Each review contains information about the ingredient’s clinical applications, formulations, dosing & administration, adverse effects, and pharmacokinetics. Learn more about our critical appraisal research or contact us for initial guidance and more information.

Coenzyme Q10 (CoQ10)

Coenzyme Q10 (CoQ10), otherwise known as ubiquinone, is a fat-soluble, non-essential nutrient that plays an important role in free radical scavenging and mitochondrial synthesis of ATP via the electron transport chain. Due to its involvement in energy production and in the reduction of oxidative stress, CoQ10 has been increasingly regarded for its anti-aging properties. (38) The human body stores between 0.5 to 1.5 g of CoQ10 and can synthesize it from tyrosine. (7)(19) CoQ10 continuously interconverts between its oxidized (ubiquinone) and reduced (ubiquinol) state to provide antioxidation and act as a electron-transporting cofactor in the production of energy. While cellular levels are typically stable, several factors may lead to CoQ10 deficiencies, including aging, genetic mutations, several conditions such as cardiomyopathies, fibromyalgia, and liver cirrhosis, and the use of pharmaceutical agents such as statins. (38)

CoQ10 supplements can be derived from living tissues or synthesized by bacteria. Bacterial synthesis of CoQ10 appears to provide several manufacturing advantages, including being more economically and environmentally viable. (7)(28)(29)(172)

Main uses

Antioxidation, anti-inflammation, and pain
Cardioprotection and cardiac function
Exercise tolerance and performance
Fatigue and depression
Fertility
Glucose and lipid modulation

Formulations

Form	Characteristics
Ubiquinone	This is the most widely available form in dietary supplements (vs. ubiquinol) and usually found in gel capsules containing a carrier lipid (e.g., soy oil, medium-chain triglycerides, etc.) since CoQ10 is a lipid-soluble molecule. (91) Water-soluble formulations (see below) can increase bioavailability compared to standard oil-based softgels. (163) They may also eliminate the need to ingest CoQ10 with meals since the use of a water-soluble formulation during a fasted state is equally as bioavailable as an oil-based formulation when administered with food. (111) Product labels may indicate that the CoQ10 was derived from fermentation, which simply means that it was manufactured using yeast (producing a bioidentical form to what is naturally produced by the body), as opposed to being produced through isolation from animal tissues. (91)
Ubiquinol	As the majority of absorbed CoQ10 is converted to ubiquinol prior to circulation in the blood, manufacturers have theorized that ubiquinol may be a more bioavailable source of CoQ10. (91) Ubiquinol has been shown to have up to ~2-3 times higher bioavailability than ubiquinone. (45)(78)(80)(87)(179)This suggests that lower doses of ubiquinol could be used to achieve the same effect as higher doses of ubiquinone. Kaneka is currently the world’s sole manufacturer of ubiquinol.
Cyclodextrin (usually found as an additional ingredient)	Increases CoQ10’s water-solubility and improves its stability (7) Increased ubiquinone’s bioavailability 2.4-fold compared to standard CoQ10 and was equivalent to ubiquinol (116) Increased ubiquinone’s bioavailability of a liquid and powdered formulation by 120% and 79%, respectively, compared to a standard oil-based gel capsule (183)
Liquid oil-based emulsions	Increased CoQ10 bioavailability ~5-fold compared to encapsulated CoQ10 powder (93)
Polysorbate nano- encapsulation	Increases CoQ10’s water-solubility Increased bioavailability ~6-fold compared to standard oil-based formulation (86)
Piperine	Increased CoQ10 bioavailability by 30% compared to a standard gel capsule (10)
Sustained- release formulation	Timed-release formulations (95) may increase bioavailability (though results were not statistically significant). (89)

Dosing & administration

Anti-oxidation
General outcomes from A-level evidence	↓ malondialdehyde (large effect, d= 0.94-1.12) ↑ total antioxidative capacity (moderate to large effect, d= 0.67-1.29), superoxide dismutase activity (small-moderate effect, d= 0.4-0.63), (2) & levels of glutathione peroxidase (small effect, d= 0.45) and catalase (large effect, d= 1.67) (136) Note: No effect on nitric oxide, glutathione, catalase, or glutathione peroxidase activity (2)
Dosing & administration	100 mg per day for at least two months to Px with various chronic diseases
Outcomes	↑ total antioxidative capacity (large effect, d= 1.5), glutathione peroxidase (small effect, d= 0.48), catalase (moderate effect, d= 0.78) & superoxide dismutase activity (moderate effect, d= 0.69) ↓ malondialdehyde (large effect, d= 1.3) (136)
Class of evidence	A
Dosing & administration	200 mg per day (as ubiquinol) for 2-4 weeks to trained individuals undergoing strenuous exercise
Outcomes	Modulated exercise induced oxidative stress and inflammation by protecting against changes via: ↑ total antioxidant status, fat soluble antioxidant, & catalase activity ↓ isoprostanes, 8-OHdG, oxidized LDL, hydroperoxides, and MCP-1 (39)(140) Prevented exercise-induced reductions in CoQ10 status and paraoxonase activity, & was associated with ~35% reduction in post-exercise intracellular ROS (114)
Class of evidence	B
Dosing & administration	100 mg twice per day for 20 days to healthy Px
Outcomes	↓ MDA (~30%) compared to placebo (150)
Class of evidence	B
Dosing & administration	1,200 mg per day for four months to Px on maintenance hemodialysis
Outcomes	↓ F2-isoprostanes (24%) compared to baseline with effects within two months of administration (120)
Class of evidence	B
Dosing & administration	300 mg per day for 2-3 weeks to trained athletes
Outcomes	↓ various indices of myocardial, muscle, and liver damage, & oxidative stress caused by exercise ↑ total antioxidative capacity and CoQ10 levels Prevented exercise-induced changes to SOD, CAT, & GPx (42)(43)(44)(77)
Class of evidence	C
Dosing & administration	100 mg per day for eight weeks to healthy and sedentary males participating in exercise tests
Outcomes	Prevented rises in lipid peroxidation (MDA) induced by exercise (58)
Class of evidence	C

Autism spectrum disorder
General outcomes from A-level evidence	No data currently available.
Dosing & administration	30 mg twice per day for three months to children with autism spectrum disorder
Outcomes	↑ total antioxidative status ↓ GPx and SOD activity, & MDA Note: associated with improvement in GI and sleep issues (105)
Class of evidence	B

Bipolar disorder
General outcomes from A-level evidence	No data currently available.
Dosing & administration	200 mg per day for eight weeks as adjuvant therapy to Px with bipolar disorders
Outcomes	↓ depression score (MADRS) with large effect vs. small effect caused by placebo ↑ ~19x odds of response compared to placebo (99)
Class of evidence	B

Cardiac surgery complications
General outcomes from A-level evidence	↓ odds of postoperative ventricular arrhythmia (95%) & need for inotropic drugs (53%) Note: no association with post-operative cardiac index, hospital stay duration, or incidence of atrial fibrillation was observed (34)
Dosing & administration	300-400 mg per day for two weeks (starting at minimum three days) prior to vascular surgery
Outcomes	↓ rises in NT-Pro BNP (a biomarker of ventricular dysfunction) post-surgery, which may have led to lower incidence of myocardial injury (by 38% comparing high vs. low NT-Pro BNP levels) and duration of hospital stay (75) ↓ mitochondrial MDA (44%) ↑ mitochondrial respiration efficiency & trabecular function (measured by recovered force) (18%) compared to placebo (125)
Class of evidence	B
Dosing & administration	20 mg three times per day starting two days prior to coronary angiography and three days post-surgery as an adjunct to trimetazidine to Px with coronary artery disease and renal insufficiency
Outcomes	↓ incidence of postoperative contrast-induced nephropathy (~14%) compared to placebo (26)
Class of evidence	B
Dosing & administration	50 mg three times per day for seven days prior to surgery
Outcomes	May have protected against reperfusion injury by preventing rises in MDA, conjugated dienes, creatine kinase, and lactate dehydrogenase during reperfusion, & reduced grade of postoperative ventricular arrhythmias (24)(25)
Class of evidence	B

Chronic kidney disease
General outcomes from A-level evidence	↓ total cholesterol (moderate effect, d= 0.58), LDL-C (small effect, d= 0.47), malondialdehyde (large effect, d= 3.0), & creatinine (large effect, d= 1.65) (12) Note: no effect was observed for FBG, insulin, HOMA-IR, & CRP (12)
Dosing & administration	60 mg (as water-soluble formulation) three times per day for 1-3e months to Px with end-stage renal failure
Outcomes	↓ proportion of Px on dialysis (40-50%), creatinine, urea, thiobarbituric acid reactive substances, diene conjugates, & MDA ↑ creatinine clearance & urine output (146)(147)
Class of evidence	C

Coronary artery disease
General outcomes from A-level evidence	↓ total cholesterol (large effect, d= 1.07), (71) malondialdehyde (large effect, d= 4.29), & conjugated diene (large effect, d = 2.4) (70) ↑ HDL-C (large effect, d= 1.3), (71) superoxide dismutase (large effect, d= 2.63), & catalase (large effect, d= 2.63) (70) Note: there may not be an effect on LDL-C, lipoprotein(a), TGs, (71) CRP, TNF-ɑ, IL-6, or glutathione peroxidase, (70) and some evidence argues that CoQ10 may not be supported in coronary heart disease (9)
Dosing & administration	Up to 150 mg per day for eight weeks to Px with coronary artery disease
Outcomes	↓ total cholesterol with large effect (d= 1.07) ↑ HDL-C with large effect (d= 1.30) (71)
Class of evidence	A
Dosing & administration	150 mg once or twice per day for 12 weeks to Px with coronary artery disease
Outcomes	↓ IL-6 compared to baseline & TNF-ɑ and MDA compared to placebo ↑ catalase, SOD, & GPx activity compared to placebo (81)(82)(83)
Class of evidence	B
Dosing & administration	60 mg (water-soluble formulation) twice per day for 4-8 weeks to Px with coronary artery disease
Outcomes	↓ heart rate (20 bpm), SBP (11.6 mmHg), DBP (9.57 mmHg), insulin (39%), FBG (2.2-34.6 mg/dL), TGs (27.5 mg/dL), lipoprotein(a) (23%), TBARS (51-56%), MDA (44-83%), & diene conjugate (19%) ↑ HDL-C (0.1 mmol/L) (149)(151)
Class of evidence	C

Dermal anti-aging
General outcomes from A-level evidence	No data currently available.
Dosing & administration	50-150 mg (as water-soluble liquid) per day for 12 weeks to healthy women with signs of skin aging
Outcomes	Improved wrinkles, microrelief lines, and skin smoothness, & prevented seasonal reductions in skin viscoelasticity (184)
Class of evidence	C

Diabetic kidney disease
General outcomes from A-level evidence	↓ FBG (large effect, d= 2.04), total cholesterol (large effect, d= 1.73), TGs (small effect, d= 0.39), & malondialdehyde (large effect. d= 1.29) ↑ HDL-C (small effect, d = 0.09) Note: no effect on HBA1C, LDL-C, or urea levels (178)
Dosing & administration	100 mg per day for 12 weeks to Px with diabetic nephropathy
Outcomes	↓ insulin, insulin resistance, HOMA-B, HbA1C, MDA, AGEs, & expression of IL-1 and TNF-ɑ genes ↑ insulin sensitivity & PPAR-y gene expression (55)(60)
Class of evidence	B
Dosing & administration	60 mg twice per day for 12 weeks to Px with diabetes on hemodialysis
Outcomes	↓ insulin (16%) & insulin resistance (18%) (46)
Class of evidence	B

Diabetes mellitus
General outcomes from A-level evidence	↓ FBG (11.2 mg/dl), HbA1C (0.29%), (177) glucose metabolism overall (small effect, d= 0.17), TGs (~23.0 mg/dl) when used alone, TGs (~63.8 mg/dl), and total cholesterol (17.4 mg/dl) when used concomitantly with fenofibrate, (159) & lipid profile overall (small effect, d= 0.13) driven by total cholesterol (small effect, d= 0.28) and LDL-C (small effect, d= 0.29) (40) ↑ HDL-C (3.53 mg/dl) (177) Note: variability in whether these biomarkers improve exists between analyses (40)(159)(177)
Dosing & administration	100-200 mg per day for 3-6 months to Px with diabetes
Outcomes	↓ TGs (~23.0 mg/dl) when used alone & TGs (~63.8 mg/Dl) and total cholesterol (17.4 mg/dL) when used concomitantly with fenofibrate (159)
Class of evidence	A
Dosing & administration	100-200 mg per day in divided doses for 8-12 weeks to Px with type II diabetes
Outcomes	↓ FBG (11%), HbA1C (0.4-0.7%), insulin (13%), insulin resistance (21%), total cholesterol (10-11%), LDL-C (12%), ferritin (36%), SBP (6.1 mmHg), DBP (2.9 mmHg), MDA (15-18%), & adipolin (24%) ↑ HDL-C (8%), adiponectin (66%), adiponectin:leptin ratio (76%), adiponectin:HOMA-IR ratio (133%), flow-mediated dilation (1.0-1.6%), asymmetric dimethylarginine, & NOx Note: biomarkers were not consistently reduced or increased across all trials. (53)(54)(59)(63)(65)(98)(101)(166)
Class of evidence	B
Dosing & administration	33 mg (as liquid ubiquinol) three times per day for 12 weeks to Px with type II diabetes
Outcomes	↓ HbA1C, catalase, and glutathione peroxidase levels compared to baseline, & prevented reductions in HDL-C compared to placebo (168)
Class of evidence	C

Diabetic neuropathy & retinopathy
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg twice per day for 12 weeks to Px with diabetic neuropathy
Outcomes	↓ insulin (12%), insulin resistance (37%), & hs-CRP (29%) ↑ insulin sensitivity (68%) & total antioxidative capacity (0.92 µmol/l) compared to placebo (3)
Class of evidence	B
Dosing & administration	400 mg per day for six months to Px with non-proliferative diabetic retinopathy
Outcomes	↓ MDA (36%), nitrites/nitrates (24%), catalase activity (19%), & GPx activity (61%) compared to baseline, but no change in placebo (121)
Class of evidence	B
Dosing & administration	400 mg per day for 12 weeks to Px with diabetic polyneuropathy
Outcomes	Improved neuropathy symptom (60%) and impairment scores (44%), lipid peroxidation (25%), & nerve conduction parameters (61)
Class of evidence	A

Dry mouth
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg per day (as ubiquinone or ubiquinol capsules or gummies) for 4-8 weeks to Px with dry mouth
Outcomes	↑ saliva excretion by 82% with ubiquinol and 72% with ubiquinone capsules compared to baseline, but no change in placebo ↑ saliva excretion by 16% with ubiquinol gummies, but not placebo Note: increased salivation was also noted in healthy subjects, but to a lesser degree (126)(164)
Class of evidence	B

Exercise tolerance and performance
General outcomes from A-level evidence	↑ exercise capacity with inconsistent effects (123) Note: other evidence indicates no effect on exercise performance in older populations (94)
Dosing & administration	200 mg per day for six weeks to athletes over the age of 50 using statins
Outcomes	Improved muscular performance as measured by time to reach anaerobic threshold and increased leg extension reps (35)
Class of evidence	C
Dosing & administration	150 mg twice per day for one week before exercise tests to healthy adults
Outcomes	Improved physical performance and fatigue perception during exercise (100)
Class of evidence	C
Dosing & administration	100 mg three times per day for one month to Px with coronary artery disease
Outcomes	↑ extracellular SOD activity (29%) & endothelial relaxation (70%) Improved various exercise capacity-related measures including peak VO2, ventilatory threshold, O2 pulse at peak exercise, and peak systolic BP (162)
Class of evidence	C
Dosing & administration	90 mg per day for six weeks to elite athletes during training
Outcomes	Improved VO2max, anaerobic threshold, & aerobic threshold indices compared to placebo (169)
Class of evidence	C
Dosing & administration	50 mg three times per day for one month to Px with stable angina pectoris
Outcomes	Improved exercise tolerance (increased exercise duration) compared to placebo (72)
Class of evidence	C

Fatigue
General outcomes from A-level evidence	↓ fatigue particularly caused by fibromyalgia or statin-related fatigue, but this effect is less likely in healthy Px (97)
Dosing & administration	200 mg per day for 12 weeks to obese Px
Outcomes	↓ fatigue severity score (17%) compared to baseline with no change in placebo (84)
Class of evidence	C

Fibromyalgia
General outcomes from A-level evidence	↓ pain severity (88)
Dosing & administration	100 mg three times per day for 40 days to Px with fibromyalgia
Outcomes	↓ fibromyalgia impact questionnaire (52%), pain (52-56%), tender joints (44%), fatigue (47%), morning tiredness (44%), & depression ↓ inflammatory gene expression, inflammasome activation, & serum IL-1β and IL-18 ↑ platelet serotonin levels, mitochondrial biogenesis & antioxidative and AMPK gene regulation compared to placebo (3)(30)(31) Improved subscores of the Symptom Checklist‐90‐R’ (SCL‐90‐R) including somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, & psychoticism compared to baseline, but placebo did not change (4)
Class of evidence	C
Dosing & administration	300 mg per day for 40 days to Px with fibromyalgia using pregabalin
Outcomes	↓ pain, fibromyalgia impact, and anxiety scores, & inflammatory protein expression (p-NFkB/NFkB ratio, NLRP3/Actin) Improved mitochondrial oxidative stress, glutathione, & SOD levels compared to pregabalin alone (141)
Class of evidence	C
Dosing & administration	200 mg (as water-soluble formulation) twice per day for three months to Px with fibromyalgia
Outcomes	↓ pain (24-37%), fatigue (22%), & sleep disturbance (33%) (37)
Class of evidence	C

Hearing loss (age-related)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	160 mg per day (as water-soluble formulation) for one month to Px with age-related hearing loss
Outcomes	Improves hearing thresholds with effects continuing six months post-discontinuation (57)(131)
Class of evidence	C

Heart failure
General outcomes from A-level evidence	↓ relative risk of mortality (31%) (85) & hospitalization (64) ↑ ejection fraction (~3.7%), (51) cardiac output (0.28L/min), stroke index (5.7 ml/m2), (134) & exercise capacity (moderate effect, d= 0.62) (85) Improved ejection fraction, stroke volume, cardiac output, cardiac index, & end diastolic volume index in 92%, 76%, 73%, 87%, & 88% more Px with congestive heart failure, respectively, using CoQ10 than placebo (155) Note: overall, a systematic review of systematic reviews concluded that CoQ10 may be useful for managing heart failure. (69) However, individual reviews have also shown no effect on improved mortality, (123) ejection fraction, (85) cardiac index, stroke volume, (134) or exercise capacity (90)
Dosing & administration	Up to 100 mg per day for 12 weeks to Px with mild chronic heart failure
Outcomes	↑ ejection fraction (4.25%) (51)
Class of evidence	A
Dosing & administration	100 mg three times per day for up to two years to Px with moderate to severe chronic heart failure using standard therapies
Outcomes	↓ likelihood of major adverse cardiovascular events (11%), all-cause mortality (8%), cardiovascular mortality (7%), & proportion of Px with an improvement of at least one grade of NYHA functional class compared to placebo (104) Note: similar effects observed in European subpopulation (103)
Class of evidence	B
Dosing & administration	2 mg/kg per day for up to one year to Px with chronic congestive heart failure using conventional therapies
Outcomes	↓ cardiac index score (36%) compared to placebo & heart rate (8 bpm) and myocardial performance index (29%) compared to baseline in children with idiopathic dilated cardiomyopathy ejection fraction percentage (13%) compared to baseline in children with idiopathic dilated cardiomyopathy (76) ↓ risk of hospitalization (14%), pulmonary edema (10%), & cardiac asthma (31%) compared to placebo (102)
Class of evidence	B
Dosing & administration	120 mg per day for up to one year to Px who experienced an acute myocardial infarction
Outcomes	↓ risk of angina (19%), arrhythmias (16%), poor ventricular function (14%), and cardiac event (16%) after one month, & risk of a cardiac event (20%) by end of year (148)(152)
Class of evidence	B
Dosing & administration	100 mg three times per day for one month to Px with chronic heart failure
Outcomes	↑ left ventricular ejection fraction (15%), peak VO2 (9%), & endothelium-dependent dilation of the brachial artery (38%) ↓ systolic wall thickening index (12%) Note: provided similar benefits to exercise therapy, but improved measures when added to exercise (16)(17)
Class of evidence	C
Dosing & administration	150-200 mg per day for 12 weeks to Px with heart failure using standard therapies
Outcomes	↓ NYHA class (0.5 points) compared to placebo ↑ exercise performance scores compared to baseline Improved left ventricular function as shown by improvements in various measures compared to baseline, but placebo did not change (107)
Class of evidence	C
Dosing & administration	60 mg (as water-soluble hybrid formulation) per day for three months to Px with end-stage heart failure
Outcomes	↓ NYHA class (from 3.1 to 2.4), nocturia, fatigue, & dyspnea Improved six-minute walk test distance (18)
Class of evidence	C
Dosing & administration	30 mg per day for 12 months to Px with heart failure using common therapies
Outcomes	↓ incidence of atrial fibrillation (72%) & MDA (31%) compared to common therapies alone (181)
Class of evidence	C

Hepatitis B immunology
General outcomes from A-level evidence	No data currently available.
Dosing & administration	60 mg three times per day starting two weeks prior to hepatitis B vaccination and for three months to Px receiving vaccination
Outcomes	↑ antibody response to hepatitis vaccination by up to 57% ↓ rises in lymphocytes and leukocytes, & eosinophil count (30%) (15)
Class of evidence	C

Hypertension
General outcomes from A-level evidence	↓ SBP (16-17 mmHg) & DBP (10 mmHg) (123)(124) Note: some evidence indicates that there was only an effect on SBP (small effect, d= 0.3), with no effect on DBP (160)
Dosing & administration	100-200 mg per day for 8-12 weeks to Px with hypertension
Outcomes	↓ SBP (16 mmHg) & DBP (10 mmHg) (123)
Class of evidence	A
Dosing & administration	60 mg (as water-soluble formulation) twice per day for 12 weeks to Px with isolated systolic hypertension
Outcomes	↓ SBP (18 mmHg) (22)
Class of evidence	B

Inflammatory and cardiometabolic profile (chronic inflammatory/metabolic diseases)
General outcomes from A-level evidence	↓ TNF-ɑ (0.45-0.49 pg/ml) (175) with a small effect (d = 0.44), IL-6 (0.72-1.61 pg/ml) (small effect, d= 0.37), (48) CRP (0.25-0.35 mg/L), (47)(96) TGs (small effect, d= 0.28), (143) lipoprotein(a) (3.54 mg/dl), (130) & FBG (8.47 mg/dl) (158) ↑ endothelial function (1.7% improvement in flow-mediated dilation) (52) Note: hs-CRP, (8) CRP, (48) IL-6, (175) total cholesterol, LDL-C, HDL-C, (143) & HBA1C (158) were not improved in individual analyses
Dosing & administration	Up to 150 mg per day for eight weeks to Px with metabolic diseases
Outcomes	↓ TNF-ɑ (moderate effect, d= 0.63), IL-6 (small effect, d= 0.49), (48) & lipoprotein(a) (9.24 mg/dl) (130)
Class of evidence	A
Dosing & administration	100 mg per day for 12 weeks to Px with cardiometabolic diseases
Outcomes	↓ CRP (0.48 mg/dl), IL-6 (2.22 pg/ml), & TNF-ɑ (0.69 pg/ml) (47)
Class of evidence	A
Dosing & administration	Up to 200 mg for 12 weeks to Px with various chronic diseases
Outcomes	↓ FBG (8.47 mg/dl) with greater effectiveness in Px with a glucose level of >108 mg/dl (158)
Class of evidence	A
Dosing & administration	100 mg per day for eight weeks to Px with metabolic syndrome
Outcomes	↓ insulin (18%), insulin resistance (18%), & HOMA-B (18%) compared to placebo (119)
Class of evidence	B
Dosing & administration	200 mg per day for eight weeks to Px with pre-diabetes
Outcomes	↓ insulin resistance (45%) & free oxygen radical levels (24%) compared to baseline, but placebo did not change (170)
Class of evidence	B
Dosing & administration	60 mg twice per day for 24 weeks to Px with dyslipidemia
Outcomes	↓ FBG (13 mg/dl), insulin (14%), HOMA-IR (24%), TGs (12 mg/dl), LDL-C (7.7 mg/dl), SBP (10 mmHg), & DBP (7 mmHg) ↑ ApoA-I (7.7%) & ApoA-I/ApoB (6.7%) (176)
Class of evidence	B
Dosing & administration	100 mg per day for 12 weeks to Px using statins on maintenance hemodialysis
Outcomes	↓ lipoprotein(a) (31%) compared to baseline, but placebo did not change (144)
Class of evidence	B
Dosing & administration	100 mg per day for 12 weeks to Px with mild hypertension
Outcomes	↑ adiponectin (15%) ↓ IL-6 (30%) & hs-CRP (26%) (11)
Class of evidence	B

Infertility (female)
General outcomes from A-level evidence	↑ odds of pregnancy ~2.2-2.4 fold in poor responders to ovarian stimulation undergoing assisted reproductive technologies (50)(180) ↓ odds of canceling IVF due to poor ovarian response (67%) (180) Note: no effects were observed on improving live birth rates or miscarriages (50)
Dosing & administration	200 mg three times per day for two months to women with low ovarian reserve undergoing in vitro fertilization or intracytoplasmic sperm injection
Outcomes	↑ number of retrieved oocytes, median number of fertilized oocytes, fertilization rates, embryo quality, & peak E2 levels ↓ cancelled embryo transfers due to poor development & gonadotropin requirement compared to control (167)
Class of evidence	C

Infertility (male)
General outcomes from A-level evidence	↑ total sperm count (10.15×106 spz/mL), concentration (5.60-8.49×106 spz/mL), motility (4.5-7.1%), & morphology (1.06-14.9%) (113)(132) with large effects in oligozoospermia, asthenozoospermia, and teratozoospermia (21)
Dosing & administration	200-300 mg per day for 3-6 months to males with idiopathic oligoasthenoteratozoospermia or idiopathic asthenozoospermia
Outcomes	↑ total sperm count (10.15×106 spz/mL), concentration (5.60-8.49×106 spz/mL), motility (4.5-7.1%), & morphology (1.06-14.9%) (79)(113)(132) Note: large effect sizes noted for oligozoospermia (d= 0.95), asthenozoospermia (d= 1.48), & moderate effect for size teratozoospermia (d= 0.63)(21)
Class of evidence	A
Dosing & administration	200-300 mg per day for six months to males with idiopathic asthenozoospermia
Outcomes	↑ total sperm count (24%), sperm concentration (31%), total sperm motility (6-24%), & forward motility (4.68%) ↓ LH (27%) & FSH (36%)(13)(127)
Class of evidence	B
Dosing & administration	200 mg (as ubiquinol) per day for six months to males with idiopathic oligoasthenoteratozoospermia
Outcomes	↑ sperm concentration (71%), motility (10%), & strict morphology (2.8%) of normal sperm compared to placebo (129)
Class of evidence	B
Dosing & administration	200 mg per day for three months to males with oligoasthenoteratozoospermia
Outcomes	↑ total antioxidative capacity, catalase, & SOD activity ↓ plasma MDA & seminal 8-isoprostane Note: normal sperm morphology, catalase, and SOD were positively correlated with CoQ10 levels (109)(110)
Class of evidence	C

Migraine headaches
General outcomes from A-level evidence	↑ migraine frequency (~1.87 per month) (115) & duration (moderate effect, d= 0.7) (174) Note: no reduction in duration, (115) migraine severity, or frequency have been observed in other analyses (112)(174)
Dosing & administration	300-400 mg in 2-3 divided doses per day for 12 weeks to Px with migraine adjunct to standard preventative medications
Outcomes	↓ migraine frequency (~1 day per month) with improved responder rate (70%), & number of days and severity of nausea/vomiting (135) ↓ migraine frequency (~5.4 per month), severity (48%), duration (~7.2 hours), calcitonin gene-related peptide (CGRP, a nociceptive biomarker) (~20%), & TNF-α (17%) compared to placebo (32)
Class of evidence	B
Dosing & administration	100 mg per day for 16 weeks as add-on therapy to children or adolescents with migraine
Outcomes	↓ migraine frequency (~3 fewer than placebo) within first four weeks of treatment (154)
Class of evidence	B

Mitochondrial dysfunction
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg three times per day for eight weeks to Px with coronary artery disease
Outcomes	↓ mitochondrial dysfunction (measured via reduced lactate:pyruvate ratio), which was significantly correlated to improved endothelial function (improved flow mediated dilation, 1.51%) (33)
Class of evidence	B
Dosing & administration	600 mg twice per day for two months or 2 mg/kg per day for nine months to Px with various mitochondrial disorders
Outcomes	↓ serum lactate after two months (56) ↑ muscle strength after six months Note: A six-month duration may be required for benefit; however, no further benefits were observed after six months, but the placebo group reverted to the previously improved lactate and strength measures (20)
Class of evidence	C
Dosing & administration	160 mg per day for three months to Px with mitochondrial encephalomyopathies
Outcomes	↑ muscle strength compared to baseline (27)
Class of evidence	C
Dosing & administration	300 mg (as ubiquinol) per day for four weeks to Px using simvastatin
Outcomes	Reverses a 15% increase in mitochondrial dysfunction (measured by phosphocreatine recovery time) caused by statin use (165)
Class of evidence	C
Dosing & administration	400 mg per day for six months to Px with diabetic retinopathy
Outcomes	↓ mitochondrial dysfunction as measured by improvements in mitochondrial membrane fluidity & reducing an inflated catabolic state induced by the condition via reductions in ATP hydrolysis (122)
Class of evidence	C

Multiple sclerosis
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg five times per day for 12 weeks to Px with multiple sclerosis
Outcomes	↑ fatigue severity scale (23%) and Beck Depression Inventory (28%), TNF-α (86%), IL-6 (57%), MMP-9 (12%), & MDA (22%) ↑ SOD (18%) compared to placebo (137)(138)(139)
Class of evidence	B

Nonalcoholic fatty liver disease (NAFLD)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg per day for 12 weeks to Px with NAFLD
Outcomes	↓ NAFLD grades, AST (18%), GGT (21%), hs-CRP (32%), & TNF-ɑ (24%) ↑ adiponectin (13%) compared to placebo (49)
Class of evidence	C

Parkinson’s disease
General outcomes from A-level evidence	Note: no high level evidence currently supports the use of CoQ10 in Parkinson’s disease (182)
Dosing & administration	300-1,200 mg per day for up to 16 months to Px with early Parkinson’s disease
Outcomes	↓ progression of disease as measured by attenuation in the Unified Parkinson Disease Rating Scale over time, with greater efficacy with higher doses (106)(145) Note: Px experiencing levodopa wear-off were of sole benefit in one trial (171)
Class of evidence	B

Peyronie disease
General outcomes from A-level evidence	No data currently available.
Dosing & administration	300 mg per day for 24 weeks to Px with Peyronie disease
Outcomes	↓ penile curvature by 54.3% and deviation angle by 12 degrees with straightening occurring for many Px within one month, & plaque size by 40%, while placebo group increased in plaque and erectile pain (86%) ↑ penile vascular status & erectile function indexes (128)
Class of evidence	B

Polycystic ovary syndrome (PCOS)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100-200 mg per day for 8-12 weeks to women with PCOS using metformin
Outcomes	↓ FBG (7%), insulin (26%), insulin resistance (30%), testosterone (30%), TGs (7%), total cholesterol, & LDL-C ↑ beta-cell function & insulin sensitivity (67)(68)(133) Improved gene expression for inflammatory factors including LDLR, PPAR-y, IL-1, IL-8, & TNF-α (118)
Class of evidence	B
Dosing & administration	60 mg three times per day with clomiphene citrate from cycle day two to the day of administration of human chorionic gonadotropin (HCG) to women with clomiphene citrate-resistant PCOS
Outcomes	↑ clinical pregnancy (31%) and ovulation rates (50%), number of >14 mm and >18 mm follicles, & endometrial thickness (25%) (41)
Class of evidence	C

Pre-eclampsia
General outcomes from A-level evidence	No data currently available.
Dosing & administration	200 mg per day from week 20 of gestation until delivery to pregnant women
Outcomes	↓ relative risk of pre-eclampsia by 44% (161)
Class of evidence	B

Rheumatoid arthritis
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg per day for eight weeks to Px with rheumatoid arthritis on conventional medication
Outcomes	↓ tender joint count, pain score (89%), disease activity score (53%), erythrocyte sedimentation rate (41%), MMP-3, MDA (33%), & TNF-ɑ (24%) compared with placebo (1)(108)
Class of evidence	B

Sepsis
General outcomes from A-level evidence	No data currently available.
Dosing & administration	100 mg twice per day for seven days during standard care to Px in the ICU with sepsis
Outcomes	↓ in-hospital mortality by 69%, & TNF-α and MDA levels compared to standard therapy alone (156)
Class of evidence	C

Statin-associated myopathy
General outcomes from A-level evidence	↓ muscle pain, weakness, cramps, and fatigue (117) Note: while supplementation may reverse statin-induced reductions in CoQ10 levels, the effect on muscle pain or statin therapy adherence may not be improved compared to placebo and may not be currently supported (6)(14)(73)(92)
Dosing & administration	100 mg once per day or 50 mg (as water-soluble formulation) twice per day for one month to Px using statins and reporting muscle pain
Outcomes	↓ pain severity (33-40%) & pain interference scores (38-40%) in 75% of Px compared to placebo or baseline (23)(153)
Class of evidence	B
Dosing & administration	100 mg (water-soluble liquid formulation) per day for three months to Px experiencing statin-induced side effects
Outcomes	↓ myalgia (29%) and VAS pain (42%) scores, with 40% more Px reporting reductions in muscular pain compared to placebo (36)
Class of evidence	B

Supranuclear palsy
General outcomes from A-level evidence	No data currently available.
Dosing & administration	5 mg/kg per day divided into three daily doses for six weeks to Px with supranuclear palsy
Outcomes	↓ Progressive Supranuclear Palsy rating scale total score and Frontal Assessment Battery score compared to placebo (157)
Class of evidence	C

Viral myocarditis
General outcomes from A-level evidence	No data currently available.
Dosing & administration	10 mg three times per day for two weeks to Px with acute viral myocarditis
Outcomes	Improved antioxidative and inflammatory profile, & heart function via: ↑ SOD (61%), GSH (39%), & LVEF (30%) ↓ MDA (23%), MCP-1 (54%), IL-8 (49%), TNF-ɑ (49%), LDH (34%), CK (60%), AST (42%), NT-proBNP (66%), CRP (81%), & cardiac troponin I (97%) compared to baseline Note: provided similar efficacy to trimetazidine, but may further improve most parameters in combination (142)
Class of evidence	C

Adverse effects

CoQ10 is considered safe and well-tolerated with low toxicity. In reviews of clinical trials, the use of 1,200 mg for up to 16 months resulted in no greater observed adverse event level than placebo and has been shown to be tolerated at doses up to 3,000 mg over eight months. (7)(62) Minor gastrointestinal-related adverse events have been attributed to the large amounts of oil in CoQ10 capsules. (66) However, systematic reviews and meta-analyses either indicate that trials generally do not report significant adverse events or that there is no difference in the prevalence of adverse events between the use of CoQ10 or placebo. (34)(50)(124)(177)(182)

Pharmacokinetics

Absorption

As a lipid-soluble nutrient, CoQ10 absorption is improved in the presence of lipids, such as when consumed with a fatty meal. (7)(19)
CoQ10 is absorbed in the small intestine in its reduced form, ubiquinol. (7)(19)
Absorption is slow, with most data showing that the highest concentrations occur within 6-8 hours post-ingestion, regardless of the formulation used. (7)(19)
Doses should be divided to avoid exceeding active transport capacity and maintain plasma concentrations for longer durations of time. (7)
After absorption, CoQ10 is packaged into chylomicrons, VLDL (16%), LDL (58%), and HDL (26%) particles for circulation. Approximately 95% of circulating CoQ10 is ubiquinol. (7)(19)

Distribution

CoQ10 exists in virtually every tissue in the body, particularly as ubiquinol. (7)(19)
Generally, greater amounts are found in higher energy-requiring organs such as the heart, kidney, liver, muscle, brain, intestine, and lungs (listed in descending order of concentration). (19)
About half of CoQ10 is found in mitochondrial membranes and lesser amounts in cytosol or individual organelles. (7)(19)

Metabolism

Little is known on the metabolism of CoQ10, though it appears to be CYP P450- mediated. (7)(173)

Excretion

CoQ10 metabolites are mainly excreted through fecal or biliary routes, though a small amount can be found in the urine. (19)
Its half-life is approximately 33 hours. (7)