CoQ10 LIPID PROFILES

The Journal of Clinical Endocrinology & Metabolism, 2023, 108, 232–249
https://doi.org/10.1210/clinem/dgac585
Advance access publication 7 October 2022
Meta-Analysis
Effects of Coenzyme Q10 Supplementation on Lipid Profiles

in Adults: A Meta-analysis of Randomized Controlled Trials
Zhihao Liu,1,2,3 Zezhong Tian,1,2,3 Dan Zhao,1,2,3 Ying Liang,1,2,3 Suming Dai,1,2,3 Meitong Liu,1,2,3
Shanshan Hou,1,2,3 Xiaoxi Dong,1 Zhaxinima,1 and Yan Yang1,2,3,4
1
School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107, Guangdong
Province, PR China
Downloaded from https://academic.oup.com/jcem/article/108/1/232/6751027 by guest on 27 March 2024

2
Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou 510080, China
3
Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou 510080, China
4
China-DRIs Expert Committee on Other Food Substances, Guangzhou 510080, China
Correspondence: Yan Yang, School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107,
Guangdong Province, PR China. Email: yangyan3@mail.sysu.edu.cn.
Abstract
Context: Previous meta-analyses have suggested that the effects of coenzyme Q10 (CoQ10) on lipid profiles remain debatable. Additionally, no
meta-analysis has explored the optimal intake of CoQ10 for attenuating lipid profiles in adults.
Objective: This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose–response
relationships in adults.
Methods: Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10,
2022. The random effects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulating lipid profiles. The
novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose–response relationships.
Results: Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis
revealed that CoQ10 supplementation significantly reduced total cholesterol (TC) (MD −5.53 mg/dL; 95% CI −8.40, −2.66; I2 = 70%),
low-density lipoprotein cholesterol (LDL-C) (MD −3.03 mg/dL; 95% CI −5.25, −0.81; I2 = 54%), and triglycerides (TGs) (MD −9.06 mg/dL;
95% CI −14.04, −4.08; I2 = 65%) and increased high-density lipoprotein cholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%).
The dose–response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day
CoQ10 largely reduced TC (χ2 = 48.54, P < .01).
Conclusion: CoQ10 supplementation decreased the TC, LDL-C, and TG levels, and increased HDL-C levels in adults, and the dosage of 400 to
500 mg/day achieved the greatest effect on TC.
Key Words: CoQ10 supplementation, lipid profiles, dyslipidemia, meta-analysis
Abbreviations: CoQ10, coenzyme Q10; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MD, mean difference; RCT,
randomized controlled trial; TC, total cholesterol; TG, triglyceride.
Dyslipidemia is an alteration in circulating lipid profiles char located in the inner mitochondrial membrane, plays an im
acterized by increased total cholesterol (TC), low-density lipo portant role in the electron transport chain. CoQ10 has basic
protein cholesterol (LDL-C), triglyceride (TG), and/or physiological functions, such as participating in oxidative
decreased high-density lipoprotein cholesterol (HDL-C) levels phosphorylation and the production of adenosine triphos
(1). Poorly controlled dyslipidemia is associated with clinical phate, activating cellular metabolism and cellular respiration,
diseases, including diabetes (2), nonalcoholic steatohepatitis regulating cytoplasmic redox potential, and inhibiting super
(3), and cancers (4), and is considered a major risk factor oxide formation (9, 10). In addition, previous in vitro and in
for atherosclerotic cardiovascular diseases (5). Moreover, ele vivo studies have shown that CoQ10 could promote lipolysis
vated LDL-C levels were attributable to 3.79 million deaths of TGs in the process of endothelial metabolism and facilitate
from ischemic heart diseases and 0.532 million deaths from is cholesterol efflux from macrophages, which might be poten
chemic stroke in 2017 globally (6). Therefore, it is essential tial mechanisms for CoQ10 to lower circulating lipid profiles
to explore effective strategies for the regulation of lipid (11–14). In general, the human body cannot synthesize a suf
profiles (7). ficient amount of CoQ10 in some pathological conditions,
For decades, nutritional strategies to reduce the risk of ath such as metabolic syndrome, hypertension, diabetes mellitus,
erosclerotic cardiovascular diseases have attracted much at and dyslipidemia (15). In addition, multiple studies have
tention. Coenzyme Q10 (CoQ10) is a nonessential nutrient shown that the serum CoQ10 levels in dyslipidemic patients
and vitamin-like fat-soluble benzoquinone (8). CoQ10, taking lipid-lowering drugs (statins) were low, which
Received: 30 June 2022. Editorial Decision: 4 October 2022. Corrected and Typeset: 7 November 2022
© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail:
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The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1 233
restricted the use of lipid-lowering drugs (16, 17). Therefore, Data Extraction
additional CoQ10 supplementation might be utilized to ad Eligible studies were independently reviewed by 2 investi
dress these health concerns. gators (Z.L. and M.L.), and extracted data included the
A number of randomized controlled trials (RCTs) have name of the first author, year of publication, country of
suggested that CoQ10 supplementation has beneficial origin, type of intervention, form of intervention, sample
effects on circulating lipid profiles (18, 19). Several previous size (in intervention and control groups), participant
meta-analyses of RCTs have shown that CoQ10 supplementa demographics (age, gender, baseline lipid profiles, and
tion was effective in improving lipid profiles, especially body mass index), CoQ10 form, dosage of CoQ10 supple
TC, LDL-C, HDL-C, and TGs, in various disease states mentation, duration of intervention, health status of par
(11, 20–22). However, some previous studies failed to show ticipants, and the changes in HDL-C, LDL-C, TC, and
beneficial effects of CoQ10 supplementation on any lipid pro TGs from baseline to end trial in both the intervention
file (23–25). These results suggest that the effect of CoQ10 on and the control groups.
circulating lipids is still controversial. Furthermore, previous
meta-analyses only focused on populations with specific dis
Quality Assessment and Certainty of Evidence

eases, such as patients with coronary artery diseases (19),
metabolic diseases (20), or diabetes (21). However, no study Study quality for this meta-analysis was independently
has explored the effect of CoQ10 on the general population, measured by 2 reviewers (Z.L. and M.L.) using the
especially the adult population. Additionally, the effective Cochrane Collaboration’s modified risk of bias tool (28).
dose of CoQ10 on the control of lipid profiles, especially the The terms “low”, “high” or “unclear” were used to rate
dose–response relationship, has not been explored. This study bias in 7 domains, including random sequence gen
knowledge gap has restricted the application of CoQ10 in con eration, allocation concealment, performance bias, detec
trolling blood lipid levels. tion bias, attrition bias, reporting bias and other bias.
We conducted this systematic review and meta-analysis to The GRADE (Grading of Recommendations Assessment,
formulate a clear role of CoQ10 supplementation on lipid Development, and Evaluation) methods were used to as
markers in adults. Furthermore, we assessed the dose– sess the overall certainty of evidence in studies by
response relationships to determine the effective dose of GRADEpro software (version 3.6). The primary outcomes
CoQ10 supplementation on improving plasma lipid profiles were classified into 4 levels (high, moderate, low, or very
in adults. low) according to study design, risk of bias, inconsistency,
indirectness, imprecision, and other considerations (such
as publication bias) (29).
Materials and Methods
This systematic review is based on the guidelines of the Statistical Analyses
Preferred Reporting Items for Systematic Reviews and Circulating concentrations of lipid profiles were collated in
Meta-Analyses (PRISMA) statement and has been registered milligrams per deciliter (mg/dL). Inverse-variance weighting
on PROSPERO (26). The registration number is was used to calculate the mean differences (MDs) and 95%
CRD42021252933. CI for net changes in circulating lipid profiles. We calculated
the net changes by using the differences (intervention minus
control) in the changes (final values minus baseline values)
Search Strategy in mean values. SDs of MDs were available in 9 studies, and
To find relevant studies on the effects of CoQ10 supplementa they were directly applied in our meta-analysis. For other
tion on lipid profiles in humans, this systematic review and studies that did not report them, we calculated the SD of the
meta-analysis conducted a comprehensive literature search MD using the following formula (30):
in online databases, including Web of Science, PubMed/
SD
Medline, Embase, and the Cochrane Library, until August 􏽱��
10, 2022. The following search terms were used in our search = (SDbaseline)2 + (SDfinal)2 − (2R × SDbaseline × SDfinal),
strategy: (triglyceride) OR (TG) OR (total cholesterol) OR
(TC) OR (low-density lipoprotein cholesterol) OR (LDL chol where R is the correlation coefficient between preinterven
esterol) OR (LDL-C) OR (high-density lipoprotein choles tion and postintervention; as R was not available in those
terol) OR (HDL cholesterol) OR (HDL-C)) AND studies, the correlation coefficient was conservatively set at
((Coenzyme Q10) OR (CoQ10) OR (Ubiquinone)). The de 0.5 as previously reported (31, 32). The random effects
tailed search strategies are reported elsewhere (Table S1 (27)). model of DerSimonian and Laird was conducted to deter
mine the overall effect sizes to minimize the effects of het
erogeneity between studies (33). Subgroup analyses were
Study Selection conducted by multiple factors, including baseline circulat
The inclusion criteria for this meta-analysis were as follows: ing concentrations on TC (<200 and ≥200 mg/dL), LDL-C
(1) RCTs with parallel or crossover designs, (2) use of (<130 and ≥130 mg/dL), HDL-C (≥50 and <50 mg/dL),
CoQ10 intervention, (3) intervention time ≥14 days, (4) meas and TGs (<150 and ≥150 mg/dL), health condition
urements of TGs, TC, LDL-C, or HDL-C at the beginning and (healthy, diabetes, dyslipidemia, cardiovascular diseases,
end of the trials, and (5) a placebo control or other suitable chronic kidney disease, and other diseases), CoQ10 form
forms of control. The exclusion criteria included (1) acute (ubiquinone and ubiquinol), type of intervention (CoQ10
feeding trials, (2) pregnant or lactating women as subjects, and CoQ10 + other), dosage of intervention (<200 and
and (3) trials with a multifactorial design. ≥200 mg/day), duration of study (<12 and ≥12 weeks),
234 The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
and whether funded by industry (Yes and No). The P value 95% CI −26.88, 3.44), and other diseases (MD −6.51 mg/
of the Cochrane’s Q test and I2 index were used to evalu dL, 95% CI −13.04, 0.02). A marginally significant subgroup
ate heterogeneity between studies. Sensitivity analyses difference was observed between CoQ10 supplemental dosage
were performed using the single-study deletion (P for subgroup difference = .08): the CoQ10 intervention ef
(leave-one-out) approach to assess the effect of each study fect on TC was −2.55 mg/dL (95% CI −5.79, 0.70) with-low
on the overall effect size. A single-stage restricted cubic dosage CoQ10 (<200 mg/day) and −7.18 mg/dL (95% CI
spline regression model was applied to explore nonlinear −11.12, −3.23) with high-dosage CoQ10 (≥200 mg/day)
dose–response relationships (34, 35). Potential publication (Table 3).
bias was indicated using Begg’s rank test, Egger’s test, and
funnel plots (36). Statistical analysis was conducted using
the meta package (version 5.1.1) (37) and the dosresmeta
The Effects of CoQ10 Supplementation on
package (version 2.0.1) (38) based on R (version 4.1.0,
Low-Density Lipoprotein Cholesterol
www.R-project.org). A 2-tailed P < .05 was considered
statistically significant. Forty-two RCTs with 1202 subjects in the CoQ10 arm and
1185 subjects in the control arm showed a significant decrease

in circulating LDL-C levels (MD −3.03 mg/dL; 95% CI
Results −5.25, −0.81; I2 = 54%, P < .01) (Fig. 3B) following supple
mentation with CoQ10 regardless of intervention type.
Flow and Characteristics of Studies
Removing any of the studies did not significantly change the
After the multiple database search, 3364 articles were identi pooled effect on LDL-C (Fig. 4B). We did not observe signifi
fied, of which 1023 were rejected due to duplication. After re cant subgroup differences, implying that there was no signifi
viewing the titles and abstracts of the articles, 2259 articles cant source of heterogeneity (all P for heterogeneity of
were excluded for the following reasons: titles and abstracts intervention effects of CoQ10 on LDL-C between subgroups
not relevant to this study (n = 1907), animal studies > .05, Table 3).
(n = 182), and review studies (n = 170). As a result, 82 articles
were reviewed for full text, of which 30 articles were excluded
because they did not meet the inclusion and exclusion criteria,
and 2 articles were excluded because they were duplicate tri The Effect of CoQ10 Supplementation on
als. Finally, this study included 50 articles that met all neces High-Density Lipoprotein Cholesterol
sary criteria for a meta-analysis (Fig. 1). Forty-one RCTs including 2409 subjects (1214 subjects in
The characteristics of the included studies are shown in the CoQ10 arm and 1195 subjects in the control arm) indi
Table 1. Fifty RCTs included 60 trial comparisons with a to cated a significant increase in circulating HDL-C concentra
tal of 2794 participants (interventions = 1408 and controls tions (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%, P <
= 1386). The included articles were published between .01) (Fig. 3C) following CoQ10 supplementation. The
1994 and 2022. Fifty-five studies were designed as parallel pooled effect of HDL-C was marginally weaker after re
studies, and the remaining 5 studies had a crossover design. moving the study of Mohseni M. 2015 (67) (MD 0.40 mg/
The CoQ10 dosages ranged from 100 mg/day to 900 mg/ dL; 95% CI −0.27, 1.06) or Singh R.B. 2003 (78) (MD
day, and durations of supplementation varied from 2 to 0.73 mg/dL; 95% CI −0.09, 1.56) (Fig. 4C). The subgroup
52 weeks. The quality assessment of the included studies analysis suggested that subjects’ health conditions were a
is provided in Fig. 2. The GRADE assessment profiles are significant source of heterogeneity across studies (P for sub
shown in Table 2. group difference = .03); the CoQ10 intervention effect on
HDL-C was (MD 3.69 mg/dL; 95% CI 0.09, 7.30) among
subjects with dyslipidemia, which was significantly stronger
The Effects of CoQ10 Supplementation on Total
than that among subjects with diabetes (MD 0.17 mg/dL;
Cholesterol
95% CI −1.37, 1.71), cardiovascular diseases (MD
Following CoQ10 supplementation, 45 RCTs with a total of 0.91 mg/dL; 95% CI −1.10, 2.91), chronic kidney disease
2616 subjects (1318 in the CoQ10 arm and 1298 in the control (MD −2.69 mg/dL; 95% CI −4.82, −0.56), other diseases
arm) reported the effects of CoQ10 supplementation on TC. (MD 0.73 mg/dL; 95% CI −0.32, 1.78), and healthy sub
Because of the significant heterogeneity between studies, a jects (MD 0.16 mg/dL; 95% CI −2.42, 2.73) (Table 3).
random-effects model was used to calculate pooled effects.
The results revealed that CoQ10 supplementation significantly
reduced plasma TC levels (MD −5.53 mg/dL; 95% CI −8.40,
−2.66; I2 = 70%, P < .01) (Fig. 3A). Removing individual stud The Effect of CoQ10 Supplementation on
ies did not materially change the pooled estimation of the Triglycerides
CoQ10 intervention effect on TC (Fig. 4A). The subgroup ana Forty-two RCTs including 1228 subjects in the CoQ10 arm
lysis suggested that subjects’ health conditions were a major and 1215 subjects in the control arm indicated an overall
source of heterogeneity across studies (P for subgroup differ effect of significantly reduced circulating TG concentrations
ence < .01); CoQ10 intervention effect on TC was significant (MD −9.06 mg/dL; 95% CI −14.04, −4.08; I2 = 65%,
(MD −12.30 mg/dL; 95% CI −14.89, −9.71) among healthy P < .01) (Fig. 3D). The pooled effect of CoQ10 on TG did
subjects, which was significantly stronger than that among not change significantly after removing any of the studies
subjects with diabetes (MD −2.08 mg/dL; 95% CI −6.18, (Fig. 4D). Despite high sources of heterogeneity, the test for
2.03), dyslipidemia (MD −4.53 mg/dL; 95% CI −15.96, subgroup differences indicated no significant effect (all Ps
6.89), cardiovascular diseases (MD −0.98 mg/dL; 95% CI for heterogeneity of intervention effects of CoQ10 on TG be
−3.66, 1.71), chronic kidney disease (MD −11.72 mg/dL; tween subgroups > .05, Table 3).

Figure 1. Flow diagram of the literature search process.
Dose–Response Relationships Between CoQ10 decreasing TC, LDL-C, and TG and increasing HDL-C lev
Supplementation and Lipid Profiles els in the adult population. The dose–response analysis re
The dose–response analysis showed that CoQ10 supplementa vealed an inverse J-shaped nonlinear pattern between
tion reduced TC with an inverse J-shaped nonlinear relation CoQ10 supplementation and TC, in which the optimal
ship: the beneficial effects increase with the CoQ10 dose was 400 to 500 mg/day. To date, this is the largest
supplementation dosage when it was below 400 mg/day and meta-analysis (60 studies included) evaluating this associ
then remained flat at that low level (χ2 = 48.54, P < .01) ation, while previous meta-analyses included fewer than
(Fig. 5). We did not find clear dose–response relationships of 25 studies (11, 20–22, 24, 25).
CoQ10 with LDL-C, HDL-C, and TG. This study quantified the potential effects of CoQ10 supple
mentation on lipid profiles: TC decreased by approximately
5.53 mg/dL, LDL-C decreased by approximately 3.03 mg/
Publication Bias dL, TG decreased by approximately 9.06 mg/dL, and
Publication bias was determined by funnel plot, and Begg’s HDL-C increased by approximately 0.83 mg/dL. Based on a
rank test and Egger’s test. As shown in Fig. 6, Begg’s rank meta-analysis quantifying the association between LDL-C
test and Egger’s test indicated no significant evidence of pub and coronary mortality, which showed a 19% reduction in
lication bias for studies evaluating the effects of CoQ10 on TC coronary mortality per mmol/L reduction in LDL-C (86).
(Begg’s: z = 1.05, P = .29; Egger’s: t = 0.21, P = .84), LDL-C This means that reducing LDL-C by 3.03 mg/dL might lower
(Begg’s: z = 1.38, P = 0.17; Egger’s: t = −1.46, P = .15), coronary mortality by approximately 1.49%. Moreover, evi
HDL-C (Begg’s: z = −0.32, P = 0.75; Egger’s: t = 0.50, dence has shown that TG levels and TC levels are positively
P = .62), and TG (Begg’s: z = 0.91, P = .36; Egger’s: t = −0.58, associated with the incidence and mortality of CVDs, while
P = .57). HDL-C is negatively correlated with those risk factors (87–
89). Therefore, the modest decrease in lipid profiles by
CoQ10 supplementation might be helpful for the early preven
Discussion tion of CVDs.
Based on 50 RCTs with 2794 subjects, the results of this sys The results of previous meta-analyses suggested the bene
tematic review and meta-analysis indicated that CoQ10 sup ficial effects of CoQ10 on some of the 4 lipid profiles but not
plementation significantly improved lipid profiles, such as all of them, as this study has shown. For example, a previous
Table 1. Characteristics of the included studies
236
Trial Country Design Dosage Duration Age (intervention, Gender (Male/ BMI Participants Intervention Control CoQ10 Sample size Presented data
comparisonsa (per day) control) Female) (Intervention, form (intervention/control)
Control)
Abdollahzad H. 2015 Iran Parallel 100 mg 2m 48.77 ± 11.58, 50.57 3/19, 3/20 30.0 ± 4.8, Rheumatoid arthritis CoQ10 Placebo Ubiquinone 45 (22/23) TG, TC
(39) ± 11.05 29.8 ± 4.7
Akbari Fakhrabadi Iran Parallel 200 mg 12 w 56.7 ± 6.4, 10/22, 6/24 28.7 ± 4.1, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 62 (32/30) TC, LDL-C,
M. 2014 (40) 54.8 ± 6.7 29.6 ± 3.1 HDL-C
Andersen C.B. 1997 Denmark Parallel 100 mg 12 w 33.5 ± 2.0, 10/7, 9/8 23.5 ± 2.89, Insulin dependent CoQ10 Placebo Ubiquinone 34 (17/17) LDL-C, HDL-C
(41) 35.3 ± 2.4 24.0 ± 2.47 diabetes mellitus
Aya N. Yasser 2021 Iraq Parallel 200 mg 12 w 59.24 ± 5.57, 58.11 ± 14/14, 13/11 32.54 ± 4.66, Dyslipidemia CoQ10 + atorvastatin Atorvastatin Ubiquinone 52 (28/24) TG, TC, LDL-C,
(42) 7.10 31.59 ± 5.08 HDL-C
Bargossi A.M. 1994 Italy Parallel 100 mg 3m 53.7 ± 10.07, 52.8 ± 10/5, 11/4 72.1 ± 13.19, Primary CoQ10 + simvastatin Simvastatin Ubiquinone 30 (15/15) TG, LDL-C,
(43) 10.84 68.8 ± 9.9 hypercholesterolemia HDL-C
Belardinelli R. 2006 I Italy Crossover 100 mg 4w 59 ± 9 20/3 NR Chronic heart failure CoQ10 + exercise Placebo + Ubiquinone 23 (23/23) TG, TC, LDL-C,
(44) exercise HDL-C
Belardinelli R. 2006 II Italy Crossover 100 mg 4w 59 ± 9 20/3 NR Chronic heart failure CoQ10 Placebo Ubiquinone 23 (23/23) TG, TC, LDL-C,
(44) HDL-C
Chew G.T. 2008 I (45) Australia Parallel 200 mg 6m 61.3 ± 4.1, 62.4 ± 8.8 13/3, 14/6 30.1 ± 4.6, Type 2 diabetes CoQ10 Placebo Ubiquinone 36 (16/20) TG, TC, LDL-C,
30.7 ± 5.0 HDL-C
Chew G.T. 2008 II (45) Australia Parallel 200 mg 6m 63.0 ± 9.4, 64.8 ± 7.3 13/6, 13/6 28.7 ± 3.4, Type 2 diabetes CoQ10 + fenofibrate Fenofibrate Ubiquinone 38 (19/19) TG, TC, LDL-C,
29.9 ± 5.6 HDL-C
Cooke M. 2008 (46) America Parallel 200 mg 14 d 25.76 ± 7.67, 25.61 ± NR NR Aerobically trained and CoQ10 Placebo Ubiquinone 41 (21/20) TG, TC, LDL-C,
8.07 untrained individuals HDL-C
Dai Y.L. 2011 (47) China Parallel 300 mg 8w 67.7 ± 9.4, 70.1 ± 9.8 27/1, 25/3 25.3 ± 3.2, Ischemic left ventricular CoQ10 Placebo Ubiquinone 56 (28/28) TG, TC, LDL-C,
24.7 ± 3.2 systolic dysfunction HDL-C
Eriksson J.G. 1999 (48) Finland Parallel 100 mg 6m 65 ± 5, 64 ± 7 NR 29.0 ± 4.2, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 23 (12/11) TG, TC, HDL-C
29.8 ± 3.4
Fallah M. 2018 (49) Iran Parallel 120 mg 12 w 59.4 ± 12.2, 64.8 ± 22/8, 18/12 26.9 ± 3.9, Diabetic hemodialysis CoQ10 Placebo Ubiquinone 60 (30/30) TG, TC, LDL-C,
11.5 26.6 ± 3.9 HDL-C
Gholami M. 2018 (50) Iran Parallel 100 mg 12 w 53.1 ± 6.23, 53.35 ± 0/68 29.44 ± 0.60, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 68 (34/34) TG, TC, LDL-C,
6.56 28.53 ± 0.53 HDL-C
Gholami M. 2019 (51) Iran Parallel 100 mg 12 w 52.97 ± 1.04, 53.68 ± 0/70 29.30 ± 0.6, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 70 (35/35) TG, TC, LDL-C,
1.14 28.51 ± 0.52 HDL-C
Gholnari T. 2018 (23) Iran Parallel 100 mg 12 w 61.1 ± 11.3, 61.6 ± 8/17, 8/17 30.4 ± 6.1, Diabetic nephropathy CoQ10 Placebo Ubiquinone 50 (25/25) TG, TC, LDL-C,
10.0 31.3 ± 4.8 HDL-C
Hamilton S.J. 2009 Australia Crossover 200 mg 12 w 68 ± 6 NR NR Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 46 (23/23) LDL-C
(52)
Hansen M. 2019 (53) Denmark Parallel 400 mg 8w 62 ± 1, 64 ± 2 14/4, 8/9 28 ± 1, 29 ± 1 Hypercholesterolemia CoQ10 Placebo Ubiquinone 35 (18/17) TG, TC, LDL-C,
HDL-C
Henriksen J.E. 1999 Denmark Parallel 100 mg 3m 35.5 ± 8.2, 35.3 ± 10/7, 9/8 23.5 ± 2.7, Type 1 diabetes mellitus CoQ10 Placebo Ubiquinone 34 (17/17) TG, TC, LDL-C,
(54) 10.0 24.0 ± 2.6 HDL-C
Hernandez-Ojeda Mexico Parallel 400 mg 12 w 55.3 ± 8.4, 57.0 ± 8.9 5/19, 6/19 29.4 ± 7.3, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 49 (24/25) TG, TC, LDL-C,
J. 2012 (55) 29.3 ± 4.3 HDL-C
Hodgson J.M. 2002 I Australia Parallel 200 mg 12 w 51.7 ± 6.97, 53.6 ± 14/5, 14/4 NR Type 2 diabetes mellitus CoQ10 + fenofibrate Fenofibrate Ubiquinone 37 (19/18) TG, TC, LDL-C,
(56) 10.18 and dyslipidemia HDL-C
Hodgson J.M. 2002 II Australia Parallel 200 mg 12 w 52.3 ± 6.1, 55.2 ± 17/2, 13/5 NR Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 37 (19/18) TG, TC, LDL-C,
(56) 9.76 and dyslipidemia HDL-C
Hosseinzadeh-Attar Iran Parallel 200 mg 12 w 45.2 ± 7.6, 47.1 ± 8.3 19/12, 18/15 29.52 ± 2.8, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 64 (31/33) TG, TC, LDL-C,
M. 2015 (57) 29.47 ± 3.24 HDL-C
Ikematsu H. 2006 I Japan Parallel 300 mg 4w 20∼60, 24∼55 11/10, 9/11 NR Healthy CoQ10 Placebo Ubiquinone 41 (21/20) TG, TC, HDL-C
(58)
Ikematsu H. 2006 II Japan Parallel 600 mg 4w 20∼60, 24∼55 11/11, 9/11 NR Healthy CoQ10 Placebo Ubiquinone 42 (22/20) TG, TC, HDL-C
(58)
The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
(continued)

Table 1. Continued
Control)
Ikematsu H. 2006 III Japan Parallel 900 mg 4w 20∼60, 24∼55 9/11, 22/0 NR Healthy CoQ10 Placebo Ubiquinone 42 (22/20) TG, TC, HDL-C
(58)
Izadi A. 2019 I (59) Iran Parallel 200 mg 8w 27.18 ± 5.77, 28.33 ± 0/43 29.28 ± 3.23, Polycystic ovary syndrome CoQ10 + vitamin E Vitamin E Ubiquinone 43 (21/22) TG, TC, LDL-C,
5.52 29.28 ± 4.24 HDL-C
Izadi A. 2019 II (59) Iran Parallel 200 mg 8w 27.64 ± 5.2, 26.0 ± 0/43 28.97 ± 2.95, Polycystic ovary syndrome CoQ10 Placebo Ubiquinone 43 (22/21) TG, TC, LDL-C,
4.53 28.73 ± 3.39 HDL-C
Jafarvand E. 2016 (60) Iran Parallel 100 mg 4w 42.7 ± 10.2, 42.2 ± 15/5 16/5 30.5 ± 3.9, Nonalcoholic fatty liver CoQ10 Placebo Ubiquinone 41 (20/21) TG, TC, LDL-C,
10.8 28.7 ± 4.02 disease HDL-C
Kaikkonen J. 2000 I Finland Parallel 200 mg 3m 60.7 ± 5.7 11/29 NR Mild hypercholesterolemia CoQ10 + α- α-Tocopherol Ubiquinone 20 (10/10) TG, TC, LDL-C,
(61) tocopherol HDL-C
Kaikkonen J. 2000 II Finland Parallel 200 mg 3m 60.7 ± 5.7 11/29 NR Mild hypercholesterolemia CoQ10 Placebo Ubiquinone 20 (10/10) TG, TC, LDL-C,
(61) HDL-C
Kuhlman A.B. 2019 Denmark Parallel 400 mg 8w 62 ± 1, 64 ± 2 14/4, 8/9 27.7 ± 2.55, Patient in primary CoQ10 Placebo Ubiquinone 35 (18/17) TG, TC
(62) 28.8 ± 2.89 prevention
with simvastatin ≥40 mg/d
Lee Y.J. 2011 (63) Korea Parallel 200 mg 12 w 42.7 ± 11.3, 42.5 ± 11/15, 10/15 27.9 ± 2.3, Obesity CoQ10 Placebo Ubiquinone 36 (17/19) TG, TC, HDL-C
11.2 27.6 ± 3.8
Mabuchi H. 2007 (64) Japan Parallel 100 mg 12 w 61 ± 8, 60 ± 8 6/18, 8/17 23.3 ± 2.7, Hypercholesterolemic CoQ10 + atorvastatin Placebo + Ubiquinone 49 (24/25) TG, TC, LDL-C,
23.9 ± 3.4 atorvastatin HDL-C
Majid Iran Parallel 100 mg 12 w 19∼54 NR 28.23 ± 3.60, Nonalcoholic fatty liver CoQ10 Placebo Ubiquinone 41 (20/21) TG, TC
Mohammadshahi F.F. 29.69 ± 5.76 disease
2014 (65)
Mohammed-Jawad Iran Parallel 150 mg 8w 49.37 ± 6.65, 51.63 ± 10/9, 8/11 28.15 ± 4.08, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 38 (19/19) TC
N.K. 2014 (66) 8.13 29.5 ± 4.29
Mohseni M. 2015 (67) Iran Parallel 200 mg 12 w 60 ± 4, 61 ± 3.5 39/13 25.91 ± 2.53, Hyperlipidemic CoQ10 Placebo Ubiquinone 52 (26/26) TG, TC, LDL-C,
26.00 ± 3.34 HDL-C
Mori T.A. 2009 I (68) Australia Parallel 200 mg 8w 56.9 ± 16.55, 53.3 ± 17/1, 12/8 30.5 ± 2.2, Chronic kidney disease CoQ10 + omega-3 Omega-3 fatty Ubiquinone 38 (18/20) TG, TC, LDL-C,
14.31 36.4 ± 2.8 fatty acids acids HDL-C
Mori T.A. 2009 II (68) Australia Parallel 200 mg 8w 55.4 ± 12.37, 58.6 ± 17/4, 8/7 26.6 ± 4.12, Chronic kidney disease CoQ10 Placebo Ubiquinone 36 (21/15) TG, TC, LDL-C,
10.07 27.6 ± 6.58 HDL-C
Nuku K. 2007 (69) Japan Parallel 900 mg 4w 40 ± 13, 38 ± 11 12/11, 11/12 21.8 ± 2.1, Healthy CoQ10 Placebo Ubiquinone 46 (23/23) TG, TC, LDL-C,
22.0 ± 1.7 HDL-C
Pek S.L. 2016 (70) Singapore Parallel 150 mg 12 w 43.1 ± 11.3, 49.2 ± 18/2, 17/3 29.2 ± 3.8, Hypercholesterolemic CoQ10 + simvastatin Simvastatin Ubiquinol 40 (20/20) TG, TC, LDL-C,
12.2 31.2 ± 6.1 HDL-C
Playford D.A. 2003 I Australia Parallel 200 mg 12 w 52.7 ± 8.05, 53.5 ± 14/6, 14/6 30.3 ± 4.02, Type 2 diabetes mellitus CoQ10 + fenofibrate Fenofibrate Ubiquinone 40 (20/20) TG, TC, LDL-C,
(71) 9.84 30.0 ± 3.58 and dyslipidemia HDL-C
Playford D.A. 2003 II Australia Parallel 200 mg 12 w 52.7 ± 6.26, 54.7 ± 18/2, 15/5 29.9 ± 3.13, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 40 (20/20) TG, TC, LDL-C,
(71) 9.39 30.9 ± 4.47 and dyslipidemia HDL-C
Pourmoghaddas Iran Parallel 200 mg 4m 50.70 ± 12.5, 54.47 ± 23/9, 22/8 NR Congestive heart failure CoQ10 + atorvastatin Atorvastatin Ubiquinone 62 (32/30) TC
M. 2014 (72) 14.6
Raitakari O.T. 2000 Australia Crossover 150 mg 4w 34 ± 10 3/9 23 ± 4 Hypercholesterolemia CoQ10 Placebo Ubiquinone 24 (12/12) LDL-C
(73) + endothelial dysfunction
Raygan F. 2016 (74) Iran Parallel 100 mg 8w 65.9 ± 12.5, 59.9 ± NR 28.2 ± 5.2, Obese, type 2 diabetes CoQ10 Placebo Ubiquinone 60 (30/30) TG, TC, LDL-C,
13.1 30.7 ± 5.9 mellitus, HDL-C
and coronary heart disease
Rodriguez-Carrizalez Mexico Parallel 400 mg 6 m 28.2 ± 3.7, 29.3 ± 0.8 11/9, 9/11 28.2 ± 3.7, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 40 (20/20) TG, TC, LDL-C,
A.D. 2016 (75) 29.3 ± 0.8 HDL-C
Samimi M. 2017 (19) Iran Parallel 100 mg 12 w 24.5 ± 4.3, 25.3 ± 5.7 0/30, 0/30 27.1 ± 4.3, Polycystic ovary syndrome CoQ10 Placebo Ubiquinone 60 (30/30) TG, TC, LDL-C,
27.9 ± 6.0 HDL-C
(continued)
237

Table 1. Continued
238
Control)
Shahad A. Bader 2022 Iraq Parallel 200 mg 3m 25∼33 0/50, 0/50 28.84 ± 6.74, Polycystic ovary syndrome CoQ10 Placebo Ubiquinone 100 (50/50) TG, TC, LDL-C,
(76) 30.12 ± 5.46 HDL-C
Shojaei M. 2011 I (77) Iran Parallel 100 mg 3m 52.8 ± 10.4, 55.3 ± 6/8, 6/6 23.3 ± 2.3, Hemodialysis CoQ10 + carnitine Carnitine Ubiquinone 26 (14/12) TG, TC, LDL-C,
15.6 24.3 ± 2.1 HDL-C
Shojaei M. 2011 II (77) Iran Parallel 100 mg 3m 53.5 ± 11.5, 51.6 ± 7/6, 6/7 23.6 ± 2.4, Hemodialysis CoQ10 Placebo Ubiquinone 26 (13/13) TG, TC, LDL-C,
19.2 23.6 ± 2.6 HDL-C
Singh R.B. 2003 (78) India Parallel 120 mg 12 m 48.0 ± 8.6, 47.6 ± 8.2 58/15, 57/14 23.8 ± 1.6, Acute myocardial infarction CoQ10 Placebo Ubiquinone 144 (73/71) TG, TC, LDL-C,
23.6 ± 1.5 HDL-C
Singh R.B. and M.A. India Parallel 120 mg 4w 48.4 ± 0.5, 47.6 ± 0.3 19/6, 18/4 23.6 ± 1.2, Acute myocardial CoQ10 Placebo Ubiquinone 47 (25/22) TC, LDL-C,
Niaz 1999 (79) 23.5 ± 1.2 infarction, HDL-C
unstable angina, angina
pectoris
Skarlovnik A. 2014 Slovenia Parallel 100 mg 30 d 64.5 ± 1.9, 65.6 ± 2.1 11/14, 12/13 25.3 ± 1.2, Statin myalgia CoQ10 Placebo Ubiquinone 50 (25/25) TG, TC, LDL-C
(80) 24.6 ± 1.5
Taylor B.A. 2015 (81) America Crossover 600 mg 8w 58 ± 10, 60 ± 10 27/16 29.6 ± 5.3 Statin myalgia CoQ10 + simvastatin Simvastatin Ubiquinol 76 (38/38) LDL-C
Toth S. 2017 (82) Slovakia Parallel 200 mg 3m 58.4 ± 13.8, 61.96 ± 17/18, 18/17 28.31 ± 3.81 Dyslipidemia CoQ10 + Omega-3 Omega-3 fatty Ubiquinone 70 (35/35) TG, TC, LDL-C,
12.2 fatty acids acids HDL-C
Yen C.H. 2018 (83) China Parallel 100 mg 12 w 61.5 ± 10.2, 59.6 ± 17/7, 14/9 28.0 ± 4.8, Type 2 diabetes mellitus CoQ10 Placebo Ubiquinol 47 (24/23) TG, TC, LDL-C,
11.7 27.3 ± 3.4 HDL-C
Young J.M. 2007 (84) New Parallel 200 mg 12 w 59 ± 9.4, 59 ± 9.4 12/10, 10/12 NR Myalgia CoQ10 + simvastatin Simvastatin Ubiquinone 44 (22/22) TG, TC, LDL-C,
Zealand HDL-C
Zahedi H. 2014 (85) Iran Parallel 150 mg 12 w 53.5 ± 9.7, 58.8 ± 9.6 11/9, 8/12 NR Type 2 diabetes mellitus CoQ10 Placebo Ubiquinone 40 (20/20) TG, TC, LDL-C,
HDL-C
Zhang P. 2018 (18) China Parallel 120 mg 24 w 51.78 ± 8.92, 50.02 ± 14/37, 18/32 25.23 ± 3.96, Dyslipidemia CoQ10 Placebo Ubiquinone 101 (51/50) TG, TC, LDL-C,
10.91 24.91 ± 3.32 HDL-C
Abbreviations: CoQ10, coenzyme Q10; d, days; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; m, months; NR, not reported; TC, total cholesterol; TG, triglyceride; w, weeks.
a
When 1 RCT included more than 1 dosage or intervention, we counted it as the corresponding number of trial comparisons, and named it as the RCT name followed by the number, such as Belardinelli R. 2006 I (CoQ10 + exercise vs placebo + exercise) and Belardinelli
R. 2006 II (CoQ10 vs placebo) were counted as 2 studies that were included in the same RCT (Belardinelli R. 2006).


Figure 2. The quality assessment of included studies. A. Review authors’ judgements about each risk of bias item presented as percentages across all
included studies; B. Review authors’ judgements about each risk of bias item for each included study.
meta-analysis in patients with coronary artery disease dem Specifically, we performed a dose–response meta-analysis
onstrated that CoQ10 supplementation significantly im to explore the potential optimal dose of CoQ10 supplementa
proved TC and HDL-C levels, but it did not significantly tion on improving lipid profiles by using a novel 1-stage
affect other lipid profiles (21). Another meta-analysis re model that allows us to include trials with only 1 interven
ported that CoQ10 significantly decreased TG, but had tion dosage. To our knowledge, this is the first dose–
no significant effect on TC, LDL-C or HDL-C among par response meta-analysis of RCTs to evaluate the effect of
ticipants with metabolic diseases (11). Furthermore, a CoQ10 supplementation on lipid profiles. We found an in
meta-analysis in diabetic patients suggested that CoQ10 verse J-shaped nonlinear relationship with the effect of
significantly reduced TC and LDL-C (90), while another CoQ10 supplementation on TC, which revealed that the
meta-analysis in patients with chronic kidney disease beneficial effects increased when CoQ10 < 400 mg/day and
showed no effects of CoQ10 on TC, LDL-C, HDL-C, and then plateaued at higher doses. However, few observational
TG (25). One major reason for the inconsistent results of studies or RCTs have supported the inverse J-shaped non
previous meta-analyses should be the study size, as each linear dose–response relationship. Despite the lack of direct
included only part of the RCTs such that each showed a evidence, there was a similar trend in the effect of CoQ10
significant intervention effect on some lipid profiles but supplementation on lipid profiles in a meta-analysis based
not on other lipid profiles, but they were all in the right on RCTs, significantly decreasing TC at lower dosages but
direction. After we summarized all of the RCTs that met not significantly at higher dosages (21). The inverse
our criteria and updated the data with 15 more RCTs, J-shaped curves provide a reference for future RCTs to ex
the intervention effects of CoQ10 supplementation on plore dose–response relationship between CoQ10 supplemen
TC, TG, LDL, and HDL all reached statistically significant tation and lipid profiles.
levels. Another potential reason is the confounding effect Several potential mechanisms have been proposed by
from diseases that might conceal the true intervention ef which CoQ10 supplementation may improve circulating
fect. We further compared the results by subgroup analysis lipids (12, 13, 91–98). In human endothelial cells, exposure
and found that 5 studies among healthy subjects indicated to CoQ10 is associated with downregulation of the lectin-
a significant intervention effect of CoQ10 on TC without like oxidized LDL receptor, stimulation of 5’ adenosine
significant heterogeneity across studies, which was stron monophosphate-activated protein kinase (AMPK), and re
ger than the intervention effect among subjects with dysli duction of reactive oxygen species (ROS)-induced endothe
pidemia, diabetes, cardiovascular diseases, chronic kidney lial damage (98). In fact, the primary effect of CoQ10 on
disease, or other diseases. Regarding the intervention ef circulating lipid profiles appears to increase LDL resistance
fect of CoQ10 on HDL-C, 10 studies among subjects to oxidative stress (92), as demonstrated in healthy adults
with dyslipidemia indicated a significant intervention ef following acute strenuous physical activity (97). In vitro,
fect of CoQ10 on HDL-C, which was stronger than the it inhibits LDL oxidation better than other antioxidant
intervention effects among healthy subjects or patients molecules such as alpha-tocopherol or beta-carotene (94,
with diabetes, cardiovascular diseases, chronic kidney dis 95). CoQ10 can also significantly improve HDL-mediated
ease, or other diseases. cholesterol efflux capacity, and this may be related to the
240
Table 2. GRADE evidence profile of CoQ10 supplementation for lipid profiles
Quality assessment No of patients Effect Quality
No. of Design Risk of bias Inconsistency Indirectness Imprecision Other CoQ10 Control MD (95% CI)
studies considerations
TC (better indicated by lower values)

45 Randomized No serious risk Seriousa No serious No serious None 1318 1298 −5.53 (−8.40, 2.66) ⊕⊕⊕OMODERATE
trials of bias indirectness imprecision
LDL-C (better indicated by lower values)
42 Randomized No serious risk Seriousb No serious No serious None 1202 1185 −3.03 (−5.25, −0.81) ⊕⊕⊕O
trials of bias indirectness imprecision MODERATE
HDL-C (better indicated by lower values)
41 Randomized No serious risk Very seriousc No serious No serious None 1214 1195 0.83 (0.01, 1.65) ⊕⊕OO LOW
TG (better indicated by lower values)
42 Randomized No serious risk Seriousd No serious No serious None 1228 1215 −9.06 (−14.04, −4.08) ⊕O MODERATE
a
The test for heterogeneity is significant, and the I2 is moderate, 70%.
b
c
The test for heterogeneity is significant, and the I2 is high, 82%.
d

Figure 3. Forest plot detailing mean differences and 95% CIs for the effect of coenzyme Q10 supplementation on plasma lipid profiles. A. Total
cholesterol; B. Low-density lipoprotein cholesterol: C. High-density lipoprotein cholesterol; D. Triglycerides.
regulation of the activator protein-1/miR-378/adenosine tissue (91). In addition, CoQ10 increases fatty acid oxida
triphosphate–binding cassette transporter G1-signaling tion, which reduces oxidative stress via a decrease in mito
pathway (14, 99). Moreover, CoQ10 may activate the chondrial free fatty acids, participates in endothelial
calcium-mediated AMPK pathway and inhibit differenti metabolism, and increases TG lipolysis (12, 13).
ation-induced adipogenesis, inducing the gene expression Furthermore, CoQ10, in its reduced state, has been shown
of peroxisome proliferator-activated receptor-γ (PPAR-γ) to inhibit the peroxidation of cell membrane lipids and re
(93), which is a main regulator of lipid storage in adipose duce the oxidation of circulating lipids (96).
Figure 4. Leave-one-out sensitivity analysis for the effect of coenzyme Q10 supplementation on plasma lipid profiles. A. Total cholesterol; B. Low-
density lipoprotein cholesterol: C. High-density lipoprotein cholesterol; D. Triglycerides.
Table 3. Overall effect and subgroup analyses of coenzyme Q10 supplementation on lipid profiles
Variable N Sample size MD (95% CI) Heterogeneity

(experimental/control)
P heterogeneity I2 % P between subgroups
TC (mg/dL)
Overall 55 1318/1298 −5.53 (−8.40, −2.66) <.01 70
Baseline TC (mg/dL)
<200 35 823/814 −6.87 (−10.14, −3.60) <.01 65 .20
≥200 20 495/484 −2.30 (−8.45, 3.84) <.01 77
Health condition
Healthy 5 109/103 −12.30 (−14.89, −9.71) .43 0 <.01
Diabetes 19 432/429 −2.08 (−6.18, 2.03) .05 37
Dyslipidemia 9 214/212 −4.53 (−15.96, 6.89) <.01 79

Cardiovascular diseases 7 230/223 −0.98 (−3.66, 1.71) .75 0
Chronic kidney disease 2 39/35 −11.72 (−26.88, 3.44) <.01 92
Other diseases 13 294/296 −6.51 (−13.04, 0.02) .04 44
CoQ10 form
ubiquinone 53 1274/1255 −5.68 (−8.61, −2.75) <.01 71 .41
Ubiquinol 2 44/43 0.47 (−13.81, 14.75) .94 0
Type of intervention
CoQ10 40 1004/988 −6.40 (−9.73, −3.07) <.01 76 .22
CoQ10 + other 15 314/310 −2.69 (−7.64, 2.27) .26 17
Dosage of intervention (mg/day)
<200 24 625/619 −2.55 (−5.79, 0.70) .13 25 .08
≥200 31 693/679 −7.18 (−11.12, −3.23) <.01 76
Duration of study (weeks)
<12 20 438/425 −7.95 (−11.99, −3.91) <.01 71 .14
≥12 35 880/873 −5.53 (−8.40, −2.66) <.01 67
Funded by industry
Yes 22 483/470 −5.01 (−9.19, −0.82) <.01 77 .78
No 33 835/828 −5.86 (−10.10, −1.62) <.01 63
LDL-C (mg/dL)
Overall 50 1202/1185 −3.03 (−5.25, −0.81) <.01 54
Baseline LDL-C (mg/dL)
<130 39 917/904 −3.53 (−6.09, −0.98) <.01 56 .46
≥130 11 285/281 −1.36 (−6.59, 3.87) .03 50
Health condition
Healthy 2 44/43 −5.00 (−15.55, 5.55) 1.00 0 .08
Diabetes 19 441/439 0.00 (−4.18, −4.19) <.01 63
Dyslipidemia 11 243/241 −2.78 (−9.11, 3.56) .01 56
Cardiovascular diseases 6 198/193 −1.34 (−3.50, 0.82) 0 1.00
Chronic kidney disease 2 39/35 −5.81 (−10.09, −1.53) .38 0
Other diseases 10 237/234 −9.19 (−15.14, −3.24) .14 34
CoQ10 form
Ubiquinone 47 1138/1124 −3.02 (−5.32, −0.72) <.01 57 .94
Ubiquinol 3 64/61 −3.40 (−12.91, 6.11) .88 0
CoQ10 34 984/866 −2.93 (−5.59, −0.26) <.01 65 .70
CoQ10 + other 16 318/319 −3.78 (−7.28, −0.28) .67 0
Dosage of intervention (mg/day)
<200 23 598/591 −3.45 (−7.03, 0.13) <.01 58 .79
≥200 27 604/594 −2.81 (−5.90, 0.29) <.01 53
<12 16 346/336 −2.40 (−4.30, −0.50) .93 0 .86
≥12 34 856/849 −2.74 (−5.91, 0.43) <.01 66
Funded by industry
Yes 20 440/434 −1.18 (−3.78, 1.41) .10 31 .10
No 30 762/751 −4.82 (−8.35, −1.30) <.01 64
HDL-C (mg/dL)
(continued)
Table 3. Continued
Variable N Sample size MD (95% CI) Heterogeneity

(experimental/control)
P heterogeneity I2 % P between subgroups
Overall 51 1214/1195 0.83 (0.01, 1.65) <.01 82

Baseline HDL-C (mg/dL)
≥50 20 425/410 −0.01 (−1.19, 1.17) <.01 73 .14
<50 31 789/785 1.30 (0.00, 2.61) .01 85
Health condition
Healthy 5 109/103 0.16 (−2.42, 2.73) <.01 70 .03
Diabetes 19 430/427 0.17 (−1.37, 1.71) <.01 59
Dyslipidemia 10 229/227 3.69 (0.09, 7.30) <.01 84
Cardiovascular diseases 6 198/193 0.91 (−1.10, 2.91) .12 42

Chronic kidney disease 2 39/35 −2.69 (−4.82, −0.56) .22 34
Other diseases 9 209/210 0.73 (−0.32, 1.78) <.01 83
CoQ10 form
Ubiquinone 49 1170/1152 0.77 (−0.05, 1.60) <.01 83 .24
Ubiquinol 2 44/43 4.74 (−1.81, 11.30) .64 0
CoQ10 36 915/899 0.72 (−0.36, 1.79) <.01 86 .69
CoQ10 + other 15 299/296 1.05 (−0.22, 2.32) .023 45
Dosage of intervention (mg/d)
<200 22 571/563 0.87 (−0.60, 2.34) <.01 60 .96
≥200 29 643/632 0.82 (−0.21, 1.86) <.01 88
<12 16 354/341 0.15 (−0.81, 1.11) <.01 69 .19
≥12 35 860/854 1.28 (−0.13, 2.68) <.01 85
Funded by industry
Yes 22 482/470 0.11 (−0.97, 1.19) <.01 76 .22
No 29 732/725 1.26 (−0.21, 2.74) <.01 85
TG (mg/dL)
Overall 52 1228/1215 −9.06 (−14.04, −4.08) <.01 65
Baseline TG (mg/dL)
<150 30 672/664 −10.11 (−17.54, −2.68) <.01 76 .22
≥150 22 556/551 −4.69 (−9.07, −0.30) .34 9
Health condition
Healthy 5 109/103 −6.47 (−29.99, 17.05) <.01 91 .99
Diabetes 17 382/381 −7.40 (−13.96, −0.84) .04 41
Dyslipidemia 10 231/229 −9.81 (−26.67, 7.06) <.01 73
Cardiovascular diseases 5 173/171 −4.76 (−13.48, 3.96) .69 0
Chronic kidney disease 2 39/35 −8.68 (−14.05, 8.68) .02 82
Other diseases 13 294/296 −8.57 (−16.47, −0.66) .93 0
CoQ10 form
Ubiquinone 50 1183/1171 −9.10 (−14.08, −4.11) <.01 65 .73
Ubiquinol 2 45/44 8.36 (−88.89, 105.61) .04 75
CoQ10 37 929/918 −9.30 (−15.08, −3.53) <.01 64 .88
CoQ10 + other 15 299/297 −8.36 (−19.20, 2.49) <.01 69
Dosage of intervention (mg/d)
<200 23 599/596 −10.11 (−18.78, −1.43) <.01 63 .75
≥200 29 629/619 −8.37 (−14.79, −1.94) <.01 66
<12 18 394/384 −6.36 (−15.02, 2.30) <.01 70 .45
≥12 34 834/831 −10.50 (−16.76, −4.24) <.01 60
Funded by industry
Yes 21 459/449 −4.22 (−12.72, 4.28) <.01 76 .12
No 31 769/766 −12.38 (−18.20, −6.56) <.01 43
Abbreviations: N, number of studies included; MD, mean difference; mg/d, milligrams per day.
A major strength of this review is the large study size: data evidence of publication bias. The included studies were high-
from the 50 RCTs provided sufficient power to examine the quality randomized and double-blind trials and were robust in
effect of CoQ10 on lipid profiles. In general, there was no sensitivity analyses, minimizing the risk of confounding and
bias. Several limitations of the present study warrant consider
ation. Most of the included studies had a small number of sub
jects, and there was a certain degree of heterogeneity.
Sampling error might lead to substantial bias in the interven
tion effect estimation; however, in our estimations, we
used the MD to evaluate the intervention effect. As Lin dem
onstrated by a series of sensitivity analyses, sampling error
did not cause noticeable bias when the effect size was the
MD (100). Furthermore, in our meta-analysis, only 1 RCT
with 3 dose groups could be included in the 2-stage model.
In order to avoid the systematic exclusion of studies with few

er than 3 dose groups and to allow the inclusion of RCTs with
only 1 comparison, we used the flexible 1-stage model to ex
plore dose–response relationships as in previous meta-
analyses (101–105). In addition, the meta-analysis of CoQ10
Figure 5. Dose–response relationship between dose of CoQ10 supplementation on HDL-C showed significant heterogeneity
supplementation and mean differences in total cholesterol. The dotted in the sensitivity analysis, which warrants further replication
lines represent 95% CI. of RCTs in the future.
Figure 6. Funnel plot revealing publication bias in the studies reporting the effects of coenzyme Q10 supplementation on plasma lipid profiles. A. Total
cholesterol; B. Low-density lipoprotein cholesterol: C. High-density lipoprotein cholesterol; D. Triglycerides.
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Author Contributions Alcalá-Diaz JF, Yubero-Serrano EM, López-Miranda J.
Coenzyme Q(10) and cardiovascular diseases. Antioxidants
Z.L. and M.L. had full access to all of the data and take re (Basel). 2021;10(6):906.
sponsibility for the integrity of the data. Concept and design: 17. Arenas-Jal M, Suñé-Negre JM, García-Montoya E. Coenzyme
Y.Y., Z.T. Acquisition, or interpretation of data: Z.L., Z.T., Q10 supplementation: efficacy, safety, and formulation chal
D.Z., Y.L., S.D., M.L., S.H., X.D., Zhaxinima, Y.Y. lenges. Compr Rev Food Sci Food Saf. 2020;19(2):574-594.
Analysis of the data and drafting of the manuscript: Z.L. 18. Zhang P, Yang C, Guo H, et al. Treatment of coenzyme Q10 for
Critical revision of the manuscript for important intellectual 24 weeks improves lipid and glycemic profile in dyslipidemic indi
content: Y.Y. Statistical analysis: Z.L. Obtained funding: viduals. J Clin Lipidol. 2018;12(2):417-427.e5.
Y.Y. Supervision: Y.Y., Z.T. 19. Samimi M, Zarezade Mehrizi M, Foroozanfard F, et al. The effects
of coenzyme Q10 supplementation on glucose metabolism and
lipid profiles in women with polycystic ovary syndrome: a
Disclosures randomized, double-blind, placebo-controlled trial. Clin
Endocrinol (Oxf). 2017;86(4):560-566.
The authors declare no conflict of interest.
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effects of coenzyme Q10 supplementation on metabolic profiles
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meta-analysis of randomized controlled trials. Curr Pharm Des.
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The Journal of Clinical Endocrinology & Metabolism, 2023, 108, 232–249

Effects of Coenzyme Q10 Supplementation on Lipid Profiles

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Table 2. GRADE evidence profile of CoQ10 supplementation for lipid profiles

Quality assessment No of patients Effect Quality

TC (better indicated by lower values)

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Variable N Sample size MD (95% CI) Heterogeneity

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Variable N Sample size MD (95% CI) Heterogeneity

Overall 51 1214/1195 0.83 (0.01, 1.65) <.01 82

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