Could Dietary Factors Reduce COVID-19 Mortality Rates? Moderating the Inflammatory State
2020; Mary Ann Liebert, Inc.; Volume: 27; Issue: 2 Linguagem: Inglês
10.1089/acm.2020.0441
ISSN1557-7708
Autores Tópico(s)COVID-19 Clinical Research Studies
ResumoThe Journal of Alternative and Complementary MedicineVol. 27, No. 2 Original ArticlesFree AccessCould Dietary Factors Reduce COVID-19 Mortality Rates? Moderating the Inflammatory StateArnold R. EiserArnold R. EiserAddress correspondence to: Arnold R. Eiser, MD, MACP, Center for Public Health Initiatives, 3620 Hamilton Walk, Philadelphia, PA 19104, USA E-mail Address: [email protected]Leonard Davis Institute, Center for Public Health Initiatives, University of Pennsylvania Perelman School of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.Search for more papers by this authorPublished Online:12 Feb 2021https://doi.org/10.1089/acm.2020.0441AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail Introduction: Hypothesizing the Inflammation–Nutrition ConnectionIt has become well known that the severity of illness and lethality in corona virus disease 2019 (COVID-19) infection is strongly associated with exuberant inflammatory cytokine activation.1 Many factors may go into determining one's preinfection inflammatory status including genetic constitution, presence of obesity, air pollution,2 exercise, and even the sauna usage. None is probably more important than the role of nutrition in determining one's inflammatory status.3This hypothesis, based on the evidence presented below, indicates that the baseline inflammatory state of an individual in the absence of disease is significantly influenced by the content of one's diet, specifically whether it contains proinflammatory or anti-inflammatory foodstuffs. Furthermore, the hypothesis suggests that the severity of illness that develops when one contracts COVID-19, that is, whether it be a mild-to-moderate upper respiratory viral illness or a fatal acute respiratory distress syndrome (ARDS) or myocarditis death is dependent on that inflammatory state.I will contrast the Japanese diet and the Mediterranean diet both known for its anti-inflammatory qualities with the Western diet, known for its proinflammatory properties as well as refer to laboratory studies addressing lethal viral infections and COVID-19 risk factors. The Mediterranean diet containing specific polyphenols, lipids, and peptides with anti-inflammatory, antithrombotic, and antioxidant properties has been suggested as offering benefit regarding COVID-19 infectious severity as well through similar mechanisms.4,5EvidenceDiet, inflammation, and risk factors for COVID-19Lethal viral infections such as COVID-19 involve activation of inflammatory cytokines that cause ARDS as well as cardiac injury and acute renal injury.6 Proinflammatory cytokines such as interleukin-6 (IL-6) and interleukin-18 (IL-18) can be reduced significantly in subjects with increased cardiovascular risk through the consumption of a Mediterranean diet as compared with a cardiac prudent diet.7 Researchers have found high levels of inflammatory markers such as the cytokine, (IL-6), and C-reactive protein (CRP) in Americans as compared with Japanese.8 The Japanese diet is rich in phytoestrogens, polyphenols, and flavonoids that reduce inflammation. In a recent study, these authors specifically noted that the consumption of fish, vegetables, and green tea was associated with lower IL-6 levels, a key marker of inflammation.9 The American diet is high in sugars and saturated and trans fats that elevate inflammatory markers.10 The inflammatory markers were higher in African Americans than in white Americans, and may be reflective of eating patterns.11 Similarly, African Americans suffer lethal COVID-19 infections at higher rates than white patients.Obesity appears to be a major factor in the promotion elevated inflammatory cytokine markers.12 These inflammatory markers have been found to correlate with the development of cardiovascular disease and dementia,13 but it has not been previously evaluated regarding pandemic mortality. Similarly, obesity has been recognized as a major risk factor for progressing to critical illness in COVID-19.14 The amount of adipose tissue correlates with the amount of increase in circulating IL-6, an inflammatory cytokine that activates other cytokines.15Elderly individuals are particularly susceptible to lethal outcomes from COVID-19 infection.16 This likely relates to the phenomenon known as inflammaging, the inflammatory state associated with aging as part of immunosecence.17 Oxidative stress and DNA degradation from environmental toxic injury lead to activation of nuclear factor kappa-light-chain-enhancer of activated B (NF-kβ) and IL1-β and stimulation of other cytokines in turn.18Diabetes has been recognized as an important risk factor for critical illness in COVID-19. Type 2 diabetes characterized by insulin resistance is also associated with substantial elevation of the inflammatory markers, CRP and IL-6 as well.19Experimental Studies: Foodstuffs that Reduce Inflammation and Viral InfectionNow consider the experimental evidence that nutrients may reduce inflammation. Anthocyanins such as cyanidin 3-glucoside, a flavonoid founds in many fruits and vegetables, have been found to reduce cytokine activation in human intestinal cells.20 Quite possibly they may do the same for lung tissues.Prevention of COVID-19 fatalities likely requires the means of reducing or eliminating excessive cytokine activation as well as viral suppression. The laboratory studies indicate that if these substances are begun before a potentially lethal virus infection, it helps reduce the percentage of fatalities but not if begun concurrently.Researchers demonstrated that severe acute respiratory syndrome corona virus 1 (SARS Cov 1) and coronavirus 229E viral replication could be suppressed by exogenous administration of arachidonic acid or linoleic acid.21 This finding was consistent with the fact that lipids play a role as viral receptors or cofactors in cell entry. The authors interpreted their findings as indicating that optimal coronaviral replication required specificity of cellular lipid composition and that any perturbation of that composition could impair viral replication. Please note that linoleic acid is also associated with reducing inflammatory cytokines.22 Linoleic acid is generally associated with improved cardiovascular health and is found in vegetable oils such as safflower oil as well as nuts and whole grains.Curcumin, derived from the Indian spice turmeric, reduces several parameters of inflammation in murine virus-induced ARDS.23 Curcumin's effect included reduction in lung collagen deposition, transforming growth factor-β2 receptor expression, cytokine release, inflammatory cell infiltrate, and signaling pathways. Reduction in expression of actin and Tenascin-C, and markers of myofibroblast differentiation were also observed. Of note, administration of curcumin was begun 5 days before inoculation with the virus in this experimental model for it to be effective. Clearly diet appears to have more of a prophylactic effect than a therapeutic effect.The main polyphenol found in green tea, epigallocatechin gallate (EGCG), has been known to exhibit antioxidant, antiallergic, and antiviral properties. Researchers in Wuhan, China, evaluated the efficacy of EGCG at preventing formation of influenza virus-induced reactive oxygen species (ROS) in both cell culture and murine studies. It was found that 20 nmol/L of EGCG could suppress ROS production in canine renal cells.24 Moreover, EGCG suppressed viral replication when added at the time of inoculation but had no efficacy if added 10 h afterward. The in vitro murine study demonstrated reduced virus-induced lung pathology as well as viral loads at dosing of 20 and 40 mg kg−1 d−1 and a mortality reduction from 83% to 33%, a magnitude similar to the antiviral oseltamivir. EGCG has also demonstrated antiviral activity regarding hepatitis C, human immunodeficiency virus, as well as adenoviruses and Epstein Barr virus.25National differences in COVID-19 lethalityIf an anti-inflammatory diet with EGCG (green tea) and curcumin is part of an effective prophylaxis preventing ARDS in COVID-19, then Japan, China, and India would be expected to have lower mortality rates than the United States and Europe because Japan and China lead in the consumption of green tea while India leads in the use of turmeric that contains curcumin, while the consumption of these substances in the United States and Europe is extremely low. India has seen a lower COVID-19 mortality rate (1.5%) despite having a less advanced health care infrastructure.26 Those countries that actually consume a Mediterranean diet such as Greece (1.4%) and the Middle Eastern countries such Jordan (1.1%) and Israel (0.8%) also have a low COVID-19 mortality rate.Japan has experienced a mortality rate of 1.7% despite having a population with a mean age 1.8 years older than Italy's. Moreover, research studies of the Italian diet have previously shown it to be proinflammatory regarding processed meats, sweets, and saturated fats combining to promote advanced glycation end products.27 Detailed population and clinical studies with careful biostatistical analysis are needed to substantiate these preliminary observations.ConclusionsNutritional research neededAs clinical research in COVID-19 develops further, consideration needs to be given to how nutrition impacts the population and how dietary modification may help to suppress the systemic inflammatory reaction. Research in this area needs to proceed in addition to the development of specific antiviral agents and effective vaccines. It may be important to combine cytokine suppression therapy with antiviral therapy. If substances such as curcumin, green tea, and linoleic acid have a suitable safety profile, then they may be used prophylactically in a pandemic. For interventions to be effective, an appropriate diet must start before the inflammatory cascade is initiated.Additional consideration should be given to specific micronutrients essential for optimal immune function such as vitamins D and C and the essential metal selenium and zinc.28Of course, nutritional substances may cause side effects, so monitoring for adverse effects needs consideration as well, but dietary changes generally have less risk than medications. Moreover, they may protect against other illnesses as well. The quantity of specific dietary interventions that may be effective also needs to be determined as most of the above research studies indicated dosage response curves. Clinical studies have been extremely scant in this area for lack of funding because of these substances' ubiquity and the minimal profitability of these products. Diets high in vegetables, nuts, whole grains, and natural polyphenols in the form of green tea, curcumin, and turmeric supplements, and linoleic acid food sources should still be subjected to vigorous clinical studies before they can be considered for clinical recommendation. It is unclear how long before an infection such a diet needs to be implemented for it to improve clinical outcomes, but this could be elucidated by clinical studies.Nutrition research in this area will require federal and foundation grant support to be done because the products involved are not patentable nor very profitable. Cytokine suppression prophylaxis through dietary modification may conceivably be beneficial in reducing lethality in a pandemic such as COVID-19. Dietary changes of the type suggested here toward an anti-inflammatory diet also have additional health benefits, including reduced cardiovascular morbidity and mortality,29 reduced prevalence of dementia, and antidiabetic effects, so the public's health could benefit more broadly than just in the COVID-19 pandemic. Research in this area is urgently needed. Can we afford not to pursue this line of research?Author Disclosure StatementNo competing financial interests to disclose.Funding InformationNo funding was received for this article.References1. Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020;26:1636–1643. Crossref, Medline, Google Scholar2. Hüls A, Krämer U, Herder C, et al. Genetic susceptibility for air pollution-induced airway inflammation in the SALIA study. Environml Res 2017;152:43–50. Crossref, Google Scholar3. Calder PC, Bosco N, Bourdet-Sicard R, et al. Health relevance of the modification of low-grade inflammation in ageing (inflammageing) and the role of nutrition. Age Res Rev 2017;40:95–119. Crossref, Medline, Google Scholar4. 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. Crossref, Google Scholar5. Maiorino MI, Bellastella G, Longo M, et al. Mediterranean diet and COVID-19: Hypothesizing potential benefits in people with diabetes. Front Endo 2020;11:574315. Crossref, Medline, Google Scholar6. Sarzi-Puttini P, Giorgi V, Sirotti S, et al. COVID-19, cytokines and immunosuppression: What can we learn from severe acute respiratory syndrome? Clin Exp Rheum 2020;38:337–342. Medline, Google Scholar7. Esposito K, Ciotola M, Giugliano D. Mediterranean diet, endothelial function and vascular inflammatory markers. Pub Health Nutr 2006;9:1073–1076. Crossref, Medline, Google Scholar8. Coe CL, Love GD, Karasawa M, et al. Population differences in proinflammatory biology: Japanese have healthier profiles than Americans. Brain Behav Immun 2011;25:494–502. Crossref, Medline, Google Scholar9. Coe CL, Miyamoto Y, Love GD, et al. Cultural and life style practices associated with low inflammatory physiology in Japanese adults. Brain Behav Immun 2020;90:385–392. Crossref, Medline, Google Scholar10. Mozaffarian D, Pischon T, Hankinson SE, et al. Dietary intake of trans fatty acids and systemic inflammation in women. Am J Clin Nutr 2004;79:606–612. Crossref, Medline, Google Scholar11. Bovell-Benjamin AC, Dawkin N, Pace RD, et al. Use of focus groups to understand African-Americans' dietary practices: Implications for modifying a food frequency questionnaire. Prevent Med 2009;48:549–554. Crossref, Medline, Google Scholar12. Panagiotakos DB, Pitsavos C, Yannakoulia M, et al. The implication of obesity and central fat on markers of chronic inflammation: The ATTICA study. Atherosclerosis 2005;183:308–315. Crossref, Medline, Google Scholar13. Zuliani G, Guerra G, Ranzini M, et al. High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia. Int J Geriatric Psych 2007;22:305–311. Crossref, Medline, Google Scholar14. Sattar N, McInnes IB, McMurray JJ. Obesity a risk factor for severe COVID-19 infection: Multiple potential mechanisms. Circulation 2020;142:4–6. Crossref, Medline, Google Scholar15. Wisse BE. The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephr 2004;15:2792–2800. Crossref, Medline, Google Scholar16. Mueller AL, McNamara MS, Sinclair DA. Why does COVID-19 disproportionately affect the elderly?. Aging 2020;12:9959–9981. Crossref, Medline, Google Scholar17. Fülöp T, Larbi A, Witkowski JM. Human inflammaging. Gerontology 2019;65:495–504. Crossref, Medline, Google Scholar18. Rea IM, Gibson DS, McGilligan V, et al. Age and age-related diseases: Role of inflammation triggers and cytokines. Front Immunol 2018;9:586. Crossref, Medline, Google Scholar19. Wang X, Bao W, Liu J, et al. Inflammatory markers and risk of type 2 diabetes: A systematic review and meta-analysis. Diabetes Care 2013;36:166–175. Crossref, Medline, Google Scholar20. Serra D, Paixão J, Nunes C, et al. Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human intestinal cells: Comparison with 5-aminosalicylic acid. PLoS One 2013;8:e73001. Crossref, Medline, Google Scholar21. Yan B, Chu H, Yang D, et al. Characterization of the lipidomic profile of coronavirus-infected cells: Implications for lipid metabolism remodeling upon coronavirus replication. Viruses 2019;11:73. Crossref, Google Scholar22. Changhua L, Jindong Y, Defa L, et al. Conjugated linoleic acid attenuates the production and gene expression of proinflammatory cytokines in weaned pigs challenged with lipopolysaccharide. J Nutr 2005;135:239–244. Crossref, Medline, Google Scholar23. Avasarala S, Zhang F, Liu G, et al. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome. PLoS One 2013;8:e57285. Crossref, Medline, Google Scholar24. Ling JX, Wei F, Li N, et al. Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea. Acta Pharmacol Sin 2012;33:1533–1541. Crossref, Medline, Google Scholar25. Steinmann J, Buer J, Pietschmann T, Steinmann E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br J Pharmacol 2013;168:1059–1073. Crossref, Medline, Google Scholar26. Johns Hopkins University Corona Virus Data Center. Online document at: https://coronavirus.jhu.edu/data/mortality, accessed November 10, 2020. Google Scholar27. Centritto F, Iacoviello L, di Giuseppe R,. Dietary patterns, cardiovascular risk factors and C-reactive protein in a healthy Italian population. Nutr Metab Cardiovasc 2009;19:697–706. Crossref, Medline, Google Scholar28. Iddir M, Brito A, Dingeo G, et al. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: Considerations during the COVID-19 crisis. Nutrients 2020;12:1562. Crossref, Medline, Google Scholar29. Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am J Med 2015;128:229–238. 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Eiser.Could Dietary Factors Reduce COVID-19 Mortality Rates? Moderating the Inflammatory State.The Journal of Alternative and Complementary Medicine.Feb 2021.176-178.http://doi.org/10.1089/acm.2020.0441Published in Volume: 27 Issue 2: February 12, 2021Online Ahead of Print:December 10, 2020PDF download
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