Editorial
Oxidative Stress in Fibromyalgia: Pathophysiology and Clinical Implications
Estrés oxidativo en la fibromialgia: fisiopatología e implicaciones clínicas
Mario D. Cordero
Corresponding author
mdcormor@upo.es
Corresponding author at: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Carretera de Utrera, km 1, 41013 Sevilla, Spain.
Corresponding author at: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Carretera de Utrera, km 1, 41013 Sevilla, Spain.
Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Sevilla, Spain
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Cordero" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Mario D." "apellidos" => "Cordero" "email" => array:1 [ 0 => "mdcormor@upo.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Sevilla, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Carretera de Utrera, km 1, 41013 Sevilla, Spain." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estrés oxidativo en la fibromialgia: fisiopatología e implicaciones clínicas" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In general, oxidative stress is defined as the imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant defense mechanisms. These toxic molecules become highly reactive in their formation because of their altered number of unpaired valence electrons. It corresponds to the mitochondria to be the main producer of ROS, generating the bulk of the respiratory chain complexes I and III, following the flow of electrons between the two complexes. However, the production of ROS under physiological conditions becomes essential for maintaining life and a baseline level of ROS are involved in numerous mechanisms such as bactericidal activity of phagocytes or signal transduction, regulation of cell growth or the redox state of cells, including others.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> High levels of oxidative stress have been implicated as the primary and/or secondary event in numerous diseases such as rheumatoid arthritis, Parkinson's, Alzheimer's, atherosclerosis, cardiovascular diseases and diabetes mellitus.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Oxidative Stress in Fibromyalgia</span><p id="par0010" class="elsevierStylePara elsevierViewall">Fibromyalgia (FM) is a chronic pain syndrome accompanied by other symptoms such as depression, anxiety, fatigue or sleep disturbances. The diagnosis is based on the classification criteria established by the American College of Rheumatology 1990 (ACR). In Spain it has a high prevalence: 2.4% of the population over 20 years and a greater presence in women than in men, with a ratio of 21:1.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Despite its high prevalence, its etiology is still unknown and there are no effective treatments.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years oxidative stress has taken a leading role in the pathophysiology of FM.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Lipid peroxidation (LP) and carbonylated proteins, end products of membrane damage induced by ROS, are increased in the plasma of patients with FM.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> Furthermore, total antioxidant capacity or antioxidant enzymes such as superoxide dismutase (SOD) and catalase are decreased in the plasma of patients with FM.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> Research has been directed to the plasma or serum of patients as a study model, with a need for cellular models, as this is the place where activation and control of the ROS-producing machinery occur. In this regard, hydrogen peroxide (H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span>), as one of the free oxygen radicals that results from the oxygen of the ROS, has been found increased in neutrophils of patients with FM. Similarly, high levels of superoxide of mitochondrial origin (O<span class="elsevierStyleInf">2</span><span class="elsevierStyleSup">−</span>) have been observed in the peripheral blood mononuclear cells of patients with FM7. In this model, patients had low levels of CoQ<span class="elsevierStyleInf">10</span>, a vital element in the mitochondrial respiratory chain whose primary mission is the electron transport from complexes I and II to III, in addition to regulating the coupling of proteins, the pore transition and mitochondrial β-oxidation of fatty acids, an important antioxidant and membrane, so that a deficiency of the cell induces a drop in the activity of complex II<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>III, complex III, and complex IV, plus reduces the expression of mitochondrial proteins involved in oxidative phosphorylation, decreases mitochondrial membrane potential and increases the production of ROS.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">But, from a physiological point of view, what relationship exists between oxidative stress and the symptoms of FM? It is known that the PL reflects the intracellular production of ROS, and it is known that ROS are involved in the etiology of one of the major symptoms of fibromyalgia: pain. The superoxide radical plays an important role in the development of pain on one side by peripheral and central nervous system sensitization and thus induces an alteration of nociception, and on the other hand contributes to it through the activation of several cytokines such as TNF-α, IL-1β, and IL-68. The role of cytokines in FM has been widely discussed, although not as an etiologic mechanism, but as a factor in the worsening of symptoms.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">8,9</span></a> Although the mechanisms by which oxidative stress can alter muscle sensitivity are still unknown, it is possible that oxidative damage interferes with the muscles by reducing local nociceptors, which causes a decrease in the pain<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> threshold. On the other hand, PL has been associated with a typical symptom of FM: fatigue. High levels of LP, as well as an interesting correlation with this symptom, have been demonstrated in chronic fatigue syndrome, a disease with a high rate of comorbidity with FM.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Another characteristic of FM symptoms: depression, has shown a high correlation between LP in erythrocytes of patients with major depression and values obtained on the Hamilton depression<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> scale, a result consistent with those obtained in FM<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>. Interestingly, significant correlations are observed between the levels of antioxidants in both plasma and serum with respect to the score on a visual analogue pain scale, and the degree of morning stiffness by patients.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> On the other hand, LP in serum has demonstrated a high degree of correlation with the level of depression presented by patients with FM4, which shows the relationship between the balance of oxidants/antioxidants and symptoms of fibromyalgia.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Clinical Implications of Oxidative Stress in Fibromyalgia</span><p id="par0030" class="elsevierStylePara elsevierViewall">From a clinical standpoint, we want to focus on one aspect of FM which still is largely uncertain and is one of the main problems of this disease: lack of effective treatments. This leads the specialists to treat the symptoms of the disease rather than its causes, sometimes leading to a worsening of the disorders side-effects, and in many cases, these drugs induce an increase in oxidative stress. CoQ<span class="elsevierStyleInf">10</span> has been shown in in vitro experiments with peripheral blood mononuclear cells of patients with FM, either through its antioxidant role or by offsetting the deficit significantly, to reduce ROS levels and to induce a mitochondrial degradation pathway known as autophagic mitophagia.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This result, in spite of being an in vitro finding, could provide insights into the beneficial effect obtained in patients after administration of CoQ<span class="elsevierStyleInf">10</span> along with Gingko biloba shown by a pilot study in which there was a significant improvement in quality of life of patients.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Fatigue, one of the most typical symptoms of FM, has been reduced by treatment with CoQ<span class="elsevierStyleInf">10</span> in both animal and human physical fatigue models after exercise.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> It should also be noted that CoQ<span class="elsevierStyleInf">10</span> has been shown to reduce muscle pain induced by statins in patients,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and animal models have proven an anti-inflammatory and antinociceptive effect,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and CoQ<span class="elsevierStyleInf">10</span> has recently been observed to regulate the expression of certain pro-inflammatory cytokine genes such as TNF-α,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> whose role has already been described in FM.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> On the other hand, melatonin, an important molecule endogenously synthesized by the body and with antioxidant properties, has been shown to reduce pain levels in FM, as well as more complex and typical symptoms of this disease such as depression, anxiety or sleeping disturbances.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Antioxidant therapies have proven effective in many pathological processes in which oxidative stress plays an important role both primarily as secondarily. CoQ<span class="elsevierStyleInf">10</span>, Vitamin E or alpha-tocopherol, vitamin C or ascorbic acid, melatonin, SOD, vitamin A or retinol, glutathione, N-acetylcysteine, etc., are some of the antioxidants used in randomized trials of patients with a variety of diseases or co-treatment with drugs that induce side-effects, such as chemotherapy. CoQ<span class="elsevierStyleInf">10</span> has been applied successfully in clinical trials in pathological processes such as Parkinson,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Alzheimer,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Friedreich's ataxia,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> migrane,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> human disorder due to deficiency of CoQ<span class="elsevierStyleInf">10</span>,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> cardiomyopathy<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> or statin induced myopathies.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The lack of results showing negative side-effects or some degree of interference with other treatments in a good way to endorse the use of antioxidant therapies. However, in the case of FM, there are still no double blind and placebo controlled trials in which the possible mechanisms demonstrate the benefits of these therapies in general and of CoQ<span class="elsevierStyleInf">10</span> in particular. The sheer complexity of this disease makes it difficult to assess effectiveness of a single treatment, thus requiring a multidisciplinary therapeutic approach in which the use of antioxidants would acquire a role as co-treatment. Although oxidative stress in the FM is an accepted fact, its role in the disease from a physiological point of view is not yet clear, and the mechanism by which high levels of free radicals, low levels of antioxidants or both processes simultaneously can have effects on the worsening of symptoms is still unknown. Therefore, further studies are necessary in this regard, as well as the design of controlled trials on the therapeutic effect of antioxidants.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Oxidative Stress in Fibromyalgia" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical Implications of Oxidative Stress in Fibromyalgia" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of Interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Cordero MD. Estrés oxidativo en la fibromialgia: fisiopatología e implicaciones clínicas. Reumatol Clin. 2011. <span class="elsevierStyleInterRef" href="doi:10.1016/j.reuma.2010.12.007">doi:10.1016/j.reuma.2010.12.007</span>.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxidative stress: the paradox of aerobic life" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K.J. Davies" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochem Soc Symp" "fecha" => "1995" "volumen" => "61" "paginaInicial" => "1" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8660387" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Free radicals and antioxidants in normal physiological functions and human disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Valko" 1 => "D. Leibfritz" 2 => "J. Moncol" 3 => "M.T. Cronin" 4 => "M. Mazur" 5 => "J. Telser" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.biocel.2006.07.001" "Revista" => array:6 [ "tituloSerie" => "Int J Biochem Cell Biol" "fecha" => "2007" "volumen" => "39" "paginaInicial" => "44" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16978905" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Documento de consenso de la Sociedad Española de Reumatología sobre la fibromialgia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Rivera" 1 => "C. Alegre" 2 => "F.J. Ballina" 3 => "J. Carbonell" 4 => "L. Carmona" 5 => "B. Castel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1699-258X(06)73084-4" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2006" "volumen" => "2" "paginaInicial" => "S55" "paginaFinal" => "S66" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21794365" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Ozgocmen" 1 => "H. Ozyurt" 2 => "S. Sogut" 3 => "O. Akyol" 4 => "O. Ardicoglu" 5 => "H. Yildizhan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00296-005-0079-y" "Revista" => array:6 [ "tituloSerie" => "Rheumatol Int" "fecha" => "2006" "volumen" => "26" "paginaInicial" => "598" "paginaFinal" => "603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16283318" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Total antioxidant capacity and the severity of the pain in patients with fibromyalgia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "O. Altindag" 1 => "H. Celik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1179/135100006X116628" "Revista" => array:6 [ "tituloSerie" => "Redox Rep" "fecha" => "2006" "volumen" => "11" "paginaInicial" => "131" "paginaFinal" => "135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16805968" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "O.F. Sendur" 1 => "Y. Turan" 2 => "E. Tastaban" 3 => "C. Yenisey" 4 => "M. Serter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00296-008-0738-x" "Revista" => array:6 [ "tituloSerie" => "Rheumatol Int" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "629" "paginaFinal" => "633" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18853166" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.D. Cordero" 1 => "M. De Miguel" 2 => "A.M. Moreno Fernández" 3 => "I.M. Carmona López" 4 => "J. Garrido Maraver" 5 => "D. Cotán" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/ar2918" "Revista" => array:5 [ "tituloSerie" => "Arthritis Res Ther" "fecha" => "2010" "volumen" => "12" "paginaInicial" => "R17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20109177" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0120" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.D. Cordero" 1 => "M. de Miguel" 2 => "A.M. Moreno-Fernández" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2011" "volumen" => "136" "paginaInicial" => "252" "paginaFinal" => "256" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrated review of the association of cytokines with fibromyalgia and fibromyalgia core symptoms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "V. Menzies" 1 => "D.E. Lyon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/1099800409348328" "Revista" => array:6 [ "tituloSerie" => "Biol Res Nurs" "fecha" => "2010" "volumen" => "11" "paginaInicial" => "387" "paginaFinal" => "394" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19933683" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Fulle" 1 => "P. Mecocci" 2 => "G. Fano" 3 => "I. Vecchiet" 4 => "A. Vecchini" 5 => "D. Racciotti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2000" "volumen" => "29" "paginaInicial" => "1252" "paginaFinal" => "1259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11118815" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.E. Lister" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Int Med Res" "fecha" => "2002" "volumen" => "30" "paginaInicial" => "195" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12025528" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antifatigue effect of coenzyme Q10 in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "X. Fu" 1 => "R. Ji" 2 => "J. Dam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/jmf.2009.0049" "Revista" => array:6 [ "tituloSerie" => "J Med Food" "fecha" => "2010" "volumen" => "13" "paginaInicial" => "211" "paginaFinal" => "215" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20136457" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antifatigue effects of coenzyme Q10 during physical fatigue" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Mizuno" 1 => "M. Tanaka" 2 => "S. Nozaki" 3 => "H. Mizuma" 4 => "S. Ataka" 5 => "T. Tahara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.nut.2007.12.007" "Revista" => array:6 [ "tituloSerie" => "Nutrition" "fecha" => "2008" "volumen" => "24" "paginaInicial" => "293" "paginaFinal" => "299" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18272335" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of coenzyme q10 on myopathic symptoms in patients treated with statins" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Caso" 1 => "P. Kelly" 2 => "M.A. McNurlan" 3 => "W.E. Lawson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjcard.2006.12.063" "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "2007" "volumen" => "99" "paginaInicial" => "1409" "paginaFinal" => "1412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17493470" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of anti-angiogenic, anti-inflammatory and antinociceptive activity of coenzyme Q(10) in experimental animals" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.J. Jung" 1 => "E.H. Park" 2 => "C.J. Lim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1211/jpp/61.10.0017" "Revista" => array:6 [ "tituloSerie" => "J Pharm Pharmacol" "fecha" => "2009" "volumen" => "61" "paginaInicial" => "1391" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19814873" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Functions of coenzyme Q10 in inflammation and gene expression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Schmelzer" 1 => "I. Lindner" 2 => "G. Rimbach" 3 => "P. Niklowitz" 4 => "T. Menke" 5 => "F. Döring" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biofactors" "fecha" => "2008" "volumen" => "32" "paginaInicial" => "179" "paginaFinal" => "183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19096114" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melatonin therapy in fibromyalgia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.J. Reiter" 1 => "D. Acuna-Castroviejo" 2 => "D.X. Tan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Pain Headache Rep" "fecha" => "2007" "volumen" => "11" "paginaInicial" => "339" "paginaFinal" => "342" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17894923" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.W. Shults" 1 => "D. Oakes" 2 => "K. Kieburtz" 3 => "M.F. Beal" 4 => "R. Haas" 5 => "S. Plumb" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Neurol" "fecha" => "2002" "volumen" => "59" "paginaInicial" => "1541" "paginaFinal" => "1550" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12374491" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H. Gutzmann" 1 => "K.P. Kühl" 2 => "D. Hadler" 3 => "M.A. Rapp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-2002-19833" "Revista" => array:6 [ "tituloSerie" => "Pharmacopsychiatry" "fecha" => "2002" "volumen" => "35" "paginaInicial" => "12" "paginaFinal" => "18" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11819153" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.M. Cooper" 1 => "L.V. Korlipara" 2 => "P.E. Hart" 3 => "J.L. Bradley" 4 => "A.H. Schapira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-1331.2008.02318.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Neurol" "fecha" => "2008" "volumen" => "15" "paginaInicial" => "1371" "paginaFinal" => "1379" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19049556" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.S. Sandor" 1 => "L. Di Clemente" 2 => "G. Coppola" 3 => "U. Saenger" 4 => "A. Fumal" 5 => "D. Magis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1212/01.WNL.0000151975.03598.ED" "Revista" => array:6 [ "tituloSerie" => "Neurology" "fecha" => "2005" "volumen" => "64" "paginaInicial" => "713" "paginaFinal" => "715" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15728298" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Montini" 1 => "C. Malaventura" 2 => "L. Salviati" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc0800582" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "358" "paginaInicial" => "2849" "paginaFinal" => "2850" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18579827" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Keogh" 1 => "S. Fenton" 2 => "C. Leslie" 3 => "C. Aboyoun" 4 => "P. Macdonald" 5 => "Y.C. Zhao" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Heart Lung Circ" "fecha" => "2003" "volumen" => "12" "paginaInicial" => "135" "paginaFinal" => "141" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18705154" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000000700000005/v1_201305061627/S2173574311000086/v1_201305061627/en/main.assets" "Apartado" => array:4 [ "identificador" => "17335" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000700000005/v1_201305061627/S2173574311000086/v1_201305061627/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574311000086?idApp=UINPBA00004M" ]
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|---|---|---|---|
| 2024 November | 31 | 18 | 49 |
| 2024 October | 195 | 41 | 236 |
| 2024 September | 161 | 32 | 193 |
| 2024 August | 171 | 45 | 216 |
| 2024 July | 158 | 39 | 197 |
| 2024 June | 194 | 48 | 242 |
| 2024 May | 174 | 47 | 221 |
| 2024 April | 193 | 36 | 229 |
| 2024 March | 166 | 46 | 212 |
| 2024 February | 140 | 37 | 177 |
| 2024 January | 140 | 44 | 184 |
| 2023 December | 115 | 59 | 174 |
| 2023 November | 109 | 65 | 174 |
| 2023 October | 154 | 40 | 194 |
| 2023 September | 145 | 46 | 191 |
| 2023 August | 132 | 31 | 163 |
| 2023 July | 135 | 37 | 172 |
| 2023 June | 126 | 30 | 156 |
| 2023 May | 102 | 24 | 126 |
| 2023 April | 84 | 21 | 105 |
| 2023 March | 157 | 32 | 189 |
| 2023 February | 127 | 38 | 165 |
| 2023 January | 140 | 49 | 189 |
| 2022 December | 178 | 50 | 228 |
| 2022 November | 136 | 52 | 188 |
| 2022 October | 163 | 50 | 213 |
| 2022 September | 123 | 53 | 176 |
| 2022 August | 164 | 61 | 225 |
| 2022 July | 152 | 64 | 216 |
| 2022 June | 136 | 49 | 185 |
| 2022 May | 169 | 65 | 234 |
| 2022 April | 151 | 69 | 220 |
| 2022 March | 161 | 74 | 235 |
| 2022 February | 122 | 69 | 191 |
| 2022 January | 176 | 54 | 230 |
| 2021 December | 107 | 47 | 154 |
| 2021 November | 99 | 52 | 151 |
| 2021 October | 308 | 69 | 377 |
| 2021 September | 194 | 48 | 242 |
| 2021 August | 108 | 50 | 158 |
| 2021 July | 129 | 39 | 168 |
| 2021 June | 138 | 68 | 206 |
| 2021 May | 256 | 78 | 334 |
| 2021 April | 362 | 157 | 519 |
| 2021 March | 162 | 55 | 217 |
| 2021 February | 136 | 34 | 170 |
| 2021 January | 109 | 36 | 145 |
| 2020 December | 111 | 21 | 132 |
| 2020 November | 98 | 40 | 138 |
| 2020 October | 100 | 18 | 118 |
| 2020 September | 108 | 41 | 149 |
| 2020 August | 159 | 29 | 188 |
| 2020 July | 85 | 27 | 112 |
| 2020 June | 173 | 29 | 202 |
| 2020 May | 81 | 27 | 108 |
| 2020 April | 46 | 30 | 76 |
| 2020 March | 27 | 10 | 37 |
| 2020 February | 3 | 0 | 3 |
| 2020 January | 4 | 0 | 4 |
| 2019 September | 6 | 0 | 6 |
| 2019 June | 2 | 0 | 2 |
| 2019 March | 2 | 0 | 2 |
| 2019 January | 1 | 0 | 1 |
| 2018 May | 15 | 0 | 15 |
| 2018 April | 109 | 13 | 122 |
| 2018 March | 103 | 22 | 125 |
| 2018 February | 170 | 9 | 179 |
| 2018 January | 78 | 5 | 83 |
| 2017 December | 91 | 8 | 99 |
| 2017 November | 62 | 9 | 71 |
| 2017 October | 79 | 10 | 89 |
| 2017 September | 131 | 10 | 141 |
| 2017 August | 204 | 18 | 222 |
| 2017 July | 121 | 19 | 140 |
| 2017 June | 149 | 11 | 160 |
| 2017 May | 137 | 21 | 158 |
| 2017 April | 203 | 7 | 210 |
| 2017 March | 115 | 22 | 137 |
| 2017 February | 77 | 12 | 89 |
| 2017 January | 82 | 7 | 89 |
| 2016 December | 101 | 24 | 125 |
| 2016 November | 100 | 7 | 107 |
| 2016 October | 133 | 17 | 150 |
| 2016 September | 149 | 16 | 165 |
| 2016 August | 145 | 13 | 158 |
| 2016 July | 73 | 9 | 82 |
| 2016 June | 0 | 15 | 15 |
| 2016 May | 0 | 18 | 18 |
| 2016 April | 1 | 0 | 1 |
| 2016 March | 1 | 20 | 21 |
| 2015 December | 3 | 0 | 3 |
| 2015 October | 0 | 20 | 20 |
| 2015 September | 1 | 0 | 1 |
| 2015 August | 2 | 0 | 2 |
| 2015 July | 46 | 5 | 51 |
| 2015 June | 78 | 15 | 93 |
| 2015 May | 109 | 18 | 127 |
| 2015 April | 94 | 27 | 121 |
| 2015 March | 109 | 11 | 120 |
| 2015 February | 124 | 15 | 139 |
| 2015 January | 82 | 12 | 94 |
| 2014 December | 80 | 18 | 98 |
| 2014 November | 64 | 18 | 82 |
| 2014 October | 99 | 18 | 117 |
| 2014 September | 57 | 13 | 70 |
| 2014 August | 77 | 12 | 89 |
| 2014 July | 71 | 13 | 84 |
| 2014 June | 76 | 12 | 88 |
| 2014 May | 84 | 13 | 97 |
| 2014 April | 97 | 15 | 112 |
| 2014 March | 79 | 16 | 95 |
| 2014 February | 91 | 21 | 112 |
| 2014 January | 50 | 18 | 68 |
| 2013 December | 36 | 10 | 46 |
| 2013 November | 51 | 20 | 71 |
| 2013 October | 69 | 14 | 83 |
| 2013 September | 59 | 19 | 78 |
| 2013 August | 69 | 28 | 97 |
| 2013 July | 65 | 19 | 84 |
| 2013 June | 50 | 22 | 72 |
| 2013 May | 76 | 22 | 98 |
| 2013 April | 53 | 37 | 90 |
| 2013 March | 47 | 21 | 68 |
| 2013 February | 38 | 15 | 53 |
| 2013 January | 53 | 23 | 76 |
| 2012 December | 37 | 29 | 66 |
| 2012 November | 26 | 19 | 45 |
| 2012 October | 24 | 9 | 33 |
| 2012 September | 15 | 1 | 16 |
| 2012 July | 3 | 0 | 3 |
| 2012 June | 7 | 0 | 7 |
| 2012 May | 8 | 0 | 8 |
| 2012 April | 8 | 0 | 8 |
| 2012 March | 8 | 0 | 8 |
| 2012 February | 6 | 0 | 6 |
| 2012 January | 8 | 0 | 8 |
| 2011 December | 12 | 0 | 12 |
| 2011 November | 9 | 0 | 9 |
| 2011 October | 8 | 0 | 8 |
Show all
