Olivas-Orozco GI, Salas-Tovar JA, De la Peña-Baca A, Pérez-Ordoñez G, Pérez-Corral D, Hernández-Centeno F, Amaro-Hernández C, Escobedo-García S, Ramos-Aguilar AL, Chacón-Flores A, Rentería-Soto D, Molina-Corral J, Sepúlveda D

Language: Spanish
References: 200
Page: 351-385
PDF size: 289.50 Kb.

ABSTRACT

The health emergency unleashed by the COVID-19 disease in Mexico and worldwide urges health professionals to find effective strategies to mitigate this serious problem. The present manuscript explores the potential use of bio-molecules contained in food as adjuvant agents in the prevention and treatment of this disease. An extensive bibliographic review was carried out to identify scientific evidence available to date regarding the preventive and therapeutic potential of consuming vitamins C and D, the minerals zinc, magnesium, and selenium, and other nutraceutical substances such as melatonin, omega-3 fatty acids, and quercetin. The use of herbs such as ginseng, ginger, and turmeric, as well as the consumption of bee products and probiotics, is also explored. This manuscript aims to highlight the potential of these natural products to be used in the combat and prevention of the disease caused by SARS-CoV-2, with special emphasis on the particular public health situation in Mexico concerning nutritional deficiencies and comorbidities, which increase the risk of contagion, the complication of the COVID-19 disease, and death. The information provided should be considered as a suggestion to complement the pharmacological or other medical treatments and recommendations. The consumption of the nutrients or supplements discussed is not intended as a substitute for appropriate medical therapy.

REFERENCES

1. WHO. Coronavirus disease (COVID-19)pandemic. World Health Organization; 2021 [cita del 28 de enero de 2021]; Disponibleen: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

2. Ibarra-Nava I, Cardenas-de la Garza JA,Ruiz-Lozano RE, Salazar-Montalvo RG.Mexico and the COVID-19 Response. DisasterMedicine and Public Health Preparedness.2020; 14:e17-e8.

3. WHO. WHO Coronavirus Disease(COVID-19) Dashboard. 2021 [Febrero 1];Disponible en: https://covid19.who.int/.

4. Giannouchos TV, Sussman RA, Mier JM,Poulas K, Farsalinos K. Characteristicsand risk factors for COVID-19 diagnosisand adverse outcomes in Mexico: an analysisof 89,756 laboratory–confirmedCOVID-19 cases. Eur Respir J 2020:enprensa.

5. INEGI. Características de las DefuncionesRegistradas en México Durante 2017. Comunicadode Prensa No. 525/18. In: GeografíaINdEy, editor.2018.

6. Barquera S, Rivera JA. Obesity in Mexico:rapid epidemiological transition and foodindustry interference in health policies.The Lancet Diabetes & Endocrinology.2020; 8:746-7.

7. Forbes. Mexicanos, de los mayores consumidoresde botanas en el mundo. 2018[cita del 29 de enero de 2021].

8. Gaona-Pineda EB, Martínez-Tapia B,Arango-Angarita A, Valenzuela-Bravo D,Gómez-Acosta LM, Shamah-Levy T, et al.Food groups consumption and sociodemographiccharacteristics in Mexican population.Salud Publica Mexico. 2018;60:272-82.

9. CONADESUCA. El alto consumo de bebidasazucaradas y comida chatarra aumentavulnerabilidad frente al COVID-19,señalan expertos. Gobierno de México;2020 [cita del 29 de enero de 2021]; Disponibleen: https://www.gob.mx/conadesuca/prensa/el-alto-consumo-de-bebidas-azucaradas-y-comida-chatarra-aumenta-vulnerabilidad-frente-al-covid-19-senalan-expertos.

10. Pereira􀇦Santos M, Costa PRdF, AssisAMOd, Santos CAdST, Santos DBd. Obesityand vitamin D deficiency: a systematicreview and meta􀇦analysis. Obes Res.2015; 16:341-9.

11. McGreevy C, Williams D. New InsightsAbout Vitamin D and Cardiovascular Disease.Ann Intern Med. 2011; 155:820-6.

12. Moser MA, Chun OK. Vitamin C and HeartHealth: A Review Based on Findings fromEpidemiologic Studies. Int J Mol Sci. 2016;17.

13. Muscogiuri G, Altieri B, Annweiler C, BalerciaG, Pal H, Boucher BJ, et al. VitaminD and chronic diseases: the current stateof the art. Arch toxicol. 2017; 91:97-107.

14. Adefegha SA. Functional Foods andNutraceuticals as Dietary Intervention inChronic Diseases; Novel Perspectives forHealth Promotion and Disease Prevention.J Diet Sup. 2018; 15:977-1009.

15. DiNicolantonio JJ, O’Keefe JH, Wilson W.Subclinical magnesium deficiency: a principaldriver of cardiovascular disease anda public health crisis. Open Heart. 2018;5:e000668.

16. Dubey P, Thakur V, Chattopadhyay M.Role of Minerals and Trace Elements in Diabetesand Insulin Resistance. Nutrients.2020; 12.

17. Bahrami M, Cheraghpour M, Jafarirad S,Alavinejad P, Cheraghian B. The role ofmelatonin supplement in metabolic syndrome:A randomized double blind clinicaltrial. Nutr & Food Sci. 2019; 49:965-77.

18. Natto ZS, Yaghmoor W, Alshaeri HK, VanDyke TE. Omega-3 Fatty Acids Effects onInflammatory Biomarkers and Lipid Profilesamong Diabetic and CardiovascularDisease Patients: A Systematic Reviewand Meta-Analysis. Scientific Reports.2019; 9:18867.

19. Strohle A, Wolters M, Hahn A. Micronutrientsat the interface between inflammationand infection ascorbic acid and calciferol.Part 1: general overview with a focus onascorbic acid. Inflamm Allergy Drug Targets(Formerly Current Drug Targets-Inflammation& Allergy). 2011; 10:54-63.

20. Granger M, Eck P. Chapter Seven - DietaryVitamin C in Human Health. In: EskinNAM, editor. Advances in Food and NutritionResearch: Academic Press; 2018. p.281-310.

21. Carr AC, Frei B. Toward a new recommendeddietary allowance for vitamin Cbased on antioxidant and health effects inhumans. Am J Clin Nutr. 1999; 69:1086-107.

22. Levine M, Conry-Cantilena C, Wang Y,Welch RW, Washko PW, Dhariwal KR, etal. Vitamin C pharmacokinetics in healthyvolunteers: evidence for a recommendeddietary allowance. Proc Natl Acad Sci.1996; 93:3704-9.

23. Simonson W. Vitamin C and Coronavirus.Geriatric Nursing (New York, Ny). 2020.

24. Lim YY, Lim TT, Tee JJ. Antioxidant propertiesof guava fruit: comparison with somelocal fruits. Sunway Acad J. 2006; 3:9-20.

25. Szeto YT, Tomlinson B, Benzie IF. Totalantioxidant and ascorbic acid content offresh fruits and vegetables: implications fordietary planning and food preservation. BrJ Nutr. 2002; 87:55-9.

26. Pedroza-Tobías A, Hernández-Barrera L,López-Olmedo N, García-Guerra A,Rodríguez-Ramírez S, Ramírez-Silva I, etal. Usual vitamin intakes by Mexican populations.J Nutr. 2016; 146:1866S-73S.

27. Rowe S, Carr AC. Global Vitamin C Statusand Prevalence of Deficiency: A Cause forConcern? Nutrients. 2020; 12:2008.

28. Smirnoff N, Wheeler GL. Ascorbic acid inplants: biosynthesis and function. Crit RevPlant Sci. 2000; 19:267-90.

29. Carr AC, Maggini S. Vitamin C and immunefunction. Nutrients. 2017; 9:1211.

30. Mousavi S, Bereswill S, Heimesaat MM.Immunomodulatory and antimicrobial effectsof vitamin C. Eur J Microbiol Immunol.2019; 9:73-9.

31. Carr AC, Rowe S. The Emerging Role ofVitamin C in the Prevention and Treatmentof COVID-19. Nutrients. 2020; 12.

32. Hemilä H, Chalker E. Vitamin C for preventingand treating the common cold.Cochrane database Syst Rev. 2013;2:129-130.

33. Vorilhon P, Arpajou B, Roussel HV, MerlinÉ, Pereira B, Cabaillot A. Efficacy of vitaminC for the prevention and treatment ofupper respiratory tract infection. A metaanalysisin children. Eur J Clin Pharmacol.2019; 75:303-11.

34. Marik PE. Hydrocortisone, ascorbic acidand thiamine (HAT therapy) for the treatmentof sepsis. Focus on ascorbic acid.Nutrients. 2018; 10:1762.

35. May JM, Harrison FE. Role of vitamin C inthe function of the vascular endothelium.Antioxid Redox Signal. 2013; 19:2068-83.

36. Arvinte C, Singh M, Marik PE. Serum Levelsof Vitamin C and Vitamin D in a Cohortof Critically Ill COVID-19 Patients of aNorth American Community Hospital IntensiveCare Unit in May 2020: A PilotStudy. Medicine in drug discovery. 2020;8:100064.

37. Hemilä H, Chalker E. Vitamin C canshorten the length of stay in the ICU: ameta-analysis. Nutrients. 2019; 11:708.

38. Hemilä H, Chalker E. Vitamin C may reducethe duration of mechanical ventilationin critically ill patients: a meta-regressionanalysis. J Intensive Care. 2020; 8:15.

39. Cheng RZ. Can early and high intravenousdose of vitamin C prevent and treat coronavirusdisease 2019 (COVID-19)? Medicinein Drug Discovery. 2020; 5:100028.

40. Buehner M, Pamplin J, Studer L, HughesRL, King BT, Graybill JC, et al. Oxalatenephropathy after continuous infusion ofhigh-dose vitamin C as an adjunct to burnresuscitation. J Burn Care Res. 2016;37:e374-e9.

41. de Grooth H-J, Manubulu-Choo W-P, ZandvlietAS, Spoelstra-de Man AM, GirbesAR, Swart EL, et al. Vitamin C pharmacokineticsin critically ill patients: a randomizedtrial of four IV regimens. Chest. 2018;153:1368-77.

42. WHO. Information note on COVID-19 andnoncommunicable diseases: World HealthOrganization 2020.

43. Denova􀇦Gutiérrez E, Lopez􀇦Gatell H, Alomia􀇦Zegarra JL, López􀇦Ridaura R, Zaragoza􀇦Jimenez CA, Dyer􀇦Leal DD, et al.The association of obesity, type 2 Diabetes,and hypertension with severe coronavirusdisease 2019 on admission amongMexican patients. Obesity. 2020; 28:1826-32.

44. Rösen P, Nawroth P, King G, Möller W,Tritschler HJ, Packer L. The role of oxidativestress in the onset and progression ofdiabetes and its complications: asummaryof a Congress Series sponsoredbyUNESCO􀇦MCBN, the American DiabetesAssociation and the German DiabetesSociety. Diabetes Metab Res Rev. 2001;17:189-212.

45. Harding A-H, Wareham NJ, Bingham SA,Khaw K, Luben R, Welch A, et al. Plasmavitamin C level, fruit and vegetable consumption,and the risk of new-onset type 2diabetes mellitus: the European prospectiveinvestigation of cancer–Norfolk prospectivestudy. Arch Intern med. 2008;168:1493-9.

46. Odum E, Ejilemele A, Wakwe V. Antioxidantstatus of type 2 diabetic patients inPort Harcourt, Nigeria. Nigerian Journal ofClinical Practice. 2012; 15.

47. Al􀇦Khudairy L, Flowers N, Wheelhouse R,Ghannam O, Hartley L, Stranges S, et al.Vitamin C supplementation for the primaryprevention of cardiovascular disease.Cochrane Database Syst Rev. 2017.

48. Afkhami-Ardekani M, Shojaoddiny-ArdekaniA. Effect of vitamin C on blood glucose,serum lipids & serum insulin in type 2 diabetespatients. Indian J Med Res. 2007;126:471.

49. Kalantar-Zadeh K, Moore LW. Impact ofnutrition and diet on COVID-19 infectionand implications for kidney health and kidneydisease management. J Ren Nutr.2020; 30:179-81.

50. Medicine NLo. Clinical Trials. 2021 [updatedJanuary 21 2021]; Available from:https://clinicaltrials.gov/.

51. Carlberg C. Vitamin D. Reference Modulein Biomedical Sciences: Elsevier; 2016.

52. Tripkovic L, Lambert H, Hart K, Smith CP,Bucca G, Penson S, et al. Comparison ofvitamin D2 and vitamin D3 supplementationin raising serum 25-hydroxyvitamin Dstatus: a systematic review and meta-analysis.Am J Clin Nutr. 2012; 95:1357-64.

53. Calvo MS, Whiting SJ, Barton CN. VitaminD fortification in the United States andCanada: current status and data needs.Am J Clin Nutr. 2004; 80:1710S-6S.

54. Bouillon R. Chapter 59 - Vitamin D: FromPhotosynthesis, Metabolism, and Action toClinical Applications. In: Jameson JL, DeGroot LJ, de Kretser DM, Giudice LC,Grossman AB, Melmed S, et al., editors.Endocrinology: Adult and Pediatric (SeventhEdition). Philadelphia: W.B. Saunders;2016. p. 1018-37.e7.

55. Calvo MS, Whiting SJ. Determinants of VitaminD Intake. In: Holick MF, editor. VitaminD: Physiology, Molecular Biology, andClinical Applications. Totowa, NJ: HumanaPress; 2010. p. 361-82.

56. Green TJ, Li W, Whiting SJ. Strategies forImproving Vitamin D Status: Focus on Fortification.In: Burckhardt P, Dawson-Hughes B, Weaver CM, editors. NutritionalInfluences on Bone Health: 8th InternationalSymposium. London: Springer London;2013. p. 247-60.

57. Palacios C, Gonzalez L. Is vitamin D deficiencya major global public health problem?J Steroid Biochem Mol Biol. 2014;144:138-45.

58. Holick MF. Vitamin D Deficiency. N Engl JMed. 2007; 357:266-81.

59. Carrillo-Vega MF, García-Peña C, Gutiérrez-Robledo LM, Pérez-Zepeda MU. VitaminD deficiency in older adults and its associatedfactors: a cross-sectional analysisof the Mexican Health and Aging Study.Arch Osteoporos. 2017; 12:8.

60. Flores M, Macias N, Lozada A, SánchezLM, Díaz E, Barquera S. Serum 25-hydroxyvitaminD levels among Mexican childrenages 2 y to 12 y: A national survey.Nutrition. 2013; 29:802-4.

61. Nagpal S, Na S, Rathnachalam R. NoncalcemicActions of Vitamin D ReceptorLigands. Endocr Rev. 2005; 26:662-87.

62. Bouillon R, Marcocci C, Carmeliet G, BikleD, White JH, Dawson-Hughes B, et al.Skeletal and Extraskeletal Actions of VitaminD: Current Evidence and OutstandingQuestions. Endocr Rev. 2018; 40:1109-51.

63. Aranow C. Vitamin D and the immune system.J Investig Med. 2011; 59:881-6.

64. Martens P-J, Gysemans C, Verstuyf A,Mathieu C. Vitamin D's Effect on ImmuneFunction. Nutrients. 2020; 12:1248.

65. Glinsky GV. Tripartite Combination of CandidatePandemic Mitigation Agents: VitaminD, Quercetin, and Estradiol ManifestProperties of Medicinal Agents for TargetedMitigation of the COVID-19 PandemicDefined by Genomics-Guided Tracingof SARS-CoV-2 Targets in HumanCells. Biomedicines. 2020; 8:129.

66. Ilie PC, Stefanescu S, Smith L. The role ofvitamin D in the prevention of coronavirusdisease 2019 infection and mortality. AgingClin Exp Res. 2020; 32:1195-8.

67. Annweiler C, Cao Z, Sabatier J-M. Point ofview: Should COVID-19 patients be supplementedwith vitamin D? Maturitas.2020; 140:24-6.

68. D'Avolio A, Avataneo V, Manca A, CusatoJ, De Nicolò A, Lucchini R, et al. 25-HydroxyvitaminD Concentrations Are Lowerin Patients with Positive PCR for SARSCoV-2. Nutrients. 2020; 12.

69. Quesada-Gomez JM, Entrenas-Castillo M,Bouillon R. Vitamin D receptor stimulationto reduce acute respiratory distress syndrome(ARDS) in patients with coronavirusSARS-CoV-2 infections: Revised MsSBMB 2020_166. J. Steroid Biochem MolBiol. 2020; 202:105719.

70. Entrenas Castillo M, Entrenas Costa LM,Vaquero Barrios JM, Alcalá Díaz JF,López Miranda J, Bouillon R, et al. “Effectof calcifediol treatment and best availabletherapy versus best available therapy onintensive care unit admission and mortalityamong patients hospitalized for COVID-19: A pilot randomized clinical study”. JSteroid Biochem Mol Biol. 2020;203:105751.

71. Marik PE, Kory P, Varon J. Does vitamin Dstatus impact mortality from SARS-CoV-2infection? Medicine in Drug Discovery.2020; 6:100041.

72. López de Romaña D, Castillo D C, DiazgranadosD. EL ZINC EN LA SALUDHUMANA -1. Rev Chil Nutr. 2010; 37:234-9.

73. Barbarán E, Vela D. El zinc: un elementoesencial para la vida. Agenda Viva.2016:14-9.

74. Pérez AV, Duerto OP, de los Reyes JRP.El zinc, micronutriente importante en lasalud humana. Revista Electrónica DrZoilo E Marinello Vidaurreta. 2014; 39.

75. Ramírez-Jaspeado R, Palacios-Rojas N,Funes J, Pérez S, Donnet ML. Identificaciónde áreas potenciales en Méxicopara la intervención con maíz biofortificadocon zinc. Rev Fitotec Mex. 2018;41:327-37.

76. del Carmen Morales-Ruán M, VillalpandoS, García-Guerra A, Shamah-Levy T,Robledo-Pérez R, Ávila-Arcos MA, et al.Iron, zinc, copper and magnesium nutritionalstatus in Mexican children aged 1 to11 years. Salud Públ Méx. 2012; 54:125-34.

77. De la Cruz-Góngora V, Gaona B, VillalpandoS, Shamah-Levy T, Robledo R.Anemia and iron, zinc, copper and magnesiumdeficiency in Mexican adolescents:National Health and Nutrition Survey 2006.salud pública de méxico. 2012; 54:135-45.

78. López de Romaña D, Castillo D C, DiazgranadosD. EL ZINC EN LA SALUDHUMANA - II. Rev Chil Nutr. 2010; 37:240-7.

79. Rodríguez-Carmona Y, Denova-GutiérrezE, Sánchez-Uribe E, Muñoz-Aguirre P,Flores M, Salmerón J. Zinc Supplementationand Fortification in Mexican Children.Food Nutr Bull. 2020; 41:89-101.

80. Aguilar B. Micronutrientes: reguladores delsistema inmunológico y su utilidad enCOVID-19. Innovare: Revista CYT. 2020;9:39-45.

81. Wessels I, Rolles B, Rink L. The potentialimpact of zinc supplementation on COVID-19 pathogenesis. Front Immunol. 2020;11:1712.

82. Nchioua R, Kmiec D, Müller JA, ConzelmannC, Groß R, Swanson CM, et al.SARS-CoV-2 Is Restricted by Zinc FingerAntiviral Protein despite Preadaptation tothe Low-CpG Environment in Humans.mBio. 2020; 11:e01930-20.

83. Junaid K, Ejaz H, Abdalla AE, Abosalif KO,Ullah MI, Yasmeen H, et al. Effective immunefunctions of micronutrients againstSars-Cov-2. Nutrients. 2020; 12:2992.

84. Skalny AV, Rink L, Ajsuvakova OP,Aschner M, Gritsenko VA, Alekseenko SI,et al. Zinc and respiratory tract infections:Perspectives for COVID􀇦19. Int J Mol Med.2020; 46:17-26.

85. Mayor-Ibarguren A, Robles-Marhuenda Á.A hypothesis for the possible role of zinc inthe immunological pathways related toCOVID-19 infection. Front Immunol. 2020;11:1736.

86. Ishida ST. Zinc (􀏩) Immune Virucidal Activitiesfor 2019-nCoV Prevention andCOVID-19 Respiratory Ailment and Pneumonia.IJMRHS. 2020; 5:21-33.

87. Derouiche S. Zinc Supplementation Preventsthe Complications of COVID-19 Infectionin Cancer Patients. Asian PacificJournal of Cancer Care. 2020; 5:137-41.

88. Jiménez Acosta SM. Alimentación y nutriciónen edades pediátricas durante laCOVID- 19. Rev Cubana Pediatr. 2020;92.

89. Pal A, Squitti R, Picozza M, Pawar A, RongiolettiM, Dutta AK, et al. Zinc and COVID-19: Basis of Current Clinical Trials. BiolTrace Elem Res. 2020.

90. Shakoor H, Feehan J, Al Dhaheri AS, AliHI, Platat C, Ismail LC, et al. Immuneboostingrole of vitamins D, C, E, zinc, seleniumand omega-3 fatty acids: Couldthey help against COVID-19? Maturitas.2021; 143:1-9.

91. Rahman MT, Idid SZ. Can Zn Be a CriticalElement in COVID-19 Treatment? BiolTrace elem Res. 2020:1-9.

92. Hernández A, Bustamante, C.; JiménezArango, F. Efectos adversos del suministrode altas dosis de zinc en conejos(Oryctolagus cuniculus). RevistaCITECSA. 2017; 9:49.

93. Gröber U, Schmidt J, Kisters K. Magnesiumin Prevention and Therapy. Nutrients.2015; 7.

94. Tang C-F, Ding H, Jiao R-Q, Wu X-X,Kong L-D. Possibility of magnesium supplementationfor supportive treatment inpatients with COVID-19. Eur J Pharmacol.2020:173546.

95. Wallace TC. Combating COVID-19 andBuilding Immune Resilience: A PotentialRole for Magnesium Nutrition? Journal ofthe American College of Nutrition. 2020:1-9.

96. van Kempen TATG, Deixler E. SARSCoV-2: influence of phosphate and magnesium,moderated by vitamin D, on energy(ATP) metabolism and on severity ofCOVID-19. Am J Physiol EndocrinolMetab. 2020; 320:E2-E6.

97. Hamada AM. Vitamins, omega-3, magnesium,manganese, and thyme can boostour immunity and protect against COVID-19. EurJ Biol Res. 2020; 10:271-95.

98. Micke O, Vormann J, Kisters K. Magnesiumand COVID-19–Some Further Comments–A Commentary on Wallace TC.Combating COVID-19 and Building ImmuneResilience: A Potential Role forMagnesium Nutrition? J Am Coll Nutr.2020; 1–9. doi: 10.1080/07315724.2020.1785971. Cited in: PMID: 32649272. J AmColl Nutr. 2020:1-3.

99. Tan CW, Ho LP, Kalimuddin S, CherngBPZ, Teh YE, Thien SY, et al. Cohort studyto evaluate effect of vitamin D, magnesium,and vitamin B12 in combination onsevere outcome progression in older patientswith coronavirus (COVID-19). Nutrition.2020; 79:111017.

100. Tarleton EK, Kennedy AG, Rose GL, LittenbergB. Relationship between MagnesiumIntake and Chronic Pain in US Adults.Nutrients. 2020; 12:2104.

101. Jayawardena R, Sooriyaarachchi P,Chourdakis M, Jeewandara C, RanasingheP. Enhancing immunity in viral infections,with special emphasis on COVID-19: A review. Diabetes & Metabolic Syndrome:Clinical Research & Reviews.2020.

102. Pooransari P, Pourdowlat G. Magnesiumsulfate: a potential adjuvant treatment onCOVID-19. Advanced Journal of EmergencyMedicine. 2020.

103. Liu Y, Peterson KE, Sánchez BN, JonesAD, Cantoral A, Mercado-García A, et al.Dietary Intake of Selenium in Relation toPubertal Development in Mexican Children.Nutrients. 2019; 11:1595.

104. Moghaddam A, Heller RA, Sun Q, SeeligJ, Cherkezov A, Seibert L, et al. Seleniumdeficiency is associated with mortality riskfrom COVID-19. Nutrients. 2020; 12:2098.

105. Lange KW, Nakamura Y. Food bioactives,micronutrients, immune function andCOVID-19. JFB. 2020; 10.

106. Zhang J, Saad R, Taylor EW, Rayman MP.Selenium and selenoproteins in viral infectionwith potential relevance to COVID-19.Redox biology. 2020:101715.

107. Hiffler L, Rakotoambinina B. Selenium andRNA virus interactions: Potential implicationsfor SARS-CoV-2 infection (COVID-19). Frontiers in Nutrition. 2020; 7:164.

108. Dharmasena A. Selenium supplementationin thyroid associated ophthalmopathy:an update. Int J Ophthalmol. 2014; 7:365.

109. Matheus N, Mendoza C, Gutiérrez JEM,Alcalde A. La melatonina, un potenteinmunomodulador. Revista del Colegio deMédicos Veterinarios del Estado Lara.2012; 1:10-9.

110. Romo-Romo A, Reyes-Torres CA, Janka-Zires M, Almeda-Valdes P. El rol de la nutriciónen la enfermedad por coronavirus2019 (COVID-19) The role of nutrition inthe coronavirus disease 2019 (COVID-2019). Rev Mex Endocrinol Metab Nutr.2020; 7:132-43.

111. Guerrero JM, Carrillo-Vico A, Lardone PJ.La melatonina. Investigación y Ciencia.2007; 373:30-8.

112. Acuña􀇦Castroviejo D, Escames G,Figueira JC, de la Oliva P, Borobia AM,Acuña􀇦Fernández C. Clinical trial to testthe efficacy of melatonin in COVID􀇦19. JPineal Res. 2020; 69:e12683.

113. Cardinali DP. High doses of melatonin asa potential therapeutic tool for the neurologicsequels of covid-19 infection. MelatoninResearch. 2020; 3:311-7.

114. Martín Giménez VM, Prado N, Diez E, ManuchaW, Reiter RJ. New proposal involvingnanoformulated melatonin targeted tothe mitochondria as a potential COVID-19treatment. Nanomedicine. 2020; 15:2819-21.

115. Shneider A, Kudriavtsev A, VakhrushevaA. Can melatonin reduce the severity ofCOVID-19 pandemic? Int Rev Immunol.2020:1-10.

116. Zhou Y, Hou Y, Shen J, Huang Y, MartinW, Cheng F. Network-based drug repurposingfor novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6:1-18.

117. Ortega-Peña M, González-Cuevas R. Fármacosde uso frecuente en dermatologíacomo terapia para COVID-19. ActasDermo-Sifiliográficas. 2020.

118. Marik PE, Kory P, Varon J, Iglesias J, MeduriGU. MATH+ protocol for the treatmentof SARS-CoV-2 infection: the scientific rationale.Expert Rev Anti Infect Ther.2020:1-7.

119. Zhang R, Wang X, Ni L, Di X, Ma B, Niu S,et al. COVID-19: Melatonin as a potentialadjuvant treatment. Life Sci. 2020:117583.

120. Giménez VMM, Inserra F, Tajer CD, MarianiJ, Ferder L, Reiter RJ, et al. Lungs astarget of COVID-19 infection: Protectivecommon molecular mechanisms of vitaminD and melatonin as a new potential synergistictreatment. Life Sci. 2020:117808.

121. Calder PC. 1 - Nutritional benefits ofomega-3 fatty acids. In: Jacobsen C, NielsenNS, Horn AF, Sørensen A-DM, editors.Food Enrichment with Omega-3 FattyAcids: Woodhead Publishing; 2013. p. 3-26.

122. Bimbo AP. 2 - Sources of omega-3 fattyacids. In: Jacobsen C, Nielsen NS, HornAF, Sørensen A-DM, editors. Food Enrichmentwith Omega-3 Fatty Acids: WoodheadPublishing; 2013. p. 27-107.

123. Saini RK, Keum Y-S. Omega-3 andomega-6 polyunsaturated fatty acids: Dietarysources, metabolism, and significance— A review. Life Sci. 2018; 203:255-67.

124. Punia S, Sandhu KS, Siroha AK, Dhull SB.Omega 3-metabolism, absorption, bioavailabilityand health benefits–A review.PharmaNutrition. 2019; 10:100162.

125. Ramírez-Silva I, Villalpando S, Moreno-Saracho JE, Bernal-Medina D. Fatty acidsintake in the Mexican population. Resultsof the National Nutrition Survey 2006. NutrMetab. 2011; 8:33.

126. Rogero MM, Leão MdC, Santana TM, PimentelMVdMB, Carlini GCG, da SilveiraTFF, et al. Potential benefits and risks ofomega-3 fatty acids supplementation topatients with COVID-19. Free Radic BiolMed. 2020; 156:190-9.

127. Arnardottir H, Pawelzik S-C, Öhlund WistbackaU, Artiach G, Hofmann R, ReinholdssonI, et al. Stimulating the Resolutionof Inflammation Through Omega-3Polyunsaturated Fatty Acids in COVID-19:Rationale for the COVID-Omega-F Trial.Frontiers in Physiology. 2021; 11:1748.

128. Weill P, Plissonneau C, Legrand P, RiouxV, Thibault R. May omega-3 fatty acid dietarysupplementation help reduce severecomplications in Covid-19 patients? Biochimie.2020.

129. Hammock BD, Wang W, Gilligan MM,Panigrahy D. Eicosanoids: The OverlookedStorm in Coronavirus Disease2019 (COVID-19)? Am J Pathol. 2020;190:1782-8.

130. Calder PC. Nutrition, immunity andCOVID-19. BMJ Nutrition, Prevention &Health. 2020; 3:79.

131. Gadek JE, DeMichele SJ, Karlstad MD,Pacht ER, Donahoe M, Albertson TE, et al.Effect of enteral feeding with eicosapentaenoicacid, gamma-linolenic acid, andantioxidants in patients with acute respiratorydistress syndrome. Crit Care Med.1999; 27.

132. Batiha GE-S, Beshbishy AM, Mulla ZS,Ikram M, El-Hack MEA, Taha AE, et al.The pharmacological activity, biochemicalproperties, and pharmacokinetics of themajor natural polyphenolic flavonoid: quercetin.Foods. 2020; 9:374.

133. Andres S, Pevny S, Ziegenhagen R,Bakhiya N, Schäfer B, Hirsch-Ernst KI, etal. Safety Aspects of the Use of Quercetinas a Dietary Supplement. Mol Nutr FoodRes. 2018; 62:1700447.

134. Colunga Biancatelli RML, Berrill M, CatravasJD, Marik PE. Quercetin and VitaminC: An Experimental, Synergistic Therapyfor the Prevention and Treatment ofSARS-CoV-2 Related Disease (COVID-19). Front Immunol. 2020; 11.

135. Russo M, Moccia S, Spagnuolo C,Tedesco I, Russo GL. Roles of flavonoidsagainst coronavirus infection. Chem BiolInteract. 2020; 328:109211.

136. Boots AW, Kubben N, Haenen GRMM,Bast A. Oxidized quercetin reacts with thiolsrather than with ascorbate: implicationfor quercetin supplementation. BiochemBiophys Res Commun. 2003; 308:560-5.

137. Anwar E, Soliman M, Darwish S. MechanisticSimilarity of Immuno-modulatory andAnti-viral Effects of Chloroquine and Quercetin(The Naturally Occurring Flavonoid).Clin Immunol Res. 2020; 4:1-6.

138. Mirzaie A, Halaji M, Dehkordi FS, RanjbarR, Noorbazargan H. A narrative literaturereview on traditional medicine options fortreatment of corona virus disease 2019(COVID-19). Complement Ther Clin Pract.2020; 40:101214.

139. Shahrajabian MH, Sun W, Cheng Q. TraditionalHerbal Medicine for the Preventionand Treatment of Cold and Flu in the Autumnof 2020, Overlapped With COVID-19. Nat Prod Commun. 2020;15:1934578X20951431.

140. Alonso-Castro AJ, Domínguez F, Maldonado-Miranda JJ, Castillo-Pérez LJ, Carranza-Álvarez C, Solano E, et al. Use ofmedicinal plants by health professionals inMexico. J Ethnopharmacol. 2017; 198:81-6.

141. Taddei-Bringas GA, Santillana-MacedoMA, Romero-Cancio JA, Romero-TéllezMB. Aceptación y uso de herbolaria enmedicina familiar. Salud Publ Mex. 1999;41:216-20.

142. Esakandari H, Nabi-Afjadi M, Fakkari-Afjadi J, Farahmandian N, Miresmaeili SM,Bahreini E. A comprehensive review ofCOVID-19 characteristics. Biol ProcedOnline. 2020; 22:1-10.

143. Kang S, Min H. Ginseng, the'immunityboost': the effects of Panax ginseng on immunesystem. Journal of ginseng research.2012; 36:354.

144. Jia L, Zhao Y. Current evaluation of themillennium phytomedicine-ginseng (I): etymology,pharmacognosy, phytochemistry,market and regulations. Curr Med Chem.2009; 16:2475-84.

145. Christensen LP. Ginsenosides: chemistry,biosynthesis, analysis, and potentialhealth effects. Adv Food Nutr Res. 2008.p. 1-99.

146. Nguyen NH, Nguyen CT. Pharmacologicaleffects of ginseng on infectious diseases.Inflammopharmacology. 2019:1-13.

147. Wang Y, Jung Y-J, Kim K-H, Kwon Y, KimY-J, Zhang Z, et al. Antiviral activity of fermentedginseng extracts against a broadrange of influenza viruses. Viruses. 2018;10:471.

148. Chikhale RV, Gurav SS, Patil RB, SinhaSK, Prasad SK, Shakya A, et al. Sars-cov-2 host entry and replication inhibitors fromIndian ginseng: an in-silico approach. J BiomolStruct Dyn. 2020:1-12.

149. Li S-r, Tang Z-j, Li Z-h, Liu X. Searchingtherapeutic strategy of new coronaviruspneumonia from angiotensin-convertingenzyme 2: the target of COVID-19 andSARS-CoV. Eur J Clin Microbiol Infect Dis.2020; 39:1021.

150. Mao Q-Q, Xu X-Y, Cao S-Y, Gan R-Y,Corke H, Li H-B. Bioactive compounds andbioactivities of ginger (Zingiber officinaleRoscoe). Foods. 2019; 8:185.

151. Srinivasan K. Ginger rhizomes (Zingiberofficinale): A spice with multiple healthbeneficial potentials. PharmaNutrition.2017; 5:18-28.

152. Chang JS, Wang KC, Yeh CF, Shieh DE,Chiang LC. Fresh ginger (Zingiber officinale)has anti-viral activity against humanrespiratory syncytial virus in human respiratorytract cell lines. J Ethnopharmacol.2013; 145:146-51.

153. Srivastava A, Chaurasia J, Khan R, DhandC, Verma S. Role of Medicinal plants ofTraditional Use in Recuperating DevastatingCOVID-19 Situation. Med AromatPlants. 2020; 9:2167-0412.20.

154. Dei Cas M, Ghidoni R. Dietary curcumin:Correlation between bioavailability andhealth potential. Nutrients. 2019; 11:2147.

155. Zahedipour F, Hosseini SA, SathyapalanT, Majeed M, Jamialahmadi T, Al􀇦RasadiK, et al. Potential effects of curcumin in thetreatment of COVID􀇦19 infection. PhytotherRes. 2020.

156. Babaei S, Rahimi S, Torshizi MAK, TahmasebiG, Miran SNK. Effects of propolis,royal jelly, honey and bee pollen on growthperformance and immune system of Japanesequails. Vet Res Forum. 2016; 7:13 -20.

157. Šver L, Oršolić N, Tadić Z, Njari B, ValpoticI, Bašic I. A royal jelly as a new potentialimmunomodulator in rats and mice. CompImmunol Microbiol Infect Dis. 1996; 19:31-8.

158. Ariel BP. Propóleo: Un potencial tratamientopara el COVID-19. Scientifica.2020.

159. Maruta H, He H. PAK1-blockers: PotentialTherapeutics against COVID-19. MedDrug Discov. 2020; 6:100039.

160. Brown H, Louise, Roberts AEL, Cooper R,Jenkins RE. A review of selected bee productsas potential anti-bacterial, anti-fungal,and anti-viral agents. Med Res Arch. 2016;4.

161. Heba H. IN Silico Approach of Some SelectedHoney Constituents as SARS-CoV2 Main Protease (COVID-19) Inhibitors.Eurasian J. Med. Oncol. 2020; 4:196-200.

162. Moataz A. S, Galal Y, Nashwa H. M, MohamedM. A-D, Yahya AN. In SilicoScreening of Potent Bioactive Compoundsfrom Honey Bee Products Against COVID-19 target enzymes. ChemRxiv. 2020; 10.

163. Mustafa MZ, Shamsuddin SH, SulaimanSA, Abdullah JM. Anti-inflammatory Propertiesof Stingless Bee Honey May Reducethe Severity of Pulmonary Manifestationsin COVID-19 Infections. Malays J Med Sci.2020; 27:165-9.

164. Samarghandian S, Farkhondeh T, SaminiF. Honey and Health: A Review of RecentClinical Research. Pharmacognosy Res.2017; 9:121-7.

165. Viuda-Martos M, Ruiz-Navajas Y, Fernandez-Lopez J, Perez-Alvarez JA. Functionalproperties of honey, propolis, and royaljelly. J Food Sci. 2008; 73:R117-24.

166. Watanabe K, Rahmasari R, Matsunaga A,Haruyama T, Kobayashi N. Anti-influenzaviral effects of honey in vitro: potent highactivity of manuka honey. Arch Med Res.2014; 45:359-65.

167. Yusof A, Ahmad NS, Hamid M.S A, KhongTK. Effects of honey on exercise performanceand health components: A systematicreview. Sci Sports. 2018; 33:267-81.

168. Güemes-Ricalde FJ, Villanueva-G R,Eaton KD. Honey production by the Mayansin the Yucatan peninsula. Bee World.2015; 84:144-54.

169. de Farias JH, Reis AS, Araujo MA, AraujoMJ, Assuncao AK, de Farias JC, et al. Effectsof stingless bee propolis on experimentalasthma. Evid Based ComplementAlternat Med. 2014; 2014:951478.

170. El-Aidy WK, Ebeid AA, Sallam Ael R, MuhammadIE, Abbas AT, Kamal MA, et al.Evaluation of propolis, honey, and royaljelly in amelioration of peripheral blood leukocytesand lung inflammation in mouseconalbumin-induced asthma model. SaudiJ Biol Sci. 2015; 22:780-8.

171. Guzman-Gutierrez SL, Nieto-Camacho A,Castillo-Arellano JI, Huerta-Salazar E,Hernandez-Pasteur G, Silva-Miranda M, etal. Mexican Propolis: A Source of Antioxidantsand Anti-Inflammatory Compounds,and Isolation of a Novel Chalcone and epsilon-Caprolactone Derivative. Molecules.2018; 23.

172. Rivera-Yanez N, Rodriguez-Canales M,Nieto-Yanez O, Jimenez-Estrada M, Ibarra-Barajas M, Canales-Martinez MM, etal. Hypoglycaemic and Antioxidant Effectsof Propolis of Chihuahua in a Model of ExperimentalDiabetes. Evid Based ComplementAlternat Med. 2018; 2018:4360356.

173. Gekker G, Hu S, Spivak M, LokensgardJR, Peterson PK. Anti-HIV-1 activity ofpropolis in CD4(+) lymphocyte and microglialcell cultures. J Ethnopharmacol.2005; 102:158-63.

174. Kwon MJ, Shin HM, Perumalsamy H,Wang X, Ahn Y-J. Antiviral effects andpossible mechanisms of action of constituentsfrom Brazilian propolis and relatedcompounds. J Apic Res. 2019; 59:413-25.

175. Nolkemper S, Reichling J, Sensch KH,Schnitzler P. Mechanism of herpes simplexvirus type 2 suppression by propolisextracts. Phytomedicine. 2010; 17:132-8.

176. Takeshita T, Watanabe W, Toyama S,Hayashi Y, Honda S, Sakamoto S, et al.Effect of brazilian propolis on exacerbationof respiratory syncytial virus infection inmice exposed to tetrabromobisphenol a, abrominated flame retardant. Evid BasedComplement Alternat Med. 2013;2013:698206.

177. Berretta AA, Silveira MAD, Condor CapchaJM, De Jong D. Propolis and its potentialagainst SARS-CoV-2 infection mechanismsand COVID-19 disease: Running title:Propolis against SARS-CoV-2 infectionand COVID-19. Biomed Pharmacother.2020; 131:110622.

178. Schnitzler P, Neuner A, Nolkemper S,Zundel C, Nowack H, Sensch KH, et al.Antiviral activity and mode of action ofpropolis extracts and selected compounds.Phytother Res. 2010; 24 Suppl1:S20-8.

179. Berretta AA, Arruda CT, Miguel FG,NathaliaBaptista, Nascimento AP,Marquele-Oliveira F, et al., editores. FunctionalProperties of Brazilian Propolis:From Chemical Composition Until the Market.En: Superfood and functional food: anoverwiew of their processing and utilization.2017; 55-98.

180. Hill C, Guarner F, Reid G, Gibson GR, MerensteinDJ, Pot B, et al. Expert consensusdocument: The International Scientific Associationfor Probiotics and Prebiotics consensusstatement on the scope and appropriateuse of the term probiotic. Nat RevGastroenterol Hepatol. 2014; 11:506.

181. Markowiak P, Śliżewska K. Effects of probiotics,prebiotics, and synbiotics on humanhealth. Nutrients. 2017; 9:1021.

182. Parvez S, Malik KA, Ah Kang S, Kim HY.Probiotics and their fermented food productsare beneficial for health. Journal ofapplied microbiology. 2006; 100:1171-85.

183. Sanders M, Merenstein D, Merrifield C,Hutkins R. Probiotics for human use. Nutrbull. 2018; 43:212-25.

184. Al Kassaa I. New insights on antiviral probiotics:from research to applications:Springer; 2016.

185. Baud D, Agri VD, Gibson GR, Reid G,Giannoni E. Using Probiotics to Flatten theCurve of Coronavirus Disease COVID-2019 Pandemic. Front Public Health.2020; 8.

186. Pastrian-Soto G. Presencia y Expresióndel Receptor ACE2 (Target de SARSCoV-2) en Tejidos Humanos y CavidadOral. Posibles Rutas de Infección en ÓrganosOrales. Int J Odontostomatol. 2020;14:501-7.

187. Anwar F, Altayb HN, Al-Abbasi FA, Al-Malki AL, Kamal MA, Kumar V. Antiviral Effectsof Probiotic metabolites on COVID-19. J Biomol Struct Dyn. 2020:1-11.

188. Senapati S, Dash J, Sethi M, ChakrabortyS. Bioengineered probiotics to controlSARS-CoV-2 infection. Res Ideas Outcomes.2020; 6:e54802.

189. Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probioticmechanisms of action. Ann NutrMetab. 2012; 61:160-74.

190. Olaimat AN, Aolymat I, Al-Holy M, AyyashM, Ghoush MA, Al-Nabulsi AA, et al. Thepotential application of probiotics andprebiotics for the prevention and treatmentof COVID-19. NPJ Sci Food. 2020; 4:1-7.

191. Infusino F, Marazzato M, Mancone M,Fedele F, Mastroianni CM, Severino P, etal. Diet Supplementation, Probiotics, andNutraceuticals in SARS-CoV-2 Infection: AScoping Review. Nutrients. 2020;12:1718.

192. Su M, Jia Y, Li Y, Zhou D, Jia J. Probioticsfor the prevention of ventilator-associatedpneumonia: a meta-analysis of randomizedcontrolled trials. Respir Care. 2020;65:673-85.

193. Olveira G, González-Molero I. Actualizaciónde probióticos, prebióticos y simbióticosen nutrición clínica. Endocrinol Nutr.2016; 63:482-94.

194. Kligler B, Cohrssen A. Probiotics. Americanfamily physician. 2008; 78:1073-8.

195. Alschuler L, Weil A, Horwitz R, Stamets P,Chiasson AM, Crocker R, et al. Integrativeconsiderations during the COVID-19 pandemic.Explore (NY). 2020; 16:354-6.

196. Hardeland R. Melatonin and inflammation—Story of a double-edged blade. JPineal Res. 2018; 65:e12525.

197. Hazra S, Chaudhuri AG, Tiwary BK,Chakrabarti N. Matrix metallopeptidase 9as a host protein target of chloroquine andmelatonin for immunoregulation in COVID-19: A network-based meta-analysis. LifeSci. 2020; 257:118096.

198. Romero A, Ramos E, López-Muñoz F, Gil-Martín E, Escames G, Reiter RJ. CoronavirusDisease 2019 (COVID-19) and ItsNeuroinvasive Capacity: Is It Time for Melatonin?Cell Mol Neurobiol. 2020; 1-12.

199. Al-Hatamleh MAI, Hatmal MmM, Sattar K,Ahmad S, Mustafa MZ, Bittencourt MD, etal. Antiviral and Immunomodulatory Effectsof Phytochemicals from Honeyagainst COVID-19: Potential Mechanismsof Action and Future Directions. Molecules.2020; 25.

200. González M, Berdiel, M., Martínez, L. OrthomolecularCOVID-19 protocols. Town-Send Letter; 2021 [cited 2021 Febrero 18];Available from: https://www.townsendletter.com/article/orthomolecular-covid-19-protocols/?fbclid=IwAR0vAuv7Vny5fggd0y1gEdTQ3hJbnMGt0OfMn3QNp0hY7hz_whmmmJKDoU.