IJCM  Vol.9 No.5 , May 2018
The Effect of Curcumin on Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Open Label Study
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), recently renamed as systemic exertion intolerance disease (SEID), is a chronic and often disabling disease. Although the exact pathophysiological mechanism of ME/CFS is unknown, immunological abnormalities may play an important role. Curcumin is a herb with powerful anti-oxidative, and anti-inflammatory properties. Therefore, we hypothesized that curcumin has favorable effects on symptomatology in ME/CFS patients. In total 52 patients participated, nine stopped the use of curcumin because of side effects. All remaining patients (n = 43) met the criteria for CFS; 72% met the criteria for ME. Before and 8 weeks after the use of curcumin complexed with phosphatidyl choline, 500 mg bid, the CDC inventory for assessment of Chronic Fatigue Syndrome was filled in. The CDC questions (n = 19) were scored and divided into 2 parts: the first being specific for CFS complaints (n = 9), the second being scores of less specific symptoms (n = 10); denoted as CDC rest score. Results showed that 8 weeks curcumin use significantly decreased the CFS related symptom scores, but not the CDC rest scores. Analyzing the data separately for ME and CFS patients, the same significance for the CFS symptom scores was present. Conclusion: in this open-labeled study, 8 weeks curcumin use in a phosphatidyl choline complex reduced ME/CFS symptomatology. Therefore, a randomized placebo controlled study is warranted to assess its efficacy in ME/CFS patients.
Cite this paper: van Campen, C. , Riepma, K. and Visser, F. (2018) The Effect of Curcumin on Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Open Label Study. International Journal of Clinical Medicine, 9, 356-366. doi: 10.4236/ijcm.2018.95031.

[1]   Joe, B. and Lokesh, B.R. (1994) Role of Capsaicin, Curcumin and Dietary n-3 Fatty Acids in Lowering the Generation of Reactive Oxygen Species in Rat Peritoneal Macrophages. Biochimica et Biophysica Acta, 1224, 255-263.

[2]   Joe, B., Vijaykumar, M. and Lokesh, B.R. (2004) Biological Properties of Curcumin-Cellular and Molecular Mechanisms of Action. Critical Reviews in Food Science and Nutrition, 44, 97-111.

[3]   Mahady, G.B., Pendland, S.L., Yun, G. and Lu, Z.Z. (2002) Turmeric (Curcuma longa) and Curcumin Inhibit the Growth of Helicobacter Pylori, a Group 1 Carcinogen. Anticancer Research, 22, 4179-4181.

[4]   Reddy, R.C., Vatsala, P.G., Keshamouni, V.G., Padmanaban, G. and Rangarajan, P.N. (2005) Curcumin for Malaria Therapy. Biochemical and Biophysical Research Communications, 326, 472-474.

[5]   Wright, L.E., Frye, J.B., Gorti, B., Timmermann, B.N. and Funk, J.L. (2013) Bioactivity of Turmeric-Derived Curcuminoids and Related Metabolites in Breast Cancer. Current Pharmaceutical Design, 19, 6218-6125.

[6]   Abdel-Daim, M.M. and Abdou, R.H. (2015) Protective Effects of Diallyl Sulfide and Curcumin Separately against Thallium-Induced Toxicity in Rats. Cell Journal, 17, 379-388.

[7]   Kang, J., Chen, J., Shi, Y., Jia, J. and Zhang, Y. (2005) Curcumin-Induced Histone Hypoacetylation: The Role of Reactive Oxygen Species. Biochemical Pharmacology, 69, 1205-1213.

[8]   Reddy, A.C. and Lokesh, B.R. (1994) Effect of Dietary Turmeric (Curcuma longa) on Iron-Induced Lipid Peroxidation in the Rat Liver. Food and Chemical Toxicology, 32, 279-283.

[9]   Jeong, G.S., Oh, G.S., Pae, H.O., Jeong, S.O., Kim, Y.C., Shin, M.K., et al. (2006) Comparative Effects of Curcuminoids on Endothelial Heme Oxygenase-1 Expression: Ortho-Methoxy Groups Are Essential to Enhance Heme Oxygenase Activity and Protection. Experimental & Molecular Medicine, 38, 393-400.

[10]   Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010) Oxidative Stress, Inflammation, and Cancer: How Are They Linked? Free Radical Biology & Medicine, 49, 1603-1616.

[11]   Sethi, G., Sung, B. and Aggarwal, B.B. (2008) Nuclear Factor-κB Activation: From Bench to Bedside. Experimental Biology and Medicine (Maywood), 233, 21-31.

[12]   Anthwal, A., Thakur, B.K., Rawat, M.S., Rawat, D.S., Tyagi, A.K. and Aggarwal, B.B. (2014) Synthesis, Characterization and in Vitro Anticancer Activity of C-5 Curcumin Analogues with Potential to Inhibit TNF-Alpha-Induced NF-KappaB Activation. BioMed Research International, 2014, Article ID: 524161.

[13]   Cho, J.W., Lee, K.S. and Kim, C.W. (2007) Curcumin Attenuates the Expression of IL-1beta, IL-6, and TNF-Alpha as Well as Cyclin E in TNF-Alpha-Treated HaCaT Cells; NF-κB and MAPKs as Potential Upstream Targets. International Journal of Molecular Medicine, 19, 469-474.

[14]   Li, R., Wang, Y., Liu, Y., Chen, Q., Fu, W., Wang, H., et al. (2013) Curcumin Inhibits Transforming Growth Factor-beta1-Induced EMT via PPARγ Pathway, Not Smad Pathway in Renal Tubular Epithelial Cells. PLoS ONE, 8, e58848.

[15]   Ruiz de Porras, V., Bystrup, S., Martinez-Cardus, A., Pluvinet, R., Sumoy, L., Howells, L., et al. (2016) Curcumin Mediates Oxaliplatin-Acquired Resistance Reversion in Colorectal Cancer Cell Lines through Modulation of CXC-Chemokine/NF-κB Signalling Pathway. Scientific Reports, 6, Article ID: 24675.

[16]   Paulino, N., Paulino, A.S., Diniz, S.N., de Mendonca, S., Goncalves, I.D., Faiao Flores, F., et al. (2016) Evaluation of the Anti-Inflammatory Action of Curcumin Analog (DM1): Effect on iNOS and COX-2 Gene Expression and Autophagy Pathways. Bioorganic & Medicinal Chemistry, 24, 1927-1935.

[17]   Nieto, C.I., Cabildo, M.P., Cornago, M.P., Sanz, D., Claramunt, R.M., Torralba, M.C., et al. (2015) Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin. Molecules, 20, 15643-15665.

[18]   Huang, C.Z., Huang, W.Z., Zhang, G. and Tang, D.L. (2013) In Vivo Study on the Effects of Curcumin on the Expression Profiles of Anti-Tumour Genes (VEGF, CyclinD1 and CDK4) in Liver of Rats Injected with DEN. Molecular Biology Reports, 40, 5825-5831.

[19]   Pulido-Moran, M., Moreno-Fernandez, J., Ramirez-Tortosa, C. and Ramirez-Tortosa, M. (2016) Curcumin and Health. Molecules, 21, 264.

[20]   Pari, L., Tewas, D. and Eckel, J. (2008) Role of Curcumin in Health and Disease. Archives of Physiology and Biochemistry, 114, 127-149.

[21]   Tenero, L., Piazza, M., Zanoni, L., Bodini, A., Peroni, D. and Piacentini, G.L. (2016) Antioxidant Supplementation and Exhaled Nitric Oxide in Children with Asthma. Allergy & Asthma Proceedings, 37, 8-13.

[22]   Ahn, J.K., Kim, S., Hwang, J., Kim, J., Lee, Y.S., Koh, E.M., et al. (2015) Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis. PLoS ONE, 10, e0145539.

[23]   Lang, A., Salomon, N., Wu, J.C., Kopylov, U., Lahat, A., Har-Noy, O., et al. (2015) Curcumin in Combination with Mesalamine Induces Remission in Patients with Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. Clinical Gastroenterology and Hepatology, 13, 1444-1449e1.

[24]   Rainey-Smith, S.R., Brown, B.M., Sohrabi, H.R., Shah, T., Goozee, K.G., Gupta, V.B., et al. (2016) Curcumin and Cognition: A Randomised, Placebo-Controlled, Double-Blind Study of Community-Dwelling Older Adults. British Journal of Nutrition, 115, 2106-2113.

[25]   Yu, J.J., Pei, L.B., Zhang, Y., Wen, Z.Y. and Yang, J.L. (2015) Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Journal of Clinical Psychopharmacology, 35, 406-410.

[26]   Mahammedi, H., Planchat, E., Pouget, M., Durando, X., Cure, H., Guy, L., et al. (2016) The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study. Oncology, 90, 69-78.

[27]   Yang, H., Xu, W., Zhou, Z., Liu, J., Li, X., Chen, L., et al. (2015) Curcumin Attenuates Urinary Excretion of Albumin in Type II Diabetic Patients with Enhancing Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) System and Repressing Inflammatory Signaling Efficacies. Experimental and Clinical Endocrinology & Diabetes, 123, 360-367.

[28]   Panahi, Y., Rahimnia, A.R., Sharafi, M., Alishiri, G., Saburi, A. and Sahebkar, A. (2014) Curcuminoid Treatment for Knee Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Trial. Phytotherapy Research, 28, 1625-1631.

[29]   Akazawa, N., Choi, Y., Miyaki, A., Tanabe, Y., Sugawara, J., Ajisaka, R., et al. (2012) Curcumin Ingestion and Exercise Training Improve Vascular Endothelial Function in Postmenopausal Women. Nutrition Research, 32, 795-799.

[30]   IOM (2015) Beyond Mayalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. The National Academies Press, Washington DC.

[31]   Twisk, F.N. (2014) The Status of and Future Research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: The Need of Accurate Diagnosis, Objective Assessment, and Acknowledging Biological and Clinical Subgroups. Frontiers in Physiology, 5, 109.

[32]   Jason, L.A. and Richman, J.A. (2008) How Science Can Stigmatize: The Case of Chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome, 14, 85-103.

[33]   Morris, G., Berk, M., Walder, K. and Maes, M. (2015) Central Pathways Causing Fatigue in Neuro-Inflammatory and Autoimmune Illnesses. BMC Medicine, 13, 28.

[34]   Nijs, J., Nees, A., Paul, L., De Kooning, M., Ickmans, K., Meeus, M., et al. (2014) Altered Immune Response to Exercise in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Literature Review. Exercise Immunology Review, 20, 94-116.

[35]   Maes, M., Bosmans, E. and Kubera, M. (2015) Increased Expression of Activation Antigens on CD8+ T Lymphocytes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Inverse Associations with Lowered CD19+ Expression and CD4+/CD8+ Ratio, But No Associations with (auto)immune, Leaky Gut, Oxidative and Nitrosative Stress Biomarkers. Neuro Enocrinology Letters, 36, 439-446.

[36]   Jason, L., Sorenson, M., Sebally, K., Alkazemi, D., Lerch, A., Porter, N., et al. (2011) Increased HDAC in Association with Decreased Plasma Cortisol in Older Adults with Chronic Fatigue Syndrome. Brain, Behavior, and Immunity, 25, 1544-1547.

[37]   Morris, G., Anderson, G., Dean, O., Berk, M., Galecki, P., Martin-Subero, M., et al. (2014) The Glutathione System: A New Drug Target in Neuroimmune Disorders. Molecular Neurobiology, 50, 1059-1084.

[38]   Blundell, S., Ray, K.K., Buckland, M. and White, P.D. (2015) Chronic Fatigue Syndrome and Circulating Cytokines: A Systematic Review. Brain, Behavior, and Immunity, 50, 186-195.

[39]   Russell, L., Broderick, G., Taylor, R., Fernandes, H., Harvey, J., Barnes, Z., et al. (2016) Illness Progression in Chronic Fatigue Syndrome: A Shifting Immune Baseline. BMC Immunology, 17, 3.

[40]   Landi, A., Broadhurst, D., Vernon, S.D., Tyrrell, D.L. and Houghton, M. (2016) Reductions in Circulating Levels of IL-16, IL-7 and VEGF-A in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Cytokine, 78, 27-36.

[41]   Hornig, M., Montoya, J.G., Klimas, N.G., Levine, S., Felsenstein, D., Bateman, L., et al. (2015) Distinct Plasma Immune Signatures in ME/CFS Are Present Early in the Course of Illness. Science Advances, 1, e1400121.

[42]   Hornig, M., Montoya, J.G., Klimas, N.G., Levine, S., Felsenstein, D., Bateman, L., et al. (2016) Distinct Plasma Ebrospinal Fluid in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Molecular Psychiatry, 21, 261-269.

[43]   Gupta, A., Vij, G., Sharma, S., Tirkey, N., Rishi, P. and Chopra, K. (2009) Curcumin, a Polyphenolic Antioxidant, Attenuates Chronic Fatigue Syndrome in Murine Water Immersion Stress Model. Immunobiology, 214, 33-39.

[44]   Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G. and Komaroff, A. (1994) The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study. International Chronic Fatigue Syndrome Study Group. Annals of Internal Medicine, 121, 953-959.

[45]   Carruthers, B.M., van de Sande, M.I., DE Meirleir, K.L., Klimas, N.G., Broderick, G., Mitchell, T., et al. (2011) Myalgic Encephalomyelitis: International Consensus Criteria. Journal of Internal Medicine, 270, 327-338.

[46]   Wagner, D., Nisenbaum, R., Heim, C., Jones, J.F., Unger, E.R. and Reeves, W.C. (2005) Psychometric Properties of the CDC Symptom Inventory for Assessment of Chronic Fatigue Syndrome. Population Health Metrics, 3, 8.

[47]   Vermeulen, R.C. (2006) Translation and Validation of the Dutch Language Version of the CDC Symptom Inventory for Assessment of Chronic Fatigue Syndrome (CFS). Population Health Metrics, 4, 12.

[48]   Morris, G., Berk, M., Galecki, P., Walder, K. and Maes, M. (2016) The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases. Molecular Neurobiology, 53, 1195-219.

[49]   Nakatomi, Y., Mizuno, K., Ishii, A., Wada, Y., Tanaka, M., Tazawa, S., et al. (2014) Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. Journal of Nuclear Medicine, 55, 945-950.

[50]   Ryu, E.K., Choe, Y.S., Lee, K.H., Choi, Y. and Kim, B.T. (2006) Curcumin and Dehydrozingerone Derivatives: Synthesis, Radiolabeling, and Evaluation for Beta-Amyloid Plaque Imaging. Journal of Medicinal Chemistry, 49, 6111-6119.

[51]   Prasad, S., Tyagi, A.K. and Aggarwal, B.B. (2014) Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: The Golden Pigment from Golden Spice. Cancer Research and Treatment, 46, 2-18.

[52]   Marczylo, T.H., Verschoyle, R.D., Cooke, D.N., Morazzoni, P., Steward, W.P. and Gescher, A.J. (2007) Comparison of Systemic Availability of Curcumin with That of Curcumin Formulated with Phosphatidylcholine. Cancer Chemotherapy and Pharmacology, 60, 171-177.

[53]   Gupta, N.K. and Dixit, V.K. (2011) Bioavailability Enhancement of Curcumin by Complexation with Phosphatidyl Choline. Journal of Pharmaceutical Sciences, 100, 1987-1995.

[54]   Maes, M., Twisk, F.N. and Johnson, C. (2012) Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) Are Distinguished Accurately: Results of Supervised Learning Techniques Applied on Clinical and Inflammatory Data. Psychiatry Research, 200, 754-760.

[55]   Jason, L.A., Brown, A., Evans, M., Sunnquist, M. and Newton, J.L. (2013) Contrasting Chronic Fatigue Syndrome versus Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fatigue, 1, 168-183.

[56]   Jason, L.A., McManimen, S., Sunnquist, M., Brown, A., Furst, J., Newton, J.L., et al. (2016) Case Definitions Integrating Empiric and Consensus Perspectives. Fatigue, 4, 1-23.

[57]   Jason, L.A., Evans, M., Brown, A., Sunnquist, M. and Newton, J.L. (2015) Chronic Fatigue Syndrome versus Sudden Onset Myalgic Encephalomyelitis. Journal of Prevention & Intervention in the Community, 43, 62-77.

[58]   Brown, M.M. and Jason, L.A. (2007) Functioning in Individuals with Chronic Fatigue Syndrome: Increased Impairment with Co-Occurring Multiple Chemical Sensitivity and Fibromyalgia. Dynamic Medicine, 6, 9.