Peptide database / Mitochondrial

NAD+

A coenzyme every cell uses for energy and DNA repair, not a peptide. Given as IV drips and injections with very little human outcome data.

Research chemical C Evidence Small or open-label human studies only

Also called Nicotinamide adenine dinucleotide, NAD, beta-NAD, Coenzyme I, NAD+ IV, NAD+ injection

All peptides Last reviewed October 13, 2026
Legal status Research chemical Not on the WADA list
Evidence grade C Small or open-label human studies only
Human studies 40 published, approximate count
Half-life Not established time for levels to halve
Route studied Intravenous infusion plus subcutaneous or intramuscular injection, oral (nad+, nr or nmn)
What it is

NAD+ is not a peptide. It is a coenzyme built from vitamin B3 and adenosine that every cell uses to turn food into ATP, and that enzymes called sirtuins and PARPs burn through to repair DNA and regulate genes. Levels fall with age in mice and in some human tissues, which is why it is sold as an anti-aging and energy treatment. It appears here because clinics usually offer it on the same menu as peptides.

There are two separate questions, and the evidence for each is very different. The first is whether taking precursors by mouth, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), raises NAD+ and does anything useful. The answer to the first half is yes: dozens of randomized trials show blood NAD+ goes up. The second half is mostly disappointing. A 2025 meta-analysis found no effect on muscle mass, grip strength or walking speed in older adults, NR did not improve insulin sensitivity in obese men, and in October 2026 a 410-patient Parkinson trial found NR did slightly worse than placebo. One small trial in 25 prediabetic women found NMN raised muscle insulin sensitivity by 25%.

Read the full overview 1 more

The second question is about NAD+ itself given by IV drip or injection, which is what most clinics sell. That has almost no data. The only published pharmacokinetic study gave 750 mg over 6 hours to 8 men: plasma NAD+ did not rise at all for the first 2 hours because the body broke it down as fast as it went in. A 2026 review found no outcome trials of IV or injected NAD+ for aging or wellness. A retrospective clinic review found NAD+ drips caused stomach upset, faster heart rate and chest pressure, forcing slower infusions that averaged 97 minutes.

Not technically a peptide. NAD+ is listed here because it is discussed and used alongside peptides, but it is not built from amino acids joined by peptide bonds.

Structure Not a peptide: a small molecule or cofactor
Ring structure, no peptide bonds
Length
Not a peptide
Molecular weight
663.4 g/mol (C21H27N7O14P2)
Origin
Endogenous dinucleotide made in the body from tryptophan, niacin, nicotinamide, NR or NMN; pharmaceutical-grade material is produced by fermentation or synthesis
Mechanism

How NAD+ works

What it binds to, and what happens inside the body after that, step by step.

Outside the cell Inside the cell
Target Redox cofactor for energy metabolism; substrate for sirtuins, PARPs and CD38

NAD+ accepts electrons in glycolysis and the Krebs cycle, becoming NADH, which feeds the mitochondrial electron transport chain to make ATP. It is also consumed as a substrate by sirtuins (gene regulation, metabolism), PARPs (DNA repair) and CD38 (immune signaling). Cells mainly rebuild it from nicotinamide through the salvage pathway; NAD+ in the blood is largely broken down outside cells before it can enter them.

  1. 1 Built from vitamin B3 Cells make NAD+ from nicotinamide, NR, NMN, niacin or tryptophan; NR and NMN taken by mouth are partly converted by gut bacteria to nicotinic acid first.
  2. 2 Carries electrons NAD+ picks up electrons from glucose and fat breakdown, becoming NADH, which drives ATP production in mitochondria.
  3. 3 Fuels repair enzymes Sirtuins and PARPs split NAD+ to deacetylate proteins and repair DNA, releasing nicotinamide.
  4. 4 Recycled through salvage NAMPT turns nicotinamide back into NMN and then NAD+; NNMT diverts some nicotinamide out of this loop for excretion.
  5. 5 Infused NAD+ is broken down In the bloodstream, enzymes such as CD38 and pyrophosphatases cleave NAD+ to nicotinamide, NMN and ADP-ribose, which cells then take up.
The research

What the studies show

Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.

C Evidence

For oral precursors (NR, NMN) there are many small RCTs: they reliably raise blood NAD+ and are well tolerated, but effects on muscle, metabolism and disease are mostly null, with one negative 410-patient Parkinson trial. For IV or injected NAD+, the form clinics sell, there is one 8-person pharmacokinetic pilot and one retrospective clinic review, and no controlled outcome trial.

How far the evidence reaches Highest rung: Randomized trials
  1. Cell studies In a dish None listed
  2. Animal studies Rodents and other models None listed
  3. Small human studies Open-label, case series 2 key studies below
  4. Randomized trials Placebo-controlled RCTs, meta-analyses 5 key studies below
  5. Regulatory approval Not approved No
Preclinical: tells you a mechanism is plausible Human: tells you what happened in people (40 published studies, approx.)

In people 7

Randomized trial 2026

Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease: The NOPARK Randomized Clinical Trial

410 patients with early Parkinson disease, 11 centers in Norway, 52 weeks

NR 500 mg twice daily worsened the MDS-UPDRS score by 2.72 points more than placebo (P = .02) and worsened non-motor symptoms; it did not slow the disease.

Read the study
Meta-analysis 2025

The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis

RCTs in adults with mean age 60.9 to 83 years

NMN had no effect on muscle mass index, grip strength, gait speed or chair-stand time; the authors conclude the evidence does not support NR or NMN for preserving muscle.

Read the study
Randomized trial 2021

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

25 postmenopausal women with prediabetes and overweight, 10 weeks

NMN 250 mg/day raised insulin-stimulated glucose disposal in muscle by 25% with no change on placebo; body composition did not change, and muscle NAD+ content did not rise.

Read the study
Show all 7 studies
Randomized trial 2018

A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects

40 sedentary men with BMI over 30, aged 40 to 70, 12 weeks

NR 1000 mg twice daily was safe but did not improve insulin sensitivity, glucose metabolism, energy expenditure or body composition.

Read the study
Randomized trial 2023

The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults

80 healthy middle-aged adults, 300, 600 or 900 mg/day NMN or placebo for 60 days

Blood NAD+ rose in all NMN groups, highest at 600 and 900 mg; six-minute walk distance improved versus placebo and HOMA-IR did not change. The trial was fully funded by the NMN manufacturers, and three authors were their employees.

Read the study
Human, open-label 2019

A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+

11 healthy men, 8 given 750 mg NAD+ IV over 6 hours, 3 given saline

Plasma NAD+ and its metabolites did not change for the first 2 hours because infused NAD+ was cleared as fast as it was given; NAD+ and methylnicotinamide appeared in urine by 6 hours. No adverse events.

Read the study
Case series 2026

Intravenous infusion of NAD+ versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting

Clinic clients given 500 mg IV NAD+ or IV NR daily for 4 days

NAD+ drips caused moderate to severe stomach symptoms, faster heart rate and chest pressure, and took 97 minutes on average versus 37 for NR; liver and kidney markers did not change. Authors employed by the clinic chain.

Read the study
Gaps in the research

What nobody has measured yet

These are questions the published research has not answered.

  1. 01 Whether IV or injected NAD+ improves energy, cognition, addiction recovery or any aging marker in a controlled trial
  2. 02 How much infused NAD+ reaches cells intact versus being broken down to nicotinamide in the blood
  3. 03 Pharmacokinetics of subcutaneous and intramuscular NAD+ injections
  4. 04 Long-term effects of repeatedly raising NAD+, including on cancer growth
  5. 05 Purity and dose accuracy of compounded NAD+, which FDA has not evaluated
History

NAD+ from discovery to today

19062026120 years of research history
  1. 1906Arthur Harden and William Young discover a heat-stable 'coferment' in yeast extract that is later identified as NAD.
  2. 1929Harden and Hans von Euler-Chelpin share the Nobel Prize in Chemistry for work on sugar fermentation and its cofactors.
  3. 2000Sirtuins identified as NAD+-dependent deacetylases, linking NAD+ to aging research.
  4. 2018A 6-week crossover RCT shows oral NR raises NAD+ metabolism in middle-aged and older adults; a 12-week RCT finds NR does not improve insulin sensitivity in obese men.
  5. 2019First published pharmacokinetic study of IV NAD+ in humans (8 men, 750 mg over 6 hours).
  6. 2021NMN raises muscle insulin sensitivity 25% in 25 prediabetic women.
  7. 2025FDA reverses its 2022 position and says NMN can be sold as a dietary supplement.
  8. 2026NOPARK trial: 52 weeks of NR does not help, and slightly worsens, early Parkinson disease. Systematic review finds no outcome trials of IV NAD+.
Approval or regulatory milestoneResearch milestone
Pharmacokinetics

How long it stays in the body

Half-life
Not established
Not defined in humans for infused NAD+; it is broken down in the blood within minutes to hours
Routes studied
Intravenous infusion, Subcutaneous or intramuscular injection, Oral (NAD+, NR or NMN)
Bioavailability
Intravenous NAD+ is largely cleaved to nicotinamide, NMN and ADP-ribose before reaching cells. Oral NAD+ is digested; oral NR and NMN raise blood NAD+ over days to weeks, partly after gut bacteria convert them to nicotinic acid.
Notes
During a 750 mg 6-hour infusion, plasma NAD+ did not rise for 2 hours. No published human pharmacokinetic data exist for subcutaneous or intramuscular NAD+ injections. In a clinic review, nausea, chest pressure and a faster heart rate forced slower NAD+ drips, averaging 97 minutes for 500 mg.

No human half-life has been published for NAD+, so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.

Members

Doses used in published studies

This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.

Doses used in published research and approved labels5 rows
Checking membershipEach row names the trial or label, the dose, route, frequency, duration and a link to the source. Free account, no card.
Safety

Side effects, higher-risk groups and interactions

2Commonroughly 1 in 10 or more
1Uncommonroughly 1 in 100 to 1 in 10
1Rareunder 1 in 100
1Frequency unknownnot measured in trials
EffectCommonUncommonRareUnknown
Nausea, cramping and stomach discomfort during IV infusionReported as moderate to severe with 500 mg NAD+ drips in a clinic review; eased by slowing the infusion.Common
Chest pressure or tightness and faster heart rate during infusionSeen with IV NAD+ in the same review; resolved when the infusion ended.Common
Mild digestive upset with oral NR or NMNTrials up to 2000 mg/day NR and 900 mg/day NMN reported no serious safety signals.Uncommon
Serious reactions when given outside medical settingsIn July 2026 the Partnership for Safe Medicines, citing a CBS News New York report, said a patient in New York City died about an hour after an NAD+ IV infusion given by a person not licensed to practice in New York. No official cause of death had been published.Rare
Flushing and headacheDescribed by infusion clinics with fast drip rates, but not counted in any published study.Frequency unknown
Groups with specific risks
  • Pregnancy and breastfeeding: no safety data for NAD+ infusions
  • Active cancer: some tumors depend on NAD+ supply; the effect of raising NAD+ is unknown
  • Heart rhythm problems or unstable heart disease: IV NAD+ raised heart rate and caused chest pressure in a clinic review
  • Competitive athletes: IV volumes over 100 mL in 12 hours require a therapeutic use exemption
Interactions
  • PARP inhibitor cancer drugs (olaparib and others): work by blocking an NAD+-consuming enzyme; effect of extra NAD+ is unknown, discuss with the oncologist
  • Blood pressure drugs: IV infusions may shift blood pressure and heart rate

Which symptoms are expected and which mean stop and get help: side effects and red flags.

Claims checked

What people say online, checked against the studies

Tap a claim to see what the studies found.

The claim"IV NAD+ goes straight into your cells"Not supportedThe evidence does not back this

In the only human pharmacokinetic study, plasma NAD+ did not rise for 2 hours because it was broken down in the blood; cells mostly rebuild NAD+ from the breakdown products.

The claim"NAD+ reverses aging"Not supportedThe evidence does not back this

Raising NAD+ improves aging markers in mice. In humans, trials show higher blood NAD+ but no consistent effect on muscle, metabolism or function, and no IV NAD+ outcome trials exist.

The claim"Oral NR and NMN raise NAD+ levels"SupportedHuman evidence backs this

Repeated RCTs show blood NAD+ rises within weeks of daily NR or NMN.

The claim"NAD+ drips treat addiction and withdrawal"UntestedNobody has measured this in people

This is a common clinic claim, but no randomized controlled trial of IV NAD+ for addiction has been published.

The claim"NR protects the brain in Parkinson disease"Not supportedThe evidence does not back this

The 410-patient NOPARK trial found NR slightly worse than placebo over 52 weeks.

Untested pairings

Combinations people discuss

These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.

NAD+ with 5-Amino-1MQ

Blocking NNMT keeps nicotinamide in the NAD+ recycling loop, so the two are promoted as complementary.

EvidenceNo study of the combination exists; 5-Amino-1MQ has no human data at all.

NAD+ with MOTS-c

Clinic 'mitochondrial' protocols pair a coenzyme for energy metabolism with an AMPK-activating mitochondrial peptide.

EvidenceNever studied together; MOTS-c has no published human efficacy data.

NAD+ with SS-31

Both are marketed for mitochondrial function: SS-31 binds the inner mitochondrial membrane, NAD+ supplies the electron carrier.

EvidenceNo combination study. SS-31 (elamipretide) has its own human trials; NAD+ infusions do not.

Handling

Storage and stability

Dry powder (lyophilized)

NAD+ powder is sensitive to moisture and light; manufacturers list refrigerated or frozen storage in a sealed container.

Mixed with water (reconstituted)

NAD+ in solution is unstable, especially at room temperature and in alkaline solutions; compounded vials are usually refrigerated with short beyond-use dates set by the pharmacy.

Guide Reconstitution and storage, explainedMembers Bacteriostatic water, fridge vs freezer, and how fast peptides break down.
Keep reading

Related peptides

The Staate peptide brief

New NAD+ research, explained when it is published

One email when a trial reads out, a label changes or the FDA acts on a peptide. Free, no selling of peptides, unsubscribe any time.

Frequently asked questions
Does NAD+ IV therapy actually work?
There are no controlled trials showing it improves energy, cognition, aging or addiction. The only human pharmacokinetic study shows most infused NAD+ is broken down in the blood first.
Is NAD+ better than NMN or NR?
Oral NR and NMN have far more evidence: dozens of RCTs show they raise blood NAD+. IV NAD+ has one 8-person pharmacokinetic study. Neither has strong evidence for health outcomes.
Why do NAD+ drips make you feel sick?
Running NAD+ in fast commonly causes nausea, cramping, chest pressure and a faster heart rate. In one clinic review these symptoms pushed average infusion time to 97 minutes.
Are NAD+ injections FDA approved?
No. There is no FDA-approved NAD+ drug. NAD is in FDA's Category 1 for compounding while it is evaluated, which is not an approval.
Is NAD+ banned for athletes?
NAD+ itself is not prohibited, but any IV infusion or injection over 100 mL in 12 hours is prohibited without a therapeutic use exemption.
Is NMN legal to buy as a supplement?
Yes in the US. FDA said in 2022 it could not be sold as a supplement, then reversed that on September 29, 2025.