Effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients with coronary …
The purpose of this study was to investigate the effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and homocysteine) in patients with coronary artery disease (CAD). Patients with CAD (n = 51) were randomly assigned to a placebo group (n = 14) or one of two coenzyme Q10-supplemented groups (60 mg/d, Q10-60 group, n = 19; 150 mg/d, Q10-150 group, n = 18). The intervention was administered for 12 wk. Plasma coenzyme Q10 concentration, inflammatory markers (hs-CRP, IL-6, and homocysteine), malondialdehyde, and superoxide dismutase activities were measured. Forty subjects with CAD completed the intervention study. The plasma coenzyme Q10 concentration increased significantly in the Q10-60 and Q10-150 groups (P < 0.01). After 12 wk of intervention, the inflammatory marker IL-6 (P = 0.03) was decreased significantly in the Q10-150 group. Subjects in the Q10-150 group had significantly lower malondialdehyde levels and those in the Q10-60 (P = 0.05) and Q10-150 (P = 0.06) groups had greater superoxide dismutase activities. Plasma coenzyme Q10 was inversely correlated with hs-CRP (r = -0.20, P = 0.07) and IL-6 (r = -0.25, P = 0.03) at baseline. After supplementation, plasma coenzyme Q10 was significantly correlated with malondialdehyde (r = -0.35, P < 0.01) and superoxide dismutase activities (r = 0.52, P < 0.01). However, there was no correlation between coenzyme Q10 and homocysteine. Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.
Applied nutritional investigation
Effects of coenzyme Q10 supplementation on inﬂammatory markers
(high-sensitivity C-reactive protein, interleukin-6, and homocysteine)
in patients with coronary artery disease
Bor-Jen Lee M.D.
, Yi-Chia Huang Ph.D.
, Shu-Ju Chen Ph.D.
, Ping-Ting Lin Ph.D.
School of Nutrition, Chung Shan Medical University, Taichung, Taiwan
Intensive Care Unit, Taichung Veterans General Hospital, Taichung, Taiwan
Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
Department of Nutrition and Health Science, Chung Chou University of Science and Technology, Changhua, Taiwan
Received 15 April 2011
Accepted 9 November 2011
High-sensitivity C-reactive protein
Coronary artery disease
Objective: The purpose of this study was to investigate the effects of coenzyme Q10 supplemen-
tation on inﬂammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6],
and homocysteine) in patients with coronary artery disease (CAD).
Methods: Patients with CAD (n ¼ 51) were randomly assigned to a placebo group (n ¼ 14) or one of
two coenzyme Q10-supplemented groups (60 mg/d, Q10-60 group, n ¼ 19; 150 mg/d, Q10-150
group, n ¼ 18). The intervention was administered for 12 wk. Plasm a coenzyme Q10 concentra-
tion, inﬂammatory markers (hs-CRP, IL-6, and homocysteine), malondialdehyde, and superoxide
dismutase activities were measured.
Results: Forty subjects with CAD completed the intervention study. The plasma coenzyme Q10
concentration increased signiﬁ cantly in the Q10-60 and Q10-150 groups (P < 0.01). After 12 wk of
intervention, the inﬂammatory marker IL-6 (P ¼ 0.03) was decreased signiﬁcantly in the Q10-150
group. Subjects in the Q10-150 group had signiﬁcantly lower malondialdehyde levels and those in
the Q10-60 (P ¼ 0.05) and Q10-150 (P ¼ 0.06) groups had greater superoxide dismutase activities.
Plasma coenzyme Q10 was inversely correlated with hs-CRP (r ¼0.20, P ¼ 0.07) and IL-6 (r ¼0.25,
P ¼ 0.03) at baseline. After supplementation, plasma coenzyme Q10 was signiﬁcantly correlated with
malondialdehyde (r ¼0.35, P < 0.01) and superoxide dismutase activities (r ¼ 0.52, P < 0.01).
However, there was no correlation between coenzyme Q10 and homocysteine.
Conclusion: Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the
inﬂammatory marker IL-6 in patients with CAD.
Ó 2012 Elsevier Inc. All rights reserved.
Coenzyme Q10 (also called ubiquinone) is a lipid-soluble
benzoquinone with 10 isoprenyl units in the side chain and is
a key component of the mitochondrial respiratory chain for
adenosine triphosphate synthesis [1,2]. Tissues with high-energy
requirements, such as the heart, kidney, liver, and skeletal
muscle cells, need a larger amount of coenzyme Q10 to synthe-
size adenosine triphosphate. Coenzyme Q10 is recognized as an
intracellular antioxidant that protects membrane phospholipids,
mitochondrial membrane protein, and low-density lipoprotein
against free radical-induced oxidative damage [3,4]. Coenzyme
Q10 can be synthesized in the tissue from farnesyl diphosphate
and tyrosine and can be obtained from the diet in an oxidized
form of which 75% to 95% is then converted into a reduced form
in the body; however, the total absorption of coenzyme Q10 is
thought to be less than 10% [5,6].
Cardiovascular disease is the leading cause of death world-
wide . There is mounting evidence that in ﬂammation plays
a role in the development of cardiovascular disease. In clinical
studies, the levels of homocysteine and high-sensitivity C-reac-
tive protein (hs-CRP) have commonly been used as inﬂammatory
markers that contribute to the earlier stages of coronary artery
disease (CAD) [8,9]. Interleukin-6 (IL-6) is a messenger cytokine
This study was supported by grant NSC 97-2320-B-040-034-MY2 from the
National Science Council, Taiwan.
Corresponding author. Tel.: þ886-4-2473-0022, ext. 12187; fax: þ886-4-
E-mail address: email@example.com (P.-T. Lin).
0899-9007/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved.
Contents lists available at ScienceDirect
journal homepage: www.nutritionjrnl.com
Nutrition 28 (2012) 767–772
that induces hepatic CRP production . The relation between
coenzyme Q10 and inﬂammation has been reported in cell [11,12]
and animal [13,14] models. In recent studies [15,16], however,
coenzyme Q10 supplementation has been found to have inﬂu-
ence on inﬂammatory markers in subjects with multiple
cardiovascular disease risk factors or in healthy subjects. To date,
fewer clinical studies have investigated the relation between
coenzyme Q10 and inﬂammation in patients with CAD. As
a result, in this study, we investigated the effect of coenzyme Q10
supplementation (60 and 150 mg/d) on inﬂammatory markers
(hs-CRP, IL-6, and homocysteine) in patients with CAD.
Materials and methods
This study was designed as a randomized, parallel, placebo-controlled study.
Patients with CAD were recruited from the cardiology clinic of Taichung Veterans
General Hospital, which is a teaching hospital in central Taiwan. Patients iden-
tiﬁed as having at least 50% stenosis of one major coronary artery by cardiac
catheterization or underwent percutaneous transluminal coronary angioplasty
were enrolled in this study. Subjects with diabetes or liver or renal diseases were
excluded to minimize the inﬂuence of other cardiovascular risk factors. Patients
under statin therapy or currently taking vitamin supplements were also
excluded. None of the subjects had developed acute myocardial infarction within
the previous 6 mo. Informed consent was obtained from each subject. This study
was approved by the institutional review board of Taichung Veterans General
With a sample size calculation, we expected that the change in the level of
hs-CRP would be 0.1 0.1 mg/dL after the coenzyme Q10 intervention; hence, the
desired power was set at 0.8 to detect a true effect and at an
value equal to 0.05
with a minimal sample 10 in each intervention group. We enrolled 59 patients
with CAD in this study; eight subjects declined to participate. Fifty-one subjects
were randomly assigned to one of three groups: a placebo group (n ¼ 14) or one
of two coenzyme Q10-supplemented groups (60 mg/d, Q10-60 group, n ¼ 19; 150
mg/d, Q10-150 group, n ¼ 18; Fig. 1). Four postmenopausal women who were not
using hormone therapy were recruited into this study. The coenzyme Q10 and
placebo (starch) capsules were commercially available preparations (New Health
Products Co., Ltd., Taichung, Taiwan). The intervention was administered for 12
wk (3 mo). Patients were instructed to take one capsule daily. To monitor
compliance, the researchers reminded patients to check the capsule bag every 4
wk to conﬁrm that the bag was empty. The age, blood pressures, and smoking
habits of the subjects were recorded. Body weight and height were measured,
and then the body mass index (kilograms per meter squared) was calculated.
Fasting venous blood samples (15 mL) were obtained to estimate hemato-
logic and vitamin statuses. Blood specimens were collected in Vacutainer tubes
(Becton Dickinson, Rutherford, NJ, USA) containing ethylenediaminetetraacetic
acid as an anticoagulant or no anticoagulant, as required. Serum and plasma were
prepared and then stored frozen (80
C) until analysis. Hematologic entities (i.e.,
serum urea nitrogen, serum creatinine, total cholesterol, triacylglycerol, low-
density lipoprotein, and high-density lipoprotein) were measured using an
automated biochemical analyzer. An automated hs-CRP measurement was
performed by particle-enhanced immunonephelometry with an Immage
analyzer (Beckman Coulter, Fullerton, CA, USA). The quantitative measurement of
the plasma IL-6 level was performed by an enzyme-linked immunosorbent assay
using commercially available kits (GEN-PROBE, Diaclone, Besancon Cedex,
France) and according to the instructions available from the supplier.
Plasma coenzyme Q10 was measured using high-performance liquid chro-
matography according to the method of Chu et al.  and Littarru et al. . The
mean intra- and interassay coefﬁcients of fasting plasma coenzyme Q10 vari-
ability were 1.8% and 4.4%, respectively. The mean analytical recovery of plasma
coenzyme Q10 was 99.8%. Plasma homocysteine was also determined by high-
performance liquid chromatography, as previously described . The mean
intra- and interassay coefﬁcients of fasting plasma homocysteine variability were
1.0% and 4.3%, respectively. The mean analytical recovery of plasma homo-
cysteine was 98.9%.
Plasma malondialdehyde (MDA) was determined using the thiobarbituric
acid-reactive substances method, as described by Botsoglou . Red blood cells
were diluted with 25 sodium phosphate buffer for the superoxide dismutase
(SOD) measurement . The protein contents of plasma and red blood cells
were determined based on the Biuret reaction of the bicinchoninic acid kit
(Thermo, Rockford, IL, USA). The MDA levels were expressed in nanomoles per
milligram of protein and the SOD level was expressed in units per milligram of
protein. All analyses were performed in duplicate.
Data were analyzed with SigmaStat 2.03 (Jandel Scientiﬁc, San Rafael, CA,
USA). The normal distribution of variables was tested by the Kolmogorov–
Smirnov test. Differences in subjects’ demographic data and hematologic
measurement data among the three intervention groups were analyzed by one-
way analysis of variance or the Kruskal–Wallis analysis of variance on ranks; the
Tukey post hoc test was then used to assess the statistically signiﬁcant differ-
ences among groups. Paired t test or the Wilcoxon signed rank test was used to
analyze the data within each group before and after the intervention. For cate-
gorical response variables, differences among the three groups were assessed by
chi-square test or the Fisher exact test. To examine the relation of coenzyme Q10
concentration to the inﬂammatory markers and the MDA and SOD levels before
and after the supplementation, the Pearson product-moment correlation or the
Spearman rank-order correlation was used. Results were considered statistically
signiﬁcant at P < 0.05. Values are presented in the text as mean standard
Table 1 presents the demographic data and health charac-
teristics of the subjects. There were no signiﬁcant differences
among the three groups with respect to age, body mass index,
blood pressure, anthropometric measurements, hematologic
entities (i.e., serum urea nitrogen, serum creatinine, and lipid
proﬁles), and the frequency of smoking at baseline.
The effect of the coenzyme Q10 supplementation on the
inﬂammation markers, lipid peroxidation, and antioxidant
enzyme activities is presented in Figure 2. The plasma coenzyme
Q10 concentration was signiﬁcantly increased after the coen-
zyme Q10 supplementation at the dosages of 60 mg/d (P ¼ 0.03)
and 150 mg/d (P < 0.01). After 12 wk of the intervention, the
inﬂammatory markers (IL-6, P ¼ 0.03) were signiﬁcantly
decreased in the Q10-150 group. Subjects in the Q10-150 group
had signiﬁcantly lower MDA levels and those in the Q10-60 (P ¼
0.05) and Q10-150 (P ¼ 0.06) groups had greater SOD activities.
The correlations among the coenzyme Q10 concentration,
inﬂammatory markers, lipid peroxidation, and antioxidant
enzyme activities are presented in Table 2. Plasma coenzyme Q10
was inversely correlated with hs-CRP (r ¼0.20, P ¼ 0.07) and
IL-6 (r ¼0.25, P ¼ 0.03) at baseline. After 12 wk of supple-
mentation, plasma coenzyme Q10 was signiﬁcantly correlated
with MDA (r ¼0.35, P < 0.01) and SOD (r ¼ 0.52, P < 0.01)
activities but not with the inﬂ ammatory markers. However,
there was no correlation of coenzyme Q10 with homocysteine.
A high inﬂammation has been associated with CAD, but few
clinical studies have examined the effect of coenzyme Q10
supplementation on inﬂammation markers. With respect to
inﬂammatory makers, the IL-6 levels were signiﬁcantdecreased by
14% after the coenzyme Q10 supplementation at dosage of 150 mg/
g. 2). However, there wasno inﬂuence on the hs-CRP level after
the coenzyme Q10 supplementation. High-sensitivity CRP is
a product of hepatic stimulation and inﬂammation and is under
the regulation of IL-6 [10,22]; IL-6 is a messenger cytokine
(proinﬂammatory cytokine) that is secreted by macrophages and
smooth muscle cells in the atherosclerotic lesion. Thus, IL-6 may
reﬂect inﬂammatory reactions with more sensitivity than hs-CRP
[23,24]. We tried to stratify the inﬂammation status according to
the levels of hs-CRP (0.1 mg/dL) or IL-6 (1.5 pg/mL) as a cutoff
B.-J. Lee et al. / Nutrition 28 (2012) 767–772768
point to deﬁne a higher inﬂammation status, which is an average
risk factor for CAD [25,26]. It wasinteresting to ﬁnd that the hs-CRP
and IL-6 levels were signiﬁcantly lower in those who received
coenzyme Q10 supplementation at a dosage of 150 mg (n ¼ 11,
hs-CRP 0.3 0.3 to 0.2 0.3 mg/dL, P ¼ 0.03; IL-6 1.5 1.5 to 1.2
1.0 pg/mL, P ¼ 0.02; data not shown). Plasma coenzyme Q10
concentration was correlated with the hs-CRP and IL-6 levels at
baseline; however, after the intervention, plasma coenzyme Q10
was signiﬁcantly correlated with MDA (r ¼0.35, P < 0.01) and
SOD (r ¼ 0.52, P < 0.01) activities but was not related to the hs-CRP
or IL-6 levels (Table 2). Gökbel et al.  reported that coenzyme
Q10 supplements at a dose of 100 mg/d had no signiﬁcant effect on
inﬂammation markers in healthy subjects. This lack of an effect in
healthy subjects may be caused by the fact that healthy subjects do
not have high levels of inﬂammation or the dosage of coenzyme
Q10 supplements (100 mg/d) was not high enough to observe an
anti-inﬂammatory effect. Also, in this study of subjects with CAD,
the coenzyme Q10 supplements at a dosage of up to 150 mg/d
produced a slightly anti-inﬂammatory effect on IL-6 but not on
hs-CRP and homocysteine concentrations.
Assessed for eligibility (n=59)
-Not meeting inclusion criteria (n=0)
-Declined to participate (n=8)
-Other reasons (n=0)
Placebo group (n=12)
-Excluded from analysis (n=0)
Lost to follow-up (n=2)
-Discontinued intervention (n=2)
Allocated to intervention (n=14):
-Received allocated Placebo group (n=14)
-Did not receive allocated intervention (n=0)
Lost to follow-up (n=6)
-Discontinued intervention: (n=6)
- 60 mg/day (n=3); 150 mg/day (n=3)
Allocated to intervention (n=37)
-Received allocated Coenzyme Q10 supplements:
Q10-60 group (n=19); Q10-150 group (n=18)
-Did not receive allocated intervention (n=0)
60 mg/day (n=14) and 150 mg/day (n=14)
-Excluded from analysis (n=3)
- 60 mg/day (n=2); 150 mg/day (n=1)
Fig. 1. Flow diagram. Q1060, coenzyme Q10 60 mg/d; Q10-150, coenzyme Q10 150 mg/d.
General baseline characteristics of subjects
Placebo (n ¼ 12) Q10-60 (n ¼ 14) Q10-150 (n ¼ 14) P
Men/women 12/0 12/2 13/1 0.39
Age (y) 77.2 7.4 75.1 4.9 79.2 5.4 0.20
Systolic blood pressure (mmHg) 136.7 13.3 132.3 13.3 130.7 8.3 0.72
Diastolic blood pressure (mmHg) 73.3 6.5 75.4 14.9 72.4 5.5 0.84
Body mass index (kg/m
) 26.9 2.8 25.6 2.8 25.2 2.6 0.26
Waist-to-hip ratio 0.8 1.0 0.9 0.1 0.9 0.1 0.95
BUN (mmol/L) 14.4 4.3 16.9 5.9 15.8 6.6 0.50
Serum creatinine (
mol/L) 114.9 26.5 123.8 44.2 123.8 26.5 0.70
TC (mmol/L) 4.7 0.8 4.9 0.7 5.3 0.8 0.16
TG (mmol/L) 1.5 0.6 1.7 1.2 1.5 1.0 0.80
LDL-C (mmol/L) 3.1 0.9 3.1 0.7 3.5 0.9 0.28
HDL-C (mmol/L) 0.9 0.2 1.0 0.2 1.0 0.3 0.88
1 (8.3%) 4 (28.6%) 2 (14.3%) 0.98
Former smoker 4 (33.3%) 2 (14.3%) 3 (21.4%) 0.60
BUN, serum urea nitrogen; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; Q10-60,
coenzyme Q10-60 mg/d; Q10-150, coenzyme Q10-150 mg/d; TC, total cholesterol; TG, triacylglycerol
Values are presented as number of subjects (percentage) or mean SD.
Currently smoking at least one cigarette per day.
B.-J. Lee et al. / Nutrition 28 (2012) 767–772 769
Cell culture experiments have demonstrated that coenzyme
Q10 can moderate the anti-inﬂammatory effects of antioxidant
activities  and by nuclear factor-
expression . In the present study, coenzyme Q10 supple-
ments at a dose of 150 mg showed a signiﬁcant antioxidization
effect in decreasing the MDA level (P ¼ 0.03) and slightly
increasing SOD activities (P ¼ 0.06) after 12 wk of intervention. In
addition, the plasma coenzyme Q10 concentration was signiﬁ-
cantly correlated with MDA and SOD (P < 0.01; Table 2)atweek
12. Notably, the activities of SOD were signiﬁcantly decreased in
the placebo group compared with baseline (P ¼ 0.02) and among
the three groups (P ¼ 0.06). The role of antioxidant enzyme
defenses against the reactive oxygen species is controversial. In
patients with CAD, SOD plays an important role in the protection
of cells against oxidative stress by ameliorating the superoxide
anion [29,30]. Coenzyme Q10 may assist SOD in the uptake of the
superoxide radical to form oxygen and hydrogen peroxide. As
a result, the protective effects of endogenous enzymatic antiox-
idants might decrease in patients with CAD [5,30,31] without
coenzyme Q10 supplementation.
Hyperhomocysteinemia is an independent risk factor of CAD
. Sixty percent of patients with CAD in this study had
mol/L). However, homocysteine
concentrations were unchanged after the coenzyme Q10
supplementation. A lower homocysteine concentration might
correlate with the status of B vitamins . Among B vitamins,
vitamin B6 (as pyridoxal 5
-phosphate) is essential for the
synthesis of coenzyme Q10 . Coenzyme Q10 supplementa-
tion and concurrent supplementation with B vitamins (vitamin
B6) not only provided a better endogenous synthesis of coen-
zyme Q10  but also decreased the homocysteine concentra-
tion . In a coadministration study, patients with breast
cancer treated with enzyme Q10 (100 mg) and B vitamins
(riboﬂavin 10 mg and niacin 50 mg) for 90 d had a signiﬁcantly
lower levels of serum cytokines, including IL-1
, IL-6, IL-8, and
tumor necrosis factor-
(P < 0.05) . Because atherosclerosis is
a chronic inﬂammatory disease, to lower the inﬂammation status
of an individual, a multivitamin supplementation might provide
a greater anti-inﬂammatory effect than a single vitamin
Our study has several limitations. First, the number of
participants was small, and the patients with CAD were stable. Of
the subjects in the present study, 33% had a high inﬂammation
status according to the level of hs-CRP (0.3 mg/dL) and 35%
Fig. 2. Concentration of plasma coenzyme Q10, inﬂammatory markers, lipid peroxidation, and antioxidant enzyme activities after intervention.
Values were signiﬁcantly
different after the intervention within the group. Values with different superscript letters were signiﬁcantly different among the three groups (P < 0.05). hs-CRP, high-
sensitivity C-reactive protein; MDA, malondialdehyde; Q1060, coenzyme Q10 60 mg/d; Q10-150, coenzyme Q10 150 mg/d; SOD, superoxide dism utase.
B.-J. Lee et al. / Nutrition 28 (2012) 767–772770
according to the level of IL-6 (1.5 pg/mL). The levels of hs-CRP
and IL-6 showed relatively small differences within the groups
after supplementation, and this may have contributed to the
observed null effect of antioxidants on the inﬂammatory
markers [38,39]. Second, the intervention duration was not long
enough to observe a signiﬁcant anti-inﬂammatory effect for this
dosage of coenzyme Q10 supplements (150 mg/d). Long-term
studies are needed to establish the beneﬁcial effects of
higher-dosage coenzyme Q10 supplementation on inﬂammation
in patients with CAD.
The authors express their sincere appreciation to the subjects
for their participation and to Dr. Hsia who kindly provided the
coenzyme Q10 supplements for this trial. They thank the nurses
at the Taichung Veterans General Hospital and the technical
advisor of the Taipei Institute of Pathology for providing expert
assistance in blood sample collection and data analysis.
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Plasma coenzyme Q10 (
mol/L), r (P)
Week 0 Week 12
Week 0 0.20 (0.07) dd
Week 12 d 0.14 (0.22) d
12-0 dd 0.13 (0.25)
Week 0 0.25
Week 12 d 0.07 (0.55) d
12-0 dd 0.16 (0.18)
Week 0 0.04 (0.74) dd
Week 12 d 0.04 (0.71) d
12-0 dd 0.07 (0.57)
MDA (nmol/mg protein)
Week 0 0.01 (0.91) dd
Week 12 d 0.35
12-0 dd 0.07 (0.54)
SOD (unit/mg protein)
Week 0 0.04 (0.75) dd
Week 12 d 0.52
12-0 d 0.22 (0.11)
12-0, change from week 0 to week 12; MDA, malondialdehyde; hs-CRP, high-
sensitivity C-reactive protein; r, correlation coefﬁcient; SOD, superoxide
P < 0.05.
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