Understand the source comparison
Research Peptides for Chronic Fatigue: Evidence Comparison
MOTS-C Mitochondrial transcription upregulation, increases ATP synthesis 30–40% Cell Metabolism 2021: improved glucose uptake 35%, reduced lactate during exertion Yes. Mitochondrial adaptations persist 8+ weeks after dosing stops Preclinical to early Phase II
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- MOTS-C
- Mitochondrial transcription upregulation, increases ATP synthesis 30–40%
- Cell Metabolism 2021: improved glucose uptake 35%, reduced lactate during exertion
- Yes. Mitochondrial adaptations persist 8+ weeks after dosing stops
- Preclinical to early Phase II
- Strongest mechanistic rationale for primary mitochondrial dysfunction. Targets cause not symptoms
- Humanin
- Mitochondrial membrane stabilisation, cardiolipin binding
- USC study: reduced oxidative stress 40–50% in aging models with mitochondrial dysfunction
- Likely. Membrane structural changes maintain after treatment
- Preclinical, some human observational data
- Best candidate for fatigue with cognitive/neurological components due to neuronal mitochondrial protection
- SS-31 (Elamipretide)
- ROS scavenging at inner mitochondrial membrane
- JAMA Neurology: +25m six-minute walk test in mitochondrial myopathy, functional fatigue improvement
- Unknown. Limited long-term follow-up data
- Phase II/III for mitochondrial diseases
- Only peptide with functional capacity data (walk distance) correlating to subjective fatigue reduction
- GHRP-2 / Ipamorelin
- GH secretagogue, pulsatile GH release via ghrelin receptor
- Transient GH increase 200–400%, early subjective energy improvement 2–4 weeks
- No. Receptor downregulation by week 10–16 requires dose escalation
- Widely studied, off-label use common
- Useful for catabolic fatigue states (illness recovery, sarcopenia), ineffective for primary mitochondrial dysfunction
- MK-677
- Sustained ghrelin receptor activation, chronic IGF-1 elevation 40–90%
- Improved lean mass/bone density in elderly, inconsistent fatigue score correlation with IGF-1 levels
- No. Effects cease when dosing stops
- Phase II completed, not FDA-approved for fatigue
- Best GH-pathway option for convenience (oral dosing), but fatigue benefits don't track reliably with anabolic markers
- Semax
- BDNF modulation, neuronal metabolic resilience
- Russian trials: improved cognition under sleep deprivation/hypoxia (neuroenergetic stress models)
- Unknown. Synaptic changes may persist, but evidence limited
- Approved in Russia, investigational elsewhere
- Strongest option specifically for cognitive fatigue component. Addresses CNS energy deficit independent of peripheral metabolism