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. 2024 Oct 26;24:592. doi: 10.1186/s12872-024-04232-z

Efficacy and safety of coenzyme Q10 in heart failure: a meta-analysis of randomized controlled trials

Jiayi Xu 5,#, Luwei Xiang 1,#, Xuwen Yin 1, Haiyan Song 1, Chen Chen 2, Bei Yang 1, Hongfang Ye 1,3,✉, Zejuan Gu 4,✉
PMCID: PMC11515203  PMID: 39462324

Abstract

Background

The effectiveness and adverse effects of coenzyme Q10 for heart failure remain unclear owing to small sample sizes and variations in the quality of existing studies in literature.

Methods

The databases of EMBASE, PubMed, Web of Science, CINAHL databases, Scopus, Cochrane Central Register of Controlled Trials, VIP, Wanfang, and CNKI were searched for randomized controlled trials on the coenzyme Q10-assisted treatment of heart failure. Relevant literature was retrieved, data were extracted, and the risk of bias of the included studies was evaluated by two investigators independently using the Review Manager 5.4 software and the STATA 15 software.

Results

In total, 33 studies were included in this meta-analysis, which showed that all-cause mortality [RR = 0.64, 95% CI (0.48, 0.85), P = 0.002; GRADE: moderate quality], hospitalization for heart failure [RR = 0.50, 95% CI (0.37, 0.67), P < 0.00001; GRADE: moderate quality], New York Heart Association classification [MD = − 0.29, 95% CI (− 0.39, − 0.19), P < 0.00001; GRADE: low quality], and brain natriuretic peptide level [MD = − 91.97, 95% CI (− 103.11, − 80.83), P < 0.00001; GRADE: low quality] were lower in the coenzyme Q10 group than in the control group. Meanwhile, left ventricular ejection fraction [MD = 0.51, 95% CI (0.31, 0.71), P < 0.00001; GRADE: low quality] and 6-min walk test result [MD = 31.70, 95% CI (19.96, 43.43), P < 0.00001; GRADE: moderate quality] were better than those in the control group.

Conclusions

According to the existing evidence, coenzyme Q10 reduces all-cause mortality, hospitalization for heart failure, New York Heart Association classification, and brain natriuretic peptide level and improves left ventricular ejection fraction and 6-min walk test result in those with heart failure without major adverse effects.

Trial registration

This study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, http://www.crd.york.ac.uk/prospero), with the registration number CRD42023493184.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-024-04232-z.

Keywords: Heart failure, Safety outcomes, Coenzyme Q10, Meta analysis, Randomized controlled trial

Introduction

Heart failure, a complex syndrome resulting from heart abnormalities, impairs heart function and manifests in symptoms like breathlessness and fatigue, along with signs of fluid buildup [1, 2]. As a prevalent syndrome affecting millions globally, it poses substantial health and economic burdens, with costs projected to escalate [3–6]. Characterized by impaired cardiac function and recurrent exacerbations, it carries a significant mortality risk, particularly for hospitalized patients [7]. The condition involves disrupted ATP production and calcium imbalance, leading to oxidative stress and mitochondrial damage, further compounded by overactive sympathetic responses [8–12].

In the past few decades, the treatment of heart failure has mainly relied on β-blockers, ACE inhibitors, and AT1 antagonists to reduce excessive neural and fluid activation and alleviate cardiac burden [13, 14]. Despite alleviating symptoms, these interventions have limited success in improving death and readmission rates [15]. The regulation of cardiac energy constitutes a novel therapeutic approach. Therapies that prevent myocardial energy consumption may play a role in the treatment and management of heart failure. As both an electron transporter and antioxidant, coenzyme Q10 boosts mitochondrial ATP production, which increases myocardial contractility [16, 17]. At present, it is used for heart failure treatment in some studies.

According to meta-analyses of randomized controlled trials (RCTs), coenzyme Q10 improves left ventricular ejection fraction (LVEF) regardless of New York Heart Association (NYHA) class [18–19]. In addition, two systematic reviews of coenzyme Q10 in heart failure reported a reduction in mortality rates [20, 21], whereas one did not [22]. Despite not being the primary treatment method for heart failure, coenzyme Q10 has been proven safe and effective. In spite of this, its efficacy and adverse reactions remain unclear due to small sample sizes and variable quality of existing studies. Thus, the present study conducted a meta-analysis to evaluate the effectiveness and safety of using coenzyme Q10 to treat patients with heart failure and provide evidence-based guidelines.

Materials and methods

The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, http://www.crd.york.ac.uk/prospero), with the registration number CRD42023493184.

Search strategy

To identify RCTs investigating the effect of coenzyme Q10 in patients with heart failure, the databases of EMBASE, PubMed, Web of Science, CINAHL, Scopus, Cochrane Central Register of Controlled Trials, VIP, Wanfang, and CNKI were searched. Next, coenzyme Q10 and heart failure concept groups were developed using medical subject headings and keywords from PubMed. Without applying any additional filters or limits, the Cochrane RCT filter for PubMed was combined with concept groups for coenzyme Q10 and heart failure. Up to April 20, 2024, all the abovementioned databases were searched by two researchers using the search strategies listed in appendix 1, and disputed areas were referred to a third researcher for resolution. To report this systematic review and meta-analysis, the recommendations in the PRISMA statement were followed [23].

Inclusion and exclusion criteria

Study design Studies published in medical journals on the effect of coenzyme Q10 on heart failure were retrieved. In order to reduce the bias of interpretation, only Chinese and English studies were included.

Participants Patients with heart failure aged > 18 years, regardless of their race, nationality, duration of illness, or LVEF were included.

Interventions The experimental group that received coenzyme Q10 as an adjuvant therapy with conventional heart failure treatment was included. For control, patients with heart failure who received only conventional treatment with or without placebo were included. In both groups, the relevant drugs were administered at any dosage for a minimum period of 1 month.

Outcomes The primary outcomes were all-cause mortality and hospitalization for heart failure. The secondary outcomes included LVEF, NYHA classification, brain natriuretic peptide (BNP) level, 6-min walk test (6MWT), and adverse events.

Exclusion criteria Non-Chinese and non-English language studies and duplicate studies were excluded. Moreover, studies without full text and with incomplete data were not considered. Finally, non-RCTs were excluded. Studies in phase1, 2 and 3 trials, observational studies, retrospective studies, reviews, and letters were excluded.

Study selection

Two authors independently screened the titles and abstracts of RCTs that used coenzyme Q10 treatment for patients with heart failure. The shortlisted literature was assessed by reading the title and abstract, and after excluding irrelevant literature, the full text was read to determine final inclusion. Any differences included in the decision were discussed and resolved after reaching a consensus. The kappa agreement index was used to evaluate the level of agreement between the two authors.

Data extraction

A self-developed data extraction form was used to extract the following data: basic information about the included studies, baseline characteristics of the study participants, specific information about the interventions, duration of treatment, and outcome indicators.

Data analysis

Meta-analysis was performed using the Review Manager 5.4 software and the STATA 15 software. For count data, the relative risk (RR) was used as the effect indicator and for measurement data, the mean difference (MD) or standardized mean difference was used. Statistically significant differences were assessed using the point estimates and 95% confidence intervals (CIs). Meanwhile, heterogeneity among the included studies was analyzed using the χ2 test (test level: α = 0.1), and I2 quantification was used to estimate its magnitude. If there was no statistical heterogeneity among the study results, a fixed-effects model was used for meta-analysis. When statistical heterogeneity was detected between the study results, the source of heterogeneity was further analyzed, and after excluding the impact of significant clinical heterogeneity, randomization was performed. A subgroup analysis, sensitivity analysis, or descriptive analysis was performed when there was evident clinical heterogeneity. The meta-analysis test level was set at α = 0.05. The publication bias was assessed according to the funnel plot, the Begg’s test and the Egger’s test. To explore the robustness of the pooled results, sensitivity analysis was carried out using the leave-one-out method.

Risk of bias assessment

Two evaluators independently assessed the risk of bias of the included RCTs using the Cochrane Handbook 5.1.0 risk of bias assessment tool [24]. A third party was consulted when necessary to ensure the accuracy of the final study results. Seven points were followed to assess quality: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting; and (7) other biases. According to the criteria of “low risk of bias,” “unknown risk of bias,” and “high risk of bias,” the quality of the included studies was comprehensively assessed.

Certainty of evidence

GRADE (Grading Recommendations, Assessment, Development, and Evaluation) was used to rate the certainty of evidence for each outcome. The GRADE assessment was carried out using the GRADEpro Guideline Development Tool. Through this approach, bias, inconsistency, indirectness, imprecision, and other considerations (e.g. publication bias) are ranked as “high”, “moderate”, “low,” or “very low.”

Results

Search results

In total, 3961 relevant records were obtained through the electronic search. Of these, 705 duplicate records were removed using the Endnote X9 software. The remaining 3256 records were assessed based on the title or abstract, resulting in the exclusion of 2814 ineligible records. Ultimately, 32 RCTs were included after reviewing the full-text of the remaining 386 records (Fig. 1). The two authors had a high agreement in study selection and data integration (kappa value = 0.825).

Fig. 1.

Fig. 1

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Literature search flow diagram

Study characteristics

The 32 RCTs included 3763 patients with heart failure: 1,898 cases in the treatment group and 1,845 cases in the control group. Among the studies, the maximum sample size was 322 cases [25] and the minimum was 6 [26]. While 22 studies were conducted in Asia [27–48], 1 study recruited participants from Europe, Australia, and Asia [49]. In the intervention group, coenzyme Q10 was combined with conventional treatment. In the control group, conventional treatment was used, with placebo in addition to conventional treatment in 12 studies [25, 26, 28, 39, 44, 48–54]. Except one study [39] that involved nasal drops, coenzyme Q10 was administered orally in all others. The characteristics of the included studies are shown in Table 1.

Table 1.

Characteristics of included studies

No. study Country Sample size
(EXP/CON)		 Age(year)
(EXP/CON)		 Baseline LVEF (%)(EXP/CON) Intervention Control Intervention duration Outcomes Follow-up
1 Permanetter et al. (1992) Germany 15/10 52 ± 9 NR CoQ10(33.3 mg, 3 times/day) + conventional therapy conventional therapy alone 4months ④ NR
2 Morisco et al. (1993) Denmark 319/322

26∽89/

30∽88

 NR coenzyme Q10 50 mg twice or 3 times daily + conventional therapy Placebo + conventional therapy 12months ①② NR
3 Morisco et al. (1994) Italy 6/6 49.8 ± 6.7 29 ± 11 CoQ10(50 mg, 3 times/day) + conventional therapy Placebo + conventional therapy 1month ③⑥ 12months
4 Hofman-Bang et al. (1995) Denmark 79/79 61 ± 10 22 ± 10 CoQ10(100 mg, 1 time/day) + conventional therapy placebo + conventional therapy 3months ①③⑥ 6months
5 Li & Li (1999) China 56/68 NR NR CoQ10(10∽20mg, 3 times/day) + conventional therapy conventional therapy alone 1month ⑦ 12months
6 Munkholm et al. (1999) Denmark 11/11

43∽73/

39∽75

31 ± 5/

26 ± 6

 oral coenzyme Q10 100 mg twice daily + conventional therapy placebo + conventional therapy 3months ①③ NR
7 Watson et al. (1999) Australia 30/30 55 ± 11 26 ± 6 CoQ10(33 mg, 3 times/day) + conventional therapy placebo + conventional therapy 3months ③ NR
8 Khatta et al. (2000) America 28/27 67 27/30 oral coenzyme Q10 200 mg/day + conventional therapy placebo + conventional therapy 1months ①③ 6months
9 Keogh et al. (2003) Australia 79/79 62 ± 7/61 ± 9 NR oral coenzyme Q10 150 mg/day + conventional therapy placebo + conventional therapy 3months ④⑥ 3months
10 Belardinelli et al. (2006) Italy 21/21 59 ± 9 37 ± 7 CoQ10(100 mg, 3 times/day) + conventional therapy placebo + conventional therapy 1month ③ NR
11 Adarsh et al. (2008) India 46/41 24.4∽77.5 NR CoQ10(100 mg, 2 times/day) + conventional therapy placebo + conventional therapy 14.5months ① 27.5months
12 Feng et al. (2010) China 109/92

69 ± 7/

68 ± 9

30.7 ± 6.3/

31.2 ± 5.8

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 24months ①③⑥ 24months
13 Pei et al. (2010) China 62/66 62.47 ± 6.48 36 ± 4 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 12months ①③ 12months
14 Bi (2012) China 27/27 49.5 ± 12.5

25.77 ± 12.59/

26.33 ± 10.43

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 3weeks ③④ NR
15 Yao et al. (2012) China 50/50 62 ± 8/61 ± 9 36 ± 8 CoQ10(100 mg, 1 time/day) + conventional therapy conventional therapy alone 3months ③④⑥ NR
16 Yang(2013) China 100/100 68.4 ± 13.85 NR CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 2months ① 12months
17 Mortensen et al. (2014) Multicenter 202/218

62.3 ± 12/

62.3 ± 11

 31 ± 10 oral coenzyme Q10 100 mg 3 times daily + conventional therapy placebo with standard HF therapy 26.5months ①②③⑦ NR
18 Wu (2014) China 35/35

84.5 ± 12.2/

86.6 ± 14.3

 NR CoQ10(10 mg, 3 times/day) + conventional therapy Placebo + conventional therapy 2months ①⑦ NR
19 Zhao et al. (2015) China 62/66 63 ± 7/62 ± 6 36 ± 4 oral coenzyme Q10 30 mg/day + conventional therapy conventional therapy alone 12months ①③ NR
20 Ping et al. (2015) China 61/61 58.3 ± 4.7

36.82 ± 8.53/

37.19 ± 7.96

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 3months ③⑥ NR
21 Zhang (2015) China 28/28

65.4 ± 10.4/

63.1 ± 10.2

 NR CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 6months ⑥⑦ NR
22 Zhang (2016) China 30/30 38∽83

29 ± 7/

31 ± 8

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 3months ②③④⑥ NR
23 Mareev (2017) Russia 101/47 NR 39.3 coenzyme Q10 nasal drops (90 mg/day = equivalent 225 mg/day for liposoluble tablets) + conventional therapy placebo + conventional therapy 6months ③⑤ NR
24 Sobirin et al. (2019) Indonesia 15/15 62 ± 8 55/58 oral coenzyme Q10 100 mg 3 times/day + conventional therapy conventional therapy alone 1month ③ 14months
25 Gan & Hu (2019) China 30/30

57.5 ± 6.1/

58.4 ± 6.7

35.1 ± 4.0/

34.5 ± 3.9

 CoQ10(30 mg, 1 time/day) + conventional therapy conventional therapy alone 12months ③ NR
26 Jiang (2019) China 100/100

61.9 ± 5.6/

61.3 ± 5.9

32.78 ± 3.40/

33.58 ± 3.76

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 1month ③⑥⑦ NR
27 Wu et al. (2019) China 34/33

55.28 ± 12.53/

55.12 ± 12.12

31.86 ± 6.53/

31.86 ± 6.38

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 2months ③⑥⑦ NR
28 Kawashima et al. (2020) Japan 10/10 70 ± 9 34.5 ± 4.0 ubiquinol 200 mg twice daily (400 mg/day) + conventional therapy placebo + conventional therapy 3months ③⑤⑦ 3months
29 Liu (2020) China 59/59

58.67 ± 7.28/

58.43 ± 7.55

33.47 ± 3.82/

32.67 ± 3.59

 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 1month ③⑥⑦ NR
30 Wan et al. (2021) China 30/30

63.52 ± 3.76/

63.41 ± 3.70

 38.25 ± 3.19 CoQ10(20 mg, 3 times/day) + conventional therapy conventional therapy alone 1.5months ③⑥⑦ NR
31 Zheng et al. (2021) China 44/34

62.0 ± 3.9/

62.8 ± 3.5

 29 CoQ10(10 mg, 3 times/day) + conventional therapy conventional therapy alone 3months ③ NR
32 Samuel et al. (2022) Israel 19/20 75.4 ± 9.48

59.1 ± 6.1/

59.3 ± 6.1

 Treatment in the CoQ10 arm consisted of 100 mg three times daily + conventional therapy placebo + conventional therapy 4months ③ 4months
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Note EXP, Experimental group; CON, Control group; NR, Not report; ①All-cause mortality; ②Hospitalization for heart failure; ③LVEF (%); ④NYHA classification; ⑤BNP (pg/mL); ⑥6MWT; ⑦Adverse events

Risk of bias of included studies

Two investigators independently assessed the risk of bias in the included studies. There was insufficient information in most studies, which made a comprehensive assessment of the risk of bias difficult. Of the 32 studies, only 6 reported randomization methods [25, 32, 40, 48, 49, 53] and only 3 reported allocation concealment [44, 48, 49]. Meanwhile, 16 studies reported participant and personnel blinding to random assignment [25, 26, 32, 33, 36, 39, 44, 48–56]. The total number of cases in one study did not correspond to the number of grouped cases [29], whereas multiple groups were analyzed in another study, of which two data sets were used in this investigation [43]. Figure 2A and B show the risk of bias of included studies.

Fig. 2.

Fig. 2

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Risk of bias summary and graph. Note A. Risk of bias summary; A. Risk of bias graph

Meta-analysis results

Primary outcomes

All-cause mortality

Eleven studies, with 2070 participants (1035 in the coenzyme Q10 group and 1035 in the control group), reported all-cause mortality [25, 28–30, 33, 34, 36, 49–51, 53]. Meta-analysis showed that all-cause mortality was significantly lower in the coenzyme Q10 group than in the control group [RR = 0.64, 95% CI (0.48, 0.85), P = 0.002; GRADE: moderate quality]. Figure 3A shows that there was no heterogeneity among the included studies (P = 0.99, I2 = 0%).

Fig. 3.

Fig. 3

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Forest plot of the effect of coenzyme Q10 on primary outcomes change. Note A. Forest Plot of the Effect of Coenzyme Q10 on All-cause Mortality Change; B. Forest Plot of the Effect of Coenzyme Q10 on Hospitalization for Heart Failure Change

Hospitalization for heart failure

Three studies reported hospitalization for heart failure as an outcome indicator [25, 38, 49]. A total of 1034 participants were included, 511 in the coenzyme Q10 group and 523 in the control group. As shown in Fig. 3B, there was no significant heterogeneity among the included studies (P = 0.93, I2 = 0%). The result showed that the coenzyme Q10 was able to reduce the hospitalization for heart failure compared to the control group. [RR = 0.50, 95% CI (0.37, 0.67), P < 0.00001; GRADE: moderate quality].

Secondary outcomes

Left ventricular ejection fraction (LVEF, %)

With regard to LVEF, 2339 patients from 24 RCTs were included (1197 in the coenzyme Q10 group and 1142 in the control group) [26, 29–32, 35, 36, 38–54]. Notably, the LVEF of patients with heart failure included in these studies was not statistically different at baseline. There was significant heterogeneity among the included studies (P < 0.00001, I2 = 80%), and a random-effects model was used for the meta-analysis. Patients with heart failure in the coenzyme Q10 group had a significantly better LVEF than those in the control group [MD = 0.51, 95% CI (0.31, 0.71), P < 0.00001; GRADE: low quality]. In the subgroup analysis by the baseline LVEF, 22 RCTs including heart failure with reduced ejection fraction (HFrEF) demonstrated that the coenzyme Q10 group had a significantly higher LVEF than the control group [MD = 0.55, 95% CI (0.34, 0.76), P < 0.00001]. (Fig. 4).

Fig. 4.

Fig. 4

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Forest plot of the effect of coenzyme Q10 on left ventricular ejection fraction (LVEF) change

NYHA classification

Five studies were included in this outcome index, covering 269 patients with heart failure (138 in the coenzyme Q10 group and 131 in the control group) [31, 32, 38, 55, 56]. The results showed that patients in the coenzyme Q10 group had a significantly lower NYHA classification than those in the control group [MD = − 0.29, 95% CI (− 0.39, − 0.19), P < 0.00001; GRADE: low quality; Fig. 5A]. Heterogeneity among the included studies was low (P = 0.10, I2 = 49%).

Fig. 5.

Fig. 5

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Forest plots of the effect of coenzyme Q10 on NYHA classification, BNP, 6MWT, adverse events change. Note A. Forest Plots of the Effect of Coenzyme Q10 on NYHA Classification; B. Forest Plots of the Effect of Coenzyme Q10 on BNP Change; C. Forest Plots of the Effect of Coenzyme Q10 on 6MWT Change; D. Forest Plots of the Effect of Coenzyme Q10 on adverse events Change

BNP (peg/mL)

Two RCTs reported BNP as an outcome indicator, including 162 participants (106 in the coenzyme Q10 group and 56 in the control group) [39, 44]. There was no significant heterogeneity among the included studies (P = 0.94, I2 = 0%), and BNP was significantly lower in the coenzyme Q10 group than in the control group [MD = − 91.97, 95% CI (− 103.11, − 80.83), P < 0.00001; GRADE: low quality; Fig. 5B].

6MWT

In total, 12 studies evaluated 6MWT in 1184 patients with heart failure, with 602 in the coenzyme Q10 group and 582 in the control group [26, 29, 32, 35, 37, 38, 42, 43, 45, 46, 50, 55]. As the included studies were highly heterogeneous (P < 0.00001, I2 = 82%), a random-effects model was applied. Compared with the control group, patients with heart failure taking coenzyme Q10 had significantly longer 6MWTs [MD = 31.70, 95% CI (19.96, 43.43), P < 0.00001; GRADE: moderate quality]. Afterward, based on the length of the course of treatment, three groups were analyzed: ≤1-month group, 1–3-month group, and > 3-month group. Figure 5C illustrates that regardless of the distances of the course of treatment, 6MWT distances were longer in patients with heart failure who received coenzyme Q10.

Adverse events

The incidence of adverse events was reported in nine studies [27, 34, 37, 42–46, 49]. A total of 1125 patients were included: 554 in the coenzyme Q10 group and 571 in the control group. Some of the adverse reactions were deep vein thrombosis, stroke, myocardial infarction, and arrhythmia. According to Fig. 5D, heterogeneity among the included studies was small (P = 0.19, I2 = 33%; GRADE: moderate quality). Meanwhile, the results were inconclusive for the risk of adverse reactions between the CoQ10 and control groups [RR = 0.85, 95% CI (0.46, 1.54), P = 0.58].

Publication bias assessment and sensitivity analysis

Funnel plots were analyzed to detect publication bias, which indicated that the included studies were evenly distributed on the left and right sides of the combined effect value line, suggesting low publication bias. At the same time, the results of both the Begg’s test and the Egger’s test showed no significant publication bias (Appendix 2). A leave-one-out sensitivity analysis was performed on the outcomes of meta-analyses. Exclusion of individual studies did not lead to significant changes in the direction or magnitude of the combined estimates, indicating that the results were reliable (Appendix 3).

Discussion

This meta-analysis, incorporating 32 randomized controlled trials and 3,763 heart failure patients, reveals promising outcomes for coenzyme Q10 supplementation in conjunction with conventional therapy.

This study has shown that coenzyme Q10 reduced all-cause mortality and hospitalization for heart failure as well as increased LVEF in patients with heart failure [17–19], crucial for improving patient outcomes and reducing healthcare utilization. Moreover, a previous meta-analysis showed that coenzyme Q10 improved the NYHA classification of patients with heart failure, in line with a similar improvement found in the current study [21]. Coenzyme Q10 is a cofactor in the mitochondrial enzyme complex and participates in oxidative phosphorylation in the respiratory chain [57, 58]. In the absence of coenzyme Q10, ATP production is reduced and heart failure may be aggravated because of increased myocardial wall pressure. This, in turn, increases energy demand, resulting in imbalanced supply and demand [59]. Previous research has shown that there is a negative correlation between coenzyme Q10 level and the exacerbation of heart failure symptoms in patients with heart failure [20]. Therefore, the supplementation of coenzyme Q10 may reduce major adverse cardiovascular events and improve heart failure symptoms.

In addition to being a biomarker of cardiac disease, BNP is used as a surrogate marker for heart failure, acute coronary syndrome, and myocardial infarction. Research has shown that it plays a significant role in stratifying heart failure severity. To some extent, the decrease of BNP level reflects the improvement of heart function [60]. The present study showed that coenzyme Q10 significantly decreased BNP levels in patients with heart failure, similar to previous research [44]. 6MWT, which examines exercise tolerance, was chosen in this study, as it is a simple and inexpensive test that is well tolerated by patients with heart failure and is considered useful in their management [61]. The results of this meta-analysis suggested that no matter how long patients with heart failure were treated with coenzyme Q10, 6MWT distances were longer and points to its utility in promoting functional independence and daily activity among heart failure patients. Despite the moderate quality of the evidence supporting this conclusion, it deserves clinical attention. Safety data, showing no increase in adverse events, reinforces coenzyme Q10’s tolerability as an adjunct therapy, important in the primary care setting where patient safety is paramount, especially for those with complex health conditions.

While recognizing the variable study quality and need for more rigorous research, our findings offer primary care physicians a basis for discussing coenzyme Q10 supplementation with suitable heart failure patients. Incorporating shared decision-making, physicians can weigh the potential benefits against the current evidence, tailoring recommendations to each patient’s circumstances. Ultimately, coenzyme Q10 emerges as a supplementary option, warranting cautious optimism and further exploration within the context of comprehensive heart failure management strategies.

Considering the importance of nonpharmacologic therapy for patients with heart failure, this study sought to explore how more data on nonpharmacologic therapy might affect outcomes. Unfortunately, few articles described non-pharmacologic treatments during the intervention, and even fewer reported whether surgically treated patients with heart failure were included. For example, one study advised patients to follow a low-fat diet during the trial, but no exercise program was provided [55]. Some studies did not make baseline comparisons related to non-pharmacological treatment for heart failure patients, such as comparing only their exercise capacity, while ignoring their exercise habits, such as their duration and frequency [49, 50]. In light of the important role exercise-based cardiac rehabilitation programs play in treating heart failure patients, further refinement is needed. Patients with heart failure were given coenzyme Q10 at doses ranging from 30 mg to 400 mg per day in the studies included. There was no determination of the minimum and optimal doses for coenzyme Q10 use, and further dose-response analyses will be required in the future.

This study significantly enhances knowledge on coenzyme Q10 (CoQ10) use in heart failure patients. By integrating recent trials with a large combined participant pool, we provide a robust update on CoQ10’s effectiveness and safety, with broadened applicability of the results. A key novelty lies in the inclusion of Chinese RCTs, addressing a demographic gap in prior reviews and deepening the global comprehension of CoQ10 benefits across diverse populations. We meticulously examined CoQ10 impact on vital clinical measures, presenting a comprehensive view of its therapeutic prowess. These outcomes reinforce CoQ10 potential as a safe and efficacious supplement, accentuating its role in bolstering cardiac function and mitigating the disease’s debilitating effects.

To overcome potential limitations, rigorous actions were undertaken. These included conducting a comprehensive literature search focusing on high-quality randomized controlled trials, implementing strict inclusion and exclusion criteria, assessing risk of bias systematically, performing subgroup and sensitivity analyses to address heterogeneity, and other measures. However, there are still some unresolved limitations. First, heterogeneity among studies related to LVEF and 6MWT was high among the outcomes included. Although subgroup analysis based on the baseline LVEF and the length of the course of treatment had been performed, the sources of heterogeneity could not be identified. It was possible, however, that heterogeneity arose from differences in drug tolerance, different environments, and differences in how the indices were measured in different patients in addition to differences in the severity of their disease. Unfortunately, additional subgroups could not be analyzed owing to the lack of relevant data. Moreover, the dosage or duration of coenzyme Q10 administration was not uniform across studies, which may have affected the reliability of the results. In addition, accessibility issues hindered the search for grey literature, which is one of the limitations of this study. Finally, the risk of bias assessment of the included studies revealed that most were of low quality and methodologically flawed. To validate the results of the present study, additional high-quality RCTs are needed in the future.

Conclusions

In summary, current evidence suggested that adjuvant coenzyme Q10 therapy in patients with heart failure not only reduced all-cause mortality, hospitalization for heart failure, NYHA classification, and BNP levels but also improved LVEF and 6MWT. However, owing to the different severities of heart failure, long gap between studies, heterogeneity among the study populations, errors in the test results of each unit, and differences in the treatment dosages and courses, additional high-quality, large-sample, long-term follow-up clinical studies are needed to validate these conclusions.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1 (127.5KB, docx)
Supplementary Material 2 (569.2KB, docx)
Supplementary Material 3 (33.5KB, docx)
Supplementary Material 4 (20.1KB, docx)

Acknowledgements

It is with great gratitude that we thank the authors of the included publications, especially their corresponding authors, for providing data to this study.

Abbreviations

ATP

Adenosine triphosphate

ROS

Reactive oxygen species

RCTs

Randomized controlled trials

LVEF

Left ventricular ejection fraction

NYHA

New York Heart Association

BNP

Brain natriuretic peptide

6MWT

6-minute walk test

RR

Relative risk

MD

Mean difference

SMD

Standardized mean difference

HFrEF

Heart failure with reduced ejection fraction

Author contributions

Designing this study: Z. G.; H. Y.; J. X.; L. X. Performed this study: J. X.; L. X.; X.Y.; H. S. Analyzing the data: J. X.; L. X.; C. C.; B. Y. Drafted the article: J. X.; L. X.; X.Y.; H. S.; C. C.; B. Y. Revised the article critically for important intellectual content: Z.G.; H. Y. All authors reviewed the manuscript.

Funding

This work was supported by the Jiangsu Provincial Medical Innovation Team (CXTDA2017019).

Data availability

The original data used during the current study can be obtained by contacting the corresponding author.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Jiayi Xu and Luwei Xiang contributed equally to this work and should be considered co-first authors.

Contributor Information

Hongfang Ye, Email: 13915969627@163.com.

Zejuan Gu, Email: jassicagu@163.com.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1 (127.5KB, docx)
Supplementary Material 2 (569.2KB, docx)
Supplementary Material 3 (33.5KB, docx)
Supplementary Material 4 (20.1KB, docx)

Data Availability Statement

The original data used during the current study can be obtained by contacting the corresponding author.

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