TABLE 2.

Summary of direction of glycaemic control, cardiovascular health, and oxidative stress impacts in included studies (mitoAOX vs. control)

	MitoAOX agent	Health condition	Sample size (n)	Acute/ chronic (n days)	Dosage	Glycaemic control outcomes	Cardiovascular health‐related outcomes						Oxidative stress‐related outcomes	Reference
							Blood pressure	Cardiac measure	Marker of cardiac function	Endothelial/vascular function	Functional/patient‐important measure	Lipids
Studies in patients with health conditions	Elamipretide	Heart failure	71	Chronic (28 d)	4 mg × once daily	n/a	n/a	↔ a , ↓ b	↔ c	n/a	↔ c	n/a	n/a	16
					40 mg × once daily	n/a	n/a	↔ c	↔ c	n/a	↔ c	n/a	n/a
		Heart failure	306	Chronic (7 d)	20 mg × once daily	n/a	n/a	n/a	↔ c	n/a	↔ c	n/a	n/a	22
		Heart failure	36	Acute	0.005 mg/kg/h	n/a	↔ c	↔ c	↔ c	n/a	n/a	n/a	↔ c	23
					0.05 mg/kg/h	n/a	↔ c	↔ a , ↓ d	↔ c	n/a	n/a	n/a	↔ c
					0.25 mg/kg/h	n/a	↔ c	↓ e	↔ c	n/a	n/a	n/a	↔ c
		Renovascular hypertension	14	Acute	0.05 mg/kg/h	n/a	↓ f	n/a	n/a	n/a	n/a	n/a	n/a	24
		STEMI	118	Acute	0.05 mg/kg/h	n/a	n/a	↔ c	↔ c	n/a	↔ c	n/a	n/a	26
		Primary mitochondrial myopathies	30	Chronic (28 d)	40 mg × once daily	n/a	n/a	n/a	n/a	n/a	↓ g	n/a	↔ c	27
		Primary mitochondrial myopathies	36	Chronic (2 h/d for 5 d)	0.01 mg/kg/h	n/a	n/a	n/a	n/a	n/a	↔ c	n/a	↔ c	17
					0.1 mg/kg/h	n/a	n/a	n/a	n/a	n/a	↔ c	n/a	↔ c
					0.25 mg/kg/h	n/a	n/a	n/a	n/a	n/a	↑ h	n/a	↔ c
		Barth syndrome	12	Chronic (84 d)	40 mg × once daily	n/a	n/a	n/a	n/a	n/a	↔ i	n/a	n/a	32
		Severe atherosclerotic renal artery stenosis	14	Acute	0.05 mg/kg/h	n/a	↓ f	n/a	n/a	n/a	n/a	n/a	n/a	34
		Heart failure	47	Chronic (28 d)	40 mg × once daily	n/a	n/a	↔ c	↔ c	n/a	↔ c	n/a	n/a	36
	MitoQ	Chronic HCV infection	30	Chronic (28 d)	40 mg × once daily	↔ c	n/a	n/a	n/a	n/a	n/a	↔ c	n/a	25
					80 mg × once daily	↔ c	n/a	n/a	n/a	n/a	n/a	↔ c	n/a
		Stage 3‐5 CKD	18	Chronic (28 d)	20 mg × once daily	n/a	↔ c	n/a	n/a	↑ j	n/a	n/a	n/a	29
		Peripheral artery disease	11	Acute	80 mg	n/a	↔ c	n/a	n/a	↑ k	↑ l	n/a	↔ a , ↑ m	30
	MitoTEMPO	CKD	20	Acute	1 mM	n/a	n/a	n/a	n/a	↑ n	n/a	n/a	n/a	28
Studies in healthy participants	MitoQ	‐	22	Chronic (28 d)	20 mg × once daily	↔ c	n/a	n/a	n/a	n/a	↔ c	↔ c	↓ o	19
		‐	20	Chronic (42 d)	20 × mg × once daily	↔ c	↔ c	n/a	↔ c	n/a	n/a	↔ c	↔ a , ↓ p	31
		‐	20	Chronic (42 d)	20 × mg × once daily	↔ c	↔ c	n/a	↔ c	↑ q	n/a	↔ c	↓ r	33
		‐	20	Chronic (21 d)	10 × mg × once daily	n/a	n/a	n/a	n/a	n/a	↔ c	n/a	↔ c	35
		‐	24	Acute	20 mg	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↔ c	37
		‐	24	Chronic (21 d)	20 × mg once daily	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↔ s
	MitoTEMPO	‐	11	Acute	1 mM	n/a	n/a	n/a	n/a	↔ c	n/a	n/a	n/a	28

Note: ↔, no statistically significant change in measured outcomes; ↑, statistically significant increase in measured outcomes; ↓, statistically significant decrease in measured outcomes.

Abbreviations: CKD, chronic kidney disease; FMD, flow‐mediated dilation; HCV, hepatitis C virus; mitoAOX, mitochondrial‐targeted antioxidant; n/a, not assessed; Neuro‐QoL, Quality of Life in Neurological Disorders; PMMSA, Primary Mitochondrial Myopathy Symptom Assessment; RCT, randomized controlled trial; ROS, reactive oxygen species; STEMI, ST‐elevation myocardial infarction.

^a No changes for most outcomes assessed, but with exceptions.

^b Left atrial volume.

^c No changes for all outcomes assessed.

^d Right systolic ventricle pressure.

^e Left ventricle end systolic volume and left ventricle end diastolic volume.

^f Systolic blood pressure change within mitoAOX group only.

^g PMMSA Total Fatigue score, PMMSA Fatigue During Activities score, patient global assessment and Neuro‐QoL Fatigue Short Form.

^h 6‐min walk test distance, when using an adjusted statistical model.

ⁱ No changes in part 1 of study (RCT), but improvements in numerous functional/patient‐important outcomes in part 2 of study (non‐controlled, open‐label trial).

^j Central pressure waveforms (forward) and brachial FMD.

^k Brachial FMD and popliteal FMD.

^l Maximal walking distance, maximum walking time and time to onset of claudication.

^m Plasma superoxide dismutase.

ⁿ Plateau phase of cutaneous vascular conductance.

^o Plasma F₂‐Isoprostanes.

^p Skeletal muscle H₂O₂ in Complex I and Complex II leak after addition of oligomycin (Leak_o state) within mitoAOX group only.

^q Brachial FMD, FMD associated with amelioration of mitochondrial ROS‐related suppression of endothelial function (assessed as the increase in FMD with acute, supratherapeutic MitoQ [160 mg] and carotid‐femoral pulse‐wave velocity in participants with elevated baseline carotid‐femoral pulse wave velocity levels.

^r Plasma LDL oxidation.

^s No changes in oxidative stress markers/antioxidants, although exercise‐induced nuclear and mitochondrial DNA damage was decreased in lymphocytes and muscle following mitoAOX supplementation.