ArticlePDF Available

Coenzyme Q10 Regulates Serotonin Levels and Depressive Symptoms in Fibromyalgia Patients: Results of a Small Clinical Trial

Authors:
Elísabet Alcocer-Gómez at University of Seville
Elísabet Alcocer-Gómez
Jose A Sánchez-Alcázar at Pablo de Olavide University
Jose A Sánchez-Alcázar
Mario D Cordero at Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA)
Mario D Cordero
  • Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA)
Download full-text PDF
Read full-text
Download citation

Figures

Figures - uploaded by Mario D Cordero
Author content
All figure content in this area was uploaded by Mario D Cordero
Content may be subject to copyright.
Content uploaded by Mario D Cordero
Author content
All content in this area was uploaded by Mario D Cordero on Feb 11, 2018
Content may be subject to copyright.
Copyright @ 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Coenzyme Q
10
Regulates
Serotonin Levels and
Depressive Symptoms in
Fibromyalgia Patients
Results of a Small Clinical Trial
To the Editors:
Despite discrepancies about the role of
the serotonergic system in the path-
ophysiology of fibromyalgia (FM), the
presence of disturbances of serotonin
function in this disease is evident. Sero-
tonin is an important modulator of pain
perception, sleep, fatigue, cognition, and
mood in normal subjects, supporting the
conclusion that disturbances in these
functions (hallmark symptoms of patients
with FM) can be the result of abnormali-
ties in serotonin content, metabolism,
or transmission. Furthermore, serotonin
function alterations have provided the
basis for several therapeutic options in
FM, being serotonin reuptake inhibitors
widely used for its treatment.
1
Coenzyme
Q (CoQ
10
) deficiency is also another
pathological alteration observed in pa-
tients with FM and it has been reported
that CoQ
10
supplementation significantly
improves the clinical symptoms associat-
ed with the disease.
2Y4
CoQ
10
possesses antidepressant prop-
erties and it has a major role in the patho-
physiology of several diseases associated
with depressive symptoms such as major
depression, myalgic encephalomyelitis, and
FM.
4,5
Following up our earlier work on the
mechanisms of therapeutic effects of CoQ
10
in FM in a clinical trial (ISRCTN 21164124),
2
here we show the effect of 40 days of CoQ
10
versus placebo supplementation on serotonin
levels in platelets from FM patients and de-
pressive symptoms improvement.
The study protocol was reviewed and
approved by the Ethical Committee of the
University of Sevilla. All the participants of
the study gave their written informed consent
before initiating the study. This study was
carried out in compliance with the Declara-
tion of Helsinki, and all the International
Conferences on Harmonisation and Good
Clinical Practice Guidelines. Twenty patients
diagnosed with FM were distributed in a
clinical trial as described in Cordero et al.
2
The patients were diagnosed with FM by
exclusion of other diseases and syndromes,
and in accordance with the American Col-
lege of Rheumatology criteria. Subjects were
randomized in a double-blind fashion,
according to a 1:1 ratio, to CoQ
10
or pla-
cebo. Ten subjects received CoQ
10
(Pharma
Nord, Vejle, Denmark) in soft gel capsules
for 40 days (300 mg/d CoQ
10
divided into
3 daily doses), whereas another group of
10 subjects received a matching placebo.
Early-morning samples of blood were
collected under fasting conditions and plate-
lets were isolated. CoQ
10
levels were deter-
mined by HPLC and serotonin levels by
ELISA (GenWay, San Diego, CA). CoQ
10
deficiency was induced in healthy platelets
by 1 mM P-aminobenzoate (PABA; Sigma
Chemical Co, St Louis, MO) treatment. De-
pression was evaluated by the Beck Depres-
sion Inventory (BDI) scale.
DISCUSSION
As expected, FM patients had mark-
edly higher levels of depression [BDI, 22.3
(6.5)] compared with healthy controls
[2.9 (1.1)] (PG0.001). CoQ
10
and sero-
tonin levels in platelets isolated from FM
patients were significantly reduced in re-
spect to controls ( F1Fig. 1A and B). Inter-
estingly, CoQ
10
and serotonin content in
platelets from nontreated patients showed a
strong positive correlation (Fig. 1C). Sev-
eral studies have suggested that platelets
are good models of neuronal serotonergic
cells.
6
Both types of cells are major storage
sites for serotonin, and interestingly sero-
tonin levels in cerebrospinal fluid are
strongly correlated with serotonin levels in
platelets.
6
Therefore, our results may re-
flect the critical role of CoQ
10
deficiency
in the functional alterations of the seroto-
ninergic system.
The evidence base for the clinical ef-
fectiveness of treatment with CoQ
10
may
be explained via its ability to ameliorate
oxidative stress and protect mitochondria.
4
However, there is no information about the
effect of CoQ
10
treatment in serotonin
levels. In our study, CoQ
10
and serotonin
levels in platelets from FM patients were
restored in the COQ
10
-treated group com-
pared to placebo group (Fig. 1A and B).
Interestingly, a notable improvement in
depressive symptoms evaluated with the
BDI scale was also observed in the CoQ
10
-
treated group compared to the placebo
group [placebo group, 24.1 (3.5); CoQ
10
group, 6.2 (1.9)] (PG0.001).
To verify the role of CoQ
10
in the se-
rotonin alterations observed in FM patients,
we induced CoQ
10
deficiency in platelets
from healthy controls by inhibiting the
endogenous biosynthesis of CoQ
10
with
PABA treatment, a competitive inhibitor
of polyprenyl-4-hydroxybenzoate transferase
(Coq2p). Platelets were cultured for 24 hours
in the presence of 1-mM PABA, or alterna-
tively PABA + 10 KM CoQ
10
, and PABA +
10 mM N-acetylcysteine (N-Acet) (Sigma
Chemical Co). Serotonin levels in platelets
were significantly reduced by PABA treat-
ment (Fig. 1D). Reduced serotonin levels in
platelets were restored in the presence of 2
antioxidants, CoQ
10
, or N-Acet, being more
significant in platelets treated with CoQ
10
.
Taken together, these results suggest that
CoQ
10
deficiency affects serotonin content in
platelets and, presumably, in other cells such
as neurons of the central nervous system.
CoQ
10
is an important component of the
mitochondrial respiratory chain enabling the
generation of adenosine triphosphate by oxi-
dative phosphorylation. Because adenosine
triphosphate levels have been observed to be
reduced in platelets from FM patients and
FM has been related with alterations of the
hypothalamic-pituitary-adrenal (HPA) axis,
and hormone and neurotransmitter secre-
tion,
7
a possible explanation for our results is
that CoQ
10
may play an essential role in the
regulation of bioenergetics status in platelets
and in other cells such as neurons of the
central nervous system and thus, it may affect
serotonin content, transmission, and function.
These results may also contribute to explain
the antidepressant effect of CoQ
10
treatment.
Our findings also support the hypothesis that
CoQ
10
supplementation can be used as an
alternative therapy for controlling depression.
Further analyses involving more pa-
tients in doubled-blind placebo-controlled
clinical trials are required to confirm these
observations. Indeed, our research group
is currently working in this direction,
based on the conclusions of the explor-
atory work discussed in this article.
AUTHOR DISCLOSURE
INFORMATION
The authors declare no conflicts of
interest.
Elı´sabet Alcocer-Go´mez, DSc
Jose Antonio Sa´nchez-Alca´zar, MD, PhD
Centro Andaluz de Biologı
´a del Desarrollo
Universidad Pablo de Olavide-CSIC-Junta de
Andalucı
´a and Centro de Investigacio
´n
Biome
´dica en Red de Enfermedades Raras
ISCIII, Sevilla, Spain
Mario D. Cordero, BSc
Research Laboratory
Dental School, University of Sevilla
Sevilla, Spain
mdcormor@us.es
LETTER TO THE EDITORS
Journal of Clinical Psychopharmacology &Volume 34, Number 2, April 2014 www.psychopharmacology.com 1
Copyeditor: Aleli L. Anacay
Copyright @ 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
REFERENCES
1. Ha¨user W, Wolfe F, To¨ lle T, et al. The role
of antidepressants in the management of
fibromyalgia syndrome: a systematic
review and meta-analysis. CNS Drugs.
2012;26:297Y307.
2. Cordero MD, Alcocer-Go
´mez E, de Miguel
M, et al. Can coenzyme Q10 improve
clinical and molecular parameters in
fibromyalgia? Antioxid Redox Signal. 2013
AQ1 .
3. Miyamae T, Seki M, Naga T, et al. Increased
oxidative stress and coenzyme Q10
deficiency in juvenile fibromyalgia:
amelioration of hypercholesterolemia and
fatigue by ubiquinol-10 supplementation.
Redox Rep. 2013;18:12Y19.
4. Morris G, Anderson G, Berk M, et al.
Coenzyme Q10 depletion in medical and
neuropsychiatric disorders: potential
repercussions and therapeutic implications.
Mol Neurobiol. 2013.
5. Aboul-Fotouh S. Coenzyme Q10
displays antidepressant-like activity with
reduction of hippocampal oxidative/
nitrosative DNA damage in chronically
stressed rats. Pharmacol Biochem Behav.
2013;104:105Y112.
6. Audhya T, Adams JB, Johansen L.
Correlation of serotonin levels in CSF,
platelets, plasma, and urine. Biochim
Biophys Acta. 2012;1820:
1496Y1501.
7. Bazzichi L, Giannaccini G, Betti L, et al.
ATP, calcium and magnesium levels in
platelets of patients with primary
fibromyalgia. Clin Biochem.
2008;41:1084Y1090.
FIGURE 1. A, CoQ
10
levels were reduced in platelets from FM patients. CoQ
10
levels were restored after oral CoQ
10
supplementation
versus placebo. B, Serotonin levels were reduced in platelets from FM patients compared with platelets from healthy controls. After
supplementation, CoQ
10
induced a significant increase of serotonin levels. *PG0.01 between before and after CoQ
10
supplementation
FM patients.
a
PG0.01 between FM patients and healthy controls. C, Correlation between CoQ
10
and serotonin levels in platelets. The
strength of the association was established by calculating Pearson correlation coefficient (r). D, Induced CoQ
10
deficiency in vitro leads to
serotonin deficiency in platelets. Reduced levels of serotonin were restored by antioxidants but more significantly with CoQ
10
treatment.
Data represent the mean (SD) of 3 separate experiments. *PG0.001 between control, PABA, and PABA with CoQ
10
; **PG0.01 between
PABA and PABA with N-Acet.
Letter to the Editors Journal of Clinical Psychopharmacology &Volume 34, Number 2, April 2014
2www.psychopharmacology.com *2013 Lippincott Williams & Wilkins
... The countries that reported those selected articles were Spain (n ¼ 11), followed by Iran (n ¼ 3), Italy (n ¼ 2), Japan (n ¼ 1), Thailand (n ¼ 1), Egypt (n ¼ 1) and the United Kingdom (n ¼ 1). Twelve studies were randomized and controlled [13e21, 25,26,31]; five were open prospective trials [22,23,28,29,32], and three were case or series of case reports [24,27,30]. Table 1 shows the evaluation in 143 RA and 53 APS patients, with mean age varying from 48.77 ± 11.58 to 51.89 ± 15.51 years old and a predominance of female patients (75 %e86.4 %). ...
... The CoQ10 dosage in these studies ranged from 40 mg to 300 mg/day, and the follow-up went from 6 to 36 weeks. After CoQ10 supplementation, FM patients observed improvement in fatigue [20,22,23], sleep [21,22], tender points count [24,26,29,30], pain [18,24e26,29,30] in the Fibromyalgia Impact Questionnaire (FIQ) scores [18,22,24,26,28], and mood disorders [18,23,29,30]. In addition, a reduction in oxidative parameters was also observed [22,26,27]. ...
... The CoQ10 dosage in these studies ranged from 40 mg to 300 mg/day, and the follow-up went from 6 to 36 weeks. After CoQ10 supplementation, FM patients observed improvement in fatigue [20,22,23], sleep [21,22], tender points count [24,26,29,30], pain [18,24e26,29,30] in the Fibromyalgia Impact Questionnaire (FIQ) scores [18,22,24,26,28], and mood disorders [18,23,29,30]. In addition, a reduction in oxidative parameters was also observed [22,26,27]. ...
View
... Recently, some emerging evidence has suggested a possible association between low peripheral serotonin and fatigue. On the one hand, low peripheral serotonin has been found during post-infectious fatigue following COVID-19 and other viruses (5) and in fibromyalgia patients (6,7). On the other hand, peripheral serotonin, once believed to mainly regulate intestinal mobility, is now understood to play key roles in regulating peripheral energy metabolism (8)(9)(10)(11)(12). ...
... As a putative bridge between carnitine and S-5-HT, increased energy production allowed by L-carnitine supplementation might promote peripheral 5-HT synthesis. This idea is indirectly supported by a study in fibromyalgia patients where supplementation with another key mitochondrial agent, CoQ 10 , increased low peripheral serotonin values (7). ...
Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome
Article
Full-text available
  • Mar 2024
Background Fatigue of unknown origin is a hallmark symptom in chronic fatigue syndrome (CFS) and is also found in 20% of hypothyroidism patients despite appropriate levothyroxine treatment. Here, we suggest that in these disorders, peripheral serotonin levels are low, and elevating them to normal range with L-carnitine is accompanied with reduced fatigue. Methods We conducted a retrospective analysis of follow-up clinical data (CFS N=12; hypothyroidism with fatigue N=40) where serum serotonin and fatigue levels were compared before vs. after 7 weeks of oral L-carnitine supplementation. Results After L-carnitine, serotonin increased (8-fold in CFS, Sig. = 0.002, 6-fold in hypothyroidism, Sig. < 0.001) whereas fatigue decreased (2-fold in both CFS and hypothyroidism, Sig. = 0.002 for CFS, Sig. < 0.001 for hypothyroidism). There was a negative correlation between serotonin level and fatigue (for CFS, rho = -0.49 before and -0.67 after L-carnitine; for hypothyroidism, rho = -0.24 before and -0.83 after L-carnitine). Conclusions These findings suggest a new link between low peripheral serotonin, L-carnitine, and fatigue.
View
... Although the precise role of Mfn2 in sustaining CoQ10 and mitochondrial function remains unclear, a study conducted by Mourier et al. [79] has revealed an unexpected function of Mfn2 in maintaining the terpenoid biosynthesis pathway, critical for CoQ10 production. Furthermore, the signaling pathway related to peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) has been demonstrated to affect Mfn2 expression, redirecting research focus from investigating the causes of FM to exploring potential strategies for symptom management [79][80][81][82]. ...
Exploring the TyG Index and the Homeostasis Model Assessment of Insulin Resistance as Insulin Resistance Markers: Implications for Fibromyalgia Management and Understanding—A Narrative Review
Article
Full-text available
  • Feb 2025
Fibromyalgia (FM) is a chronic musculoskeletal disease with a higher prevalence among women. To date, there has been no definitive laboratory or imaging assessment for FM, and hence, the diagnosis criteria for FM remained based on subjective assessment of symptoms with high overlap with other rheumatological disorders. Many patients with FM suffer from metabolic disorders leading to insulin resistance (IR). There have been several methods to assess IR, among which the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the triglyceride–glucose (TyG) index have been used more frequently, with the latter being more available and cost-effective. As higher IR has been reported for patients with FM with various mechanisms, in this review, we sought to investigate the association between IR and FM using the current evidence. One of the possible underlying mechanisms of this association might be mitochondrial dysfunction and oxidative stress observed in IR conditions and its role in FM. Studies have also shown that IR indices are higher in patients with FM, compared to healthy controls, while higher HOMA-IR levels were also reported for higher severities of FM based on Fibromyalgia Impact Questionnaire—Revised (FIQR) scores. While these findings suggest the possible involvement of IR in FM pathophysiology and add to the value of IR measurement in FM clinical assessment, further large-scale studies are needed to establish a definitive causal association between them.
View
... By improving muscle metabolic parameters, the intake of Coenzyme Q10 can reduce pain and asthenia. The improvement in depressive symptoms after Coenzyme Q10 supplementation seems to be linked to the normalization of serotonin levels in the central nervous system [81,82]. The combined supplementation of Coenzyme Q10, B vitamins (B12, B6, B1), folic acid, and carnitine should have superior and synergistic effects compared to individual nutrient supplementation, resulting in an even greater clinical efficacy in the treatment of FM. ...
Management of Fibromyalgia: Novel Nutraceutical Therapies Beyond Traditional Pharmaceuticals
Article
Full-text available
  • Jan 2025
The pathophysiology of fibromyalgia, a condition that causes chronic pain throughout the body, involves abnormal pain signaling, genetic predispositions, and abnormal neuroendocrine function, significantly impairing quality of life. Fibromyalgia is commonly characterized by musculoskeletal pain, chronic fatigue, and severe sleep alterations. Changes in the central processing of sensory input and defects in endogenous pain inhibition could be the basis of enhanced and persistent pain sensitivity in individuals with fibromyalgia. The term central sensitivity syndrome was chosen as an umbrella term for fibromyalgia and related illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome, migraine, and irritable bowel syndrome. Given the substantial impact of fibromyalgia on health, there is a need for new prevention and treatment strategies, particularly those involving bioavailable nutraceuticals and/or phytochemicals. This approach is particularly important considering the adverse effects of current fibromyalgia pharmaceutical treatments, such as antidepressants and anticonvulsants, which can lead to physical dependence and tolerance. Natural products have recently been considered for the design of innovative analgesics and antinociceptive agents to manage fibromyalgia pain. Polyphenols show promise in the management of neuropathic pain and fibromyalgia, especially considering how anti-inflammatory treatments, including corticosteroids and nonsteroidal medical drugs, are effective only when inflammatory processes coexist and are not recommended as the primary treatment for fibromyalgia.
View
... A randomised controlled clinical study by Cordero et al. [33] in 20 fibromyalgia patients found supplementation with CoQ10 (300 mg/day for 40 days) significantly reduced (by more than 50%) pain and fatigue; there was a corresponding improvement in mitochondrial ATP energy generation and reduced oxidative stress and inflammation. In this study, psychopathological symptoms (including depression) were also significantly improved; this was linked to the effect of supplemental CoQ10 in reducing oxidative stress and inflammation, as well as increased levels of serotonin [35,36]. In addition, Cordero et al. [37] correlated headache symptoms with reduced CoQ10 levels and increased oxidative stress in fibromyalgia patients, with headache symptoms and oxidative stress levels significantly improving following CoQ10 supplementation (300 mg/day for 3 months). ...
Coenzyme Q10 and Autoimmune Disorders: An Overview
Article
Full-text available
Some 90 autoimmune disorders have been described in medical literature, affecting most of the tissues within the body. Autoimmune disorders may be difficult to treat, and there is a need to develop novel therapeutic strategies for these disorders. Autoimmune disorders are characterised by mitochondrial dysfunction, oxidative stress, and inflammation; there is therefore a rationale for a role for coenzyme Q10 in the management of these disorders, on the basis of its key role in normal mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. In this article, we have therefore reviewed the potential role of CoQ10, in terms of both deficiency and/or supplementation, in a range of autoimmune disorders.
View
... A randomised controlled clinical study by Cordero et al. [75] conducted in 20 FM patients found supplementation with CoQ10 (300 mg/day for 40 days) significantly reduced (by more than 50%) chronic pain and fatigue; there was a corresponding improvement in mitochondrial energy generation and reduced oxidative stress and inflammation. In this study, psychopathological symptoms (including anxiety/depression) were also significantly improved; this was linked to the effect of supplemental CoQ10 in reducing oxidative stress and inflammation, as well as increased levels of serotonin [76,77]. In addition, Cordero et al. [78] correlated headache symptoms with reduced CoQ10 levels and increased oxidative stress in the FM patients, with headache symptoms and oxidative stress levels significantly improved following CoQ10 supplementation (300 mg/day for 3 months). ...
Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview
Article
Full-text available
Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.
View
Effects of Coenzyme Q10, Tryptophan, and Magnesium Supplementation on Fatigue in Patients with Fibromyalgia - A Randomized Trial
Article
  • Mar 2025
Fibromyalgia (FM) is a prevalent and multifactorial condition requiring pharmacological and non-pharmacological interventions for its management. Coenzyme Q10 (CoQ10), magnesium, and tryptophan are associated with FM symptoms, but their combined effects in this condition are poorly understood. The objective of the study was to assess the effects of CoQ10, tryptophan, and magnesium supplementation in patients with FM. This single-center, randomized, double-blind, placebo-controlled, two-period, two-sequence crossover study included adult patients diagnosed with FM for at least two years. The study comprised two periods of three months each, and a one-month washout period between them. Participants were randomized to receive the dietary supplement or placebo. The primary endpoint was the change in the item fatigue of the combined index of fibromyalgia impact in patients (ICAF). Secondary outcomes included changes in the remaining ICAF factors and items and in the total score. Of 110 enrolled patients, 89 (mean age: 51.0 years; 96.6% women) completed the study. Most participants (94.4%) were on pharmacological treatment for FM. Fatigue improved significantly in the placebo group, with a non-significant reduction in the dietary supplement group. Pain intensity significantly decreased in both groups, while sleep quality and functional impact showed a significant reduction in the dietary supplement group. The ICAF total score improved significantly after 3 months of receiving the dietary supplement. Adverse events (n = 35) were mild and homogenously distributed between groups. The dietary supplement was efficacious in improving physical aspects of FM, including pain, sleep quality, and impact, and showed good tolerability.
View
New ways to repurpose salmeterol in an animal model of fibromyalgia
Article
  • Nov 2024
Background Fibromyalgia (FM) is a syndrome of pervasive chronic pain accompanied by low mood, sleep disorders, and cognitive decline. The dysfunction of central pain processing systems along with neurotransmitter disturbances are possible contributing mechanisms. Genetic polymorphism of the 𝛽2 adrenergic receptors is reported in FM patients. It is reported that chronic β2 agonists administration is effective for neuropathic pain alleviation. No current information, however, exists on their potential to alleviate nociplastic pain, such as FM. Therefore, the purpose of the current study is to examine salmeterol's potential antiallodynic effects in experimentally produced FM and explore some of the possible contributing mechanisms. Methods Thirty rats are allocated into three groups ( n = 10): a normal group, a reserpine group that received reserpine (1 mg/kg; s.c.) for 3 days, and a reserpine + salmeterol group that received salmeterol (1 mg/kg; i.p.) for 21 consecutive days following last reserpine injection. Results Reserpine administration resulted in behavioral and biochemical changes consistent with FM, including thermal and mechanical hyperalgesia, depressive behavior, and motor incoordination. This is coupled with disturbed spinal monoamine levels, depressed cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, disturbed mitochondrial function/dynamics, and compromised blood‐nerve barrier integrity. Treatment with salmeterol conceivably reversed these effects. Conclusion β2 receptor agonists such as salmeterol could be regarded as a promising strategy for the management of FM.
View
View
View
Coenzyme Q10 Depletion in Medical and Neuropsychiatric Disorders: Potential Repercussions and Therapeutic Implications
Article
Full-text available
  • Jun 2013
  • MOL NEUROBIOL
Coenzyme Q10 (CoQ10) is an antioxidant, a membrane stabilizer, and a vital cofactor in the mitochondrial electron transport chain, enabling the generation of adenosine triphosphate. It additionally regulates gene expression and apoptosis; is an essential cofactor of uncoupling proteins; and has anti-inflammatory, redox modulatory, and neuroprotective effects. This paper reviews the known physiological role of CoQ10 in cellular metabolism, cell death, differentiation and gene regulation, and examines the potential repercussions of CoQ10 depletion including its role in illnesses such as Parkinson's disease, depression, myalgic encephalomyelitis/chronic fatigue syndrome, and fibromyalgia. CoQ10 depletion may play a role in the pathophysiology of these disorders by modulating cellular processes including hydrogen peroxide formation, gene regulation, cytoprotection, bioenegetic performance, and regulation of cellular metabolism. CoQ10 treatment improves quality of life in patients with Parkinson's disease and may play a role in delaying the progression of that disorder. Administration of CoQ10 has antidepressive effects. CoQ10 treatment significantly reduces fatigue and improves ergonomic performance during exercise and thus may have potential in alleviating the exercise intolerance and exhaustion displayed by people with myalgic encepholamyletis/chronic fatigue syndrome. Administration of CoQ10 improves hyperalgesia and quality of life in patients with fibromyalgia. The evidence base for the effectiveness of treatment with CoQ10 may be explained via its ability to ameliorate oxidative stress and protect mitochondria.
View
Can Coenzyme Q 10 Improve Clinical and Molecular Parameters in Fibromyalgia?
Article
Full-text available
  • Mar 2013
  • ANTIOXID REDOX SIGN
Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide. Its pathophysiological mechanisms are difficult to identify and current drug therapies demonstrate limited effectiveness. Both mitochondrial dysfunction and coenzyme Q10 (CoQ10) deficiency have been implicated in FM pathophysiology. We have investigated the effect of CoQ10 supplementation. We carried out a randomized, double-blind, placebo-controlled trial to evaluate clinical and gene expression effects of forty days of CoQ10 supplementation (300mg/day), in twenty FM patients. This study was registered with controlled-trials.com (ISRCTN 21164124). An important clinical improvement was shown after CoQ10 vs placebo treatment showing a reduction of FIQ (P<0.001), and a most prominent reduction in pain (P<0.001), fatigue and morning tiredness (P˂0.01) subscales from FIQ. Furthermore, we observed an important reduction in pain visual scale (P<0.01) and a reduction in tender points (P<0.01), including recovery of inflammation, antioxidant enzymes, mitochondrial biogenesis and AMPK gene expression levels, associated with phosphorilation of AMPK activity. These results lead to the hypothesis that CoQ10 have a potential therapeutic effect in FM, and indicate new potential molecular targets for the therapy of this disease. AMPK could be implicated in the pathophysiology of FM.
View
Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: Amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation
Article
Full-text available
Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n = 10) and in healthy control subjects (n = 67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.
View
Correlation of serotonin levels in CSF, platelets, plasma, and urine
Article
Full-text available
  • Jun 2012
  • Biochim Biophys Acta
Neurotransmitter levels are best measured in the cerebrospinal fluid (CSF), but that requires an invasive procedure. Samples were collected from humans and rats. Eighteen women age 38-51years with fibromyalgia provided samples of CSF, plasma, platelets, and urine. Samples of CSF, plasma, platelets, and urine were also collected from Sprague-Dawley rats, adult male, 6months old. One group of rats was treated with p-chlorophenylalanine to decrease their levels of serotonin, and another group of rats was treated with amphetamine to increase their levels of serotonin. Methodological improvements include: 1) the use of siliconized glassware, plasticware, and tubing to prevent adsorption of serotonin, 2) the extraction of serotonin from the CSF, plasma, and platelets, 3) repeated washing of the platelets with an improved buffer, and 4) early morning sample collection. HPLC/MS was used to measure serotonin after extraction. For serotonin, the new method of measuring platelet levels resulted in a very high correlation with levels of serotonin in CSF in rats (r=0.97) and humans (r=0.97). There were lower correlations of levels of serotonin in CSF with levels in plasma (r=0.77 for rats and r=0.57 in humans) and urine (r=0.67 in rats and r=0.62 in humans). This method of measuring serotonin levels in platelets results in a very strong correlation with levels in CSF, so in most cases platelet measurements will be preferable since it is much less invasive to collect. Levels of serotonin in plasma and urine are significantly but less strongly correlated with levels in CSF.
View
The Role of Antidepressants in the Management of Fibromyalgia Syndrome
Article
Full-text available
  • Apr 2012
Background: The role of antidepressants in the management of fibromyalgia syndrome (FMS) still needs to be determined. Objective: The objective of this study was to provide a quantitative analysis (meta-analysis) of the efficacy and harms of antidepressants in the management of adult FMS patients. Data sources: The data sources used were the databases MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (until December 30, 2010), the reference lists of included articles, and the websites of the US National Institutes of Health (NIH) and the Pharmaceutical Research and Manufacturers of America (PhRMA). Study selection: Studies with a randomized controlled trial (RCT) design comparing any types of antidepressants with pharmacological placebo or head-to-head comparisons of different types of antidepressants in FMS patients were included. RCTs in which antidepressants were combined with any other defined treatment or antidepressants were tested against anything but drug placebo were excluded. Patients diagnosed with FMS according to predefined criteria of any age were included. To be included, studies had to assess at least one key domain of FMS (pain, sleep, fatigue, health-related quality of life [HRQOL]) as outcomes of efficacy and report total treatment discontinuation rates and/or dropout rates due to adverse events as outcomes for harms. Data extraction: Data were extracted according to protocols of previous systematic reviews on antidepressants in FMS. Methodology quality was assessed by the van Tulder score. Data synthesis: Standardized mean differences (SMD) were calculated for continuous outcomes by means and standard deviations and relative risks (RR) for 30% pain reduction and total dropout rate for comparisons of antidepressants with placebo. Examination of the combined results was performed by a random effects model. We used Cohen's categories to evaluate the magnitude of the effect size, calculated by SMD. Heterogeneity was tested by the I2 statistic. Thirty-five studies were included in the meta-analysis. The SMDs of serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) on pain, sleep, fatigue, depression and HRQOL were significant. Based on Cohen's categories, the effect size on pain was small and the ones on sleep, fatigue, depression and HRQOL were not substantial. 1481/3528 (42.0%) patients with SNRIs and 737/2304 (32.0%) patients with placebo reported a 30% pain reduction (number needed to treat [NNT] 10.0; 95% CI 8.00, 13.4; I2 = 4%). The RR of dropouts due to adverse events was 1.83 (95% CI 1.53, 2.18; I2 = 33%). The SMDs of selective serotonin reuptake inhibitors (SSRIs) on pain, sleep, depression and HRQOL were significant. Based on Cohen's categories, the effect sizes on pain, depression and HRQOL were small and the one on sleep not substantial. 72/198 (36.4%) patients with SSRIs and 40/194 (20.6%) patients with placebo reported a 30% pain reduction (NNT 6.3; 95% CI 4.1, 14.1). The RR of dropouts due to adverse events was 1.60 (95% CI 0.84, 3.04; I2 = 0%). The SMDs of tricyclic antidepressants (TCAs) on pain, sleep, fatigue and HRQOL were significant. Based on Cohen's categories, the effect sizes on pain and sleep were moderate and the ones on fatigue and HRQOL were small. 140/290 (48.3%) patients with TCAs and 70/252 (27.8%) patients with placebo reported a 30% pain reduction (NNT 4.9; 95% CI 3.5, 8.0). The RR of dropouts due to adverse events was 0.84 (95% CI 0.46, 1.52; I2 = 0%). Conclusions: The TCA amitriptyline and the SNRIs duloxetine and milnacipran are first-line options for the treatment of FMS patients. Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.
View
Coenzyme Q10 Displays Antidepressant-like Activity with Reduction of Hippocampal Oxidative/Nitrosative DNA Damage in Chronically Stressed Rats.
Article
  • Jan 2013
Unlabelled: Multiple evidences suggest that depression is accompanied by an induction of oxidative/nitrosative stress (O&NS) pathways and by a reduced antioxidant status. Coenzyme Q10 (CoQ10) is an essential cofactor in the mitochondrial electron transport pathway and has a powerful antioxidant capacity. Methods: This study investigated the effect of chronic treatment with CoQ10 (25, 50, 100 and 150 mg/kg/day, i.p. for 3 weeks) on depressive-like behavior and hippocampal, O&NS, and DNA damage, induced by chronic restraint stress (CRS), an experimental model of depression, in rats. Results: CoQ10 showed a significant antidepressant effect, as evidenced by amelioration of CRS-induced behavioral aberrations in forced swimming and open field tests, elevated corticosterone level and body weight loss. Moreover, CoQ10 dose-dependently restored the hippocampal catalase, glutathione peroxidase and reduced glutathione and decreased the hippocampal malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine levels, which indicated a potential protective effect of CoQ10 against hippocampal O&NS lipid peroxidation and DNA damage. Conclusion: CoQ10 possesses antidepressant activity and can protect against CRS-induced hippocampal DNA damage which could be mediated in part by maintaining mitochondrial function and its well documented antioxidant properties. Therefore, CoQ10 may have a potential therapeutic value for the management of depressive disorders. However, further research, is still required to characterize the mechanism of the antidepressant effect of CoQ10 and extend these results before the safe application in humans.
View
ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia
Article
  • Sep 2008
To evaluate the intracellular levels of the high energy adenosine triphosphate nucleotide ATP and essential divalent cations, calcium and magnesium, in platelets of patients affected by primary fibromyalgia syndrome (FMs). Platelet ATP and cation concentrations were measured in 25 patients affected by FMs and 25 healthy volunteers through a chemiluminescent and a fluorimetric assay, respectively. Significant lower ATP levels were observed inside platelets of FM patients (fmol ATP/plt: 0.0169+/-0.0012 vs. healthy controls, fmol ATP/plt: 0.0306+/-0.0023, mean+/-SEM) (*** P<0.0001). A trend towards higher calcium concentrations (P=0.06) together with significant increased magnesium levels were also reported in platelets of patients by comparison with controls (P=0.02). This preliminary study suggests that disturbances in the homeostasis of platelet ATP metabolism-signaling and calcium-magnesium flows might have a relevance in the pathogenesis of FMs.
View
The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis.
  • Jan 2012
  • 297
  • Hauser