Table 1.

Key papers for ME/CFS patient studies.

Activity	Reference	Finding	Therapeutic Investigated	Cell Type/Tissue Investigated
Mitochondrial metabolic pathways	Fluge et al 2016100	Impaired pyruvate dehydrogenase, consistent with inadequate ATP production, excessive lactate on exertion	NA	PBMCs
Metabolic response to exercise	Brown et al 2015101	Impaired AMP kinase activation, glucose uptake	NA	Skeletal muscle cells
Cellular metabolism	Naviaux et al 201623	Reduced metabolites in 20 biochemical pathways consistent with hypometabolic syndrome	NA	Plasma
Mitochondrial metabolism	Comhaire et al 201852	Reduction in fatigue severity consistent with existing mitochondrial hypometabolism and impaired pyruvate dehydrogenase	Sodium Dichloroacetate (Oral administration)	NA
Mitochondrial metabolism	Forsyth et al 199953	31% of patients had a positive reaction to NADH	NADH (Oral administration ENADA)	NA
Cellular energy synthesis	Teitelbaum et al 200650	Improvement in energy, sleep, mental clarity, pain intensity and well-being	d-ribose (Oral administration)	NA
Cellular stress, Inflammation	Sweetman et al 2019102	Transcriptome -changes in stress, inflammation pathways, metabolic regulation, mitochondrial function, and circadian clock.	NA	PBMCs
Metabolic, Immune and Neurological	Helliwell et al 2020103	Changes in DNA methylation indicate abnormal immune, neurological and metabolic functions	NA	PBMCs
Oxidative stress	Jammes et al 2005104	Incremental exercise resulted in oxidative stress with alterations in muscle membrane	NA	Blood samples
Mitochondrial stress	Tomas et al 201721	Lower maximal respiration indicating inability to compensate for stress	NA	PBMCs
Mitochondrial ATP production	Lawson et al 201634	Increased cristae density in patients. Increased ATP from non-mitochondrial sources	NA	PBMCs
Mitochondrial ATP production	Missailidis et al 202022	Complex V inefficiency in ATP production	NA	Immortalised lymphocytes
Mitochondrial complex activity	Tomas et al 201932	No observed differences in mitochondrial complex activity	NA	PBMCs, skeletal muscle cells
Mitochondrial Complexes, ATP production and oxidative stress	Sweetman et al 20208	Disturbances in proteins of (a) mitochondrial complexes I & V, (b) regulating reactive oxygen species, and in mitochondrial pathways	NA	PBMCs
CoQ10	Maes et al 200976	Deficiency in CoQ10 in patient group correlating with symptom severity	CoQ10	Plasma
CoQ10	Castro-Marrero et al 201548	Improvement in fatigue levels and biochemical parameters (NAD+, CoQ10, ATP, citrate synthase and lipoperoxides)	CoQ10 (Oral supplementation)
CoQ10/MitoQ	Wood 202078	An association of CoQ10 levels with mitochondrial function, enhanced by supplementation of cells with exogenous C0Q10. Supplementation of MitoQ orally improved bioenergetic profiles of a subject.	CoQ10 MitoQ (oral supplementation)	PBMCs,
∗MitoQ	Kelso et al 200187	MitoQ protects mitochondria from hydrogen peroxide-induced apoptosis	MitoQ	Human osteosarcoma cells
∗MitoQ	James et al 200579	MitoQ10 was an effective antioxidant against lipid peroxidation, peroxynitrite and superoxide.	MitoQ	Rat heart mitochondria

^∗Non-patient studies showing MitoQ is a powerful antioxidant in mitochondria. PBMC: Peripheral blood mononuclear cell; NA: Not applicable; NADH: Reduced nicotinamide adenine dinucleotide; CoQ10: Coenzyme Q10.