Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial
Kirti S Pawar, Rahul N Mastud, Satheesh K Pawar, Samragni S Pawar, Rahul R Bhoite, Ramesh R Bhoite, Meenal V Kulkarni, Aditi R Deshpande
Frontiers in Pharmacology, doi:10.3389/fphar.2021.669362
Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, antithrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19. Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India. Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5 mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomes were assessed for the duration of hospitalization. Results: Patients with mild, moderate, and severe symptoms who received curcumin/ piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group. Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events.
ETHICS STATEMENT The studies involving human participants were reviewed and approved by The Royal Pune Independent Ethics Committee. The patients/participants provided their written informed consent to participate in this study.
AUTHOR CONTRIBUTIONS KP contributed to study design, data interpretation, writing of the manuscript, and literature search; RM, SKP, and SSP contributed to data collection and literature search. RhB and RmB performed the literature search; and MK and AD performed the data analysis.
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2021.669362/ full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Aggarwal, Harikumar, Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases, Int. J. Biochem. Cel Biol,
doi:10.1016/j.biocel.2008.06.010
Anand, Kunnumakkara, Newman, Aggarwal, Bioavailability of Curcumin: Problems and Promises, Mol. Pharmaceutics,
doi:10.1021/mp700113r
Biswas, Rahman, Modulation of Steroid Activity in Chronic Inflammation: a Novel Anti-inflammatory Role for Curcumin, Mol. Nutr. Food Res,
doi:10.1002/mnfr.200700259
Conti, Caraffa, Gallenga, Ross, Kritas et al., IL-1 Induces Throboxane-A2 (TxA2) in COVID-19 Causing Inflammation and Micro-thrombi: Inhibitory Effect of the IL-1 Receptor Antagonist
De Almeida Alvarenga, Leal, Borges, Silva De Aguiar, Faxén-Irving et al., Curcumin -A Promising Nutritional Strategy for Chronic Kidney Disease Patients, J. Funct. Foods,
doi:10.1016/j.jff.2017.12.015
Ghosh, Gehr, Ghosh, Curcumin and Chronic Kidney Disease (CKD): Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase, Molecules,
doi:10.3390/molecules191220139
Han, The Effects of Black Pepper on the Intestinal Absorption and Hepatic Metabolism of Drugs, Expert Opin. Drug Metab. Toxicol,
doi:10.1517/17425255.2011.570332
Keihanian, Saeidinia, Bagheri, Johnston, Sahebkar, None
Leong, The Spice for Hypertension: Protective Role of Curcuma Longa, Biomed. Pharmacol. J,
doi:10.13005/bpj/1555
Liu, Ying, The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and its Potential Use in the Associated Severe Pneumonia, Front Cel Dev Biol,
doi:10.3389/fcell.2020.00479
Loeber, Buechner, Dissertatio Inauguralis Medica de Curcuma Officinarum Ejusque Genuinis Virtutibus
Maurya, Kumar, Prasad, Bhatt, Saxena, Structure-based Drug Designing for Potential Antiviral Activity of Selected Natural Products from Ayurveda against SARS-CoV-2 Spike Glycoprotein and its Cellular Receptor, VirusDis,
doi:10.1007/s13337-020-00598-8
Mollazadeh, Cicero, Blesso, Pirro, Majeed et al., Immune Modulation by Curcumin: The Role of Interleukin-10, Crit. Rev. Food Sci. Nutr,
doi:10.1080/10408398.2017.1358139
Moriyuki, Sekiguchi, Matsubara, Nishikawa, Kawabata, Curcumin Inhibits the Proteinase-Activated Receptor-2-Triggered Prostaglandin E2 Production by Suppressing Cyclooxygenase-2 Upregulation and Akt-dependent Activation of Nuclear Factor-Κb in Human Lung Epithelial Cells, J. Pharmacol. Sci,
doi:10.1254/jphs.10126sc
Poolsup, Suksomboon, Kurnianta, Deawjaroen, Effects of Curcumin on Glycemic Control and Lipid Profile in Prediabetes and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis, PloS one,
doi:10.1371/journal.pone.0215840
Ravindran, Prasad, Aggarwal, Curcumin and Cancer Cells: How many Ways Can Curry Kill Tumor Cells Selectively?, AAPS J,
doi:10.1208/s12248-009-9128-x
Salehi, Stojanović-Radić, Matejić, Sharifi-Rad, Anil Kumar et al., The Therapeutic Potential of Curcumin: A Review of Clinical Trials, Eur. J. Med. Chem,
doi:10.1016/j.ejmech.2018.12.016
Shanmugam, Rane, Kanchi, Arfuso, Chinnathambi et al., The Multifaceted Role of Curcumin in Cancer Prevention and Treatment, Molecules,
doi:10.3390/molecules20022728
Sharma, Chopra, Kulkarni, Agrewala, Resveratrol and Curcumin Suppress Immune Response through CD28/CTLA-4 and CD80 Costimulatory Pathway, Clin. Exp. Immunol,
doi:10.1111/j.1365-2249.2006.03257.x
Sharma, Nehru, Munshi, Jyothy, Antioxidant Potential of Curcumin against Oxidative Insult Induced by Pentylenetetrazol in Epileptic Rats, Methods Find Exp. Clin. Pharmacol,
doi:10.1358/mf.2010.32.4.1452090
Shoba, Joy, Joseph, Majeed, Rajendran et al., Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers, Planta Med,
doi:10.1055/s-2006-957450
Singh, Potential Role of Curcumin against Viral Infections with a View on Structure and Pathogenesis of COVID-19, AIJR Preprints,
doi:10.21467/preprints.213
Suresh, Srinivasan, Tissue Distribution & Elimination of Capsaicin, Piperine & Curcumin Following Oral Intake in Rats, Indian J. Med. Res
Toden, Goel, The Holy Grail of Curcumin and its Efficacy in Various Diseases: Is Bioavailability Truly a Big Concern?, J Restorat Med,
doi:10.14200/jrm.2017.6.0101
Vogel, Pelletier, Examen chimique de la racine de Curcuma, J. Pharm
Zahedipour, Hosseini, Sathyapalan, Majeed, Jamialahmadi et al., Potential Effects of Curcumin in the Treatment of COVID -19 Infection, Phytotherapy Res,
doi:10.1002/ptr.6738
Zhang, -W, Fu, Gao, Liu, Curcumin and Diabetes: a Systematic Review. Evidence-Based Complement, Altern. Med,
doi:10.1155/2013/636053