Cardiac Mitochondrial Support Protocol (SS-31 focused)

Improve cardiac mitochondrial function, reduce oxidative stress in cardiomyocytes, support heart failure management, and enhance exercise capacity in patients with documented cardiac mitochondrial impairment.

Patient profile: Adults with heart failure (HFrEF or HFpEF), age-related cardiac decline, or post-cardiac surgery recovery. Must be under active cardiological supervision. Not for primary prevention in healthy individuals.

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⚠️

This protocol is an educational example only. It does not apply to your specific health situation. Medical supervision is required. Peptide therapy is not approved by regulatory bodies for many of the described indications.

Protocol Stack

SS-31 (Elamipretide)

Primary

Dose

2–4 mg

Frequency

Daily

Timing

Morning SC injection; start at 2 mg, increase to 4 mg at week 4 if tolerated

Duration

16 weeks; assess continuation based on echocardiographic response

MOTS-c

Supporting

Dose

5 mg

Frequency

2× per week

Timing

Before supervised cardiac rehabilitation exercise sessions

Duration

Weeks 4–16 (introduce after SS-31 tolerance established)

Thymosin Alpha-1

Optional

Dose

1.6 mg

Frequency

2× per week

Timing

Any time, SC

Duration

12 weeks (weeks 4–16)

Monitoring Parameters

✓Mandatory baseline: echocardiography (LVEF, LVEDV, E/e'), BNP or NT-proBNP, 6-minute walk test, VO2max
✓Week 4: NT-proBNP, 6MWT, symptoms review, HR and BP assessment
✓Week 8: echocardiography repeat, NT-proBNP, full metabolic panel
✓Week 16: full repeat of baseline panel; decision on continuation
✓Continuous: daily resting HR and BP monitoring (patient self-report); report any new arrhythmia immediately
✓Safety: renal function (eGFR) at baseline and week 8 — SS-31 studied in renal ischaemia; dose adjustment if eGFR <30

Expected Outcomes

Weeks 1–4: improved symptom scores (NYHA class, fatigue); initial NT-proBNP reduction

Weeks 4–8: 6MWT improvement of 30–60 m (consistent with Phase 2 STELR trial data for SS-31)

Weeks 8–16: echocardiographic improvement in diastolic parameters (E/e' ratio); subjective exercise tolerance normalisation

Long-term: slowing of cardiac remodelling progression; SS-31 effects on inner mitochondrial membrane may be durable

Contraindications

✗Active decompensated heart failure (hospitalisation, IV diuretics) — stabilise first
✗Severe renal impairment (eGFR <15) — dose adjustment mandatory; consult nephrologist
✗Active malignancy — Thymosin Alpha-1 is immune-activating
✗Pregnancy
✗No cardiological supervision — this protocol must not be used without specialist oversight

Clinical Notes

SS-31 is the most clinically validated mitochondrial peptide, with Phase 2 RCT data (STELR trial, Barth syndrome trials) supporting its use in cardiac mitochondrial dysfunction. This protocol is designed as adjunctive therapy alongside standard-of-care heart failure treatment (ACEi/ARB/ARNI, beta-blockers, MRA, SGLT2i). It does not replace guideline-directed medical therapy. MOTS-c is added as a supporting agent for its complementary AMPK activation and skeletal muscle benefits during cardiac rehabilitation. Cardiological co-management is non-negotiable.

Case Study

Clinical Practice Example

Male, 67, HFrEF (LVEF 32%), on optimal medical therapy (carvedilol, sacubitril/valsartan, eplerenone, dapagliflozin), stable for 8 months but persistently symptomatic (NYHA class III, 6MWT 280 m, NT-proBNP 1,840 pg/mL). Added SS-31 2 mg/day SC; MOTS-c 5 mg 2×/week added at week 4. Week 16 assessment: 6MWT improved to 356 m (+76 m); NT-proBNP reduced to 1,210 pg/mL; NYHA downgraded to class II. Repeat echo showed E/e' improved from 18 to 13. Patient reported resuming walking 3 km daily without dyspnoea.

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