N=1 After 40

Completed experiment

SS-31 / Elamipretide

A one-month cycle produced no subjective signal. The more useful conclusion is that subjective feel was probably the wrong instrument for this test. Personal experiment record, not medical advice, prescribing, sourcing guidance, or an instruction to copy.

Outcome: One month at 2-10 mg per day produced no detectable fatigue, training, or recovery signal. The dose sat below pivotal-trial exposure and subjective feel was a weak instrument, so this is shelved pending a better-designed test with objective markers.

Research Summary

What it is

SS-31 is a cell-penetrating tetrapeptide that concentrates inside mitochondria. Under its drug name, elamipretide (also MTP-131, formerly Bendavia), it is the same molecule that has been through multiple Phase 2 and Phase 3 human trials. That makes it one of the few mitochondria-targeted peptides with a real clinical record rather than only preclinical and anecdotal support.

Mechanism

It binds cardiolipin, a lipid found almost exclusively on the inner mitochondrial membrane. Cardiolipin anchors the electron-transport-chain complexes, holds the folded cristae structure together, and supports the supercomplexes that make energy production efficient. When cardiolipin is damaged by oxidation, mutation, or age, cristae flatten, the chain leaks electrons, and those electrons form reactive oxygen species. By stabilizing cardiolipin, SS-31 is proposed to keep that machinery organized: better electron transfer, more ATP, less electron leak, less oxidative stress. The mechanism is well characterized at the cellular level. Whether it produces a benefit you can feel in an already-healthy person is a separate question.

Human evidence

This is where I want to correct my own earlier note, which called SS-31 one of the cleaner human bets among mitochondrial candidates. The accurate statement is narrower: it is the most clinically studied mitochondria-targeted peptide, but the trial record is mixed and mostly did not hit its primary endpoints. The Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy (40 mg/day subcutaneous, 24 weeks, 218 people) missed both co-primary endpoints, with improvement only in a nuclear-DNA subgroup. The PROGRESS-HF heart-failure trial tested both 4 mg and 40 mg and saw no change in the primary cardiac measure at four weeks. The TAZPOWER trial in Barth syndrome showed nothing over its 12-week randomized phase; the functional gains only appeared later, in a multi-year open-label extension against a natural-history comparison. The pattern across programs is consistent: little to nothing on short-term primary endpoints, with signals surfacing mainly in subgroups, on objective measures, and over long timeframes. "Most-studied" is not the same as "proven," and I had blurred the two.

Why the effect is hard to feel

Reading those trials changed how I judged my own null result. Even the studies that eventually found something needed objective instruments, walk-test distance, cardiac imaging, retinal function, measured over months. None of it was the kind of effect a person notices as a mood or an energy shift. If a 218-person controlled trial at 40 mg over 24 weeks struggles to separate this compound from placebo with instruments, then one person watching for a feeling at a quarter of that dose over a month has essentially no measurement power. Not feeling anything is not strong evidence that nothing happened; it mostly reflects the wrong instrument.

Route and pharmacokinetics

SS-31 has to be injected. As a peptide it is destroyed by gastric enzymes, so oral bioavailability is effectively zero. Subcutaneous dosing, which is what I used, absorbs well and clears with a short half-life of roughly four hours, with dose-proportional exposure. That short half-life, combined with the cumulative, structural nature of the mechanism, is why titrating the dose upward over a month is not a way to surface an acute signal. Raising the dose raised my exposure; it was never going to produce something to feel on a given day.

Safety boundary

In the trials SS-31 was generally well tolerated, with injection-site reactions the most common issue, but long-term safety in healthy people using it off-label is not characterized. This page documents one person's short cycle and reasoning. It is not a protocol, a dose to copy, or sourcing guidance.

Sources

The Experiment

Protocol

A one-month subcutaneous cycle. I started at 2 mg per day, moved to 4 mg, then 5 mg, and ran the final week at 10 mg per day. For context, the pivotal human trials dosed 40 mg per day, so even my top dose was about a quarter of the clinical exposure.

Why I tested it

SS-31 was my repair-lane candidate: the idea that steadier mitochondrial membrane function could show up as less fatigue friction, better training tolerance, and cleaner recovery. It was also deliberate preparation for a MOTS-c cycle I am planning next. The loose logic was to service the mitochondrial hardware first, then apply a metabolic-signaling stimulus on top of it. That sequencing is a reasonable story, not something the literature validates, and I am holding it as my rationale rather than a proven protocol.

Hypothesis

Qualitative, like my other N-of-1 tests: whether better mitochondrial efficiency would translate into anything I could actually notice and sustain in hard training, without a stimulant-style effect.

The reading problem

The reason I could not learn much from this cycle is worth stating plainly, because it also affects the MOTS-c experiment that follows. My working read on MOTS-c has been that my body is not reacting much to it, which I took as a sign of being in reasonable metabolic shape, since MOTS-c does most of its work correcting metabolic dysfunction and there may be less to correct in someone who trains. But notice that two different explanations, that the SS-31 cycle helped, and that I was already metabolically healthy, both predict the same muted MOTS-c response. If anything, a successful SS-31 cycle would reduce the dysfunction MOTS-c acts on and mute the response further. So the quiet MOTS-c response cannot tell those apart, and it certainly cannot be used as evidence that SS-31 did something. I never ran an A/B comparison or a washout, so there is no clean attribution to be had here, and I want the page to say that rather than imply a benefit.

Result

No detectable signal. Across the month and through every step up in dose, I did not notice a change in fatigue, training tolerance, recovery, or general energy. Given the sub-clinical dose, the short window, the fact that this is not a compound you feel, and a baseline that is already reasonably healthy, a null was the most likely outcome before I started.

Decision

I am filing this cycle as no signal and shelving it, not closing it. I still intend to reopen it in roughly six to twelve months. Two things change next time. First, a higher starting dose, since there is clear headroom below the 40 mg trial exposure. Second, and more important, the higher dose alone will not fix the detection problem; even 40 mg did not read out as a feeling in the trials. So the next cycle only makes sense if I instrument it: pre-defined objective proxies measured before, during, and after, things like VO2max or heart rate at a fixed Zone 2 power, resting heart rate and HRV, recovery markers, and a metabolic panel. Dose up and measure, or expect another honest but uninformative null.