Table 1.
Clinical Trials.
| Trial | Population | Design | CoQ10 Dose and Duration | Results |
|---|---|---|---|---|
| Langsjoen et al. (1985) [64] | 18 HF patients, NYHA class: III–IV | Double-blind and double-crossover trial | CoQ10 33 mg 3/d for 3 months | Significant improvement of SV and EF (p < 0.0001) measured by mean value from baseline to 12 weeks of CoQ10 supplementation vs. mean values after placebo period). |
| Permanetter et al. (1992) [65] | 25 patients suffering from IDCM | Placebo-controlled, double-blind crossover trial | CoQ10 30 mg 4/d vs. placebo for 4 months | No statistically significant difference in ECG, LVEF (at rest and on exercise), LVESD, LVEDD, CI, SV, CT ratio, exercise tolerance and incidence of cardiac arrhythmias in chronic treatment with ubiquinone vs. placebo in patients suffering from IDCM. |
| Morisco et al. (1993) [52] | 641HFrEF patients (mixed pathogeneses) NYHA class: III–IV | Double-blind placebo-controlled trial | CoQ10 50 mg 2/d or 3/d vs. placebo for 1 year | Decreased hospitalization for HF in CoQ10 group (n = 73) vs. placebo (n = 118; p < 0.001). Decreased episodes of pulmonary edema in CoQ10 group (n = 20) vs. placebo (n = 51; p < 0.001). Decreased episodes of cardiac asthma in CoQ10 group (n = 97) versus placebo (n = 198; p < 0.001). |
| Rengo et al. (1993) [66] | 60 HFrEF patients NYHA class: III | Single-blind placebo randomized trial | CoQ10 100 mg/d vs. placebo for 7 months | Increase of LVEF % (15.79%) in CoQ10 group and decrease in placebo group (2%) vs. baseline (p < 0.001). Decrease of LVESD in CoQ10 (2%) and in placebo group (0.16%), (p < 0.001). Increase of FS in CoQ10 group (15.6%) vs. decrease in placebo group (2.19%, p < 0.001). |
| Baggio et al. (1994) [67] | 2664 HF patients NYHA class: II and III | Open, non-comparative trial in 173 Italian centers | CoQ10 50–150 mg/d for 3 months | Significant improvement in BP, heart rate and respiratory rate, clinical signs and symptoms (at last 3 symptoms in 52.2% of patients) after CoQ10 supplementation. |
| Hofman-Bang et al. (1995) [59] | 79 stable HFrEF patients | Double-blind, crossover placebo-controlled trial | CoQ10 50 mg 3/d vs. placebo for 3 months | CoQ10 therapy showed significant improvement in EF during a slight volume load: 25% ± 13% vs. 23% ± 12% (p < 0.05), EF at rest (mean value: 0.5, 95% CI = 1.0–2.0) increase of maximal exercise capacity: 100 ± 34 W vs. placebo 94 ± 31 W (p < 0.05), significantly increase of total score for the QoL assessment: 113 ± 22 vs. placebo 107 ± 23 (p < 0.05). |
| Watson et al. (1998) [68] | 30 HFrEF patients (mixed pathogeneses) | Double-blind, crossover placebo-controlled trial | CoQ10 33 mg 3/d vs. placebo for 3 months | No significantly difference in EF from baseline (26% ± 6%) and after CoQ10 treatment (31% ± 9%) vs. placebo (p < 0.98), CI from baseline (2.7 ± 0.7) and after Coq10 treatment (2.9 ± 0.7) vs. placebo (p < 0.46), same results in Left Ventricular Diastolic Volume (p < 0.16) and Left Ventricular Systolic Volume (p < 0.26). No difference in QoL scores compared with placebo. |
| Munkholm et al. (1999) [60] | 22 HF patients (mixed pathogeneses) NYHA class: II and III | Double-blind placebo-controlled randomized trial | CoQ10 100 mg 2/d vs. placebo for 1 year | Improvement of SI from baseline (31.28 ± 3.43) to 12 weeks in CoQ10 group (36.2 ± 2.72, p < 0.005) vs. no change in placebo group. Reduction of pulmonary capillary wedge pressure (PCWP) from baseline (40 ± 16 mm Hg) to 12 weeks in CoQ10 group (32 ± 15 mm Hg, p < 0.02) vs. no change in placebo group. Improvement in mean pulmonary artery pressure from baseline (27 ± 10 mm Hg) to 12 weeks in CoQ10 group (21 ± 7 mm Hg, p = 0.02) vs. no change in placebo group. |
| Khatta et al. (2000) [62] | 55 HFrEF patients (mixed pathogeneses), NYHA class: III or IV | Randomized, double-blind placebo-controlled trial | CoQ10 200 mg/d vs. placebo for 6 months | No significantly difference in: Maximal oxygen consumption in CoQ10 group increase of 0.21 ± 3.4 mL/kg/min (95% CI = 1.25–1.68) vs. decrease in placebo group 0.49 ± 2.4 mL/kg/min (95% CI = 1.54–0.55) and in exercise duration 9.1 ± 3.4 min after CoQ10 treatment vs. 7.5 ± 2.9 min after placebo. No difference of EF measured by Radionuclide Ventriculography in CoQ10 group (decrease 0.3% ± 8%, CI = 3.7%–3.1%) vs. placebo (decrease 0.2% ± 8.6%, CI = 4.0%–3.6%). |
| Keogh et al. (2003) [52] | 39 HFrEF patients (mixed pathogeneses) NYHA class: II or III | Randomized, double-blind placebo-controlled trial | CoQ10 50 mg 3/d vs. placebo for 3 months | Improvement of NYHA score in CoQ10 group (2.9 ± 0.06) from baseline (2.4 ± 0.12, p = 0.001) vs. no change between placebo and CoQ10 group (p = 0.01). No difference in CoQ10 group vs. placebo in Canadian-specific activity scale score (p = 0.29), 6 min walk test (p = 0.29) and Fractional Shortening (p = 0.9). |
| Berman et al. (2004) [53] | 32 patients with HFrEF awaiting heart transplantation | Randomized controlled trial | CoQ10 60 mg 2/d vs. placebo for 3 months | Improvement in 6 min walk test from baseline (269.5–382.2 m, p < 0.0001) and vs. placebo group (254–177 m, p < 0.0001). Improvement of NYHA class in CoQ10 group from baseline (3.1–2.4, p = 0.01), no changes vs. placebo group (p = 0.01). No improvement in Fractional shortening. |
| Soongswang et al. (2005) [58] | 15 idiopathic chronic DCM patients, median age: 4.4 years (range, 0.6–16.3) | Open-label prospective study | CoQ10 3.1 ± 0.6 mg/kg/d for 9 months | Significantly improvement of NYHA functional class (p < 0.005); CT Ratio: median 0.62 (0.55–0.78) vs. 0.58 (0.50–0.80, p < 0.022); QRS duration: median 82 msec (80–160) vs. 80 msec (60–149, p < 0.017), after supplementation therapy with CoQ10 when compared to baseline and post-discontinuation of CoQ10 at 9 months (depolarization in children with chronic idiopathic DCM). |
| Belardinelli et al. (2006) [63] | 23 HF patients (secondary to ischemic heart disease) NYHA class II and III |
Double-blind, placebo-controlled crossover trial | CoQ10 100 mg orally 4/d vs. placebo for 4 weeks | Significantly improvement of: peak VO2 after CoQ10 treatment (19.6 ± 4.8 mL/kg/min) and after CoQ10 + ET (21.5 ± 4.7ml/kg/min) vs. placebo (p < 0.0001); endothelium-dependent dilation of the brachial artery (EDDBA): 5.64% ± 1.95% compared with placebo: 4.19% ± 1.9% (p < 0.01); resting LVEF 43% ± 8.7% vs. placebo 37.9% ± 8% (p < 0.0023). |
| Kocharian et al. (2009) [69] | 38 IDCM patients; < 18 years | Double-blind placebo-controlled trial | CoQ10 2 mg/kg/d over 2 or 3 doses increased to 10 mg/kg/d according to tolerance or side effects for 6 months | Improvement after CoQ10 supplementation therapy of CI (5.8 ± 4) vs. placebo (9 ± 4.2), p = 0.024; EF improvement: 42.1% ± 14.7% in CoQ10 group vs. placebo group 37.6% ± 9.7% (p < 0.267); FS improvement 18.5 ± 7.9 vs. placebo 14.9 ± 3.2 (p < 0.1). |
| Lee et al. (2013) [65] | 51 Patients with 50% stenosis of one major coronary artery and treated with statin for last 1 month | Randomized placebo-controlled trial | CoQ10 300 mg/d for 12 weeks | Increase of plasma levels of CoQ10 (P < 0.001), antioxidant enzymes activities (p < 0.05) and vitamin E (p = 0.043) after CoQ10 supplementation vs. placebo. Decrease of inflammatory markers levels (TNF-α, p = 0.039) after CoQ10 supplementation. |
| Pourmoghaddas et al. (2014) [54] | 62 patients with HFrEF (mixed pathogeneses) NYHA class: II–IV | Randomized double-blind placebo-controlled trial | CoQ10 100 mg 2/d with atorvastatin 10 mg/day vs. placebo for 4 months | Improvement of EF in CoQ10 group (24.2% ± 14.5%) from baseline 18.7 ± 10.3%, p = 0.003) and vs. placebo (26.2% ± 9.1% to 25.8% ± 9.7%, p = 0.006). Improvement of NYHA classification from baseline (2.7 ± 0.7) in CoQ10 group (2.3 ± 0.7, p = 0.025) and vs. placebo (2.9 ± 0.8 to 2.7 ± 0.7, p = 0.002). |
| Mortensen et al. (2014) [61] | 420 HFrEF patients(mixed pathogeneses) NYHA class: I–II | Randomized double-blind placebo-controlled trial | CoQ10 100 mg orally 3/d vs. placebo for 2 years | Reduced risk of all-cause death in CoQ10 group: HR, 0.51 (95% CI = 0.30–0.89; p = 0.018); reduced composite risk including cardiovascular death, mechanical assist implantation, or urgent cardiac transplantation: HR, 0.50 (95% C =, 0.32–0.80; p = 0.003). No difference between groups for NYHA functional class, 6 min walk test or functional status. |
| Zhao et al. (2015) [70] | 102 HF patients | Randomized double-blind, placebo-controlled trial | CoQ10 2 mg/kg/d divided in 2 or 3 doses for 1 year | Significant reduction in CoQ10 group of TNF-α, IL-6, hs-CRP and Malonylaldehyde plasma levels; significant increase of LVEF after 12 months (mean 46% ± 6%) vs. placebo (43% ± 5%, p < 0.05) and decrease of LVED (53 ± 3 mm) vs. placebo (54 ± 4 mm). |
| Chen et al. (2018) [71] | 10 children diagnosed with DCM | Open-label trial | Liquid ubiquinol supplementation: 10 mg/kg body weight/d for 24 weeks | Liquid ubiquinol supplementation in children with DCM increased significantly the level of CoQ10 (3.9 ± 1.45 μM) from baseline (0.43 ± 0.12, p < 0.01). Improvement of EF after 24 weeks of treatment (65.67% ± 9.63%) from baseline (62.56 ± 7.47, p < 0.15) and FS after 24 weeks of treatment (36.59% ± 6.86%) from baseline (34.2 ± 5.22, p < 0.19). CoQ10 plasma level was moderately positively correlated with EF (r = 0.37, p = 0.28) and FS (r = 0.26, p = 0.45) after 24 weeks of supplementation. |
| Alehagen et al. (2018) [72] | 443 elderly healthy participants | Prospective randomized double-blind placebo-controlled trial | CoQ10 200 mg/d for 4 years | Supplementation with CoQ10 and selenium for 4 years in elderly healthy subjects reduced significantly CV mortality (28.1%) vs. placebo (38.7%) after 12 years of follow-up; Reduced of CV mortality risk in treatment group in 12 years follow-up (HR: 0.58; 95% CI = 0.42–0.70; p = 0.007) significantly in patients with ischemic heart disease (HR: 0.52, p = 0.02, 95% CI = 0.3–0.9) diabetes (HR: 0.50, p = 0.03, 95% CI = 0.27–0.93), hypertension (HR: 0.59, p = 0.005, 95% CI = 0.41–0.85) and impaired functional capacity (NYHA III HR: 0.49, p = 0.02, 95% CI = 0.27–0.88). |
| Mortensen et al. (2019) [55] | 420 HF patients (moderate to severe HF) | Randomized double-blind placebo-controlled trial | CoQ10 300 mg/d vs. placebo in addition to standard therapy for 2 years | Increase of CoQ10 plasma level (3.42 ± 0.21 μg/mL) from baseline (0.95 ± 0.08 μg/mL, p < 0.001) vs. decrease in placebo (0.76 ± 0.04 μg/mL). Reduction of NT-proBNP after 3 months of CoQ10 treatment vs. baseline (p = 0.052). Reduction of composite risk assessed by MACE: HR: 0.23; 95% CI = 0.11–0.51, p < 0.001. Improvement of at least 1 grade of NHYA class after 2 years of CoQ10 supplementation vs. placebo (48% vs. 25%, p = 0.003), significant improvement in Coq10 group of 6% from baseline in LVEF (p = 0.021) but not vs. placebo (p = 0.234). |
| Sobirin et al. (2019) [73] | 30 HFpEF patients | Single center, unblinded randomized controlled trial | CoQ10 100 mg 3/d for 30 days | Decrease of E/e’ ratio in CoQ10 group (15.1 ± 4.3) vs. baseline (18.9 ± 3.8) and vs. placebo (15.8 ± 5.6); improvement in LAVI: 26 ± 7 mL/m2 vs. baseline 32 ± 9 mL/m2 (p = 0.04) and vs. placebo (30 ± 8 mL/m2); increase of LVEF: 56% ± 8% vs. baseline 55% ± 4% (p = 0.73) and vs. placebo (57% ± 7%). |
Captions: AF: Atrial Fibrillation; CoQ10: Coenzyme Q10; CRP: C-reactive protein; CT ratio: Cardiothoracic ratio; CV mortality: Cardiovascular mortality; DCM: Dilated Cardiomyopathy; ECG: Electrocardiogram; EF: Ejection Fraction; ESR: erythrocyte sedimentation rate; ET: Exercise Training; FS: Fractional Shortening; HF: Heart Failure; HFpEF: Heart Failure with preserved Ejection Fraction; HFrEF: Heart Failure with reduced Ejection Fraction; HR: Hazard Ratio; hs-CRP: High Sensitivity C-Reactive Protein; IDCM: Idiopathic Dilated Cardiomyopathy; LAVI: Left Atrial Volume Index; LV: Left Ventricle; LVEF: Left Ventricular Ejection Fraction; LVESD: Left Ventricular End-Systolic Dimension; MACE: Major Adverse Cardiovascular Events; m: meters; msec: millisecond; NYHA: New York Heart Association; QoL: Quality of Life.