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Campisi, L.;  Motta, C.L. Coenzyme Q10 in Fibromyalgia. Encyclopedia. Available online: (accessed on 21 June 2024).
Campisi L,  Motta CL. Coenzyme Q10 in Fibromyalgia. Encyclopedia. Available at: Accessed June 21, 2024.
Campisi, Luca, Concettina La Motta. "Coenzyme Q10 in Fibromyalgia" Encyclopedia, (accessed June 21, 2024).
Campisi, L., & Motta, C.L. (2022, December 07). Coenzyme Q10 in Fibromyalgia. In Encyclopedia.
Campisi, Luca and Concettina La Motta. "Coenzyme Q10 in Fibromyalgia." Encyclopedia. Web. 07 December, 2022.
Coenzyme Q10 in Fibromyalgia

The coenzyme Q10 is a naturally occurring benzoquinone derivative widely prescribed as a food supplement for different physical conditions and pathologies. Thanks to its favourable combination of functional activity and safety profile, it is widely prescribed for an ever increasing number of physical conditions. Ageing, myopathy, cardiomyopathy, high blood pressure, dyslipidemia, migraine, diabetes, infertility, Friedreich's ataxia, and neurologic disorders like Parkinson’s and Huntington’s diseases, are but a few examples that today prompt practitioners to prescribe CoQ10. To this already extensive list, fibromyalgia has been added, once it has been clear that CoQ10 deficiency and mitochondrial dysfunction are both implicated in its pathophysiology. 

ubiquinone ubiquinol coenzyme Q CoQ10

1. Fibromyalgia: Key Characteristics and Therapeutic Approaches

Fibromyalgia (FM) is a pathology characterized by chronic and widespread musculoskeletal pain, often associated with asthenia and fatigue and a large set of somatic and neuro-vegetative symptoms. Sleep disorders are also present, characterized by frequent nocturnal awakenings which exacerbate the fatigue condition. In particular, the so-called alpha-delta anomaly is considered to be specific to FM, as once deep sleep is reached, characterized by delta waves at the electroencephalogram, there is a sharp return to superficial sleep, characterized by alpha waves. Cognitive disorders are present in the majority of patients, being related to difficulty in concentration and short-term memory loss [1].
To date, the prevalence of FM is estimated between 5 and 7%, while the incidence level ranges between 7–11 cases per 1000 people per year. It is more frequent in women than in men, with 11 vs. 7 cases per 1000 people, respectively [2][3]. Moreover, it can develop at any age. Actually, a juvenile fibromyalgia syndrome (JFM) is known constituting a complex condition that affects approximately 2–7% of school-aged children showing chronic musculoskeletal and diffuse pain, fatigue, and sleep and mood disturbances [4]. At the same time, FM can also be diagnosed in people at an advanced age. According to some reports, the prevalence of FM reaches a peak between the age of 55–65 years, and the main challenge is a timely and correct diagnosis as patients are frequently identified with rheumatoid arthritis, arthrosis, and rheumatic polymyalgia [5]. Obesity is also commonly associated with FM [6], with a prevalence ranging from 47 to 73% [7]. Stress, depression, anxiety, chronic sleep deprivation, and low physical activity have been linked to an increase in body weight in FM patients. Vincent and co-workers recently assessed the complex relationship between BMI, physical, and psychological factors in these patients but failed to highlight a clear relationship. In fact, they found that with an increase in BMI, it becomes more difficult for the patient to engage in physical activity, leading to a worsening of the symptoms of FM [7].
Currently, the diagnosis of FM is carried out according to the American College of Rheumatology (ACR) 2016 criteria, based on the scores of the widespread pain index (WPI) and the symptom severity scale (SSS) [8]. Mainly based on clinical parameters, these diagnostic criteria frequently overlap with those of other diseases, thus, making FM hard to uncover. In fact, on average, a period of 2.3 years from the first complaint is necessary to get to a definitive diagnosis, excluding those diseases having symptoms, but not causes, common to FM by the evaluation of selected markers.
For some time now, researchers have been calling for specific biomarkers. As thoroughly reviewed by Ablin and co-workers, it should be possible to highlight both a predisposition to FM (from a genetic point of view) and the manifestations of the disease. However, those investigated so far, including serological alterations and instrumental investigations, are for research purposes only [9].
The etiology of FM has not yet been fully understood, and uncertainty still exists concerning the pathophysiological framework. The preeminent hypothesis calls into question a dysregulation in the mechanisms of pain control by the central nervous system (CNS) [10][11][12][13][14][15][16][17][18], while according to other studies, FM would be supported by an inflammation of the small peripheral fibers [19].
Anyhow, FM is clearly characterized by mitochondrial dysfunction [20]. Sprott and co-workers demonstrated a change in the number and size of mitochondria in patients with symptomatic FM [21], and this evidence has been corroborated by additional studies, proving reduced mitochondrial DNA concentrations and CoQ10 levels accompanied by the increased expression of pro-inflammatory interleukins IL-1β and IL-18, higher levels of TNF-α [22], and the activation of NLRP3 (NOD-like receptor family, pyrin domain containing 3) and caspase-1. Also, Bullon and co-workers demonstrated that AMPK was not phosphorylated in the fibroblasts of FM patients, and this was in charge of decreased mitochondrial biogenesis, reduced oxygen consumption, decreased antioxidant-enzyme-expression levels, and mitochondrial dysfunction. Moreover, AMPK impairment also results in a marked NLRP3 inflammasome protein activation and a subsequent increase in the serum levels of IL-1β and IL-18 [23][24].
The multifaceted nature of FM requires a multimodal and multidisciplinary approach, mainly aimed at reducing the severity of the symptoms. However, on the basis of the scientific evidence available to date, there are no fully satisfying protocols. Moreover, poor adherence to the therapeutic indications and the presence of comorbidities are two very frequent factors that can modulate the worsening of symptomatology, leading to its chronicity [25][26][27][28].
Over the last decade, the use of personalized dietary regimes has become increasingly important. The supplementation of minerals, such as selenium, zinc, iron, and magnesium, but also vitamins like B9, B12, A, and D, as well as antioxidants, is pursued to complement the nutritional strategy, avoiding nutritional deficits, taking control of oxidative stress, and supporting the immune system [29][30][31][32][33]. Among the plethora of compounds exploited for their antioxidant properties, CoQ10 has the preeminent role of supplementing FM patients, as is thoroughly discussed below.

2. Coenzyme Q10 as a Key Functional Derivative

Coenzyme Q (CoQ) is a widely distributed naturally occurring lipophilic benzoquinone, firstly discovered by Crane and co-workers more than 60 years ago in beef mitochondria [34]. From a chemical point of view, the molecule is characterized by the presence of a quinoid structure, bearing a main side chain comprised of the repetition of several isoprenyl units. As for humans and many mammals, 10 residues are featured in the predominant form of the coenzyme, while other homologous forms are also present. Most of the CoQ10 in our body is produced endogenously, but a small amount is also ingested daily through the diet, being mainly present in meat and fish and, in much lower quantities, in some vegetables. Due to its wide prevalence in living organisms, this coenzyme is further referred to as ubiquinone [35].
Since the first pioneering study by Crane and co-workers, the crucial function of CoQ10 in the mechanisms of ATP production at the mitochondrial level was deciphered and acknowledged. In particular, the intense research activity carried out by Peter Mitchell, who, thanks to these studies, was awarded the Nobel Prize, clarified CoQ10 role as a key cofactor in the oxidative phosphorylation.
As thoroughly reviewed by several authors [36][37][38], CoQ10 acts as a mobile electron carrier in the electron transfer chain at the inner mitochondrial membrane, but it is also located in blood lipoproteins and cell membranes, where it plays a key antioxidant role once in its reduced form. Indeed, as CoQ10H2, it is able to quench free radicals and regenerate α-tocopherol and ascorbate [39][40][41]. Several NAD(P)H-dependent reductases ensure the generation of ubiquinol from ubiquinone, possibly via the ubisemiquinone intermediate, depending on the oxidation state of the cofactor (Figure 1). They include NAD(P)H:quinone reductase 1 (NQO1), catalyzing the reduction of the coenzyme to CoQH2 through a two-electron reaction, and NADH-cytochrome b5 reductase and NADPH-cytochrome P450 reductase, which are one-electron reductases [42][43][44][45][46][47][48]. Combined with ubiquinol, these enzymes give rise to the trans-plasma membrane antioxidant system, contributing to the maintenance of the cell antioxidant activities.
Figure 1. Redox cycling of Coenzime Q10.
In addition to redox activity, more recent data revealed that CoQ10 influences the expression of a significant number of genes. Investigated in HeLa cells by Gorelick and co-workers, it was proved to alter 264 sequences, enriching, in particular, lipid-related genes [49]. Using the human intestinal cell line CaCo-2, Groneberg and co-workers demonstrated that CoQ10 treatment increases the expression of 694 genes encoding proteins involved in cell signaling, intermediary metabolism, transport, transcription control, disease mutation, phosphorylation, embryonal development, and binding [50][51], thus, confirming the crucial functional role of this compound. 

The number of investigations aiming at demonstrate the effectiveness of CoQ10 in the management of FM has been increasing over time, outlining a positive causal relationship between the amount of its supplementation and the relief in FM symptoms, first and foremost the feeling of fatigue. Therefore, according on the outcomes obtained so far, CoQ10 might be reasonably regarded as the gold standard supplement for people affected by FM.

However, a closer look at the available data highlights the lack of a sound and clear scientific basis justifying this trumpeted claim. Actually, most, but not all, the authors highlighted reduced levels of CoQ10 in FM patients, therefore the consensus of the scientific community on this condition is not unanimous. Moreover, scientific investigations claiming the functional efficacy of this supplementation suffers from clear and obvious limits. In particular, besides biased reading of the experimental outcomes, the number of patients enrolled in the studies are often limited, even consisting of a single patient [94], thus inadequate to provide evidences expendable for the whole FM population. Therefore, prospective and randomized trial with hundreds of patients per study group are now required, to corroborate the efficacy of CoQ10 in the management of FM observed in pilot studies.


  1. Häuser, W.; Ablin, J.; Fitzcharles, M.-A.; Littlejohn, G.; Luciano, J.V.; Usui, C.; Walitt, B. Fibromyalgia. Nat. Rev. Dis. Prim. 2015, 13, 15022.
  2. Marques, A.P.; de Sousa do Espirito Santo, A.; Berssaneti, A.A.; Matsutani, L.A.; Yuan, S.L.K. Prevalence of fibromyalgia: Literature review update. Rev. Bras. Reumatol. Engl. Ed. 2017, 57, 356–363.
  3. Creed, F. A review of the incidence and risk factors for fibromyalgia and chronic widespread pain in population-based studies. PAIN 2020, 161, 1169–1176.
  4. Kashikar-Zuck, S.; Ting, T.V. Juvenile fibromyalgia: Current status of research and future developments. Nat. Rev. Rheumatol. 2014, 10, 89–96.
  5. Jacobson, S.A.; Simpson, R.G.; Lubahn, C.; Hu, C.; Belden, C.M.; Davis, K.J.; Nicholson, L.R.; Long, K.E.; Osredkar, T.; Lorton, D. Characterization of fibromyalgia symptoms in patients 55 to 95 years old: A longitudinal study showing symptom persistence with suboptimal treatment. Aging Clin. Exp. Res. 2015, 27, 75–82.
  6. Ursini, F.; Naty, S.; Grembiale, R.D. Fibromyalgia and obesity: The hidden link. Rheumatol. Int. 2011, 31, 1403–1408.
  7. Vincent, A.; Clauw, D.; Oh, T.H.; Whipple, M.O.; Toussaint, L.L. Decreased physical activity attributable to higher body mass index influences fibromyalgia symptoms. PM R 2014, 6, 802–807.
  8. Salaffi, F.; Di Carlo, M.; Farah, S.; Atzeni, F.; Buskila, D.; Ablin, J.N.; Häuser, W.; Sarzi-Puttini, W. Diagnosis of fibromyalgia: Comparison of the 2011/2016 ACR and AAPT criteria and validation of the modified Fibromyalgia Assessment Status. Rheumatology 2020, 59, 3042–3049.
  9. Ablin, J.N.; Buskila, D.; Clauw, D.J. Biomarkers in fibromyalgia. Curr. Pain Headache Rep. 2009, 13, 343–349.
  10. Harris, R.E.; Clauw, D.J.; Scott, D.J.; McLean, S.A.; Gracely, R.H.; Zubieta, J.K. Decreased central mu-opioid receptor availability in fibromyalgia. J. Neurosci. 2007, 27, 10000–10006.
  11. Watkins, L.R.; Hutchinson, M.R.; Rice, K.C.; Maier, S.F. The “toll” of opioid-induced glial activation: Improving the clinical efficacy of opioids by targeting glia. Trends Pharmacol. Sci. 2009, 30, 581–591.
  12. Harris, R.E.; Sundgren, P.C.; Craig, A.D.; Kirshenbaum, E.; Sen, A.; Napadow, V.; Clauw, D.J. Elevated insular glutamate (Glu) in fibromyalgia (FM) is associated with experimental pain. Arthritis Rheum. 2009, 60, 3146–3152.
  13. Foerster, B.R.; Petrou, M.; Edden, R.A.; Sundgren, P.C.; Schmidt-Wilcke, T.; Lowe, S.E.; Harte, S.E.; Clauw, D.J.; Harris, R.E. Reduced insular gamma-aminobutyric acid in fibromyalgia. Arthritis Rheum. 2012, 64, 579–583.
  14. Petrovic, P.; Kalso, E.; Petersson, K.M.; Ingvar, M. Placebo and opioid analgesia-- imaging a shared neuronal network. Science 2002, 295, 1737–1740.
  15. Littlejohn, G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat. Rev. Rheumatol. 2015, 11, 639–648.
  16. Guedj, E.; Taieb, D.; Cammilleri, S.; Lussato, D.; de Laforte, C.; Niboyet, J.; Mundler, O. 99mTc-ECD brain perfusion SPECT in hyperalgesic fibromyalgia. Eur. J. Nucl. Med. Mol. Imaging 2007, 34, 130–134.
  17. Gracely, R.H.; Petzke, F.; Wolf, J.M.; Clauw, D.J. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002, 46, 1333–1343.
  18. Feraco, P.; Bacci, A.; Pedrabissi, F.; Passamonti, L.; Zampogna, G.; Pedrabissi, F.; Malavolta, N.; Leonardi, M. Metabolic abnormalities in pain-processing regions of patients with fibromyalgia: A 3T MR spectroscopy study. Am. J. Neuroradiol. 2011, 32, 1585–1590.
  19. Üçeyler, N.; Zeller, D.; Kahn, A.-K.; Kewenig, S.; Kittel-Schneider, S.; Schmid, A.; Casanova-Molla, J.; Reiners, K.; Sommer, C. Small fibre pathology in patients with fibromyalgia syndrome. Brain 2013, 136, 1857–1867.
  20. Castro-Marrero, J.; Cordero, M.D.; Saez-Francas, N.; Jimenez-Gutierrez, C.; Auilar-Montilla, F.J.; Aliste, L.; Alegre-Martin, J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid. Redox Signal 2013, 19, 1855–1860.
  21. Sprott, H.; Salemi, S.M.; Gay, R.E.; Bradley, L.A.; Alarcon, G.S.; Oh, S.J.; Michel, B.A.; Gay, S. Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres. Ann. Rheum. Dis. 2004, 63, 245–251.
  22. Cordero, M.D.; De Miguel, M.; Moreno Fernández, A.M.; Carmona López, I.M.; Maraver, J.G.; Cotán, D.; Gómez Izquierdo, L.; Bonal, P.; Campa, F.; Bullon, P.; et al. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: Implications in the pathogenesis of the disease. Arthritis Res. Ther. 2010, 12, R17.
  23. Bullon, P.; Alcocer-Gómez, E.; Carrión, A.M.; Marín-Aguilar, F.; Garrido-Maraver, J.; Román-Malo, L.; Ruiz-Cabello, J.; Culic, O.; Ryffel, B.; Apetoh, L.; et al. AMPK phosphorylation modulates pain by activation of NLRP3 inflammasome. Antioxid. Redox Signal 2016, 24, 157–170.
  24. Alcocer-Gómez, E.; Sánchez-Alcazar, J.A.; Battino, M.; Bullón, P.; Cordero, M.D. Aging-related changes in inflammatory and LKB1/AMPK gene expression in fibromyalgia patients. CNS Neurosci. Ther. 2014, 20, 476–478.
  25. Macfarlane, G.J.; Kronisch, C.; Dean, L.E.; Atzeni, F.; Hauser, W.; Flu, E.; Cho, E.; Kosek, E.; Amris, K.; Branco, J.; et al. EULAR revised recommendations for the management of fibromyalgia. Ann. Rheum. Dis. 2017, 76, 318–328.
  26. Hauser, W.; Klose, P.; Langhorst, J.; Moradi, B.; Steinbach, M.; Schiltenwolf, M.; Busch, A. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: A systematic review and meta-analysis of randomised controlled trials. Arthritis Res. Ther. 2010, 12, R79.
  27. Cazzola, M.; Atzeni, F.; Salaffi, F.; Stisi, S.; Cassisi, G.; Sarzi-Puttini, P. Which kind of exercise is best in fibromyalgia therapeutic programmes? A practical review. Clin. Exp. Rheumatol. 2010, 28, S117–S124.
  28. Larsson, A.; Palstam, A.; Löfgren, M.; Ernberg, M.; Bjersing, J.; Bileviciute-Ljungar, I.; Gerdle, B.; Kosek, E.; Mannerkorpi, K. Resistance exercise improves muscle strength, health status and pain intensity in fibromyalgia--a randomized controlled trial. Arthritis Res. Ther. 2015, 17, 161.
  29. Pagliai, G.; Giangrandi, I.; Dinu, M.; Sofi, F.; Colombini, B. Nutritional interventions in the management of fibromyalgia syndrome. Nutrients 2020, 12, 2525.
  30. Lowry, E.; Marley, J.; McVeigh, J.G.; Mc Sorley, E.; Allsopp, P.; Kerr, D. Dietary interventions in the management of fibromyalgia: A systematic review and best-evidence synthesis. Nutrients 2020, 12, 2664.
  31. Kadayifci, F.Z.; Bradley, M.J.; Onat, A.M.; Shi, H.N.; Zheng, S. Review of nutritional approaches to fibromyalgia. Nutr. Rev. 2022, nuac036.
  32. Fernández-Araque, A.; Verde, Z.; Torres-Ortega, C.; Sainz-Gil, M.; Velasco-Gonzalez, V.; González-Bernal, J.J.; Mielgo-Ayuso, J. Effects of antioxidants on pain perception in patients with fibromyalgia-A systematic review. J. Clin. Med. 2022, 11, 2462.
  33. Haddad, H.W.; Mallepalli, N.R.; Scheinuk, J.E.; Bhargava, P.; Cornett, E.M.; Urits, I.; Kaye, A.D. The Role of nutrient supplementation in the management of chronic pain in fibromyalgia: A narrative review. Pain Ther. 2021, 10, 827–848.
  34. Crane, F.L.; Hatefi, Y.; Lester, R.L.; Widmer, C. Isolation of a quinone from beef heart mitochondria. Biochim. Biophys. Acta 1957, 25, 220–221.
  35. Morton, R.A. Ubiquinone. Nature 1958, 182, 1764–1767.
  36. Ernster, L.; Dallner, G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim. Biophys. Acta 1995, 1271, 195–204.
  37. Frederick, L.; Crane, F.L. Biochemical functions of Coenzyme Q10. J. Am. Coll. Nutr. 2001, 20, 591–598.
  38. Turunen, M.; Sindelar, P.; Dallner, G. Induction of endogenous coenzyme Q biosynthesis by administration of peroxisomal inducers. Biofactors 1999, 9, 131–139.
  39. Arroyo, A.; Kagan, V.E.; Tyurin, V.A.; Burgess, J.R.; de Cabo, R.; Navas, P.; Villalba, J.M. NADH and NADPH dependent reduction of coenzyme Q at the plasma membrane. Antioxid. Redox Signal 2000, 2, 251–262.
  40. Thomas, S.R.; Witting, P.K.; Stocker, R. A role for reduced coenzyme Q in atherosclerosis. Biofactors 1999, 9, 207–224.
  41. Schneider, D.; Elstner, E.F. Coenzyme Q10, vitamin E and dihydrothioctic acid cooperatively prevent diene conjugation in isolated low density lipoprotein. Antioxid. Redox Signal 2000, 2, 327–333.
  42. Takahashi, T.; Okamoto, T.; Mori, K.; Sayo, H.; Kishi, T. Distribution of ubiquinone and ubiquinol homologues in rat tissues and subcellular fraction. Lipids 1993, 28, 803–809.
  43. Quinn, P.J.; Fabisiak, J.P.; Kagan, V.E. Expansion of antioxidant function of vitamin E by coenzyme Q. Biofactors 1999, 9, 149–154.
  44. Crane, F.L. New functions for coenzyme Q. Protoplasma 2000, 213, 127–133.
  45. Villalba, J.M.; Navas, P. Plasma membrane redox system in the control of stress-induced apoptosis. Antioxid. Redox Signal 2000, 2, 213–230.
  46. Sun, I.L.; Sun, E.E.; Crane, F.L.; Morré, D.J.; Lindgren, A.; Löw, H. A requirement for coenzyme Q in plasma membrane electron transport. Proc. Nat. Acad. Sci. USA 1992, 89, 11126–11130.
  47. Takahashi, T.; Okamoto, T.; Kishi, T. Characterization of NADPH dependent ubiquinone reductase activity in rat liver cytosol. J. Biochem. 1996, 119, 256–263.
  48. Navarro, F.; Arroyo, A.; Martin, S.F.; Bello, R.I.; de Cabo, R.; Burgess, J.R.; Navas, P.; Villalba, J.M. Protective role of ubiquinone in vitamin E and selenium deficient plasma membranes. Biofactors 1999, 9, 163–170.
  49. Gorelick, C.; Lopez-Jones, M.; Goldberg, G.L.; Romney, S.L.; Khabele, D. Coenzyme Q10 and lipid-related gene induction in HeLa cells. Am. J. Obstet. Gynecol. 2004, 190, 1432–1434.
  50. Groneberg, D.A.; Kindermann, B.; Althammer, M.; Klapper, M.; Vormann, J.; Littarru, G.P.; Döring, F. Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. Int. J. Biochem. Cell Biol. 2005, 37, 1208–1218.
  51. Schmelzer, C.; Lindner, I.; Rimbach, G.; Niklowitz, P.; Menke, T.; Döring, F. Functions of coenzyme Q10 in inflammation and gene expression. Biofactors 2008, 32, 179–183.
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