THE RELATIONSHIP BETWEEN LOW LEVELS OF COENZYME Q10 AND OXIDATIVE DAMAGE IN PATIENTS WITH FIBROMYALGIA

Öz

Fibromyalgia (FM) is a condition associated with various symptoms, mainly pain and fatigue, and its exact cause is unclear. Many factors such as mitochondrial dysfunction, genetics, epigenetic factors and western-style diet cause the disease. Mitochondrial dysfunction and associated oxidative damage play a role in the basic pathogenesis of FM. Decreased levels of coenzyme q10, an antioxidant compound, in FM patients is one of the important causes of this condition. When the blood parameters of the patients are analysed, it is seen that most of them have sub-optimal coenzyme q10 values. Coenzyme Q10 is a fat-soluble antioxidant molecule responsible for energy production in mitochondria. Since it is involved in important physiological mechanisms related to oxidative stress such as cell signalling, gene expression and redox reactions, many studies have recently been conducted on its use in fibromyalgia treatment. In this review, the relationship between low coenzyme q10 levels and oxidative damage-related chronic pain, fatigue and sleep symptoms in fibromyalgia patients was investigated. The results obtained, the direct effect of coenzyme q10 on mitochondrial function and its antioxidant role have been associated with the prevention of oxidative damage. Increasing coenzyme q10 levels has been shown to alleviate disease symptoms such as pain, fatigue and insomnia. In order to increase coenzyme q10 levels in fibromyalgia patients, a personalised nutrition plan containing antioxidant-rich foods should be prepared and nutritional supplements containing coenzyme q10 should be added to the diet plan.

Anahtar Kelimeler

• Fibromyalgia
• coenzyme q10
• oxidative damage
• antioxidant

The relationship between low levels of coenzyme Q10 and oxidative damage in patients with fibromyalgia

Öz

Fibromyalgia (FM) is a condition associated with various symptoms, mainly widespread body pain and fatigue, and its exact cause is unclear. Many factors such as mitochondrial dysfunction, genetics, epigenetic factors and western-style diet cause the disease. Mitochondrial dysfunction and associated oxidative damage play a role in the basic pathogenesis of FM. Decreased levels of coenzyme Q10, an antioxidant compound, in FM patients is one of the important causes of this condition. When the blood parameters of the patients are analysed, it is seen that most of them have sub-optimal coenzyme Q10 values. Coenzyme Q10 is a fat-soluble antioxidant molecule responsible for energy production in mitochondria. Since it is involved in important physiological mechanisms related to oxidative stress such as cell signalling, gene expression and redox reactions, many studies have recently been conducted on its use in fibromyalgia treatment. In this review, the relationship between low coenzyme Q10 levels and oxidative damage-related chronic pain, fatigue and sleep symptoms in fibromyalgia patients investigated. The results obtained, the direct effect of coenzyme Q10 on mitochondrial function and its antioxidant role have been associated with the prevention of oxidative damage. Increasing coenzyme Q10 levels has been shown to alleviate disease symptoms such as pain, fatigue and insomnia. In order to increase coenzyme Q10 levels in fibromyalgia patients, a personalised nutrition plan containing antioxidant-rich foods should be prepared and nutritional supplements containing coenzyme Q10 can be added to the diet plan.

Anahtar Kelimeler

• Antioxidant
• coenzyme Q10
• fibromyalgia
• oxidative damage

Kaynakça

1. Referans1 Martínez-Lara, A., Moreno-Fernández, A. M., Jiménez-Guerrero, M., Díaz-López, C., De-Miguel, M., Cotán, D., &Sánchez-Alcázar, J. A. (2020). Mitochondrial ımbalance as a new approach to the study of fibromyalgia. Open Access Rheumatology: Research and Reviews, 12, 175–185. https://doi.org/10.2147/OARRR.S257470
2. Referans2 Galvez-Sánchez, C. M., &Reyes Del Paso, G. A. (2020). Diagnostic criteria for fibromyalgia: critical review and future perspectives. Journal of Clinical Medicine, 9(4), 1219. https://doi.org/10.3390/jcm9041219
3. Referans3 D'Agnelli, S., Arendt-Nielsen, L., Gerra, M. C., Zatorri, K., Boggiani, L., Baciarello, M., &Bignami, E. (2019). Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers. Molecular Pain, 15. https://doi.org/10.1177/1744806918819944
4. Referans4 Bigatti, S. M., Hernandez, A. M., Cronan, T. A., &Rand, K. L. (2008). Sleep disturbances in fibromyalgia syndrome: relationship to pain and depression. Arthritis and Rheumatism, 59(7), 961–967. https://doi.org/10.1002/art.23828
5. Referans5 Clauw, D., Sarzi-Puttini, P., Pellegrino, G., &Shoenfeld, Y. (2023). Is fibromyalgia an autoimmune disorder? Autoimmunity Reviews, 23(1), 103424. https://doi.org/10.1016/j.autrev.2023.103424
6. Referans6 Fields HL and Martin JB (1998) Pain: pathophysiology and management. In Harrison’s Principles of Internal Medicine edn 14, 53–58 (Eds Fauci AS et al.) New York: McGraw-Hill
7. Referans7 Fischer-Jbali, L. R., Alacreu, A., Galvez-Sánchez, C. M., &Montoro, C. I. (2024). Measurement of event-related potentials from electroencephalography to evaluate emotional processing in Fibromyalgia Syndrome: A systematic review and meta-analysis. International Journal of Psychophysiology, 198, 1-21. https://doi.org/10.1016/j.ijpsycho.2024.112327
8. Referans8 Galvez-Sánchez, C. M., Montoro, C. I., Duschek, S., &Del Paso, G. A. R. (2020). Pain catastrophizing mediates the negative influence of pain and trait-anxiety on health-related quality of life in fibromyalgia. Quality of Life Research, 29(7), 1871–1881. https://doi.org/10.1007/s11136-020-02457-x

9. Referans9 Kocyigit, B. F., &Akyol, A. (2022). Fibromyalgia syndrome: epidemiology, diagnosis and treatment. Reumatologia, 60(6), 413–421. https://doi.org/10.5114/reum.2022.123671
10. Referans10 Marques, A. P., Santo, A. S. D. E., Berssaneti, A. A., Matsutani, L. A., &Yuan, S. L. K. (2017). Prevalence of fibromyalgia: literature review update. Revista Brasileira de Reumatologia, 57(4), 356–363. https://doi.org/10.1016/j.rbre.2017.01.005
11. Referans11 Creed, F. (2020). A review of the incidence and risk factors for fibromyalgia and chronic widespread pain in population-based studies. Pain, 161(6), 1169–1176. https://doi.org/10.1097/j.pain.0000000000001819
12. Referans12 Bullón, 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., Ghiringhelli, F., Battino, M., Sánchez-Alcazar, J. A., &Cordero, M. D. (2016). AMPK Phosphorylation modulates pain by activation of nlrp3 ınflammasome. Antioxidants & Redox Signaling, 24(3), 157–170. https://doi.org/10.1089/ars.2014.6120
13. Referans13 Alcocer-Gómez, E., Sánchez-Alcazar, J. A., Battino, M., Bullón, P., &Cordero, M. D. (2014). Aging-related changes in inflammatory and LKB1/AMPK gene expression in fibromyalgia patients. CNS Neuroscience & Therapeutics, 20(5), 476–478. https://doi.org/10.1111/cns.12255
14. Referans14 Alcocer-Gómez, E., Cano-García, F. J., &Cordero, M. D. (2013). Effect of coenzyme Q10 evaluated by 1990 and 2010 ACR Diagnostic Criteria for Fibromyalgia and SCL-90-R: four case reports and literature review. Nutrition, 29, 11-12. https://doi.org/10.1016/j.nut.2013.05.005
15. Referans15 Lenaz, G., Fato, R., Formiggini, G., &Genova, M. L. (2007). The role of coenzyme Q in mitochondrial electron transport. Mitochondrion, 7, 8–33. https://doi.org/10.1016/j.mito.2007.03.009
16. Referans16 Littarru, G. P., &Tiano, L. (2010). Clinical aspects of coenzyme Q10: an update. Nutrition, 26(3), 250–254. https://doi.org/10.1016/j.nut.2009.08.008
17. Referans17 Maes, M., Mihaylova, I., Kubera, M., Uytterhoeven, M., Vrydags, N., &Bosmans, E. (2009). Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinology Letters, 30(4), 470–476.
18. Referans18 Haas, R. H. (2007). The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease. Mitochondrion, 7, 136–145. https://doi.org/10.1016/j.mito.2007.03.008
19. Referans19 Mehrabani, S., Askari, G., Miraghajani, M., Tavakoly, R., &Arab, A. (2019). Effect of coenzyme Q10 supplementation on fatigue: a systematic review of interventional studies. Complementary Therapies in Medicine, 43, 181–187. https://doi.org/10.1016/j.ctim.2019.01.022
20. Referans20 Carrasco-Querol, N., Cabricano-Canga, L., Bueno Hernández, N., Gonçalves, A. Q., Caballol, Angelats, R., Pozo Ariza, M., Martín-Borràs, C., Montesó-Curto, P., Castro-Blanco, E., Dalmau Llorca, M. R., &Aguilar-Martín, C. (2024). Nutrition and chronobiology as key components of multidisciplinary therapeutic ınterventions for fibromyalgia and associated chronic fatigue syndrome: a narrative and critical review. Nutrients, 16(2), 182. https://doi.org/10.3390/nu16020182
21. Referans21 Arnold, L. M., Hudson, J. I., Hess, E. V., Ware, A. E., Fritz, D. A., Auchenbach, M. B., Starck, L. O., &Keck, P. E. (2004). Family study of fibromyalgia. Arthritis and Rheumatism, 50(3), 944–952. https://doi.org/10.1002/art.20042
22. Referans22 Dönmez, A., &Erdoğan, N. (2009). Fibromiyalji sendromu. Klinik Gelişim, 22(3), 60-65.
23. Referans23 Russell, I. J., Kamin, M., Bennett, R. M., Schnitzer, T. J., Green, J. A., &Katz, W. A. (2000). Efficacy of tramadol in treatment of pain in fibromyalgia. Journal of Clinical Rheumatology, 6(5), 250–257. https://doi.org/10.1097/00124743-200010000-00004
24. Referans24 Moldofsky, H. (2001). Sleep and pain. Sleep Medicine Reviews. 5(5), 385–396. https://doi.org/10.1053/smrv.2001.0179
25. Referans25 Späth, M. (2002). Current experience with 5-HT3 receptor antagonists in fibromyalgia. Rheumatic Diseases Clinics of North America, 28(2), 319–328. https://doi.org/10.1016/s0889-857x(01)00014-x
26. Referans26 Fernández-Araque, A., Verde, Z., Torres-Ortega, C., Sainz-Gil, M., Velasco-Gonzalez, V., González-Bernal, J. J., &Mielgo-Ayuso, J. (2022). Effects of antioxidants on pain perception in patients with fibromyalgia-a systematic review. Journal of Clinical Medicine, 11(9), 2462. https://doi.org/10.3390/jcm11092462
27. Referans27 Popkin, B. M., D'Anci, K. E., &Rosenberg, I. H. (2010). Water, hydration, and health. Nutrition Reviews, 68(8), 439–458. https://doi.org/10.1111/j.1753-4887.2010.00304.x
28. Referans28 Maria Gomez-Arguelles, J., Caceres, O., Blanco, M., Maest, C., &Martin, F. (2022). Improvement of digestive symptoms in fibromyalgia patients following a diet modification according to histamine release test-an observational study. Rheumatology/Reumatologia, 60(3).
29. Referans29 Arranz, L. I., Canela, M. A., &Rafecas, M. (2010). Fibromyalgia and nutrition, what do we know?. Rheumatology International, 30(11), 1417–1427. https://doi.org/10.1007/s00296-010-1443-0
30. Referans30 Bennett, R. M., Jones, J., Turk, D. C., Russell, I. J., &Matallana, L. (2007). An internet survey of 2,596 people with fibromyalgia. BMC Musculoskeletal Disorders, 8, 27. https://doi.org/10.1186/1471-2474-8-27
31. Referans31 Kaartinen, K., Lammi, K., Hypen, M., Nenonen, M., Hanninen, O., &Rauma, A. L. (2000). Vegan diet alleviates fibromyalgia symptoms. Scandinavian Journal ofRrheumatology, 29(5), 308–313. https://doi.org/10.1080/030097400447697
32. Referans32 Lowry, E., Marley, J., McVeigh, J. G., McSorley, E., Allsopp, P., &Kerr, D. (2020). Dietary Interventions in the Management of Fibromyalgia: A Systematic Review and Best-Evidence Synthesis. Nutrients, 12(9), 2664. https://doi.org/10.3390/nu12092664
33. Referans33 İnan, C. M., Canbolat, E., Özçelik, A. O., &Çakıroğlu, F. P. (2021). Beslenme ve ağrı, 4th International Congress on Agriculture, Environment and Health. Mersin.
34. Referans34 Cordero, M. D., Alcocer-Gómez, E., de Miguel, M., Culic, O., Carrión, A. M., Alvarez-Suarez, J. M., Bullón, P., Battino, M., Fernández-Rodríguez, A., &Sánchez-Alcazar, J. A. (2013). Can coenzyme Q10 improve clinical and molecular parameters in fibromyalgia?. Antioxidants & Redox Signaling, 19(12), 1356–1361. https://doi.org/10.1089/ars.2013.5260
35. Referans35 Cordero, M. D., Cotán, D., del-Pozo-Martín, Y., Carrión, A. M., de Miguel, M., Bullón, P., &Sánchez-Alcazar, J. A. (2012). Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient. Nutrition (Burbank, Los Angeles County, Calif.), 28(11-12), 1200–1203. https://doi.org/10.1016/j.nut.2012.03.018
36. Referans36 Gómez-Centeno, A., Ramentol, M., &Alegre, C. (2022). Nutritional Supplementation With Coenzyme Q10, Tryptophan and Magnesium in Fibromyalgia Treatment: A Letter to Editor. Reumatologia clinica, 18(1), 62–63. https://doi.org/10.1016/j.reumae.2020.04.016
37. Referans37 Crane, F. L. (2001). Biochemical functions of coenzyme q10, Journal of the American Collage of Nutrition, 20(6), 591-598. https://doi.org/10.1080/07315724.2001.10719063
38. Referans38 Varela-Lopez, A., Giampieri, F., Battino, M., &Quiles, J. L. (2016). Coenzyme Q and ıts role in the dietary therapy against aging, Molecules, 21(3), 373. https://doi.org/10.3390/molecules21030373
39. Referans39 Craft, N. E., Tucker, R. T., Chitchumroonchokchai, C., Failla, M., &Bhagavan, H. N. (2005). Assessment of coenzyme Q10 bioavailability using a coupled in vitro digestion/caco-2 human ıntestinal cell model. FASEN J, 19, 449.
40. Referans40 Campisi, L., &Concettina, L. M. (2022). The use of the coenzyme q10 as a food supplement in the management of fibromyalgia: a critical review. Antioxidants, 11, 1969. https://doi.org/10.3390/antiox11101969.
41. Referans41 Ernster, L., &Dallner, G. (1995). Biochemical, Physiological and Medical Aspects of Ubiquinone Function, Biochim. Biophys, 1271, 195-204.
42. Referans42 Toprak, K., &Ayaz, A. (2019). Koenzim Q10: biyolojik aktivitesi ve sağlık üzerine etkisine güncel bakış, Haccettepe Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 6(2), 95-111. https://doi.org/10.21020/husbfd.450217
43. Referans43 Willis, R., Anthony, M., Sun, L., Honse, Y., &Qiao, G. (1999). Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status. BioFactors, 9(2-4), 359–363. https://doi.org/10.1002/biof.5520090236
44. Referans44 Stocker, R. (2023, December 29). “Coenzyme Q10” reviewed, linus pauling ınstitute micronutrient research for optimum health, http://lpi.oregonstate.edu/infocenter/othernuts/coq10/
45. Referans45 Kettawan, A. (2004). “The content of coenzyme Q10 in foods, animal sources and vegetable oils”, research project, Mahidol University, Thailand.
46. Referans46 ERNA (2023, November 20). The European Responsible Nutrition Allianca, Coenzyme Q10, http://www.erna.org/userfiles/coq10.pdf
47. Referans47 Ercan, P., &El, S. N. (2010). Koenzim q10’un beslenme ve sağlık açısından önemi ve biyoyararlılığı, Türk Bilim Araştırma Vakfı Bilim Dergisi, 3(2), 192-200.
48. Referans48 Cordero, M. D., Moreno-Fernández, A. M., deMiguel, M., Bonal, P., Campa, F., Jiménez-Jiménez, L. M., Ruiz-Losada, A., Sánchez-Domínguez, B., Sánchez Alcázar, J. A., Salviati, L., & Navas, P. (2009). Coenzyme Q10 distribution in blood is altered in patients with fibromyalgia. Clinical Biochemistry, 42(7-8), 732–735. https://doi.org/10.1016/j.clinbiochem.2008.12.010
49. Referans49 Cordero, M.D.; Cano-García, F.J.; Alcocer-Gómez, E.; De Miguel, M.; Sánchez-Alcázar, J. A. (2012). Oxidative stress correlates with headache symptoms in fibromyalgia: Coenzyme Q10 effect on clinical improvement. PLoS ONE, 7, e35677.
50. Referans50 Lopez-Llunch, G., Rodriguez-Aguilera, J., Santos-Ocana, C., &Navas, P. (2010). Is coenzyme Q a key factor in aging?, Mechanisms of Ageing and Developent, 131(4), 225-235. DOI: 10.1016/j.mad.2010.02.003
51. Referans51 Alcazar-Fabra, M., Navas, P., &Brea-Calvo, G. (2016). Coenzyme Q biosynthesis and ıts role in the respiratory chain structure, Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1857(8), 1073-1078. https://doi.org/10.1016/j.bbabio.2016.03.010
52. Referans52 Yunus, M. B., &Inanici, F. (2002). Fibromyalgia syndrome: Clinical features, diagnosis and biopathophysiologic mechanisms. Myofascial Pain And Fibromyalgia, 3, 31.
53. Referans53 Larson, A. A., Giovengo, S. L., Russel, I. J., &Michalek, J. E. (2000). Changes in the concentrations of aminoacids in the CSF that correlate with pain in fibromyalgia:implications for nitric oxide pathways. Pain, 87, 201-11
54. Referans54 Pall, M. L. (2001). Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrate. Med Hypoth, 57:138-45.
55. Referans55 Talebi, S., Shani, M. H. P., Zeraattalab-Motlagh, S., Asoudeh, F., Ranjbar, M., Hemmati, A., Talebi, A., Wong, A., &Mohammadi, H. (2024). The effects of coenzyme Q10 supplementation on biomarkers of exercise-induced muscle damage, physical performance, and oxidative stress: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Clinical Nutrition ESPEN, 60, 122-134. https://doi.org/10.1016/j.clnesp.2024.01.015
56. Referans56 Skinner, M. K, Manikkam, M., &Guerrero-Bosagna, C. (2010). Epigenetic transgenerational actions of environmental factors in disease etiology. Trends in Endocrinology and Metabolism: TEM, 21(4), 214–222. https://doi.org/10.1016/j.tem.2009.12.007
57. Referans57 Cordero, M. D., Alcocer-Gómez, E., Culic, O., Carrión, A. M., de Miguel, M., Díaz-Parrado, E., Pérez-Villegas, E. M., Bullón, P., Battino, M., &Sánchez-Alcazar, J. A. (2014). NLRP3 inflammasome is activated in fibromyalgia: the effect of coenzyme Q10. Antioxidants & Redox Signaling, 20(8), 1169–1180. https://doi.org/10.1089/ars.2013.5198
58. Referans58 Fan, l., Feng, Y., Chen, G. C., Qin, L. Q., Fu, C. I., &Chen, L. H. (2017). Effects of coenzyme Q10 supplementation on ınflammatory markers: a systematic review and meta-analysis of randomized controlled trials, Pharmacological Research, 119, 128-136. https://doi.org/10.1016/j.phrs.2017.01.032
59. Referans59 Al-Johani, N. S., Al-Zharani, M., Aljarba, N. H., Alhoshani, N. M., Alkeraishan, N., & Alkahtani, S. (2022). Antioxidant and anti-Inflammatory activities of coenzyme-Q10 and piperine against cyclophosphamide-induced cytotoxicity in HuH-7 Cells. BioMed research international, 8495159. https://doi.org/10.1155/2022/8495159
60. Referans60 Abiri, B., Vafa, M. (2021). Impact of coenzyme Q10 on inflammatory biomarkers and its role in future therapeutic strategies. Clinical Nutrition ESPEN, 43, 25-30. https://doi.org/10.1016/j.clnesp.2021.04.005
61. Referans61 Farsi F, Heshmati J, Keshtkar A, Irandoost P, Alamdari NM, &Akbari A. (2019). Can coenzyme Q10 supplementation effectively reduce human tumor necrosis factor-a and interleukin-6 levels in chronic inflammatory diseases? A systematic review and meta-analysis of randomized controlled trials. Pharmacol, 148, 104290. https://doi.org/10.1016/j.phrs.2019.104290.
62. Referans62 Perez-Sanchez C, Aguirre MA, Ruiz-Limon P, Abalos-Aguilera MC, JimenezGomez Y, &Arias-De La Rosa I. (2017). Ubiquinol effects on antiphospholipid syndrome prothrombotic profile: a randomized, placebo-controlled trial. Arterioscler Thromb Vasc Biol, 37, 1923e32. https://doi.org/10.1161/ATVBAHA.117.309225.
63. Referans63 Dabbaghi Varnousfaderani, S., Musazadeh, V., Ghalichi, F., Kavyani, Z., Razmjouei, S., Faghfouri, A. H., Ahrabi, S. S., Seyyed Shoura, S. M., &Dehghan, P. (2023). Alleviating effects of coenzyme Q10 supplements on biomarkers of inflammation and oxidative stress: results from an umbrella meta-analysis. Frontiers in pharmacology, 14, 1191290. https://doi.org/10.3389/fphar.2023.1191290
64. Referans64 Liu, H. T. (2016). Effects of coenzyme Q10 supplementation on antioxidant capacity and inflammation in hepatocellular carcinoma patients after surgery: a randomized, placebocontrolled trial. Nutrition Journal, 15(1), 85.