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The objective of this study was to evaluate the possible benefits of coenzyme Q and selenium supplementation administered to patients with statin-associated myopathy (SAM). Sixty eligible patients entered the pilot study. Laboratory examination (CoQ10, selenium, creatin kinase) and intensity of SAM (visual scale) were performed at baseline, after 1 month, and at the end of study at month 3. Plasma levels of CoQ10 increased from 0.81 ± 0.39 to 3.31 ± 1.72 μmol/L in the active group of patients treated by CoQ10, compared with the placebo (p = 0.001). Also, the symptoms of SAM significantly improved in the active group (p < 0.001): the intensity of muscle pain decreased from 6.7 ± 1.72 to 3.2 ± 2.1 (p < 0.01, -53.4 ± 28.2%); muscle weakness decreased from 7.0 ± 1.63 to 2.8 ± 2.34 (p < 0.01, -60 ± 24.0%); muscle cramps decreased from 5.33 ± 2.06 to 1.86 ± 2.42, p < 0.01, -65 ± 28%); tiredness decreased from the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p < 0.01, -82 ± 22%). We did not observe any significant changes in the placebo group. In conclusion, supplementation of statin-treated patients with CoQ10 resulted in a decrease in the symptoms of SAM, both in absolute numbers and intensity. Additional selenium supplementation was not associated with any statistically significant decrease of SAM. However, it is not possible to draw any definite conclusions, even though this study was carried out in double-blind fashion, because it involved a small number of patients.
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Volume 91
An NRC Research
Press Journal
Une revue de
NRC Research
Canadian Society of Pharmacology
and Therapeutics
et de la
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et de thérapeutique
In cooperation with Avec le concours de la
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and Pharmacology
Revue canadienne de
et pharmacologie
Coenzyme Q
and selenium in statin-associated myopathy treatment
Jan Fedacko, Daniel Pella, Petra Fedackova, Osmo Hänninen, Petri Tuomainen, Peter Jarcuska, Tomas Lopuchovsky, Lucia Jedlickova,
Lucia Merkovska, and Gian Paolo Littarru
Abstract: The objective of this study was to evaluate the possible benefits of coenzyme Q
and selenium supplementation
administered to patients with statin-associated myopathy (SAM). Sixty eligible patients entered the pilot study. Laboratory
examination (CoQ10, selenium, creatin kinase) and intensity of SAM (visual scale) were performed at baseline, after 1 month, and
at the end of study at month 3. Plasma levels of CoQ10 increased from 0.81 ± 0.39 to 3.31 ± 1.72 mol/L in the active group of
patients treated by CoQ10, compared with the placebo (p= 0.001). Also, the symptoms of SAM significantly improved in the active
group (p< 0.001): the intensity of muscle pain decreased from 6.7 ± 1.72 to 3.2 ± 2.1 (p< 0.01, –53.4 ± 28.2%); muscle weakness
decreased from 7.0 ± 1.63 to 2.8 ± 2.34 (p< 0.01, –60 ± 24.0%); muscle cramps decreased from 5.33 ± 2.06 to 1.86 ± 2.42, p< 0.01,
–65 ± 28%); tiredness decreased from the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p< 0.01, –82 ± 22%). We did not observe any significant
changes in the placebo group. In conclusion, supplementation of statin-treated patients with CoQ10 resulted in a decrease in the
symptoms of SAM, both in absolute numbers and intensity. Additional selenium supplementation was not associated with any
statistically significant decrease of SAM. However, it is not possible to draw any definite conclusions, even though this study was
carried out in double-blind fashion, because it involved a small number of patients.
Key words: coenzyme Q10, selenium, statins, statins side effects, statin-associated myopathy, muscle pain, muscle cramps.
Résumé : L'objectif de cette étude était d'évaluer les bénéfices possibles d'un supplément de coenzyme Q10 (CoQ10) et de
sélénium administré a
`des patients atteints d'une myopathie associée aux statines (MAS). Soixante patients éligibles ont été
recrutés dans l'étude pilote. Des examens de laboratoire (CoQ10, sélénium, créatine kinase) et de l'intensité de la MAS (échelle
visuelle) ont été réalisés au départ, après un mois et a
`la fin de l'étude après trois mois. Les niveaux plasmatiques de CoQ10
augmentaient de 0,81 ± 0,39 a
`3,31 ± 1,72 mol/L chez le groupe patients actifs traités a
`la CoQ10 comparativement au placébo
(p= 0,001). Les symptômes de MAS s'amélioraient aussi significativement chez le groupe actif (p< 0,001). L'intensité de douleur
musculaire diminuait de 6,7 ± 1,72 a
`3,2 ± 2,1 (p< 0,01, −53,4 ± 28,2 %). La faiblesse musculaire diminuait de 7,0 ± 1,63 a
`2,8 ± 2,34
(p< 0,01, −60 ± 24,0 %), les crampes musculaires diminuaient de 5,33 ± 2,06 a
`1,86 ± 2,42 (p< 0,01, −65 ± 28 %). La fatigue diminuait
de 6,7 ± 1,34 a
`1,2 ± 1,32 (p< 0,01, −82 ± 22 %). Dans le groupe placébo, aucun changement significatif n'était observé. En
conclusion, un supplément de CoQ10 donné a
`des patients traités aux statines a résulté en une diminution des symptômes de la
MAS en valeur absolue et en intensité. Un supplément additionnel de sélénium n'était pas associé de manière significative a
diminution de la MAS. Il n'est pas possible de tirer des conclusions définitives, malgré le fait que cette étude ait été réalisée a
double-insu, car elle impliquait un faible nombre de patients. [Traduit par la Rédaction]
Mots-clés : coenzyme Q
, sélénium, statines, effets secondaires des statines, myopathie associée aux statines, douleur musculaire,
crampes musculaires.
It has been found that many of the beneficial effects of statins
cannot be explained simply by the lowering of atherogenic lipids
alone. Some pleiotropic effects not related to the lipid lowering of
statins have been shown, which are likely responsible for this
additional benefit (Davignon 2004). Besides the positive pleiotro-
pic effects of statins, there are probably also unwanted effects like
inhibition of geranyl pyrophosphate synthesis and, subsequently,
dekaprenyl-4-benzoate, which is a precursor of coenzyme Q10
(CoQ10) (Ghirlanda et al. 1993). Moreover, statins inhibit endoge-
nous synthesis of several selenoproteins (cholesterol, CoQ10, and
the aforementioned selenoproteins share the same biosynthetic
pathway, which is inhibited by statins; Fig. 1)(Moosmann and Behl
2004a). This fact, plus the role of CoQ10 in mitochondrial energy
production, has prompted the hypothesis that statin-induced
CoQ10 deficiency is involved in the pathogenesis of statin
CoQ10 (ubiquinone) is one of the key substances in myocardial
energetic metabolism, and is also important for cell membrane
stability, and with CoQ10 deficiency, myocytes could be prone to
damage in the form of myopathy or myositis, or even rhabdomy-
olysis (Crane 2001). Although CoQ10 depletion does not appear to
play an etiopathogenic role in statin-induced myopathy, it is
highly probable that it is a critical predisposing factor, especially
in subjects for whom other CoQ10-depleting conditions coexist.
As mentioned, selenoproteins also play a very important role as
antioxidants, and their deficiency may lead to the development of
arterial hypertension, cardiomyopathy (Keshan disease), or pe-
ripheral muscle disease (Nawrot et al. 2007;Boosalis 2008).
The aim of our study was not to demonstrate that statin associ-
ated myalgia is caused by the deficiency of CoQ10 and (or) sele-
Received 11 April 2012. Accepted 6 November 2012.
J. Fedacko, D. Pella, P. Jarcuska, T. Lopuchovsky, L. Jedlickova, and L. Merkovska. Pavol Jozef Safarik University, 1st Department of Internal Medicine, Centre of
Excellency for Atherosclerosis Research, Trieda SNP 1, 041 90 Kosice, Slovakia.
P. Fedackova. Pavol Jozef Safarik University, Department of Experimental Medicine, Kosice, Slovakia.
O. Hänninen. University of Kuopio, Department of Physiology, Kuopio, Finland.
P. Tuomainen. University of Kuopio, Department of Cardiology, Kuopio, Finland.
G.P. Littarru. Marche Polytechnic University, Department of Odontostomatological and Clinical Sciences, Ancona, Italy.
Corresponding author: Jan Fedacko (e-mail:;
Can. J. Physiol. Pharmacol. 91: 165–170 (2013) Published at on 5 December 2012.
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nium, but to confirm that in such statin-treated patients
(susceptible to myopathy usually with coexisting predisposing
risk factors) supplementation with CoQ10 and (or) selenium (in
reasonable doses) may have a clinical benefit.
Up to now, no previous clinical study has been reported testing
the efficacy and safety of both CoQ10 and selenium supplementa-
tion in statin-treated patients who present mild adverse effects
(mild to moderate statin-associated myopathy). The background
of our pilot, double blind, randomized single centre prospective
3-month study using2×2factorial design (200 mg CoQ10/day
compared with 200 ug selenium/day, compared with their combi-
nation, compared with a placebo administered to statin-treated
patients with mild side effects, but not leading to treatment with-
drawal) was to evaluate possible benefits of CoQ10 and selenium
Materials and methods
Study population
We screened 1142 patients, treated with statins following the
current guidelines, at the outpatient cardiology clinic in Kosice,
Slovakia, during the period from January 2006 to December 2007.
Of that number, we selected 60 eligible patients reporting statin-
associated myopathy (muscle pain, muscle weakness, tiredness,
or muscle cramps) with or without increased plasma levels of
creatine kinase. The local ethical committee approved the study
protocol, and written informed consent was obtained from all
Patients were randomly divided among study subgroups: ran-
domization 1, 200 mg CoQ10 daily or the corresponding placebo;
randomization 2, 200 ug selenium daily or the corresponding
placebo. Four subgroups were studied: (i) group Q10Se, 200 mg of
CoQ10 (active) + 200 ug of selenium (active) (daily);(ii) group
Q10SePla, 200 mg CoQ10 (active) + selenium placebo (daily);
(iii) group Q10PlaSe, CoQ10 placebo + 200 g selenium (active)
(daily);and (iv) group Q10PlaSePla, CoQ10 placebo and selenium
The inclusion criteria were as follows: statin-treated patients
with muscle pain, and (or) muscle weakness, and (or) tiredness,
and (or) muscle cramps, with or without elevated levels of crea-
tine kinase (less than 10-times over upper limit of the normal
value range) not leading to statin withdrawal.
The exclusion criteria shared by the 2 components of the study
(CoQ10 and selenium) were (i) known hypersensitivity to study
treatments; (ii) conditions that in the opinion of the investigator
would be associated with poor adherence to the protocol; (iii) any
serious noncardiac morbidity (e.g., cancer, muscle disease) or any
acute disease that may influence plasma CoQ10 or selenium lev-
els. In addition to the above mentioned criteria, patients were
excluded if their background therapy during last 3 months in-
cluded CoQ10 or selenium supplements.
Study procedures
At the beginning of the study, all patients underwent a physical
examination and a laboratory examination (plasma level of CoQ10
and selenium, lipid profile, liver enzymes, creatine kinase, glycae-
mia, BUN (blood urea nitrogen), creatinine, uric acid, sodium, and
potassium levels). Physical and laboratory examinations were re-
peated after 1 month and at the end of study. The presence and
severity of adverse effects from statin therapy was checked at all
study visits, and when needed during the duration of the study
duration. For qualification of statin-associated myopathy (muscle
pain, muscle weakness, tiredness, or muscle cramps) we used a
visual scale scoring system (10 is given to the worst pain ever, and
0 is given to no pain at all) at baseline, after 1 month, and at the
end of the study at month 3.
In each phase of the study, blood was withdrawn from the
cubital vein and coagulated in heparin. Plasma was separated and
kept at –80 °C until the analytical procedure was to be performed.
Total CoQ10 concentration was measured by the HPLC–UV
method already described (Littarru et al. 2004). Briefly 200 Lof
plasma was supplemented with 50 L of 1.4 benzoquinone solu-
tion (2 mg/mL), vortexed for 10 s, and extracted with 1 mL
n-propanol. The benzoquinone treatment fully oxidizes CoQ10
present in the sample; the propanol extract was then directly
injected into the HPLC apparatus. The mobile phase was ethanol–
methanol (65%:35%), and the flux was 1 mL/min. The analytical
column was a Supelcosil LC18 (Supelco, Milano Italy), 25 cm ×
0.46 cm, inner diameter 5 m. Detection was performed at 275
nm, which quantifies oxidized CoQ10. Interassay precision
showed a day-to-day CV% close to 2. The inductively coupled
plasma – mass spectrometry method was used to quantify the
selenium content (Dr. Bayer Laboratory, Bopserwaldstraße 26, D
70184 Stuttgart, Germany).
Study interventions
All participants were randomly distributed among the test
groups in a double-blind manner, and given either a combination
of 200 mg/day CoQ10 capsules (Bio-Quinon 100 mg B.I.D, Pharma
Nord, Vejle, Denmark) and 200 g/day of organic selenium yeast
tablets (SelenoPrecise 200 g, Pharma Nord, Vejle, Denmark), or
an equivalent amount of placebo. The study supplements were
taken in addition to regular medication. All study medication
capsules (active drug and placebo) not consumed were returned
and counted. The selenium source was a patented pharmaceutical
grade selenium yeast, SelenoPrecise
, with a documented batch-
to-batch stability in its composition of selenium species (Larsen
et al. 2003,2004;Bugel et al. 2008). Previous results from the
Precise pilot studies showed low levels of adverse effects and good
absorption (Larsen et al. 2004) in doses up to 300 g/day. It has
been approved as a pharmaceutical drug in Denmark by the Dan-
ish Medicines Agency for many years (appr. No. 6233603). The
CoQ10 preparations have shown good absorption and efficacy in
previous controlled trials (Folkers et al 1994;Weis et al. 1994) and
the capsules were identical to medicinal quality capsules regis-
tered for treatment of heart failure in a European Union Member
State (Myoqinon
, authorization No. OGYI 11494-2010).
Statistical analysis
Statistical analysis for testing the hypothesis was performed
with either a t-test or ANOVA. A non-parametric t-test or paramet-
ric t-test was used where appropriate. Where a normal (Gaussian)
Fig. 1. Cholesterol (mevalonate) synthesis pathway. PP, pyrophos-
phate; CoA, coenzyme A; HMG, hydroxyl methyl glutaryl; 4-OH,
Acetyl CoA
HMG-CoA reductase
isopentanyl- PP → selenoproteins
geranyl-PP→ dekaprenyl-PP→ dekaprenyl 4-OH benzoate→ CoQ10
squalene farnesyl-PP farnesylated proteins
cholesterol geranylated proteins
166 Can. J. Physiol. Pharmacol. Vol. 91, 2013
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distribution was expected, non-parametric Mann Whitney Uor
Wilcox parametric test was used. For testing mean values of more
groups, a 1-way ANOVA was used with a post-hoc LSD test. For
testing of influence of different factors (CoQ10, Se), a 2-way
ANOVA was used. The data are expressed as the mean ± SD. The
statistical analysis of symptoms was performed with
test or
Fisher's exact test.
During the 2 year period from January 2006 to December 2007
we screened 1142 patients treated with statins. Tables 1aand 1b
show that the study population was comparable among the
2 groups of patients. Most of them were treated with atorvastatin
457 (40%), followed by fluvastatin 342 (29.9%), rosuvastatin 229
(20.1%), and simvastatin 114 (9.98%). Of that number, we randomly
selected 60 patients with statin-associated myopathy (5.25%). Ad-
verse effects of statins were most common with the simvastatin-
treated group (n= 14; 12.2%), followed by rosuvastatin-treated
group; (n= 16; 6.98%), then the atorvastatin treated (n= 25; 5.47%),
and least for the group treated with fluvastatin (n= 5; 1.46%).
Plasma levels of CoQ10 in the CoQ10 active group increased
from baseline 0.81 ± 0.39 mol/L to 3.31 ± 1.72 mol/L at month 3
(p= 0.001) without any significant alteration in the placebo group
(Table 2). Comparison of all 4 study subgroups of patients revealed
a statistically significant increase of CoQ10 plasma levels in both
CoQ10-active group of patients. The rise in CoQ10 was more pro-
nounced in the group where the active form of selenium was
supplemented simultaneously with CoQ10, compared with the
selenium placebo group; however, it did not reach statistical sig-
nificance (p= 0.106). Selenium plasma levels in the active group of
patients increased from 70.45 ± 12.90 g/L to to 145.42 ± 22.01 g/L
(month 3) in comparison with the placebo group 73.15 ± 19.20 g/L
(comparison of both examinations of the placebo group; p= 0.001).
Creatine kinase plasma levels decribed in Table 1 were not associ-
ated with the severity of statin-associated pain, and CoQ10 had no
statistically significant impact on its change.
Statin-associated myopathy showed significant improvement
in the CoQ10 active group without any benefit in the placebo
group (Table 3). Selenium supplementation showed no beneficial
effects (Table 4). Because there was no effect from selenium sup-
plementation, we decided to present the following data for statin-
associated myopathy related to the CoQ10 active treatment group
compared with the CoQ10 placebo group only.
The intensity of muscle pain was statistically significantly
higher in the CoQ10-active treatment group of patients compared
with the placebo group at baseline (6.7 ± 1.72 vs. 5.3 ± 1.60,
p< 0.05). After 3 months of active treatment, the intensity of
muscle pain decreased to 3.2 ± 2.1 (p< 0.01), and already after
1 month of treatment the change was statistically significant (5 ±
1.8, p< 0.01). After 3 months of treatment with the placebo, mus-
cle pain intensity remained unchanged (Table 5). Absolute
decrease in muscle pain intensity after 3 months for the CoQ10-
active treatment group was significantly greater, compared with
the placebo group (–3.5 ± 1.87 vs. –0.1 ± 0.7, p< 0.01).
Table 1. Data for the study population and statin treatment showing that the study population was comparable
among the 2 groups of patients (treatment with coenzyme Q10 (CoQ10) or selenium).
Baseline End of study
Placebo CoQ10 pPlacebo CoQ10 p
a.Study population
No. of patients 26 34 NS 26 34 NS
Men/women 7/19 12/22 NS 7/19 12/22 NS
Age (years) 55.4±12.4 59.6±8.9 NS 56.3±13.1 60.1±9.7 NS
BMI (kg/m
) 27.2±4.1 29.0±6.1 NS 27.3 ±4.4 29.2±6.5 NS
Treatment with statins (months) 18.3±16.4 15.0±14.5 NS 21.3±16.4 18.0±14.5 NS
Plasma levels of CoQ10 (mol/L) 0.74±0.31 0.81±0.39 NS 0.68±0.31 3.31±1.72 <0.001
TCH (mmol/L) 5.15±1.1 4.8±1,0.4 NS 5.3±1.2 4.9±1.2 NS
LDL (mmol/L) 2.97±1.97 2.61±0.97 NS 3.13±1.14 2.60±0.93 NS
HDL (mmol/L) 1.53±0.36 1.43±0.31 NS 1.5±0.4 1.4±0.3 NS
TG (mmol/L) 1.41±0.67 1.62±0.73 NS 1.5±0.9 1.7±1.0 NS
Glycaemia (mmol/L) 5.59±1.67 5.55±1.56 NS 5.63±1.94 5.66±1.89 NS
CK (kat/L) 2.20±1.21 3.51±2.96 0.04 2.15±0.98 3.1±4.77 NS
AST (kat/L) 0.43±0.30 0.40±0.11 NS 0.39±0.17 0.39±0.10 NS
ALT (kat/L) 0.43±0.28 0.40±0.16 NS 0.45±0.28 0.41±0.22 NS
GMT (kat/L) 0.49±0.29 0.61±0.61 NS 0.56±0.39 0.60±0.44 NS
ALP (kat/L) 1.10±0.30 1.18±0.31 NS 1.10±0.30 1.2±0.4 NS
Urea (mmol/L) 4.87±1.31 5.01±1.27 NS 5.0±1.41 5.27±1.61 NS
Creatinine (mol/L) 85.70±13.52 86.47±16.03 NS 86.08±10.32 88.21±15.78 NS
sBP (mm Hg) 130.12±16.11 128.79±13.39 NS 130.2±11.7 128.2±12.7 NS
dBP (mm Hg) 82.04±8.88 79.12±6.69 NS 82.2±9.1 79.2±6.9 NS
b. Statin treatment
No. of patients 26 34 NS 26 34 NS
Type of statin
Atorvastatin (n)1114NS1114NS
Mean dose (mg/day) 16.7±8.7 18.1±9.1 16.7±7.4 18.1±8.8
Rosuvastatin (n)79NS79NS
Mean dose (mg/day) 12.1±5.3 10.4±3.2 12.1±4.3 10.4±2.8
Simvastatin (n)68NS68NS
Mean dose (mg/day) 26.9±7.4 25.4±6.5 26.9±8.2 25.4±6.9
Fluvastatin (n)23NS23NS
Mean dose (mg/day) 80±0 80±0 80±0 80±0
Note: BMI, body mass index; TCH, total cholesterol; LDL, LDL cholesterol; HDL, HDL cholesterol; TG, triglycerides; CK, creatin kinase;
AST, aspartate aminotransferase; ALT, alanine transaminase; GMT, glutamyl transferase; ALP, alkaline phosphatise; sBP, systolic blood
pressure; dBP, diastolic blood pressure; 1 mm Hg = 133.322 Pa.
Fedacko et al. 167
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After 3 months of treatment with the placebo, no significant
improvement in the intensity of muscle weakness was observed
(6.14 ± 1.35 vs. 5.3 ± 1.70, p= NS) (Table 6), whereas in the CoQ10
treatment group, the absolute change of intensity of muscle
weakness after 3 months was significantly higher than in placebo
group higher (–4.2 ± 2.7 vs. –0.84 ± 1.5, p< 0.01).
Muscle cramps worsened in 1 patient, remained unchanged in
3 patients, and improved in only 1 patient in the CoQ10 placebo
groups, compared to 11 improved and 2 unchanged in the CoQ10-
active form group of patients (Table 3). Changes in cramp inten-
sity are shown in Table 7, and the absolute change of intensity at
the end of the trial was statistically higher in the CoQ10-active
treatment group compared with the placebo group (–3.47 ± 2.9 vs.
–0.43 ± 1.8, p< 0.01).
Statin-associated fatigue disappeared in all patients (n= 10) in
the CoQ10-active group, while in the CoQ10 placebo group we
observed worsening in 2 patients, 6 patients remained un-
changed, and improvement was found in only 4 patients (Table 3).
In the CoQ10-active treatment group, tiredness decreased from
the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p< 0.01) compared with no
significant changes in the placebo group (Table 8). Changes in the
overall intensity of tiredness in the CoQ10 active group were sta-
tistically significant compared with the placebo group (–5.5 ± 3.7
vs. –2 ± 2.8, p< 0.01).
The most frequent adverse effects associated with statins are
asymptomatic increases in liver transaminases and myopathy
(Law and Rudnicka 2006). Statin-associated myopathy represents a
broad clinical spectrum of disorders (Thompson et al. 2003). The
mechanisms of statin-associated myopathy are still unknown, but
possibly include decreased sarcolemmal cholesterol, reduction in
small guanosine triphosphate-binding proteins, increased intra-
cellular lipid production and lipid myopathy, increased myocel-
lular phytosterols, and last but not least, possible decrease of
(intramitochondrial) CoQ10 (Corsini 2005). A hypothesis pub-
lished by Moosmann and Behl (2004a) identified a possible role of
selenium deficiency and its association with possible adverse
effects of statins, namely myopathy and polyneuropathy. They
noted that the pattern of side effects associated with statins
resembles the pathology of selenium deficiency, and postu-
lated that the mechanism lay in a well-established biochemical
pathway the isopentylation of selenocysteine-tRNA. A nega-
tive effect of statins on selenoprotein synthesis might explain
many of the enigmatic effects and side effects of statins.
In a systematic review of the role of CoQ10 in statin-associated
myopathy, the authors concluded that up to now there is insuffi-
cient evidence to prove the etiologic role of CoQ10 deficiency in
statin-associated myopathy and large, well-designed clinical trials
are required to address this issue. The epidemiology of statin-
associated myopathy is poorly described and mainly focused on
rhabdomyolysis. The occurence of both myopathy and rhabdomy-
olysis in clinical trials is rare; the incidence of severe myopathy is
Table 2. Plasma levels of coenzyme Q10 (CoQ10) and selenium (Se).
a. Coenzyme Q10
CoQ10 placebo
CoQ10 active
(mol/L) p
Se placebo
Se active
(g/L) p
CoQ10 baseline 0.74±0.31 0.81±0.39 0.503 0.75±0.36 0.81±0.35 0.559
CoQ10 month 1 0.86±0.80 3.16±1.78 <0.001 1.98±1,63 2.44±2.05 0.365
CoQ10 month 3 0.68±0.31 3.31±1.72 <0.001 1.86±1.60 2.35±2.05 0.344
b. Selenium
Se placebo
Se active
(g/L) p
CoQ10 placebo
CoQ10 active
(mol/L) p
Se baseline 68.00±9.70 70.45±12.90 0.421 70.20±9.48 68.37±12.80 0.551
Se month 1 71.08±15.79 129.84±31.81 <0.001 101.79±43.11 98.37±35.09 0.747
Se month 3 73.15±19.20 145.42±22.01 <0.001 105.24±46.98 108.62±38.06 0.778
Table 3. Symptoms in patients treated with coenzyme Q10 (CoQ10)
active compared with CoQ10 placebo.
No. of
change Decrease Increase p
Muscle pain
CoQ10 active 22 5 17 0 <0.001
CoQ10 placebo 18 15 1 2
Muscle weakness
CoQ10 active 13 1 12 0 0.011
CoQ10 placebo 7 4 2 1
CoQ10 active 10 0 10 0 0.005
CoQ10 placebo 12 6 4 2
CoQ10 active 13 2 11 0 0.024
CoQ10 placebo 5 3 1 1
Table 4. Symptoms of statin-associated myopathy in patients treated
with coenzyme Q10 (CoQ10) active/CoQ10 placebo + selenium (Se) ac-
tive/selenium placebo.
CoQ10 Selenium
No. of
change Decrease Increase p
Muscle pain
CoQ10 active Se active 10 1 9 0 0.194
CoQ10 active Se placebo 12 4 8 0
CoQ10 placebo Se active 7 5 1 1 0.392
CoQ10 placebo Se placebo 11 10 0 1
Muscle weakness
CoQ10 active Se active 6 0 6 0 0.335
CoQ10 active Se placebo 7 1 6 0
CoQ10 placebo Se active 2 2 0 0 0.449
CoQ10 placebo Se placebo 6 3 2 1
CoQ10 active Se active 4 0 4 0 0.325
CoQ10 active Se placebo 6 0 6 0
CoQ10 placebo Se active 6 4 2 0 0.263
CoQ10 placebo Se placebo 6 2 2 2
CoQ10 active Se active 6 2 4 0 0.097
CoQ10 active Se placebo 7 0 7 0
CoQ10 placebo Se active 1 0 1 0 0.082
CoQ10 placebo Se placebo 4 3 0 1
168 Can. J. Physiol. Pharmacol. Vol. 91, 2013
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0.1%–0.5%, while the incidence of rhabdomyolysis is 0.02%–0.04%
(Rosenson 2004). Clinical trial protocols, however, often exclude
patients more prone to myopathy, such as those with a history of
muscle pain with another lipid-lowering therapy, history of ele-
vated creatine kinase activity, hypothyroidism, elderly patients,
and others. Moreover, mild muscular symptoms are often over-
looked by doctors (a similar situation found during screening of
the patients for our study), and their frequency is therefore prob-
ably underestimated. Muscular symptoms in the PRIMO survey
were reported by 832 of 7924 (10.5%) hyperlipidemic patients re-
ceiving high-dosage statin therapy as their usual care, with a me-
dian time of onset of 1 month following initiation of statin
therapy (the lowest rate of muscular symptoms (5.1%) was ob-
served with fluvastatin treatment, the highest rate (18.2%) with
simvastatin treatment; Bruckert et al. 2005).
We have confirmed these data, but in this double-blind, ran-
domised study, no positive effects were observed from supple-
mentation with selenium. Interestingly, there is probably some
association between selenium and CoQ10 deficiency. In our study
we observed a higher increase of CoQ10 levels when supple-
mented together with selenium. It is not easy to explain these
findings, but in a small experimental study, the effect of long-
term (18 months) selenium deficiency on the levels of liver CoQ10
was studied in rats. Levels of CoQ10 in the liver of selenium-
deficient rats were 40% and 67% of the levels in selenium-adequate
animals, respectively. The results are similar to the findings of a
study using a shorter feeding period (Vadhanavikit and Ganther
1994). Reduction of ubiquinone by thioredoxin reductase is
selenium dependent and probably connects the antioxidant
ubiquinol to the essential trace element selenium. A combined
therapeutic approach with selenium and CoQ10 could constitute
an exciting area for future research, because such a combination
could probably be useful for the treatment of statin-associated
myopathy. In contrast, selenium supplementation in atheroscle-
rosis seems to be contraindicated, owing to possible atherogenic
influences (Nordman et al 2003;Moosmann and Behl 2004b).
At the present time we may only speculate that deficiency of
CoQ10 could be worsened by coincidental deficiency of selenium.
There is not enough evidence to support the general recommen-
dation of simultaneous administration of CoQ10 and selenium to
Table 5. Muscle pain intensity changes in coenzyme Q10 (CoQ10) active (n= 22) compared with the
CoQ10 placebo group of patients (n= 18).
Placebo group muscle pain CoQ10 treatment group muscle pain
Baseline M1 M3 Baseline M1 M3 p
Baseline 5.3±1.60 6.7±1.72 <0.05
M1 NS* 5.05±1.6 NS*** <0.01* 5±1.8 <0.01*** NS
M3 NS** 5.2±1.5 <0.01** 3.2±2.1 <0.001
Note: M1, month 1 of test period; M3, month 3 (end) of test period; *, comparison between baseline and M1;
**, comparison between baseline and M3; ***, comparison between M1 and M3; NS, not statistically significant.
Table 6. Muscle weakness intensity changes in the coenzyme Q10 (CoQ10) active treatment group
(n= 13) compared with the placebo group of patients (n= 7).
Placebo group muscle weakness CoQ10 group muscle weakness
Baseline M1 M3 Baseline M1 M3 p
Baseline 6.14±1.35 7±1.63 <0.083
M1 NS* 5.42±1.51 NS*** <0.01* 5.4±2.06 <0.01*** NS
M3 NS** 5.3±1.7 <0.01** 2.8±2.34 <0.001
Note: M1, month 1 of test period; M3, month 3 (end) of test period; *, comparison between baseline and M1;
**, comparison between baseline M3; ***, comparison between M1 and M3; NS, not statistically significant.
Table 7. Muscle cramps intensity changes in the coenzyme Q10 (CoQ10) active treatment group
(n= 13) compared with the placebo group of patients (n= 5).
Placebo group muscle cramps CoQ10 group muscle cramps
Baseline M1 M3 Baseline M1 M3 p
Baseline 5.43±1.4 5.33±2.06 NS
M1 NS* 5.43±1.4 NS*** <0.01* 2.66±2.16 <0.01*** <0.01
M3 NS** 5.86±1.57 <0.01** 1.86±2.42 <0.001
Note: M1, month 1 of test period; M3, month 3 (end) of test period; *, comparison between baseline and M1;
**, comparison between baseline and M3; ***, comparison between M1 and M3; NS, not statistically significant.
Table 8. Tiredness intensity intensity changes in conenzyme Q10 (CoQ10) active group (n= 10)
compared with the placebo group of patients (n= 12).
Placebo group tiredness CoQ10 group tiredness
Baseline M1 M3 Baseline M1 M3 p
Baseline 6.5±1.52 6.7±1.34 NS
M1 NS* 5±2.16 NS*** <0.01* 3.4±2.07 <0.01*** <0.01
M3 NS** 4.5±2.37 <0.01** 1.2±1.32 <0.001
Note: M1, month 1 of test period; M3, month 3 (end) of test period; *, comparison between baseline and M1;
**, comparison between baseline and M3; ***, comparison between M1 and M3; NS, not statistically significant.
Fedacko et al. 169
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every statin-treated patient with adverse effects from such ther-
apy. Although carried out in a randomized and double-blind fash-
ion, the present study involved a relatively small number of
patients, and the data must be considered in light of this.
Our results show that supplementation of statin-treated pa-
tients with CoQ10 diminishes the symptoms of statin-associated
myopathy. In our study, supplementation with selenium was not
associated with clinically significant benefits. In conclusion, our
double-blind randomized study showed that CoQ10 supplementa-
tion (200 mg daily) to statin-treated patients presenting with mild
to moderate statin-associated myopathy may lead not only to sta-
tistically significant increase of plasma CoQ10 levels, but is asso-
ciated with a significant reduction of statin side effects, even
without interruption of statin therapy. Thus, CoQ10 supplemen-
tation may decrease the need to withdraw these drugs if adverse
effects appear. This may be of great importance, owing to fact that
statins represent the basic treatment for secondary prevention of
atherosclerosis, and their prescription rate during recent decades
has increased dramatically. Although there is a positive outcome
from this pilot study, it is not possible to draw any definite con-
clusions, despite the study being carried out in double-blind fash-
ion, because it involved a small number of patients. Thus, further
research in this field is needed.
Conflict of interest
The authors declare that there are no conflicts of interest asso-
ciated with this study.
This investigator-initiated trial was supported by research grant
VEGA 1/2317/2005 from the Slovak Ministry of Education. The au-
thors gratefully acknowledge Pharma Nord for providing the stud-
ied medications and support for laboratory analyses, and Labor
Dr. Bayer, Postfach, Stuttgart for selenium analyses.
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170 Can. J. Physiol. Pharmacol. Vol. 91, 2013
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... Indeed, statins are associated with myopathy caused by the inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase, which is a key player in CoQ biosynthesis [121]. A small group of patients with statin-associated myopathy has been treated with CoQ supplementation showing decreased muscle pain and fatigue [122]. This result is promising; however, it was conducted with a small number of patients and is not sufficient to state whether CoQ supplementation attenuates the side effects of chronic statin treatment. ...
... elderly subjects exercise performance [109] Parkinson's disease patients decreased development of disability [116] no effect on motor symptoms [105,113] cardiovascular impairment decreased systemic blood pressure [107] preventing arrhythmias in cardiac surgery-subjected patients [114] increased left ventricular ejection fraction [115] decreased cardiovascular events in patients with chronic heart failure [116] diabetes decreased blood glucose [117] no differences in glycemic control [118] counteracting statins side-effects decreased muscle impairment [122] ...
Full-text available
Mitochondria participate in the maintenance of cellular homeostasis. Firstly, mitochondria regulate energy metabolism through oxidative phosphorylation. In addition, they are involved in cell fate decisions by activating the apoptotic intrinsic pathway. Finally, they work as intracellular signaling hubs as a result of their tight regulation of ion and metabolite concentrations and other critical signaling molecules such as ROS. Aging is a multifactorial process triggered by impairments in different cellular components. Among the various molecular pathways involved, mitochondria are key regulators of longevity. Indeed, mitochondrial deterioration is a critical signature of the aging process. In this scenario, we will focus specifically on the age-related decrease in CoQ levels, an essential component of the electron transport chain (ETC) and an antioxidant, and how CoQ supplementation could benefit the aging process. Generally, any treatment that improves and sustains mitochondrial functionality is a good candidate to counteract age-related mitochondrial dysfunctions. In recent years, heightened attention has been given to natural compounds that modulate mitochondrial function. One of the most famous is resveratrol due to its ability to increase mitochondrial biogenesis and work as an antioxidant agent. This review will discuss recent clinical trials and meta-analyses based on resveratrol and CoQ supplementation, focusing on how these compounds could improve mitochondrial functionality during aging.
... After removing duplicate articles and excluding nonrelevant articles by an examination of titles and abstracts, we ultimately included 13 RCTs in the final analysis (Berman et al., 2004;Lee et al., 2011;Cordero et al., 2013;Lesser et al., 2013;Castro-Marrero et al., 2015;Fukuda et al., 2015;Peel et al., 2015;Sanoobar et al., 2016;Di Pierro et al., 2017;Morikawa et al., 2019;Mizuno et al., 2020;Mousavi et al., 2020;Castro-Marrero et al., 2021). The articles excluded in the final stage and the reasons for exclusion are listed in Supplementary Table S3 (Singh et al., 2003;Langsjoen et al., 2005;Kumar et al., 2007;Mizuno et al., 2008;Gökbel et al., 2010;Cordero et al., 2012a;Cordero et al., 2012b;Fedacko et al., 2013;Gharahdaghi et al., 2013;Miyamae et al., 2013;Castro-Marrero et al., 2016;Fukuda et al., 2016;Iwase et al., 2016;Menon et al., 2017;Langsjoen et al., 2019;Moccia et al., 2019;Negro et al., 2019;Gomez-Centeno et al., 2020;Schweiger et al., 2020;Suzuki et al., 2021). Details of data extraction from included randomized controlled trials are summarized in Supplementary Table S4. ...
... August 2022 | Volume 13 | Article 883251 8 capacity as compared with placebo-treated group (Lei and Liu, 2017). In 2019, Mehrabani et al. published a systematic review (Mehrabani et al., 2019) reported that CoQ10 was effective against fatigue in patients with myopathy associated with statin use (Fedacko et al., 2013) as well as in patients with fibromyalgia (Cordero et al., 2012a;Cordero et al., 2013;Miyamae et al., 2013;Di Pierro et al., 2017). However, the aforementioned review did not quantify the fatigue-reducing effect of CoQ10. ...
Full-text available
Coenzyme Q10 (CoQ10) is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date. Hence, we conducted this meta-analysis with the aim of investigating the effectiveness of fatigue reduction via CoQ10 supplementation. More specifically, we searched electronic databases for randomized controlled trials (RCTs) published from the database inception to January 2022. A random effects model was implemented to conduct the meta-analysis among 13 RCTs (with a total of 1,126 participants). As compared with the placebo groups evaluated in each RCT, the CoQ10 group showed a statistically significant reduction in fatigue scores (Hedges’ g = −0.398, 95% confidence interval = −0.641 to −0.155, p = 0.001). The directions of the treatment effects were consistent between the healthy and diseased participants. Compared with the placebo group, the effect of reducing fatigue was statistically significant in the subgroup using the CoQ10-only formulation but not in the subgroup using CoQ10 compounds. The results of our meta-regression demonstrate that increases in the daily dose (coefficient = −0.0017 per mg, p < 0.001) and treatment duration (coefficient = −0.0042 per day, p = 0.007) of CoQ10 supplementation were correlated with greater fatigue reduction. There was only one adverse (gastrointestinal) event in the 602 participants who underwent the CoQ10 intervention. Based on the results of this meta-analysis, we conclude that CoQ10 is an effective and safe supplement for reducing fatigue symptoms. Systematic Review Registration: , identifier INPLASY202210113
... The combined CoQ 10 and selenium supplementation substantially elevated the relevant serum levels in patients taking statins but did not significantly mitigate their myopathy symptoms in two 2013 RCTs [214,215]. However, three months on CoQ 10 and carnitine supplementation showed a significant reduction of serum lipoprotein(a) in hemodialysis patients with statin therapy [216]. ...
... Therefore, CoQ 10 supplementation has been proposed as a complementary statin therapy in some patients in order to improve SAMS. Nevertheless, there is some controversy about the efficiency of these treatments, since some studies were able to find significant improvement of SAMS upon CoQ 10 supplementation [23][24][25], whereas other studies were not able to identify any positive effect [26,27]. One relevant factor is CoQ 10 bioavailability and absorption due to its low water solubility [28,29]. ...
Full-text available
Heredity of familial hypercholesterolemia (FH) can present as a dominant monogenic disorder of polygenic origin or with no known genetic cause. In addition, the variability of the symptoms among individuals or within the same families evidence the potential contribution of additional factors than monogenic mutations that could modulate the development and severity of the disease. In addition, statins, the lipid-lowering drugs which constitute the first-line therapy for the disease, cause associated muscular symptoms in a certain number of individuals. Here, we analyze the evidence of the mitochondrial genetic variation with a special emphasis on the role of CoQ10 to explain this variability found in both disease symptoms and statins side effects. We propose to use mtDNA variants and copy numbers as markers for the cardiovascular disease development of FH patients and to predict potential statin secondary effects and explore new mechanisms to identify new markers of disease or implement personalized medicine strategies for FH therapy.
... The combined CoQ 10 and selenium supplementation substantially elevated the relevant serum levels in patients taking statins but did not significantly mitigate their myopathy symptoms in two 2013 RCTs [214,215]. However, three months on CoQ 10 and carnitine supplementation showed a significant reduction of serum lipoprotein(a) in hemodialysis patients with statin therapy [216]. ...
Full-text available
Coenzyme Q10 (CoQ10) is a compound with a crucial role in mitochondrial bioenergetics and membrane antioxidant protection. Despite the ubiquitous endogenous biosynthesis, specific medical conditions are associated with low circulating CoQ10 levels. However, previous studies of oral CoQ10 supplementation yielded inconsistent outcomes. In this article, we reviewed previous CoQ10 trials, either single or in combination with other nutrients, and stratified the study participants according to their metabolic statuses and medical conditions. The CoQ10 supplementation trials in elders reported many favorable outcomes. However, the single intervention was less promising when the host metabolic statuses were worsening with the likelihood of multiple nutrient insufficiencies, as in patients with an established diagnosis of metabolic or immune-related disorders. On the contrary, the mixed CoQ10 supplementation with other interacting nutrients created more promising impacts in hosts with compromised nutrient reserves. Furthermore, the results of either single or combined intervention will be less promising in far-advanced conditions with established damage, such as neurodegenerative disorders or cancers. With the limited high-level evidence studies on each host metabolic category, we could only conclude that the considerations of whether to take supplementation varied by the individuals’ metabolic status and their nutrient reserves. Further studies are warranted.
... This finding is empathized with [66,67] which declared that CoQ10 deficiencies are associated with elevated CK and myopathy. In the same context, Fedacko et al. [68] found an absolute decrease in muscle pain intensity after 3 months for the Q10active treatment group was significantly greater, compared with the placebo group. ...
Full-text available
The prevalence of metabolic syndrome (MetS) has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. MetS is generally linked to complications in lipid metabolism, oxidative stress and low grade inflammation. The aim of the current study was to evaluate the effect of rosuvastatin, co-enzyme Q10 (CoQ10), and their combination on blood pressure, blood sugar, dyslipidemia, and liver function in rats with MetS induced by high fructose and high fat diet (HF-HFD) and the possible underlying mechanism. Oral administration of rosuvastatin (10 mg/kg/day), CoQ10 (10 mg/kg/ day) and their combination for 4 weeks in HF-HFD-fed rats elevated serum high density lipoprotein and reduced glutathione. On the other hand, treatment with rosuvastatin, CoQ10 or their combination decreased the serum levels of malondialdehyde, triglycerides, total cholesterol, and low density lipoprotein-cholesterol as well as systolic blood pressure, body weight and fasting blood glucose level. In addition, the drugs or their combination declined serum pro-inflammatory cytokines, namely tumor necrosis factor-α and interleukin-1β. In conclusion, our results showed that rosuvastatin or CoQ10 protected against HF-HFD-induced MetS through the regulation of dyslipidemia, elevated blood glucose, elevated blood pressure, antioxidant defenses and inflammatory response. Rosuvastatin or CoQ10 also alleviated the impairment of liver function that was induced by HF-HFD. Interestingly , CoQ10 augmented rosuvastatin's effect in ameliorating MetS, via exerting synergistic modulatory effects on oxidative stress and inflammation. Thus, rosuvastatin and CoQ10 combination therapy may have possible applications in ameliorating metabolic disorders.
... As expected, there was an increase in plasma CoQ10 concentration in the CoQ10 group which confirms adherence to the intervention, and that the CoQ10 was well absorbed. We chose a dose and supplementation period in the high end of the range reported in similar studies (100-600 mg for 30 days to 12 weeks) [20][21][22][23][24][25][26]53,54]. Thus, it is unlikely that our null result is explained by inadequate doses of CoQ10 in the supplementation period. ...
Full-text available
Myalgia and new-onset of type 2 diabetes have been associated with statin treatment, which both could be linked to reduces coenzyme Q10 (CoQ10) in skeletal muscle and impaired mitochondrial function. Supplementation with CoQ10 focusing on levels of CoQ10 in skeletal muscle and mitochondrial function has not been investigated in patients treated with statins. To investigate whether concomitant administration of CoQ10 with statins increases the muscle CoQ10 levels and improves the mitochondrial function, and if changes in muscle CoQ10 levels correlate with changes in the intensity of myalgia. 37 men and women in simvastatin therapy with and without myalgia were randomized to receive 400 mg CoQ10 daily or matched placebo tablets for eight weeks. Muscle CoQ10 levels, mitochondrial respiratory capacity, mitochondrial content (using citrate synthase activity as a biomarker), and production of reactive oxygen species were measured before and after CoQ10 supplementation, and intensity of myalgia was determined using the 10 cm visual analogue scale. Muscle CoQ10 content and mitochondrial function were unaltered by CoQ10 supplementation. Individual changes in muscle CoQ10 levels were not correlated with changes in intensity of myalgia. CoQ10 supplementation had no effect on muscle CoQ10 levels or mitochondrial function and did not affect symptoms of myalgia.
... Fedacko et al found that the symptoms of SAM improved significantly in the active group, with the intensity of muscle pain decreasing (-53.4± 28.2 percent), muscle weakness decreasing (-60± 24.0 percent), muscle cramps decreasing (-65 ±28 percent) and tiredness decreasing from the initial (-82± 22 percent) and plasma levels of CoQ10 increasing in the active group (Fedacko et al, 2013). Moreover, a strong negative correlation between muscle pain, weakness and fatigue, and serum CoQ10 level among patients, who received CoQ10 supplements after 3 months (P-value ≤ 0.01). ...
Full-text available
Abstract: Background: Different grade of muscle symptoms, so-called statin-associated muscle symptoms induced by statins, reported from milder complaints of SAMS like to major functional loss. Serum CoQ10 concentrations are reduced by statin therapy, but still routine supplementation with CoQ10 in clinical practice is controversial. Objective:Study the effectiveness of Coenzyme Q10 (CoQ10) co-administration to atorvastatin treatment in patients who experienced statin-associated muscle symptoms. Methods: This interventional prospective randomized controlled, open-label study. recruited patients reported statin-induced muscle symptoms during atorvastatin treatment. The presence of statin-related myalgia will be confirmed by a dechallenge -rechallenge trial during which the presence and absence of symptoms will be documented. Patients were randomized either to received 200 mg/day of CoQ10 adjuvant therapy ,or patients on atorvastatin (20, 40) mg both followed for 12 weeks. Subjective tools of statin-related muscle symptoms, patient adherence were assessed. Results:Effect of study intervention on statin-associated myalgia revealed highly significant decrease (P-value ≤ 0.01) in Clinical Index Score, musclepain(severityandinterference)usingBriefPain Inventory Score(BPI), and Muscle SymptomsIntensity using(Box Scale-11)amongpatientsingroup1comparedwithgroup2 patients, after 12 weeks.Alsosignificantinversecorrelations (P-value≤0.01)revealed betweenCoQ10serumendline and the above subjective assessment of statin-related muscle symptoms amongpatientsingroup1 only. Moreover, a significantincreaseinspecificnecessitymean (P-value≤0.01) anda highlysignificant differencewiththedecreaseinspecificconcerns,generalharm,generaloverusefor group1patients(P-value≤0.01) as a domain for patient adherence assessment tool (BMQ). Conclusions: The current study revealed gradual improvement in the muscle symptoms after CoQ10 adjuvant therapy among patients with statin-associated muscle symptoms, this resulted in increased patients' adherence concomitantly with decreasing muscle compliance. Keyword:Coenzyme Q10, Statin- Myopathy (SAMS), Dyslipidemia.
... Importantly, ubiquinone supplementation rescues lost mitochondrial volume induced by statins during treatment of cardiovascular disease (Vaughan et al., 2013). Several placebo-controlled trials of coenzyme Q10 supplementation reported a significant reduction in the myalgia on long term statin therapy (Fedacko et al., 2013;Pourmoghaddas et al., 2014), which may be due to the differences in supplement composition and methods of pain assessment (Bogsrud et al., 2013). ...
Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) treat dyslipidaemia and cardiovascular disease by inhibiting cholesterol biosynthesis. They also have immunomodulatory and anti-inflammatory properties. Beyond cardiovascular disease, cholesterol and inflammation appear to be components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Statins may therefore afford some therapeutic benefit in mood disorders. In this paper, we review the pathophysiology of mood disorders with a focus on pharmacologically relevant pathways, using major depressive disorder and bipolar disorder as exemplars. Statins are discussed in the context of these disorders, with particular focus on the putative mechanisms involved in their anti-inflammatory and immunomodulatory effects. Recent clinical data suggest that statins may have antidepressant properties, however given their interactions with many known biological pathways, it has not been fully elucidated which of these are the major determinants of clinical outcomes in mood disorders. Moreover, it remains unclear what the appropriate dose, or appropriate patient phenotype for adjunctive treatment may be. High quality randomised control trials in concert with complementary biological investigations are needed if the potential clinical effects of statins on mood disorders, as well as their biological correlates, are to be better understood.
Aim: To determine the association of coenzyme Q10 (CoQ10) use with the resolution of statin-associated muscle symptoms (SAMS). Patients & methods: Retrospective analysis of a large, multi-center survey study of SAMS (total n = 511; n = 64 CoQ10 users). Univariate and multivariate logistic regression models assessed the association between CoQ10 use and the resolution of SAMS. Results: The frequency of SAMS resolution was similar between CoQ10 users and non-users (25% vs 31%, respectively; unadjusted odds ratio [OR]: 0.75 [95% CI: 0.41–1.38]; p = 0.357). Similarly, CoQ10 use was not significantly associated with the resolution of SAMS in multivariable models adjusted for SAMS risk factors (OR: 0.84 [95% CI: 0.45–1.55]; p = 0.568) or adjusted for significant differences among CoQ10 users and non-users (OR: 0.82 [95% CI: 0.45–1.51]; p = 0.522). Conclusion: CoQ10 was not significantly associated with the resolution of SAMS.
Full-text available
The purpose of this study was to evaluate the pharmacokinetics of a single dose of Selenium (Se) from yeast given to humans with a habitual long-term daily intake at a supra-nutritional level. Twelve healthy males with a daily supplemental intake of 300 microg Se as selenised yeast over 10 weeks were supplemented with a single dose of 327 microg as stable (77)Se incorporated into selenised yeast manufactured by the same standardised process (SelenoPrecise(R), Pharma Nord, Denmark). Absorption of Se from (77)Se-enriched yeast was 89+/-4% and the retention was 74+/-6%. The (77)Se excretion from the single-dose was 47+/-15 microg in urine and 37+/-13 microg in faeces. The maximum, enriched (77)Se concentration in plasma was 9.8+/-1.5 microg/l and the time to maximum was 9.2 hours. The plasma halftime of (77)Se was longer with increasing time; 1.7 days for the initial phase ((1/2)-2 days), 3.0 days for the middle phase (2-3 days) and 11.1 days for the later phase (3-14 days). The Se from the standardised Se-enriched yeast was well absorbed and retained in the body.
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Coenzyme Q is well defined as a crucial component of the oxidative phosphorylation process in mitochondria which converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis. New roles for coenzyme Q in other cellular functions are only becoming recognized. The new aspects have developed from the recognition that coenzyme Q can undergo oxidation/reduction reactions in other cell membranes such as lysosomes. Golgi or plasma membranes. In mitochondria and lysosomes, coenzyme Q undergoes reduction/oxidation cycles during which it transfers protons across the membrane to form a proton gradient. The presence of high concentrations of quinol in all membranes provides a basis for antioxidant action either by direct reaction with radicals or by regeneration of tocopherol and ascorbate. Evidence for a function in redox control of cell signaling and gene expression is developing from studies on coenzyme Q stimulation of cell growth, inhibition of apoptosis, control of thiol groups, formation of hydrogen peroxide and control of membrane channels. Deficiency of coenzyme Q has been described based on failure of biosynthesis caused by gene mutation, inhibition of biosynthesis by HMG coA reductase inhibitors (statins) or for unknown reasons in ageing and cancer. Correction of deficiency requires supplementation with higher levels of coenzyme Q than are available in the diet.
A batch of 77Se-labelled and enriched yeast was characterised with regard to isotopic composition and content of selenium species for later use in a human absorption study based on the method of enriched stable isotopes. The abundance of the six stable selenium isotopes was determined by ICP-MS equipped with a dynamic reaction cell (DRC). The results showed that the 77Se isotope was enriched to 98.5 atom-%, whereas the remaining selenium was present as the other five isotopes at low abundance. The low-molecular 77Se containing species, which were biosynthesised by the yeast during fermentation using the enriched 77Se-selenite as substrate, were released by enzymatic hydrolysis using (I), a β-glucosidase followed by a protease mixture, and (II), a commercial protease preparation. For selenium speciation the chromatographic selectivity of the cation exchange HPLC system was adjusted to the separation of over 30 selenium species occurring in the hydrolysates by applying gradient elution using pyridinium formate as mobile phase. The quantitative results obtained by detection with ICP-DRC-MS of 77Se and 80Se showed that both enzymatic sample preparation systems released 90–95% of the yeast's selenium content. The total area of the cation exchange chromatograms, however, amounted to 64% of the total selenium content in the yeast, which was 1390 µg g−1. In the enzymatic extracts selenomethionine (SeMet) constituted 82% of all separated and quantified selenium species, which was equivalent to 53% of the total selenium content in the yeast. Oxidation of SeMet to selenomethionine-Se-oxide (SeOMet) occurred during sample preparation. The degree of formation of SeOMet was large and variable when using enzyme system I, but low when using enzyme II.
Cited By (since 1996): 40, Export Date: 21 September 2011, Source: Scopus
Twenty-one healthy subjects received oral Coenzyme Q10 supplementation in soft capsules of 30 mg t.i.d. for 9 months, followed by a withdrawal period of 3 months. Blood samples were taken before start of supplementation, after 3 and 9 months of supplementation, and finally 3 months after withdrawal. Average blood coenzyme Q10 concentration increased from about 1 mg/l before supplementation to about 2 mg/l after 3 and 9 months of supplementation, and returned to the pretreatment level after withdrawal. The rise of coenzyme Q10 concentration was statistically significant (P < 0.001, t-test).
The bioavailability of four different Coenzyme Q10 (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatin capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatin capsules containing: 100 mg of CoQ with 400 mg of soy bean oil (Bioquinon); 100 mg of CoQ with 20 mg of polysorbate 80, 100 mg of lecithin and 280 mg of soy bean oil; and 100 mg of CoQ with 20 mg of polysorbate 80 and 380 mg of soy bean oil, respectively. The result suggests that the soya bean oil suspension of CoQ (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o. administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile.
The effect of long-term (18 months) selenium deficiency on the levels of liver coenzyme Q was studied in the rat. Levels of coenzyme Q9 and coenzyme Q10 in the liver of selenium-deficient rats were 40 and 67% of the levels in selenium-adequate animals, respectively. The results are similar to the findings using a shorter feeding period.
Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.