Brain
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.
5,095
people in trials
7
human studies
0
compounds, animal or cell only
2
trials found nothing
Measured in people
Ranked by how many people, which is a fact about the evidence and not a judgement about the compound. The one at the top is the most studied, which is not the same as the best. Counts are never added across compounds, because the same person can appear in more than one trial.
- 4,038 people1 human study
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
- 728 people1 human study
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
- 218 people1 human study1 found nothing
found nothing218 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
- 82 people1 human study
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
- 26 people1 human study
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
- 3 people1 human study
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
- no headcount stated1 human study1 found nothing
found nothingThe 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 · no headcount in the line
What people using these actually report
Uncontrolled self-reports, gathered from clinic write-ups, regulatory complaint records and public forums, and reproduced here as written. They are the best guide on this page to what people actually do, what they expect, and what goes wrong, and they cannot show that anything works, because nobody was measured against a placebo and the people who saw no effect mostly stopped posting. Both halves of that are true at once. The negative 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 gastrointestinal 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.
- Outside the Long COVID community, the goals people describe are cardiovascular prevention in a general sense (better circulation, arterial health, blood pressure) and, in a smaller but vocal group, an attempt to address suspected microclots. In the Long COVID and ME/CFS survey specifically, respondents were taking it for fatigue, brain fog, and other post-viral symptoms tied to a microclot hypothesis that has not been established in controlled trials; about 60% of survey respondents reported some benefit, most 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.
- Generally described as easy to tolerate, which is consistent with the clinical record, with headache, nausea and fatigue 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.
- People genuinely low on B12 describing a real and lasting change in fatigue, which is a different situation from everyone else in 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.
- Fatigue early in a cycle, which people often attribute to eating far less rather than to the drug.
Sources: Trial adverse event 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.
- Better exercise tolerance, particularly in people with long-standing fatigue.
Sources: Peptide forums including r/peptides, chronic fatigue communities and clinic write-ups. Uncontrolled self-reports in a symptom domain that fluctuates substantially on its own.
- Flu-like symptoms or fatigue 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.
Why the trial record looks like this
A missing trial is usually a missing sponsor. Nobody runs a nine-figure programme on a molecule they cannot own, so the compounds with the thinnest human records are often the oldest and most freely available ones rather than the weakest. Taking Erythropoietin as the example, because it states the problem most clearly:
Erythropoietin is the clearest example in this catalogue of a biomarker that looked like an outcome. Anaemia predicts death in kidney disease, EPO corrects anaemia, and the inference that correcting it fully would reduce death was tested three times in randomised trials and failed three times, once with a doubling of stroke. The regulatory response was a boxed warning that says in plain language that no target, dose or strategy has been found that avoids the risk. That sequence is worth holding onto whenever a compound is recommended because it moves a number in the right direction.
The doping history runs alongside. EPO transformed endurance sport in the 1990s, it is prohibited in and out of competition under the World Anti-Doping Agency's section S2, and the randomised evidence in healthy volunteers does show improvements in maximal power output and time to exhaustion, which is unusual: most doping agents have a thinner evidence base than their reputation suggests. The thrombotic risk that the kidney trials documented in patients is the same mechanism that makes covert use in athletes dangerous, and the dose and haematocrit involved in doping are higher than anything the trials tested.
One peptide on this site descends directly from this hormone: ARA-290, a non-erythropoietic EPO-derived peptide designed to keep the tissue-protective signalling without raising red cell mass. That design choice exists precisely because of the trials described above.
A compound appears here only when a citation on its own page states this outcome and reports a result for it; naming it is not enough. Human, animal and cell work are counted separately and never merged. Participant counts are read from the study lines and deliberately undercount. Nothing here is advice, and nothing here is a recommendation to take or to avoid anything.