Dietary supplements for the management of COVID-19 symptoms
pdf

Keywords

COVID-19
Dietary supplement
Hydroxytyrosol
Vitamin
SARS-CoV-2

Abstract

SARS-CoV-2, the etiological agent of COVID-19, caused a pandemic in 2020, which is only recently slowing down. The symptoms of COVID-19 range from cough to fever and pneumonia and may persist beyond the active state of the infection, in a condition called post-COVID syndrome. The aim of this paper is to review the relationship between COVID-19 and nutrition and to discuss to most up-to-date dietary supplements proposed for COVID-19 treatment and prevention. Nutrition and nutritional dysregulations, such as obesity and malnutrition, are prominent risk factors for severe COVID-19. These factors exert anti-inflammatory and proinflammatory effects on the immune system, thus exacerbating or reducing the immunological response against the virus. As for the nutritional habits, the Western diet induces a chronic inflammatory state, whereas the Mediterranean diet exerts anti-inflammatory effects and has been proposed for ameliorating COVID-19 evolution and symptoms. Several vaccines have been researched and commercialized for COVID-19 prevention, whereas several drugs, although clinically tested, have not shown promising effects. To compensate for the lack of treatment, several supplements have been recommended for preventing or ameliorating COVID-19 symptoms. Thus, it is critical to review the dietary supplements proposed for COVID-19 treatment. Supplements containing α-cyclodextrin and hydroxytyrosol exhibited promising effects in several clinical trials and reduced the severity of the outcomes and the duration of the infection. Moreover, a supplement containing hydroxytyrosol, acetyl L-carnitine, and vitamins B, C, and D improved the symptoms of patients with post-COVID syndrome.

https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2764
pdf

References

[1] Muthuvattur Pallath M, Ahirwar AK, Chandra Tripathi S, Asia P, Sakarde A, Gopal N. COVID-19 and nutritional deficiency: a review of existing knowledge. Horm Mol Biol Clin Investig 2021;42:77-85. https://doi.org/10.1515/hmbci-2020-0074
[2] HASÖKSÜZ M, KILIÇ S, SARAÇ F. Coronaviruses and SARS-COV-2. Turk J Med Sci 2020;50:549-56. https://doi.org/10.3906/sag-2004-127
[3] Kiani AK, Dhuli K, Anpilogov K, Bressan S, Dautaj A, Dundar M, Beccari T, Ergoren MC, Bertelli M. Natural Compounds as Inhibitors of SARS-CoV-2 Endocytosis: a promising approach against COVID-19. Acta Biomed 2020;91:e2020008. https://doi.org/10.23750/abm.v91i13-S.10520
[4] Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 2020;92:418-23. https://doi/10.1002/jmv.25681
[5] Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG, Siddell SG, Stamou DG, Wilson IA, Kuhn P, Buchmeier MJ. A structural analysis of M protein in Coronavirus assembly and morphology. J Struct Biol 2011;174:11-22. https://doi.org/10.1016/j.jsb.2010.11.021
[6] Satija N, Lal SK. The molecular biology of SARS Coronavirus. Ann N Y Acad Sci 2007;1102:26-38. https://doi.org/10.1196/annals.1408.002
[7] Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J 2019;16:69. https://doi.org/10.1186/s12985-019-1182-0
[8] Ma Q, Liu J, Liu Q, Kang L, Liu R, Jing W, Wu Y, Liu M. Global percentage of asymptomatic SARS-CoV-2 Infections among the tested population and individuals with confirmed COVID-19 diagnosis. JAMA Netw Open 2021;4:e2137257. https://doi.org/10.1001/jamanetworkopen.2021.37257
[9] Bezerra Espinola MS, Bertelli M, Bizzarri M, Unfer V, Laganà AS, Visconti B, Aragona C. Inositol and vitamin D may naturally protect human reproduction and women undergoing assisted reproduction from COVID-19 risk. J Reprod Immunol 2021;144:103271. https://doi.org/10.1016/j.jri.2021.103271
[10] Çalıca Utku A, Budak G, Karabay O, Güçlü E, Okan HD, Vatan A. Main symptoms in patients presenting in the COVID-19 period. Scott Med J 2020;65:127-32. https://doi.org/10.1177/0036933020949253
[11] Kawasuji H, Takegoshi Y, Kaneda M, Ueno A, Miyajima Y, Kawago K, Fukui Y, Yoshida Y, Kimura M, Yamada H, Sakamaki I, Tani H, Morinaga Y, Yamamoto Y. Transmissibility of COVID-19 depends on the viral load around onset in adult and symptomatic patients. PLOS ONE 2020;15:e0243597. https://doi.org/10.1371/journal.pone.0243597
[12] Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, Pan P, Wang W, Hu D, Liu X, Zhang Q, Wu J. Coronavirus infections and immune responses. J Med Virol 2020;92:424-32. https://doi.org/10.1002/jmv.25685
[13] Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and leukocyte changes in mild versus severe SARS‐CoV‐2 infection: Review of 3939 COVID‐19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol 2020;108:17-41. https://doi.org/10.1002/JLB.3COVR0520-272R
[14] McGonagle D, Sharif K, O’Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 2020;19:102537. https://doi.org/10.1016/j. autrev.2020.102537
[15] Silberstein M. COVID-19 and IL-6: why vitamin D (probably) helps but tocilizumab might not.. Eur J Pharmacol 2021;899:174031. https://doi.org/10.1016/j.ejphar.2021.174031
[16] Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: the inflammation link and the role of nutrition in potential mitigation. Nutrients 2020;12:1466. https://doi.org/10.3390/nu12051466
[17] Tao K, Tzou PL, Nouhin J, Bonilla H, Jagannathan P, Shafer RW. SARS-CoV-2 antiviral therapy. Clin Microbiol Rev 2021;34. https://doi.org/10.1128/CMR.00109-21
[18] Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 2018;9. https://doi.org/10.1128/mBio.00221-18
[19] Gordon CJ, Tchesnokov EP, Schinazi RF, Götte M. Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template. J Biol Chem 2021;297:100770. https://doi.org/10.1016/j. jbc.2021.100770
[20] Menéndez CA, Byléhn F, Perez-Lemus GR, Alvarado W, de Pablo JJ. Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease. Sci Adv 2020;6. https://doi.org/10.1126/sciadv.abd0345
[21] Ma C, Sacco MD, Hurst B, Townsend JA, Hu Y, Szeto T, Zhang X, Tarbet B, Marty MT, Chen Y, Wang J. Boceprevir, GC-376, and calpain inhibitors iI, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res 2020;30:678-92. https://doi.org/10.1038/s41422-020-0356-z
[22] Szabó GT, Mahiny AJ, Vlatkovic I. COVID-19 MRNA Vaccines: platforms and current developments. Mol Ther 2022;30:1850-68. https://doi.org/10.1016/j.ymthe.2022.02.016
[23] Rashedi R, Samieefar N, Masoumi N, Mohseni S, Rezaei N. COVID‐19 vaccines mix‐and‐match: the concept, the efficacy and the doubts. J Med Virol 2022;94:1294-9. https://doi.org/10.1002/jmv.27463
[24] Mohamed K, Rzymski P, Islam MS, Makuku R, Mushtaq A, Khan A, Ivanovska M, Makka SA, Hashem F, Marquez L, Cseprekal O, Filgueiras IS, Fonseca DLM, Mickael E, Ling I, Arero AG, Cuschieri S, Minakova K, Rodríguez-Román E, Abarikwu SO, Faten AB, Grancini G, Cabral-Marques O, Rezaei N. COVID‐19 vaccinations: the unknowns, challenges, and hopes. J Med Virol 2022;4:1336-49. https://doi.org/10.1002/jmv.27487
[25] de Faria Coelho-Ravagnani C, Corgosinho FC, Sanches FLFZ, Prado CMM, Laviano A, Mota JF. Dietary recommendations during the COVID-19 pandemic. Nutr Rev 2021;79:382-93. https://doi.org/10.1093/nutrit/nuaa067
[26] Butler MJ, Barrientos RM. The Impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun 2020;87:53-4. https://doi.org/10.1016/j.bbi.2020.04.040
[27] Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr 2005;81:341-54. https://doi.org/10.1093/ajcn.81.2.341
[28] Butler MJ, Barrientos RM. The Impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun 2020;87:53-4. https://doi.org/10.1016/j.bbi.2020.04.040
[29] Dharmasena S, Bessler DA, Capps O. Food environment in the united states as a complex economic system. Food Policy 2016;61:163-75. https://doi.org/10.1016/j.foodpol.2016.03.003
[30] Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients 2020;12. https://doi.org/10.3390/nu12010236
[31] El-Sharkawy AM, Sahota O, Lobo DN. Acute and chronic effects of hydration status on health. Nutr Rev 2015;73 (Suppl 2):97-109. https://doi.org/10.1093/nutrit/nuv038
[32] Casas R, Sacanella E, Estruch R. The Immune protective effect of the mediterranean diet against chronic low-grade inflammatory diseases. Endocr Metab Immune Disord Drug Targets 2014;14:245-54. https://doi.org/10.2174/18715303146 66140922153350
[33] Stefan N, Birkenfeld AL, Schulze MB, Ludwig DS. Obesity and impaired metabolic health in patients with COVID-19. Nat Rev Endocrinol 2020;16:341-2. https://doi.org/10.1038/s41574-020-0364-6
[34] Zhou Y, Chi J, Lv W, Wang Y. Obesity and diabetes as high‐risk factors for severe coronavirus disease 2019 COVID‐19. Diabetes Metab Res Rev 2021;7. https://doi.org/10.1002/dmrr.3377
[35] Jiang Y, Rubin L, Peng T, Liu L, Xing X, Lazarovici P, Zheng W. Cytokine storm in COVID-19: From Viral infection to immune responses, diagnosis and therapy. Int J Biol Sci 2022;18:459-72. https://doi.org/10.7150/ijbs.59272
[36] Popkin BM, Du S, Green WD, Beck MA, Algaith T, Herbst CH, Alsukait RF, Alluhidan M, Alazemi N, Shekar M. Individuals with obesity and COVID‐19: a global perspective on the epidemiology and biological relationships. Obes Rev 2020;2. https://doi.org/10.1111/obr.13128
[37] van der Meij BS, Ligthart-Melis GC, de van der Schueren MAE. Malnutrition in patients with COVID-19: assessment and consequences. Curr Opin Clin Nutr Metab Care 2021;24:543-54. https://doi.org/10.1097/MCO.0000000000000783
[38] Mehta S. Nutritional status and COVID-19: an opportunity for lasting change? Clin Med (Lond) 2020;20:270-3. https://doi.org/10.7861/clinmed.2020-0187
[39] Fedele D, de Francesco A, Riso S, Collo A. Obesity, malnutrition, and trace element deficiency in the coronavirus disease (COVID-19) pandemic: an overview. Nutrition 2021;81:111016. https://doi.org/10.1016/j.nut.2020.111016
[40] Hughes S. Diabetes: support for those at risk of malnutrition in the community. Br J Community Nurs 2012;17:529-34. https://doi.org/10.12968/bjcn.2012.17.11.529
[41] Baglivo M, Baronio M, Natalini G, Beccari T, Chiurazzi P, Fulcheri E, Petralia PP, Michelini S, Fiorentini G, Miggiano GA, Morresi A, Tonini G, Bertelli M. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? Acta Biomed 2020;91:161-4. https://doi.org/10.23750/abm. v91i1.9402
[42] Filippini A, D’Amore A, Palombi F, Carpaneto A. Could the inhibition of endo-lysosomal Two-Pore Channels (TPCs) by the natural flavonoid naringenin represent an option to fight SARS-CoV-2 infection? Front Microbiol 2020;11. https://doi.org/10.3389/fmicb.2020.00970
[43] Shaik FB, Swarnalatha K, Mohan MC, Thomas A, Chikati R, Sandeep G, Maddu N. Novel antiviral effects of chloroquine, hydroxychloroquine, and green tea catechins against SARS CoV-2 Main Protease (Mpro) and 3C-like Protease for COVID-19 treatment. Clin Nutr Open Sci 2022;42:62-72. https://doi.org/10.1016/j.nutos.2021.12.004
[44] Hu B, Huang S, Yin L. The cytokine storm and COVID‐19. J Med Virol 2021;93:250-6. https://doi.org/10.1002/jmv.26232
[45] Paolacci S, Kiani AK, Shree P, Tripathi D, Tripathi YB, Tripathi P, Tartaglia GM, Farronato M, Farronato G, Connelly ST, Ceccarini MR, Coatto M, Ergoren MC, Sanlidag T, Dautaj A, Bertelli M. Scoping review on the role and interactions of hydroxytyrosol and alpha-cyclodextrin in lipid-raft-mediated endocytosis of SARS-CoV-2 and bioinformatic molecular docking studies. Eur Rev Med Pharmacol Sci 2021;25:90-100. https://doi.org/10.26355/eurrev_202112_27338
[46] Naureen Z, Capodicasa N, Paolacci S, Anpilogov K, Dautaj A, Dhuli K, Camilleri G, Connelly ST, Gasparetto A, Bertelli M. Prevention of the proliferation of oral pathogens due to prolonged mask use based on α-cyclodextrin and hydroxytyrosol mouthwash. Eur Rev Med Pharmacol Sci 2021;25:74-80. https://doi.org/10.26355/eurrev_202112_27336
[47] Naureen Z, Dautaj A, Nodari S, Fioretti F, Dhuli K, Anpilogov K, Lorusso L, Paolacci S, Michelini S, Guda T, Kallazi M, Bertelli M. Proposal of a Food supplement for the management of Post-COVID syndrome. Eur Rev Med Pharmacol Sci 2021;25:67-73. https://doi.org/10.26355/eurrev_202112_27335
[48] Moscatelli F, Sessa F, Valenzano A, Polito R, Monda V, Cibelli G, Villano I, Pisanelli D, Perrella M, Daniele A, Monda M, Messina G, Messina A. COVID-19: role of nutrition and supplementation. Nutrients 2021;13:976. https://doi.org/10.3390/nu13030976
[49] Rhodes JM, Subramanian S, Laird E, Kenny RA. Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees north supports vitamin D as a factor determining severity. Aliment Pharmacol Ther 2020;51:1434-7. https://doi.org/10.1111/apt.15777
[50] Paolacci S, Ceccarini MR, Codini M, Manara E, Tezzele S, Percio M, Capodicasa N, Kroni D, Dundar M, Ergoren MC, Sanlidag T, Beccari T, Farronato M, Farronato G, Tartaglia GM, Bertelli M. Pilot Study for the evaluation of safety profile of a potential inhibitor of SARS-CoV-2 endocytosis. Acta Biomed 2020;91:e2020009. https://doi.org/10.23750/abm. v91i13-S.10583
[51] Paolacci S, Ergoren MC, De Forni D, Manara E, Poddesu B, Cugia G, Dhuli K, Camilleri G, Tuncel G, Kaya Suer H, Sultanoglu N, Sayan M, Dundar M, Beccari T, Ceccarini MR, Gunsel IS, Dautaj A, Sanlidag T, Connelly ST, Tartaglia GM, Bertelli M. In vitro and clinical studies on the efficacy of α-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection. Eur Rev Med Pharmacol Sci 2021;25:81-9. https://doi.org/10.26355/eurrev_202112_27337
[52] Ergoren MC, Paolacci S, Manara E, Dautaj A, Dhuli K, Anpilogov K, Camilleri G, Suer HK, Sayan M, Tuncel G, Sultanoglu N, Farronato M, Tartaglia GM, Dundar M, Farronato G, Gunsel IS, Bertelli M, Sanlidag T. A pilot study on the preventative potential of alpha-cyclodextrin and hydroxytyrosol against SARS-CoV-2 transmission. Acta Biomed 2020;91:e2020022. https://doi.org/10.23750/abm.v91i13-S.10817