Does it improve endurance or work capacity?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01MOTS-cPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.6 reported

   30 people given it1 trial, 1 watch-only1 found nothing

   • Exercise did not move MOTS-c. Thirty adults were assigned to a bout of endurance exercise, a bout of weight training, or nothing at all. Humanin, a related peptide, rose after the endurance session and not after the weights. MOTS-c leaned upward but not enough to call it a real change. Neither peptide tracked how fit anyone was, by running capacity, by strength, or by the amount of mitochondrial DNA in their muscle. Thirty people is too few to settle a small effect.

     The numbers 30 adults randomized to endurance exercise, resistance exercise or control: circulating humanin rose significantly after acute endurance exercise but not resistance exercise; MOTS-c showed only a non-significant trend upward, and neither peptide correlated with fitness (VO2max, strength or muscle mtDNA copy number).

     Journal of Applied Physiology, 2021· 30 people

   • found nothingProfessional athletes carried less MOTS-c in their blood than people who do not train, which is the opposite of what a fitness marker should do. Seventy-five athletes were compared with thirty sedentary adults. Nobody was given anything. Humanin, the related peptide, went the other way and was higher in the athletes. Among the athletes themselves, the endurance specialists had no more MOTS-c than the rest. Comparing groups who differ in many ways cannot show that training changed the level.

     The numbers 30 sedentary controls versus 75 professional athletes: professional athletes had lower serum MOTS-c and higher humanin than sedentary controls; MOTS-c did not differ between high- and low/moderate-endurance athletes.

     Reviews in Cardiovascular Medicine, 2022· number of people not givenobserved only, nobody was given it

   What people using it report

   • What people describe most is more energy and a sharper mind in the first one to two weeks. Some say it is strong enough that you should not take it near bedtime. People also expect better endurance and body shape when they pair it with training and eating less. Several sources say plainly that MOTS-c is not a fat burner on its own. People who do not also diet or train report no visible change in body shape.
2. 02HumaninPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.6 reported

   30 people given it1 trial, 1 watch-only

   • A single endurance session raises humanin in the blood. Lifting weights does not. Thirty adults were assigned to one bout of endurance exercise, one bout of weight training, or nothing. Humanin went up only after the endurance session. It did not track how fit anyone was, measured by running capacity, by strength, or by the amount of mitochondrial DNA in their muscle. So the rise looks like a short term response to that one effort. Nobody was followed to see whether it mattered.

     The numbers 30 adults randomized to endurance exercise, resistance exercise or control: circulating humanin rose significantly after a single bout of endurance exercise but not resistance exercise, and did not correlate with fitness (VO2max, strength or muscle mtDNA copy number).

     Journal of Applied Physiology, 2021· 30 people

   • Athletes carried more humanin than people who do not train, but more training did not mean more humanin. Seventy-five professional athletes were compared with thirty sedentary adults. Nobody was given anything. The athletes had higher levels overall. Inside the athlete group the pattern reversed, because the hardest endurance specialists had less humanin than teammates of the same age and sex. If humanin simply rose with fitness, that reversal should not happen. Groups who differ in many ways cannot show what caused the difference.

     The numbers 30 sedentary controls versus 75 professional athletes: professional athletes had higher serum humanin than sedentary controls, but within the athlete group, high-endurance athletes had lower humanin than low/moderate-endurance athletes of the same age and sex.

     Reviews in Cardiovascular Medicine, 2022· number of people not givenobserved only, nobody was given it

3. 03EpitalonPeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 266 people given it.6 reported

   0 people given it1 trial

   • The same small group of Kiev heart patients, followed for much longer. 39 heart patients took six courses of epithalamin over three years alongside their usual treatment. 40 others had usual treatment only. The treated group was reported to age more slowly in the heart and blood vessels, keep more stamina, recover a normal melatonin rhythm and die less often. Seventy-nine people is a very small base for a claim about dying. The title says pituitary gland; the preparation studied is the pineal one.

     The numbers The same Kiev cohort at 15 years: 39 coronary patients given 6 courses of Epithalamin over 3 years plus basic therapy versus 40 on basic therapy alone, reporting slower cardiovascular aging, preserved physical endurance, normalized melatonin rhythm and significantly lower mortality. The title says pituitary; the text is about the pineal preparation Epithalamin.

     Bulletin of Experimental Biology and Medicine, 2011· number of people not given

4. 04VIPPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

   0 people given it1 trial

   • A small, early study in a serious lung condition, with everyone knowing what they were getting. People with high blood pressure in the lungs breathed in VIP. Pressures in the lung circuit improved and they could walk further. All of them were short of VIP to begin with, which is the best case there is for giving it back. There was no dummy group and nobody was kept in the dark, so how much of this was the drug is unknown.

     The numbers Small open study: inhaled VIP improved hemodynamics and exercise capacity in primary pulmonary hypertension patients deficient in VIP.

     Journal of Clinical Investigation, 2003· number of people not given

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01PQQSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 116 people given it.5 reported

   23 people given it1 trial1 found nothing

   • found nothingPQQ added nothing on top of training. 23 untrained men took 20 mg a day or a dummy while doing the same supervised six week endurance programme. Both groups got fitter, from the training. Neither peak oxygen uptake nor how long they lasted separated the two groups. One protein linked to building new mitochondria rose more in the PQQ group, which is a laboratory measurement and not a performance. The authors say PQQ does not appear to help performance or body composition.

     The numbers 23 untrained men randomised to 20 mg a day of PQQ or placebo alongside a supervised six-week endurance training programme. There were no significant differences between groups in aerobic performance after endurance training (p > 0.05). Peak oxygen uptake and total test duration improved in both groups, from the training. PGC-1alpha protein rose significantly more in the PQQ group. The authors conclude PQQ does not appear to elicit ergogenic effects on aerobic performance or body composition.

     Journal of the American College of Nutrition, 2020· 23 people

   What people using it report

   • Doses described sit around 10 to 20 mg a day. Several people describe running that range for a year or more and concluding it did nothing for energy or endurance.
2. 02NMNSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 94 people given it.6 reported

   0 people given it1 trial1 found nothing

   • found nothingA high dose NMN tablet raised NAD in the blood and moved weight and cholesterol, but not muscle. 30 overweight or obese adults took MIB-626, 1000 mg twice a day, or a dummy pill, for 28 days. Weight fell 1.9 kg. The lower blood pressure number and LDL cholesterol fell too. Strength, tiredness, fitness and stair climbing power did not change. Neither did the body's response to insulin. The maker paid for it.

     The numbers 30 overweight or obese adults aged 45 and over randomised 2:1 to MIB-626 (microcrystalline NMN) 1000 mg twice daily or placebo for 28 days. Weight -1.9 kg, diastolic BP -7.01 mmHg, LDL -18.73 mg/dL versus placebo. Muscle strength, fatigability, aerobic capacity and stair-climbing power did not differ. Insulin sensitivity unchanged. Funder: Metro International Biotech.

     Journal of Clinical Endocrinology and Metabolism, 2023· number of people not given

   What people using it report

   • Where people do report a change, it is energy, strength or endurance in training, and the ones reporting it most often are taking it under the tongue rather than swallowing it. Whether taking it under the tongue makes any difference is one of the longest-running arguments in the discussion and is not settled by anyone.
3. 03Urolithin ASupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.4 reported

   0 people given it1 trial, 1 watch-only1 found nothing

   • found nothingFour months of it improved muscle endurance and blood chemistry, and left the headline measures untouched. Older adults took the supplement or a dummy. How far they could walk in six minutes did not differ, and neither did the peak energy their muscles could produce. What improved was how long a muscle could keep going, plus several markers. A genuine result, and a narrow one.

     The numbers 4 months of urolithin A improved muscle endurance and plasma biomarkers, though 6-minute walk and peak ATP did not differ from placebo.

     JAMA Network Open, 2022· number of people not given

   • Strength improved, and the trial still missed the thing it was built to show. Muscle strength in middle-aged adults rose about 12 percent, and fitness and walking distance improved as well. But peak power, the one measure chosen before the trial began, did not. When a study misses the measure it named first and hits others instead, those others carry less weight.

     The numbers About 12% gain in muscle strength and improved VO2 peak and 6-minute walk, though the primary peak-power endpoint was not met.

     Cell Reports Medicine, 2022· number of people not givenobserved only, nobody was given it

   What people using it report

   • The most detailed negative account describes four months of daily use of the branded powder with no change in strength, endurance or power output, and frames the spend of several hundred dollars as wasted. Another describes overwhelming fatigue while taking it. A third describes a clean lift in energy.
4. 04(R/S)-1,3-ButanediolSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

   0 people given it1 trial

   • It raised ketones in the blood, made people feel ill, and did not make them faster. Nine trained male cyclists took either 1,3-butanediol or a dummy drink before and during 85 minutes of steady riding, then a time trial. Each rider did both, in turn. Blood ketones rose several times over, so the compound does what it should chemically. Five of the nine had moderate to severe stomach and bowel problems. Time trial results came out the same either way.

     The numbers Randomised crossover, 9 trained male cyclists, 0.35 g/kg racemic 1,3-butanediol or placebo before and during 85 minutes of steady exercise then a time trial. Blood D-beta-hydroxybutyrate 0.44 to 0.79 mmol/L during exercise (placebo 0.11 to 0.16), peak 1.38 mmol/L after. Moderate to severe gastrointestinal symptoms in 5 of 9; dizziness, nausea or euphoria in 2. Time trial 28.7 versus 28.5 minutes, p = 0.62; power 286 versus 290 W, p = 0.50. No performance benefit. Academic study.

     International Journal of Sport Nutrition and Exercise Metabolism, 2019· number of people not given

5. 05MIB-626SupplementModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 107 people given it.1 reported

   0 people given it1 trial1 found nothing

   • found nothingThe tablet moved some body measurements and left every measure of physical function untouched. 30 overweight or obese adults aged 45 and over took MIB-626 or a dummy tablet for four weeks. Weight fell by about two kilograms. Blood pressure and cholesterol both came down. Strength, stamina, how quickly muscles tired and stair climbing power did not change. Insulin sensitivity, liver fat and belly fat did not change either. The manufacturer helped fund it. This study looked at many things at once, so treat any single result as a hint.

     The numbers Randomised 2:1, 30 overweight or obese adults aged 45 and over, MIB-626 two 500 mg tablets twice daily for 28 days. Body weight fell 1.9 kg (95 percent CI -3.3 to -0.5, P=.008), diastolic blood pressure fell 7.01 mmHg (-13.44 to -0.59, P=.034), total cholesterol fell 26.89 mg/dL (P=.004) and LDL fell 18.73 mg/dL (P=.007). Muscle strength, muscle fatigability, aerobic capacity and stair-climbing power did not change. Insulin sensitivity, hepatic fat and intra-abdominal fat did not change in either group. Metro International Biotech, the manufacturer, is a listed funder. This is a physiologic study with multiple outcomes rather than a trial powered on one of them.

     Journal of Clinical Endocrinology and Metabolism, 2023· number of people not given

6. 06Urolithin BSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.

   0 people given it1 trial1 found nothing

   • found nothingThis is urolithin A, not urolithin B, and it sits here because urolithin B has nothing like it. Older adults took urolithin A or a dummy. Muscle endurance improved and some blood markers moved. The six minute walk test did not improve, and neither did the peak energy output measured inside muscle. So even the better studied sibling comes out mixed. Urolithin B has never been tested this way, or in any other way, in a person.

     The numbers Included as the contrast, and it is not urolithin B. This is a randomised trial of urolithin A in older adults, in which muscle endurance and plasma biomarkers improved while the six-minute walk and peak ATP did not differ from placebo. Urolithin B has no trial of this kind, or of any kind.

     JAMA Network Open, 2022· number of people not given

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01ClenbuterolSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 11 people given it.5 reported

   11 people given it1 trial1 found nothing

   • found nothingClenbuterol does build muscle in people, and it wrecks your fitness while it does. 11 healthy young men took the drug for two weeks and a dummy for two weeks, in turn, with three weeks between. Lean mass rose by just under a kilogram. Fat mass did not move at all, which matters because fat loss is why most people buy it. The most oxygen their bodies could use fell 7 percent, and exercise capacity fell 4 percent. The muscle response faded across the two weeks.

     The numbers The first randomised controlled trial. 11 healthy men aged 18 to 40, two 2-week cycles of oral clenbuterol at 80 micrograms a day versus placebo with a 3-week washout. Lean mass +0.91 kg (95% CI 0.02 to 1.81, p < 0.05), no effect on fat mass, maximal oxygen uptake -7% (p < 0.001), exercise capacity -4% (p < 0.001), no change in left ventricular mass, blood volume or haemoglobin mass. Muscle protein content rose while 3-hydroxyacyl CoA dehydrogenase activity and OXPHOS complex V fell. The beta-2 signalling response declined across the 2 weeks.

     The Journal of Physiology, 2025· 11 people

2. 02Metformin plus rapamycinSmall moleculePreliminary. Studied in people, but no published study has had people take it. 2 registered with no result.2 reported

   0 people given it1 trial

   • The one trial testing this pair cannot tell the two drugs apart. 30 people are enrolled by AgelessRx, an online company that prescribes these drugs, and it is no longer signing people up. Every group stacks rapamycin and metformin together with low-dose naltrexone, NAD+ up the nose, glutathione on the skin and a house-brand supplement. With six things given at once, no result could be traced to either drug. Nothing has been posted.

     The numbers 30 participants, sponsor AgelessRx (a telehealth prescriber), active not recruiting. Arms combine rapamycin 2 to 6 mg weekly, metformin 500 mg daily, low-dose naltrexone, intranasal NAD+, topical glutathione and a proprietary supplement; primary endpoints VO2 max, a cognitive composite and an inflammation index. Cannot isolate either drug. No results posted.

     ClinicalTrials.gov, 2025· number of people not given

Peptides and blends

1. 015-amino-1MQ with SLU-PP-332BlendAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.7 reported

   1 animal or lab study

   What people using it report

   • Better endurance in training after two to three weeks. This is the main claimed effect.

   Measured in animals or in the lab

   • In muscle cells in a dish, SLU-PP-332 made the cells' energy makers work harder. In mice, it raised the number of endurance-type muscle fibres, let the mice run longer, and switched on the same genes that aerobic exercise does. This was cells and mice. There is no data in people.

     The numbers SLU-PP-332 is a synthetic pan agonist at all three estrogen-related receptors with highest potency at ERR alpha. It increased mitochondrial function and cellular respiration in a skeletal muscle cell line, and in mice increased type IIa oxidative skeletal muscle fibres, enhanced exercise endurance and induced an ERR alpha dependent acute aerobic exercise gene programme. Mice, with no human data.

     ACS Chemical Biology, 2023· animal study

2. 02VilonPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, 1 lab study, no human study.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Vilon given from 6 months of age made female mice more active, gave them more stamina, helped them live longer and cut tumors.

     The numbers Lys-Glu from month 6 of life increased physical activity and endurance, prolonged lifespan and reduced spontaneous tumors in female CBA mice.

     Bulletin of Experimental Biology and Medicine, 2000· animal study

Supplements

1. 01ApigeninSupplementPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. This is the strongest evidence for blocking CD38, and it did not use apigenin. A strong, precise blocker called 78c reversed the fall in NAD with age. It improved blood sugar control, muscle function, exercise ability and heart function, in mice that aged normally or fast. An author holds a patent on CD38 blockers. 78c is not for sale and has no human data.

     The numbers The strongest evidence for the CD38 strategy, and it was not generated with apigenin. 78c, a highly potent and specific thiazoloquinazolinone CD38 inhibitor, reversed age-related NAD decline and improved glucose tolerance, muscle function, exercise capacity and cardiac function in mouse models of natural and accelerated ageing. The effects depended on tissue NAD levels and were reversed by inhibiting NAD synthesis. A declared conflict: an author holds a patent on the use of CD38 inhibitors for metabolic disease. 78c is not commercially available and has no human data.

     Cell Metabolism, 2018· animal study

Other compounds

1. 01SLU-PP-332Small moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.8 reported

   1 animal or lab study

   What people using it report

   • Where effects are described they are heavy sweating, better endurance in conditioning work and steadier glucose, almost always by people running several other compounds at the same time, which nothing in the threads separates.

   Measured in animals or in the lab

   • In mice: SLU-PP-332 switched on the same muscle genes that aerobic exercise turns on, and the mice could run longer.

     The numbers SLU-PP-332 triggered an aerobic-exercise-like transcriptional program in muscle and increased running endurance in mice.

     ACS Chemical Biology, 2023· animal study

2. 02CardarineSmall moleculePreliminary. Studied in people, but no published study has had people take it. 1 registered with no result.7 reported

   1 animal or lab study

   What people using it report

   • Endurance is what people say they want from it and what the favourable accounts describe, usually inside the first week or two. Those accounts sit directly alongside people describing the opposite, including endurance getting worse during long distance training, which makes this one of the more contradictory pictures in this set.

   Measured in animals or in the lab

   • In mice. With training, it improved endurance.

     The numbers GW501516 plus training improved endurance in mice.

     Cell, 2008· animal study

3. 03GW0742Small moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, 1 lab study, no human study.3 reported

   1 animal or lab study

   What people using it report

   • The effects attributed to it, endurance and fat loss with muscle preserved, are stated as expectations rather than as anything anyone reports having experienced.

   Measured in animals or in the lab

   • In mice trained on a treadmill for four weeks. AICAR alone boosted endurance. AICAR plus GW0742 raised running time by 138 to 179 percent against trained mice. The mice burned more fat and saved their sugar stores. This is mice, with a drug pair, not GW0742 alone in a person.

     The numbers Balb/c mice, treadmill trained for 4 weeks with AICAR and GW0742. AICAR alone potentiated endurance; the combination increased running time by 138 to 179 percent relative to exercised groups and 355 percent relative to non-exercised groups, with a fuel shift toward fat, glycogen sparing and upregulation of Pgc1a, Pdk4, Cd36 and Lpl in muscle. Mice, in combination with AICAR, not GW0742 alone in a human.

     Physiological Reports, 2016· animal study

4. 04AICARSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 3,080 people given it.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. It raised endurance in mice that did not train by about 44%.

     The numbers AICAR raised endurance in untrained mice by about 44%.

     Cell, 2008· animal study

5. 05Rapamycin plus acarboseSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 7 animal studies, no human study.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Each drug alone, started at 4 or 16 months, helped old mice of both sexes balance on a spinning rod and keep going longer, and shrank their enlarged hearts. Acarbose changed the fats in the heart more than rapamycin. Some benefits showed up in males only. These are health measures for each drug alone, not for the pair.

     The numbers Each drug alone, started at 4 or 16 months, improved rotarod and endurance and reduced cardiac hypertrophy in aged UM-HET3 mice of both sexes; acarbose changed the cardiac lipidome more than rapamycin; some benefits male-only. Healthspan measures for the single drugs, not the combination.

     Journals of Gerontology Series A, 2023· animal study

6. 06Senolytic CAR T cellsBiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. A single dose of the uPAR-hunting T cells helped normally ageing mice exercise more. It helped old mice and mice on a high-fat diet handle blood sugar better. The effect lasted, and it also worked as prevention.

     The numbers Mouse. uPAR-positive senescent cells accumulate with age and were targetable with senolytic CAR T cells. A single administration improved exercise capacity in physiologically ageing mice and ameliorated metabolic dysfunction, including glucose tolerance, in aged and high-fat-diet mice, with long-lasting therapeutic and preventive effect.

     Nature Aging, 2024· animal study

7. 07IrisinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 7 people given it.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • found nothingMostly in a dish, plus muscle samples from people. The human irisin gene has a broken start signal. With that signal, cells in a dish made only about 1 percent of the normal protein. In muscle samples from two human exercise studies, the gene did not get more active after cardio or weight training. In a dish, irisin did not turn human fat cells into energy burning fat. Public money paid for the work.

     The numbers Human FNDC5 has an ATA rather than ATG start codon; a human construct with ATA produced about 1 percent of full-length protein. FNDC5 mRNA in human muscle biopsies from two exercise studies was unchanged by endurance or strength training, and recombinant FNDC5 or irisin did not brown human preadipocytes where BMP7 did. Non-US government funded.

     PLoS One, 2013· lab (cells in a dish)