MOTS-c vs NAD+: differences, evidence and safety
Answer first
MOTS-c is a peptide of 16 amino acid building blocks whose blueprint sits in mitochondrial DNA. NAD+ is not a peptide but a coenzyme every cell makes. Neither is approved as a medicine in any of the seven markets checked. MOTS-c is banned in sport by name. No direct comparison of the two could be found in the sources reviewed.
At a glance
How they work
For MOTS-c, every proposed mechanism comes from cells in a dish or from animals, so each point is a hypothesis [1]. For NAD+, the basic chemistry is established; whether adding more changes anything in a person is open [2], [3].
MOTS-c. The body reads this peptide off a short stretch of code inside a gene of the mitochondria, the power plants of the cell [4].
- The cell's energy sensor. The peptide is said to block a chain of reactions built around folate. A substance called AICAR then piles up and may switch on the cell's fuel gauge, the enzyme AMP-activated protein kinase [4].
- A message to the nucleus. In sugar-starved cultured cells, MOTS-c moved into the nucleus and settled next to genes that defend against chemical stress [5].
- A second enzyme. One group reported that it binds and switches on casein kinase 2 in skeletal muscle. That route would not involve the energy sensor at all [6].
- Findings that point the other way. Peptides of this family made worn-out cells release more inflammatory signals [7]. In human connective tissue cells, MOTS-c weakened the ability to repair damage [8].
NAD+. Nicotinamide adenine dinucleotide is a coenzyme, a small helper molecule that enzymes need in order to work [9].
- A carrier of electrons. It shuttles between two forms, NAD+ and NADH, in the reactions that release energy from food [2].
- Raw material that gets used up. Several enzyme families break it apart as part of their work. Among them are the sirtuins, the DNA-repair enzymes called PARPs, and the surface enzymes CD38 and CD157 [2].
- A decline with age of unclear meaning. Reviews describe falling tissue levels as a possible contributor to age-related disease. They say plainly that this is a hypothesis, not a proven cause in people [2], [10].
- Taken apart before it gets in. During the only human infusion measurement, the substances in urine matched NAD+ being split by enzymes outside cells [11]. The large, charged molecule does not slip through cell membranes on its own [9].
The core difference is chemical. MOTS-c is a chain of 16 amino acids weighing 2,174.6 g/mol [12]. NAD+ weighs 663.43 g/mol and contains no amino acid at all [9]. One is proposed as a signal that switches enzymes on; the other is the helper and raw material of enzymes, not a receptor target [2].
What the studies show
No study that compares MOTS-c and NAD+ directly could be found in the published record reviewed for this page. The two records also rest on different kinds of evidence. For MOTS-c, almost everything about giving it comes from mice. For NAD+, nearly all controlled human data concern two swallowed building blocks, NR and NMN [3].
MOTS-c in mice
Animal data In two strains of mice, with 6 to 8 animals per group, a daily injection helped the animals clear sugar from the blood. Their tissues also responded more strongly to insulin. On a fattening diet they neither grew obese nor became resistant to insulin [4].
The whole field rests on this result, and no controlled human study repeating it could be found in the sources reviewed.
Animal data In mice aged 2, 12 and 22 months, in groups of 5 to 10, treadmill running improved at every age [13]. In untrained mice, a single dose lengthened running time by 12 percent and running distance by 15 percent [14].
MOTS-c in people: measured, not given
Observational In ten young men who took no regular exercise, hard interval training raised MOTS-c in their muscle and blood [13]. Nobody was given anything. The study describes the body's own peptide reacting to training.
Observational In 10 lean people and 10 people with obesity, blood levels were much the same. The values were 0.48 ± 0.16 against 0.52 ± 0.15 nanograms per millilitre, a gap well within chance (p = 0.60) [15].
Observational In 26 people with metabolic syndrome, a cluster of metabolic problems occurring together, the level was higher rather than lower. It reached 315 picograms per millilitre (315 ± 27) and climbed with the fat in their livers [16]. A higher level is not a better one.
Registry No verified trial giving MOTS-c itself to people could be found in the sources reviewed for this page. One registry entry claims such a study. Its sponsor filed further entries that call themselves mock or fictional records, so it is not counted [17].
CB4211, a different molecule
Phase 1 (press release only) CB4211 is a chemically altered relative of MOTS-c built by the company CohBar. An early-stage trial ran in 88 participants between July 2018 and April 2021 [18]. In its third part, 20 people with obesity and fatty liver disease were treated for four weeks [19].
Phase 1 (press release only) The company reported that two liver enzymes fell by 21 and 28 percent. On placebo, one rose by 4 percent and the other fell by 11 percent. Blood sugar fell by 6 percent against no change (p < 0.05 for each) [19].
No independent experts checked these figures, and no results were posted in the registry [18]. The company later declared the preparation unsuitable for further development [20].
NAD+ given into a vein
Human pilot study Eleven healthy men aged 30 to 55 took part. Eight received NAD+ as a slow drip over six hours, and three served as controls. Through the first two hours, neither NAD+ nor any breakdown product rose in the blood [11].
Human pilot study After six hours, methylnicotinamide and NAD+ appeared in the urine. The authors read this as rapid removal from the plasma at that infusion rate [11].
Record review A provider's review of its own records compared NAD+ drips with drips of NR. The NAD+ drips had to be slowed and took 97 minutes on average, against 37 minutes for NR [21]. The review was retrospective and uncontrolled, and seven of its authors worked for the company providing the infusions [21].
Registry A search of the American trial register identified no randomised, placebo-controlled efficacy trial of NAD+ into a vein [22]. A 2026 review concludes that intravenous longevity therapy should be regarded as experimental rather than evidence-based practice [23].
The swallowed building blocks NR and NMN
Randomised trial In overweight adults, whole-blood NAD+ rose by 22, 51 and 142 percent at three ascending dose levels of NR over eight weeks [24]. That shows the substance reached its biochemical target, not that it brought a health benefit. The trial was run for the manufacturer of the product [24].
Randomised trial, endpoint missed In 40 obese men, twelve weeks of NR did not improve insulin sensitivity, glucose production or glucose uptake. Body composition was unchanged too [25].
Randomised trial, endpoint missed In 20 older adults with mild cognitive problems, ten weeks of NR raised blood NAD+ 2.6-fold. The cognitive score did not change [26].
Systematic review A 2026 review screened the years 2010 to 2025 and found 113 eligible studies, 33 of them human trials. NR and NMN reliably hit their biochemical target. Effects on function, metabolism and blood vessels were mixed and often absent, and none of the studies was an outcome trial [3].
These trials tested NR and NMN, not NAD+. A result for a swallowed building block does not describe what a drip or an injection does [3].
Why the numbers cannot be compared
The MOTS-c results come mostly from mice given the peptide itself, the NAD+ results mostly from people who swallowed other substances. Species, doses, measures and time spans all differ, so the figures cannot be set against each other.
Doses used in the studies
The doses below are simply what the cited studies gave, listed so that the results can be understood. They are not advice on how to use anything.
| Study | Substance | Model | Dose | Route | Duration | Ref |
|---|---|---|---|---|---|---|
| Lee 2015 | MOTS-c | CD-1 mice, normal diet | 5 mg/kg/day, split in two | Intraperitoneal | 4 days | [4] |
| Lee 2015 | MOTS-c | C57BL/6 mice, normal and high-fat diet | 5 mg/kg/day | Intraperitoneal | 7 days to 8 weeks | [4] |
| Reynolds 2021 | MOTS-c | CD-1 mice, 12 weeks old | 5 and 15 mg/kg/day | Intraperitoneal | 2 weeks | [13] |
| Reynolds 2021 | MOTS-c | C57BL/6N mice, from 23.5 months | 15 mg/kg/day, three times weekly | Intraperitoneal | To end of life | [13] |
| Hyatt 2022 | MOTS-c | Untrained mice | 15 mg/kg, single dose | Not specified in the abstract | Single | [14] |
| CohBar phase 1a/1b, part C | CB4211, an analogue | Humans, n = 20 | 25 mg daily | Subcutaneous | 4 weeks | [19], [18] |
| Grant 2019, infusion pharmacokinetics | NAD+ | Humans, n = 11 healthy men | 750 mg in total, about 2 mg a minute | Into a vein | 6 hours, once | [11] |
| Reyna 2026, provider record review | NAD+, and NR for comparison | Humans, n not stated | 500 mg per infusion | Into a vein | 4 consecutive days | [21] |
| Conze 2019, dose response | NR | Humans, overweight adults | 100, 300 or 1000 mg a day | By mouth | 8 weeks | [24] |
| Dollerup 2018, obese men | NR | Humans, n = 40 | 2000 mg a day | By mouth | 12 weeks | [25] |
Doses given per kilogram of mouse cannot be converted into a dose for a person. The one human MOTS-c row belongs to a different molecule, in a preparation its maker later abandoned [20]. For NAD+ into a vein, the 750 mg in the pilot study was a scheme taken over from clinics, not the result of dose-finding [11].
Safety
Neither substance has a side-effect profile of the kind a licensed medicine has. This page does not rank the two.
MOTS-c
- No side-effect list for the peptide itself. No verified trial giving it to people could be found in the sources reviewed [17].
- Injection-site reactions with the relative. In the four-week part of the CB4211 trial, the only complaints affecting more than one participant in ten were short-lived needle-site reactions [19].
- Nothing serious reported in that trial. No serious side effects were reported among its 88 participants [19], [18].
- Reports from outside trials. People who said they had bought MOTS-c online reported a faster heartbeat, palpitations, sleeplessness, immune reactions and fever. The cause was not checked, and the products were not analysed [27].
- Regulator concerns. The American regulator flagged possible immune reactions, impurities in the material and a substance not characterised well enough [28], [29].
NAD+
- Symptoms during the drip. The provider's record review describes moderate to severe gut symptoms, a rising heart rate and chest pressure during NAD+ drips. All faded when the drip ended [21].
- One small study saw nothing. No side effects were observed in the eight men of the six-hour infusion study. One infusion in eight people is not a safety result [11].
- Swallowed forms were tolerated. Across 33 human trials, NR and NMN were generally well tolerated over weeks to months, at the doses and durations tested [3].
- Voluntary reports. The American side-effect database held 44 reports under the product name "NAD", 28 of them classed as serious. Such reports carry no proof of cause [30].
- A warning signal from mice. In a mouse model of triple-negative breast cancer, giving NR increased both the frequency of tumours and their spread to the brain [31]. Whether this applies to people is not known.
- Risks of any drip. Infection at the puncture site, vein inflammation, fluid load and errors in preparing the solution apply whatever the drip contains [23].
For MOTS-c, no data in pregnancy, breastfeeding or children could be found in the sources reviewed. The 2026 European assessment of the building block NMN excludes pregnant and breastfeeding women [32]. Missing data are not evidence of safety.
Legal status
Neither substance is approved as a medicine in any of the seven markets examined [28], [33]. The checks ran on 6 September 2026 for MOTS-c and 7 September 2026 for NAD+. In July 2026 an American advisory committee voted against the regulator's proposal to keep MOTS-c off the compounding list. No final decision followed [34], [35]. In the European Union, only the precursor NR chloride is authorised, as a novel food [36]. MOTS-c is banned in sport at all times under section S4.4.1 [37]. NAD+ is not named, but section M2.2 bans infusions above 100 mL per 12 hours [38]. More detail is at peptides banned in sport.
Used together?
The directory lists one product that contains both, the MitoPrime blend. Its third component is 5-Amino-1MQ, a small synthetic molecule that blocks NNMT, the enzyme that methylates nicotinamide [39].
The directory gives the product's declared contents as 10 mg of 5-Amino-1MQ, 10 mg of MOTS-c and 100 mg of NAD+. These figures describe a product label. They are not a dose.
No study of this mixture, or of MOTS-c and NAD+ given together, could be found in the published record reviewed for this page. No measurement of how the body handles the components side by side could be found either. MOTS-c and NAD+ are approved nowhere as medicines [28], [33], and 5-Amino-1MQ is not approved either.
For athletes, a product containing MOTS-c falls under section S4.4.1 of the prohibited list [37].
This page gives no amounts to use and no schedule. MOTS-c and NAD+ each have a full monograph.
Frequently asked questions
Which is better, MOTS-c or NAD+?
The evidence does not allow either to be called better. No study comparing them directly could be found in the sources reviewed for this page. MOTS-c results come mostly from mice given the peptide, while the human data around NAD+ concern mostly the swallowed building blocks NR and NMN.
Is MOTS-c or NAD+ safer?
That cannot be answered. No verified trial giving MOTS-c itself to people could be found, and the only human safety observations come from its altered relative CB4211. For NAD+ drips there is one small pilot study and one uncontrolled record review describing gut symptoms, a rising heart rate and chest pressure. Missing data are not evidence of safety.
What is the difference between MOTS-c and NAD+?
MOTS-c is a peptide of 16 amino acid building blocks, encoded in the mitochondria and proposed to act on the cell's energy sensor. NAD+ is a coenzyme with no amino acids that carries electrons and is used up by several enzyme families. They differ in chemistry, in the kind of evidence behind them and in their sport status.
Can MOTS-c and NAD+ be taken together?
This page answers only what the research shows, not how to use anything. No study of the two together could be found in the published record reviewed for this page. The directory lists one product, MitoPrime, that contains both alongside 5-Amino-1MQ, and none of its three components is approved as a medicine.
Is NAD+ a peptide like MOTS-c?
No. NAD+ is a dinucleotide, two nucleotides joined by a phosphate bridge, and it contains no amino acids and no peptide bonds. MOTS-c is a genuine peptide of 16 amino acids. NAD+ appears beside peptides because it is sold as an injection through the same channels.
Are MOTS-c and NAD+ banned in sport?
MOTS-c is banned at all times and is named in section S4.4.1 of the 2026 Prohibited List. NAD+ as a substance is not named. Infusions or injections of more than 100 millilitres per 12 hours are banned as a method outside hospital treatment, surgery and clinical diagnosis. Ordinary NAD+ drips exceed that volume.
Have MOTS-c and NAD+ been tested in people?
The human studies of MOTS-c found for this page only measure the body's own peptide. The one trial of a relative tested CB4211, a different molecule. For NAD+ into a vein there is one pilot study in eleven men and one record review.
Is NAD+ the same as NMN or NR?
No. They are links in one chain but differ in size, route and legal status: NAD+ at 663 g/mol, NMN at 334 and NR at 255. Almost all the controlled human evidence concerns NR and NMN taken by mouth, so those results do not describe an NAD+ injection.
Sources
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- ClinicalTrials.gov. NCT03998514, phase 1a/1b study of CB4211 in healthy non-obese subjects and subjects with nonalcoholic fatty liver disease; sponsor CohBar, Inc.; n = 88; completed 19 April 2021; no results posted. Retrieved 6 September 2026. https://clinicaltrials.gov/study/NCT03998514
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