Brain · part of Brain, memory and mood and Sleep
Will I feel less tired?
One of the most commonly reported effects and one of the least reliably measured, because fatigue scales move easily on placebo.
5,145
people in trials
8
studies in people
0
compounds, animal or lab only
15
compounds people report on
2
trials found nothing
Measured in people
A trial that gave people the compound comes first. A study that only watched people, who happened to have more or less of something related, comes after. Both are studies in people and both are here. Only the first kind tested the thing you are asking about, and the watch-only ones are labelled. Within that, the most people come first. That is a fact about the studies, not a judgement about the compound. Counts are never added up across compounds, because the same person can be in more than one trial.
Peptides and blends
3 compounds · 247 people given one of themWhat 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.
- 01ElamipretidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 487 people given it.6 reported218 people given it1 trial1 found nothing
found nothingIt was tested properly, at full scale, and it failed. 218 people with an inherited muscle disease caused by faulty mitochondria got elamipretide or a dummy injection, and nobody involved knew which. Both of the things the trial was built to settle came out flat. Walking distance in six minutes was 3.2 metres worse on the drug than on the dummy. The journal graded this as the strongest class of evidence that elamipretide does not improve walking or fatigue at six months.
The numbers 218 participants, phase 3, randomised and placebo controlled. Both primary endpoints missed. The six minute walk difference was minus 3.2 metres, favouring placebo, and the paper carries a Class I evidence classification that elamipretide does not improve walking distance or fatigue at 24 weeks.
Neurology, 2023· 218 people
- 02MelittinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 658 people given it.4 reported26 people given it1 trial
Bee sting therapy failed on every measure it was tested on. Twenty six people with relapsing multiple sclerosis were stung up to twenty times a session, three times a week, for six months. Brain scans showed no fewer new lesions. Relapses, disability, fatigue and quality of life were all unchanged. Nobody was seriously harmed. The comparison was against no treatment at all, so everyone knew what they were getting. A Dutch team ran it.
The numbers Live bee stings, up to 20 per session three times weekly for 24 weeks, versus no treatment, in 26 people with relapsing MS. No reduction in new gadolinium enhancing MRI lesions, T2 lesion load, relapse rate, disability, fatigue or quality of life. No serious adverse events. Academic trial, Netherlands.
Neurology, 2005· 26 people
- 03Melanotan IIPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,310 people given it.9 reported3 people given it1 trial
The first look at this compound in people was tiny, and the side effect it turned up became the reason people buy it. Three male volunteers took shots under the skin for two weeks. Their skin darkened, which was the point. Most doses made them feel sick, and the highest left them drowsy and tired. They also got spontaneous erections lasting one to five hours. Three people cannot tell you how common any of that is, or whether the compound is safe.
The numbers Three male volunteers dosed subcutaneously for two weeks: increased pigmentation, mild nausea at most doses, somnolence and fatigue at 0.03 mg/kg, and spontaneous penile erections lasting 1 to 5 hours after dosing.
Life Sciences, 1996· 3 people
Supplements
1 compound · 82 people given one of themVitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.
- 01OxaloacetateSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 112 people given it.4 reported82 people given it1 trial
Oxaloacetate cut fatigue more than the comparison group in people with ME and chronic fatigue syndrome. 82 people took 2,000 mg a day for three months, assigned by chance, and nobody involved knew who got what. Fatigue fell by more than a quarter in the treated group against roughly a tenth in the controls. About 40.5 percent were strong responders, averaging a 63 percent drop. It was well tolerated at that dose. Fatigue here is what people reported about themselves, and no other team has repeated this result.
The numbers 82 participants, three months, randomised and double-blinded, 2,000 mg oxaloacetate daily against control. Fatigue fell by more than 25 percent from baseline in the treated group against roughly 10 percent in controls, with the between-group comparison significant at p equals 0.0039. About 40.5 percent of the treated group were classified as enhanced responders with an average 63 percent fatigue reduction. The compound was well tolerated at the dose tested.
Frontiers in Neurology, 2024· 82 people
Other compounds
4 compounds · 4,816 people given one of themApproved 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.
- 01ErythropoietinBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 4,641 people given it.6 reported4,038 people given it1 trial
This drug did not extend life or save kidneys, and it doubled the risk of stroke. 4,038 people with type 2 diabetes, kidney disease and anaemia got darbepoetin alfa or a dummy shot, with rescue treatment if counts dropped too low. Death and heart events came out the same. Kidney failure came out the same. Strokes hit 101 people on the drug against 53 on the dummy. Fewer needed transfusions, and tiredness improved a little. Amgen, which sells it, paid for the study.
The numbers TREAT: 4,038 people with type 2 diabetes, chronic kidney disease and anaemia randomised to darbepoetin alfa targeting 13 g/dL or to placebo with rescue below 9 g/dL. Death or a cardiovascular event, hazard ratio 1.05 (0.94 to 1.17); death or end-stage renal disease, hazard ratio 1.06 (0.95 to 1.19). Fatal or non-fatal stroke 101 versus 53, hazard ratio 1.92, 95 percent confidence interval 1.38 to 2.68, p < 0.001. Fewer transfusions (297 versus 496) and only a modest improvement in fatigue. Sponsor Amgen.
New England Journal of Medicine, 2009· 4,038 people
- 02BromantaneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 728 people given it.6 reported728 people given it1 trial
The largest study of bromantane had nothing to compare itself against. 728 patients at 28 Russian clinics took it for four weeks. Nine in ten were rated improved by their doctor. Side effects were rare and almost nobody quit. Here is the problem. Everybody got the drug, everybody knew it, and the score was a doctor's overall impression. Exhaustion is the condition where dummy treatments perform best, so a nine in ten success rate in this design tells you very little.
The numbers The largest human dataset: 28 Russian clinical centres, analysis on 728 patients with psychoautonomic syndrome and asthenic disorders, 50 to 100 mg per day for 28 days. Responder rates 76.0% on CGI-S and 90.8% on CGI-I, adverse effects in 3%, discontinuation in 0.8%. There is no placebo arm. A 90.8% response rate on an open-label clinician global impression scale in a fatigue syndrome is close to uninterpretable, because that is the exact design in which placebo response peaks. The same study is also indexed at PMID 20559263.
Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova, 2010· 728 people
- 03MifepristoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 320 people given it.4 reported50 people given it1 trial
In Cushing's syndrome, where cortisol is the problem, blocking its receptor with mifepristone improved blood sugar, blood pressure and weight over six months. 50 adults took part, and there was no dummy pill group. Tiredness, nausea, headache and low potassium were common. This is the approved use, not a study of ageing.
The numbers 50 adults with endogenous Cushing's syndrome, after failed treatment, were given mifepristone 300 to 1,200 mg daily for 24 weeks, open-label, at 17 US centres. In the diabetes or impaired glucose tolerance group 60% had a glucose AUC response; HbA1c fell from 7.43% to 6.29% and fasting glucose from 149 to 105 mg/dL. In the hypertension group 38% had a diastolic pressure response. Mean weight change -5.7%; 87% judged clinically improved. Fatigue, nausea, headache, low potassium, arthralgia, vomiting, oedema and endometrial thickening were common.
The Journal of Clinical Endocrinology and Metabolism, 2012· 50 people
- 04TestosteroneHormoneModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 5,246 people given it.10 reportednobody was given it1 watch-only study1 found nothing
found nothingTestosterone helped older men with sex and did much less for everything else. It raised their levels to what a man in his twenties or thirties would have. Sex drive, sexual activity and erections all clearly got better. Energy did not get better at all. Walking distance only improved when three studies were lumped together, which is a weaker way to find a result. Mood was slightly better. Side effects were no more common than on the dummy gel.
The numbers The T-Trials. Treatment raised testosterone into the mid-normal range for men aged 19 to 40. Sexual activity, sexual desire and erectile function all improved significantly. Vitality did not improve on the fatigue scale. The proportion improving 6-minute walking distance by at least 50 m did not differ in the Physical Function Trial but did when all three trials were pooled, 20.5% against 12.6%, p = 0.003. Mood and depressive symptoms were slightly better. Adverse event rates were similar.
New England Journal of Medicine, 2016· number of people not givenobserved only, nobody was given it
What people using these actually report
These are people describing their own use. They come from clinic write-ups, complaint records kept by regulators, and public forums, and they are shown as written. They are the best guide on this page to what people actually do, what they expect, and what goes wrong. They cannot show that anything works. Nobody was compared with people on a dummy pill, and people who saw no effect mostly stopped posting. Both things are true at once. The bad reports are kept in for the same reason.
- Persistent fatigue is the negative raised most often, described by some as continuing for months and as distinct from what the same people experienced on semaglutide or tirzepatide. Nausea and the usual stomach and gut complaints appear as well, and a recurring counter-theme is other users telling someone their reported fatigue is not real, which those posters push back on.
Sources: Public discussion in r/Retatrutide, r/PEDs, r/zepbound_support and adjacent weight loss subreddits, read through the PullPush Reddit archive on 2026-09-13 because Reddit's own endpoints are unreachable from this environment. 86 comments reviewed. Nothing above is attributed to any specific post and no comment is reproduced.
- Cost is raised concretely, with figures in the low hundreds of dollars for a short course, and vendor recommendations circulate freely. Side effect discussion is thin beyond headache, nausea and fatigue being listed as possibilities, and a separate long-running thread exists purely about whether a compound that promotes tissue growth could promote tumour growth, which remains unresolved in the discussion itself.
Sources: Peptide and injury threads on ExcelMale, plus a long-running safety thread on LongeCity, found by site-restricted search and read in September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- The reports that recur most on the positive side are energy and mood in people who describe long-standing fatigue, and the effect is usually described as appearing quickly rather than building.
Sources: Supplements, Brain Health and Mental Health threads on LongeCity on methylcobalamin reactions, anxiety and sedation, plus ExcelMale dosing discussion, found by site-restricted search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- 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.
Sources: LongeCity supplement threads reached through site-restricted search extracts because that board timed out on direct fetch from this environment, together with ExcelMale threads read directly which turned out to carry article content rather than member experience, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- The most commonly reported experience is mild fatigue on the day of dosing, lasting about a day, and several people describe no side effects at all at these intermittent doses.
Sources: Senolytics and dosing threads on LongeCity, reached through site-restricted search extracts of the threads because the site itself would not load from this environment, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Adverse effects raised include lowered HDL, raised liver enzymes and fatigue, and the standing position in these threads is that what vendors of these compounds publish about them is not accurate.
Sources: SARM threads on ExcelMale, including a personal trial thread and a safety and effectiveness thread, found by site-restricted search and read directly, with MESO-Rx threads surfaced by the same search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Severe tiredness is the most common bad report, and several people describe stopping within three or four days because of it while noting that it is the reverse of what they expected. Itchy rashes across the back are described by more than one person, in one case still visible months later.
Sources: Cardarine threads on ExcelMale and MESO-Rx, with T-Nation and LongeCity threads surfaced by the same site-restricted search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Outside Long COVID, people take it for heart health in general: better circulation, artery health and blood pressure. A smaller, vocal group takes it for suspected microclots. In the Long COVID and ME/CFS survey, people took it for tiredness, brain fog and other after-virus symptoms, based on a microclot idea no controlled trial has proven. About 60% said they got some benefit, mostly within 2 weeks.
Sources: A published pharmacist-run survey of the Long COVID and ME/CFS supplement-using community (Martha Eckey, PharmD, writing on Substack), which is the only named, citable source for dosing and outcome patterns used here; the Health Canada licensed natural health product label and the Canadian NHPID ingredient entry, which supply the specific warfarin and bleeding-disorder caution language quoted in the legal status section; Memorial Sloan Kettering's integrative medicine monograph on nattokinase, which was used to cross-check the case reports and mechanism claims against a clinical secondary source; and the case-report and clinical literature cited directly elsewhere on this page. Reddit's r/Supplements and r/Biohackers, and any other Reddit community, could not be retrieved for this entry.
- Fatigue and grogginess are reported more than anything else, and specifically at the higher end. The workarounds people describe are moving the dose to the evening or lowering it, and the reports conflict directly: some describe morning dosing causing grogginess, others describe evening dosing causing insomnia.
Sources: DHEA safety, dosing and side effect threads on ExcelMale, plus supplement threads on LongeCity, found by site-restricted search and read in September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Most people describe it as easy to take. That matches the medical record. Headache, nausea and tiredness are the most common early complaints.
Sources: Longevity forums and clinic write-ups. Uncontrolled self-report, useful for what to watch for, not evidence of effect.
- More serious complaints exist and are specific: headache from a single low dose, heart palpitations after a couple of months, and a stretch of severe irritability, fatigue, low mood and carbohydrate craving. These are individual accounts rather than a majority pattern, but they are not isolated either.
Sources: Supplements and Brain Health threads on LongeCity, including the multi-page verdict thread, the experience threads and threads on arrhythmia and insomnia, found by site-restricted search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- People who are truly low on B12 describe a real, lasting change in tiredness. That is a different situation from everyone else on this list.
Sources: The infusion reactions and the price complaints come from IV clinic write-ups and user forums and are not trial data. The B6 neuropathy signal comes from published case reports and from the cell work cited on this page. The fatigue improvement in genuine deficiency comes from clinical literature. The Myers cocktail trial is the only controlled comparison here, and it is the reason to treat the post-drip lift as unproven rather than as a finding.
- Tiredness early on. People often put this down to eating far less, not to the drug.
Sources: Trial side-effect tables supply the nausea and diarrhoea figures. The comparison between B12 and non-B12 preparations comes from forums including r/Semaglutide and telehealth patient communities, and is uncontrolled.
- Flu-like symptoms or tiredness in the first days, which people describe as an immune response.
Sources: Clinic write-ups, chronic infection and peptide forums. Uncontrolled self-reports in a domain where seasonal variation dominates and where infection frequency is rarely counted before starting.
- The clearest negative is the opposite of the effect most people are after. Fatigue on it, resolving after stopping, is reported by multiple people, and blood pressure dropping is offered by some as the reason.
Sources: Supplements and Brain Health threads on LongeCity comparing ubiquinol, ubiquinone and idebenone, plus threads on CoQ10 and fatigue, found by site-restricted search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
Why the trial record looks like this
A missing trial usually means nobody would pay for it. Nobody spends hundreds of millions of dollars on a molecule they cannot own. So the compounds with the thinnest record in people are often the oldest and easiest to get, not the weakest. Taking Erythropoietin as the example, because it states the problem most clearly:
EPO is the clearest example on this site of a lab number that looked like a health outcome. Anaemia predicts death in kidney disease. EPO fixes anaemia. So the thinking was that fixing it fully would cut deaths. Big studies tested that three times, and it failed three times, once with twice as many strokes. The FDA answered with a boxed warning. It says in plain words that no target, dose or plan has been found that avoids the risk. Hold on to that story whenever a compound is pushed because it moves a number the right way.
The doping story runs alongside. EPO changed endurance sport in the 1990s. It is banned in and out of competition under the World Anti-Doping Agency's section S2. Studies in healthy volunteers do show gains in peak power and time to exhaustion. That is unusual, because most doping drugs have thinner evidence than their reputation. The clot risk the kidney studies found in patients comes from the same process that makes secret use in athletes dangerous. And doping doses and blood counts run higher than anything the studies tested.
One peptide on this site comes straight from this hormone. ARA-290 is a piece of EPO built to keep the tissue-protecting signal without raising red cell counts. That design exists precisely because of the studies above.
A compound shows up here only when a study on its own page names this goal and reports a result for it. Just naming it is not enough. Work in people, in animals and in the lab is counted separately and never mixed. People counts come from the study lines, and when in doubt they count low. Nothing here is advice. Nothing here tells you to take or to avoid anything.