Comparative analysis of COVID-19 responses in Japan and Africa: diet, phytochemicals, vitamin D, and gut microbiota in reducing mortality—A systematic review and meta-analysis
Kazuki Santa, Raita Tamaki, Kenji Watanabe, Isao Nagaoka
Frontiers in Nutrition, doi:10.3389/fnut.2024.1465324
Background: As the novel coronavirus disease 2019 (COVID-19) pandemic subsides, the clinical sequelae are becoming more problematic. Interestingly, the statistical data indicate that Africa has experienced the lowest number of cases and deaths, with an unexpected phenomenon where the number of deaths from COVID-19 has not increased significantly. Several studies have investigated the relationship between diet and coronavirus. However, no systematic review/ meta-analysis has conclusively linked diet (phytochemicals and vitamin D) and the gut microbiota in the context of COVID-19. Methods: This study examined the responses to COVID-19 in Japan and Africa, formulating the following hypotheses: (1) a healthy diet is effective against COVID-19, (2) blood vitamin D levels are associated with COVID-19 mortality, and (3) COVID-19 is associated with the gut microbiota. To investigate these hypotheses, a keyword search and meta-analysis were conducted using PubMed, and each hypothesis was tested. Results: This study found that a healthy diet, particularly rich in phytochemicals such as polyphenols and flavonoids, is effective against COVID-19. An association was detected between blood vitamin D levels and COVID-19 mortality. The gut microbiota was linked to COVID-19 and its amelioration. These findings may have significant implications for not only understanding COVID-19 but also future prevention of pneumonia.
Ethics statement Ethical approval was not required for the studies involving humans because all data used are publicly available. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/ next of kin in accordance with the national legislation and institutional requirements because all data used are publicly available.
Author contributions
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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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.
Supplementary material The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2024.1465324/ full#supplementary-material Frontiers in Nutrition 20 frontiersin.org
References
Aborode, Ogunsola, Adeyemo, A crisis within a crisis: COVID-19 and hunger in African children, Am J Trop Med Hyg,
doi:10.4269/ajtmh.20-1213Adebayo, Itkonen, Öhman, Skaffari, Saarnio et al., Vitamin D intake, serum 25-hydroxyvitamin D status and response to moderate vitamin D3 supplementation: a randomised controlled trial in east African and Finnish women, Br J Nutr,
doi:10.1017/S000711451700397XAdom, Villiers, Puoane, Kengne, A scoping review of policies related to the prevention and control of overweight and obesity in Africa, Nutrients,
doi:10.3390/nu13114028Ahmadi, Mehrabi, Zare, Ghadir, Masoumi, Efficacy of Nanocurcumin as an add-on treatment for patients hospitalized with COVID-19: a double-blind, randomized clinical trial, Int J Clin Pract,
doi:10.1155/2023/5734675Annweiler, Beaudenon, Gautier, Gonsard, Boucher et al., High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): a multicenter, open-label, randomized controlled superiority trial, PLoS Med,
doi:10.1371/journal.pmed.1003999Ao, Kikuta, Ishii, The effects of vitamin D on immune system and inflammatory diseases, Biomol Ther,
doi:10.3390/biom11111624Aparicio, Gold, Weiss, Litonjua, Lee-Sarwar et al., Association of vitamin D Level and maternal gut microbiome during pregnancy: findings from a randomized controlled trial of antenatal vitamin D supplementation, Nutrients,
doi:10.3390/nu15092059Arabnezhad, Mohammadifard, Rahmani, Majidi, Ferns et al., Effects of curcumin supplementation on vitamin D levels in women with premenstrual syndrome and dysmenorrhea: a randomized controlled study, BMC Complement Med Ther,
doi:10.1186/s12906-022-03515-2Aryan, Farahani, Chamanara, Elyasi, Jaafari et al., Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: a double-blind placebo-controlled clinical trial, Phytother Res,
doi:10.1002/ptr.7537Asano, Kushida, Yamamoto, Tomata, Tsuji et al., Abdominal fat in individuals with overweight reduced by consumption of a 1975 Japanese diet: a randomized controlled trial, Obesity,
doi:10.1002/oby.22448Babszky, Torma, Aczel, Bakonyi, Gombos et al., COVID-19 infection alters the microbiome: elite athletes and sedentary patients have similar bacterial Flora, Genes,
doi:10.3390/genes12101577Bell, Schultz, Relative burdens of the COVID-19, malaria, tuberculosis, and HIV/AIDS epidemics in sub-Saharan Africa, Am J Trop Med Hyg,
doi:10.4269/ajtmh.21-0899Bellerba, Serrano, Johansson, Pozzi, Segata et al., Colorectal cancer, vitamin D and microbiota: a double-blind phase II randomized trial (ColoViD) in colorectal cancer patients, Neoplasia,
doi:10.1016/j.neo.2022.100842Blackett, Sun, Purpura, Margolis, Elkind et al., Decreased gut microbiome tryptophan metabolism and serotonergic signaling in patients with persistent mental health and gastrointestinal symptoms after COVID-19, Clin Transl Gastroenterol,
doi:10.14309/ctg.0000000000000524Bouillon, Marcocci, Carmeliet, Bikle, White et al., Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions, Endocr Rev,
doi:10.1210/er.2018-00126Brunvoll, Nygaard, Ellingjord-Dale, Holland, Istre et al., Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial, BMJ,
doi:10.1136/bmj-2022-071245Bychinin, Klypa, Mandel, Yusubalieva, Baklaushev et al., Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU, Sci Rep,
doi:10.1038/s41598-022-22045-yCaballero-García, Pérez-Valdecantos, Guallar, Caballero-Castillo, Roche et al., Effect of vitamin D supplementation on muscle status in old patients recovering from COVID-19 infection, Medicina,
doi:10.3390/medicina57101079Cannata-Andía, Díaz-Sottolano, Fernández, Palomo-Antequera, Herrero-Puente et al., A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial, BMC Med,
doi:10.1186/s12916-022-02290-8Carrouel, Valette, Gadea, Esparcieux, Illes et al., Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial, Clin Microbiol Infect,
doi:10.1016/j.cmi.2021.05.028Cashman, Kiely, Andersen, Grønborg, Madsen et al., Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate dietary reference values for vitamin D, Eur J Nutr,
doi:10.1007/s00394-020-02298-xCesur, Atasever, Özoran, Impact of vitamin D3 supplementation on COVID-19 vaccine response and immunoglobulin G antibodies in deficient women: a randomized controlled trial, Vaccine,
doi:10.1016/j.vaccine.2023.03.046D'ascanio, Vitelli, Cingolani, Maranzano, Brenner et al., Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and frontiersin.org Luteolin": preliminary results, Eur Rev Med Pharmacol Sci,
doi:10.26355/eurrev_202106_26059D'ecclesiis, Gavioli, Martinoli, Raimondi, Chiocca et al., Vitamin D and SARS-CoV2 infection, severity and mortality: a systematic review and meta-analysis, PLoS One,
doi:10.1371/journal.pone.0268396De Filippo, Cavalieri, Paola, Ramazzotti, Poullet et al., Correlation analysis between gut microbiota alterations and the cytokine response in patients with coronavirus disease during hospitalization, Proc Natl Acad Sci,
doi:10.1128/spectrum.01689-21De Ligt, Hesselink, Jorgensen, Hoebers, Blaak et al., Resveratrol supplementation reduces ACE2 expression in human adipose tissue, Adipocytes,
doi:10.1080/21623945.2021.1965315De Luca, Camaioni, Marra, Salzano, Carriere et al., Effect of ultramicronized Palmitoylethanolamide and Luteolin on olfaction and memory in patients with long COVID: results of a longitudinal study, Cells,
doi:10.3390/cells11162552Elamir, Amir, Lim, Rana, Lopez et al., Impact of vitamin D supplementation on the clinical outcomes of COVID-19 pneumonia patients: a single-center randomized controlled trial, BMC Complement. Med. Ther,
doi:10.1186/s12906-024-04393-6Entrenas, Costa, Barrios, Díaz, López et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: a pilot randomized clinical study, J Steroid Biochem Mol Biol,
doi:10.1016/j.jsbmb.2020.105751Faber, Malan, Kruger, Asare, Visser et al., Potential of egg as complementary food to improve nutrient intake and dietary diversity, Nutrients,
doi:10.3390/nu14163396Federico, Dallio, Masarone, Sarno, Tuccillo et al., Evaluation of the effect derived from Silybin with vitamin D and vitamin E administration on clinical, metabolic, endothelial dysfunction, oxidative stress parameters, and serological worsening markers in nonalcoholic fatty liver disease patients, Oxidative Med Cell Longev,
doi:10.1155/2019/8742075Fernandes, Murai, Reis, Sales, Santos et al., Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19, Am J Clin Nutr,
doi:10.1093/ajcn/nqab426Fincham, Hohlfeld, Clarke, Kredo, Mccaul, Exploring trial publication and research waste in COVID-19 randomised trials of hydroxychloroquine, corticosteroids, and vitamin D: a meta-epidemiological cohort study, BMC Med Res Methodol,
doi:10.1186/s12874-023-02110-4Forsgård, Rode, Lobenius-Palmér, Kamm, Patil et al., Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial, Gut Microbes,
doi:10.1080/19490976.2023.2229938Gao, Ye, Lei, Zhang, Luo et al., Dendrobium officinale aqueous extract influences the immune response following vaccination against SARS-CoV-2, Biomed Pharmacother,
doi:10.1016/j.biopha.2023.114702Ghareghani, Reiter, Zibara, Farhadi, Latitude et al., melatonin, and gut microbiota act in concert to initiate multiple sclerosis: a New mechanistic pathway, Front Immunol,
doi:10.1038/nature05414Gill, Mwananyanda, Leod, Kwenda, Pieciak et al., What is the prevalence of COVID-19 detection by PCR among deceased individuals in Lusaka, Zambia? A postmortem surveillance study, BMJ Open,
doi:10.1136/bmjopen-2022-066763Golabi, Ghasemi, Adelipour, Bagheri, Suzuki et al., Oxidative stress and inflammatory status in COVID-19 outpatients: a health center-based analytical cross-sectional study, Antioxidants,
doi:10.3390/antiox11040606Greene, Roberts, Frugé, Negative association between Mediterranean diet adherence and COVID-19 cases and related deaths in Spain and 23 OECD countries: an ecological study, Front Nutr,
doi:10.3389/fnut.2021.591964Gualtieri, Marchetti, Frank, Smeriglio, Trombetta et al., Antioxidant-enriched diet on oxidative stress and inflammation gene expression: a randomized controlled trial, Genes,
doi:10.3390/genes14010206Gutiérrez-Castrellón, Gandara-Martí, Abreu, Ay, Nieto-Rufino et al., Probiotic improves symptomatic and viral clearance in COVID 19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial, Gut Microbes,
doi:10.1080/19490976.2021.2018899Haas, Brandl, Schinhammer, Skurk, Individualized supplementation of Immunoactive micronutrients and severity of upper respiratory infection symptoms-a randomized intervention study, Nutrients,
doi:10.3390/nu16101400Halfmann, Hatta, Chiba, Maemura, Fan et al., Transmission of SARS-CoV-2 in domestic cats, N Engl J Med,
doi:10.1056/NEJMc2013400Hosseini, El Abd, Ducharme, Effects of vitamin D supplementation on COVID-19 related outcomes: a systematic review and meta-analysis, Nutrients,
doi:10.3390/nu14102134Houeze, Wang, Zhou, Zhang, Wang, Comparison study of Beninese and Chinese herbal medicines in treating COVID-19, J Ethnopharmacol,
doi:10.1016/j.jep.2023.116172Hurtado-Barroso, Trius-Soler, Lamuela-Raventós, Zamora-Ros, Vegetable and fruit consumption and prognosis among Cancer survivors: a systematic review and Meta-analysis of cohort studies, Adv Nutr,
doi:10.1093/advances/nmaa082Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res,
doi:10.1007/s40520-020-01570-8Itkonen, Andersen, Björk, Brugård, Eneroth et al., Vitamin D status and current policies to achieve adequate vitamin D intake in the Nordic countries, Scand J Public Health,
doi:10.1177/1403494819896878Jamieson, Smart, Bouranis, Choi, Danczak et al., Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults, Gut Microbes,
doi:10.1080/19490976.2024.2315633Jastrzębska, Skalska, Radzimiński, López-Sánchez, Weiss et al., Changes of 25(OH)D concentration, bone resorption markers and physical performance as an effect of Sun exposure, supplementation of vitamin D and lockdown among young soccer players during a one-year training season, Nutrients,
doi:10.3390/nu14030521Jolliffe, Vivaldi, Chambers, Cai, Li et al., Vitamin D supplementation does not influence SARS-CoV-2 vaccine efficacy or immunogenicity: sub-studies nested within the CORONAVIT randomised controlled trial, Nutrients,
doi:10.3390/nu14183821Kamer, Rinott, Tsaban, Kaplan, Yaskolka et al., Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial, Gut Microbes,
doi:10.1080/19490976.2023.2264457Karonova, Chernikova, Golovatyuk, Bykova, Grant et al., Vitamin D intake may reduce SARS-CoV-2 infection morbidity in health care workers, Nutrients,
doi:10.3390/nu14030505Kawaguchi, Kikuchi, Hasunuma, Maruyama, Yoshikawa et al., A citrus flavonoid hesperidin suppresses infection-induced endotoxin shock in mice, Biol Pharm Bull,
doi:10.1248/bpb.27.679Klein, Wood, Jaycox, Dhodapkar, Lu et al., Distinguishing features of long COVID identified through immune profiling, Nature,
doi:10.1038/s41586-023-06651-yKogan, Gantt, Swerdlow, Viboud, Semakula et al., Leveraging Serosurveillance and postmortem surveillance to quantify the impact of coronavirus disease 2019 in Africa, Clin Infect Dis,
doi:10.1093/cid/ciac897Kumazawa, Takimoto, Matsumoto, Kawaguchi, Potential use of dietary natural products, especially polyphenols, for improving type-1 allergic symptoms, Curr Pharm Des,
doi:10.2174/138161282006140220120344Kushida, Sugawara, Asano, Yamamoto, Fukuda et al., Effects of the 1975 Japanese diet on the gut microbiota in younger adults, J Nutr Biochem,
doi:10.1016/j.jnutbio.2018.10.011Lackner, Mahnert, Moissl-Eichinger, Madl, Habisch et al., Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes-secondary analysis of a randomized placebocontrolled parallel intervention trial, Microbiome,
doi:10.1186/s40168-024-01774-4Lacy, Khan, Deb, Das, Igoe et al., Geographic disparities and predictors of COVID-19 vaccination in Missouri: a retrospective ecological study, Front Public Health,
doi:10.3389/fpubh.2024.1329382Lau, Su, Lau, Ching, Wong et al., A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial, Lancet Infect Dis,
doi:10.1016/S1473-3099(23)00685-0Lee, Park, Kang, Choi, Park et al., High dose intramuscular vitamin D3 supplementation impacts the gut microbiota of patients with Clostridioides difficile infection, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2022.904987Li, Watanabe, Kawashima, Plichta, Wang et al., Identification of trypsin-degrading commensals in the large intestine, Nature,
doi:10.1038/s41586-022-05181-3Losso, Losso, Toc, Inungu, Finley, The young age and plant-based diet hypothesis for low SARS-CoV-2 infection and COVID-19 pandemic in sub-Saharan Africa, Plant Foods Hum Nutr,
doi:10.1007/s11130-021-00907-6Lowe, Maiyar, Norman, Vitamin D-mediated gene expression, Crit Rev Eukaryot Gene Expr
Maghbooli, Sahraian, Jamalimoghadamsiahkali, Asadi, Zarei et al., Treatment with 25-Hydroxyvitamin D(3) (Calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in hospitalized patients with COVID-19: a pilot multicenter, randomized, placebocontrolled, double-blinded clinical trial, Endocr Pract,
doi:10.3390/nu15071736Mahjoub, Youssef, Yaakoubi, Salah, Jaballah et al., Melatonin, vitamins and minerals supplements for the treatment of COVID-19 and COVID-like illness: a prospective, randomized, double-blind multicenter study, Explore,
doi:10.1016/j.explore.2023.06.009Mariani, Antonietti, Tajer, Ferder, Inserra et al., High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: multicentre randomized controlled clinical trial, Nutrition,
doi:10.1016/j.nut.2022.111899Marseglia, Licari, Leonardi, Papale, Zicari et al., A polycentric, randomized, parallel-group, study on Lertal ® , a multicomponent nutraceutical, as preventive treatment in children with allergic rhinoconjunctivitis: phase II, Ital J Pediatr,
doi:10.1186/s13052-019-0678-yMathrani, Yip, Sequeira-Bisson, Barnett, Stevenson et al., Effect of a 12-week polyphenol Rutin intervention on markers of pancreatic β-cell function and gut microbiota in adults with overweight without diabetes, Nutrients,
doi:10.3390/nu15153360Mc, Schnell, Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19), Sci Rep,
doi:10.1038/s41598-022-13920-9Middelkoop, Stewart, Walker, Delport, Jolliffe et al., Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids), Int J Infect Dis,
doi:10.1016/j.ijid.2023.05.010Miyamoto, Kawakami, Hanafusa, Nakanishi, Miyasaka et al., Determination of a serum 25-Hydroxyvitamin D reference ranges in Japanese adults using fully automated liquid chromatography-tandem mass spectrometry, J Nutr,
doi:10.1016/j.tjnut.2023.01.036Mogire, Mutua, Kimita, Kamau, Bejon et al., Prevalence of vitamin D deficiency in Africa: a systematic review and meta-analysis, Lancet Glob Health,
doi:10.1016/S2214-109X(19)30457-7Mullish, Marchesi, Mcdonald, Pass, Masetti et al., Probiotics reduce self-reported symptoms of upper respiratory tract infection in overweight and obese adults: should we be considering probiotics during viral pandemics?, Gut Microbes,
doi:10.1080/19490976.2021.1900997Murai, Fernandes, Antonangelo, Gualano, Pereira, Effect of a single high-dose vitamin D3 on the length of hospital stay of severely 25-Hydroxyvitamin D-deficient patients with COVID-19, Clinics,
doi:10.6061/clinics/2021/e3549Murai, 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.2020.26848Murakami, Shinozaki, Livingstone, Yuan, Tajima et al., Associations of food choice values and food literacy with overall diet quality: a nationwide cross-sectional study in Japanese adults, Br J Nutr,
doi:10.1017/S000711452300082XNaderpoor, Mousa, Gomez Arango, Barrett, Dekker et al., Effect of vitamin D supplementation on Faecal microbiota: a randomised clinical trial, Nutrients,
doi:10.3390/nu11122888Nagai, Moriyama, Ishii, Mori, Watanabe et al., Acute and subacute oral toxicity characterization and safety assessment of COVID organics ® (Madagascar's anti-COVID herbal tea) in animal models, Environ Sci Pollut Res Int
Nagaoka, Tamura, Reich, Therapeutic potential of cathelicidin peptide LL-37, an antimicrobial agent, in a murine Sepsis model, Int J Mol Sci,
doi:10.3390/ijms21175973Nagata, Takeuchi, Masuoka, Aoki, Ishikane et al., Human gut microbiota and its metabolites impact immune responses in COVID-19 and its complications, Gastroenterology,
doi:10.1053/j.gastro.2022.09.024Niet, Trémège, Coffiner, Rousseau, Calmes et al., Vitamin D3 supplementation at 5000 IU daily for the prevention of influenza-like illness in healthcare workers: a pragmatic randomized clinical trial, Placebo-Controlled Trial Nutr,
doi:10.3390/nu15010180Odai, Terauchi, Kato, Hirose, Miyasaka, Effects of grape seed proanthocyanidin extract on vascular endothelial function in participants with prehypertension: a randomized, double-blind, Placebo-Controlled Study Nutrients,
doi:10.3390/nu11122844Page, Mckenzie, Bossuyt, Boutron, Hoffmann et al., The PRISMA 2020 statement: an updated guideline for reporting systematic reviews, BMJ,
doi:10.1136/bmj.n71Pham, Fehlbaum, Seifert, Richard, Bruins et al., Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome-a pilot study, Gut Microbes,
doi:10.1080/19490976.2021.1875774Rabbi, Oláh, Popp, Máté, Kovács, Food security and the COVID-19 crisis from a consumer buying behaviour perspective-the case of Bangladesh, Food Secur,
doi:10.3390/foods10123073Riccia, Cafaro, John, Van Helmond, Mitrev et al., Healthcare costs and healthcare utilization outcomes of vitamin D3 supplementation at 5000 IU daily during a 10.9 month observation period within a pragmatic randomized clinical trial, Nutrients,
doi:10.3390/nu15204435Rodríguez-Argente, Alba-Domínguez, Díaz-Martínez, Vergara, Díaz-Márques et al., Buccopharyngeal route administered high polyphenolic olive oil and COVID-19: a pilot clinical trial, Immun Inflamm Dis,
doi:10.1002/iid3.1054Sabico, 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/nu13072170Santa, Healthy diet, grape phytochemicals, and vitamin D: preventing chronic inflammation and keeping good microbiota, Endocr Metab Immune Disord Drug Targets,
doi:10.2174/1871530323666221017151705Santa, Kumazawa, Nagaoka, The potential use of grape phytochemicals for preventing the development of intestine-related and subsequent inflammatory diseases, Endocr Metab Immune Disord Drug Targets,
doi:10.2174/1871530319666190529105226Santa, Kumazawa, Watanabe, Nagaoka, The potential use of vitamin D3 and phytochemicals for their anti-ageing effects, Int J Mol Sci,
doi:10.3390/ijms25042125Santa, Kumazawa, Watanabe, Nagaoka, The recommendation of the Mediterranean-styled Japanese diet for healthy longevity, Endocr Metab Immune Disord Drug Targets,
doi:10.2174/0118715303280097240130072031Santa, Watanabe, Kumazawa, Nagaoka, Phytochemicals and vitamin D for a healthy life and prevention of diseases, Int J Mol Sci,
doi:10.3390/ijms241512167Sarhan, Warda, Sarhan, Boshra, Mostafa-Hedeab et al., Evidence for the efficacy of a high dose of vitamin D on the hyperinflammation state in moderate-to-severe COVID-19 patients: a randomized clinical trial, Medicina
Sayama, Okamoto, Saito, Tamaki, Saito-Obata et al., Lack of zoonotic coronavirus species detected among children hospitalized with pneumonia in the Philippines, Clin Infect Dis,
doi:10.1093/cid/ciad430Scaturro, Vitagliani, Tomasello, Sconza, Respizzi et al., Combined rehabilitation with alpha lipoic acid, acetyl-L-carnitine, resveratrol, and cholecalciferolin discogenic sciatica in young people: a randomized clinical trial, Medicina,
doi:10.3390/medicina59122197Sevillano-Jiménez, Romero-Saldaña, Carrascal-Laso, García-Rodríguez, Molina-Luque et al., Impact of high prebiotic and probiotic dietary education in the SARS-CoV-2 era: improved cardio-metabolic profile in schizophrenia spectrum disorders, BMC Psychiatr,
doi:10.1186/s12888-022-04426-9Shin-Ya, Nakashio, Ohgitani, Suganami, Kawamoto et al., Effects of tea, catechins and catechin derivatives on omicron subvariants of SARS-CoV-2, Sci Rep,
doi:10.1038/s41598-023-43563-3Shohan, Nashibi, Mahmoudian-Sani, Abolnezhadian, Ghafourian et al., The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: a randomized controlled trial, Eur J Pharmacol,
doi:10.1016/j.ejphar.2021.174615Stadio, 'ascanio, Vaira, Cantone, Luca et al., Ultramicronized Palmitoylethanolamide and Luteolin supplement combined with olfactory training to treat post-COVID-19 olfactory impairment: a multi-center doubleblinded randomized placebo-controlled clinical trial, Curr Neuropharmacol,
doi:10.2174/1570159X20666220420113513Stadio, Gallina, Cocuzza, Luca, Ingrassia et al., Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial, Eur Arch Otorrinolaringol,
doi:10.1007/s00405-023-08085-8Sugawara, Kushida, Iwagaki, Asano, Yamamoto et al., The 1975 type Japanese diet improves lipid metabolic parameters in younger adults: a randomized controlled trial, J Oleo Sci,
doi:10.5650/jos.ess17259Tadayon, Rayner, Shokraee, Shokraie, Panahi et al., Obesity as an independent risk factor for COVID-19 severity and mortality, Cochrane Database Syst Rev,
doi:10.1002/14651858.CD015201Takabayashi, Okada, Hirata, Takimoto, Nakamura et al., Nutritional adequacy assessment of the Japanese diet using the number of dishes compared to existing dietary diversity indices: a cross-sectional analysis from the 2012 national health and nutrition survey, Japan, J Nutr Sci Vitaminol,
doi:10.3906/sag-2108-239Tiwari, Dicks, Popov, Karaseva, Ermakov et al., Probiotics at war against viruses: what is missing from the picture?, Front Microbiol,
doi:10.3389/fmicb.2020.01877Torres, Casado, Vigón, Rodríguez-Mora, Mateos et al., Multidisciplinary group of study of COVID-19 (MGS-COVID); contributing members of the multidisciplinary group of study of COVID-19 (in alphabetical order). Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D, Biomed Pharmacother,
doi:10.1016/j.biopha.2022.112965Tosi, Favari, Bresciani, Flanagan, Hornberger et al., Unravelling phenolic metabotypes in the frame of the COMBAT study, a randomized, controlled trial with cranberry supplementation, Food Res Int,
doi:10.1016/j.foodres.2023.113187Van Brummelen, Van Brummelen, The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19-a formulator's perspective, Biomed Pharmacother,
doi:10.1016/j.biopha.2022.112767Versace, Ortelli, Dezi, Ferrazzoli, Alibardi et al., Coultramicronized palmitoylethanolamide/luteolin normalizes GABA(B)-ergic activity and cortical plasticity in long COVID-19 syndrome, Clin Neurophysiol,
doi:10.1016/j.clinph.2022.10.017Villasis-Keever, López-Alarcón, Miranda-Novales, Zurita-Cruz, Barrada-Vázquez et al., Effect of cholecalciferol supplementation on the clinical features and inflammatory markers in hospitalized COVID-19 patients: a randomized, open-label, Single-Center Study Nutr,
doi:10.3390/nu14132602Watson, Alhaffar, Mehchy, Whittaker, Akil et al., Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections, Arch Dis Child,
doi:10.1136/archdischild-2020-320338Wattanathorn, Tong-Un, Thukham-Mee, Paholpak, Rangseekhajee, A randomized, double-blind, placebo-controlled study of an anthocyanin-rich functional ingredient on cognitive function and eye dryness in late adulthood volunteers: roles of epigenetic and gut microbiome modulations, Nutrients,
doi:10.3390/nu15163499Weisberg, Connors, Zhu, Baldwin, Lin et al., Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum, Nat Immunol,
doi:10.1038/s41590-020-00826-9Wong, Zaw, Xian, Howe, Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomized. Placebo-Controlled Trial, J Bone Miner Res,
doi:10.1002/jbmr.4115Wong, Zhang, Ching, Mak, Huang et al., Effects of gut microbiome modulation on reducing adverse health outcomes among elderly and diabetes patients during the COVID-19 pandemic: a randomised, double-blind, placebo-controlled trial (IMPACT study), Nutrients,
doi:10.3390/nu15081982Worldometer, Population
Wu, Le, Maeda-Minami, Yoshino, Horiba et al., Relationship between conventional medicine chapters in ICD-10 and Kampo pattern diagnosis: a crosssectional study, Front Pharmacol,
doi:10.3389/fphar.2021.751403Xue, Honda, Hibi, Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients, World J Gastroenterol,
doi:10.3748/wjg.v29.i15.2283Yaskolka, Keller, Hoffmann, Rinott, Tsaban et al., The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial, BMC Med,
doi:10.1186/s12916-023-03067-3Yuki, Nojima, Hosono, Tanaka, Kimura et al., Oral MucoRice-CTB vaccine for safety and microbiota-dependent immunogenicity in humans: a phase 1 randomised trial, Lancet Microbe,
doi:10.1016/S2666-5247(20)30196-8Zekeya, Mamiro, Ndossi, Kilonzo, Kisingo et al., Screening and evaluation of cytotoxicity and antiviral effects of secondary metabolites from water extracts of Bersama abyssinica against SARS-CoV-2 Delta, BMC Complement. Med. Ther,
doi:10.1186/s12906-022-03754-3Zhang, Verma, Feng, Melo, Mcquillan et al., Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection, Proc Natl Acad Sci,
doi:10.3390/ijms22168912
