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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

Khan et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.898062, NCT05130671
May 2022  
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Recovery 33% Improvement Relative Risk CRP reduction 39% Viral clearance 50% Quercetin  Khan et al.  EARLY TREATMENT  RCT Is early treatment with quercetin + curcumin and vitamin D beneficial for COVID-19? RCT 50 patients in Pakistan (September - November 2021) Improved viral clearance with quercetin + curcumin and vitamin D (p=0.0086) c19early.org Khan et al., Frontiers in Pharmacology, May 2022 Favorsquercetin Favorscontrol 0 0.5 1 1.5 2+
Quercetin for COVID-19
24th treatment shown to reduce risk in July 2021, now with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 110 treatments. c19early.org
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.
This is the 7th of 10 COVID-19 RCTs for quercetin, which collectively show efficacy with p=0.0049.
This is the 8th of 11 COVID-19 controlled studies for quercetin, which collectively show efficacy with p=0.0031.
Study covers vitamin D, curcumin, and quercetin.
risk of no recovery, 33.3% lower, RR 0.67, p = 0.15, treatment 10 of 25 (40.0%), control 15 of 25 (60.0%), NNT 5.0.
relative CRP reduction, 39.1% better, RR 0.61, p = 0.006, treatment 25, control 25.
risk of no viral clearance, 50.0% lower, RR 0.50, p = 0.009, treatment 10 of 25 (40.0%), control 20 of 25 (80.0%), NNT 2.5.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Khan et al., 1 May 2022, Randomized Controlled Trial, Pakistan, peer-reviewed, 7 authors, study period 2 September, 2021 - 28 November, 2021, this trial uses multiple treatments in the treatment arm (combined with curcumin and vitamin D) - results of individual treatments may vary, trial NCT05130671 (history). Contact: amjadkhan@lumhs.edu.pk.
This PaperQuercetinAll
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
Amjad Khan, Somia Iqtadar, Sami Ullah Mumtaz, Michael Heinrich, Domingo A Pascual-Figal, Shona Livingstone, Sajid Abaidullah
Frontiers in Pharmacology, doi:10.3389/fphar.2022.898062
Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 in a pilot open-label, randomized controlled trial conducted at
ETHICS STATEMENT The study was approved by the Institutional Review Board (IRB) of King Edward Medical University, Lahore, with approval No. 785/RC/KEMU. The patients/participants provided their written informed consent to participate in this study. AUTHOR CONTRIBUTIONS AK contributed to the study design, data interpretation, writing of the manuscript, and literature search; SI, SM, and SA contributed to the study design, data collection, data interpretation, and literature search; DP-F and MH critically reviewed and edited the manuscript; and SL helped in data analysis and revision of the manuscript. All authors approved the final 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': [[2022, 6, 7]], 'date-time': '2022-06-07T15:42:45Z', 'timestamp': 1654616565317}, 'reference-count': 96, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2022, 6, 7]], 'date-time': '2022-06-07T00:00:00Z', 'timestamp': 1654560000000}, '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:p><jats:bold>Background:</jats:bold> Curcumin, quercetin, and vitamin D3 ' '(cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit ' 'promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant ' 'activities.</jats:p><jats:p><jats:bold>Objective:</jats:bold> The present study aimed to ' 'investigate the possible therapeutic benefits of a single oral formulation containing ' 'supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as ' 'an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a ' 'pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical ' 'University, Lahore, Pakistan.</jats:p><jats:p><jats:bold>Methods:</jats:bold> Reverse ' 'transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic ' 'COVID-19 outpatients were randomized to receive either the standard of care (SOC) ' '(<jats:italic>n</jats:italic> = 25) (control arm) or a daily oral co-supplementation of ' '168\xa0mg curcumin, 260\xa0mg quercetin, and 9\xa0µg (360 IU) of cholecalciferol, as two oral ' 'soft capsules b.i.d. as an add-on to the SOC (<jats:italic>n</jats:italic> = 25) (CQC arm) ' 'for 14\xa0days. The SOC includes paracetamol with or without antibiotic (azithromycin). ' 'Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and ' 'biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, ' 'and complete blood count were evaluated at baseline and follow-up day ' 'seven.</jats:p><jats:p><jats:bold>Results:</jats:bold> Patients who received the CQC adjuvant ' 'therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. ' 'five (20.0%) of the control arm, <jats:italic>p</jats:italic> = 0.009. COVID-19- associated ' 'acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the ' 'control arm, <jats:italic>p</jats:italic> = 0.154. Patients in the CQC arm experienced a ' 'greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, ' '16.0)\xa0mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, ' '25.0)\xa0mg/dl, <jats:italic>p</jats:italic> = 0.006. The adjuvant therapy of ' 'co-supplementation of CQC was safe and well-tolerated by all 25 patients and no ' 'treatment-emergent effects, complications, side effects, or serious adverse events were ' 'reported.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The co-supplementation of CQC ' 'may possibly have a therapeutic role in the early stage of COVID-19 infection including ' 'speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and ' 'modulation of the hyperinflammatory response. In combination with routine care, the adjuvant ' 'co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to ' 'moderate symptoms of COVID-19. Further research is ' 'warranted.</jats:p><jats:p><jats:bold>Clinical Trial ' 'Registration:</jats:bold><jats:ext-link>Clinicaltrials.gov</jats:ext-link>, identifier ' 'NCT05130671</jats:p>', 'DOI': '10.3389/fphar.2022.898062', 'type': 'journal-article', 'created': {'date-parts': [[2022, 6, 7]], 'date-time': '2022-06-07T15:05:34Z', 'timestamp': 1654614334000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, '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', 'prefix': '10.3389', 'volume': '13', 'author': [ {'given': 'Amjad', 'family': 'Khan', 'sequence': 'first', 'affiliation': []}, {'given': 'Somia', 'family': 'Iqtadar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sami Ullah', 'family': 'Mumtaz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Michael', 'family': 'Heinrich', 'sequence': 'additional', 'affiliation': []}, {'given': 'Domingo A.', 'family': 'Pascual-Figal', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shona', 'family': 'Livingstone', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sajid', 'family': 'Abaidullah', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2022, 6, 7]]}, 'reference': [ { 'key': 'B1', 'doi-asserted-by': 'publisher', 'first-page': '1693', 'DOI': '10.1016/j.ijbiomac.2020.07.235', 'article-title': 'Structural Stability of SARS-CoV-2 3CLpro and Identification of ' 'Quercetin as an Inhibitor by Experimental Screening', 'volume': '164', 'author': 'Abian', 'year': '2020', 'journal-title': 'Int. 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