Exercise Mimetics Ranked: Which Ones Actually Work?
Which exercise mimetic or mitochondrial compound is actually worth taking?
This page ranks by the live endurance-cardio subrating, not by BioHarmony overall, and the order flips. SLU-PP-332 leads at 6.5–7.0/10 despite carrying the lowest overall score on the page. Humanin sits last at 1.0–1.5/10, below two compounds it beats on overall.
- Ranked by endurance and cardio fitness, not overall. SLU-PP-332 leads at 6.5–7.0/10 on this use case, the compound literally designed to mimic training, even though its BioHarmony overall, 4.5–5.0/10, is the lowest of the seven.
- MOTS-c jumps from last place on this page's old cellular-senescence order to third here, at 5.0–5.5/10. It carries one of the best overall scores in the category, 6.5–7.0/10, and on endurance and cardio that score finally matches the rank.
- Ca-AKG drops from first to second, at 5.5–6.0/10, still the highest overall in the category at 6.5–7.0/10.
- Only two of the seven are ordinary supplements. Five have no legal retail channel, and four have never been given to a human being in a published trial.
- SS-31 has an FDA approval and the highest mitochondrial subrating in the category. That approval is for one rare genetic disease and does not transfer to healthy people, and it falls to sixth on endurance-cardio at 2.5–3.0/10.
- The order is the live subrating. When a member's endurance-cardio score moves, this page moves with it.
The Ranking
7 interventions, ordered by their live Endurance and cardio fitness rating.
Scores are shown as a range because repeat scoring moves by up to ±0.8 on the 0-10 scale; printing one decimal would claim more precision than the method has. The order below is computed from the exact values, so two entries can share a range and still be ranked apart.
How this order works: Endurance and cardio fitness first, not the overall number
This page is ordered by each option's Endurance and cardio fitness rating: how well it works for that one goal, and nothing else.
The overall BioHarmony number beside it is a different measure. It weighs safety, cost, evidence and practicality across every goal an intervention is used for, so it answers "how good is this thing in general?" rather than "how good is it at this?".
That is why an option with a lower overall BioHarmony number can sit above one with a higher number here. It is the better choice for Endurance and cardio fitness, even though the other scores better taken as a whole.
Rank 1: SLU-PP-332
Endurance and cardio fitness rating 6.5–7.0 / 10Overall BioHarmony 4.5–5.0 / 10 🤷 NeutralPan-ERR agonist, the literal exercise mimetic. Preclinical only. Leads this category on the endurance-cardio subrating. Overall 4.5–5.0/10, neutral.
Ranked above options with a higher overall BioHarmony number because it is stronger for Endurance and cardio fitness specifically.
Rank 2: Ca-AKG (Calcium Alpha-Ketoglutarate)
Endurance and cardio fitness rating 5.5–6.0 / 10Overall BioHarmony 6.5–7.0 / 10 Worth tryingSecond on endurance and cardio fitness at 5.5–6.0/10, just behind SLU-PP-332, while carrying the highest overall score in the category, 6.5–7.0/10. Shahmirzadi 2020 found longer life and compressed late-life frailty in aged mice, with IL-10 signalling required for the effect. Chin 2014 extended lifespan in C. elegans, and Filip 2007 is the one controlled human endpoint in this whole category: lower CTX bone-resorption markers in postmenopausal women over 24 weeks. None of that is a treadmill or exercise-capacity result, which is the whole reason it trails the compound whose one core study directly measured endurance in mice. Pick it when you want the broadest systemic case at the lowest price. The weak link is the biological-age claim everyone quotes, which comes from an uncontrolled brand-funded study of 42 users.
Krebs-cycle intermediate and epigenetic cofactor. Retail supplement. Second on the endurance-cardio subrating, with the highest overall score in the category. Overall 6.5–7.0/10, worth trying.
Rank 3: MOTS-c
Endurance and cardio fitness rating 5.0–5.5 / 10Overall BioHarmony 6.5–7.0 / 10 Worth tryingThird on endurance and cardio fitness at 5.0–5.5/10, tied for the best overall score in the category at 6.5–7.0/10 along with Ca-AKG and urolithin A. This page's earlier cellular-senescence order put MOTS-c last; on endurance-cardio it jumps to third, because Lee 2015 identified MOTS-c as a peptide encoded in mitochondrial DNA that activates AMPK, the same energy sensor training activates, and Reynolds 2021 showed exercise induces it in humans and that it affects physical capacity in mice — the closest thing to a training-specific human signal in this category, even though it measures induction by exercise, not administration of the peptide. It still trails Ca-AKG and SLU-PP-332 here because neither study is a dosed human endurance trial. No published trial has ever dosed exogenous MOTS-c and measured an outcome, and it has no legal way to buy it.
Mitochondrial-derived peptide, AMPK activator. Research vial only. One of the best overall scores on this page (6.5–7.0/10) and third on endurance-cardio.
Rank 4: Urolithin A
Endurance and cardio fitness rating 4.5–5.0 / 10Overall BioHarmony 6.5–7.0 / 10 Worth tryingFourth on endurance and cardio fitness at 4.5–5.0/10, the lowest of the three members tied on overall at 6.5–7.0/10. Andreux 2019 showed measurable acylcarnitine and skeletal-muscle mitochondrial gene-expression shifts after four weeks of oral dosing, and Liu 2022 found muscle-endurance and biomarker gains in adults aged 65 to 90 — the strongest human trial record in this category. That trial's headline six-minute-walk and maximal-ATP-production endpoints were not clearly significant versus placebo, and that missed functional endpoint is exactly why it trails Ca-AKG and MOTS-c here despite otherwise having the most human data of the seven. Mitophagy clears damaged mitochondria rather than driving exercise capacity directly. Pick it over Ca-AKG when the target is muscle mitochondria specifically and you are older or sedentary.
PINK1/Parkin mitophagy inducer. Retail supplement. Fourth on the endurance-cardio subrating despite the strongest human trial record in the category. Overall 6.5–7.0/10, worth trying.
Rank 5: 5-Amino-1MQ
Endurance and cardio fitness rating 3.0–3.5 / 10Overall BioHarmony 4.5–5.0 / 10 🤷 NeutralFifth on endurance and cardio fitness at 3.0–3.5/10, and the only compound in this category that works by mouth. Neelakantan 2018 found obese mice lost roughly 5% of body weight with over 30% smaller fat cells through NNMT inhibition, and Neelakantan 2019 nearly doubled muscle-fibre size in aged injured mice — neither a trained-endurance result. There are zero registered human trials of this or any NNMT inhibitor, so its endurance-cardio subrating rests on the same rodent file as its overall score, 4.5–5.0/10. Ranked above SS-31 despite SS-31's higher overall score, 6.0–6.5/10: SS-31 holds the category's strongest mitochondrial credentials, but its one dedicated human endurance trial missed both of its endpoints, and that failure shows up directly here. Pick 5-Amino- 1MQ over the injectables if the felt energy effect is what you are after and you dose orally at 50 to 150 mg, the only route with pharmacokinetic support.
Oral NNMT inhibitor. No human trial. Fifth on the endurance-cardio subrating. Overall 4.5–5.0/10, neutral.
Ranked above options with a higher overall BioHarmony number because it is stronger for Endurance and cardio fitness specifically.
Rank 6: SS-31 (Elamipretide)
Endurance and cardio fitness rating 2.5–3.0 / 10Overall BioHarmony 6.0–6.5 / 10 Worth tryingSixth on endurance and cardio fitness at 2.5–3.0/10, the widest gap on this page between rank and overall score: SS-31 carries 6.0–6.5/10 overall, the highest mitochondrial subrating in the category, and the only FDA approval, and still finishes second to last here. MMPOWER-3 missed both co-primary endpoints, the six-minute walk test and fatigue, in 218 patients with mitochondrial myopathy — the field's one dedicated human endurance trial of SS-31, and it failed. The Barth syndrome approval behind Forzinity, a 95.9 metre six-minute-walk gain, is a rare-disease result, not a healthy-endurance one. Stabilising cardiolipin is structural repair, not the signalling that flips exercise-responsive pathways, which is the ceiling on this row. Self-directed use means a daily injection of gray-market material at $200 to $500 a month.
Cardiolipin-binding tetrapeptide. FDA approved for Barth syndrome only. Sixth on the endurance-cardio subrating despite the highest mitochondrial subrating in the category. Overall 6.0–6.5/10, worth trying.
Rank 7: Humanin
Endurance and cardio fitness rating 1.0–1.5 / 10Overall BioHarmony 5.5–6.0 / 10 🤷 NeutralLast on endurance and cardio fitness at 1.0–1.5/10, the lowest score on this page for this specific goal despite a more middling overall score, 5.5–6.0/10. Hashimoto 2001 cloned it from surviving neurons in an Alzheimer's brain, which is cytoprotection, not exercise mimicry. Muzumdar 2009 showed central dosing improved whole-body insulin sensitivity in rodents, and Yen 2020 found children of centenarians carry markedly higher circulating levels, while the largest human cohort, 693 people in Conte 2019, tied high levels to worse outcomes in the oldest old, a signal that points both directions. None of that evidence targets endurance or cardiovascular capacity, which is why the compound most people expect near the top of a mitochondrial-peptide list finishes last on this specific metric. No human interventional trial of administered humanin exists, and it has no legal channel.
Mitochondrial-derived peptide, cytoprotective. No human interventional trial. Overall 5.5–6.0/10, neutral. Last on the endurance-cardio subrating.
Best Pick by Use Case
| Use Case | Winner | Runner-Up | Why |
|---|---|---|---|
| Mitochondrial | SS-31 (Elamipretide) 8.5 | Urolithin A 7.0 | The highest subrating anywhere on this page, and the one row where an approved drug exists. SS-31 binds cardiolipin directly and stabilises cristae, which is repair rather than signalling. Urolithin A's 7.0–7.5/10 is the best score any purchasable member holds here. The two lowest, humanin and 5-Amino-1MQ, are low because nothing has been measured in a person, not because the mechanism is weaker. |
| Endurance & Cardio | SLU-PP-332 6.5 | Ca-AKG (Calcium Alpha-Ketoglutarate) 5.8 | The compound with the lowest overall score on this page, 4.5–5.0/10, wins the row the category is now ranked on, on eight days of treadmill data in sedentary mice. That is the whole argument of this page in one line. SS-31 sits at 2.5–3.0/10 here despite the highest mitochondrial subrating, because MMPOWER-3 missed its six-minute-walk endpoint in people. Humanin scores lowest of the seven here, at 1.0–1.5/10. |
| Body Composition | SLU-PP-332 6.0 | MOTS-c 5.5 | Both winners are mouse results. SLU-PP-332 reduced fat mass in diet-induced obesity models and MOTS-c prevented diet-induced obesity in the discovery paper. 5-Amino-1MQ's 4.5/10 rests on roughly 5% weight loss in obese mice with over 30% smaller adipocytes. Nothing in this category has changed a human body composition in a published trial, and none of it substitutes for a calorie deficit. Humanin is not scored here. |
| Energy & Fatigue | SLU-PP-332 5.5 | Ca-AKG (Calcium Alpha-Ketoglutarate) 5.4 | A tenth of a point between them, so treat this row as a coin flip. The interesting entry is the one that loses: 5-Amino-1MQ's 3.5–4.0/10 rests on published evidence, and it is the compound in this category Nick most reliably feels, within about thirty minutes of an oral dose. Subjective energy is the endpoint with the widest gap between what people report and what has been measured. |
| Metabolic Health | SLU-PP-332 6.5 | MOTS-c 6.0 | Both rest on rodent metabolic-syndrome models: improved energy expenditure and glucose handling in obese mice for SLU-PP-332, improved insulin sensitivity and diet-induced obesity measures for MOTS-c. Urolithin A's 3.5–4.0/10 reflects that its own systematic review found no clear anthropometric effect in humans. This row is where the mimetic idea is strongest in theory and weakest in evidence. |
| Blood Sugar | MOTS-c 6.0 | SLU-PP-332 5.5 | MOTS-c wins on AMPK-mediated glucose disposal and mouse insulin sensitivity from Lee 2015. Urolithin A's 1.0–1.5/10 is the lowest score in this table and it is correct: nothing in the urolithin A literature supports a glycemic effect. If blood sugar is the reason you are reading, none of these seven belongs ahead of the things that actually move it. |
| Healthspan | Ca-AKG (Calcium Alpha-Ketoglutarate) 7.2 | Urolithin A 5.0 | The widest gap on the page, 2.2 points, and the row that carries Ca-AKG's ranking. It comes from aged mice living longer with compressed frailty in Shahmirzadi 2020 plus the bone-turnover RCT in Filip 2007. Read the second one precisely: it measured CTX markers in postmenopausal women at 6 g a day, not healthspan and not fracture prevention. |
| Longevity & Lifespan | Ca-AKG (Calcium Alpha-Ketoglutarate) 7.0 | Urolithin A 5.0 | Mouse and worm lifespan on one side, an uncontrolled 42-person methylation-age study on the other. No member of this category has been measured against a human mortality or aging endpoint. MOTS-c's 4.0/10 comes from Fuku 2015, which associated a MOTS-c gene variant with exceptional longevity in Japanese centenarians, and an inherited variant is not a dosing result. |
| Anti-Inflammatory | Ca-AKG (Calcium Alpha-Ketoglutarate) 6.8 | Urolithin A 5.5 | In Shahmirzadi 2020, IL-10 signalling was necessary for the mouse lifespan and frailty benefit, which is where Ca-AKG's inflammatory case comes from. Urolithin A's 5.5/10 rests on the immune-metabolic signal in Denk 2025. Neither has moved a disease-level inflammatory outcome in a person. |
| Muscle Growth | Ca-AKG (Calcium Alpha-Ketoglutarate) 5.2 | Urolithin A 5.0 | The tightest and least meaningful row here. Note what is missing: MOTS-c's 3.0–3.5/10 reflects that AMPK activation competes with the mTOR signalling hypertrophy runs on. An exercise mimetic that mimics endurance training is not automatically good for building muscle, and may work against it. Humanin is not scored for this use case. |
| Cardiovascular | SS-31 (Elamipretide) 5.5 | SLU-PP-332 5.5 | A dead heat, so read this as a tie rather than a win. SS-31's 5.5–6.0/10 comes from cardiolipin biology and acute heart-failure signals, SLU-PP-332's matching score from a mouse heart-failure model with preserved ejection fraction. No cardiovascular outcome trial has reported on any member of this category, and the highest score in the row is still modest. |
| Neuroprotection | Ca-AKG (Calcium Alpha-Ketoglutarate) 5.6 | SS-31 (Elamipretide) 5.5 | A tenth of a point apart and both preclinical. The name people expect to see at the top of this row is humanin, which was cloned from surviving neurons in an Alzheimer's brain and holds 3.0–3.5/10 here. That gap is the scoring model refusing to reward the best origin story in the category. |
At a Glance
SLU-PP-332
- Efficacy Strong
- Breadth Strong
- Evidence Limited
- Speed Strong
- Durability Limited
- Bioindividuality Moderate
- Safety Risk High
- Side Effects Moderate
- Cost premium Moderate
- Effort Moderate
- Opportunity Cost Moderate
- Dependency Moderate
- Reversibility Moderate
- Mitochondrial
- Endurance & Cardio
- Metabolic Health
- Body Composition
Pan-ERR agonist, the literal exercise mimetic. Preclinical only. Leads this category on the endurance-cardio subrating. Overall 4.5–5.0/10, neutral.
Ca-AKG (Calcium Alpha-Ketoglutarate)
- Efficacy Moderate
- Breadth Moderate
- Evidence Moderate
- Speed Limited
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Low
- Effort Negligible
- Opportunity Cost Low
- Dependency Negligible
- Reversibility Negligible
- Geriatric & Aging
- Bone & Joint
- Healthspan
- Longevity & Lifespan
Krebs-cycle intermediate and epigenetic cofactor. Retail supplement. Second on the endurance-cardio subrating, with the highest overall score in the category. Overall 6.5–7.0/10, worth trying.
MOTS-c
- Efficacy Moderate
- Breadth Strong
- Evidence Moderate
- Speed Moderate
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Negligible
- Side Effects Negligible
- Cost premium Moderate
- Effort Moderate
- Opportunity Cost Moderate
- Dependency Negligible
- Reversibility Negligible
- Mitochondrial
- Metabolic Health
- Blood Sugar
- Body Composition
Mitochondrial-derived peptide, AMPK activator. Research vial only. One of the best overall scores on this page (6.5–7.0/10) and third on endurance-cardio.
Urolithin A
- Efficacy Moderate
- Breadth Moderate
- Evidence Moderate
- Speed Limited
- Durability Moderate
- Bioindividuality Strong
- Safety Risk Negligible
- Side Effects Negligible
- Cost premium High
- Effort Negligible
- Opportunity Cost Low
- Dependency Low
- Reversibility Negligible
- Mitochondrial
- Anti-Inflammatory
- Geriatric & Aging
- Muscle Growth
PINK1/Parkin mitophagy inducer. Retail supplement. Fourth on the endurance-cardio subrating despite the strongest human trial record in the category. Overall 6.5–7.0/10, worth trying.
5-Amino-1MQ
- Efficacy Moderate
- Breadth Moderate
- Evidence Limited
- Speed Strong
- Durability Moderate
- Bioindividuality Moderate
- Safety Risk Moderate
- Side Effects Low
- Cost premium High
- Effort Moderate
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Body Composition
- Muscle Growth
- Energy & Fatigue
- Metabolic Health
Oral NNMT inhibitor. No human trial. Fifth on the endurance-cardio subrating. Overall 4.5–5.0/10, neutral.
SS-31 (Elamipretide)
- Efficacy Strong
- Breadth Moderate
- Evidence Strong
- Speed Limited
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium High
- Effort Moderate
- Opportunity Cost Low
- Dependency Low
- Reversibility Negligible
- Mitochondrial
- Antioxidant
- Cardiovascular
- Neuroprotection
Cardiolipin-binding tetrapeptide. FDA approved for Barth syndrome only. Sixth on the endurance-cardio subrating despite the highest mitochondrial subrating in the category. Overall 6.0–6.5/10, worth trying.
Humanin
- Efficacy Moderate
- Breadth Moderate
- Evidence Limited
- Speed Moderate
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort Moderate
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Mitochondrial
- Metabolic Health
- Neuroprotection
- Longevity & Lifespan
Mitochondrial-derived peptide, cytoprotective. No human interventional trial. Overall 5.5–6.0/10, neutral. Last on the endurance-cardio subrating.
Cost Comparison
| Intervention | Monthly Cost | Notes |
|---|---|---|
| Ca-AKG | $15 to $30 | Retail supplement, priced 2026-09-08 at the 1 g/day generic dose this report scores. The cheapest line on the table and one of only two you can buy without a vendor certificate of analysis. The branded Rejuvant formulation runs closer to $150 a month, and since the human biological-age data behind that brand is the uncontrolled Demidenko 2021, the premium is hard to defend on the evidence. |
| Urolithin A | $50 to $100 | Retail supplement, priced 2026-09-08 at 500 mg/day. This prices the branded material, which is the only form validated in the human trials. Generic urolithin A is cheaper and has documented purity and label-claim problems, so the cheaper number is not the same product. |
| SLU-PP-332 | $30 to $80 | Estimated, September 2026 prices, research-chemical channel, at 3 to 5 mg a day oral. The second-cheapest line on the table belongs to the compound with the lowest overall score on this page and no human dose, which is the trap this ranking exists to describe. The real cost includes independent identity and purity testing, because there is no product standard behind the label. |
| 5-Amino-1MQ | $95 to $190 | Estimated from the report's own $190 per 3,000 mg source pricing, September 2026, at the 50 to 100 mg daily oral dose with pharmacokinetic support. The report's own framing is the right one: you are paying clinical-grade prices for preclinical-grade certainty, on a compound with zero human trials. |
| MOTS-c | $100 to $200 | Estimated, September 2026 prices, research-vendor channel, at 5 to 10 mg subcutaneous three times weekly. Add syringes, bacteriostatic water and cold-chain shipping on top. No pharmacy exists, no insurance applies, and FDA has flagged the substance on the compounding-warning side. |
| Humanin | $100 to $300 | Estimated, September 2026 prices, research-vial channel, at roughly 1 mg subcutaneous twice weekly. The report states only that a real cycle runs into the low hundreds per month, so treat this as an order of magnitude rather than a quote. Note that the marquee metabolic research used the more potent HNG analogue, which is a different molecule from what you would be buying. |
| SS-31 (elamipretide) | $200 to $500 | Estimated, September 2026 prices, gray-market channel, at 5 to 10 mg a day. The most expensive line here, and the approved route is worse rather than better: Forzinity is priced and distributed as an ultra-rare-disease orphan drug. Higher daily doses push monthly spend into the thousands with no prescription coverage. |
| The difference | $15 to $500, and the cheap end is the legal end | Two of the seven have a real retail price: Ca-AKG at $15 to $30 and urolithin A at $50 to $100. Those are also the two highest-ranked purchasable members, which makes this category unusual. Normally the legal option costs more.Everything else on the table is an estimated research-vial or research-chemical cost, and the ordering inside that group tells you nothing about quality. SLU-PP-332 is the second-cheapest line on the page and has never been given to a human. SS-31 is the most expensive and is the only member with an FDA approval, which you almost certainly cannot use. Every figure carries a pricing date because this channel moves. |
Who Should Pick What?
You want one thing from this list and you want it to be legal
Ca-AKG (Calcium Alpha-Ketoglutarate)
It takes five of the twelve use-case rows, it is an ordinary supplement, and it is the cheapest way into this category. Track total supplemental calcium while you use it, because each gram of Ca-AKG carries roughly 200 mg of elemental calcium and Anderson 2016 supports caution around supplemental calcium and coronary artery calcification.
Older or sedentary, and muscle mitochondria are the target
Urolithin A
This is where the human trial signal actually lives. Andreux 2019 and Liu 2022 both studied older adults, and the mitochondrial subrating of 7.0/10 is the highest any purchasable member holds. Buy the branded material that matches the trials rather than generic urolithin A, and give it four months rather than four weeks.
Already fit, training hard, and hoping one of these adds a gear
Tie
None of the seven. The trial populations that responded were older, sedentary, injured or obese, and the compound built specifically for trained endurance has been tested in mice for eight days. Nick ran urolithin A at 500 mg a day for about 90 days from an already-fit baseline and recorded no clearly noticeable subjective effect. This is the row where the answer is to keep training.
Documented mitochondrial dysfunction with objective markers
SS-31 (Elamipretide)
An 8.5/10 mitochondrial subrating and the only regulatory approval in the category. Two hard qualifiers: the approval covers Barth syndrome in patients over 30 kg and nothing else, and MMPOWER-3 missed both co-primary endpoints in 218 patients with primary mitochondrial myopathy. If you have a diagnosis, this is a specialist conversation. If you do not, it is a daily injection of gray-market peptide at $200 to $500 a month.
You want the felt effect, not the biomarker
5-Amino-1MQ
It is the only member here that works orally, and the one Nick reports actually noticing, within about thirty minutes at 50 to 100 mg as a pre-workout. Understand exactly what you are buying: zero human trials, a quinolinium scaffold whose genotoxicity is unconfirmed rather than ruled out, and a WADA ban. The injectable microgram protocols sold alongside it are almost certainly too low to do anything.
You are chasing the actual exercise-mimetic idea
SLU-PP-332
It is the real thing conceptually and the worst bet practically, which is why it carries the lowest overall score on this page while winning four rows. There is no human dose, no pharmacokinetic curve, and no safety package. Nick ran two cycles and was progressively fatigued, drained and burnt out within about two weeks both times, resolving within days of stopping. Follow the ERR literature instead of buying the compound.
Insulin resistance is the reason you are here
MOTS-c
It holds the top blood-sugar subrating in the category at 6.0/10, on AMPK mediated glucose disposal and mouse insulin-sensitivity data. That is still a mouse. Before a research vial, the honest sequence is the things with human outcome data behind them, and MOTS-c after them rather than instead of them.
Building a longevity stack and deciding what earns a slot
Tie
Two of these seven, Ca-AKG and urolithin A, cost less than a month of most peptides and can be bought without a vendor certificate of analysis. The other five ask you to inject unapproved material for signals measured in worms, mice and cell culture. Take the two that are supplements, skip the five that are not, and revisit when a human trial publishes.
How This Ranking Is Built
- Ranked by
- Ranked by the live Endurance and cardio fitness rating (the Endurance & Cardio subrating) This page is ordered by each option's Endurance and cardio fitness rating: how well it works for that one goal, and nothing else. The overall BioHarmony number beside it is a different measure. It weighs safety, cost, evidence and practicality across every goal an intervention is used for, so it answers "how good is this thing in general?" rather than "how good is it at this?". That is why an option with a lower overall BioHarmony number can sit above one with a higher number here. It is the better choice for Endurance and cardio fitness, even though the other scores better taken as a whole.
- What is included
- Every published BioHarmony intervention report whose primary mechanism is activation of a pathway that endurance training activates, or direct repair of the mitochondria that training remodels. That covers the mitochondrial derived peptides encoded in mitochondrial DNA, direct agonists of the transcriptional machinery behind mitochondrial biogenesis, mitophagy inducers, and compounds that stabilise the inner mitochondrial membrane. Substrate and cofactor repletion is out, which is why the NAD precursors and CoQ10 are excluded despite sharing the search cluster. Exercise itself is out. Adding a new report inside this boundary adds a row.
- Kept current
- Positions and scores are read live from each intervention report on every page load, so the order re-renders the moment any member is rescored. Membership is rebuilt nightly against the inclusion rule above.
Ranked by the live Endurance and cardio fitness rating (the Endurance & Cardio subrating), read from each member's report when the page renders. This is the use case category-rules.json names as the defining criterion for exercise mimetics, so it sets the order here instead of the whole-report BioHarmony overall. When a member's endurance-cardio subrating changes, the row moves that night.
Two numbers appear for every member. The ranked number is the endurance-cardio subrating, and that is what decides the order. The overall BioHarmony score sits underneath it, visible, and never sets the order. The gap between the two is the point of this page: a member can carry a strong overall score built on dimensions this use case does not touch, and still rank low here.
SLU-PP-332 is the clearest case. It holds the lowest overall score in the category and the highest endurance-cardio subrating on the page. Its evidence is eight days of treadmill data in sedentary mice, aimed directly at the mechanism endurance training uses, while its overall score is dragged down by having never been dosed in a human being. Ca-AKG, MOTS-c and urolithin A also carry higher overall scores than SLU-PP-332 and still rank below it here, for the same reason: this ranking measures one goal, not the whole report.
5-Amino-1MQ ranks above SS-31 here despite SS-31's higher overall score, 6.0–6.5/10: SS-31 carries the highest mitochondrial subrating in the category, but its one dedicated human endurance trial, MMPOWER-3, missed both co-primary endpoints, and that failure shows up directly in this subrating.
Two facts about this category matter more than the ordering. Five of the seven have no legal retail channel. And four of the seven, MOTS-c, humanin, 5-Amino-1MQ and SLU-PP-332, have never been administered to a human being in a published trial. Every score they carry is extrapolated from cells, rodents or correlations. Only urolithin A, Ca-AKG and SS-31 have human interventional data of any kind, and Ca-AKG's amounts to one controlled endpoint measuring bone-turnover markers.
The use-case table uses twelve rows drawn from the subratings the members share. Four of the seven carry a full 66-use-case subrating set; humanin is scored across 15 use cases and 5-Amino-1MQ across 22, so humanin is absent from the body composition and muscle growth rows. Where a member is not scored for a use case the note says so, rather than letting a blank read as a zero.
Costs in the table are estimates with a pricing date except where a retail product exists, and for the research-vial members they are the price of material sold not for human use with vendor-dependent purity. Treat them as channel estimates, not quotes.
Research Highlights
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Mechanism Difference
Four different mechanisms sit under the phrase exercise mimetic and they are not interchangeable. MOTS-c and humanin are peptides your own mitochondria encode and secrete, discovered in mitochondrial DNA rather than designed: MOTS-c is the metabolic, AMPK-activating half of that family and humanin the cytoprotective half. SLU-PP-332 is the only true designed mimetic, a synthetic pan-ERR agonist built to flip the transcriptional switch endurance training flips.Urolithin A works one layer down, inducing PINK1 and Parkin-dependent mitophagy so damaged mitochondria are cleared rather than stimulated. SS-31 works one layer down again, binding cardiolipin in the inner membrane to hold cristae together, which is structural repair rather than signalling. Ca-AKG is a Krebs-cycle intermediate that doubles as an epigenetic cofactor, and 5-Amino-1MQ blocks NNMT to spare methyl groups and nicotinamide. Reading this list as one idea getting progressively better misses the point entirely. These are six different bets on what part of exercise is worth copying.
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Evidence Maturity
The most useful number on this page is not the top score. It is that four of the seven members have never been administered to a human being in a published trial. MOTS-c, humanin, 5-Amino-1MQ and SLU-PP-332 carry subratings built entirely from cell culture, rodents and correlation.Of the three that do have human data, the depth varies more than the scores suggest. Urolithin A has genuine randomised trials, sponsor-funded and with missed primary endpoints, but real. SS-31 has an entire multi-indication clinical programme and an FDA approval, and also two large negative readouts. Ca-AKG has exactly one controlled human endpoint, a 24-week bone-turnover-marker trial in postmenopausal women at 6 g a day, plus an uncontrolled 42-person methylation-age study that its own report calls the weak link. That is what the top of this ranking is built on. It is more than the bottom has, and it is much less than the marketing implies.
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Safety Comparison
There is no class-wide contraindication here, because these seven are not a class. What repeats across the reports is the sourcing risk rather than the pharmacology: five of the seven name unverified vials or unverified product as a reason not to proceed, and for the four with no human data that procurement risk is larger than any documented effect of the molecule itself.The compound-specific cautions are where the mechanisms show. Humanin is pro-survival and engages the IGFBP-3 axis, so its report flags active or suspected cancer as a real theoretical concern. SLU-PP-332 carries the same shape of flag for a different reason, because ERR biology is entangled with tumour metabolism. 5-Amino-1MQ sits in a quinolinium chemical family that includes known mutagens and its genotoxicity is unconfirmed rather than ruled out. SS-31 has an actual drug label with actual boundaries: serious hypersensitivity, a benzyl-alcohol neonatal warning, renal dose adjustment. Ca-AKG's caution is the least exotic and the most likely to apply to you, which is the elemental calcium load.
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Cost Comparison
The price spread in this category runs roughly ten to one, and it does not track the ranking. The two cheapest routes are the two ordinary supplements at the top, which is unusual and worth saying plainly: here, the legal option is also the cheap option.The expensive end is SS-31, at $200 to $500 a month for gray-market material at 5 to 10 mg a day, and higher still through the approved orphan-drug channel that most readers cannot use anyway. The oddity is 5-Amino-1MQ, where an eight-week oral cycle at the top of the dose range runs several hundred dollars for a compound with zero human trials. You are paying clinical prices for preclinical certainty. Every figure here carries a pricing date because the research-vial channel moves.
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Editorial Verdict
For most people the answer in this category is Ca-AKG or urolithin A, and which one depends on whether you want the broadest systemic case or the one with the most direct muscle-mitochondria evidence. Both are supplements, both cost less than a month of any peptide here, and both have something human behind them.The other five are worth understanding and mostly not worth buying. SS-31 is a real drug with a real approval that is not for you unless you have a diagnosis. MOTS-c and humanin are legitimate endogenous signals with empty human files. 5-Amino-1MQ is the one with a genuine felt effect and the least evidence to explain it. And SLU-PP-332 is the most conceptually exciting compound on this page, the winner of four use-case rows, and the one where the recorded personal experience was clearly negative twice. None of that is a reason to buy a vial labelled not for human use.
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Ranking Stability
This ranking is not an opinion that gets refreshed quarterly. The order is the live endurance-cardio subrating for each member, resolved when the page loads, so a rescoring of any one report's subrating reorders the page that night without an editorial pass. The overall BioHarmony score, shown alongside it, never sets this order, which is exactly why SLU-PP-332 can carry the lowest overall score on the page and still finish first here.Expect movement, and expect it from a specific direction. Several members sit low on this use case largely because their evidence column is empty, not because the mechanism is weak. A single clean human trial on any of them would raise evidence quality and plausibly efficacy at the same time, which is the combination that produces a large score change. Each of those reports names its own trigger: a Phase 2 confirming oral fat loss for 5-Amino-1MQ, a first human interventional trial for humanin, a Phase 1 safety and pharmacokinetic package for SLU-PP-332. None of them has happened yet.
Frequently Asked Questions
- What is the best exercise mimetic?
- On this page's ranking, the endurance-cardio subrating, SLU-PP-332 leads at 6.5–7.0/10, though it's preclinical with no legal retail channel. Among purchasable options, Ca-AKG is second at 5.5–6.0/10. On BioHarmony overall, a different question, MOTS-c, Ca-AKG and urolithin A all tie for the best score in the category at 6.5–7.0/10 despite ranking behind SLU-PP-332 here. If the question means which one most closely imitates endurance training, the answer is still SLU-PP-332, which is designed to do exactly that and now leads the page built around that exact goal.
- Does any of this replace exercise?
- No, and nothing in these seven reports claims it does. The best endurance evidence in the category is eight days of treadmill data in sedentary mice. Every human trial that showed anything studied older, sedentary or injured populations, which is the group furthest from trained. The honest framing is a possible adjunct to training for specific people, not a substitute for it.
- Why does SLU-PP-332 rank first here despite the lowest overall score in the category?
- Because this page ranks by the endurance-cardio subrating, not by BioHarmony overall. SLU-PP-332's overall score, 4.5–5.0/10, is the lowest of the seven, dragged down by having no human dose, no pharmacokinetic curve and no safety package. Its endurance-cardio subrating, 6.5–7.0/10, is the best on this page, because its one core study is eight days of treadmill data in sedentary mice, aimed directly at the mechanism this page measures. A strong overall score doesn't guarantee a strong score on every single use case, and this ranking exists to make that visible rather than hide it behind one blended number.
- Is MOTS-c or SS-31 better?
- It depends what you're asking. On this page's endurance-cardio ranking, MOTS-c places third and SS-31 sixth. On BioHarmony overall, MOTS-c's 6.5–7.0/10 beats SS-31's 6.0–6.5/10. SS-31 holds the highest mitochondrial subrating in the category and is the only member with an FDA approval, though that approval covers Barth syndrome and nothing else, and its one dedicated human endurance trial, MMPOWER-3, missed both co-primary endpoints. MOTS-c holds the highest blood-sugar subrating. Nick has run both and describes MOTS-c as the software upgrade and SS-31 as the hardware upgrade, and reports noticing more from MOTS-c.
- Which one is cheapest?
- The two supplements at the top of the ranking, Ca-AKG and urolithin A, are the cheapest legal routes into this category. That is unusual and worth saying plainly: here the legal option is also the cheap one. The expensive end is SS-31 at $200 to $500 a month for gray-market material, and 5-Amino-1MQ, where an eight-week oral cycle at the top of the dose range costs several hundred dollars for a compound with zero human trials.
- Are the research-vial versions the same compound?
- There is no way to know from the label. Five of the seven have no legal retail channel, so the real-world supply is material sold not for human use, with no product standard behind it and vendor-dependent purity. All five of those reports name unverified product as a reason not to proceed. Purity verification is not an optional extra on that channel, and it is part of why those members score low on access regardless of their preclinical data.
- How often does this ranking change?
- Whenever any member's endurance-cardio subrating changes. That is the number pulled from each report at render time to set the order here, and a rescoring reorders the page that night with no editorial pass. Several members sit low on this use case largely because their human-evidence column is empty, so a single clean trial on any of them would move this list.
- Should I stack these?
- The reports name two pairings and neither is tested. MOTS-c and humanin are the metabolic and cytoprotective halves of the same peptide family and are commonly run together, and Nick's own note is that MOTS-c works best after an SS-31 cycle. Both are community practice, not trial evidence. Stacking two compounds with no human data does not produce one compound with human data.
Evidence Sources
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance Discovery paper. MOTS-c is encoded in mitochondrial 12S rRNA and activates AMPK by inhibiting ATIC and raising AICAR. Improved insulin sensitivity and diet-induced obesity measures in mice.
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis Exercise induces endogenous MOTS-c in humans, and MOTS-c affected late-life physical capacity in mice. Endogenous exercise response is not the same as exogenous dosing.
- Circulating MOTS-c levels across metabolic states: a biomarker meta-analysis Pooled human biomarker studies showing circulating MOTS-c differs by metabolic state. Measures associations, not outcomes after dosing.
- A mitochondrial-derived peptide variant and exceptional longevity in Japanese centenarians Associated the K14Q MOTS-c variant with exceptional longevity. An inherited variant, not a result of taking the peptide.
- FDA: certain bulk drug substances for use in compounding may present significant safety risks FDA lists MOTS-c among bulk substances flagged for compounding safety risk. There is no legal compounding pathway for it.
- The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans First-in-human trial. Four weeks of oral urolithin A shifted plasma acylcarnitines and skeletal-muscle mitochondrial gene expression in older adults, with favourable short-term tolerability.
- Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults Adults aged 65 to 90. Muscle-endurance and biomarker improvements, but six-minute walk distance and maximal ATP production were not clearly significant versus placebo.
- Urolithin A in human health: a systematic review Five human studies in 250 healthy individuals. Mitochondrial, autophagy and inflammation signals, but no clear effect on cardiovascular outcomes, anthropometrics, gut microbiota or broad physical function.
- Urolithin A and immune aging: a four-week human study Four-week immune-aging signal with naive-like CD8+ cell expansion and improved immune-cell fatty-acid oxidation.
- Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents The foundational preclinical signal: lifespan extension in worms and muscle-function gains in rodents through induced mitophagy.
- Urolithin metabotypes: interindividual variability in urolithin production from dietary ellagitannins Adults differ substantially in the ability to make urolithin A from dietary ellagitannins, so many people are low or non-producers regardless of intake.
- Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice Aged mice fed Ca-AKG lived longer with compressed late-life frailty. IL-10 signalling was necessary for the effect. The strongest anchor behind Ca-AKG's healthspan and longevity subratings.
- The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR AKG extended lifespan in C. elegans through ATP synthase and TOR inhibition, giving a second species and a coherent mechanism.
- Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen in postmenopausal women The one controlled human endpoint in this category. 6 g/day AKG plus calcium lowered CTX bone-resorption markers over 24 weeks in postmenopausal osteopenic women. Markers, not fractures.
- Rejuvant, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging 42 users, large reported methylation-age improvement. Uncontrolled, brand-funded and vitamin-confounded. The weakest link in Ca-AKG's file and the most quoted.
- Calcium intake from diet and supplements and the risk of coronary artery calcification (MESA) Does not test Ca-AKG, but supports caution around supplemental calcium and coronary artery calcification. Relevant because each gram of Ca-AKG carries roughly 200 mg of elemental calcium.
- The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin Mechanism paper. SS-31 binds cardiolipin, protects cristae membranes and accelerates ATP recovery after ischemia in preclinical kidney models.
- Efficacy and safety of elamipretide in primary mitochondrial myopathy: MMPOWER-3 randomized clinical trial 218 patients. Missed both co-primary endpoints, the six-minute walk test and fatigue. The largest negative readout in this category.
- Long-term elamipretide treatment in Barth syndrome: open-label extension A 95.9 metre six-minute-walk gain in open-label extension. The clinical evidence behind the FDA accelerated approval.
- FDA grants accelerated approval to first treatment for Barth syndrome Forzinity (elamipretide) approved September 2025 for Barth syndrome in patients weighing at least 30 kg. The only regulatory approval held by any member of this category, and it is one rare disease wide.
- Elamipretide in dry age-related macular degeneration: ReCLAIM-2 randomized trial Missed primary endpoints in dry AMD, with adverse events more frequent than placebo and mainly injection-site reactions.
- A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta Humanin cloned from an Alzheimer's brain; abolished neuronal death from a wide spectrum of familial Alzheimer's insults in cells.
- Humanin: a novel central regulator of peripheral insulin action Central humanin improved whole-body insulin sensitivity through hypothalamic STAT3 in rodents. The marquee metabolic work leaned on the more potent HNG analogue.
- Humanin prevents age-related cognitive decline and correlates with lifespan Children of centenarians carry markedly higher circulating humanin than age-matched controls, and levels decline with age. The single most cited reason people find this peptide interesting.
- Human aging and longevity are characterized by high levels of mitokines 693-person cohort. High circulating humanin was tied to worse outcomes in the oldest old, pointing the opposite way to the centenarian-offspring story.
- Selective inhibition of nicotinamide N-methyltransferase reduces adiposity in diet-induced obese mice Obese mice lost roughly 5% of body weight with over 30% smaller fat cells, driven by increased fat burning rather than reduced appetite. The single strongest 5-Amino-1MQ finding, and it is a mouse.
- Nicotinamide N-methyltransferase inhibition enhances regeneration in aged skeletal muscle Nearly doubled muscle-fibre size and raised peak torque after injury in aged mice. The benefit appeared only in aged or injured animals.
- NNMT inhibition improves grip strength in aged mice About 40% higher grip strength in aged mice, adding a second independent aged-muscle signal for NNMT inhibition.
- 1-Methylnicotinamide and vascular function The basis for the concern that chronically suppressing the metabolite 1-MNA could carry a cardiovascular cost. The reason 5-Amino-1MQ's safety score stays elevated despite no proven toxicity.
- Synthetic ERR agonist SLU-PP-332 increases exercise capacity in mice Eight days of daily intraperitoneal dosing raised treadmill endurance and oxidative-muscle gene programs in sedentary mice. The core study, and the corrected PubMed record after the original v0 citation pointed at an unrelated paper.
- ERR agonism in diet-induced obesity: metabolic-syndrome improvements in mice Improved energy expenditure, reduced fat mass and better glucose handling in obese mouse models over several weeks.
- SLU-PP-332 and SLU-PP-915 in a mouse model of heart failure Enhanced cardiac fatty-acid oxidation, preserved ejection fraction and reduced fibrosis, on high-dose regimens that may not translate safely.
- Estrogen-related receptor alpha and tumour metabolism ERR biology is intertwined with tumour metabolism. Does not show SLU-PP-332 causes cancer; shows the pathway is not harmless background biology to manipulate chronically.
- WADA prohibited list MOTS-c and 5-Amino-1MQ are banned in tested sport, and SLU-PP-332 is of active doping-control interest. Relevant to any competing athlete reading this ranking.
Glossary
Quick reference for the medical and technical terms used in this comparison.
- AMPK AMP-Activated Protein Kinase
- The cell's energy sensor, switched on by exercise and caloric stress. MOTS-c activates it, which is the entire basis of the exercise-mimetic claim for that peptide.
- ERR Estrogen-Related Receptor
- A family of orphan nuclear receptors that work with PGC-1 alpha to control mitochondrial biogenesis and oxidative muscle-fibre programs. SLU-PP-332 is a synthetic agonist of all three.
- MDP Mitochondrial-Derived Peptide
- A peptide encoded inside mitochondrial DNA rather than the nucleus. MOTS-c and humanin are the two in this ranking; MOTS-c is the metabolic half of the family and humanin the cytoprotective half.
- Mitophagy Selective mitochondrial autophagy
- The quality-control process that clears damaged mitochondria. Urolithin A induces it through the PINK1 and Parkin pathway, which is cleanup rather than stimulation.
- Cardiolipin Inner mitochondrial membrane phospholipid
- The lipid that organises cristae, the folds where the electron transport chain sits. SS-31 binds it directly, and Barth syndrome is a genetic failure to remodel it.
- NNMT Nicotinamide N-Methyltransferase
- An enzyme that consumes nicotinamide and methyl groups. 5-Amino-1MQ blocks it, sparing both, which is the proposed route to its fat and muscle effects.
- AKG Alpha-Ketoglutarate
- A Krebs-cycle intermediate that also acts as a cofactor for the enzymes that demethylate DNA. Sold as the calcium salt, which is where the elemental calcium load comes from.
- CTX C-terminal telopeptide of type I collagen
- A blood marker of bone resorption. The endpoint that moved in Filip 2007, and the only controlled human result in this entire category.
- PGC-1 alpha Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
- The master regulator of mitochondrial biogenesis, and the switch endurance training flips. Every compound on this page is trying to reach it or its downstream effects by a different route.
- 6MWT Six-Minute Walk Test
- How far someone walks in six minutes. The functional endpoint SS-31 gained 95.9 metres on in Barth syndrome and missed in mitochondrial myopathy, and that urolithin A missed in older adults.
- Metabotype Urolithin producer status
- Whether your gut bacteria can convert dietary ellagitannins into urolithin A. Many people cannot at all, which is the main argument for supplementing the finished molecule.
- Preclinical Before human testing
- Cells and animals. Four of the seven members here have nothing else, which is the single fact that most explains the shape of this ranking.
First on endurance and cardio fitness at 6.5–7.0/10, the highest of the seven, despite carrying the lowest overall score on the page, 4.5–5.0/10. Billon 2023 showed eight days of daily injection raised treadmill endurance and oxidative-muscle gene programs in sedentary mice, the core study behind this row. Billon 2024 extended the same mechanism to fat mass and glucose handling, and Xu 2024 to cardiac function with preserved ejection fraction. It is the only compound here explicitly built to flip the switch endurance training flips, which is why it leads the metric the category is named after. Every other member on this page carries a higher overall score, because the low overall reflects no human trial, no human dose, no pharmacokinetic curve, ERR biology entangled with tumour metabolism, and Nick's own two cycles ending in progressive fatigue and burnout.