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Effect of Coenzyme Q10 on Oxidative Stress, Glycemic Control and Inflammation in Diabetic Neuropathy: A Double Blind Randomized Clinical Trial

  • Reproductive Immunology Research Center Shahid Sadoughi University of Medical Sciences and Health Services

Abstract and Figures

This 12-week randomized placebo controlled clinical trial investigated the effect of Coenzyme Q10 (CoQ10) on diabetic neuropathy, oxidative stress, blood glucose and lipid profile of patients with type 2 diabetes. Diabetic patients with neuropathic signs (n = 70) were randomly assigned to CoQ10 (200 mg/d) or placebo for 12 weeks. Blood samples were collected for biochemical analysis and neuropathy tests before and after the trial. There were no significant differences between the two groups in terms of mean fasting blood glucose, HbA1c and the lipid profile after the trial. The mean insulin sensitivity and total antioxidant capacity (TAC) concentration significantly increased in the Q10 group compared to the placebo after the trial (P < 0.05). C-reactive protein (hsCRP) significantly decreased in the intervention group compared to placebo after the trial (P < 0.05). In the control group, insulin sensitivity decreased and HOMA-IR increased, which revealed a significant difference between groups after the trial. Neuropathic symptoms and electromyography measurements did not differ between two groups after the trial. According to the present study, CoQ10, when given at a dose of 200 mg/d for 12 weeks to a group of neuropathic diabetic patients, did not improve the neuropathy signs compared to placebo, although it had some beneficial effects on TAC and hsCRP and probably a protective effect on insulin resistance.
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Internatio nal Journal for Vit amin and Nutrition Res earch Vol. 84 · Number 5 – 6
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Effect of Coenzyme Q10 on Oxidative Stress, Glycemic Control and
Inflammation in Diabetic Neuropathy: A Double Blind Randomized
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Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern DOI 10.1024/0300-9831/a000211
Original Communication
Effect of Coenzyme Q10 on
Oxidative Stress, Glycemic
Control and Inflammation in
Diabetic Neuropathy: A Double
Blind Randomized Clinical Trial
Maryam Akbari Fakhrabadi1, Ahmad Zeinali Ghotrom2, Hassan Mozaffari-
Khosravi1, Hossein Hadi Nodoushan3, and Azadeh Nadjarzadeh4
1Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2Department of Neuroscience, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4Nutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Received: May 29, 2014; Accepted: January 12, 2015
Abstract: Objective: This 12-week randomized placebo controlled clinical trial investigated the effect
of Coenzyme Q10 (CoQ10) on diabetic neuropathy, oxidative stress, blood glucose and lipid profile of
patients with type 2 diabetes. Methods: Diabetic patients with neuropathic signs (n = 70) were randomly
assigned to CoQ10 (200 mg/d) or placebo for 12 weeks. Blood samples were collected for biochemical
analysis and neuropathy tests before and after the trial. Results: There were no significant differences
between the two groups in terms of mean fasting blood glucose, HbA1c and the lipid profile after the
trial. The mean insulin sensitivity and total antioxidant capacity (TAC) concentration significantly in-
creased in the Q10 group compared to the placebo after the trial (P < 0.05). C-reactive protein (hsCRP)
significantly decreased in the intervention group compared to placebo after the trial (P < 0.05). In the
control group, insulin sensitivity decreased and HOMA-IR increased, which revealed a significant dif-
ference between groups after the trial. Neuropathic symptoms and electromyography measurements
did not differ between two groups after the trial. Conclusions: According to the present study, CoQ10,
when given at a dose of 200 mg/d for 12 weeks to a group of neuropathic diabetic patients, did not im-
prove the neuropathy signs compared to placebo, although it had some beneficial effects on TAC and
hsCRP and probably a protective effect on insulin resistance.
Key words: diabetic neuropathy, oxidative stress, blood glucose, lipid profile, insulin sensitivity
Author's personal copy (e-offprint)
253M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
Type 2 diabetes is a clinical syndrome with variable
phenotypic expression rather than a single disease
with a specific etiology. The main etiology of the syn-
drome includes β-cell insufficiency and insulin resis-
tance, which leads to increased blood glucose. High
blood glucose level determines the overproduction of
reactive oxygen species (ROS) by the mitochondria
electron transport chain. High reactivity of ROS deter-
mines chemical changes in virtually all cellular compo-
nents, leading to DNA and protein modification and
lipid peroxidation[1]. One of the chief injuries arising
from hyperglycemia is injury to vasculature, which is
classified as either small vascular injury (microvascu-
lar disease) including retinopathy, nephropathy and
neuropathy, or injury to the large blood vessels of the
body (macrovascular disease) [2]. Diabetic periph-
eral neuropathy (DPN) is one of the most prevalent
long-term complications of diabetes. More than 50 %
of all diabetic patients may suffer from some degree
of neuropathy [3]. DPN is considered the cause of
considerable morbidities and can affect the quality
of life [3, 4]. It is characterized by the progressive
deterioration of nerves predisposing neuropathic foot
ulceration, Charcot neuroarthropathy, and lower ex-
tremity amputation [4]. Diabetic neuropathies are
divided into symmetrical and asymmetrical types;
symmetrical forms include distal sensory or sensory
polyneuropathy, small-fiber neuropathy, autonomic
neuropathy and large-fiber neuropathy [5]. Older age,
long duration of diabetes and poor glycemic control
are well established risk factors for DPN [6]. Chronic
hyperglycemia causes oxidative stress in tissues sus-
ceptible to complications in diabetic patients. The
mechanisms underlying oxidative stress in chronic
hyperglycemia and neuropathy development have
been studied in experimental models [7]. As a result,
ameliorating oxidative stress through treatment with
antioxidants might be an effective strategy for the
reduction of DPN [8].
Coenzyme Q10 is a quinone which was first isolated
from bovine heart mitochondria. It is also known as
ubiquinone, because it is found in virtually all human
cells. The reduced form of Coenzyme Q10 acts as
an antioxidant, combats free radicals, prevents lipid
peroxidation, and protects mitochondrial DNA. Co-
enzyme Q10 has been suggested to increase plasma
antioxidant activity [9].
The effect of Coenzyme Q10 on oxidative diseases
such as diabetes, coronary artery disease and hyper-
tension has been studied [10 12]. There are limited
data regarding the effect of Coenzyme Q10 on diabetic
neuropathy [13] and oxidative stress. Therefore, the
aim of this study was to investigate the effect of Co-
enzyme Q10 supplementation on oxidative stress in a
group of diabetic patients suffering from neuropathy.
Materials and Methods
The subjects for this randomized, double-blind, pla-
cebo-controlled, parallel group study were recruited
from Yazd Diabetes Research Center, Iran. The trial
has been done from October 2011 to February 2012
(RCT code: IRCT201109127541N1) and was planned
for 12 weeks (Figure 1).
The study protocol was approved by the Ethics
Committee of Shahid Sadoughi University of Medical
Sciences, Yazd, Iran. The sampling was performed
by randomizing patients who fulfilled our inclusion
criteria. All participants were referred to a single en-
docrinologist. Subjects who were recruited for the trial
(blinded to group assignment) were informed about
the aims, procedures and possible risks of the study
and gave written informed consent. The inclusion cri-
teria were age between 35 and 65 years, type 2 dia-
betes defined by the American Diabetes Association
criteria (1997), diabetes duration > 5 years, Michigan
Neuropathy Screening Instrument (MNSI) score ≥ 8,
impaired knee and Achilles reflex, abnormal nerve
conduction velocity and on a stable dose of medica-
tions for diabetic control in the month prior to enrol-
ment. The patients should not have taken antioxidant
supplements during the last three months. Subjects
with liver, kidney or other neurologic diseases were
Participants were randomly allocated in a 1:1 ratio
to receive the supplement or matched placebo daily for
12 weeks. After randomization, patients received an
unmarked bottle of capsules with either 100 mg CoQ10
(Health Burst, USA) or the placebo. They were in-
structed to take CoQ10 or placebo capsules twice daily
with their meals, and to leave unused capsules in the
bottles. Participants were instructed to follow their
habitual diet and physical activity and not to change
their prescribed medications and dosage. The placebo
capsule contents consisted of microcrystalline cellu-
lose, with a similar appearance to the active capsules.
Participants and providers were blinded to patient
intervention assignment; our biostatistician broke the
code only for the final analyses without revealing any
specific assignment information to others.
Height was measured without shoes against a wall-
fixed tape and weight with light clothing and without
Author's personal copy (e-offprint)
254 M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
shoes on a platform scale with a 1.0 kg subtraction to
correct for the weight of the clothing. The body mass
index (BMI) was calculated as weight/height (kg/m2).
Peripheral blood sample was collected after a
10 hour fasting period from each subject for biochemi-
cal parameters, including fasting glucose, lipid profile,
fasting insulin, HbA1C, hsCRP and total antioxidant
capacity (TAC) at baseline and at the end of the study.
Blood glucose was measured using the glucose peroxi
dase method with the auto analyzer device (Echoplus,
Italy). HbA1c was measured by using a chromatog-
raphy method. Total cholesterol, HDL cholesterol
and triglycerides were measured using the enzymatic
methods including cholesterol oxidase and glycerol
oxidase with the auto analyzer (Echoplus, Italy).
Fasting insulin and hsCRP in serum were measured
using the ELISA method (Dia Metra, Italy). Total
antioxidant capacity (TAC) was determined with a
method developed for the evaluation of this parameter
in blood plasma. The assay is based on the ability of
antioxidants in the sample to inhibit the oxidation of
+ by a peroxidase. The amount of
ABTS+ produced can be monitored by reading the
absorbance at 734 nm. The assay was conducted at
37 °C to be similar to physiological conditions. Tem-
perature was controlled by a thermoelectric controller
probe model CE 2004, Cecil Instrument Ltd, United
Kingdom. HOMA Calculator ver. 2.2 (University of
Oxford) by analyzing the two parameters fasting glu-
cose and fasting insulin: insulin sensitivity (%S) and
HOMA (insulin resistance), which is the reciprocal of
%S (100/%S), were measured.
The phenotypic neuropathy assessed in this trial
was sensorimotor distal symmetric polyneuropathy,
which was assessed by two types of measurements:
Physical assessments and nerve conduction study
(NCS) using the electromyography machine (Sierra
Wave Caldwell Company) at the onset and end of the
trial. The indices for physical assessments included
deep and superficial sensation assessments, muscle
strength and deep tendon reflexes (DTR). All as-
sessments were performed on both sides of the body.
Superficial sensation included pain and temperature.
Pain (pin prick) was assessed using a sterile needle
for determining the length of abnormal area from
the toe to the knee. Temperature was assessed by a
cool glass and measuring the length of the unfeeling
area from the toe to the knee. The deep sensation as-
sessments included joint position and vibration. Joint
position was assessed by moving the terminal pha-
lanx of the great toes and coding the patient’s feeling
of the joint position. Vibration was assessed using a
128 diapason and measuring the length of the unfeel-
ing area from the toe to the knee. Reflex assessment
(DTR) of the Achilles tendon was scored as 2 (nor-
mal), 1 (decreased), or 0 (absent). Muscle strength was
scored as 5 (normal), 4 (good), 3 (fair), 2 (poor: grav-
ity eliminated), 1 (trace: no joint motion produced)
and 0 (no muscle contraction). It is notable that we
measured the length of the unfeeling area from the
toes to the knees in order to assess the progression of
the diabetes neuropathy after the trial. The tempera-
tures and conditions used for the assessment were the
same before and after the trial. Electrophysiological
tests included: Deep peroneal nerve (DPN) velocity,
sural nerve action potential (SNAP) amplitude and
H -reflex. In the DPN nerve conduction study (NCS),
proximal and distal stimulations were performed at
the fibular neck and ankle, respectively. The indices
were recorded from the extensor digitorum brevis
muscle. Sural NCS was performed by stimulation of
the nerve trunk at a distance of 14 cm from the lateral
ankle border where the recording electrodes were
placed. A visual analogue scale (VAS) was used to
compare the percent of improvement of neuropathy
symptoms after the trial. Each patient was asked to
give a number from 0 – 10 according to the symptoms
of neuropathy that they felt (0 = no symptoms to 10
= untolerable symptoms) before and after the trial
[(VAS2-VAS1) × 100].
In order to investigate variations in their food in-
take and to control diet-related confounding factors,
three 24 h dietary recalls were recorded from the pa-
tients before and after the trial. The average intake
was calculated for each macro- and micronutrient be-
fore and after the intervention. The Food Processor
II software (ESHA Research, Salem, Oregon, USA)
was used to process macronutrient and micronutrient
intakes based on the dietary reference intakes. The
physical activity was assessed by the Persian version
of the International Physical Activity Questionnaire
(IPAQ) before and after the trial.
With a sample size calculation, we expected that the
change in the level of TAC would be 0.5 µmol/L after
the coenzyme Q10 intervention; hence, the desired
power was set at 0.8 to detect a true effect. At an alpha
value equal to 0.05 and S = 0.7, a minimal sample of 30
in each intervention group and assuming any sample
loss, 35 patients were collected in each group. Data
were analyzed with the SPSS statistical software. The
distribution of the data was evaluated by the Shapiro
wilk test. Frequencies of categorical data were ana-
lyzed using the Chi-square test or Fisher’s exact test,
when appropriate. The independent T test (2 tailed)
was used to analyze the mean changes between groups,
while the paired T test was used for within-group
Author's personal copy (e-offprint)
255M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
analyses after intervention for normal data. For data
which were not normal, the Mann Whitney test was
used to analyze the median changes between groups.
Log transformation was used for some non-normal
distributed data. Adjustment was performed by AN-
COVA test considering the baseline concentration as
a covariate for normal distributed data.
The baseline characteristics of participants are given
in Table I. Subjects who received CoQ10 were not
statistically different from the placebo group with
regard to age, weight, BMI, duration of disease and
gender at onset of the trial. Of the 62 participants, 18
were taking oral hypoglycemic agents and 44 were
taking insulin. The two groups were similar in all of
the observed variables after randomization. Both the
CoQ10 capsules and placebo were well-tolerated, and
the overall adherence was 96 % during the trial. Pre-
post dietary intakes of energy, fat, protein, carbohy-
drate, and some antioxidant vitamins such as vitamin
C, E are featured according to intervention groups
(Table II). No significant differences were observed
between groups over time. Likewise, no differences
were observed for physical activity.
Participants in the CoQ10 group revealed a sig-
nificant increase in total antioxidant capacity after
the trial (P < 0.001). There was a significant decrease
in hs-CRP in the CoQ10 group which indicated a
significant difference between groups after the trial
(P = 0.03). A significant decrease in insulin sensitivity
Table I: Baseline characteristics of participants of the
CoQ10 trial.
Variable CoQ10
(n = 32) p
(n = 30)
Age (y) 56.7 ± 6.4 54.8 ± 6.7
Male gender (n, %) 10 (31.25) 6 (20)
Weight (kg) 75.7 ± 10.3 77.0 ± 10.6
BMI (kg/m2)28.7 ± 4.1 29.6 ± 3.1
Duration of diabetes (y) 16.3 ± 7.3 16.2 ± 7.2
Onset age of diabetes (y) 40.7 ± 8.1 38.4 ± 8.5
Use of oral hypoglycemic
agent (%) 9 (28.1) 9 (30)
Insulin users (%) 23 (71.9) 21 (70)
Data are mean ± standard deviation or number (%).
Figure 1: CONSORT flow
diagram for studying the
effect of CoQ10 on diabetic
neuropathy in patients with
type two 2 diabetes.
Author's personal copy (e-offprint)
256 M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
(P = 0.04) and a significant increase in insulin resistance
(HOMA-IR) (P = 0.02) and fasting insulin (P = 0.04) in
the placebo group was revealed after the trial, which
showed a significant difference between groups after
the trial for these three parameters (P = 0.01, P = 0.01,
P = 0.02) (Table III). (P = 0.01). The mean changes
of insulin sensitivity, HOMA-IR and TAC were sig-
nificant between groups after the trial (Table IV). No
significant changes were reported for the lipid profile.
The data for neuropathic parameters are classified in
Table V, which demonstrates no significant difference
between two groups. The results of the VAS showed
that there was no significant difference in the percent-
age of improvement of neuropathic symptoms in the
Q10 group compared to placebo (Q10: 34.4 + 28.2 vs.
placebo: 43.9 + 30.8 P = 0.2).
CoQ10 is an intermediate molecule of the mitochondrial
electron transport chain. It regulates cytoplasmic redox
potential and can inhibit oxidative stress [14]. A defi-
Table III: Biochemical parameters before and after 12 weeks of CoQ10 supplementation.
CoQ10 Placebo P value* CoQ10 Placebo P value*
166.2 + 48.3
157 + 58
163.6 + 51.6
170.3 + 44.8
LDL-c (mg/dl)
105.3 + 21.9
105.5 + 25
108.6 + 25.5
109.1 + 21
HbA1c (%)
9.05 + 1.9
8.7 + 1.8
9.6 + 1.6
9.4 + 1.6
HDL-c (mg/dl)
32.1 + 9.9
29.9 + 4.7
33.6 + 7.1
33.0 + 9.02
Insulin sensitivity (%)
88.5 + 71
100 + 81.4
78.7 + 53.6
59.56 + 45.5
TAC (µmol/l)
7.79 + 1.99
9.04 + 2.02
< 0.001
8.23 + 2.06
8.5 + 1.41
2.24 + 2.16
2.11 + 2.05
2.15 + 1.71
3.33 + 3.87
**CRP (µg/ml)
3.77 + 4.47
2.65 + 2.81
3.49 + 3.74
3.62 + 3.47
Total Cholesterol
174.8 + 34.9
179.7 + 31.1
176.4 + 38.7
181.4 + 32.9
**Fasting Insulin
(µIU/ml )
16.18 + 17.41
15.71 + 18.23
14.64 + 12.57
17.76 + 13.64
Data are presented as mean ± Standard Deviation*ANCOVA was used considering baseline data as covariate ** log
transformed data were used due to un-normal distribution. FBP, fasting blood glucose; CRP, c-reactive protein; TAC,
total antioxidant capacity.
Table II: Dietary intake and physical activity levels of participants of the CoQ10 trial.
CoQ10 (n = 32) Placebo (n = 30)
Week 0 Week 12 Week 0 Week 12
Energy (kcal/d) 1853.5 ± 115.9 1723 ± 105.0 1835.4 ± 120.8 1805 ± 110.0
Carbohydrate (g/d) 485.8 ± 46.5 466.0 ± 51. 0 501.2 ± 48.7 482.0 ± 52.0
Protein (g/d) 58.4 ± 16.7 57.5 ± 12.7 62.3 ± 18.3 61.2 ± 15.3
Fat (g/d) 48.4 ± 16.6 46.2 ± 13.4 46.3 ± 12.6 45.1 ± 11.7
Vitamin C (mg/d) 46.0 ± 5.6 47.0 ± 4.3 48.2 ± 4.7 47.0 ± 3.8
Vitamin E (mg/d) 9.4 ± 1.1 8.9 ± 0.9 8.9 ± 1.3 8.6 ± 1.2
Physical activity (Mets /week) 88.2 ± 30.2 87.5 ± 29.8 85.2 ± 27.2 85.9 ± 25.9
Data are presented as mean ± standard deviation.
Author's personal copy (e-offprint)
257M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
ciency of CoQ10 can occur in diabetes due to impaired
mitochondrial substrate metabolism and increased oxi-
dative stress [7, 15, 16]. Low serum CoQ10 concentra-
tions have been negatively correlated with poor glycemic
control and diabetic complications [12, 17].
In diabetes, the beta cells of the pancreas are dis-
posed to extreme oxidative stress which is due to
the impaired antioxidant system. CoQ10 is naturally
present in all cells. In increased oxidative stress, the
amount of antioxidants including CoQ10 is reduced,
which causes beta cell dysfunction and leads to im-
paired glucose and lipid metabolism [18].
Our study did not show any direct improvement in
FBS or glycated hemoglobin, but in the control group,
the insulin sensitivity decreased and the fasting insulin
and insulin resistance increased, which shows a protec-
tive effect in our intervention group during the trial.
Several trials have been performed in these fields, with
different findings. In a placebo-controlled trial, Hodg-
son et al. showed that CoQ10 supplementation lowers
glycated hemoglobin significantly in the intervention
group [19]. Shargorodsky et al. studied a multi-antiox-
idant capsule containing vitamin C (500 mg), vitamin
E (200 IU), CoQ10 (60 mg) and selenium (100 mcg)
in patients with multiple cardiovascular risk factors.
The results showed a significant decrease in HbA1c
and TG but had no influence on FBG and HOMA-IR
[20]. In an open-labeled pilot study, Mezawa et al. con-
cluded that supplementation of ubiquinol in subjects
with type 2 diabetes, in addition to conventional anti-
hyperglycemic medications, improves glycemic control
by improving insulin secretion [12]. In the current study,
no significant difference in the lipid profile of patients
was observed after the trial between two groups. Modi
Table IV: Mean and CI of changes in biochemical parameters 12 weeks after supplementation with CoQ10 vs. placebo.
Variable Co Q10 (n = 32) Placebo (n = 30) p-value*
FBG(mg/dl) – 9.10 (– 26.71_8.41) 6.64 (– 9.91_23.20) 0.1
HbA1c (%) – 0.29 (– 0.71_0.20) – 0.21 (– 0.61_0.20) 0.8
Insulin sensitivity (%) 12.10 (11.20_36.41) – 19.10 (– 37.80_0.41) 0.04
HOMA-IR – 0.13 (– 0.55_ 0.28) 1.18 (– 0.27_2.63) 0.02
Total Cholesterol (mg/dl) 4.81 (– 4.40_14.12) 5.01 (– 7.21_17.30) 0.9
LDL-c (mg/dl) 0.18 (– 0.76_8.04) 0.43 (– 8.12_9.04) 0.9
HDL-c (mg/dl) – 2.10 (– 5.51_1.16) 0.43 (– 8.14_9.04) 0.5
TAC (µmol/l) 1.24 (0.56_1.94) 0.32 (– 0.31_0.95) 0.04
hsCRP (µg/ml)
Fasting Insulin (µIU/ml )
– 1.12 (– 2.15_-0.09)
– 0.47 (– 4.13_3.18)
0.13 (– 0.79_ 1.05)
3.11 (– 0.67_6.90)
*Student t-test
Table V: Changes in neuropathic parameters 12 weeks after supplementation with CoQ10 vs. placebo.
variable CoQ10 (n = 32) Placebo (n = 30) Treatment diffe-
rence (p = value)
Baseline 12 weeks Baseline 12 weeks
Pain (Cm) 19.32 ± 17.12 18.23 ± 24.75 23.25 ± 13.25 24.23 ± 32.32 0.22*
Vibration (Cm) 0.0 ± 14.00 0.0 ± 17.88 0.0 ± 21.50 0.0 ± 22.0 0.3**
Temperature (Cm) 7.75 ± 22.50 6.5 ± 21.75 20.0 ± 29.25 8.0 ± 30.0 0.2**
Strength (score) 5.0 ± 1.0 5.0 ± 1.0 5.0 ± 1.0 5.0 ± 1.0 0.9**
DTR (score) 1 ± 0.0 1 ± 0.0 1 ± 0.0 1 ± 0.0 0.4**
Deep peroneal nerve
(DPN) (m/s) 38.98 ± 5.33 39.50 ± 5.27 37.39 ± 6.13 38.41 ± 6.14 0.7*
Sural SNAP (µv) 4.75 ± 8.0 4.25 ± 8.88 5.0 ± 9.50 2.0 ± 10.75 0.4**
H-Reflex (ms) 60.50 ± 65.5 21.50 ± 32.0 33.0 ± 62.0 15.50 ± 31.0 0.6**
*ANCOVA using baseline values as covariate, data are presented as mean ± SD. DTR, deep tendon reflexes; SNAP, sural
nerve action; H-Reflex, Hoffmann’s reflex.
**Mann Whitney test was used for analyzing the median between groups after trial; Data are presented as median + inter-
quartile range.
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258 M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
et al. showed an improvement in lipid and glucose me-
tabolism in diabetic mice. The potential mechanism was
a reduction in the peroxidation of lipids [21]. The lipid
peroxidation was not assessed in this trial.
Oxidative stress has been considered by many as an
explanation for the tissue damage that accompanies
chronic hyperglycemia. It has been reported that eryth-
rocytes from diabetic patients contain low levels of the
reduced form of GSH, high levels of the oxidized form
(GSSG), and a 51 % reduction in the GSH/GSSG ratio
[22]. This has led to many reports of experiments de-
signed to assess whether antioxidant drugs and supple-
ments can be used to protect against oxidative stress in
models of type 1 and type 2 diabetes. There are limited
studies which have investigated the effect of CoQ10
on the antioxidant state and inflammatory biomarkers
in diabetes. The current study showed a significant
increase in total antioxidant capacity in the interven-
tion group after the trial (within group comparison)
and there was a significant decrease in hs-CRP in the
intervention group after the trial compared to placebo
(between group comparisons). Lee et al. investigated
two different dosages of CoQ10 (60 vs. 150) compared
with placebo in CAD. After 12 weeks of intervention,
the results showed that the inflammatory marker IL-6
decreased significantly in the Q10 – 150 group. Subjects
in the Q10 – 150 group had significantly lower malondi-
aldehyde levels and those in the Q10 – 60 and Q10 – 150
groups had greater superoxide dismutase activities [23].
The findings of our study showed that supplementa-
tion with CoQ10 did not improve the signs and symp-
toms of neuropathy. In contrast to our study, Her-
nandez-Ojeda et al., using a randomized clinical trial,
observed a significant improvement in neuropathic
symptoms/impairment scores, sural sensory nerve am-
plitude, and peroneal motor nerve conduction velocity
with 12 weeks of 400 mg/day CoQ10 compared with
baseline values [24]. One of the possible reasons for
the results may be supplementing different dosages of
CoQ10 (200 mg vs. 400 mg). On the other hand, the
discrepancy between the results may be due to the
longer duration of diabetes and using insulin in most
of our participants.
Currently, there are no treatments for neuropathy,
other than treating the diabetic condition per se, but
elevated oxidative stress is a well-accepted explana-
tion in the development and progress of complications
in diabetes mellitus. Increased free radical-mediated
toxicity has been documented in clinical diabetes
[25] and animal models of this disease [26]. Oxida-
tive stress is one of the most important determinants
of the development of peripheral nerve damage in
diabetic neuropathy [7]. The elevated level of toxic
oxidants in diabetic state may be due to processes such
as glucose oxidation and lipid peroxidation [27, 28].
As a result, there are several clinical trials regarding
the effect of dietary antioxidants such as α-lipoic acid
and vitamin E on diabetic neuropathy. The results of
a meta-analysis showed that treatment with α-lipoic
acid (600 mg/day i. v.) over 3 weeks significantly im-
proves both positive neuropathic symptoms and neu-
ropathic deficits to a clinically meaningful degree in
diabetic patients with symptomatic polyneuropathy
[29]. In the NATHAN 1 trial, the researchers evalu-
ated the efficacy and safety of α-lipoic acid (ALA) over
4 years in mild-to-moderate diabetic distal symmetric
sensorimotor polyneuropathy. This trial resulted in a
clinically meaningful improvement and prevention
of progression of neuropathic impairments [30]. A
randomized, double-blind, placebo-controlled trial
involving 21 patients with type 2 diabetes and mild-
to-moderate neuropathy was performed to investigate
the effect of vitamin E on nerve function parameters.
Patients received 900 IU of vitamin E or placebo for
6 months. Both median and tibial motor nerve con-
duction velocity were significantly improved in the
vitamin E group compared with placebo; regardless,
no significant changes were revealed in the glycemic
parameters [31].
Coenzyme Q10 (CoQ10) is another antioxidant
and has bioenergetics and anti-inflammatory effects.
It has protective effects against apoptosis of neurons
[32] and may be considered an adjuvant therapy with
which to treat DPN. Beneficial effects of CoQ10 on
DPN have been shown in an animal model [33], and
prevented neuropathic pain related behaviors. The
analgesic effect of CoQ10 may result from anti-oxi-
dative stress and a further decrease of stress-sensitive
and pain-related signaling pathways such as MAPK,
NF-κB and TLR4 [34, 35]. However, in some clinical
trials with short-term treatment, antioxidants lacked
therapeutic effects in diabetes and its neuropathy [3].
This is partly due to the more chronic, severe, and
extensive nature of damage to the nervous system
in human diabetes [36]. It seems that combination
therapy could provide more effective results. Block-
ing multiple pathway components by using several
antioxidants would in turn block multiple causes of
oxidative stress and prevent nervous system injury.
It is recommended to study the effects of a cocktail
of antioxidants in DPN.
The limitations of this study were the small sample
size, long duration of diabetes in the subjects, and the
short period of intervention, which in particular seems
to have less power to change neuropathy measures
in this limited time. The strengths of this study were
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259M. Akbari Fakhrabadi et al.: CoQ10 in Diabetes
Int. J. Vitam. Nutr. Res. 84 (5 – 6) © 2014 Hans Huber Publishers, Hogrefe AG, Bern
the use of human participants and accurate follow-up
with the control of some confounding factors such as
nutrient intake and physical activity.
In summary, the intake of 200 mg/d of CoQ10, may
not improve diabetic neuropathy but can reduce insu-
lin resistance, oxidative stress, and inflammation and
also increase insulin sensitivity. Thus, future studies
should emphasize longer periods of supplementation
and larger doses in milder situations of neuropathy,
which may increase the bioactive effects of CoQ10.
This study was supported by a collaboration of the
faculty of Health and Yazd Diabetes Research Center
of Shahid Sadoughi University of Medical Sciences as
an MSc dissertation. We extend our sincerest thanks
to all subjects who participated in the study.
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Azadeh Nadjarzadeh
Assistant Professor
Nutrition and Food Security Research Centre
Shahid Sadoughi University of Medical Sciences
Yazd, Iran
Tel.: 00989122185325
Author's personal copy (e-offprint)
... Although several randomized controlled trials (RCTs) investigated the effect of CoQ10 supplementation on oxidative stress, a considerable controversy exists over this subject. Some studies indicated that CoQ10 supplementation had some beneficial impacts on oxidative stress (Fakhrabadi, Ghotrom, Mozaffari-Khosravi, Nodoushan, & Nadjarzadeh, 2014;Farhangi, Alipour, Jafarvand, & Khoshbaten, 2014;Gholnari et al., 2018;Sanoobar et al., 2013), whereas no significant effect was observed in other surveys (Abdollahzad, Aghdashi, Jafarabadi, & Alipour, 2015;Dai et al., 2011). For example, a significant reduction was reported in MDA level among patients with relapsing-remitting multiple sclerosis (Sanoobar et al., 2013) and rheumatoid arthritis (Abdollahzad et al., 2015) following the CoQ10 supplementation. ...
... However, no significant impact was found on MDA among patients with nonalcoholic fatty liver disease (NAFLD) (Farhangi et al., 2014). The results of another study among diabetic patients with neuropathic signs demonstrated a significant increase in TAC concentration after supplementation with CoQ10 (Fakhrabadi et al., 2014), while a significant reduction in TAC concentration was found among patients with NAFLD (Farhangi et al., 2014). These controversies were also reported for antioxidant enzymes such as GPx (Sanoobar et al., 2013;Yen, Chu, Lee, Lin, & Lin, 2018) and SOD (Dai et al., 2011;Lee, Huang, Chen, & Lin, 2012). ...
... All studies had a RCT parallel design except one trial that had cross-over design (Hamilton, Chew, & Watts, 2009). In addition, all participants were patients with various diseases such as type two diabetes mellitus (Fakhrabadi et al., 2014;Fallah, Askari, Soleimani, Feizi, & Asemi, 2019;Gholami, Zarei, Sadeghi Sedeh, Rafiei, & Khosrowbeygi, 2018;Gholnari et al., 2018;Hamilton et al., 2009;Moazen, Mazloom, Ahmadi, Dabbaghmanesh, & Roosta, 2015;Yen et al., 2018;Zarei et al., 2018), NAFLD (Farhangi et al., 2014), multiple sclerosis (Sanoobar et al., 2013), rheumatoid arthritis (Abdollahzad et al., 2015), ischemic left ventricular systolic dysfunction (Dai et al., 2011), coronary artery disease (Lee et al., 2012;Lee, Tseng, Yen, & Lin, 2013), chronic renal failure (Rivara et al., 2017;Singh, Khanna, & Niaz, 2000;Singh et al., 2003), hepatocellular carcinoma (Liu et al., 2015), metabolic syndrome (Raygan, Rezavandi, Tehrani, Farrokhian, & Asemi, 2016), and dyslipidemia (Zhang et al., 2018). ...
Full-text available
Some evidence exists in supporting the beneficial effects of coenzyme Q10 (CoQ10) on oxidative stress. Since the findings of studies over the impact of CoQ10 supplementation on oxidative stress are contradictory, this study was conducted. The aim was to evaluate CoQ10 supplementation effect on total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) levels using data collected from randomized controlled trials (RCTs). Several databases including PubMed, Web of Science, Google Scholar, and Scopus were comprehensively searched up to 23 January 2019 to identify RCTs. A random‐effects model, standardized mean difference (SMD), and 95% confidence interval (CI) were applied for data analysis. According to the meta‐analysis results on 19 eligible studies, CoQ10 increased the levels of TAC (SMD = 1.29; 95% CI = 0.35–2.23; p = .007), GPX (SMD = 0.45; 95% CI = 0.17–0.74; p = .002), SOD (SMD = 0.63; 95% CI = 0.29–0.97; p < .0001), and CAT (SMD = 1.67; 95% CI = 0.29–3.10; p = .018) significantly. This supplementation also caused a significant reduction in MDA levels (SMD = −1.12; 95% CI = −1.58 to −0.65; p < .0001). However, the results of SOD and CAT should be stated carefully due to the publication bias. In conclusion, this research indicated that CoQ10 supplementation had beneficial effects on oxidative stress markers. However, further studies are needed to confirm these findings. This systematic review and meta‐analysis evaluated the effect of coenzyme Q10 (CoQ10) supplementation on oxidative stress markers including TAC, MDA, GPx, SOD, and CAT using data collected from RCTs. Several databases were comprehensively searched up to 23 January 2019 to identify RCTs. A random‐effects model, standardized mean difference, and 95% CI were applied for data analysis. According to the findings, CoQ10 significantly increased the levels of TAC, GPX, SOD, and CAT and in contrast decreased MDA levels.
... Insulin resistance was improved in T2DM patients taking fiber [161,162], unsaturated fatty acids [137], chromium [152,156], magnesium [139], vitamin C [141], vitamin E [141], coenzyme Q10 [163], almonds (source of unsaturated fatty acids, magnesium, fiber, and vitamin E) [160], cinnamon [147], or Brewer's yeast [149]. ...
... Blood pressure was reduced after supplementation with chromium [156], vitamin C [140], vitamin E [164], or cinnamon [145]. Oxidative stress and the anti-oxidant system improved in T2DM patients taking fiber [161], magnesium [139], vitamin C [141], and coenzyme Q10 [163]. Inflammatory responses were reduced in T2DM patients taking fiber [161][162], magnesium [139], coenzyme Q10 [163], and sesamin [150]. ...
... Oxidative stress and the anti-oxidant system improved in T2DM patients taking fiber [161], magnesium [139], vitamin C [141], and coenzyme Q10 [163]. Inflammatory responses were reduced in T2DM patients taking fiber [161][162], magnesium [139], coenzyme Q10 [163], and sesamin [150]. ...
Type 2 diabetes mellitus (T2DM) and sleep disorders (SD) have become important and costly health issues worldwide, particularly in China. Both are common diseases related to brain functional and structural abnormalities involving the hypothalamic-pituitary-adrenal (HPA) axis. The brains of individuals who suffer from both diseases simultaneously might be different compared to healthy individuals. This review assesses current clinical and neuroimaging findings to develop alternative targeted treatments for curing T2DM and sleep disorders. The bibliographic databases PubMed and Web of Science were searched for relevant articles published between January 2002 and September 2021. Generalized treatment methods for T2DM include dietary/weight-loss management, metformin or a combination of two non-insulin drugs and melatonin for SD, although alternative therapies including electroacupuncture (EA) have been utilized in treating both of these diseases separately because they are convenient, affordable, and safe. Standard and alternative treatments for T2DM were somehow effective in treating SD. Neuroimaging studies of these disorders can achieve higher treatment efficacy by targeting brain areas, such as the hypothalamus, as visualized via diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). DTI and fMRI can map the human brain and are utilized in many experiments. Thus, we propose that neuroimaging studies can be used in diagnosis and treatment of sleep disorders in T2DM.
... Moreover, high sensible Creactive protein (hsCRP) levels were found significantly decreased in the CoQ10 group compared to placebo. Despite a clear improvement of the biochemical markers, the evaluation of neuropathic symptoms and electromyography measurements did not highlight significant differences between the two groups after the trial [90]. ...
Full-text available
Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients’ health and quality of life.
... Potential studies were screened based on title or abstract. Among the 31 full text studies evaluated for eligibility, 17 RCTs met the inclusion criteria and were used for the final systematic review and meta-analysis [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. A diagram of the study selection process is presented in Fig. 1. ...
Full-text available
PurposeOxidative stress (OS) is associated with several chronic complications and diseases. The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine clinical therapy against metabolic diseases has shown to be beneficial. However, the impact of CoQ10 as a preventive agent against OS has not been systematically investigated.MethodsA systematic literature search was performed using the PubMed, SCOPUS, EMBASE, and Cochrane Library databases to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model.ResultsSeventeen randomized clinical trials met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD − 0.94; 95% CI − 1.46, − 0.41; I2 = 87.7%) and a significant increase in total antioxidant capacity (TAC) (SMD 0.67; 95% CI 0.28, 1.07; I2 = 74.9%) and superoxide dismutase (SOD) activity (SMD 0.40; 95% CI 1.12, 0.67; I2 = 9.6%). The meta-analysis found no statistically significant impact of CoQ10 supplementation on nitric oxide (NO) (SMD − 1.40; 95% CI − 0.12, 1.93; I2 = 92.6%), glutathione (GSH) levels (SMD 0.41; 95% CI − 0.09, 0.91; I2 = 70.0%), catalase (CAT) activity (SMD 0.36; 95% CI − 0.46, 1.18; I2 = 90.0%), or glutathione peroxidase (GPx) activities (SMD − 1.40; 95% CI: − 0.12, 1.93; I2 = 92.6%).Conclusion CoQ10 supplementation, in the tested range of doses, was shown to reduce MDA concentrations, and increase TAC and antioxidant defense system enzymes. However, there were no significant effects of CoQ10 on NO, GSH concentrations, or CAT activity.
... In a murine study of neuropathy, it was found that treating animals with ubiquinone could prevent apoptosis, halt degeneration of dorsal root ganglion neurons, and improve motor function [92]. However, in a doubleblind randomized clinical trial of diabetic patients with neuropathy (n = 70), coenzyme Q10 at doses of 200 mg/day for 12 weeks did not reduce neuropathic symptoms compared to placebo [93]. ...
Full-text available
The frequently prescribed drug class of statins have pleiotropic effects and have been implicated in neuropathic pain syndromes. This narrative review examines studies of statin-induced neuropathic pain which to date have been conducted only in animal models. However, the pathophysiology of diabetic neuropathy in humans may shed some light on the etiology of neuropathic pain. Statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans. While there are certain postulated mechanisms offering elucidation as to how statins might be associated with neuropathic pain, there is, as the American Heart Association stated, to date no definitive association between statins and neuropathic pain. Statins are important drugs that reduce cardiovascular risk factors and should be prescribed to appropriate patients with these risk factors but some of this population is also at elevated risk for neuropathic pain from other causes.
... Diabetic microangiopathy includes diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Most of these diseases interact with endothelial injury and oxidative stress [24][25][26]. Here, we showed that carnosol improves t-BHP-induced endothelial injury in HMVEC Cells. ...
Full-text available
Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein−protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.
Background and aims Controlling glycemic levels is crucial for patients with diabetes mellitus to improve their disease management and health outcomes. Beyond lifestyle modification and pharmacotherapy, some supplements have been shown to lower blood glucose as well as mitigate diabetic complications. Methods Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Only original human trials were used, and those published within the past two decades were primarily chosen. However, background information may contains review articles. Results Some non-herbal supplements have been suggested to lower fasting blood glucose, postprandial glucose, glycated glucose (HbA1c), lipid profiles, oxidative stress, and inflammation, as well as improving body composition, insulin sensitivity, blood pressure, and nephropathy. Conclusion This review discusses ten non-herbal supplements that have been reported to have beneficial effects among different types of patients with diabetes as well as potiential future clinical application. However, more long-term studies with a larger amount and more diverse participants need to be conducted for a robust conclusion. Also, mechanisms of action of antidiabetic effects are poorly understood and need further research.
This systematic review and meta-analysis assessed the antidiabetic effect of pharmaconutrients as an add-on in type 2 diabetes mellitus patients by pooling data from currently available randomized controlled trials (RCTs). Data sources included the PubMed and EMBASE, Cochrane Central Register of Controlled Trials. RCTs reporting changes in glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), or homeostasis model assessment of insulin resistance (HOMA-IR) levels following add-on pharmaconutritional therapies for T2DM patients consuming antidiabetic drugs were targeted. Using random-effects meta-analyses, we identified pharmaconutrients with effects on glycemic outcomes. Heterogeneity among studies was presented using I2 values. Among 9537 articles, 119 RCTs with nine pharmaconutrients (chromium; coenzyme Q10; omega-3 fatty acids; vitamins C, D, and E; alpha-lipoic acid; selenium; and zinc) were included. Chromium (HbA1c, FBG, and HOMA-IR), coenzyme Q10 (HbA1c and FBG), vitamin C (HbA1c and FBG), and vitamin E (HbA1c and HOMA-IR) significantly improved glycemic control. Baseline HbA1c level and study duration influenced the effects of chromium and vitamin E on HbA1c level. Sensitivity analyses did not modify the pooled effects of pharmaconutrients on glycemic control. Administration of chromium, coenzyme Q10, and vitamins C and E for T2DM significantly improved glycemic control. This study has been registered in PROSPERO (CRD42018115229).
Background: Coenzyme Q10 (CoQ10) has been known as ubiquinone or ubidecarenone, which is a kind of lipid-soluble and vitamin-like antioxidant. It has a potent antioxidant effect against oxidation status via various mechanisms, including its ability to regenerate other antioxidants, such as vitamin E and vitamin C, and to increase antioxidant enzymes. Moreover, CoQ10 can quench free radicals and prevent lipid peroxidation. The aim of this systematic review and meta-analysis was to evaluate the effect of CoQ10 on oxidative stress variables. Methods: A comprehensive electronic database search in Scopus, Web of Science, Embase, Cochrane Library, and Medline was performed to identify eligible randomized clinical trials. A meta-analysis of included studies was performed on selected variables using a random-effects model. Quality assessment was conducted by means of the Cochrane risk of bias assessment tool. Results: To evaluate the effect of CoQ10 supplementation, 17 trials and 972 participants were included for the meta-analysis. The pooled analysis of primary studies showed that CoQ10 increased serum total antioxidant capacity (standardized mean difference [SMD] 0.62 mmol/L, 95% CI 0.18-1.05, I2 = 76.1%, p ˂ 0.001) and superoxide dismutase (SMD 0.40 U/mg, 95% CI 0.12-0.67, I2 = 9.6%, p ˂ 0.345) levels and decreased malondialdehyde (SMD -1.02 mmol/L, 95% CI -1.60 to -0.44, I2 = 88.2%, p ˂ 0.001) level significantly compared to the placebo group. Although the effect of CoQ10 on nitric oxide (SMD 1.01 µmol/L, 95% CI -1.53 to 3.54, p ˂ 0.001, I2 = 97.8%) and glutathione peroxidase (SMD -0.01 mmol/L, 95% CI -0.86 to 0.84, p ˂ 0.001, I2 = 88.6%) was not significant, CoQ10 can be mentioned as an improvement in antioxidant defense status against reactive oxygen species. Conclusion: These supplements have positive effects on antioxidant defense against oxidizing agents and elevate antioxidant enzyme levels in the body. However, due to limited research the results should be taken with caution.
Aim: This study aimed to determine the effect of exercise training alone and in combination with coenzyme Q10 (Q10) supplementation on the Q10 level, oxidative damage, and antioxidant defense markers in blood and skeletal muscle tissue in young and aged rats. Methods: The study included 4-month old (young) and 20-month old (aged) rats. Each group was further divided into control, exercise training, Q10 supplementation, and Q10 supplementation plus exercise training groups. The exercise training program consisted of swimming for 8 weeks, and Q10 or vehicle during the same period. Results: The Q10 concentration in plasma (P < 0.05), but not in skeletal muscle (P > 0.05) increased significantly following Q10 supplementation in both the young and aged rats. Plasma SOD and CAT activity were significantly higher in the aged rats in the Q10 and Q10 plus exercise training groups than in the other groups (P < 0.05); however, there was no significant difference between the groups in skeletal muscle (P > 0.05). Additionally, plasma and skeletal GSH levels did not differ between the groups (P > 0.05). Conclusion: The present findings indicate that Q10 supplementation increased the Q10 concentration in blood but not in skeletal muscle tissue. On the other hand, Q10 administration alone and in combination with exercise challenge improved antioxidant enzyme capacity especially in the aged rats.
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Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes. Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db(-)/db(-) mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. Diabetic mice at 8 mo of age exhibited loss of sensation, hypoalgesia (an increase in mechanical threshold), and decreases in mechanical hyperalgesia, cold allodynia, and sciatic nerve conduction velocity. All these changes were virtually completely absent after the 6-mo, daily CoQ10 treatment in db(-)/db(-) mice when started at 7 wk of age. There was a 33% neuronal loss in the lumbar 5 dorsal root ganglia (DRGs) of the db(-)/db(-) mouse versus controls at 8 mo of age, which was significantly attenuated by CoQ10. There was no difference in neuron number in 5/6-wk-old mice between diabetic and control mice. We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. Many of the phenotypic, neurochemical regulations encountered in lumbar DRGs in standard models of peripheral nerve injury were not observed in diabetic mice at 8 mo of age. These results suggest that reactive oxygen species and reduced PLCβ3 expression may contribute to the sensory deficits in the late-stage diabetic db(-)/db(-) mouse, and that early long-term administration of the antioxidant CoQ10 may represent a promising therapeutic strategy for type 2 diabetes neuropathy.
Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia. The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding. ### Diabetic retinopathy Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …
Unlabelled: The early onset of type 2 diabetes mellitus (DM), driven by increasing obesity, is associated with peripheral neuropathy. Here, we characterize diabetic neuropathic pain in New Zealand obese diabetic mice (NZO/HILtJ) as a polygenic model of obesity with type 2 diabetes and investigate the role of coenzyme Q10 (CoQ10) in the prevention and treatment of diabetic neuropathic pain. Since the overexpression of mitogen-activated protein kinase (MAPK), nuclear factor-κB proteins (NF-Kb), toll-like receptor 4 (TLR4) and downstream cytokines (such as CCL2, CXCL10) are considered important factors contributing to the development of neuropathic pain, the expression of these factors and the inhibitory effects of CoQ10 were evaluated. NZO/HILtJ mice spontaneously developed type 2 DM and increased body mass with diabetic neuropathic pain. CoQ10 treatment decreased pain hypersensitivity and long-term supplementation prevented the development of diabetic neuropathic pain but did not attenuate diabetes. Spinal cord, blood serum, liver tissue, and dorsal root ganglia (DRG) from diabetic mice demonstrated increased lipid peroxidation, which was decreased by CoQ10 treatment. The percentage of positive neurons of p65 (the activated marker of NF-KB) and MAPK in DRG were significantly higher in DM mice compared to controls. However, CoQ10 treatment significantly decreased p65 and MAPK positive neurons in the DRG of DM mice. RT-PCR demonstrated that elevated levels of mRNA of CCL2, CXCL10 or TLR4 in the spinal cord of DM mice decreased significantly when DM mice were treated with CoQ10. Conclusion: This model may be useful in understanding the mechanisms of neuropathic pain in type 2 DM induced neuropathic pain and may facilitate preclinical testing of therapies. CoQ10 may decrease oxidative stress in the central and peripheral nervous system by acting as an anti-oxidant and free-radical scavenger. These results suggest that CoQ10 might be a reasonable preventative strategy for long-term use and using CoQ10 treatment may be a safe and effective long-term approach in the treatment of diabetic neuropathy.
Background: Oxidative stress is a key factor implicated in the development of diabetic neuropathy. This study evaluates the prophylactic and antinociceptive effects of the antioxidant coenzyme Q10 (CoQ10) on diabetes-induced neuropathic pain in a diabetic mouse model. Methods: Total 56 mice with type 1 diabetes induced by streptozotocin were used, 20 normal mice were used as control. Mechanical and thermal nociceptive behavioral assays were applied to evaluate diabetic neuropathic pain. Tissue lipid peroxidation, immunohistochemistry, reverse transcription, and polymerase chain reaction were used to evaluate the molecular mechanisms of CoQ10. Data are presented as mean ± SEM. Results: CoQ10 administration was associated with reduced loss of body weight compared with nontreated diabetic mice, without affecting blood glucose levels. Low dose and long-term administration of CoQ10 prevented the development of neuropathic pain. Treatment with CoQ10 produced a significant dose-dependent inhibition of mechanical allodynia and thermal hyperalgesia in diabetic mice. Dorsal root ganglia, sciatic nerve, and spinal cord tissues from diabetic mice demonstrated increased lipid peroxidation that was reduced by CoQ10 treatment. CoQ10 administration was also noted to reduce the proinflammatory factors in the peripheral and central nervous system. Conclusions: The results of this study support the hypothesis that hyperglycemia induced neuronal oxidative damage and reactive inflammation may be pathogenic in diabetic neuropathic pain. CoQ10 may be protective by inhibiting oxidative stress and reducing inflammation by down-regulating proinflammatory factors. These results suggest that CoQ10 administration may represent a low-risk, high-reward strategy for preventing or treating diabetic neuropathy.
The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol-induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K-ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative-nitrosative stress, TNF-α, IL-1β, and IL-4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α-tocopherol (100 mg/kg) combination-treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α-tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido-nitrosative stress, release of pro-inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination.
Coenzyme Q10 (CoQ10) provides the energy for vital cellular functions and is known to act as an antioxidant. We conducted an open label study to examine the clinical effects of supplementation of the reduced form of CoQ10, ubiquinol, in addition to conventional glucose-lowering agents in patients with type 2 diabetes. Nine subjects (3 males and 6 females) with type 2 diabetes and receiving conventional medication were recruited. The subjects were assigned to receive an oral dose of 200 mg ubiquinol daily for 12 weeks. The effect of ubiquinol on blood pressure, lipid profile, glycemic control, oxidative stress, and inflammation were examined before and after ubiquinol supplementation. In addition, five healthy volunteers were also assigned to receive an oral dose of 200 mg ubiquinol daily for 4 weeks to examine the effects of ubiquinol on insulin secretion. In patients with diabetes, there were no differences with respect to blood pressure, lipid profile, oxidative stress marker, and inflammatory markers. However, there were significant improvements in glycosylated hemoglobin (53.0 ± 4.3 to 50.5 ± 3.7 mmol/mol, P = 0.01) (7.1 ± 0.4 to 6.8 ± 0.4%, P = 0.03). In healthy volunteers, the insulinogenic index (0.65 ± 0.29 to 1.23 ± 0.56, P = 0.02) and the ratio of proinsulin to insulin were significantly improved (3.4 ± 1.8 to 2.1 ± 0.6, P = 0.03). The results of our study are consistent with the suggestion that the supplementation of ubiquinol in subjects with type 2 diabetes, in addition to conventional antihyperglycemic medications, improves glycemic control by improving insulin secretion without any adverse effects.© 2012 International Union of Biochemistry and Molecular Biology, Inc.
Diabetes is a chronic disease and as a consequence of the overproduction of reactive oxygen species (ROS), is related with oxidative stress. There are different sources of ROS, of which mitochondria is the main one. Oxidative stress seems to play an important role in mitochondria- mediated disease processes, though the exact molecular mechanisms responsible remain elusive. There are evidences which supports the idea that impaired mitochondrial function is a cause of the insulin insensitivity in different type of cells that arised as a result of an insufficient supply of energy or defects in the insulin signaling pathway. ROS are generally necessary for the proper functioning of the cell, but excessive ROS production can be harmful, which makes antioxidant defenses essential. Moreover, some substances with antioxidant properties, such as vitamin C or vitamin E, erradicate the oxidative stress associated with diabetes. The results of clinical trials employing anti-oxidative stress reagents in patients with diabetes are contradictory, which may be a result of inadequate study design or selected targets. This review considers the process of diabetes from a mitochondrial perspective, and describes the role of autophagy in the development of diabetes. Furthermore, we discuss the possible beneficial effects of selectively targeting antioxidants to mitochondria as a strategy for modulating mitochondrial function in diabetes.