NevadaBob
GLP-1 Novice
🚫No Source Discussion🚫
So does SS-31 repair your mitochondria and give you more energy?
Effects vs Outcomes
Methods
What they were measuring and why:
Dosing:
What they were measuring and why:
Practical outcomes:
What they were measuring and why:
What they were measuring and why:
What they were measuring and why: Barth Syndrome is a rare genetic disorder that only affects boys, causing weak muscles, fatigue, and heart problems because their mitochondria can’t work properly. The study measured walking endurance, muscle strength, balance, and fatigue.
Dosing: 40 mg injected under the skin once daily for 12 weeks in the crossover phase, then up to 192 weeks in the open-label extension.
Practical outcomes:
What they were measuring and why: In heart failure with reduced ejection fraction, the heart muscle is like a squeeze bottle that’s lost its squeezing power. The researchers tested two SS-31 doses to see if they could make the squeeze bottle work better.
Dosing: Either 4 mg or 40 mg injected under the skin once daily for 28 days.
Practical outcomes:
What they were measuring and why: This was the largest and most rigorous test of SS-31 for mitochondrial myopathy — the “final exam” meant to prove the drug worked well enough for regulatory approval. It measured walking distance and fatigue in 218 patients across 27 sites in 7 countries.
Dosing: 40 mg injected under the skin once daily for 24 weeks.
Practical outcomes:
What they were measuring and why: This study offered patients from a previous trial the chance to keep taking SS-31 long-term, mainly to track safety over years of use. It also measured walking distance, fatigue, and quality of life.
Dosing: 40 mg injected subcutaneously once daily for up to 260 weeks.
Practical outcomes:
What do you think?
- I reviewed the actual science on SS-31 to see if it was worth me continuing to spend money on.
Effects vs Outcomes
- So much peptide chatter is about fascinating effects (more ATP production, better insulin response, AMPK signalling, telomere lengthening, etc etc)
- Yes, true. But are those effects temporary, or do they actually produce long term outcomes?
Methods
- I used Elicit to comb through 100M+ studies and generate a report. Cross reference results with ChatGPT and Grok.
Study 1: Jump-Starting Old Batteries — Elderly Muscle Dysfunction (NCT02245620)
What they were measuring and why:
- As people age, the mitochondria in their muscles start running like old engines that can’t produce full power.
- This study tested whether a single 2-hour IV drip of SS-31 could “tune up” those old engines in people aged 60–85 who had proven mitochondrial problems in their hand muscles.
- They measured ATP production (how fast the engines could make energy) and muscle force (grip resilience and fatigue).
Dosing:
- A single IV infusion of 0.25 mg/kg/hr for 2 hours — just one treatment session on one day.
- For a 75kg (165 pound person): 38mg
- Think of it like giving an old car engine a shot of premium fuel — there was a brief power boost, but it faded. ATP production jumped by 0.17 mM/sec at 2 hours (vs. 0.12 for placebo), but by day 7 the difference had shrunk to 0.09 vs. 0.06.
- The paper’s main protocol-specified analysis found no significant effect on fatigue resistance. Some post-hoc analyses suggested possible improvement, but that is weaker evidence.
- This is the closest study to testing SS-31 in a “near-healthy” older population, but with only 41 participants and no reported statistical significance, the results are suggestive rather than definitive.
Study 2: Testing the Engine at Three Power Levels — Mitochondrial Myopathy (NCT02367014)
What they were measuring and why:
- People with mitochondrial myopathy have a genetic defect that breaks their cells’ power plants, making them exhausted and weak — like trying to run a race with a car that only has a quarter tank of gas.
- This study tested three different IV doses to find the best one, measuring how far people could walk in 6 minutes and how well their bodies used oxygen during exercise.
- Three dose levels given as IV infusions over 2 hours, once daily for 5 days: low (0.01 mg/kg/hr), intermediate (0.10 mg/kg/hr), and high (0.25 mg/kg/hr).
- High dose: for a 75kg (165 pound person): 38mg
Practical outcomes:
- More drug meant more walking.
- The high-dose group walked 64.5 meters farther in 6 minutes, while the placebo group only improved by 20.4 meters.
- The intermediate dose gave the best oxygen uptake boost (+2.36 ml/kg/min) and power output improvement (+13.9 watts). Breathing comfort also improved, with the intermediate dose reducing breathlessness by 2.2 points on a 10-point scale.
- But all of this was measured after only 5 days of treatment, and there is no data showing whether benefits lasted beyond day 7.
Study 3: Shielding the Heart During a Heart Attack — EMBRACE-STEMI (NCT01572909)
What they were measuring and why:
- When a heart attack happens, a blood clot blocks an artery and starves part of the heart of oxygen. Doctors rush to reopen the artery, but the sudden flood of blood back into starved tissue can cause extra damage.
- This study tested whether SS-31 could act as a protective shield
- IV infusion of 0.05 mg/kg/hr for 1 hour, started before the artery was reopened during primary PCI.
- This study did not show a clear benefit. The drug failed to significantly reduce heart damage
- MTP-131 also did not improve prespecified MRI, angiographic, ECG, or clinical outcomes.
- Exploratory analyses suggested possible signals for fewer early heart-failure events, but these were not prespecified or definitive.
Study 4: A Month of Daily Shots for Weak Muscles — MMPOWER Crossover (NCT02805790)
What they were measuring and why:
- Testing whether a month of treatment could help people with mitochondrial myopathy walk farther and feel less tired.
- Because it used a crossover design, each person served as their own comparison — like being your own “before and after” photo.
- 40 mg injected under the skin once daily for 4 weeks, with a 4-week washout period between treatment and placebo phases.
- Participants walked farther, difference of 19.8 m (the length of a standard bowling lane), but this did not reach statistical significance.
- Fatigue outcomes looked more encouraging: Neuro-QoL Fatigue improved by about 4 points vs placebo, and PMMSA fatigue-related scores also improved significantly. Patient and physician global assessments also favored SS-31.
- However, this was a small crossover study with only 30 participants, lasted just 4 weeks per treatment phase.
Study 5: Recharging Boys with Barth Syndrome — TAZPOWER (NCT03098797)
What they were measuring and why: Barth Syndrome is a rare genetic disorder that only affects boys, causing weak muscles, fatigue, and heart problems because their mitochondria can’t work properly. The study measured walking endurance, muscle strength, balance, and fatigue.
Dosing: 40 mg injected under the skin once daily for 12 weeks in the crossover phase, then up to 192 weeks in the open-label extension.
Practical outcomes:
- During the 12-week blinded crossover phase, SS-31 did not beat placebo. Walking distance was essentially identical, about 443.1 m on SS-31 vs. 443.9 m on placebo, and fatigue scores were also nearly unchanged.
- In the open-label extension (all participants knew they were receiving active drug) found significant improvement in 6-minute walk distance, with a cumulative 96.1 m improvement at week 168, along with improved fatigue scores and cardiac measures.
- However, because the extension had no placebo group and involved only 8 participants, it is impossible to know how much of the improvement came from SS-31 versus growth, training effects, placebo effects, regression to the mean, or other factors.
Study 6: Helping a Tired Heart Pump Better — Heart Failure (NCT02788747)
What they were measuring and why: In heart failure with reduced ejection fraction, the heart muscle is like a squeeze bottle that’s lost its squeezing power. The researchers tested two SS-31 doses to see if they could make the squeeze bottle work better.
Dosing: Either 4 mg or 40 mg injected under the skin once daily for 28 days.
Practical outcomes:
- The drug did not clearly outperform placebo on the main measure
- Heart pumping efficiency (ejection fraction) improved slightly in both drug groups (2.2% for 4 mg, 1.5% for 40 mg) but this was not dramatically different from placebo.
Study 7: The Big Test That Failed — MMPOWER-3 Phase 3 (NCT03323749)
What they were measuring and why: This was the largest and most rigorous test of SS-31 for mitochondrial myopathy — the “final exam” meant to prove the drug worked well enough for regulatory approval. It measured walking distance and fatigue in 218 patients across 27 sites in 7 countries.
Dosing: 40 mg injected under the skin once daily for 24 weeks.
Practical outcomes:
- The drug failed its major phase 3 test. At week 24, SS-31 did not outperform placebo 6-minute walk distance or PMMSA Total Fatigue Score.
- The placebo group improved slightly more on walking distance, and fatigue scores were essentially indistinguishable. Earlier numerical walking improvements at weeks 4 and 12 did not translate into a significant week-24 benefit.
Study 8: The Long Road — Open-Label Extension for Mitochondrial Myopathy (NCT02976038)
What they were measuring and why: This study offered patients from a previous trial the chance to keep taking SS-31 long-term, mainly to track safety over years of use. It also measured walking distance, fatigue, and quality of life.
Dosing: 40 mg injected subcutaneously once daily for up to 260 weeks.
Practical outcomes:
- The picture was mixed and hard to interpret. Early open-label data suggested patients maintained 6-minute walk distance over 12 months while reporting improvements in fatigue and quality-of-life measures.
- However, longer-term registry results appear less encouraging for walking distance, with decline from baseline by later time points. Fatigue and some patient-reported outcomes showed improvement, but without a control group, these subjective changes could reflect placebo effects, adaptation, survivorship bias, or changes in expectations rather than a true drug effect.
- The study was terminated early after the larger registration trial failed its primary endpoints, so participants did not complete the full planned 260-week treatment period.
Verdict
- To me, results seem unremarkable.
- And even if you take a positive interpretation of the results, the cost to use these dosages would be astronomical. The most common dosage was 40mg per day.
What do you think?
