IV infusion
  • ▲Transient fatigue or a flu-like feeling after injection
  • ▲Headache
  • ▲Possible depletion of methyl groups at large doses, a debated concern
  • ▲Injections sting and can cause redness, swelling, or a temporary flu-like feeling.
  • ▲IV infusions given too fast cause chest tightness, nausea, cramping, and flushing; slow infusion is standard for that reason.
  • ▲Large doses generate a lot of nicotinamide, which uses up methyl groups for clearance; the practical significance is debated.
  • ▲Human evidence for functional benefit is far weaker than the marketing implies.
  • ▲Compounded NAD+ quality varies and the solution degrades quickly; discolored vials should be discarded.
Stop and reassess if
  • ■Chest pressure, palpitations, or shortness of breath during or after dosing
  • ■Injection site infection or spreading redness
  • ■No noticeable benefit after 4 to 8 weeks
  • ■The vial has turned yellow or cloudy, which means the NAD+ has degraded; discard it and reassess the supplier
Educational only. Dose ranges describe what appears in published research and community protocols. This is not medical advice and most of these compounds are not approved for human use. Talk to a clinician who knows your history.

Community poll

Self-reported by visitors. Not clinical evidence.
What is your experience with NAD+?
If you have used it, how well did it work for you?
Any side effects?
Where did you first hear about it?

NAD+: frequently asked

Is NAD+ a peptide?

No. It is a coenzyme made of two nucleotides. It gets grouped with peptides only because it is sold and injected the same way. Chemically and biologically it is unrelated to peptides.

Do injections work better than NMN or NR pills?

Nobody knows. Oral precursors have controlled trials showing they raise blood NAD+. Injected NAD+ has a small pharmacokinetic study and a lot of anecdote. Since injected NAD+ likely gets broken down to precursors before entering cells anyway, the advantage of injection over a good oral precursor is not established.

What does an NAD+ injection feel like?

Many people report a flush, mild nausea, or a wave of fatigue for 20 to 60 minutes after subcutaneous or intramuscular injection, followed by a sense of energy later in the day. Slower absorption from subcutaneous injection tends to be more comfortable than IM.

Why do IV infusions take hours?

Rapid NAD+ infusion causes chest pressure, cramping, and nausea, probably related to its breakdown products and effects on smooth muscle. Clinics drip it slowly over two to six hours to keep those symptoms tolerable.

Does it help with aging?

In mice, restoring NAD+ improves several aging markers. In humans, raising NAD+ is easy but showing it improves anything meaningful has been difficult. Treat anti-aging claims as hypothesis, not established benefit.

References

  1. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Frontiers in Aging Neuroscience, 2019
  2. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metabolism, 2018
  3. NAD+ intermediates: the biology and therapeutic potential of NMN and NR. Cell Metabolism, 2018
  4. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 2021