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The Natural Products Journal


ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Clinical Trial

Effect of Coenzyme Q10 Supplementation on Urinary and Salivary Oxidative Stress Biomarkers in Bipolar Patients During the Depressive Episode

Author(s): Seyyede-Nadia Hosseini-Ghalibaf, Akram Ranjbar, Fatemeh Yasrebifar, Ehsan Mirzaei, Mahtabalsadat Mirjalili, Younes Mohammadi and Maryam Mehrpooya*

Volume 10 , Issue 5 , 2020

Page: [664 - 672] Pages: 9

DOI: 10.2174/2210315509666190624102012

Price: $65


Background: Although depression is the predominant phase in Bipolar Disorder (BPD) and causes the most psychosocial disability, optimal pharmacotherapy of bipolar depression is not known yet. Advances in research on BPD neurobiology have demonstrated that oxidative toxic stress (OTS) may be involved in the pathophysiology of BPD.

Objective: The present study aimed to evaluate the effects of adjuvant CoQ10, supplement with potent antioxidant properties, on salivary and urinary OTS biomarkers in patients with BPD during the depressive episode.

Material and Methods: 89 BPD patients with current depressive episode were allocated into either CoQ10 (200 mg/day) or placebo group by block randomization method. The salivary and urinary levels of OTS biomarkers including Total Antioxidant Capacity (TAC) and DNA damage were measured at baseline and 8 weeks after treatment.

Results: At baseline, urinary and salivary levels of TAC and DNA damage were statistically comparable between the two groups. After 8 weeks treatment with CoQ10, patients showed significantly higher increment in urinary TAC level compared to placebo, while salivary level of TAC did not display significant differences between the two groups. Although changes in salivary and urinary DNA damage levels were greater in CoQ10 group, the changes reached significant level only in the urine sample.

Conclusion: Our findings suggest that CoQ10 can improve OTS status in BPD patients during depressive episode. As activation of oxidative stress is one of the mechanisms responsible for BPD, it seems that CoQ10 due to its proven antioxidant properties, as add on therapy to standard treatment may be a promising agent in treating bipolar depression.

Keywords: Bipolar disorder, co-enzyme Q10, oxidative stress, total antioxidant capacity, DNA damage, depression.

Graphical Abstract
Goldberg, J.F.; Harrow, M.; Grossman, L.S. Course and outcome in bipolar affective disorder: a longitudinal follow-up study. Am. J. Psychiatry, 1995, 152(3), 379-384.
[ ] [PMID: 7864263]
Hirschfeld, R.M.; Lewis, L.; Vornik, L.A. Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J. Clin. Psychiatry, 2003, 64(2), 161-174.
[ ] [PMID: 12633125]
Gonda, X.; Pompili, M.; Serafini, G.; Montebovi, F.; Campi, S.; Dome, P.; Duleba, T.; Girardi, P.; Rihmer, Z. Suicidal behavior in bipolar disorder: epidemiology, characteristics and major risk factors. J. Affect. Disord., 2012, 143(1-3), 16-26.
[ ] [PMID: 22763038]
Kessler, R.C.; Demler, O.; Frank, R.G.; Olfson, M.; Pincus, H.A.; Walters, E.E.; Wang, P.; Wells, K.B.; Zaslavsky, A.M. Prevalence and treatment of mental disorders, 1990 to 2003. N. Engl. J. Med., 2005, 352(24), 2515-2523.
[ ] [PMID: 15958807]
Keck, P.E., Jr; Nelson, E.B.; McElroy, S.L. Advances in the pharmacologic treatment of bipolar depression. Biol. Psychiatry, 2003, 53(8), 671-679.
[ ] [PMID: 12706953]
Paykel, E.S.; Abbott, R.; Morriss, R.; Hayhurst, H.; Scott, J. Sub-syndromal and syndromal symptoms in the longitudinal course of bipolar disorder. Br. J. Psychiatry, 2006, 189(2), 118-123.
[ ] [PMID: 16880480]
Baldessarini, R.J.; Salvatore, P.; Khalsa, H-M.K.; Tohen, M. Dissimilar morbidity following initial mania versus mixed-states in type-I bipolar disorder. J. Affect. Disord., 2010, 126(1-2), 299-302.
[ ] [PMID: 20427091]
Angst, J.; Sellaro, R. Historical perspectives and natural history of bipolar disorder. Biol. Psychiatry, 2000, 48(6), 445-457.
[ ] [PMID: 11018218]
Mohammed, Z.; Grunze, H. Acute pharmacological treatment strategies for bipolar depression. Neuropsychiatry (London), 2016, 6(3), 96-111.
Craddock, N.; Sklar, P. Genetics of bipolar disorder. Lancet, 2013, 381(9878), 1654-1662.
[ ] [PMID: 23663951]
Schneider, M.R.; DelBello, M.P.; McNamara, R.K.; Strakowski, S.M.; Adler, C.M. Neuroprogression in bipolar disorder. Bipolar Disord., 2012, 14(4), 356-374.
[ ] [PMID: 22631620]
McGorry, P.D.; Hickie, I.B.; Yung, A.R.; Pantelis, C.; Jackson, H.J. Clinical staging of psychiatric disorders: S heuristic framework for choosing earlier, safer and more effective in-terventions. Australian & New Zealand. J. Psychiatry, 2006, 40(8), 616-622.
[PMID: 16866756]
Sun, X.; Wang, J-F.; Tseng, M.; Young, L.T. Down regulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. J. Psychiatry Neurosci., 2006, 31(3), 189-196.
[PMID: 16699605]
Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J., 2012, 5(1), 9-19.
[ ] [PMID: 23268465]
Andreazza, A.C.; Kauer-Sant’anna, M.; Frey, B.N.; Bond, D.J.; Kapczinski, F.; Young, L.T.; Yatham, L.N. Oxidative stress markers in bipolar disorder: A meta-analysis. J. Affect. Disord., 2008, 111(2-3), 135-144.
[ ] [PMID: 18539338]
Berk, M.; Kapczinski, F.; Andreazza, A.C.; Dean, O.M.; Giorlando, F.; Maes, M.; Yücel, M.; Gama, C.S.; Dodd, S.; Dean, B.; Magalhães, P.V.; Amminger, P.; McGorry, P.; Malhi, G.S. Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors. Neurosci. Biobehav. Rev., 2011, 35(3), 804-817.
[ ] [PMID: 20934453]
Cui, J.; Shao, L.; Young, L.T.; Wang, J-F. Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate. Neuroscience, 2007, 144(4), 1447-1453.
[ ] [PMID: 17184924]
Berk, M.; Copolov, D.L.; Dean, O.; Lu, K.; Jeavons, S.; Schapkaitz, I.; Anderson-Hunt, M.; Bush, A.I. N-acetyl cysteine for depressive symptoms in bipolar disorder-A double-blind randomized placebo-controlled trial. Biol. Psychiatry, 2008, 64(6), 468-475.
[ ] [PMID: 18534556]
Bhagavan, H.N.; Chopra, R.K. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic. Res., 2006, 40(5), 445-453.
[ ] [PMID: 16551570]
Villalba, J.M.; Parrado, C.; Santos-Gonzalez, M.; Alcain, F.J. Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations. Expert Opin. Investig. Drugs, 2010, 19(4), 535-554.
[ ] [PMID: 20367194]
Mancuso, M.; Orsucci, D.; Calsolaro, V.; Choub, A.; Siciliano, G. Coenzyme Q10 and neurological diseases. Pharmaceuticals (Basel), 2009, 2(3), 134-149.
[ ] [PMID: 27713230]
Mehrpooya, M.; Yasrebifar, F.; Haghighi, M.; Mohammadi, Y.; Jahangard, L. Evaluating the effect of coenzyme Q10 Augmentation on treatment of bipolar depression: a double-blind controlled clinical trial. J. Clin. Psychopharmacol., 2018, 38(5), 460-466.
[ ] [PMID: 30106880]
Forester, B.P.; Zuo, C.S.; Ravichandran, C.; Harper, D.G.; Du, F.; Kim, S.; Cohen, B.M.; Renshaw, P.F. Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression. J. Geriatr. Psychiatry Neurol., 2012, 25(1), 43-50.
[ ] [PMID: 22467846]
Sanoobar, M.; Eghtesadi, S.; Azimi, A.; Khalili, M.; Jazayeri, S.; Reza Gohari, M. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with relapsing-remitting multiple sclerosis. Int. J. Neurosci., 2013, 123(11), 776-782.
[ ] [PMID: 23659338]
Yang, X.; Yang, Y.; Li, G.; Wang, J.; Yang, E.S. Coenzyme Q10 attenuates β-amyloid pathology in the aged transgenic mice with Alzheimer presenilin 1 mutation. J. Mol. Neurosci., 2008, 34(2), 165-171.
[ ] [PMID: 18181031]
Il’yasova, D.; Scarbrough, P.; Spasojevic, I. Urinary biomarkers of oxidative status. Clin. Chim. Acta, 2012, 413(19-20), 1446-1453.
[ ] [PMID: 22683781]
Lee, Y-H.; Wong, D.T. Saliva: an emerging biofluid for early detection of diseases. Am. J. Dent., 2009, 22(4), 241-248.
[PMID: 19824562]
Kapoor, P.; Kapoor, A. Coenzyme Q10—a novel molecule. J. Indian Acad. Clin. Med., 2013, 14(1), 37-45.
Bonakdar, R.A.; Guarneri, E. Coenzyme Q10. Am. Fam. Physician, 2005, 72(6), 1065-1070.
[PMID: 16190504]
Ahmadpanah, M.; Sheikhbabaei, M.; Haghighi, M.; Roham, F.; Jahangard, L.; Akhondi, A.; Sadeghi Bahmani, D.; Bajoghli, H.; Holsboer-Trachsler, E.; Brand, S. Validity and test–retest reliability of the Persian version of the Montgomery–Asberg depression rating scale. Neuropsychiatr. Dis. Treat., 2016, 12, 603-607.
[PMID: 27022265]
Benzie, I.F.; Strain, J.J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal. Biochem., 1996, 239(1), 70-76.
[ ] [PMID: 8660627]
Vawter, M.P.; Freed, W.J.; Kleinman, J.E. Neuropathology of bipolar disorder. Biol. Psychiatry, 2000, 48(6), 486-504.
[ ] [PMID: 11018222]
Rahman, T.; Hosen, I.; Islam, M.T.; Shekhar, H.U. Oxidative stress and human health. Adv. Biosci. Biotechnol., 2012, 3(07), 997.
Tang, V.; Wang, J-F. Mitochondrial dysfunction and oxidative stress in bipolar disorder. Systems Biology of Free Radicals and Antioxidants; Springer: Berlin, Germany, 2014, pp. 2411-2429.
Salim, S. Oxidative stress and psychological disorders. Curr. Neuropharmacol., 2014, 12(2), 140-147.
[ ] [PMID: 24669208]
Magalhães, P.V.; Dean, O.M.; Bush, A.I.; Copolov, D.L.; Malhi, G.S.; Kohlmann, K.; Jeavons, S.; Schapkaitz, I.; Anderson-Hunt, M.; Berk, M. N-acetylcysteine for major depressive episodes in bipolar disorder. Br. J. Psychiatry, 2011, 33(4), 374-378.
[ ] [PMID: 22189927]
Gyurászová, M.; Kovalčíková, A.; Janšáková, K.; Šebeková, K.; Celec, P.; Tóthová, Ľ. Markers of oxidative stress and antioxidant status in the plasma, urine and saliva of healthy mice. Physiol. Res., 2018, 67(6), 921-934.
[ ] [PMID: 30204460]
Brown, N.C.; Andreazza, A.C.; Young, L.T. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res., 2014, 218(1-2), 61-68.
[ ] [PMID: 24794031]
Andreazza, A.C.; Cassini, C.; Rosa, A.R.; Leite, M.C.; de Almeida, L.M.; Nardin, P.; Cunha, A.B.; Ceresér, K.M.; Santin, A.; Gottfried, C.; Salvador, M.; Kapczinski, F.; Gonçalves, C.A. Serum S100B and antioxidant enzymes in bipolar patients. J. Psychiatr. Res., 2007, 41(6), 523-529.
[ ] [PMID: 16956621]
Bakare, A.; Shao, L.; Cui, J.; Young, L.T.; Wang, J-F. Mood stabilizing drugs lamotrigine and olanzapine increase expression and activity of glutathione S-transferase in primary cultured rat cerebral cortical cells. Neurosci. Lett., 2009, 455(1), 70-73.
[ ] [PMID: 19429109]
Gałecki, P.; Mossakowska-Wójcik, J.; Talarowska, M. The anti-inflammatory mechanism of antidepressants–SSRIs, SNRIs. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2017, 80, 291-294.
[PMID: 28342944]
Machado-Vieira, R.; Andreazza, A.C.; Viale, C.I.; Zanatto, V.; Cereser, V., Jr; da Silva Vargas, R.; Kapczinski, F.; Portela, L.V.; Souza, D.O.; Salvador, M.; Gentil, V. Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects. Neurosci. Lett., 2007, 421(1), 33-36.
[ ] [PMID: 17548157]
Frangou, S.; Lewis, M.; McCrone, P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br. J. Psychiatry, 2006, 188(1), 46-50.
[ ] [PMID: 16388069]
Amr, M.; El-Mogy, A.; Shams, T.; Vieira, K.; Lakhan, S.E. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo controlled pilot study. Nutr. J., 2013, 12(1), 31.
[ ] [PMID: 23510529]
Crane, F.L. Biochemical functions of coenzyme Q10. J. Am. Coll. Nutr., 2001, 20(6), 591-598.
[ ] [PMID: 11771674]
Stocker, R.; Bowry, V.W.; Frei, B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc. Natl. Acad. Sci. USA, 1991, 88(5), 1646-1650.
[ ] [PMID: 2000375]
Mirmalek, S.A.; Gholamrezaei Boushehrinejad, A.; Yavari, H.; Kardeh, B.; Parsa, Y.; Salimi-Tabatabaee, S.A.; Yadollah-Damavandi, S.; Parsa, T.; Shahverdi, E.; Jangholi, E. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine induced acute pancreatitis in rat. Oxid. Med. Cell. Longev., 2016.
Lee, B-J.; Tseng, Y-F.; Yen, C-H.; Lin, P-T. Effects of coenzyme Q10 supplementation (300 mg/day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy: A randomized, placebo-controlled trial. Nutr. J., 2013, 12(1), 142.
[ ] [PMID: 24192015]
Rivara, M.B.; Yeung, C.K.; Robinson-Cohen, C.; Phillips, B.R.; Ruzinski, J.; Rock, D.; Linke, L.; Shen, D.D.; Ikizler, T.A.; Himmelfarb, J. Effect of coenzyme Q10 on biomarkers of oxidative stress and cardiac function in hemodialysis patients: The CoQ10 biomarker trial. Am. J. Kidney Dis., 2017, 69(3), 389-399.
[ ] [PMID: 27927588]
Kędziora-Kornatowska, K.; Czuczejko, J.; Motyl, J.; Szewczyk-Golec, K.; Kozakiewicz, M.; Pawluk, H.; Kędziora, J.; Błaszczak, R.; Banach, M.; Rysz, J. Effects of coenzyme Q10 supplementation on activities of selected antioxidative enzymes and lipid peroxidation in hypertensive patients treated with indapamide. A pilot study. Arch. Med. Sci., 2010, 6(4), 513-518.
[ ] [PMID: 22371793]
Fallah, M.; Askari, G.; Soleimani, A.; Feizi, A.; Asemi, Z. Clinical trial of the effects of Coenzyme Q10 supplementation on biomarkers of inflammation and oxidative stress in diabetic hemodialysis patients. Int. J. Prev. Med., 2019, 10, 12.
[ ] [PMID: 30774846]
Wang, J.; Schipper, H.M.; Velly, A.M.; Mohit, S.; Gornitsky, M. Salivary biomarkers of oxidative stress: A critical review. Free Radic. Biol. Med., 2015, 85, 95-104.
[ ] [PMID: 25889823]
Anderson, G.; Maes, M. Coenzyme Q10 Depletion: Role in depression and depression-associated disorders. CoEnzyme Q10: From fact to fiction; Nova Science Publishers: New York, USA, 2015, pp. 147-170.
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, 105-112.
[ ] [PMID: 23313551]
Kagal, U.A.; Angadi, N.B. Effect of coenzyme Q10 on depression paradigms in male Wistar rats and Swiss albino mice. Natl. J. Physiol. Pharm. Pharmacol., 2017, 7(8), 802.
Forester, B.P.; Harper, D.G.; Georgakas, J.; Ravichandran, C.; Madurai, N.; Cohen, B.M. Antidepressant effects of open label treatment with coenzyme Q10 in geriatric bipolar depression. J. Clin. Psychopharmacol., 2015, 35(3), 338-340.
[ ] [PMID: 25874916]
Pandya, C.D.; Howell, K.R.; Pillai, A. Antioxidants as potential therapeutics for neuropsychiatric disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 46, 214-223.
[ ] [PMID: 23123357]
Shults, C.W.; Flint Beal, M.; Song, D.; Fontaine, D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson’s disease. Exp. Neurol., 2004, 188(2), 491-494.
[] [PMID: 15246848]

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