What are epitalon, MOTS-c, thymosin alpha-1 and SS-31?

What they are

Epitalon, MOTS-c, thymosin alpha-1 and SS-31 (elamipretide) are unrelated peptides, short chains of amino acids, the building blocks of proteins. Only elamipretide is FDA-approved, and only to improve muscle strength in Barth syndrome, a rare inherited disease of mitochondria, the energy-producing parts of cells. FDA documents show that each has been promoted or proposed for aging, or for immunity in older people.^1,2,3,4,5,6

Epitalon is a lab-made peptide of four amino acids, modeled on epithalamin, an extract of cattle pineal glands. The pineal gland, in the brain, makes melatonin, a hormone involved in sleep. Most studies of epitalon’s effects came from one group, led by Vladimir Khavinson in St Petersburg, Russia, the FDA’s 2026 review found.^3,7

The genetic code for MOTS-c, a 16-amino-acid peptide, sits in the DNA of mitochondria, not in the cell’s nucleus. Researchers at the University of Southern California described it in 2015 and found it in the blood of people and rodents.^8,4

The body makes thymosin alpha-1, a 28-amino-acid peptide first isolated in 1977 from calf thymus, an immune gland. A lab-made version is called thymalfasin. An FDA review lists approvals abroad, mainly for chronic hepatitis B and, in Italy, as an add-on to flu vaccination for people with weakened immune systems.^9,5

Like epitalon, elamipretide is a lab-made chain of four amino acids. It belongs to the Szeto-Schiller family of peptides, the SS in SS-31, which collect in the inner membrane of mitochondria. There it binds cardiolipin, a fat molecule found only in that membrane.^2,10

How they work

How epitalon acts in the body has not been established. Khavinson’s group reported in 2003 that it switched on telomerase in human fetal cells grown in a dish. Telomerase is an enzyme that lengthens telomeres, protective chromosome caps that shorten each time a cell divides. In one study in older monkeys, epitalon raised evening melatonin, but in a lab test it did not make rat pineal glands release more.^7,3

In a 2015 study in mice, MOTS-c appeared to act mainly on muscle and switched on AMPK, an enzyme that helps cells manage energy. Mice on a high-fat diet given it gained less weight and stayed more sensitive to insulin than untreated mice. All such studies have been in rodents, the FDA notes, and the molecule MOTS-c acts on is unknown.^8,4

In lab and animal studies, thymosin alpha-1 activates toll-like receptors, sensors that immune cells use to detect infection. Most of those studies used doses far above those in human trials, so their relevance is unclear, the FDA says.⁵

Barth syndrome is caused by faults in a gene called TAZ, which leave cardiolipin abnormal. Elamipretide’s FDA-approved label says the drug improves the structure and function of mitochondria.^11,2

How they are taken

What the research in people shows

Reviewing epitalon for one proposed use, insomnia, the FDA found three published studies that gave it to people, all by Khavinson or his co-authors. Two, both from 2021, gave it under the tongue to night-shift workers. The third, from 2002, gave injections next to the eye to people with retinitis pigmentosa, an inherited eye disease.³

One of the night-shift studies was randomized and placebo-controlled. Forty women aged 40 to 50 with low levels of a melatonin by-product got an epitalon or placebo spray under the tongue for 20 days. The by-product rose with epitalon but not with placebo. The study was small and short and did not measure sleep or say who knew which spray each woman got, the FDA noted.³

No published study has given MOTS-c to people, the FDA found in 2026; published human studies have measured only the MOTS-c the body makes. A 12-week placebo-controlled trial of MOTS-c in adults with prediabetes and excess weight, planned to enroll 120, began in China in February 2026.^4,15,16

A modified version, CB4211, was tested in a randomized, placebo-controlled safety trial of 88 adults, some with fatty liver disease, that ended in April 2021. As of November 14, 2026, neither its registry entry nor PubMed, an index of medical research, lists results. A draft policy from the Department of Health and Human Services (HHS) says an unnamed randomized, placebo-controlled trial of a modified version of MOTS-c reported no serious adverse events. CB4211’s sponsor, CohBar, licensed the rights to MOTS-c, and the 2015 discovery paper’s senior author owned CohBar shares.^12,46,17,8

The FDA’s 2024 review of 12 uses of thymosin alpha-1, including hepatitis B, sepsis and COVID-19, found a lack of evidence for every one, partly because the studies were small or flawed. Two large double-blind trials, in which neither patients nor doctors knew who got the drug, found no benefit on their main outcomes.^5,18,19

A 2026 Cochrane review, which pools all eligible trials under fixed rules, covered 10 randomized trials in 1,349 people with chronic hepatitis B. It found results favoring thymosin alpha-1, but rated the evidence too uncertain to say it reduces deaths. A 2025 review of 11 sepsis trials found fewer deaths overall, but not among better-designed or multicenter trials.^20,21

The evidence in elamipretide’s label comes from 12 males with Barth syndrome. In a double-blind crossover trial, each took elamipretide and placebo for 12 weeks apiece, in random order. The drug did no better than placebo on walking distance or fatigue, the main measures. The strength of the thigh muscles that straighten the knee (knee extensor strength) rose only in the open-label extension that followed, where everyone knew they were on the drug. Eight took it for more than three years.^2,11

The trial’s authors reported that walking distance and fatigue also improved during the extension. In 2025 the FDA judged those gains unreliable. The walking test depends on effort, patients knew they were on the drug, and both measures had also improved on placebo during the double-blind phase.^22,23

Stealth BioTherapeutics, the approval holder, sponsored 20 of 22 elamipretide studies on ClinicalTrials.gov as of November 13, 2026. Its larger published randomized trials in other conditions missed their main goals. They enrolled 300 adults treated for a first heart attack (2016), 218 people with a genetic mitochondrial muscle disease (2023) and 176 with dry macular degeneration, an eye disease (2024). In 39 healthy people aged 60 to 85, one infusion brought only a borderline, short-lived rise in a muscle energy measure.^{30,24,13,25,26,27,14}

Side effects and risks

For all three unapproved peptides, the FDA raises immunogenicity: the chance the immune system reacts against the peptide. Clumps and manufacturing impurities raise that risk, which may be higher with injections under the skin. Reactions range from symptom-free antibodies to life-threatening ones. Because the body makes its own MOTS-c and thymosin alpha-1, antibodies could also block the body’s own.^28,3,4,5

The FDA warned that products sold under informal names like epitalon and MOTS-c can contain a different form of the peptide or even a different substance from the one prescribed. The agency’s adverse event database held no reports on either, though compounding pharmacies generally do not report adverse events to it.^3,4

The FDA found no clinical data on epitalon’s safety and no data on how people absorb or clear it. FDA staff raised a cancer question: epitalon switches on telomerase in lab studies, and longer telomeres are generally linked to higher cancer risk. Researchers including Khavinson reported fewer tumors in female mice given epitalon, but the FDA judged those studies too limited and found no two-year cancer study in animals. A 2025 lab study found epitalon lengthened telomeres in human breast cancer cells as well as normal cells.^3,29

For MOTS-c, the FDA found no human safety data and no animal toxicity studies. With its target unknown, it is hard to predict which organs MOTS-c might affect, the FDA says.⁴

The most common side effects in thymosin alpha-1 trials were irritation, redness or discomfort where it was injected. TESTS found no difference in safety outcomes. In its planned look at people under 60, though, more died on thymosin alpha-1 than on placebo. The authors said differences between the groups at the start may explain part of this.^5,18

Labels abroad rule out thymosin alpha-1 for children and in pregnancy or breastfeeding, and advise against it for transplant recipients and others whose immune systems are deliberately suppressed. They urge caution with allergies, other immune-acting drugs and autoimmune disease. After stem cell transplants, the FDA said, it could trigger or worsen graft-versus-host disease, an attack by transplanted immune cells on the body, or cause graft failure. In one small study, 1 of 6 people given it after a half-matched stem cell transplant died of an immune attack on their red blood cells. That person had also received donor immune cells; the FDA said it is unclear whether the peptide contributed.⁵

Elamipretide’s label warns of allergic reactions, including serious ones that needed emergency treatment, starting minutes to months after the first dose. Anyone who has had a serious allergic reaction to it or its ingredients must not use it. Its preservative, benzyl alcohol, has caused fatal reactions in premature and low-birth-weight newborns given it into a vein; elamipretide is not approved for newborns.²

In the Barth trial, all 12 patients had injection-site reactions on elamipretide, against 8 of 12 on placebo. Symptom-free rises in eosinophils, a type of white blood cell, were common with use of 30 days or more. The label calls for a lower dose in adults with severe kidney impairment and says the drug has not been studied in people on dialysis.²

FDA status

On September 19, 2025, the FDA granted elamipretide accelerated approval to improve muscle strength in people with Barth syndrome who weigh at least 30 kilograms (66 pounds). Accelerated approval rests on a measure the FDA judges reasonably likely to predict a real benefit, here knee extensor strength. Continued approval may depend on a randomized, placebo-controlled trial that began in July 2026 and is due to finish in 2029.^1,30,2,31

The approved ingredient is elamipretide hydrochloride, a salt form: the peptide combined with hydrochloric acid. Because it is part of an FDA-approved drug, state-licensed pharmacies may compound with it, subject to the law’s other conditions. Other salt forms of a peptide count as different ingredients. The law also bars pharmacies from compounding what are essentially copies of a commercially available drug, such as the approved product, regularly or in inordinate amounts. Compounded elamipretide is not FDA-approved.^{30,2,32,3,33,34}

SS-31 sold online is not the approved drug either. FDA warning letters in August 2026 told online sellers that their SS-31, despite research-use-only labels, was an unapproved new drug marketed with claims about mitochondria and aging. Injected products bypass some of the body’s defenses against toxins and germs, the FDA warned.^6,35

Thymosin alpha-1, epitalon and MOTS-c are not FDA-approved. None has an official quality standard (a USP monograph) or is part of an approved drug. So federal law lets a state-licensed pharmacy (compounding under section 503A) use them only if the FDA adds them to the 503A bulks list, its list of extra ingredients for compounding.^5,3,4,32

On October 30, 2026, HHS, the FDA’s parent department, announced its draft policy on six peptides. They include epitalon and MOTS-c, but not thymosin alpha-1 or SS-31. HHS says it does not intend to take enforcement action against state-licensed pharmacies, federal facilities or licensed physicians compounding them under section 503A when all ten of its conditions are met. For these two, it covers only the acetate salt form of each, injected under the skin or into a muscle, and epitalon only when dispensed in intermittent courses.^34,46

Its conditions include one active ingredient per product, so no blends. The draft is not binding, is not an approval and adds nothing to the 503A bulks list.^46,34

All three were once in Category 2, substances that “may present significant safety risks”. Their nominations, which had confused the plain peptides with their acetate salts, were withdrawn, and the FDA reviewed them anyway. None is now in Category 1, the group the FDA’s own interim policy does not act against.^{28,3,4,5,39,32}

Rules in sport

The World Anti-Doping Agency’s 2026 Prohibited List bans MOTS-c at all times. It names thymosin beta-4, a different peptide, but not thymosin alpha-1, epitalon or elamipretide. A catch-all section also bans substances that no government health regulator has approved for human use, and from 2027 it names peptides among its examples.^40,41

What isn’t known

Questions to ask a clinician