SS-31

Also known as: Bendavia; Elamipretide; MTP131

Overview

SS-31 is a mitochondria-targeting tetrapeptide that binds cardiolipin to stabilize mitochondrial membranes, reduce oxidative stress, and enhance ATP synthesis. It supports neuro-, cardio-, and nephro-protection.

Benefits

- Mitochondrial enhancement

- Anti-inflammatory

- Heart protection

- Brain health

- Kidney protection

- Anti-aging support

Consider This Peptide If You Want To

- Boost mitochondrial performance

- Support neurological and cardiovascular recovery

Dosage & Administration

Dosage Guidelines

Recommended Dosage

• Amount:5 mg

• Frequency:weekdays

• Duration:6 weeks

• Rest Period:8 weeks

• Time of Day:morning

• Ingestion:subcutaneous

Administration Routes:Subcutaneous

Research Findings on Dosage:

Subcutaneous Injection

• Commonly Reported Dosage: 5 mg subcutaneous injection (50 units) daily, titrating to 10 mg/day as tolerated. May dose as high as 40 mg per day depending on the application

• [5 days on, two days off]{.mark}

• Duration: Administer daily for at least 10 days, longer for advanced mitochondrial repair.

Mechanism of Action

Mechanism of Action

How this peptide works in the body

Cardiolipin Binding:

SS-31 selectively binds to cardiolipin, a phospholipid unique to the inner mitochondrial membrane (IMM), stabilizing mitochondrial cristae and preventing cytochrome c dissociation. This preserves mitochondrial integrity and inhibits apoptotic cascade activation, reducing cell death in energy-demanding tissues.

Electron Transport Chain Optimization:

By stabilizing cardiolipin, SS-31 enhances electron flow through complex I and complex III of the electron transport chain (ETC), reducing electron leakage and minimizing reactive oxygen species (ROS) production. This improves proton gradient efficiency, leading to enhanced ATP synthesis via ATP synthase, optimizing cellular energy availability.

Oxidative Stress Reduction:

SS-31 directly scavenges superoxide (O₂⁻) and hydroxyl radicals (OH•), preventing lipid peroxidation and mitochondrial DNA (mtDNA) damage. Additionally, it upregulates endogenous antioxidant defense mechanisms by activating superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), reducing oxidative stress at the mitochondrial level.

Anti-Inflammatory Effects:

SS-31 suppresses nuclear factor kappa B (NF-κB) activation, downregulating pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β). This dampens chronic inflammation, protecting against mitochondrial dysfunction-driven inflammatory diseases like neurodegeneration and cardiovascular disorders.

Mitochondrial Biogenesis:

SS-31 promotes mitochondrial biogenesis by activating peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and nuclear respiratory factor 1 (NRF1). This upregulates mitochondrial transcription factor A (TFAM), stimulating mitochondrial DNA replication and promoting the formation of new, functionally efficient mitochondria.

Consider Stacking With

- Any GHRP

- Any GHRH

- BPC-157

- TB-4

- MOTS-c

- ARA-290

- 5-Amino-1MQ

Side Effects & Cautions

Common Side Effects

- Injection site redness/swelling

- Abdominal pain

- Dizziness

- Headache

Research & References

Research Highlights

Mitochondrial Disorders:

SS-31 improves ATP production and mitochondrial health in primary mitochondrial myopathies. (Neurology, 2023)

Cardioprotection:

Demonstrated efficacy in reducing ischemic damage in human and animal models. (J Am Soc Nephrol, 2013)

Neurodegeneration:

Shown to reduce mitochondrial oxidative stress in Alzheimer's models, improving cognitive function and neuronal survival. (Front Aging Neurosci, 2021)

Kidney Disease:

Alleviated renal mitochondrial dysfunction and reduced oxidative damage in preclinical studies. (Oxid Med Cell Longev, 2022)

References

Karaa A., et al. "Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial." Neurology. 2023; 101

Liu Y., et al. "Elamipretide improves hippocampal connectivity following prolonged neuroinflammation in aged rats." Front Aging Neurosci. 2021;13:600484

Zhu Y., et al. "SS-31 ameliorates kidney disease." Oxid Med Cell Longev. 2022;2022:1295509

Birk A., et al. "SS-31 reenergizes ischemic mitochondria." J Am Soc Nephrol. 2013;24(8):1250-1261

Smuder A.J., et al. "SS-31 prevents cancer-induced cardiorespiratory muscle weakness." Oncotarget.2020;11:3502-3514