Antosiyaninin Depresyon Üzerindeki Potansiyel Etkileri: Bir Derleme
Yıl 2024,
, 291 - 297, 02.06.2024
Emine Kurtbeyoglu
,
Gül Akduman
,
Fatma Yüksel
,
Seher Usta Heybet
,
Ahmet Hulusi Dinçoğlu
Öz
Beslenme, depresyon hastalarında depresyonun önlenmesinde ve semptomlarının azaltılmasında yardımcıdır. Çünkü depresyonun patofizyolojisi incelendiğinde bazı besinlerde eksiklikler görülür. Oksidatif stresin ayrıca hastalığın patofizyolojisine katkıda bulunabilecek inflamasyona neden olduğu bilinmektedir. Antioksidan olduğu bilinen antosiyaninin depresyon üzerindeki etkisi incelenmiştir. Web of Science veritabanında “Antosiyanidin” VEYA “Antosiyanidinler” VEYA “Antosiyanin” VEYA “Leucoantosiyanidinler” VE “depresyon” terimleri taranmış ve bu tarama sonucunda çıkan makaleler incelenmiştir. Tarama sonucunda 71 makale bulunmuş ve özeti incelenmiştir. Uygun görülen 55 makalenin tam metini incelenmiş ve 7 makale dahil edilme kriterlerinin tümünü karşılamıştır. Bu çalışmalara göre, antosiyanin depresyona karşı koruma sağlayabilir ve depresyonun semptomlarını hafifletebilir. Oksidatif stres ve nörogenezdeki bozulma inflamasyonun arkasında yatan mekanizmalardır. Çeşitli insan, hayvan ve in vitro çalışmalar, antosiyaninlerin güçlü anti-enflamatuar ve antioksidan özelliklere sahip olduğunu göstermektedir.
Kaynakça
- Helvacı Çelik F, Hocaoğlu Ç. Major Depresif Bozukluk Tanımı, Etyolojisi ve Epidemiyolojisi: Bir Gözden Geçirme. J Contemp Med [Internet]. 2016;6(1). Available from: http://dergipark.gov.tr/doi/10.16899/ctd.03180
- WHO. Depression and other common mental disorders: global health estimates [Internet]. Geneva PP - Geneva: World Health Organization; 2017. Available from: https://apps.who.int/iris/handle/10665/254610
- Xiong J, Lipsitz O, Nasri F, Lui LMW, Gill H, Phan L, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord [Internet]. 2020 Dec;277:55–64. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0165032720325891
- Racine N, McArthur BA, Cooke JE, Eirich R, Zhu J, Madigan S. Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19. JAMA Pediatr [Internet]. 2021 Nov 1;175(11):1142. Available from: https://jamanetwork.com/journals/ jamapediatrics/fullarticle/2782796
- Kris-Etherton PM, Petersen KS, Hibbeln JR, Hurley D, Kolick V, Peoples S, et al. Nutrition and behavioral health disorders: depression and anxiety. Nutr Rev [Internet]. 2021 Feb 11;79(3):247–60. Available from: https:// academic.oup.com/nutritionreviews/article/79/3/247/5843529
- Özenoğlu A. Duygudurumu, Besin ve Beslenme İlişkisi. Acibadem Univ Saglik Bilim Derg [Internet]. 2018 Jan 1;0–0. Available from: http:// acibadem.dergisi.org/pdf/pdf_AUD_483.pdf
- Yıldırım H. Nutrition in Patients with Mental Health Disorders. Turkiye Klin. 2021;77–81.
- Yoldaş İlktaş İ, Hızlı H. Nutrition and positive power. Turkiye Klin. 2019;26–30.
- Ali S, Corbi G, Maes M, Scapagnini G, Davinelli S. Exploring the Impact of Flavonoids on Symptoms of Depression: A Systematic Review and Meta-Analysis. Antioxidants [Internet]. 2021 Oct 20;10(11):1644. Available from: https://www.mdpi.com/2076-3921/10/11/1644
- Park S-J, Jaiswal V, Lee H-J. Dietary Intake of Flavonoids and Carotenoids Is Associated with Anti-Depressive Symptoms: Epidemiological Study and In Silico—Mechanism Analysis. Antioxidants [Internet]. 2021 Dec 27;11(1):53. Available from: https://www.mdpi.com/2076-3921/11/1/53
- Liu J, Zhou H, Song L, Yang Z, Qiu M, Wang J, et al. Anthocyanins: Promising Natural Products with Diverse Pharmacological Activities. Molecules [Internet]. 2021 Jun 22;26(13):3807. Available from: https:// www.mdpi.com/1420-3049/26/13/3807
- Kapoor L, Simkin AJ, George Priya Doss C, Siva R. Fruit ripening: dynamics and integrated analysis of carotenoids and anthocyanins. BMC Plant Biol [Internet]. 2022 Dec 11;22(1):27. Available from: https:// bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-021-03411-w
- Lee Y-M, Yoon Y, Yoon H, Park H-M, Song S, Yeum K-J. Dietary Anthocyanins against Obesity and Inflammation. Nutrients [Internet]. 2017 Oct 1;9(10):1089. Available from: http://www.mdpi.com/2072- 6643/9/10/1089
- Jesulola E, Micalos P, Baguley IJ. Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model - are we there yet? Behav Brain Res [Internet]. 2018 Apr;341:79– 90. Available from: https://linkinghub.elsevier.com/retrieve/pii/ S0166432817318521
- Spohr L, Luduvico KP, Soares MSP, Bona NP, Oliveira PS, de Mello JE, et al. Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide. Nutr Neurosci [Internet]. 2022 Apr 3;25(4):857–70. Available from: https://www.tandfonline.com/doi/full/10. 1080/1028415X.2020.1819104
- Ramos-Hryb AB, Cunha MP, Kaster MP, Rodrigues ALS. Natural Polyphenols and Terpenoids for Depression Treatment: Current Status. In: Studies in Natural Products Chemistry [Internet]. 2018. p. 181–221. Available from: https://linkinghub.elsevier.com/retrieve/pii/ B9780444640680000061
- Kontogianni MD, Vijayakumar A, Rooney C, Noad RL, Appleton KM, McCarthy D, et al. A High Polyphenol Diet Improves Psychological Well- Being: The Polyphenol Intervention Trial (PPhIT). Nutrients [Internet]. 2020 Aug 14;12(8):2445. Available from: https://www.mdpi.com/2072- 6643/12/8/2445
- Gamage E, Orr R, Travica N, Lane MM, Dissanayaka T, Kim JH, et al. Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research. Neurosci Biobehav Rev [Internet]. 2023 Aug;151:105225. Available from: https:// linkinghub.elsevier.com/retrieve/pii/S014976342300194X
- Fang J-L, Luo Y, Jin S-H, Yuan K, Guo Y. Ameliorative effect of anthocyanin on depression mice by increasing monoamine neurotransmitter and up-regulating BDNF expression. J Funct Foods [Internet]. 2020 Mar;66:103757. Available from: https://linkinghub. elsevier.com/retrieve/pii/S1756464619306814
- Khalifa I, Zhu W, Li K, Li C. Polyphenols of mulberry fruits as multifaceted compounds: Compositions, metabolism, health benefits, and stability—A structural review. J Funct Foods [Internet]. 2018 Jan;40:28–43. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1756464617306527
- Xie L, Su H, Sun C, Zheng X, Chen W. Recent advances in understanding the anti-obesity activity of anthocyanins and their biosynthesis in microorganisms. Trends Food Sci Technol [Internet]. 2018 Feb;72:13–24. Available from: https://linkinghub.elsevier.com/retrieve/ pii/S092422441730626X
- Nabavi SM, Daglia M, Braidy N, Nabavi SF. Natural products, micronutrients, and nutraceuticals for the treatment of depression: A short review. Nutr Neurosci [Internet]. 2017 Mar 16;20(3):180–94. Available from: https://www.tandfonline.com/doi/full/10.1080/102841 5X.2015.1103461
- Dreiseitel A, Korte G, Schreier P, Oehme A, Locher S, Domani M, et al. Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B. Pharmacol Res [Internet]. 2009 May;59(5):306–11. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043661809000449
- Chang S-C, Cassidy A, Willett WC, Rimm EB, O’Reilly EJ, Okereke OI. Dietary flavonoid intake and risk of incident depression in midlife and older women. Am J Clin Nutr [Internet]. 2016 Sep 1;104(3):704–14. Available from: https://academic.oup.com/ajcn/article/104/3/704/4564688
- Varadinova M, Drenska D, Boyadjieva N. Effects of anthocyanins on experimental depression in male rats. COMPTES RENDUS-ACADEMIE Bulg DES Sci. 2007;60(6):697–700.
- Shewale P, Hiray Y, Patil R. Antidepressant-like activity of anthocyanidins from Hibiscus rosa-sinensis flowers in tail suspension test and forced swim test. Indian J Pharmacol [Internet]. 2012;44(4):454. Available from: http://www.ijp-online.com/text.asp?2012/44/4/454/99303
- Xu Y, Li S, Chen R, Li G, Barish PA, You W, et al. Antidepressant-like effect of low molecular proanthocyanidin in mice: Involvement of monoaminergic system. Pharmacol Biochem Behav [Internet]. 2010 Jan;94(3):447–53. Available from: https://linkinghub.elsevier.com/ retrieve/pii/S0091305709003074
- Sanchez-Villegas A, Martínez-González MA. Diet, a new target to prevent depression? BMC Med [Internet]. 2013 Dec 3;11(1):3. Available from: http://bmcmedicine.biomedcentral.com/ articles/10.1186/1741-7015-11-3
- Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, Kosti R, Scarmeas N. Mediterranean diet, stroke, cognitive impairment, and depression: A meta‐analysis. Ann Neurol [Internet]. 2013 Oct 16;74(4):580–91. Available from: https://onlinelibrary.wiley.com/ doi/10.1002/ana.23944
- Oddo VM, Welke L, McLeod A, Pezley L, Xia Y, Maki P, et al. Adherence to a Mediterranean Diet Is Associated with Lower Depressive Symptoms among U.S. Adults. Nutrients [Internet]. 2022 Jan 11;14(2):278. Available from: https://www.mdpi.com/2072-6643/14/2/278
- Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry [Internet]. 2019 Jul 26;24(7):965–86. Available from: http:// www.nature.com/articles/s41380-018-0237-8
- Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga A-M. ROS and Brain Diseases: The Good, the Bad, and the Ugly. Oxid Med Cell Longev [Internet]. 2013;2013:1–14. Available from: http://www.hindawi.com/ journals/omcl/2013/963520/
- Fratelli M, Demol H, Puype M, Casagrande S, Eberini I, Salmona M, et al. Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc Natl Acad Sci U S A. 2002;99(6):3505–10.
- Salzano S, Checconi P, Hanschmann E-M, Lillig CH, Bowler LD, Chan P, et al. Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proc Natl Acad Sci [Internet]. 2014 Aug 19;111(33):12157–62. Available from: https://pnas.org/doi/full/10.1073/pnas.1401712111
- Howren MB, Lamkin DM, Suls J. Associations of Depression With C-Reactive Protein, IL-1, and IL-6: A Meta-Analysis. Psychosom Med [Internet]. 2009 Feb;71(2):171–86. Available from: https://journals.lww. com/00006842-200902000-00006
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- Guo S, Kim WJ, Lok J, Lee S-R, Besancon E, Luo B-H, et al. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci [Internet]. 2008 May 27;99(6):3505–10. Available from: https://pnas.org/doi/full/10.1073/ pnas.0801105105
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Potential Effects of Anthocyanin on Depression: A Review
Yıl 2024,
, 291 - 297, 02.06.2024
Emine Kurtbeyoglu
,
Gül Akduman
,
Fatma Yüksel
,
Seher Usta Heybet
,
Ahmet Hulusi Dinçoğlu
Öz
Nutrition is helpful in preventing depression and reducing its symptoms in depressed patients. This is because when the pathophysiology of depression is examined, deficiencies in certain nutrients are observed. Oxidative stress is also known to cause inflammation, which can contribute to the pathophysiology of the disease. We examined the effectiveness of anthocyanin, which is known to be an antioxidant, on depression. Related articles were searched in the Web of Science database. The combinations of the following terms were used for the search: “Anthocyanidin” OR “Anthocyanidins” OR “Anthocyanin” OR “Leucoanthocyanidins” AND “depression”. 71 abstracts were reviewed, 55 full-text articles were examined, and 7 papers met all of the inclusion criteria. According to these studies, anthocyanin may offer protection against depression and can alleviate its symptoms. Oxidative stress and deterioration in neurogenesis are the mechanisms behind inflammation. Various human, animal, and in vitro studies demonstrate that anthocyanins possess strong anti-inflammatory and antioxidant properties.
Kaynakça
- Helvacı Çelik F, Hocaoğlu Ç. Major Depresif Bozukluk Tanımı, Etyolojisi ve Epidemiyolojisi: Bir Gözden Geçirme. J Contemp Med [Internet]. 2016;6(1). Available from: http://dergipark.gov.tr/doi/10.16899/ctd.03180
- WHO. Depression and other common mental disorders: global health estimates [Internet]. Geneva PP - Geneva: World Health Organization; 2017. Available from: https://apps.who.int/iris/handle/10665/254610
- Xiong J, Lipsitz O, Nasri F, Lui LMW, Gill H, Phan L, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord [Internet]. 2020 Dec;277:55–64. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0165032720325891
- Racine N, McArthur BA, Cooke JE, Eirich R, Zhu J, Madigan S. Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19. JAMA Pediatr [Internet]. 2021 Nov 1;175(11):1142. Available from: https://jamanetwork.com/journals/ jamapediatrics/fullarticle/2782796
- Kris-Etherton PM, Petersen KS, Hibbeln JR, Hurley D, Kolick V, Peoples S, et al. Nutrition and behavioral health disorders: depression and anxiety. Nutr Rev [Internet]. 2021 Feb 11;79(3):247–60. Available from: https:// academic.oup.com/nutritionreviews/article/79/3/247/5843529
- Özenoğlu A. Duygudurumu, Besin ve Beslenme İlişkisi. Acibadem Univ Saglik Bilim Derg [Internet]. 2018 Jan 1;0–0. Available from: http:// acibadem.dergisi.org/pdf/pdf_AUD_483.pdf
- Yıldırım H. Nutrition in Patients with Mental Health Disorders. Turkiye Klin. 2021;77–81.
- Yoldaş İlktaş İ, Hızlı H. Nutrition and positive power. Turkiye Klin. 2019;26–30.
- Ali S, Corbi G, Maes M, Scapagnini G, Davinelli S. Exploring the Impact of Flavonoids on Symptoms of Depression: A Systematic Review and Meta-Analysis. Antioxidants [Internet]. 2021 Oct 20;10(11):1644. Available from: https://www.mdpi.com/2076-3921/10/11/1644
- Park S-J, Jaiswal V, Lee H-J. Dietary Intake of Flavonoids and Carotenoids Is Associated with Anti-Depressive Symptoms: Epidemiological Study and In Silico—Mechanism Analysis. Antioxidants [Internet]. 2021 Dec 27;11(1):53. Available from: https://www.mdpi.com/2076-3921/11/1/53
- Liu J, Zhou H, Song L, Yang Z, Qiu M, Wang J, et al. Anthocyanins: Promising Natural Products with Diverse Pharmacological Activities. Molecules [Internet]. 2021 Jun 22;26(13):3807. Available from: https:// www.mdpi.com/1420-3049/26/13/3807
- Kapoor L, Simkin AJ, George Priya Doss C, Siva R. Fruit ripening: dynamics and integrated analysis of carotenoids and anthocyanins. BMC Plant Biol [Internet]. 2022 Dec 11;22(1):27. Available from: https:// bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-021-03411-w
- Lee Y-M, Yoon Y, Yoon H, Park H-M, Song S, Yeum K-J. Dietary Anthocyanins against Obesity and Inflammation. Nutrients [Internet]. 2017 Oct 1;9(10):1089. Available from: http://www.mdpi.com/2072- 6643/9/10/1089
- Jesulola E, Micalos P, Baguley IJ. Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model - are we there yet? Behav Brain Res [Internet]. 2018 Apr;341:79– 90. Available from: https://linkinghub.elsevier.com/retrieve/pii/ S0166432817318521
- Spohr L, Luduvico KP, Soares MSP, Bona NP, Oliveira PS, de Mello JE, et al. Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide. Nutr Neurosci [Internet]. 2022 Apr 3;25(4):857–70. Available from: https://www.tandfonline.com/doi/full/10. 1080/1028415X.2020.1819104
- Ramos-Hryb AB, Cunha MP, Kaster MP, Rodrigues ALS. Natural Polyphenols and Terpenoids for Depression Treatment: Current Status. In: Studies in Natural Products Chemistry [Internet]. 2018. p. 181–221. Available from: https://linkinghub.elsevier.com/retrieve/pii/ B9780444640680000061
- Kontogianni MD, Vijayakumar A, Rooney C, Noad RL, Appleton KM, McCarthy D, et al. A High Polyphenol Diet Improves Psychological Well- Being: The Polyphenol Intervention Trial (PPhIT). Nutrients [Internet]. 2020 Aug 14;12(8):2445. Available from: https://www.mdpi.com/2072- 6643/12/8/2445
- Gamage E, Orr R, Travica N, Lane MM, Dissanayaka T, Kim JH, et al. Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research. Neurosci Biobehav Rev [Internet]. 2023 Aug;151:105225. Available from: https:// linkinghub.elsevier.com/retrieve/pii/S014976342300194X
- Fang J-L, Luo Y, Jin S-H, Yuan K, Guo Y. Ameliorative effect of anthocyanin on depression mice by increasing monoamine neurotransmitter and up-regulating BDNF expression. J Funct Foods [Internet]. 2020 Mar;66:103757. Available from: https://linkinghub. elsevier.com/retrieve/pii/S1756464619306814
- Khalifa I, Zhu W, Li K, Li C. Polyphenols of mulberry fruits as multifaceted compounds: Compositions, metabolism, health benefits, and stability—A structural review. J Funct Foods [Internet]. 2018 Jan;40:28–43. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1756464617306527
- Xie L, Su H, Sun C, Zheng X, Chen W. Recent advances in understanding the anti-obesity activity of anthocyanins and their biosynthesis in microorganisms. Trends Food Sci Technol [Internet]. 2018 Feb;72:13–24. Available from: https://linkinghub.elsevier.com/retrieve/ pii/S092422441730626X
- Nabavi SM, Daglia M, Braidy N, Nabavi SF. Natural products, micronutrients, and nutraceuticals for the treatment of depression: A short review. Nutr Neurosci [Internet]. 2017 Mar 16;20(3):180–94. Available from: https://www.tandfonline.com/doi/full/10.1080/102841 5X.2015.1103461
- Dreiseitel A, Korte G, Schreier P, Oehme A, Locher S, Domani M, et al. Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B. Pharmacol Res [Internet]. 2009 May;59(5):306–11. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043661809000449
- Chang S-C, Cassidy A, Willett WC, Rimm EB, O’Reilly EJ, Okereke OI. Dietary flavonoid intake and risk of incident depression in midlife and older women. Am J Clin Nutr [Internet]. 2016 Sep 1;104(3):704–14. Available from: https://academic.oup.com/ajcn/article/104/3/704/4564688
- Varadinova M, Drenska D, Boyadjieva N. Effects of anthocyanins on experimental depression in male rats. COMPTES RENDUS-ACADEMIE Bulg DES Sci. 2007;60(6):697–700.
- Shewale P, Hiray Y, Patil R. Antidepressant-like activity of anthocyanidins from Hibiscus rosa-sinensis flowers in tail suspension test and forced swim test. Indian J Pharmacol [Internet]. 2012;44(4):454. Available from: http://www.ijp-online.com/text.asp?2012/44/4/454/99303
- Xu Y, Li S, Chen R, Li G, Barish PA, You W, et al. Antidepressant-like effect of low molecular proanthocyanidin in mice: Involvement of monoaminergic system. Pharmacol Biochem Behav [Internet]. 2010 Jan;94(3):447–53. Available from: https://linkinghub.elsevier.com/ retrieve/pii/S0091305709003074
- Sanchez-Villegas A, Martínez-González MA. Diet, a new target to prevent depression? BMC Med [Internet]. 2013 Dec 3;11(1):3. Available from: http://bmcmedicine.biomedcentral.com/ articles/10.1186/1741-7015-11-3
- Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, Kosti R, Scarmeas N. Mediterranean diet, stroke, cognitive impairment, and depression: A meta‐analysis. Ann Neurol [Internet]. 2013 Oct 16;74(4):580–91. Available from: https://onlinelibrary.wiley.com/ doi/10.1002/ana.23944
- Oddo VM, Welke L, McLeod A, Pezley L, Xia Y, Maki P, et al. Adherence to a Mediterranean Diet Is Associated with Lower Depressive Symptoms among U.S. Adults. Nutrients [Internet]. 2022 Jan 11;14(2):278. Available from: https://www.mdpi.com/2072-6643/14/2/278
- Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry [Internet]. 2019 Jul 26;24(7):965–86. Available from: http:// www.nature.com/articles/s41380-018-0237-8
- Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga A-M. ROS and Brain Diseases: The Good, the Bad, and the Ugly. Oxid Med Cell Longev [Internet]. 2013;2013:1–14. Available from: http://www.hindawi.com/ journals/omcl/2013/963520/
- Fratelli M, Demol H, Puype M, Casagrande S, Eberini I, Salmona M, et al. Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc Natl Acad Sci U S A. 2002;99(6):3505–10.
- Salzano S, Checconi P, Hanschmann E-M, Lillig CH, Bowler LD, Chan P, et al. Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proc Natl Acad Sci [Internet]. 2014 Aug 19;111(33):12157–62. Available from: https://pnas.org/doi/full/10.1073/pnas.1401712111
- Howren MB, Lamkin DM, Suls J. Associations of Depression With C-Reactive Protein, IL-1, and IL-6: A Meta-Analysis. Psychosom Med [Internet]. 2009 Feb;71(2):171–86. Available from: https://journals.lww. com/00006842-200902000-00006
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