All Studies Meta Analysis

Effect of an Immune-Boosting, Antioxidant and Anti-Inflammatory Food Supplement in Hospitalized COVID-19 Patients: A Prospective Randomized Pilot Study

Reino-Gelardo et al., Nutrients, doi:10.3390/nu15071736, NCT04666116

Apr 2023

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Download Image

Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 109 treatments. c19early.org

RCT 162 late stage (65% on oxygen) patients in Spain, 78 treated with probiotics, prebiotics, vitamin D, zinc, and selenium, showing lower mortality with treatment, statistically significant only within the patients with high severity at baeline.

Treatment included bifidobacterium lactis BPL1, lactobacillus rhamnosus CNCM I-4036, bifidobacterium longum ES1, 1.5mg of zinc, 8.25μg of selenium, and 0.75μg of vitamin D.

Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 69% [47‑82%] lower risk vs. 39% [27‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.

Important missing comments or errors? Let us know.

Study covers vitamin D, selenium, zinc, and probiotics.

risk of death, 60.5% lower, RR 0.39, p = 0.05, treatment 8 of 67 (11.9%), control 15 of 78 (19.2%), adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk.

risk of death, 91.4% lower, RR 0.09, p < 0.001, treatment 1 of 15 (6.7%), control 7 of 9 (77.8%), NNT 1.4, baseline high severity.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Reino-Gelardo et al., 1 Apr 2023, Randomized Controlled Trial, Spain, peer-reviewed, mean age 68.7, 10 authors, study period 31 March, 2020 - 15 November, 2020, this trial uses multiple treatments in the treatment arm (combined with probiotics, prebiotics, vitamin D, zinc, and selenium) - results of individual treatments may vary, trial NCT04666116 (history).

This Paper Vitamin D All

Effect of an Immune-Boosting, Antioxidant and Anti-Inflammatory Food Supplement in Hospitalized COVID-19 Patients: A Prospective Randomized Pilot Study

Lianliang Liu, Qixiao Zhai, Sandra Reino-Gelardo, Marta Palop-Cervera, Nieves Aparisi-Valero, Ignac Espinosa-San, Noelia Lozano-Rodríguez, Gonzalo Llop-Furque, Laura Sanchis-Artero, Ernesto Cortés-Castell, Mercedes Rizo-Baeza, Xavier Cortés-Rizo

doi:10.3390/nu15071736

Background: COVID-19 disease is a serious global health problem. Few treatments have been shown to reduce mortality and accelerate time to recovery. The aim of this study was to evaluate the potential effect of a food supplement (probiotics, prebiotics, vitamin D, zinc and selenium) in patients admitted with COVID-19. Methods: A prospective randomized non-blinded clinical trial was conducted in a sample of 162 hospitalized patients diagnosed with COVID-19 recruited over eight months. All patients received standard treatment, but the intervention group (n = 67) was given one food supplement stick daily during their admission. After collecting the study variables, a statistical analysis was performed comparing the intervention and control groups and a multivariate analysis controlling for variables that could act as confounding factors. Results: ROC curve analysis with an area under the curve (AUC) value of 0.840 (p < 0.001; 95%CI: 0.741-0.939) of the food supplement administration vs. recovery indicated good predictive ability. Moreover, the intervention group had a shorter duration of digestive symptoms compared with the control group: 2.6 ± 1.3 vs. 4.3 ± 2.2 days (p = 0.001); patients with non-severe disease on chest X-ray had shorter hospital stays: 8.1 ± 3.9 vs. 11.6 ± 7.4 days (p = 0.007). Conclusions: In this trial, the administration of a food supplement (Gasteel Plus ® ) was shown to be a protective factor in the group of patients with severe COVID-19 and allowed early recovery from digestive symptoms and a shorter hospital stay in patients with a normal-mild-moderate chest X-ray at admission (ClinicalTrials.gov number, NCT04666116).

Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/nu15071736/s1, Figure S1 : ROC curve for evaluation of the potential effect of the food supplement Gasteel as a protector factor in the response. The value of the area under the curve (AUC) indicates the ability of the parameters studied as variable of exitus response; Table S1 : Summary of the main treatment administered during hospitalization of the study population, according the local guide. The p values were obtained with the χ 2 test and the Student's t test; Table S2 . Evolution of the main analytical parameters for recovery evaluation during admission and discharge period; Table S3 . Pharmacological treatment algorithm in the patients recruited from March to April 2020; Table S4 . Pharmacological treatment algorithm in the patients recruited September to November 2020. References [42] [43] [44] [45] [46] [47] are cited in the supplementary materials. Informed Consent Statement: Informed consent was obtained from all subjects involved in this study. Conflicts of Interest: The authors declare no conflict of interest. The authors would like to note that the use of probiotics is only addressed to supplement nutritionally patients with the aim of contributing to their microbiome's recovery.

References

Aranow, Vitamin D and the immune system, J. Investig. Med, doi:10.2310/JIM.0b013e31821b8755

Arribas, García-Vidal, Recomendaciones SEIMC Para El Manejo Clínico De Pacientes Con COVID-19

Arthur, Mckenzie, Beckett, Selenium in the immune system, J. Nutr, doi:10.1093/jn/133.5.1457S

Bae, Kim, Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19, Molecules, doi:10.3390/molecules25225346

Balboni, Zagnoli, Filippini, Fairweather-Tait, Vinceti, Zinc and selenium supplementation in COVID-19 prevention and treatment: A systematic review of the experimental studies, J. Trace Elem. Med. Biol, doi:10.1016/j.jtemb.2022.126956

Ballini, Santacroce, Cantore, Bottalico, Dipalma et al., Pro-biotics efficacy on oxidative stress values in inflammatory bowel disease: A randomized double-blinded placebo-controlled pilot study, Endocr. Metab. Immune Disord-Drug Targets, doi:10.2174/1871530319666181221150352

Bassatne, Basbous, Chakhtoura, El Zein, Rahme et al., The link between COVID-19 and Vitamin D (VIVID): A systematic review and meta-analysis, Metabolism, doi:10.1016/j.metabol.2021.154753

Baud, Dimopoulou Agri, Gibson, Reid, Giannoni, Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic, Front Public Health, doi:10.3389/fpubh.2020.00186

Budden, Gellatly, Wood, Cooper, Morrison et al., Emerging pathogenic links between microbiota and the gut-lung axis, Nat. Rev. Microbiol, doi:10.1038/nrmicro.2016.142

Casas-Rojo, Antón-Santos, Millán-Núñez-Cortés, Lumbreras-Bermejo, Ramos-Rincón et al., Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry, Rev. Clin. Esp, doi:10.1016/j.rce.2020.07.003

Chamorro, Tascón, Sanz, Vélez, Nacenta, Radiologic diagnosis of patients with COVID-19, Radiologia, doi:10.1016/j.rx.2020.11.001

Conte, Toraldo, Targeting the gut-lung microbiota axis by means of a high-fibre diet and probiotics may have antiinflammatory effects in COVID-19 infection, Ther. Adv. Respir. Dis, doi:10.1177/1753466620937170

D'ettorre, Ceccarelli, Marazzato, Campagna, Pinacchio et al., Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19, Front. Med, doi:10.3389/fmed.2020.00389

Dhar, Mohanty, Gut microbiota and COVID-19-possible link and implications, Virus Res, doi:10.1016/j.virusres.2020.198018

Dong, Du, Gardner, An interactive web-based dashboard to track COVID-19 in real time, Lancet Inf. Dis, doi:10.1016/S1473-3099(20)30120-1

Fraker, King, Laakko, Vollmer, The dynamic link between the integrity of the immune system and zinc status, J. Nutr, doi:10.1093/jn/130.5.1399S

Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with COVID-19, N. Engl. J. Med

Gupta, Madhavan, Sehgal, Nair, Mahajan et al., Extrapulmonary manifestations of COVID-19, Nat. Med, doi:10.1038/s41591-020-0968-3

Han, Mclaughlin, Criner, Martinez, Pulmonary diseases and the heart, Circulation

Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, doi:10.1016/S0140-6736(20)30183-5

Jin, Lian, Hu, Gao, Zheng et al., Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms, Gut, doi:10.1136/gutjnl-2020-320926

Kalil, Patterson, Mehta, Tomashek, Wolfe et al., ACTT-2 Study Group Members. Baricitinib plus Remdesivir for Hospitalized Adults with COVID-19, N. Engl. J. Med, doi:10.1056/NEJMoa2031994

Khaled, Probiotics, prebiotics, and COVID-19 infection: A review article, Saudi J. Biol. Sci, doi:10.1016/j.sjbs.2020.11.025

Leal, Costa, Arroja, Goncalves, Alves, Gastrointestinal manifestations of COVID-19: Results from a European centre, Eur. J. Gastroenterol. Hepatol, doi:10.1097/MEG.0000000000002152

Liu, Zhu, He, Zhu, Hu et al., Probiotics for treating novel coronavirus with diarrhea: A protocol for systematic review and meta-analysis, Medicine, doi:10.1097/MD.0000000000021617

Molina, Delaugerre, Le Goff, Mela-Lima, Ponscarme et al., No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection, Med. Mal. Infect, doi:10.1016/j.medmal.2020.03.006

Olivares, Laparra, Sanz, Influence of Bifidobacterium longum CECT 7347 and gliadin peptides on intestinal epithelial cell proteome, J. Agric. Food Chem, doi:10.1021/jf201212m

Pan, Mu, Yang, Sun, Wang et al., Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study, Am. J. Gastroenterol, doi:10.14309/ajg.0000000000000620

Pedrosa, Barros, Leite-Lais, Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk and clinical outcomes of COVID-19: A narrative review, Clin. Nutr. ESPEN, doi:10.1016/j.clnesp.2021.11.003

Raisi-Estabragh, Martineau, Curtis, Moon, Darling et al., Vitamin D and coronavirus disease 2019 (COVID-19): Rapid evidence review, Aging Clin. Exp. Res, doi:10.1007/s40520-021-01894-z

Redinbo, The microbiota, chemical symbiosis, and human disease, J. Mol. Biol, doi:10.1016/j.jmb.2014.09.011

Rosas, Bräu, Waters, Go, Hunter et al., Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia, N. Engl. J. Med, doi:10.1056/NEJMoa2028700

Santacroce, Charitos, Bottalico, A successful history: Probiotics and their potential as antimicrobials, Expert Rev. Anti Infect. Ther, doi:10.1080/14787210.2019.1645597

Santacroce, Inchingolo, Topi, Del Prete, Di Cosola et al., Potential beneficial role of probiotics on the outcome of COVID-19 patients: An evolving perspective, Diabetes Metab. Syndr, doi:10.1016/j.dsx.2020.12.040

Schleiermacher, Hoffmann, Pulmonary abnormalities in inflammatory bowel disease, J. Crohns Colitis

Schmulson, Dávalos, Berumen, Beware: Gastrointestinal symptoms can be a manifestation of COVID-19, Rev. Gastroenterol. Mex, doi:10.1016/j.rgmxen.2020.04.001

Seimc, Recomendaciones SEIMC para el Manejo Clínico de Pacientes con COVID-19

Shi, Balakrishnan, Thiagarajah, Ismail, Yin, Beneficial properties of probiotics, Trop. Life Sci. Res, doi:10.21315/tlsr2016.27.2.6

Sundararaman, Ray, Ravindra, Halami, Role of probiotics to combat viral infections with emphasis on COVID-19, Appl. Microbiol. Biotechnol, doi:10.1007/s00253-020-10832-4

Tang, Tong, Wang, Dai, Li et al., Detection of Novel Coronavirus by RT-PCR in Stool Specimen from Asymptomatic Child, China, Emerg. Infect. Dis, doi:10.3201/eid2606.200301

The, Group, Dexamethasone in Hospitalized Patients with COVID-19, N. Engl. J. Med, doi:10.1056/NEJMoa2021436

Wang, Xu, Gao, Lu, Han et al., Detection of SARS-CoV-2 in Different Types of Clinical Specimens, JAMA, doi:10.1001/jama.2020.3786

Xiao, Tang, Zheng, Liu, Li et al., Evidence for Gastrointestinal Infection of SARS-CoV-2, Gastroenterology, doi:10.1053/j.gastro.2020.02.055

Zhang, Garrett, Sun, Gastrointestinal symptoms, pathophysiology, and treatment in COVID-19, Genes Dis, doi:10.1016/j.gendis.2020.08.013

Zuo, Zhang, Lui, Yeoh, Li et al., Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization, Gastroenterology, doi:10.1053/j.gastro.2020.05.048

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0