MOTS-c and NAD+ are often sold side by side, sometimes by the same clinic, as two ways to make your mitochondria work harder. They are very different things. One is an experimental peptide FDA found no human data on at all [1]. The other is a natural coenzyme that pharmacies may compound while FDA evaluates it [3]. Neither has a trial showing more energy or slower aging in healthy adults.
A peptide and a coenzyme, both sold as "mitochondrial"
MOTS-c is a 16-amino-acid peptide encoded in the DNA of mitochondria themselves, first described in 2015 [7]. In cells and mice it acted mainly on skeletal muscle and switched on AMPK, an energy-sensing enzyme [7]. What's sold online is a lab-made version.
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell and central to how cells turn food into energy. Levels fall with age, which is the whole basis of "NAD+ boosting" [11]. The supplements and shots sold for it are trying to top up something the body already makes.
Side by side: a status split and an evidence split
| MOTS-c | NAD+ | |
|---|---|---|
| What it is | A 16-amino-acid peptide from mitochondrial DNA [1] | A coenzyme in every cell |
| Human evidence | None for the drug; FDA found no human data by any route [1] | Small IV studies; no wellness outcome trials [11] |
| FDA status | Never approved; in no 503A category since April 2026 [3] | Not FDA-approved; 503A Category 1, under evaluation [3] |
| Can a pharmacy compound it? | No: not on the bulks list; FDA's July 2026 briefing weighs against listing | Yes, under FDA's interim policy for Category 1 substances [5] |
| Forms sold | Injection vials, mostly labeled "research use only" | Compounded injection, IV infusion, nasal spray |
| Sport | Prohibited at all times, WADA S4.4.1 (AMPK activators) [12] | Not among the substances WADA's 2026 list names |
Category 1 lets pharmacies compound NAD+ while FDA decides. It is not an approval, and compounded drugs are not FDA-reviewed for safety or effectiveness.
Which is better for energy? Neither has a human trial showing more
The energy claim for MOTS-c rests on mice. In one study, MOTS-c improved physical performance in young, middle-aged and old mice, and late-life treatment increased physical capacity [8]. The same paper's human data show something else: exercise raised people's own MOTS-c levels in muscle and blood. Nobody in that study was given MOTS-c.
The energy claim for NAD+ rests on biology, not outcomes. A 2026 review of 33 human trials found that oral precursors reliably raise NAD-related markers, but effects on function were mixed and often null. It found no eligible outcome trial of IV or injected NAD+ itself for anti-aging or wellness [11]. More detail is on do NAD injections work.
MOTS-c's record: mouse studies, then an FDA review that found no human data
The founding study reported that MOTS-c prevented age-related and high-fat-diet insulin resistance in mice, and diet-induced obesity [7]. The later study added physical capacity in aging mice [8]. Two senior authors of these studies disclosed that they consult for and hold shares in CohBar, a company developing MOTS-c-based drugs.
FDA's 2026 review then looked for anything in people. It found no clinical studies or human exposure data "via any route of administration," and no pharmacokinetic studies. FDA concluded that potential risks in humans "are unknown" [1]. FDA also didn't evaluate the uses MOTS-c was nominated for, including obesity and longevity, because the nomination lacked the information needed. More on fat-loss claims is in does MOTS-c burn fat.
NAD+'s record: fast clearance, one heart-failure trial, no wellness outcomes
The first human study of infused NAD+ was a pilot that tracked blood and urine during a 6-hour IV drip. Plasma NAD+ didn't change for the first 2 hours; the authors wrote that it was "rapidly and completely removed from the plasma" in that window [9]. Two co-authors were affiliated with an NAD+ research company and a wellness clinic.
The strongest trial is in a specific disease. In 180 adults with heart failure from ischemic heart disease, 7 days of IV NAD+ on top of standard care raised heart pumping function at 1 month more than placebo: ejection fraction 45.44% against 42.44% [10]. Fewer heart events at 6 months was a trend that didn't reach significance. That says nothing about healthy adults looking for energy. IV drips specifically are covered in NAD+ IV therapy.
| Study | Substance | Who | What it found |
|---|---|---|---|
| Lee 2015 [7] | MOTS-c | Mice and cells | Less diet-induced obesity and insulin resistance |
| Reynolds 2021 [8] | MOTS-c | Mice; people exercising (no MOTS-c given) | Better physical capacity in mice; exercise raised people's own MOTS-c |
| FDA briefing 2026 [1] | MOTS-c | Literature review | No human data by any route |
| Grant 2019 [9] | NAD+ (IV) | Small pilot in adults | Plasma NAD+ unchanged for the first 2 hours |
| Yu 2026 [10] | NAD+ (IV) | 180 adults with heart failure | Ejection fraction 45.44% vs 42.44% at 1 month |
| Gallagher 2026 [11] | NAD+ and precursors | Review of 33 human trials | No outcome trial of injected or IV NAD+ for wellness |
The 2026 review's author owns a management firm serving an aesthetics clinic that, per the disclosure, doesn't offer NAD+.
Safety: unknown for MOTS-c, unlabeled for NAD+
FDA searched its adverse-event database for MOTS-c reports through March 2025 and found none [1]. FDA also notes that 503A pharmacies generally don't report side effects to it, so an empty search says little. Its main concern is the peptide itself. A 16-amino-acid chain can clump during manufacturing, and clumps and impurities raise the risk of immune reactions.
NAD+ has no FDA label either, so there is no FDA-reviewed list of side effects for compounded shots or drips. What the human studies report is short-term tolerance in small groups. What is and isn't known is on are NAD injections safe.
Status and access: NAD+ has a pharmacy route, MOTS-c does not
NAD+ is not an FDA-approved drug. FDA keeps it in Category 1 of its 503A list, substances under evaluation [3]. Under FDA's interim policy, licensed pharmacies may compound Category 1 substances while FDA decides [5]. Prescriber programs and their prices are on the NAD+ page.
MOTS-c went the other way. FDA placed it in Category 2 on September 29, 2023 [4] and removed it in April 2026, after the nomination was withdrawn. It is in no category on the current list [3]. FDA still took it to its advisers on July 23, 2026, with a briefing that said the criteria "weigh against" listing it [1].
FDA has posted no minutes or vote from that meeting [2]. A trade journal reported that the committee voted 7 to 5, with 2 abstentions, to recommend MOTS-c anyway [6]. A vote is advice, and FDA has issued no rule as of this update. Vials sold as "research use only" are not made or tested for people. The status question in full is on is MOTS-c FDA approved.
Related matchup: NMN vs NAD+. How this site weighs evidence and status is in how we check.