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The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial

Din Ujjan et al., Frontiers in Nutrition, doi:10.3389/fnut.2022.1023997, NCT04603690
Jan 2023  
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Recovery 29% Improvement Relative Risk Recovery (b) 71% Recovery (c) 77% Recovery (d) 86% Viral clearance, day 14 91% Viral clearance, day 7 74% Curcumin  Din Ujjan et al.  EARLY TREATMENT  RCT Is early treatment with curcumin + quercetin and vitamin D beneficial for COVID-19? RCT 50 patients in Pakistan (September 2021 - January 2022) Improved recovery with curcumin + quercetin and vitamin D (not stat. sig., p=0.11) c19early.org Din Ujjan et al., Frontiers in Nutrition, Jan 2023 Favorscurcumin Favorscontrol 0 0.5 1 1.5 2+
Curcumin for COVID-19
14th treatment shown to reduce risk in February 2021
 
*, now with p = 0.000000015 from 26 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19early.org
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
This is the 17th of 20 COVID-19 RCTs for curcumin, which collectively show efficacy with p=0.0000033.
This is the 23rd of 26 COVID-19 controlled studies for curcumin, which collectively show efficacy with p=0.000000015 (1 in 66 million).
Study covers vitamin D, curcumin, and quercetin.
risk of no recovery, 28.6% lower, RR 0.71, p = 0.11, treatment 15 of 25 (60.0%), control 21 of 25 (84.0%), NNT 4.2, no symptoms, day 7.
risk of no recovery, 71.4% lower, RR 0.29, p < 0.001, treatment 6 of 25 (24.0%), control 21 of 25 (84.0%), NNT 1.7, <= 1 symptom, day 7.
risk of no recovery, 76.9% lower, RR 0.23, p = 0.005, treatment 3 of 25 (12.0%), control 13 of 25 (52.0%), NNT 2.5, <= 2 symptoms, day 7.
risk of no recovery, 85.7% lower, RR 0.14, p = 0.23, treatment 0 of 25 (0.0%), control 3 of 25 (12.0%), NNT 8.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), <= 3 symptoms, day 7.
risk of no viral clearance, 90.9% lower, RR 0.09, p = 0.05, treatment 0 of 25 (0.0%), control 5 of 25 (20.0%), NNT 5.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 14.
risk of no viral clearance, 73.7% lower, RR 0.26, p < 0.001, treatment 5 of 25 (20.0%), control 19 of 25 (76.0%), NNT 1.8, day 7.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Din Ujjan et al., 18 Jan 2023, Randomized Controlled Trial, Pakistan, peer-reviewed, 6 authors, study period 21 September, 2021 - 21 January, 2022, this trial uses multiple treatments in the treatment arm (combined with quercetin and vitamin D) - results of individual treatments may vary, trial NCT04603690 (history).
This PaperCurcuminAll
The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
Ikram Din Ujjan, Saeed Khan, Roohi Nigar, Hammad Ahmed, Sagheer Ahmad, Amjad Khan
Frontiers in Nutrition, doi:10.3389/fnut.2022.1023997
A (2023) The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial.
Ethics statement The study was approved by the Research Ethics Committee (REC), Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro, Pakistan via Ref. No. LUMHS/REC/-137. The patients/participants provided their written informed consent to participate in this study. Author contributions IU: study design, data collection, data interpretation, supervision, and critical revision of the manuscript. SK: study design, data interpretation, and manuscript revision. RN: data collection, supervision, and manuscript revision. HA: study administration, data collection, and manuscript 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. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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{ 'indexed': {'date-parts': [[2024, 3, 4]], 'date-time': '2024-03-04T18:59:12Z', 'timestamp': 1709578752533}, 'reference-count': 69, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2023, 1, 18]], 'date-time': '2023-01-18T00:00:00Z', 'timestamp': 1674000000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>Curcumin (CUR) and quercetin (QUE), two ' 'natural polyphenols, possess diverse biological activities including broad-spectrum ' 'antiviral, antioxidant, and immunomodulatory effects. Both CUR and QUE have shown inhibition ' 'of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in <jats:italic>in ' 'vitro</jats:italic> ' 'assays.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>In the present ' 'study we aimed to assess the possible treatment benefits of a combined curcumin and quercetin ' '(CUR-QUE) oral supplement, alongside standard of care (SOC), in the ' '<jats:italic>early-stage</jats:italic> COVID-19 ' 'infection.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This was an ' 'exploratory, pragmatic, open-label, randomized controlled clinical trial, conducted at the ' 'Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, PK. The ' 'study compared the treatment effect of an oral CUR-QUE supplement ' '<jats:italic>plus</jats:italic> SOC vs. SOC alone, in the ' '<jats:italic>early-stage</jats:italic>/mild to moderately symptomatic COVID-19 outpatients. ' 'Patients were randomized in a 1:1 ratio to CUR-QUE (<jats:italic>n</jats:italic> = 25) and ' 'control (<jats:italic>n</jats:italic> = 25) treatment groups. The CUR-QUE supplementation ' 'consisted of a daily intake of 168 mg curcumin and 260 mg quercetin, as two soft capsules, to ' 'be taken twice a day at home for 14 ' 'days.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After one-week of ' 'treatment, most of the patients in the CUR-QUE group showed an expedited clearance of the ' 'viral infection i.e., 18 (72.0%) vs. 6 (24.0%) patients in the control group tested negative ' 'for SARS-CoV-2 in the nasal-oropharyngeal swab reverse transcription-polymerase chain ' 'reaction (RT-PCR) analysis (<jats:italic>p</jats:italic> = 0.0002). In addition, ' 'COVID-19-associated acute symptoms were also speedily resolved in the CUR-QUE treated ' 'patients, i.e., 10 (40.0%) vs. 4 (16.0%) patients in the control group ' '(<jats:italic>p</jats:italic> = 0.061). The CUR-QUE supplementation therapy was ' 'well-tolerated by all 25 patients and no treatment-emergent effects or serious adverse events ' 'were reported.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The ' 'results revealed in this exploratory study suggest a possible therapeutic role of curcumin ' 'and quercetin in the <jats:italic>early-stage</jats:italic> of COVID-19. It is proposed that ' 'the two agents possibly acting in synergy, interfere the SARS-CoV-2 replication, and thus ' 'help a speedy recovery in the <jats:italic>early-stage</jats:italic> of COVID-19. Further ' 'research is highly encouraged.</jats:p></jats:sec><jats:sec><jats:title>Clinical trial ' 'registration</jats:title><jats:p><jats:ext-link>Clinicaltrials.gov</jats:ext-link>, ' 'Identifier NCT04603690.</jats:p></jats:sec>', 'DOI': '10.3389/fnut.2022.1023997', 'type': 'journal-article', 'created': {'date-parts': [[2023, 1, 18]], 'date-time': '2023-01-18T06:41:35Z', 'timestamp': 1674024095000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 2, 'title': 'The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results ' 'from a pragmatic randomized clinical trial', 'prefix': '10.3389', 'volume': '9', 'author': [ {'given': 'Ikram Din', 'family': 'Ujjan', 'sequence': 'first', 'affiliation': []}, {'given': 'Saeed', 'family': 'Khan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Roohi', 'family': 'Nigar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hammad', 'family': 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'volume': '12', 'author': 'Rattis', 'year': '2021', 'journal-title': 'Front Pharmacol.'}, { 'key': 'B21', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.heliyon.2021.e06350', 'article-title': 'Antiviral and immunomodulatory activity of curcumin: a case for ' 'prophylactic therapy for COVID-19.', 'volume': '7', 'author': 'Thimmulappa', 'year': '2021', 'journal-title': 'Heliyon.'}, { 'key': 'B22', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2020.01451', 'article-title': 'Quercetin and vitamin C: an experimental, synergistic therapy for the ' 'prevention and treatment of SARS-CoV-2 related disease (COVID-19).', 'volume': '11', 'author': 'Colunga Biancatelli', 'year': '2020', 'journal-title': 'Front Immunol.'}, { 'key': 'B23', 'doi-asserted-by': 'publisher', 'first-page': '1230', 'DOI': '10.1002/ptr.6887', 'article-title': 'A role for quercetin in coronavirus disease 2019 (COVID-19).', 'volume': '35', 'author': 'Derosa', 'year': '2021', 'journal-title': 'Phytother Res.'}, { 'key': 'B24', 'doi-asserted-by': 'publisher', 'first-page': '29', 'DOI': '10.1016/j.jpha.2021.09.009', 'article-title': 'Antiviral, immunomodulatory, and anticoagulant effects of quercetin and ' 'its derivatives: potential role in prevention and management of ' 'COVID-19.', 'volume': '12', 'author': 'Manjunath', 'year': '2022', 'journal-title': 'J Pharm Analy.'}, { 'key': 'B25', 'doi-asserted-by': 'publisher', 'first-page': '5215', 'DOI': '10.1002/fsn3.1858', 'article-title': 'Curcumin (a constituent of turmeric): new treatment option against ' 'COVID-19.', 'volume': '8', 'author': 'Babaei', 'year': '2020', 'journal-title': 'Food Sci Nutr.'}, { 'key': 'B26', 'doi-asserted-by': 'publisher', 'first-page': '40', 'DOI': '10.1016/j.biocel.2008.06.010', 'article-title': 'Potential therapeutic effects of curcumin, the anti-inflammatory agent, ' 'against neurodegenerative, cardiovascular, pulmonary, metabolic, ' 'autoimmune and neoplastic diseases.', 'volume': '41', 'author': 'Aggarwal', 'year': '2009', 'journal-title': 'Int J Biochem Cell Biol.'}, { 'key': 'B27', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/1475-2891-13-11', 'article-title': 'Comparative absorption of curcumin formulations.', 'volume': '13', 'author': 'Jäger', 'year': '2014', 'journal-title': 'Nutr J.'}, { 'key': 'B28', 'doi-asserted-by': 'publisher', 'first-page': '133', 'DOI': '10.1016/j.phrs.2016.11.017', 'article-title': 'Curcumin use in pulmonary diseases: state of the art and future ' 'perspectives.', 'volume': '115', 'author': 'Lelli', 'year': '2017', 'journal-title': 'Pharmacol Res.'}, { 'key': 'B29', 'doi-asserted-by': 'publisher', 'first-page': '4087', 'DOI': '10.1021/jm070295s', 'article-title': 'Specific plant terpenoids and lignoids possess potent antiviral ' 'activities against severe acute respiratory syndrome coronavirus.', 'volume': '50', 'author': 'Wen', 'year': '2007', 'journal-title': 'J Med Chem.'}, { 'key': 'B30', 'doi-asserted-by': 'publisher', 'DOI': '10.1155/2014/186864', 'article-title': 'Review on antibacterial, antiviral, and antifungal activity of ' 'curcumin.', 'volume': '2014', 'author': 'Zorofchian Moghadamtousi', 'year': '2014', 'journal-title': 'BioMed Res Int.'}, { 'key': 'B31', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.foodchem.2021.131594', 'article-title': 'Inhibition of the SARS-CoV-2 3CL(pro) main protease by plant ' 'polyphenols.', 'volume': '373', 'author': 'Bahun', 'year': '2022', 'journal-title': 'Food Chem.'}, { 'key': 'B32', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/v13101914', 'article-title': 'Turmeric root and its bioactive ingredient curcumin effectively ' 'neutralize SARS-CoV-2 in vitro.', 'volume': '13', 'author': 'Bormann', 'year': '2021', 'journal-title': 'Viruses.'}, { 'key': 'B33', 'doi-asserted-by': 'publisher', 'first-page': '3013', 'DOI': '10.1002/ptr.7463', 'article-title': 'In vitro antiviral activity against SARS-CoV-2 of common herbal ' 'medicinal extracts and their bioactive compounds.', 'volume': 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'10.1002/ptr.7004', 'article-title': 'Oral nano-curcumin formulation efficacy in management of mild to ' 'moderate hospitalized coronavirus disease-19 patients: an open label ' 'nonrandomized clinical trial.', 'volume': '35', 'author': 'Saber-Moghaddam', 'year': '2021', 'journal-title': 'Phytother Res.'}, { 'key': 'B54', 'doi-asserted-by': 'publisher', 'first-page': '1023', 'DOI': '10.1002/ptr.7375', 'article-title': 'Antiinflammatory potential of nano-curcumin as an alternative ' 'therapeutic agent for the treatment of mild-to-moderate hospitalized ' 'COVID-19 patients in a placebo-controlled clinical trial.', 'volume': '36', 'author': 'Asadirad', 'year': '2022', 'journal-title': 'Phytother Res.'}, { 'key': 'B55', 'doi-asserted-by': 'publisher', 'first-page': '6417', 'DOI': '10.1002/ptr.7294', 'article-title': 'A triple-blind, placebo-controlled, randomized clinical trial to ' 'evaluate the effect of curcumin-containing nanomicelles on cellular ' 'immune responses subtypes and clinical outcome in COVID-19 patients.', 'volume': '35', 'author': 'Hassaniazad', 'year': '2021', 'journal-title': 'Phytother Res.'}, { 'key': 'B56', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.eujim.2020.101122', 'article-title': 'Effects of nanocurcumin on inflammatory factors and clinical outcomes ' 'in critically ill patients with sepsis: a pilot randomized clinical ' 'trial.', 'volume': '36', 'author': 'Karimi', 'year': '2020', 'journal-title': 'Eur J Int Med.'}, { 'key': 'B57', 'doi-asserted-by': 'publisher', 'first-page': '5325', 'DOI': '10.1002/jcp.30233', 'article-title': 'Immunomodulatory effects of nanocurcumin on Th17 cell responses in mild ' 'and severe COVID-19 patients.', 'volume': '236', 'author': 'Tahmasebi', 'year': '2021', 'journal-title': 'J Cell Physiol.'}, { 'key': 'B58', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lfs.2021.119437', 'article-title': 'Nanocurcumin improves Treg cell responses in patients with mild and ' 'severe SARS-CoV2.', 'volume': '276', 'author': 'Tahmasebi', 'year': '2021', 'journal-title': 'Life Sci.'}, { 'key': 'B59', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.intimp.2020.107088', 'article-title': 'Nano-curcumin therapy, a promising method in modulating inflammatory ' 'cytokines in COVID-19 patients.', 'volume': '89', 'author': 'Valizadeh', 'year': '2020', 'journal-title': 'Int Immunopharmacol.'}, { 'key': 'B60', 'doi-asserted-by': 'publisher', 'first-page': '2359', 'DOI': '10.2147/IJGM.S318720', 'article-title': 'Possible therapeutic effects of adjuvant quercetin supplementation ' 'against early-stage COVID-19 infection: a prospective, randomized, ' 'controlled, and open-label study.', 'volume': '14', 'author': 'Di Pierro', 'year': '2021', 'journal-title': 'Int J Gen Med.'}, { 'key': 'B61', 'doi-asserted-by': 'publisher', 'first-page': '2807', 'DOI': '10.2147/IJGM.S318949', 'article-title': 'Potential clinical benefits of quercetin in the early stage of ' 'COVID-19: results of a second, pilot, randomized, controlled and ' 'open-label clinical trial.', 'volume': '14', 'author': 'Di Pierro', 'year': '2021', 'journal-title': 'Int J Gen Med.'}, { 'key': 'B62', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.12.22.20245993', 'article-title': 'Evaluation of the effect of zinc, quercetin, bromelain and vitamin C on ' 'COVID-19 patients.', 'author': 'Kamel', 'year': '2020', 'journal-title': 'medRxiv'}, { 'key': 'B63', 'doi-asserted-by': 'publisher', 'first-page': '518', 'DOI': '10.3906/biy-2104-16', 'article-title': 'Treatment of COVID-19 patients with quercetin: a prospective, single ' 'center, randomized, controlled trial.', 'volume': '45', 'author': 'Onal', 'year': '2021', 'journal-title': 'Turk J Biol.'}, { 'key': 'B64', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/life12010066', 'article-title': 'Promising effects of 3-month period of quercetin phytosome((R)) ' 'supplementation in the prevention of symptomatic COVID-19 disease in ' 'healthcare workers: a pilot study.', 'volume': '12', 'author': 'Rondanelli', 'year': '2022', 'journal-title': 'Life.'}, { 'key': 'B65', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ejphar.2021.174615', 'article-title': 'The therapeutic efficacy of quercetin in combination with antiviral ' 'drugs in hospitalized COVID-19 patients: a randomized controlled trial.', 'volume': '914', 'author': 'Shohan', 'year': '2022', 'journal-title': 'Eur J Pharmacol.'}, { 'key': 'B66', 'doi-asserted-by': 'publisher', 'first-page': '636', 'DOI': '10.14739/2310-1210.2021.5.231714', 'article-title': 'Efficacy of quercetin in patients with pneumonia associated with ' 'coronavirus disease (COVID-19).', 'volume': '23', 'author': 'Zupanets', 'year': '2021', 'journal-title': 'Zaporizhia Med J.'}, { 'key': 'B67', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fphar.2022.898062', 'article-title': 'Oral co-supplementation of curcumin, quercetin, and vitamin D3 as an ' 'adjuvant therapy for mild to moderate symptoms of COVID-19-results from ' 'a pilot open-label, randomized controlled trial.', 'volume': '13', 'author': 'Khan', 'year': '2022', 'journal-title': 'Front Pharmacol.'}, { 'key': 'B68', 'first-page': '2895', 'article-title': 'Phase I clinical trial of curcumin, a chemopreventive agent, in ' 'patients with high-risk or pre-malignant lesions.', 'volume': '21', 'author': 'Cheng', 'year': '2001', 'journal-title': 'Anticancer Res.'}, { 'key': 'B69', 'doi-asserted-by': 'publisher', 'first-page': '2179', 'DOI': '10.1016/j.fct.2007.05.015', 'article-title': 'A critical review of the data related to the safety of quercetin and ' 'lack of evidence of in vivo toxicity, including lack of ' 'genotoxic/carcinogenic properties.', 'volume': '45', 'author': 'Harwood', 'year': '2007', 'journal-title': 'Food Chem Toxicol.'}], 'container-title': 'Frontiers in Nutrition', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 1, 18]], 'date-time': '2023-01-18T06:41:39Z', 'timestamp': 1674024099000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 1, 18]]}, 'references-count': 69, 'alternative-id': ['10.3389/fnut.2022.1023997'], 'URL': 'http://dx.doi.org/10.3389/fnut.2022.1023997', 'relation': {}, 'ISSN': ['2296-861X'], 'subject': ['Nutrition and Dietetics', 'Endocrinology, Diabetes and Metabolism', 'Food Science'], 'container-title-short': 'Front. Nutr.', 'published': {'date-parts': [[2023, 1, 18]]}}
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