Potential Interventions
1 Mitochondrial Support
1.1 Cofactors and Substrates
Supporting mitochondrial function may help:
- Coenzyme Q10: Electron carrier in ETC; antioxidant
- L-carnitine/acetyl-L-carnitine: Fatty acid transport; neuroprotection
- B vitamins: Cofactors for multiple metabolic enzymes
- Magnesium: Required for ATP utilization
- D-ribose: Substrate for ATP synthesis
- Alpha-lipoic acid: Antioxidant; mitochondrial cofactor
1.2 Mitochondrial-Targeted Therapies
Emerging approaches target mitochondria specifically:
- MitoQ: Mitochondria-targeted antioxidant
- SS-31 (Elamipretide): Cardiolipin-binding peptide
- Nicotinamide riboside: NAD+ precursor
- Urolithin A: Promotes mitophagy
2 Antioxidants
2.1 Glutathione Support
Restoring glutathione may be beneficial:
- N-acetylcysteine (NAC): Provides cysteine for glutathione synthesis (a dose-response trial using brain MRS is underway; see Appendix Ongoing and Planned ME/CFS Research Studies, Section Clinical Trials (Interventional))
- Liposomal glutathione: May improve absorption
- Glycine supplementation: Second rate-limiting substrate
- Selenium: Required for glutathione peroxidase
2.2 Other Antioxidants
- Vitamin C: Water-soluble antioxidant; cofactor for catecholamine synthesis
- Vitamin E: Fat-soluble membrane antioxidant
- Polyphenols: Plant-derived antioxidants (resveratrol, quercetin)
- Melatonin: Potent antioxidant with mitochondrial effects
3 Addressing Catecholamine Deficiency
3.1 Precursor Support
Supporting neurotransmitter synthesis:
- Tyrosine: Catecholamine precursor
- Phenylalanine: Converted to tyrosine
- BH4 support: Sapropterin or folate to support BH4 recycling
- Cofactors: Iron, B6, vitamin C, copper
3.2 Pharmacological Approaches
Medications affecting catecholamine systems:
- Stimulants: Methylphenidate, amphetamines (increase catecholamine release)
- Bupropion: Norepinephrine-dopamine reuptake inhibitor
- SNRIs: Serotonin-norepinephrine reuptake inhibitors
- MAO-B inhibitors: Reduce dopamine breakdown