Efficacy of highly bioavailable oral curcumin in asymptomatic or mild COVID-19 patients: a double-blind, randomized, placebo-controlled trial

{ 'indexed': {'date-parts': [[2024, 6, 25]], 'date-time': '2024-06-25T00:30:08Z', 'timestamp': 1719275408875}, 'reference-count': 22, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2024, 6, 24]], 'date-time': '2024-06-24T00:00:00Z', 'timestamp': 1719187200000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2024, 6, 24]], 'date-time': '2024-06-24T00:00:00Z', 'timestamp': 1719187200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' ' <jats:title>Introduction</jats:title>\n' ' <jats:p>Even after the peak of the COVID-19 pandemic, the number of mild ' 'cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory ' 'properties, can suppress vital proliferation and cytokine secretion in animal models. We ' 'developed a highly absorbable curcumin, curcuRouge<jats:sup>®</jats:sup> (cR), which is ' 'approximately 100 times more orally bioavailable than conventional curcumin. We evaluated the ' 'effect of cR on the inhibition of disease progression in asymptomatic or mildly symptomatic ' 'COVID-19 patients.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>This study evaluated the effect of 7-day oral intake of cR (360\xa0mg ' 'twice daily). Patients within 5\xa0days of COVID-19 diagnosis were randomly assigned to a ' 'placebo or cR group in a double-blind manner.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Primary endpoint events [body temperature (BT)\u2009≥\u200937.5\xa0°C ' 'and saturation of percutaneous oxygen (SpO2)\u2009&lt;\u200996%] were fewer than expected, ' 'and the rate of these events was 2.8% in the cR group (2/71) and 6.0% in the placebo group ' '(4/67); hazard ratio (HR)\u2009=\u20090.532, 95% confidence interval (CI) 0.097–2.902. ' 'Patients receiving cR tended to take fewer antipyretic medications than those receiving ' 'placebo (HR\u2009=\u20090.716, 95% CI 0.374–1.372). Among patients with a normal range of BT ' 'at baseline, the BT change rate was significantly (<jats:italic>p</jats:italic>\u2009=\u2009' '0.014) lower in the cR group (−\u20090.34%) versus placebo (−\u20090.01%).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusion</jats:title>\n' ' <jats:p>The relative suppression of event rates and antipyretic medications ' 'taken, and significant decrease of subclinical BT support the anti-inflammatory effects of cR ' 'in asymptomatic or mildly symptomatic patients with COVID-19.</jats:p>\n' ' <jats:p><jats:italic>Trial registration</jats:italic>: Japan Registry of ' 'Clinical Trials (CRB5200002).</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s41043-024-00584-6', 'type': 'journal-article', 'created': {'date-parts': [[2024, 6, 24]], 'date-time': '2024-06-24T15:01:42Z', 'timestamp': 1719241302000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Efficacy of highly bioavailable oral curcumin in asymptomatic or mild COVID-19 patients: a ' 'double-blind, randomized, placebo-controlled trial', 'prefix': '10.1186', 'volume': '43', 'author': [ {'given': 'Atsuhiro', 'family': 'Kishimoto', 'sequence': 'first', 'affiliation': []}, {'given': 'Maki', 'family': 'Komiyama', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hiromichi', 'family': 'Wada', 'sequence': 'additional', 'affiliation': []}, {'given': 'Noriko', 'family': 'Satoh-Asahara', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hajime', 'family': 'Yamakage', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yoichi', 'family': 'Ajiro', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hiroki', 'family': 'Aoyama', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yasuhiro', 'family': 'Katsuura', 'sequence': 'additional', 'affiliation': []}, {'given': 'Atsushi', 'family': 'Imaizumi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tadashi', 'family': 'Hashimoto', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yoichi', 'family': 'Sunagawa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tatsuya', 'family': 'Morimoto', 'sequence': 'additional', 'affiliation': []}, {'given': 'Masashi', 'family': 'Kanai', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hideaki', 'family': 'Kakeya', 'sequence': 'additional', 'affiliation': []}, {'given': 'Koji', 'family': 'Hasegawa', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2024, 6, 24]]}, 'reference': [ { 'issue': '13', 'key': '584_CR1', 'doi-asserted-by': 'publisher', 'first-page': '1239', 'DOI': '10.1001/jama.2020.2648', 'volume': '323', 'author': 'Z Wu', 'year': '2020', 'unstructured': 'Wu Z, McGoogan JM. Characteristics of and important lessons from the ' 'coronavirus disease 2019 (COVID-19) outbreak in china: summary of a ' 'report of 72 314 cases from the Chinese Center for disease control and ' 'prevention. JAMA. 2020;323(13):1239–42.', 'journal-title': 'JAMA'}, { 'key': '584_CR2', 'unstructured': 'Ministry of Health, Labor and Welfare (MHLW). New Coronavirus Infections ' 'COVID19 Guide to Clinical Practice, Version 10.0, Japan. 2023.'}, { 'key': '584_CR3', 'doi-asserted-by': 'publisher', 'first-page': '17532', 'DOI': '10.1016/j.ejphar.2022.175321', 'volume': '935', 'author': 'T Abe', 'year': '2022', 'unstructured': 'Abe T, Horisawa Y, Kikuchi O, Ozawa-Umeta H, Kishimoto A, Katsuura Y, ' 'Imaizumi A, Hashimoto T, Shirakawa K, Takaori-Kondo A, Yusa K, Asakura ' 'T, Kakeya H, Kanai M. Pharmacologic characterization of TBP1901, a ' 'prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for ' 'therapeutic targets of aglycone curcumin. Eur J Pharmacol. ' '2022;935:17532.', 'journal-title': 'Eur J Pharmacol'}, { 'issue': '5', 'key': '584_CR4', 'doi-asserted-by': 'publisher', 'first-page': '457', 'DOI': '10.1111/irv.12459', 'volume': '11', 'author': 'Y Xu', 'year': '2017', 'unstructured': 'Xu Y, Liu L. Curcumin alleviates macrophage activation and lung ' 'inflammation induced by influenza virus infection through inhibiting the ' 'NF-κB signaling pathway. Influenza Other Respir Viruses. ' '2017;11(5):457–63.', 'journal-title': 'Influenza Other Respir Viruses'}, { 'issue': '17', 'key': '584_CR5', 'doi-asserted-by': 'publisher', 'first-page': '4087', 'DOI': '10.1021/jm070295s', 'volume': '50', 'author': 'CC Wen', 'year': '2007', 'unstructured': 'Wen CC, Kuo YH, Jan JT, Liang PH, Wang SY, Liu HG, Lee CK, Chang ST, Kuo ' 'CJ, Lee SS, Hou CC, Hsiao PW, Chien SH, Shyur LF, Yang NS. Specific ' 'plant terpenoids and lignoids possess potent antiviral activities ' 'against severe acute respiratory syndrome corona virus. J Med Chem. ' '2007;50(17):4087–95.', 'journal-title': 'J Med Chem'}, { 'issue': '11', 'key': '584_CR6', 'doi-asserted-by': 'publisher', 'first-page': '5053', 'DOI': '10.1080/07391102.2020.1866669', 'volume': '40', 'author': 'P Umadevi', 'year': '2020', 'unstructured': 'Umadevi P, Manivannan S, Fayad AM, Shelvy S. In silico analysis of ' 'phytochemicals as potential inhibitors of proteases involved in ' 'SARS-CoV-2 infection. J Biomol Struct Dyn. 2020;40(11):5053–9.', 'journal-title': 'J Biomol Struct Dyn'}, { 'key': '584_CR7', 'doi-asserted-by': 'publisher', 'first-page': '104443', 'DOI': '10.1016/j.jff.2021.104443', 'volume': '81', 'author': 'Y Sunagawa', 'year': '2021', 'unstructured': 'Sunagawa Y, Miyazaki Y, Funamoto M, Shimizu K, Shimizu S, Nurmila S, ' 'Katanasaka Y, Ito M, Ogawa T, Ozawa-Umeta H, Hasegawa K, Morimoto T. A ' 'novel amorphous preparation improved curcumin bioavailability in healthy ' 'volunteers: a single-dose, double- blind, two-way crossover study. J ' 'Funct Foods. 2021;81:104443.', 'journal-title': 'J Funct Foods'}, { 'key': '584_CR8', 'doi-asserted-by': 'crossref', 'unstructured': 'IJCPT. Comparative pharmacokinetics of Theracurmin, a highly ' 'bioavailable curcumin, in healthy adult subjects. Int J Clin Pharmacol ' 'Ther. 2021;59(10):684–90.', 'DOI': '10.5414/CP204058'}, { 'key': '584_CR9', 'doi-asserted-by': 'crossref', 'unstructured': 'IJCPT. Comparative pharmacokinetics of new curcumin preparations and ' 'evidence for increased bioavailability in healthy adult participants. ' 'Int J Clin Pharmacol Ther. 2022;60(12):530–8.', 'DOI': '10.5414/CP204257'}, { 'issue': '4', 'key': '584_CR10', 'doi-asserted-by': 'publisher', 'first-page': '249', 'DOI': '10.3177/jnsv.67.249', 'volume': '67', 'author': 'A Kishimoto', 'year': '2021', 'unstructured': 'Kishimoto A, Imaizumi A, Wada H, Yamakage H, Satoh-Asahara N, Hashimoto ' 'T, Hasegawa K. Newly developed highly bioavailable curcumin formulation, ' 'curcuRougeTM, reduces neutrophil/lymphocyte ratio in the elderly: a ' 'double-blind, placebo-controlled clinical trial. J Nutr Sci Vitaminol ' '(Tokyo). 2021;67(4):249–52.', 'journal-title': 'J Nutr Sci Vitaminol (Tokyo)'}, { 'issue': '2', 'key': '584_CR11', 'doi-asserted-by': 'publisher', 'first-page': '117', 'DOI': '10.30714/j-ebr.2020259176', 'volume': '3', 'author': 'S Bilgin', 'year': '2020', 'unstructured': 'Bilgin S, Kurtkulagi O, Kahveci GB, Duman TT, Atak Tel BM. Millennium ' 'pandemic: a review of coronavirus disease (COVID-19). Exp Biomed Res. ' '2020;3(2):117–25.', 'journal-title': 'Exp Biomed Res'}, { 'issue': '5', 'key': '584_CR12', 'first-page': '596', 'volume': '90', 'author': 'ME Demirkol', 'year': '2022', 'unstructured': 'Demirkol ME, Bilgin S, Kahveci G, Kurtkulagi O, Atak Tel BM, Duman TT, ' 'Aktas G. C-reactive protein-to-lymphocyte ratio is a reliable marker in ' 'patients with COVID-19 infection: the CLEAR COVID study. Cir Cir. ' '2022;90(5):596–601.', 'journal-title': 'Cir Cir'}, { 'issue': '1', 'key': '584_CR13', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1590/1806-9282.67.01.001', 'volume': '67', 'author': 'G Aktas', 'year': '2021', 'unstructured': 'Aktas G. Hematological predictors of novel Coronavirus infection. Rev ' 'Assoc Méd Bras. 2021;67(1):1–2.', 'journal-title': 'Rev Assoc Méd Bras'}, { 'issue': '03', 'key': '584_CR14', 'first-page': '415', 'volume': '04', 'author': 'Y Nakagawa', 'year': '2023', 'unstructured': 'Nakagawa Y, Yamada S, Mukai S, Akiyoshi K, Katsuura Y, Hashimoto T. ' 'Efficacy of high- and low-dose, highly bioavailable curcumin ' '(CurcuRouge®) for treating knee osteoarthritis: a randomized, ' 'double-blind. Placebo-Control Prospect Study Clin Med Insights. ' '2023;04(03):415–29.', 'journal-title': 'Placebo-Control Prospect Study Clin Med Insights'}, { 'issue': '11', 'key': '584_CR15', 'doi-asserted-by': 'publisher', 'first-page': '6417', 'DOI': '10.1002/ptr.7294', 'volume': '35', 'author': 'M Hassaniazad', 'year': '2021', 'unstructured': 'Hassaniazad M, Eftekhar E, Inchehsablagh BR, Kamali H, Tousi A, Jaafari ' 'MR, Rafat M, Fathalipour M, Nikoofal-Sahlabadi S, Gouklani H, Alizade H, ' 'Nikpoor AM. 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. Phytother Res. 2021;35(11):6417–27.', 'journal-title': 'Phytother Res'}, { 'key': '584_CR16', 'doi-asserted-by': 'publisher', 'first-page': '669362', 'DOI': '10.3389/fphar.2021.669362', 'volume': '12', 'author': 'KS Pawar', 'year': '2021', 'unstructured': 'Pawar KS, Mastud RN, Pawar SK, Pawar SS, Bhoite RR, Bhoite RR, Kulkarni ' 'MV, Deshpande AR. Oral curcumin with piperine as adjuvant therapy for ' 'the treatment of COVID-19: a randomized clinical trial. Front Pharmacol. ' '2021;12:669362.', 'journal-title': 'Front Pharmacol'}, { 'key': '584_CR17', 'doi-asserted-by': 'publisher', 'first-page': '5734675', 'DOI': '10.1155/2023/5734675', 'volume': '2023', 'author': 'S Ahmadi', 'year': '2023', 'unstructured': 'Ahmadi S, Mehrabi Z, Zare M, Ghadir S, Masoumi SJ. Efficacy of ' 'nanocurcumin as an add-on treatment for patients hospitalized with ' 'COVID-19: a double-blind, randomized clinical trial. Int J Clin Pract. ' '2023;2023:5734675.', 'journal-title': 'Int J Clin Pract'}, { 'key': '584_CR18', 'unstructured': 'Roche. Media & Investor Release. Phase III prevention trial showed ' 'subcutaneous administration of investigational antibody cocktail ' 'casirivimab and imdevimab reduced risk of symptomatic COVID-19 ' 'infections by 81%. 2021.'}, { 'issue': '1', 'key': '584_CR19', 'doi-asserted-by': 'publisher', 'first-page': '31', 'DOI': '10.1016/j.neuron.2018.02.022', 'volume': '98', 'author': 'CL Tan', 'year': '2018', 'unstructured': 'Tan CL, Knight ZA. Regulation of body temperature by the nervous system. ' 'Neuron. 2018;98(1):31–48.', 'journal-title': 'Neuron'}, { 'issue': '1', 'key': '584_CR20', 'doi-asserted-by': 'publisher', 'first-page': '17', 'DOI': '10.3390/diseases9010017', 'volume': '9', 'author': 'EM Kozlov', 'year': '2021', 'unstructured': 'Kozlov EM, Ivanova E, Grechko AV, Wu WK, Starodubova AV, Alexander N. ' 'Involvement of oxidative stress and the innate immune system in ' 'SARS-CoV-2 infection. Diseases. 2021;9(1):17.', 'journal-title': 'Diseases'}, { 'issue': '3', 'key': '584_CR21', 'doi-asserted-by': 'publisher', 'first-page': '1015', 'DOI': '10.1016/j.jfda.2017.12.006', 'volume': '26', 'author': 'SM Richart', 'year': '2018', 'unstructured': 'Richart SM, Li YL, Mizushina Y, Chang YY, Chung TY, Chen GH, Tzen JTC, ' 'Shia KS, Hsu WL. Synergic effect of curcumin and its structural analogue ' '(Monoacetylcurcumin) on anti-influenza virus infection. J Food Drug ' 'Anal. 2018;26(3):1015–23.', 'journal-title': 'J Food Drug Anal'}, { 'key': '584_CR22', 'doi-asserted-by': 'crossref', 'unstructured': 'de Matos PH, da Silva TP, Mansano AB, Gancedo NC, Tonin FS, Pelloso FC, ' 'Petruco MV, de Melo EB, Fernandez-Llimos F, Sanches ACC, de Mello JCP, ' 'Chierrito D, de DCM Araújo. Bioactive compounds as potential ' 'angiotensin-converting enzyme II inhibitors against COVID-19: a scoping ' 'review. 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M. Kanai and H. Kakeya own equity and they are ' 'the scientific consultants of Therabiopharma Inc.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '93'}