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

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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
acterized by increased total cholesterol (TC), low-density lipo­
protein cholesterol (LDL-C), triglyceride (TG), and/or
decreased high-density lipoprotein cholesterol (HDL-C) levels
(1). Poorly controlled dyslipidemia is associated with clinical
diseases, including diabetes (2), nonalcoholic steatohepatitis
(3), and cancers (4), and is considered a major risk factor
for atherosclerotic cardiovascular diseases (5). Moreover, ele­
vated LDL-C levels were attributable to 3.79 million deaths
from ischemic heart diseases and 0.532 million deaths from is­
chemic stroke in 2017 globally (6). Therefore, it is essential
to explore effective strategies for the regulation of lipid
profiles (7).
For decades, nutritional strategies to reduce the risk of ath­
erosclerotic cardiovascular diseases have attracted much at­
tention. Coenzyme Q10 (CoQ10) is a nonessential nutrient
and vitamin-like fat-soluble benzoquinone (8). CoQ10,
located in the inner mitochondrial membrane, plays an im­
portant role in the electron transport chain. CoQ10 has basic
physiological functions, such as participating in oxidative
phosphorylation and the production of adenosine triphos­
phate, activating cellular metabolism and cellular respiration,
regulating cytoplasmic redox potential, and inhibiting super­
oxide formation (9, 10). In addition, previous in vitro and in
vivo studies have shown that CoQ10 could promote lipolysis
of TGs in the process of endothelial metabolism and facilitate
cholesterol efflux from macrophages, which might be poten­
tial mechanisms for CoQ10 to lower circulating lipid profiles
(11–14). In general, the human body cannot synthesize a suf­
ficient amount of CoQ10 in some pathological conditions,
such as metabolic syndrome, hypertension, diabetes mellitus,
and dyslipidemia (15). In addition, multiple studies have
shown that the serum CoQ10 levels in dyslipidemic patients
taking lipid-lowering drugs (statins) were low, which

Received: 30 June 2022. Editorial Decision: 4 October 2022. Corrected and Typeset: 7 November 2022
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The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
restricted the use of lipid-lowering drugs (16, 17). Therefore,
additional CoQ10 supplementation might be utilized to ad­
dress these health concerns.
A number of randomized controlled trials (RCTs) have
suggested that CoQ10 supplementation has beneficial
effects on circulating lipid profiles (18, 19). Several previous
meta-analyses of RCTs have shown that CoQ10 supplementa­
tion was effective in improving lipid profiles, especially
TC, LDL-C, HDL-C, and TGs, in various disease states
(11, 20–22). However, some previous studies failed to show
beneficial effects of CoQ10 supplementation on any lipid pro­
file (23–25). These results suggest that the effect of CoQ10 on
circulating lipids is still controversial. Furthermore, previous
meta-analyses only focused on populations with specific dis­
eases, such as patients with coronary artery diseases (19),
metabolic diseases (20), or diabetes (21). However, no study
has explored the effect of CoQ10 on the general population,
especially the adult population. Additionally, the effective
dose of CoQ10 on the control of lipid profiles, especially the
dose–response relationship, has not been explored. This
knowledge gap has restricted the application of CoQ10 in con­
trolling blood lipid levels.
We conducted this systematic review and meta-analysis to
formulate a clear role of CoQ10 supplementation on lipid
markers in adults. Furthermore, we assessed the dose–
response relationships to determine the effective dose of
CoQ10 supplementation on improving plasma lipid profiles
in adults.
Materials and Methods
This systematic review is based on the guidelines of the
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement and has been registered
on PROSPERO (26). The registration number is
CRD42021252933.
Search Strategy
To find relevant studies on the effects of CoQ10 supplementa­
tion on lipid profiles in humans, this systematic review and
meta-analysis conducted a comprehensive literature search
in online databases, including Web of Science, PubMed/
Medline, Embase, and the Cochrane Library, until August
10, 2022. The following search terms were used in our search
strategy: (triglyceride) OR (TG) OR (total cholesterol) OR
(TC) OR (low-density lipoprotein cholesterol) OR (LDL chol­
esterol) OR (LDL-C) OR (high-density lipoprotein choles­
terol) OR (HDL cholesterol) OR (HDL-C)) AND
((Coenzyme Q10) OR (CoQ10) OR (Ubiquinone)). The de­
tailed search strategies are reported elsewhere (Table S1 (27)).
Study Selection
The inclusion criteria for this meta-analysis were as follows:
(1) RCTs with parallel or crossover designs, (2) use of
CoQ10 intervention, (3) intervention time ≥14 days, (4) meas­
urements of TGs, TC, LDL-C, or HDL-C at the beginning and
end of the trials, and (5) a placebo control or other suitable
forms of control. The exclusion criteria included (1) acute
feeding trials, (2) pregnant or lactating women as subjects,
and (3) trials with a multifactorial design.
233
Data Extraction
Eligible studies were independently reviewed by 2 investi­
gators (Z.L. and M.L.), and extracted data included the
name of the first author, year of publication, country of
origin, type of intervention, form of intervention, sample
size (in intervention and control groups), participant
demographics (age, gender, baseline lipid profiles, and
body mass index), CoQ10 form, dosage of CoQ10 supple­
mentation, duration of intervention, health status of par­
ticipants, and the changes in HDL-C, LDL-C, TC, and
TGs from baseline to end trial in both the intervention
and the control groups.
Quality Assessment and Certainty of Evidence
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Study quality for this meta-analysis was independently
measured by 2 reviewers (Z.L. and M.L.) using the
Cochrane Collaboration’s modified risk of bias tool (28).
The terms “low”, “high” or “unclear” were used to rate
study bias in 7 domains, including random sequence gen­
eration, allocation concealment, performance bias, detec­
tion bias, attrition bias, reporting bias and other bias.
The GRADE (Grading of Recommendations Assessment,
Development, and Evaluation) methods were used to as­
sess the overall certainty of evidence in studies by
GRADEpro software (version 3.6). The primary outcomes
were classified into 4 levels (high, moderate, low, or very
low) according to study design, risk of bias, inconsistency,
indirectness, imprecision, and other considerations (such
as publication bias) (29).
Statistical Analyses
Circulating concentrations of lipid profiles were collated in
milligrams per deciliter (mg/dL). Inverse-variance weighting
was used to calculate the mean differences (MDs) and 95%
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)
in mean values. SDs of MDs were available in 9 studies, and
they were directly applied in our meta-analysis. For other
studies that did not report them, we calculated the SD of the
MD using the following formula (30):
SD
􏽱�������������������������������������������������������������������
= (SDbaseline)2 + (SDfinal)2 − (2R × SDbaseline × SDfinal),
where R is the correlation coefficient between preinterven­
tion and postintervention; as R was not available in those
studies, the correlation coefficient was conservatively set at
0.5 as previously reported (31, 32). The random effects
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
conducted by multiple factors, including baseline circulat­
ing concentrations on TC (<200 and ≥200 mg/dL), LDL-C
(<130 and ≥130 mg/dL), HDL-C (≥50 and <50 mg/dL),
and TGs (<150 and ≥150 mg/dL), health condition
(healthy, diabetes, dyslipidemia, cardiovascular diseases,
chronic kidney disease, and other diseases), CoQ10 form
(ubiquinone and ubiquinol), type of intervention (CoQ10
and CoQ10 + other), dosage of intervention (<200 and
≥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
of the Cochrane’s Q test and I2 index were used to evalu­
ate heterogeneity between studies. Sensitivity analyses
were performed using the single-study deletion
(leave-one-out) approach to assess the effect of each study
on the overall effect size. A single-stage restricted cubic
spline regression model was applied to explore nonlinear
dose–response relationships (34, 35). Potential publication
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
package (version 2.0.1) (38) based on R (version 4.1.0,
www.R-project.org). A 2-tailed P < .05 was considered
statistically significant.
Results
Flow and Characteristics of Studies
After the multiple database search, 3364 articles were identi­
fied, of which 1023 were rejected due to duplication. After re­
viewing the titles and abstracts of the articles, 2259 articles
were excluded for the following reasons: titles and abstracts
not relevant to this study (n = 1907), animal studies
(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
als. Finally, this study included 50 articles that met all neces­
sary criteria for a meta-analysis (Fig. 1).
The characteristics of the included studies are shown in
Table 1. Fifty RCTs included 60 trial comparisons with a to­
tal of 2794 participants (interventions = 1408 and controls
= 1386). The included articles were published between
1994 and 2022. Fifty-five studies were designed as parallel
studies, and the remaining 5 studies had a crossover design.
The CoQ10 dosages ranged from 100 mg/day to 900 mg/
day, and durations of supplementation varied from 2 to
52 weeks. The quality assessment of the included studies
is provided in Fig. 2. The GRADE assessment profiles are
shown in Table 2.
The Effects of CoQ10 Supplementation on Total
Cholesterol
Following CoQ10 supplementation, 45 RCTs with a total of
2616 subjects (1318 in the CoQ10 arm and 1298 in the control
arm) reported the effects of CoQ10 supplementation on TC.
Because of the significant heterogeneity between studies, a
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
ies did not materially change the pooled estimation of the
CoQ10 intervention effect on TC (Fig. 4A). The subgroup ana­
lysis suggested that subjects’ health conditions were a major
source of heterogeneity across studies (P for subgroup differ­
ence < .01); CoQ10 intervention effect on TC was significant
(MD −12.30 mg/dL; 95% CI −14.89, −9.71) among healthy
subjects, which was significantly stronger than that among
subjects with diabetes (MD −2.08 mg/dL; 95% CI −6.18,
2.03), dyslipidemia (MD −4.53 mg/dL; 95% CI −15.96,
6.89), cardiovascular diseases (MD −0.98 mg/dL; 95% CI
−3.66, 1.71), chronic kidney disease (MD −11.72 mg/dL;
95% CI −26.88, 3.44), and other diseases (MD −6.51 mg/
dL, 95% CI −13.04, 0.02). A marginally significant subgroup
difference was observed between CoQ10 supplemental dosage
(P for subgroup difference = .08): the CoQ10 intervention ef­
fect on TC was −2.55 mg/dL (95% CI −5.79, 0.70) with-low
dosage CoQ10 (<200 mg/day) and −7.18 mg/dL (95% CI
−11.12, −3.23) with high-dosage CoQ10 (≥200 mg/day)
(Table 3).
The Effects of CoQ10 Supplementation on
Low-Density Lipoprotein Cholesterol
Forty-two RCTs with 1202 subjects in the CoQ10 arm and
1185 subjects in the control arm showed a significant decrease
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in circulating LDL-C levels (MD −3.03 mg/dL; 95% CI
−5.25, −0.81; I2 = 54%, P < .01) (Fig. 3B) following supple­
mentation with CoQ10 regardless of intervention type.
Removing any of the studies did not significantly change the
pooled effect on LDL-C (Fig. 4B). We did not observe signifi­
cant subgroup differences, implying that there was no signifi­
cant source of heterogeneity (all P for heterogeneity of
intervention effects of CoQ10 on LDL-C between subgroups
> .05, Table 3).
The Effect of CoQ10 Supplementation on
High-Density Lipoprotein Cholesterol
Forty-one RCTs including 2409 subjects (1214 subjects in
the CoQ10 arm and 1195 subjects in the control arm) indi­
cated a significant increase in circulating HDL-C concentra­
tions (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%, P <
.01) (Fig. 3C) following CoQ10 supplementation. The
pooled effect of HDL-C was marginally weaker after re­
moving the study of Mohseni M. 2015 (67) (MD 0.40 mg/
dL; 95% CI −0.27, 1.06) or Singh R.B. 2003 (78) (MD
0.73 mg/dL; 95% CI −0.09, 1.56) (Fig. 4C). The subgroup
analysis suggested that subjects’ health conditions were a
significant source of heterogeneity across studies (P for sub­
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
than that among subjects with diabetes (MD 0.17 mg/dL;
95% CI −1.37, 1.71), cardiovascular diseases (MD
0.91 mg/dL; 95% CI −1.10, 2.91), chronic kidney disease
(MD −2.69 mg/dL; 95% CI −4.82, −0.56), other diseases
(MD 0.73 mg/dL; 95% CI −0.32, 1.78), and healthy sub­
jects (MD 0.16 mg/dL; 95% CI −2.42, 2.73) (Table 3).
The Effect of CoQ10 Supplementation on
Triglycerides
Forty-two RCTs including 1228 subjects in the CoQ10 arm
and 1215 subjects in the control arm indicated an overall
effect of significantly reduced circulating TG concentrations
(MD −9.06 mg/dL; 95% CI −14.04, −4.08; I2 = 65%,
P < .01) (Fig. 3D). The pooled effect of CoQ10 on TG did
not change significantly after removing any of the studies
(Fig. 4D). Despite high sources of heterogeneity, the test for
subgroup differences indicated no significant effect (all Ps
for heterogeneity of intervention effects of CoQ10 on TG be­
tween subgroups > .05, Table 3).
The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
Figure 1. Flow diagram of the literature search process.
Dose–Response Relationships Between CoQ10
Supplementation and Lipid Profiles
The dose–response analysis showed that CoQ10 supplementa­
tion reduced TC with an inverse J-shaped nonlinear relation­
ship: the beneficial effects increase with the CoQ10
supplementation dosage when it was below 400 mg/day and
then remained flat at that low level (χ2 = 48.54, P < .01)
(Fig. 5). We did not find clear dose–response relationships of
CoQ10 with LDL-C, HDL-C, and TG.
Publication Bias
Publication bias was determined by funnel plot, and Begg’s
rank test and Egger’s test. As shown in Fig. 6, Begg’s rank
test and Egger’s test indicated no significant evidence of pub­
lication bias for studies evaluating the effects of CoQ10 on TC
(Begg’s: z = 1.05, P = .29; Egger’s: t = 0.21, P = .84), LDL-C
(Begg’s: z = 1.38, P = 0.17; Egger’s: t = −1.46, P = .15),
HDL-C (Begg’s: z = −0.32, P = 0.75; Egger’s: t = 0.50,
P = .62), and TG (Begg’s: z = 0.91, P = .36; Egger’s: t = −0.58,
P = .57).
Discussion
Based on 50 RCTs with 2794 subjects, the results of this sys­
tematic review and meta-analysis indicated that CoQ10 sup­
plementation significantly improved lipid profiles, such as
235
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decreasing TC, LDL-C, and TG and increasing HDL-C lev­
els in the adult population. The dose–response analysis re­
vealed an inverse J-shaped nonlinear pattern between
CoQ10 supplementation and TC, in which the optimal
dose was 400 to 500 mg/day. To date, this is the largest
meta-analysis (60 studies included) evaluating this associ­
ation, while previous meta-analyses included fewer than
25 studies (11, 20–22, 24, 25).
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/
dL, TG decreased by approximately 9.06 mg/dL, and
HDL-C increased by approximately 0.83 mg/dL. Based on a
meta-analysis quantifying the association between LDL-C
and coronary mortality, which showed a 19% reduction in
coronary mortality per mmol/L reduction in LDL-C (86).
This means that reducing LDL-C by 3.03 mg/dL might lower
coronary mortality by approximately 1.49%. Moreover, evi­
dence has shown that TG levels and TC levels are positively
associated with the incidence and mortality of CVDs, while
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
tion of CVDs.
The results of previous meta-analyses suggested the bene­
ficial effects of CoQ10 on some of the 4 lipid profiles but not
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)
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Table 1. Continued

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)

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
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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

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Table 1. Continued
238

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)

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).
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The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
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
onstrated that CoQ10 supplementation significantly im­
proved TC and HDL-C levels, but it did not significantly
affect other lipid profiles (21). Another meta-analysis re­
ported that CoQ10 significantly decreased TG, but had
no significant effect on TC, LDL-C or HDL-C among par­
ticipants with metabolic diseases (11). Furthermore, a
meta-analysis in diabetic patients suggested that CoQ10
significantly reduced TC and LDL-C (90), while another
meta-analysis in patients with chronic kidney disease
showed no effects of CoQ10 on TC, LDL-C, HDL-C, and
TG (25). One major reason for the inconsistent results of
previous meta-analyses should be the study size, as each
included only part of the RCTs such that each showed a
significant intervention effect on some lipid profiles but
not on other lipid profiles, but they were all in the right
direction. After we summarized all of the RCTs that met
our criteria and updated the data with 15 more RCTs,
the intervention effects of CoQ10 supplementation on
TC, TG, LDL, and HDL all reached statistically significant
levels. Another potential reason is the confounding effect
from diseases that might conceal the true intervention ef­
fect. We further compared the results by subgroup analysis
and found that 5 studies among healthy subjects indicated
a significant intervention effect of CoQ10 on TC without
significant heterogeneity across studies, which was stron­
ger than the intervention effect among subjects with dysli­
pidemia, diabetes, cardiovascular diseases, chronic kidney
disease, or other diseases. Regarding the intervention ef­
fect of CoQ10 on HDL-C, 10 studies among subjects
with dyslipidemia indicated a significant intervention ef­
fect of CoQ10 on HDL-C, which was stronger than the
intervention effects among healthy subjects or patients
with diabetes, cardiovascular diseases, chronic kidney dis­
ease, or other diseases.
239
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Specifically, we performed a dose–response meta-analysis
to explore the potential optimal dose of CoQ10 supplementa­
tion on improving lipid profiles by using a novel 1-stage
model that allows us to include trials with only 1 interven­
tion dosage. To our knowledge, this is the first dose–
response meta-analysis of RCTs to evaluate the effect of
CoQ10 supplementation on lipid profiles. We found an in­
verse J-shaped nonlinear relationship with the effect of
CoQ10 supplementation on TC, which revealed that the
beneficial effects increased when CoQ10 < 400 mg/day and
then plateaued at higher doses. However, few observational
studies or RCTs have supported the inverse J-shaped non­
linear dose–response relationship. Despite the lack of direct
evidence, there was a similar trend in the effect of CoQ10
supplementation on lipid profiles in a meta-analysis based
on RCTs, significantly decreasing TC at lower dosages but
not significantly at higher dosages (21). The inverse
J-shaped curves provide a reference for future RCTs to ex­
plore dose–response relationship between CoQ10 supplemen­
tation and lipid profiles.
Several potential mechanisms have been proposed by
which CoQ10 supplementation may improve circulating
lipids (12, 13, 91–98). In human endothelial cells, exposure
to CoQ10 is associated with downregulation of the lectin-
like oxidized LDL receptor, stimulation of 5’ adenosine
monophosphate-activated protein kinase (AMPK), and re­
duction of reactive oxygen species (ROS)-induced endothe­
lial damage (98). In fact, the primary effect of CoQ10 on
circulating lipid profiles appears to increase LDL resistance
to oxidative stress (92), as demonstrated in healthy adults
following acute strenuous physical activity (97). In vitro,
it inhibits LDL oxidation better than other antioxidant
molecules such as alpha-tocopherol or beta-carotene (94,
95). CoQ10 can also significantly improve HDL-mediated
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
trials of bias indirectness imprecision
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
trials of bias indirectness imprecision

a
The test for heterogeneity is significant, and the I2 is moderate, 70%.
b
The test for heterogeneity is significant, and the I2 is moderate, 54%.
c
The test for heterogeneity is significant, and the I2 is high, 82%.
d
The test for heterogeneity is significant, and the I2 is moderate, 65%.
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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
triphosphate–binding cassette transporter G1-signaling
pathway (14, 99). Moreover, CoQ10 may activate the
calcium-mediated AMPK pathway and inhibit differenti­
ation-induced adipogenesis, inducing the gene expression
of peroxisome proliferator-activated receptor-γ (PPAR-γ)
(93), which is a main regulator of lipid storage in adipose
tissue (91). In addition, CoQ10 increases fatty acid oxida­
tion, which reduces oxidative stress via a decrease in mito­
chondrial free fatty acids, participates in endothelial
metabolism, and increases TG lipolysis (12, 13).
Furthermore, CoQ10, in its reduced state, has been shown
to inhibit the peroxidation of cell membrane lipids and re­
duce the oxidation of circulating lipids (96).
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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.
The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1 243

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

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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
Type of intervention
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
Duration of study (weeks)
<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)
244 The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1

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

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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
Type of intervention
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
Duration of study (weeks)
<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
Type of intervention
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
Duration of study (weeks)
<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.
The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
A major strength of this review is the large study size: data
from the 50 RCTs provided sufficient power to examine the
effect of CoQ10 on lipid profiles. In general, there was no
Figure 5. Dose–response relationship between dose of CoQ10
supplementation and mean differences in total cholesterol. The dotted
lines represent 95% CI.
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.
245
evidence of publication bias. The included studies were high-
quality randomized and double-blind trials and were robust in
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
Downloaded from https://academic.oup.com/jcem/article/108/1/232/6751027 by guest on 27 March 2024
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
supplementation on HDL-C showed significant heterogeneity
in the sensitivity analysis, which warrants further replication
of RCTs in the future.
246 The Journal of Clinical Endocrinology & Metabolism, 2023, Vol. 108, No. 1
In conclusion, this comprehensive systematic review and
meta-analysis demonstrated that CoQ10 supplementation
might have promising effects on lipid profiles by decreas­
ing TC, TGs, and LDL-C levels and increasing HDL-C lev­
els. For LDL-C, the CoQ10 intervention effect is the
greatest when the dosage is 400 to 500 mg/day. More
RCTs are warranted to determine the dose–response rela­
tionships between CoQ10 supplementation and other lipid
profiles.
Acknowledgments
The authors acknowledge the help of American journal ex­
perts in editing this manuscript.
Funding
The authors would like to acknowledge the Key Program of
the National Natural Science Foundation of China (no.
82030098), the National Natural Science Foundation of
China (no. 81872617), Science, Technology and Innovation
Commission of Shenzhen Municipality (no.
JCYJ20180307153228190), CNS Research Fund for DRI
for financial support, and the National College Students
Innovation and Entrepreneurship Training Program (no.
202210558159 and 202210558161).
Author Contributions
Z.L. and M.L. had full access to all of the data and take re­
sponsibility for the integrity of the data. Concept and design:
Y.Y., Z.T. Acquisition, or interpretation of data: Z.L., Z.T.,
D.Z., Y.L., S.D., M.L., S.H., X.D., Zhaxinima, Y.Y.
Analysis of the data and drafting of the manuscript: Z.L.
Critical revision of the manuscript for important intellectual
content: Y.Y. Statistical analysis: Z.L. Obtained funding:
Y.Y. Supervision: Y.Y., Z.T.
Disclosures
The authors declare no conflict of interest.
Data Availability
Original data generated and analyzed during this study are in­
cluded in the data repositories listed in reference (106).
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