NASAFYTOL® supplementation in adults hospitalized with COVID-19 infection: results from an exploratory open-label randomized controlled trial
Jean Gérain, Melanie Uebelhoer, Bérénice Costes, Julie Herman, Sandra Pietri, Anne-Françoise Donneau, Justine Monseur, Yves Henrotin
Frontiers in Nutrition, doi:10.3389/fnut.2023.1137407
Objectives: The effect and safety of Nasafytol ® , a food supplement combining curcumin, quercetin, and Vitamin D, on hospitalized COVID-19-positive patients as support to standard of care were to be assessed.
Methods: This exploratory, open-label, randomized, controlled trial was carried out among hospitalized adults with COVID-19 infection. Participants were randomly assigned to receive Nasafytol ® or Fultium ® control. The improvement of the clinical condition and occurrence of (serious) adverse events were evaluated. The study was registered on clincaltrials.gov with the identifier NCT04844658. Results: Twenty-five patients received Nasafytol ® , and 24 received Fultium ® . Demographic characteristics were well balanced between the groups. On day 14 (or at hospital leave if < 14 days), no difference was observed between groups regarding their clinical condition, fever, or the need of oxygen therapy. At day 7, however, 19 participants had been discharged from the hospital in the Nasafytol ® arm compared to 10 participants in the Fultium ® arm. No participants were transferred to the ICU or died in the Nasafytol ® arm, vs. 4 transfers and 1 death in the Fultium ® arm. The clinical condition of participants in the Nasafytol ® arm had improved, as evidenced by a decrease in the COVID-19 WHO score. Interestingly, five SAEs occurred with Fultium ® , while no SAE was observed with Nasafytol ® . Conclusion: Supplementation with Nasafytol ® , in addition to standard-of-care treatment, led to a faster discharge from the hospital, improved clinical conditions of participants, and a reduced risk of serious outcomes, including transfer to the intensive care unit or death, in patients hospitalized with COVID-19.
Ethics statement The studies involving human participants were reviewed and approved by Ethics Committee of the University Hospital of Brussels (Erasme-ULB) in Belgium (Comité d'Ethique Hospitalo-Facultaire Erasme-ULB) (protocol code B4062020000305 on January 15, 2021). The patients/participants provided their written informed consent to participate in this study.
Author contributions BC and YH: conceptualization. JG, BC, JH, and YH: methodology. A-FD and JM: statistical analysis. JG: investigation. MU and YH: writing-original draft preparation. JG, BC, JH, SP, A-FD, and JM: writing-review and editing. MU, BC, and JH: project administration. JG, MU, BC, JH, SP, A-FD, JM, and YH had full access to all the data in the study and had final responsibility for the decision to submit for publication. BC, JH, and YH accessed and verified the data. All authors contributed to the article and approved the submitted version.
Conflict of interest YH is the founder and president of Artialis SA, a spin-off company of the University of Liège. YH has also received consulting and speaker fees from Tilman SA, Nestlé, Laboratoire Expanscience, Heel,
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..
References
Aburto, Cisterna, Acuña, Ruíz, Viscardi et al., Obesity as a risk factor for severe COVID-19 in hospitalized patients: epidemiology and potential mechanisms, Healthcare,
doi:10.3390/healthcare10101838Ader, Bouscambert-Duchamp, Hites, Peiffer-Smadja, Poissy et al., Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial, Lancet Infect Dis,
doi:10.1016/S1473-3099(21)00485-0Andres, Pevny, Ziegenhagen, Bakhiya, Schäfer et al., Safety aspects of the use of quercetin as a dietary supplement, Mol Nutr Food Res,
doi:10.1002/mnfr.201700447Babaei, Nassiri-Asl, Hosseinzadeh, Curcumin (a constituent of turmeric): new treatment option against COVID-19, Food Sci Nutr,
doi:10.1002/fsn3.1858Bayati, Noroozi, Ghanbari-Jahromi, Jalali, Inequality in the distribution of Covid-19 vaccine: a systematic review, IJEqH,
doi:10.1186/s12939-022-01729-xBeigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of Covid-19-final report, N Engl J Med,
doi:10.1056/NEJMoa2007764Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., MECHANISMS IN ENDOCRINOLOGY: vitamin D and COVID-19, Eur J Endocrinol,
doi:10.1530/EJE-20-0665Cheng, Hsu, Lin, Hsu, Ho et al., Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions, Anticancer Res
Choi, Song, Kwon, Quercetin 3-rhamnoside exerts antiinfluenza a virus activity in mice, Phytother Res,
doi:10.1002/ptr.3529Dai, Gu, Su, Wang, Zhao et al., Inhibition of curcumin on influenza a virus infection and influenza pneumonia via oxidative stress, TLR2/4, p38/ JNK MAPK and NF-κB pathways, Int Immunopharmacol,
doi:10.1016/j.intimp.2017.11.009Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988Han, Xu, Guo, Huang, Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production, Clin Exp Pharmacol Physiol,
doi:10.1111/1440-1681.12848Khan, Iqtadar, Mumtaz, Heinrich, Pascual-Figal et al., 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, Front Pharmacol,
doi:10.3389/fphar.2022.898062Lee, Yu, Trimpert, Benthani, Mairhofer et al., Virusinduced senescence is a driver and therapeutic target in COVID-19, Nature,
doi:10.1038/s41586-021-03995-1Leyva-López, Gutierrez-Grijalva, Perez, Heredia, Flavonoids as cytokine modulators: a possible therapy for inflammation-related diseases, Int J Mol Sci,
doi:10.3390/ijms17060921Mercola, Grant, Wagner, Evidence regarding vitamin D and risk of COVID-19 and its severity, Nutrients,
doi:10.3390/nu12113361Moscatelli, Sessa, Valenzano, Polito, Monda et al., COVID-19: role of nutrition and supplementation, Nutrients,
doi:10.3390/nu13030976Murai, Fernandes, Sales, Pinto, Goessler et al., Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial, JAMA,
doi:10.1001/jama.2020.26848Park, Yoon, Kim, Lee, Chong, Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV), Arch Pharm Res,
doi:10.1007/s12272-012-0108-9Pierro, Derosa, Maffioli, Bertuccioli, Togni et al., Possible therapeutic effects of adjuvant quercetin supplementation against early-stage COVID-19 infection: a prospective, randomized, controlled, and open-label study, Int J Gen Med,
doi:10.2147/IJGM.S318720Qiu, Kroeker, He, Kozak, Audet et al., Prophylactic efficacy of quercetin 3-β-O-d-glucoside against Ebola virus infection, Antimicrob Agents Chemother,
doi:10.1128/AAC.00307-16Recovery Collaborative Group, Horby, Lim, Emberson, Mafham et al., Dexamethasone in hospitalized patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2021436Sabico, Enani, Sheshah, Aljohani, Aldisi et al., Effects of a 2-week 5000 IU versus 1000 IU vitamin D3 supplementation on recovery of symptoms in patients with mild to moderate Covid-19: a randomized clinical trial, Nutrients,
doi:10.3390/nu13072170Sharma, Prateeksha, Singh, Singh, Rao et al., Nanocurcumin potently inhibits SARS-CoV-2 spike protein-induced cytokine storm by deactivation of MAPK/NF-κB Signaling in epithelial cells, ACS Appl Bio Mater,
doi:10.1021/acsabm.1c00874Sterne, Murthy, Diaz, Slutsky, Villar, Association between Administration of Systemic Corticosteroids and Mortality among Critically ill Patients with COVID-19: a meta-analysis, JAMA,
doi:10.1001/jama.2020.17023Vahedian-Azimi, Abbasifard, Rahimi-Bashar, Guest, Majeed et al., Effectiveness of curcumin on outcomes of hospitalized COVID-19 patients: a systematic review of clinical trials, Nutrients,
doi:10.3390/nu14020256Who, Trial Consortiumpan, Peto, Henao-Restrepo, Preziosi et al., Repurposed antiviral drugs for Covid-19-interim WHO solidarity trial results, N Engl J Med,
doi:10.1056/NEJMoa2023184Wu, Effect of curcumin on nasal symptoms and airflow in patients with perennial allergic rhinitis, Ann Allergy Asthma Immunol,
doi:10.1016/j.anai.2016.09.427Wu, Li, Li, He, Jiang et al., Quercetin as an antiviral agent inhibits influenza a virus (IAV) entry. Viruses,
doi:10.3390/v8010006Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3
