Rev Med UAS
Vol. 11: No. 4. Octubre-Diciembre 2021
ISSN 2007-8013

Moléculas bioactivas de los alimentos como un aporte hacia una estrategia integral para el manejo de la enfermedad COVID-19 en México.

Bioactive food molecules as a contribution towards a comprehensive strategy for the management of the COVID-19 disease in Mexico.

Dr. Guadalupe I. Olivas-Orozco, M.C. Jesús A. Salas-Tovar, M.C. Alejandro De la Peña-Baca, M.C. Gerardo Pérez-Ordoñez, M.C. Daniel Pérez-Corral, M.C. Francisco Hernández-Centeno, M.C. Cristian Amaro-Hernández, M.C. Saraí Escobedo-García, M.C. Ana L. Ramos-Aguilar, M.C. Aracely Chacón-Flores, M.C. Diana Rentería-Soto, M.C. F. Javier Molina-Corral, Dr. David Sepúlveda

Centro de Investigación en Alimentación y Desarrollo, A.C

*Autor de correspondencia:Guadalupe Isela Olivas Orozco
Centro de Investigación en Alimentación y Desarrollo.
Av. Río Conchos S/N, Parque 8 Industrial, Cd. Cuauhtémoc, Chihuahua, 31570, México.
golivas@ciad.mx ; Teléfono: 625 581 2921 ext 118

DOI http://dx.doi.org/10.28960/revmeduas.2007-8013.v11.n4.009

Texto Completo PDF

Recibido 17 de marzo 2021, aceptado 06 de mayo 2021

RESUMEN
La situación de emergencia sanitaria desatada por la enfermedad COVID-19 en México y en todo el mundo urge a los profesionales de la salud a encontrar estrategias efectivas para mitigar este grave problema. El presente manuscrito explora el potencial uso de bio-moléculas contenidas en los alimentos, como agentes coadyuvantes en la prevención y tratamiento de esta enfermedad. Una extensa revisión bibliográfica concentra la evidencia científica disponible a la fecha respecto al potencial preventivo y terapéutico del consumo de vitaminas C y D, los minerales zinc, magnesio y selenio, así como de otras sustancias nutracéuticas como la melatonina, los ácidos grasos omega-3 y la quercetina. El consumo de hierbas medicinales como el ginseng, el jengibre, y la cúrcuma, así como el consumo de productos apícolas y probióticos es explorado también. El objetivo de este manuscrito es destacar el potencial de estos productos naturales para ser empleados en el combate y prevención de la enfermedad causada por el SARS-CoV-2, haciendo especial énfasis en la situación de salud pública particular de México en lo referente a deficiencias nutrimentales y comorbilidades, las cuales incrementan el riesgo de contagio, complicación de la enfermedad COVID-19, y muerte. La información proporcionada debe ser considerada como sugerencia de complemento a los tratamientos y recomendaciones médicas farmacológicas o de otro tipo. No se propone el consumo de los nutrientes o complementos discutidos como sustituto de apropiada terapia médica.
Palabras clave: SARS-CoV-2, medicina integral, suplementos, vitamina C, vitamina D, zinc

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.
Key words: SARS-CoV-2, integrative medicine, dietary supplements, vitamin C, vitamin D, zinc

REFERENCIAS

  1. WHO. Coronavirus disease (COVID-19) pandemic. World Health Organization; 2021 [cita del 28 de enero de 2021]; Disponible en: 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. Disaster Medicine 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. Characteristics and risk factors for COVID-19 diagnosis and adverse outcomes in Mexico: an analysis of 89,756 laboratory–confirmed COVID-19 cases. Eur Respir J 2020:en prensa.
  5. INEGI. Características de las Defunciones Registradas en México Durante 2017. Comunicado de Prensa No. 525/18. In: Geografía INdEy, editor.2018.
  6. Barquera S, Rivera JA. Obesity in Mexico: rapid epidemiological transition and food industry interference in health policies. The Lancet Diabetes & Endocrinology. 2020; 8:746-7.
  7. Forbes. Mexicanos, de los mayores consumidores de 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 sociodemographic characteristics in Mexican population. Salud Publica Mexico. 2018; 60:272-82.
  9. CONADESUCA. El alto consumo de bebidas azucaradas y comida chatarra aumenta vulnerabilidad frente al COVID-19, señalan expertos. Gobierno de México; 2020 [cita del 29 de enero de 2021]; Disponible en: 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, Assis AMOd, Santos CAdST, Santos DBd. Obesity and vitamin D deficiency: a systematic review and meta‐analysis. Obes Res. 2015; 16:341-9.
  11. McGreevy C, Williams D. New Insights About Vitamin D and Cardiovascular Disease. Ann Intern Med. 2011; 155:820-6.
  12. Moser MA, Chun OK. Vitamin C and Heart Health: A Review Based on Findings from Epidemiologic Studies. Int J Mol Sci. 2016; 17.
  13. Muscogiuri G, Altieri B, Annweiler C, Balercia G, Pal H, Boucher BJ, et al. Vitamin D and chronic diseases: the current state of the art. Arch toxicol. 2017; 91:97-107.
  14. Adefegha SA. Functional Foods and Nutraceuticals as Dietary Intervention in Chronic Diseases; Novel Perspectives for Health Promotion and Disease Prevention. J Diet Sup. 2018; 15:977-1009.
  15. DiNicolantonio JJ, O’Keefe JH, Wilson W. Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart. 2018; 5:e000668.
  16. Dubey P, Thakur V, Chattopadhyay M. Role of Minerals and Trace Elements in Diabetes and Insulin Resistance. Nutrients. 2020; 12.
  17. Bahrami M, Cheraghpour M, Jafarirad S, Alavinejad P, Cheraghian B. The role of melatonin supplement in metabolic syndrome: A randomized double blind clinical trial. Nutr & Food Sci. 2019; 49:965-77.
  18. Natto ZS, Yaghmoor W, Alshaeri HK, Van Dyke TE. Omega-3 Fatty Acids Effects on Inflammatory Biomarkers and Lipid Profiles among Diabetic and Cardiovascular Disease Patients: A Systematic Review and Meta-Analysis. Scientific Reports. 2019; 9:18867.
  19. Strohle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection ascorbic acid and calciferol. Part 1: general overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2011; 10:54-63.
  20. Granger M, Eck P. Chapter Seven - Dietary Vitamin C in Human Health. In: Eskin NAM, editor. Advances in Food and Nutrition Research: Academic Press; 2018. p. 281-310.
  21. Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999; 69:1086-107.
  22. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary 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 properties of guava fruit: comparison with some local fruits. Sunway Acad J. 2006; 3:9-20.
  25. Szeto YT, Tomlinson B, Benzie IF. Total antioxidant and ascorbic acid content of fresh fruits and vegetables: implications for dietary planning and food preservation. Br J Nutr. 2002; 87:55-9.
  26. Pedroza-Tobías A, Hernández-Barrera L, López-Olmedo N, García-Guerra A, Rodríguez-Ramírez S, Ramírez-Silva I, et al. Usual vitamin intakes by Mexican populations. J Nutr. 2016; 146:1866S-73S.
  27. Rowe S, Carr AC. Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern? Nutrients. 2020; 12:2008.
  28. Smirnoff N, Wheeler GL. Ascorbic acid in plants: biosynthesis and function. Crit Rev Plant Sci. 2000; 19:267-90.
  29. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017; 9:1211.
  30. Mousavi S, Bereswill S, Heimesaat MM. Immunomodulatory and antimicrobial effects of vitamin C. Eur J Microbiol Immunol. 2019; 9:73-9.
  31. Carr AC, Rowe S. The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19. Nutrients. 2020; 12.
  32. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane database Syst Rev. 2013; 2:129-130.
  33. Vorilhon P, Arpajou B, Roussel HV, Merlin É, Pereira B, Cabaillot A. Efficacy of vitamin C for the prevention and treatment of upper respiratory tract infection. A meta-analysis in children. Eur J Clin Pharmacol. 2019; 75:303-11.
  34. Marik PE. Hydrocortisone, ascorbic acid and thiamine (HAT therapy) for the treatment of sepsis. Focus on ascorbic acid. Nutrients. 2018; 10:1762.
  35. May JM, Harrison FE. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013; 19:2068-83.
  36. Arvinte C, Singh M, Marik PE. Serum Levels of Vitamin C and Vitamin D in a Cohort of Critically Ill COVID-19 Patients of a North American Community Hospital Intensive Care Unit in May 2020: A Pilot Study. Medicine in drug discovery. 2020; 8:100064.
  37. Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients. 2019; 11:708.
  38. Hemilä H, Chalker E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. J Intensive Care. 2020; 8:15.
  39. Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)? Medicine in Drug Discovery. 2020; 5:100028.
  40. Buehner M, Pamplin J, Studer L, Hughes RL, King BT, Graybill JC, et al. Oxalate nephropathy after continuous infusion of high-dose vitamin C as an adjunct to burn resuscitation. J Burn Care Res. 2016; 37:e374-e9.
  41. de Grooth H-J, Manubulu-Choo W-P, Zandvliet AS, Spoelstra-de Man AM, Girbes AR, Swart EL, et al. Vitamin C pharmacokinetics in critically ill patients: a randomized trial of four IV regimens. Chest. 2018; 153:1368-77.
  42. WHO. Information note on COVID-19 and noncommunicable diseases: World Health Organization 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 coronavirus disease 2019 on admission among Mexican patients. Obesity. 2020; 28:1826-32.
  44. Rösen P, Nawroth P, King G, Möller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO‐MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev. 2001; 17:189-212.
  45. Harding A-H, Wareham NJ, Bingham SA, Khaw K, Luben R, Welch A, et al. Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer–Norfolk prospective study. Arch Intern med. 2008; 168:1493-9.
  46. Odum E, Ejilemele A, Wakwe V. Antioxidant status of type 2 diabetic patients in Port Harcourt, Nigeria. Nigerian Journal of Clinical Practice. 2012; 15.
  47. Al‐Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, et al. Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017.
  48. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007; 126:471.
  49. Kalantar-Zadeh K, Moore LW. Impact of nutrition and diet on COVID-19 infection and implications for kidney health and kidney disease management. J Ren Nutr. 2020; 30:179-81.
  50. Medicine NLo. Clinical Trials. 2021 [updated January 21 2021]; Available from: https://clinicaltrials.gov/.
  51. Carlberg C. Vitamin D. Reference Module in Biomedical Sciences: Elsevier; 2016.
  52. Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012; 95:1357-64.
  53. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr. 2004; 80:1710S-6S.
  54. Bouillon R. Chapter 59 - Vitamin D: From Photosynthesis, Metabolism, and Action to Clinical Applications. In: Jameson JL, De Groot LJ, de Kretser DM, Giudice LC, Grossman AB, Melmed S, et al., editors. Endocrinology: Adult and Pediatric (Seventh Edition). Philadelphia: W.B. Saunders; 2016. p. 1018-37.e7.
  55. Calvo MS, Whiting SJ. Determinants of Vitamin D Intake. In: Holick MF, editor. Vitamin D: Physiology, Molecular Biology, and Clinical Applications. Totowa, NJ: Humana Press; 2010. p. 361-82.
  56. Green TJ, Li W, Whiting SJ. Strategies for Improving Vitamin D Status: Focus on Fortification. In: Burckhardt P, Dawson-Hughes B, Weaver CM, editors. Nutritional Influences on Bone Health: 8th International Symposium. London: Springer London; 2013. p. 247-60.
  57. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014; 144:138-45.
  58. Holick MF. Vitamin D Deficiency. N Engl J Med. 2007; 357:266-81.
  59. Carrillo-Vega MF, García-Peña C, Gutiérrez-Robledo LM, Pérez-Zepeda MU. Vitamin D deficiency in older adults and its associated factors: a cross-sectional analysis of the Mexican Health and Aging Study. Arch Osteoporos. 2017; 12:8.
  60. Flores M, Macias N, Lozada A, Sánchez LM, Díaz E, Barquera S. Serum 25-hydroxyvitamin D levels among Mexican children ages 2 y to 12 y: A national survey. Nutrition. 2013; 29:802-4.
  61. Nagpal S, Na S, Rathnachalam R. Noncalcemic Actions of Vitamin D Receptor Ligands. Endocr Rev. 2005; 26:662-87.
  62. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, et al. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. 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 Immune Function. Nutrients. 2020; 12:1248.
  65. Glinsky GV. Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells. Biomedicines. 2020; 8:129.
  66. Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. 2020; 32:1195-8.
  67. Annweiler C, Cao Z, Sabatier J-M. Point of view: Should COVID-19 patients be supplemented with vitamin D? Maturitas. 2020; 140:24-6.
  68. D'Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, et al. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients. 2020; 12.
  69. Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R. Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166. J. Steroid Biochem Mol Biol. 2020; 202:105719.
  70. Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcalá Díaz JF, López Miranda J, Bouillon R, 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. 2020; 203:105751.
  71. Marik PE, Kory P, Varon J. Does vitamin D status impact mortality from SARS-CoV-2 infection? Medicine in Drug Discovery. 2020; 6:100041.
  72. López de Romaña D, Castillo D C, Diazgranados D. EL ZINC EN LA SALUD HUMANA -1. Rev Chil Nutr. 2010; 37:234-9.
  73. Barbarán E, Vela D. El zinc: un elemento esencial para la vida. Agenda Viva. 2016:14-9.
  74. Pérez AV, Duerto OP, de los Reyes JRP. El zinc, micronutriente importante en la salud humana. Revista Electrónica Dr Zoilo E Marinello Vidaurreta. 2014; 39.
  75. Ramírez-Jaspeado R, Palacios-Rojas N, Funes J, Pérez S, Donnet ML. Identificación de áreas potenciales en México para la intervención con maíz biofortificado con zinc. Rev Fitotec Mex. 2018; 41:327-37.
  76. del Carmen Morales-Ruán M, Villalpando S, García-Guerra A, Shamah-Levy T, Robledo-Pérez R, Ávila-Arcos MA, et al. Iron, zinc, copper and magnesium nutritional status in Mexican children aged 1 to 11 years. Salud Públ Méx. 2012; 54:125-34.
  77. De la Cruz-Góngora V, Gaona B, Villalpando S, Shamah-Levy T, Robledo R. Anemia and iron, zinc, copper and magnesium deficiency 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, Diazgranados D. EL ZINC EN LA SALUD HUMANA - II. Rev Chil Nutr. 2010; 37:240-7.
  79. Rodríguez-Carmona Y, Denova-Gutiérrez E, Sánchez-Uribe E, Muñoz-Aguirre P, Flores M, Salmerón J. Zinc Supplementation and Fortification in Mexican Children. Food Nutr Bull. 2020; 41:89-101.
  80. Aguilar B. Micronutrientes: reguladores del sistema inmunológico y su utilidad en COVID-19. Innovare: Revista CYT. 2020; 9:39-45.
  81. Wessels I, Rolles B, Rink L. The potential impact of zinc supplementation on COVID-19 pathogenesis. Front Immunol. 2020; 11:1712.
  82. Nchioua R, Kmiec D, Müller JA, Conzelmann C, Groß R, Swanson CM, et al. SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the 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 immune functions of micronutrients against Sars-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 in the immunological pathways related to COVID-19 infection. Front Immunol. 2020; 11:1736.
  86. Ishida ST. Zinc (Ⅱ) Immune Virucidal Activities for 2019-nCoV Prevention and COVID-19 Respiratory Ailment and Pneumonia. IJMRHS. 2020; 5:21-33.
  87. Derouiche S. Zinc Supplementation Prevents the Complications of COVID-19 Infection in Cancer Patients. Asian Pacific Journal of Cancer Care. 2020; 5:137-41.
  88. Jiménez Acosta SM. Alimentación y nutrición en edades pediátricas durante la COVID- 19. Rev Cubana Pediatr. 2020; 92.
  89. Pal A, Squitti R, Picozza M, Pawar A, Rongioletti M, Dutta AK, et al. Zinc and COVID-19: Basis of Current Clinical Trials. Biol Trace Elem Res. 2020.
  90. Shakoor H, Feehan J, Al Dhaheri AS, Ali HI, Platat C, Ismail LC, et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas. 2021; 143:1-9.
  91. Rahman MT, Idid SZ. Can Zn Be a Critical Element in COVID-19 Treatment? Biol Trace elem Res. 2020:1-9.
  92. Hernández A, Bustamante, C.; Jiménez Arango, F. Efectos adversos del suministro de altas dosis de zinc en conejos (Oryctolagus cuniculus). Revista CITECSA. 2017; 9:49.
  93. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015; 7.
  94. Tang C-F, Ding H, Jiao R-Q, Wu X-X, Kong L-D. Possibility of magnesium supplementation for supportive treatment in patients with COVID-19. Eur J Pharmacol. 2020:173546.
  95. Wallace TC. Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? Journal of the American College of Nutrition. 2020:1-9.
  96. van Kempen TATG, Deixler E. SARS-CoV-2: influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP) metabolism and on severity of COVID-19. Am J Physiol Endocrinol Metab. 2020; 320:E2-E6.
  97. Hamada AM. Vitamins, omega-3, magnesium, manganese, and thyme can boost our immunity and protect against COVID-19. EurJ Biol Res. 2020; 10:271-95.
  98. Micke O, Vormann J, Kisters K. Magnesium and COVID-19–Some Further Comments–A Commentary on Wallace TC. Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? J Am Coll Nutr. 2020; 1–9. doi: 10.1080/07315724.2020. 1785971. Cited in: PMID: 32649272. J Am Coll Nutr. 2020:1-3.
  99. Tan CW, Ho LP, Kalimuddin S, Cherng BPZ, Teh YE, Thien SY, et al. Cohort study to evaluate effect of vitamin D, magnesium, and vitamin B12 in combination on severe outcome progression in older patients with coronavirus (COVID-19). Nutrition. 2020; 79:111017.
  100. Tarleton EK, Kennedy AG, Rose GL, Littenberg B. Relationship between Magnesium Intake and Chronic Pain in US Adults. Nutrients. 2020; 12:2104.
  101. Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, Ranasinghe P. 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. Magnesium sulfate: a potential adjuvant treatment on COVID-19. Advanced Journal of Emergency Medicine. 2020.
  103. Liu Y, Peterson KE, Sánchez BN, Jones AD, Cantoral A, Mercado-García A, et al. Dietary Intake of Selenium in Relation to Pubertal Development in Mexican Children. Nutrients. 2019; 11:1595.
  104. Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, et al. Selenium deficiency is associated with mortality risk from COVID-19. Nutrients. 2020; 12:2098.
  105. Lange KW, Nakamura Y. Food bioactives, micronutrients, immune function and COVID-19. JFB. 2020; 10.
  106. Zhang J, Saad R, Taylor EW, Rayman MP. Selenium and selenoproteins in viral infection with potential relevance to COVID-19. Redox biology. 2020:101715.
  107. Hiffler L, Rakotoambinina B. Selenium and RNA virus interactions: Potential implications for SARS-CoV-2 infection (COVID-19). Frontiers in Nutrition. 2020; 7:164.
  108. Dharmasena A. Selenium supplementation in thyroid associated ophthalmopathy: an update. Int J Ophthalmol. 2014; 7:365.
  109. Matheus N, Mendoza C, Gutiérrez JEM, Alcalde A. La melatonina, un potente inmunomodulador. Revista del Colegio de Médicos 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 nutrición en la enfermedad por coronavirus 2019 (COVID-19) The role of nutrition in the 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 test the efficacy of melatonin in COVID‐19. J Pineal Res. 2020; 69:e12683.
  113. Cardinali DP. High doses of melatonin as a potential therapeutic tool for the neurologic sequels of covid-19 infection. Melatonin Research. 2020; 3:311-7.
  114. Martín Giménez VM, Prado N, Diez E, Manucha W, Reiter RJ. New proposal involving nanoformulated melatonin targeted to the mitochondria as a potential COVID-19 treatment. Nanomedicine. 2020; 15:2819-21.
  115. Shneider A, Kudriavtsev A, Vakhrusheva A. Can melatonin reduce the severity of COVID-19 pandemic? Int Rev Immunol. 2020:1-10.
  116. Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020; 6:1-18.
  117. Ortega-Peña M, González-Cuevas R. Fármacos de uso frecuente en dermatología como terapia para COVID-19. Actas Dermo-Sifiliográficas. 2020.
  118. Marik PE, Kory P, Varon J, Iglesias J, Meduri GU. MATH+ protocol for the treatment of 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 potential adjuvant treatment. Life Sci. 2020:117583.
  120. Giménez VMM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, et al. Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment. Life Sci. 2020:117808.
  121. Calder PC. 1 - Nutritional benefits of omega-3 fatty acids. In: Jacobsen C, Nielsen NS, Horn AF, Sørensen A-DM, editors. Food Enrichment with Omega-3 Fatty Acids: Woodhead Publishing; 2013. p. 3-26.
  122. Bimbo AP. 2 - Sources of omega-3 fatty acids. In: Jacobsen C, Nielsen NS, Horn AF, Sørensen A-DM, editors. Food Enrichment with Omega-3 Fatty Acids: Woodhead Publishing; 2013. p. 27-107.
  123. Saini RK, Keum Y-S. Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance — A review. Life Sci. 2018; 203:255-67.
  124. Punia S, Sandhu KS, Siroha AK, Dhull SB. Omega 3-metabolism, absorption, bioavailability and health benefits–A review. PharmaNutrition. 2019; 10:100162.
  125. Ramírez-Silva I, Villalpando S, Moreno-Saracho JE, Bernal-Medina D. Fatty acids intake in the Mexican population. Results of the National Nutrition Survey 2006. Nutr Metab. 2011; 8:33.
  126. Rogero MM, Leão MdC, Santana TM, Pimentel MVdMB, Carlini GCG, da Silveira TFF, et al. Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19. Free Radic Biol Med. 2020; 156:190-9.
  127. Arnardottir H, Pawelzik S-C, Öhlund Wistbacka U, Artiach G, Hofmann R, Reinholdsson I, et al. Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated 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, Rioux V, Thibault R. May omega-3 fatty acid dietary supplementation help reduce severe complications in Covid-19 patients? Biochimie. 2020.
  129. Hammock BD, Wang W, Gilligan MM, Panigrahy D. Eicosanoids: The Overlooked Storm in Coronavirus Disease 2019 (COVID-19)? Am J Pathol. 2020; 190:1782-8.
  130. Calder PC. Nutrition, immunity and COVID-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 eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress 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, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: quercetin. Foods. 2020; 9:374.
  133. Andres S, Pevny S, Ziegenhagen R, Bakhiya N, Schäfer B, Hirsch-Ernst KI, et al. Safety Aspects of the Use of Quercetin as a Dietary Supplement. Mol Nutr Food Res. 2018; 62:1700447.
  134. Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol. 2020; 11.
  135. Russo M, Moccia S, Spagnuolo C, Tedesco I, Russo GL. Roles of flavonoids against coronavirus infection. Chem Biol Interact. 2020; 328:109211.
  136. Boots AW, Kubben N, Haenen GRMM, Bast A. Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation. Biochem Biophys Res Commun. 2003; 308:560-5.
  137. Anwar E, Soliman M, Darwish S. Mechanistic Similarity of Immuno-modulatory and Anti-viral Effects of Chloroquine and Quercetin (The Naturally Occurring Flavonoid). Clin Immunol Res. 2020; 4:1-6.
  138. Mirzaie A, Halaji M, Dehkordi FS, Ranjbar R, Noorbazargan H. A narrative literature review on traditional medicine options for treatment of corona virus disease 2019 (COVID-19). Complement Ther Clin Pract. 2020; 40:101214.
  139. Shahrajabian MH, Sun W, Cheng Q. Traditional Herbal Medicine for the Prevention and Treatment of Cold and Flu in the Autumn of 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 of medicinal plants by health professionals in Mexico. J Ethnopharmacol. 2017; 198:81-6.
  141. Taddei-Bringas GA, Santillana-Macedo MA, Romero-Cancio JA, Romero-Téllez MB. Aceptación y uso de herbolaria en medicina familiar. Salud Publ Mex. 1999; 41:216-20.
  142. Esakandari H, Nabi-Afjadi M, Fakkari-Afjadi J, Farahmandian N, Miresmaeili S-M, Bahreini E. A comprehensive review of COVID-19 characteristics. Biol Proced Online. 2020; 22:1-10.
  143. Kang S, Min H. Ginseng, the'immunity boost': the effects of Panax ginseng on immune system. Journal of ginseng research. 2012; 36:354.
  144. Jia L, Zhao Y. Current evaluation of the millennium phytomedicine-ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations. Curr Med Chem. 2009; 16:2475-84.
  145. Christensen LP. Ginsenosides: chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2008. p. 1-99.
  146. Nguyen NH, Nguyen CT. Pharmacological effects of ginseng on infectious diseases. Inflammopharmacology. 2019:1-13.
  147. Wang Y, Jung Y-J, Kim K-H, Kwon Y, Kim Y-J, Zhang Z, et al. Antiviral activity of fermented ginseng extracts against a broad range of influenza viruses. Viruses. 2018; 10:471.
  148. Chikhale RV, Gurav SS, Patil RB, Sinha SK, Prasad SK, Shakya A, et al. Sars-cov-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach. J Biomol Struct Dyn. 2020:1-12.
  149. Li S-r, Tang Z-j, Li Z-h, Liu X. Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-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 and bioactivities of ginger (Zingiber officinale Roscoe). Foods. 2019; 8:185.
  151. Srinivasan K. Ginger rhizomes (Zingiber officinale): A spice with multiple health beneficial 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 human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. 2013; 145:146-51.
  153. Srivastava A, Chaurasia J, Khan R, Dhand C, Verma S. Role of Medicinal plants of Traditional Use in Recuperating Devastating COVID-19 Situation. Med Aromat Plants. 2020; 9:2167-0412.20.
  154. Dei Cas M, Ghidoni R. Dietary curcumin: Correlation between bioavailability and health potential. Nutrients. 2019; 11:2147.
  155. Zahedipour F, Hosseini SA, Sathyapalan T, Majeed M, Jamialahmadi T, Al‐Rasadi K, et al. Potential effects of curcumin in the treatment of COVID‐19 infection. Phytother Res. 2020.
  156. Babaei S, Rahimi S, Torshizi MAK, Tahmasebi G, Miran SNK. Effects of propolis, royal jelly, honey and bee pollen on growth performance and immune system of Japanese quails. Vet Res Forum. 2016; 7:13 - 20.
  157. Šver L, Oršolić N, Tadić Z, Njari B, Valpotic I, Bašic I. A royal jelly as a new potential immunomodulator in rats and mice. Comp Immunol Microbiol Infect Dis. 1996; 19:31-8.
  158. Ariel BP. Propóleo: Un potencial tratamiento para el COVID-19. Scientifica. 2020.
  159. Maruta H, He H. PAK1-blockers: Potential Therapeutics against COVID-19. Med Drug Discov. 2020; 6:100039.
  160. Brown H, Louise, Roberts AEL, Cooper R, Jenkins RE. A review of selected bee products as potential anti-bacterial, anti-fungal, and anti-viral agents. Med Res Arch. 2016; 4.
  161. Heba H. IN Silico Approach of Some Selected Honey Constituents as SARS-CoV-2 Main Protease (COVID-19) Inhibitors. Eurasian J. Med. Oncol. 2020; 4:196-200.
  162. Moataz A. S, Galal Y, Nashwa H. M, Mohamed M. A-D, Yahya AN. In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 target enzymes. ChemRxiv. 2020; 10.
  163. Mustafa MZ, Shamsuddin SH, Sulaiman SA, Abdullah JM. Anti-inflammatory Properties of Stingless Bee Honey May Reduce the Severity of Pulmonary Manifestations in COVID-19 Infections. Malays J Med Sci. 2020; 27:165-9.
  164. Samarghandian S, Farkhondeh T, Samini F. Honey and Health: A Review of Recent Clinical Research. Pharmacognosy Res. 2017; 9:121-7.
  165. Viuda-Martos M, Ruiz-Navajas Y, Fernandez-Lopez J, Perez-Alvarez JA. Functional properties of honey, propolis, and royal jelly. J Food Sci. 2008; 73:R117-24.
  166. Watanabe K, Rahmasari R, Matsunaga A, Haruyama T, Kobayashi N. Anti-influenza viral effects of honey in vitro: potent high activity of manuka honey. Arch Med Res. 2014; 45:359-65.
  167. Yusof A, Ahmad NS, Hamid M.S A, Khong TK. Effects of honey on exercise performance and health components: A systematic review. Sci Sports. 2018; 33:267-81.
  168. Güemes-Ricalde FJ, Villanueva-G R, Eaton KD. Honey production by the Mayans in the Yucatan peninsula. Bee World. 2015; 84:144-54.
  169. de Farias JH, Reis AS, Araujo MA, Araujo MJ, Assuncao AK, de Farias JC, et al. Effects of stingless bee propolis on experimental asthma. Evid Based Complement Alternat Med. 2014; 2014:951478.
  170. El-Aidy WK, Ebeid AA, Sallam Ael R, Muhammad IE, Abbas AT, Kamal MA, et al. Evaluation of propolis, honey, and royal jelly in amelioration of peripheral blood leukocytes and lung inflammation in mouse conalbumin-induced asthma model. Saudi J 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, et al. Mexican Propolis: A Source of Antioxidants and 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, et al. Hypoglycaemic and Antioxidant Effects of Propolis of Chihuahua in a Model of Experimental Diabetes. Evid Based Complement Alternat Med. 2018; 2018:4360356.
  173. Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK. Anti-HIV-1 activity of propolis in CD4(+) lymphocyte and microglial cell cultures. J Ethnopharmacol. 2005; 102:158-63.
  174. Kwon MJ, Shin HM, Perumalsamy H, Wang X, Ahn Y-J. Antiviral effects and possible mechanisms of action of constituents from Brazilian propolis and related compounds. J Apic Res. 2019; 59:413-25.
  175. Nolkemper S, Reichling J, Sensch KH, Schnitzler P. Mechanism of herpes simplex virus type 2 suppression by propolis extracts. 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 exacerbation of respiratory syncytial virus infection in mice exposed to tetrabromobisphenol a, a brominated flame retardant. Evid Based Complement Alternat Med. 2013; 2013:698206.
  177. Berretta AA, Silveira MAD, Condor Capcha JM, De Jong D. Propolis and its potential against SARS-CoV-2 infection mechanisms and COVID-19 disease: Running title: Propolis against SARS-CoV-2 infection and 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 of propolis extracts and selected compounds. Phytother Res. 2010; 24 Suppl 1:S20-8.
  179. Berretta AA, Arruda CT, Miguel FG, NathaliaBaptista, Nascimento AP, Marquele-Oliveira F, et al., editores. Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market. En: Superfood and functional food: an overwiew of their processing and utilization. 2017; 55-98.
  180. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014; 11:506.
  181. Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients. 2017; 9:1021.
  182. Parvez S, Malik KA, Ah Kang S, Kim HY. Probiotics and their fermented food products are beneficial for health. Journal of applied microbiology. 2006; 100:1171-85.
  183. Sanders M, Merenstein D, Merrifield C, Hutkins R. Probiotics for human use. Nutr bull. 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 the Curve of Coronavirus Disease COVID-2019 Pandemic. Front Public Health. 2020; 8.
  186. Pastrian-Soto G. Presencia y Expresión del Receptor ACE2 (Target de SARS-CoV-2) en Tejidos Humanos y Cavidad Oral. Posibles Rutas de Infección en Órganos Orales. Int J Odontostomatol. 2020; 14:501-7.
  187. Anwar F, Altayb HN, Al-Abbasi FA, Al-Malki AL, Kamal MA, Kumar V. Antiviral Effects of Probiotic metabolites on COVID-19. J Biomol Struct Dyn. 2020:1-11.
  188. Senapati S, Dash J, Sethi M, Chakraborty S. Bioengineered probiotics to control SARS-CoV-2 infection. Res Ideas Outcomes. 2020; 6:e54802.
  189. Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab. 2012; 61:160-74.
  190. Olaimat AN, Aolymat I, Al-Holy M, Ayyash M, Ghoush MA, Al-Nabulsi AA, et al. The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19. NPJ Sci Food. 2020; 4:1-7.
  191. Infusino F, Marazzato M, Mancone M, Fedele F, Mastroianni CM, Severino P, et al. Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review. Nutrients. 2020; 12:1718.
  192. Su M, Jia Y, Li Y, Zhou D, Jia J. Probiotics for the prevention of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Respir Care. 2020; 65:673-85.
  193. Olveira G, González-Molero I. Actualización de probióticos, prebióticos y simbióticos en nutrición clínica. Endocrinol Nutr. 2016; 63:482-94.
  194. Kligler B, Cohrssen A. Probiotics. American family physician. 2008; 78:1073-8.
  195. Alschuler L, Weil A, Horwitz R, Stamets P, Chiasson AM, Crocker R, et al. Integrative considerations during the COVID-19 pandemic. Explore (NY). 2020; 16:354-6.
  196. Hardeland R. Melatonin and inflammation—Story of a double-edged blade. J Pineal Res. 2018; 65:e12525.
  197. Hazra S, Chaudhuri AG, Tiwary BK, Chakrabarti N. Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis. Life Sci. 2020; 257:118096.
  198. Romero A, Ramos E, López-Muñoz F, Gil-Martín E, Escames G, Reiter RJ. Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive 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, et al. Antiviral and Immunomodulatory Effects of Phytochemicals from Honey against COVID-19: Potential Mechanisms of Action and Future Directions. Molecules. 2020; 25.
  200. González M, Berdiel, M., Martínez, L. Orthomolecular COVID-19 protocols. TownSend Letter; 2021 [cited 2021 Febrero 18]; Available from: https://www.townsendletter.com/article/orthomolecular-covid-19-protocols/?fbclid=IwAR0vAuv7V-ny5fggd0y1gEdTQ3hJbnMGt0OfMn3QNp0hY7hz_whmmmJKDoU.