{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:28:33Z","timestamp":1792099713336,"version":"4.4.0"},"reference-count":61,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Research Fund","award":["022\/2012"],"award-info":[{"award-number":["022\/2012"]}]},{"name":"Thailand Research Fund","award":["29\/2013"],"award-info":[{"award-number":["29\/2013"]}]},{"name":"Thai Traditional Medical Knowledge Fund, Ministry of Public Health","award":["022\/2012"],"award-info":[{"award-number":["022\/2012"]}]},{"name":"Thai Traditional Medical Knowledge Fund, Ministry of Public Health","award":["29\/2013"],"award-info":[{"award-number":["29\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Type 2 diabetes and depression co-occur in a bidirectional manner. Curcumin supplements exhibit antidepressant effects that may mitigate depression by modulating neurotransmitters and reducing inflammatory and oxidative stress pathways. This study aimed to evaluate the efficacy of curcumin in improving depression severity in obese type 2 diabetes patients. The study employed a randomized, double-blind, placebo-controlled trial design with 227 participants. The primary end-point was depression severity assessed using the Patient Health Questionnaire-9. Biomarkers were measured at baseline and at 3-, 6-, 9-, and 12-month intervals. The biomarkers assessed were serotonin levels, pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), antioxidant activities (total antioxidant status, glutathione peroxidase, and superoxide dismutase), and malondialdehyde. After 12 months, the curcumin group exhibited significantly improved depression severity (p = 0.000001). The curcumin group had higher levels of serotonin (p &lt; 0.0001) but lower levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha (p &lt; 0.001 for all) than the placebo group. Total antioxidant status, glutathione peroxidase activity, and superoxide dismutase activity were elevated in the curcumin group, whereas malondialdehyde levels were greater in the placebo group (p &lt; 0.001 for all). These findings suggest curcumin may have antidepressant effects on obese type 2 diabetes patients.<\/jats:p>","DOI":"10.3390\/nu16152414","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T11:43:44Z","timestamp":1721907824000},"page":"2414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Curcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"16","author":[{"given":"Metha","family":"Yaikwawong","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laddawan","family":"Jansarikit","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwanon","family":"Jirawatnotai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence for Precision Medicine and Systems Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somlak","family":"Chuengsamarn","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Faculty of Medicine, HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Nakhon Nayok 26120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/S0140-6736(20)32374-6","article-title":"The Lancet Commission on diabetes: Using data to transform diabetes care and patient lives","volume":"396","author":"Chan","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_3","first-page":"107","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Hashim","year":"2020","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jdiacomp.2005.02.003","article-title":"Risk factors for heart disease and stroke among diabetic persons, by disability status","volume":"19","author":"Okoro","year":"2005","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_5","unstructured":"American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Forth Edition Text Revision (DSM-IV-TR), American Psychiatric Association."},{"key":"ref_6","unstructured":"(2024, May 11). Word Health Organization. Depressive Disorder (Depression), Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/depression."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1001\/jama.289.23.3095","article-title":"The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R)","volume":"289","author":"Kessler","year":"2003","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1016\/S0165-0327(12)70004-6","article-title":"Epidemiology of depression and diabetes: A systematic review","volume":"142","author":"Roy","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_9","first-page":"120","article-title":"The association between Diabetes mellitus and Depression","volume":"9","author":"Kobylinska","year":"2016","journal-title":"J. Med. Life"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.2337\/dc08-0985","article-title":"Depression and Type 2 Diabetes Over the Lifespan: A meta-analysis","volume":"31","author":"Mezuk","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1002\/oby.22969","article-title":"Antidepressant Medications and Weight Change: A Narrative Review","volume":"28","author":"Gill","year":"2020","journal-title":"Obesity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"k3222","DOI":"10.1136\/bmj.k3222","article-title":"Antidepressant induced weight gain associated with anti-histaminergic activity","volume":"362","author":"Salvi","year":"2018","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1016\/S0924-977X(99)00030-9","article-title":"Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders","volume":"9","author":"Nutt","year":"1999","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e759","DOI":"10.1038\/tp.2016.25","article-title":"Is increased antidepressant exposure a contributory factor to the obesity pandemic?","volume":"6","author":"Lee","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_15","first-page":"43","article-title":"How to control weight gain when prescribing antidepressants","volume":"6","author":"Schwartz","year":"2007","journal-title":"Curr. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/bph.13621","article-title":"Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases","volume":"174","author":"Kunnumakkara","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","first-page":"141","article-title":"Anti-inflammatory properties of curcumin, a major constituent","volume":"14","author":"Julie","year":"2009","journal-title":"Altern. Med. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cbi.2008.05.003","article-title":"Antioxidant and radical scavenging properties of curcumin","volume":"174","author":"Ak","year":"2008","journal-title":"Chem.-Biol. Interact."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Aggarwal, B.B., Surh, Y.-J., and Shishodia, S. (2007). Antioxidant and anti-inflammatory properties of curcumin. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer US.","DOI":"10.1007\/978-0-387-46401-5"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ejphar.2005.06.002","article-title":"The effects of curcumin on depressive-like behaviors in mice","volume":"518","author":"Xu","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00213-008-1300-y","article-title":"Antidepressant activity of curcumin: Involvement of serotonin and dopamine system","volume":"201","author":"Kulkarni","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejphar.2007.08.045","article-title":"The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors","volume":"578","author":"Wang","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.brainres.2007.05.071","article-title":"Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats","volume":"1162","author":"Xu","year":"2007","journal-title":"Brain Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.jep.2006.09.042","article-title":"Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test","volume":"110","author":"Xia","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/s11655-015-2160-z","article-title":"An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial","volume":"21","author":"Esmaily","year":"2015","journal-title":"Chin. J. Integr. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jad.2014.06.001","article-title":"Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study","volume":"167","author":"Lopresti","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/ptr.6571","article-title":"Beneficial effects of nano-curcumin supplement on depression and anxiety in diabetic patients with peripheral neuropathy: A randomized, double-blind, placebo-controlled clinical trial","volume":"34","author":"Asadi","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.clnesp.2020.09.029","article-title":"Curcumin administration and the effects on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes and coronary heart disease","volume":"40","author":"Shafabakhsh","year":"2020","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2017). Standards of medical care in diabetes\u20142017 abridged for primary care providers. Clin. Diabetes, 35, 5\u201326.","DOI":"10.2337\/cd16-0067"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lotrakul, M., Sumrithe, S., and Saipanish, R. (2008). Reliability and validity of the Thai version of the PHQ-9. BMC Psychiatry, 8.","DOI":"10.1186\/1471-244X-8-46"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kroenke, K., and Spitzer, R.L. (2002). The PHQ-9: A New Depression Diagnostic and Severity Measure, Slack Incorporated.","DOI":"10.3928\/0048-5713-20020901-06"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S0377-1237(09)80120-2","article-title":"Serum Serotonin Abnormality in Depression","volume":"65","author":"Saldanha","year":"2009","journal-title":"Med. J. Armed Forces India"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1017\/SJP.2021.20","article-title":"Depressive Symptoms are Associated with low Serotonin Levels in Plasma but are not 5\u2013HTTLPR Genotype Dependent in Older Adults","volume":"24","year":"2021","journal-title":"Span. J. Psychol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1089\/107555303321223035","article-title":"Safety and anti-inflammatory activity of curcumin: A component of tumeric (Curcuma longa)","volume":"9","year":"2003","journal-title":"J. Altern. Complement. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"Erel","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jdiacomp.2013.12.002","article-title":"Association between serum uric acid level and microalbuminuria to chronic vascular complications in Thai patients with type 2 diabetes","volume":"28","author":"Chuengsamarn","year":"2014","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41572-023-00454-1","article-title":"Major depressive disorder","volume":"9","author":"Marx","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s40265-015-0347-4","article-title":"Depression in Type 2 Diabetes Mellitus: Prevalence, Impact, and Treatment","volume":"75","author":"Semenkovich","year":"2015","journal-title":"Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.pnpbp.2013.07.009","article-title":"Antidepressant-like effects of curcumin in chronic mild stress of rats: Involvement of its anti-inflammatory action","volume":"47","author":"Jiang","year":"2013","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fan, C., Song, Q., Wang, P., Li, Y., Yang, M., and Yu, S.Y. (2019). Neuroprotective effects of curcumin on IL-1\u03b2-induced neuronal apoptosis and depression-like behaviors caused by chronic stress in rats. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00516"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.intimp.2017.01.016","article-title":"Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-\u03baB translocation","volume":"44","author":"Afrin","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2174\/1381612822666161006151605","article-title":"Curcumin: An effective inhibitor of interleukin-6","volume":"23","author":"Ghandadi","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12235","DOI":"10.1039\/D1FO02696H","article-title":"Curcumin supplementation improves biomarkers of oxidative stress and inflammation in conditions of obesity, type 2 diabetes and NAFLD: Updating the status of clinical evidence","volume":"12","author":"Mokgalaboni","year":"2021","journal-title":"Food Funct."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: From evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/npp.2011.205","article-title":"Psychoneuroimmunology meets neuropsychopharmacology: Translational implications of the impact of inflammation on behavior","volume":"37","author":"Haroon","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1179\/135100003225003393","article-title":"Oxidative damage and major depression: The potential antioxidant action of selective serotonin re-uptake inhibitors","volume":"8","author":"Khanzode","year":"2003","journal-title":"Redox Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.bbi.2012.11.011","article-title":"Dysregulated relationship of inflammation and oxidative stress in major depression","volume":"31","author":"Rawdin","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S1734-1140(11)70600-4","article-title":"Lipoic acid\u2013biological activity and therapeutic potential","volume":"63","author":"Piechota","year":"2011","journal-title":"Pharmacol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Benameur, T., Soleti, R., Panaro, M.A., La Torre, M.E., Monda, V., Messina, G., and Porro, C. (2021). Curcumin as prospective anti-aging natural compound: Focus on brain. Molecules, 26.","DOI":"10.3390\/molecules26164794"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2019.02.020","article-title":"Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review","volume":"406","author":"Abrahams","year":"2019","journal-title":"Neuroscience"},{"key":"ref_52","first-page":"CC04","article-title":"Oxidative stress and major depression","volume":"8","author":"Bajpai","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_53","first-page":"37","article-title":"Weight gain and antidepressants","volume":"61","author":"Fava","year":"2000","journal-title":"J. Clin. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"979","DOI":"10.4088\/JCP.09r05346blu","article-title":"Antidepressants and body weight: A comprehensive review and meta-analysis","volume":"71","author":"Serretti","year":"2010","journal-title":"J. Clin. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1464-5491.1990.tb01375.x","article-title":"Obesity, Weight Loss and Prognosis in Type 2 Diabetes","volume":"7","author":"Lean","year":"1990","journal-title":"Diabet. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1055\/s-0043-100019","article-title":"Efficacy and safety of phytosomal curcumin in non-alcoholic fatty liver disease: A randomized controlled trial","volume":"67","author":"Panahi","year":"2017","journal-title":"Drug Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Saadati, S., Sadeghi, A., Mansour, A., Yari, Z., Poustchi, H., Hedayati, M., Hatami, B., and Hekmatdoost, A. (2019). Curcumin and inflammation in non-alcoholic fatty liver disease: A randomized, placebo controlled clinical trial. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-1055-4"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/ptr.5659","article-title":"Treatment of non-alcoholic fatty liver disease with curcumin: A randomized placebo-controlled trial","volume":"30","author":"Rahmani","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_59","first-page":"e2900","article-title":"Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions","volume":"21","author":"Hsieh","year":"2001","journal-title":"Anticancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pnpbp.2017.04.035","article-title":"IDO chronic immune activation and tryptophan metabolic pathway: A potential pathophysiological link between depression and obesity","volume":"80","author":"Lima","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Correia, A.S., Cardoso, A., and Vale, N. (2023). Oxidative stress in depression: The link with the stress response, neuroinflammation, serotonin, neurogenesis and synaptic plasticity. Antioxidants, 12.","DOI":"10.3390\/antiox12020470"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/15\/2414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:23:18Z","timestamp":1760109798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/15\/2414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":61,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["nu16152414"],"URL":"https:\/\/doi.org\/10.3390\/nu16152414","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,25]]}}}