Negative Association Between Mediterranean Diet Adherence and COVID-19 Cases and Related Deaths in Spain and 23 OECD Countries: An Ecological Study
Michael W Greene, Alexis P Roberts, Andrew D Frugé
Frontiers in Nutrition, doi:10.3389/fnut.2021.591964
In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) emerged in Wuhan, China, sparking the Coronavirus disease 2019 (COVID-19) pandemic. The high prevalence of nutrition-related COVID-19 risk factors including obesity, type 2 diabetes, and hypertension, suggests that healthy dietary approaches may mitigate COVID-19 related outcomes and possibly SARS-CoV-2 infection. Based on the fundamental role of nutrition in immune function and the well-documented association between Mediterranean diet consumption and risk reduction for chronic diseases that are comorbidities in COVID-19 patients, we hypothesized that there would be a relationship between Mediterranean diet adherence and COVID-19 cases and related deaths. In this perspective, we examined the association between regional adherence to a Mediterranean diet and COVID-19 cases and deaths using an ecological study design. We observed that Mediterranean diet adherence was negatively associated with both COVID-19 cases and related deaths across 17 regions in Spain and that the relationship remained when adjusted for factors of well-being. We also observed a negative association between Mediterranean diet adherence and COVID-19 related deaths across 23 countries when adjusted for factors of well-being and physical inactivity. The anti-inflammatory properties of the Mediterranean diet -likely due to the polyphenol content of the diet -may be a biological basis to explain our findings. However, there are confounding factors unrelated to dietary factors driving COVID-19 cases and related deaths across the regions in Spain and the 23 countries examined in our analysis. Our findings will need to be confirmed and further explored in cohort studies.
AUTHOR CONTRIBUTIONS MG conceived of the work, performed data and statistical analysis, contributed to the writing, and offered critical comments. AR performed data analysis, wrote the first draft of the manuscript, and provided critical revisions to the content. AF provided critical revisions to the content. All authors contributed to the article and approved the submitted version.
Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Abarca-Gómez, Abdeen, Hamid, Abu-Rmeileh, Acosta-Cazares et al., Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128• 9 million children, adolescents, and adults, Lancet,
doi:10.1016/S0140-6736(17)32129-3Bach-Faig, Fuentes-Bol, Ramos, Carrasco, Roman et al., The Mediterranean diet in spain: adherence trends during the past two decades using the mediterranean adequacy index, Public Health Nutr,
doi:10.1017/S1368980010002752Bonaccio, Pounis, Cerletti, Donati, Iacoviello et al., Mediterranean diet, dietary polyphenols and low grade inflammation: results from the moli-sani study, Br J Clin Pharmacol,
doi:10.1111/bcp.12924Brownstein, Pena, Mandl, Characterizing socioeconomic disparities in the burden of influenza and RSV using surveillance data, Adv Dis Surveill
Cavaliere, Marchi, Banterle, Exploring the adherence to the Mediterranean diet and its relationship with individual lifestyle: the role of healthy behaviors, pro-environmental behaviors, income, and education, Nutrients,
doi:10.3390/nu10020141Cavicchia, Steck, Hurley, Hussey, Ma et al., A new dietary inflammatory index predicts interval changes in serum high-sensitivity c-reactive protein, J Nutr,
doi:10.3945/jn.109.114025Chandrasekhar, Sloan, Mitchel, Ndi, Thomas, Social determinants of influenza hospitalization in the United States, Influenza Other Respir Viruses,
doi:10.1111/irv.12483Chen, Chen, Wang, Qin, Bai, Dietary fiber and metabolic syndrome: a meta-analysis and review of related mechanisms, Nutrients,
doi:10.3390/nu10010024Chrysohoou, Panagiotakos, Pitsavos, Das, Stefanadis, Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA study, J Am Coll Cardiol,
doi:10.1016/j.jacc.2004.03.039Cordoba, Aiello, Social determinants of influenza illness and outbreaks in the United States, North Carolina Med J,
doi:10.18043/ncm.77.5.341De Lucena, Da, Santos, De Lima Fabrício, De et al., Mechanism of inflammatory response in associated comorbidities in COVID-19, Diabetes Metab Syndr Clin Res Rev,
doi:10.1016/j.dsx.2020.05.025Degiuli, Caring for a Living: Migrant Women, Aging Citizens, and Italian Families
Eichelmann, Schwingshackl, Fedirko, Aleksandrova, Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials, Obes Rev,
doi:10.1111/obr.12439Estruch, Salas-Salvadó, Covas, Arós, Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts, New Eng J Med,
doi:10.1056/NEJMoa1800389Farhadi, Ovchinnikov, The relationship between nutrition and infectious diseases: a review, Biomed Biotechnol Res J,
doi:10.4103/bbrj.bbrj_69_18Finicelli, Squillaro, Cristo, Salle, Melone et al., Metabolic syndrome, Mediterranean diet, and polyphenols: evidence and perspectives, J Cell Physiol,
doi:10.1002/jcp.27506Fung, Mccullough, Newby, Manson, Meigs et al., Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction, Am J Clin Nutr,
doi:10.1093/ajcn/82.1.163Goel, Jain, Hooda, Malhotra, Johal et al., Clinical characteristics and in-hospital mortality for COVID-19 across the globe, Cardiol Therapy,
doi:10.1007/s40119-020-00189-0Gombart, Pierre, Maggini, A review of micronutrients and the immune System-Working in harmony to reduce the risk of infection, Nutrients,
doi:10.3390/nu12010236González-Candelas, Astray, Alonso, Castro, Cantón et al., Sociodemographic Factors and Clinical Conditions Associated to Hospitalization in Influenza A (H1N1) 2009 Virus Infected Patients in Spain, 2009-2010, PLoS ONE,
doi:10.1371/journal.pone.0033139González-Gallego, García-Mediavilla, Sánchez-Campos, Tuñón, Fruit polyphenols, immunity and inflammation, Br J Nutr,
doi:10.1017/S0007114510003910Guh, Zhang, Bansback, Amarsi, Birmingham et al., The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis, BMC public health,
doi:10.1186/1471-2458-9-88Khosrawipour, Lau, Khosrawipour, Kocbach, Ichii et al., Failure in initial stage containment of global COVID-19 epicenters, J Med Virol,
doi:10.1002/jmv.25883Knight, Jackson, Rahman, Burnett, Frugé et al., The Mediterranean diet in the Stroke Belt: a cross-sectional study on adherence and perceived knowledge, barriers, and benefits, Nutrients,
doi:10.3390/nu11081847Koivumaa-Honkanen, Honkanen, Viinamäki, Heikkilä, Kaprio et al., Self-reported life satisfaction and 20-year mortality in healthy finnish adults, Am J Epidemiol,
doi:10.1093/aje/152.10.983Legido-Quigley, García, Campos, Gea-Sánchez, Muntaner et al., The resilience of the Spanish health system against the COVID-19 pandemic, lancet Public Health,
doi:10.1016/S2468-2667(20)30060-8Levy, Nguyen, Westheimer, Layton, Disparities in the severity of influenza illness: a descriptive study of hospitalized and nonhospitalized novel H1N1 influenza-positive patients in New York City 2009-2010 Influenza Season, J Public Health Manag Pract,
doi:10.1097/PHH.0b013e31824155a2Lowcock, Rosella, Foisy, Mcgeer, Crowcroft, The social determinants of health and pandemic H1N1 2009 influenza severity, Am J Public Health,
doi:10.2105/AJPH.2012.300814Marco, Baker, Daszak, Barro, Eskew et al., Opinion: sustainable development must account for pandemic risk, Proc Natl Acad Sci,
doi:10.1073/pnas.2001655117Martínez-González, Salas-Salvadó, Estruch, Corella, Fitó, Benefits of the Mediterranean diet: insights from the PREDIMED study, Prog Cardiovasc Dis,
doi:10.1016/j.pcad.2015.04.003Mdsmoho, Actualización n • 131
Medina-Remón, Casas, Tressserra-Rimbau, Martínez-González, Fitó, Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a substudy of the PREDIMED trial, Br J Clin Pharmacol,
doi:10.1111/bcp.12986Mendonça, Carvalho, Martin-Moreno, Pimenta, Lopes et al., Total polyphenol intake, polyphenol subtypes and incidence of cardiovascular disease: the SUN cohort study, Nutr Metab Cardiovasc Dis,
doi:10.1016/j.numecd.2018.09.012Merad, Martin, Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages, Nat Rev Immunol,
doi:10.1038/s41577-020-0331-4Noale, Nardi, Limongi, Siviero, Caregaro et al., Adolescents in southern regions of Italy adhere to the Mediterranean diet more than those in the northern regions, Nutr Res,
doi:10.1016/j.nutres.2014.08.001Onder, Rezza, Brusaferro, Case-Fatality rate and characteristics of patients dying in relation to COVID-19 in Italy, JAMA,
doi:10.1001/jama.2020.4683Pelucchi, Galeone, Negri, Vecchia, Trends in adherence to the Mediterranean diet in an Italian population between 1991 and 2006, Eur J Clin Nutr,
doi:10.1038/ejcn.2010.158Pettit, Mackenzie, Ridgway, Pursell, Ash et al., Obesity is associated with increased risk for mortality among hospitalized patients with COVID-19, Obesity,
doi:10.1002/oby.22941Razquin, Martinez-Gonzalez, A traditional Mediterranean diet effectively reduces inflammation and improves cardiovascular health, Nutrients,
doi:10.3390/nu11081842Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area, JAMA,
doi:10.1001/jama.2020.6775Rodrigues, Caraher, Trichopoulou, Almeida, Portuguese households' diet quality (adherence to Mediterranean food pattern and compliance with WHO population dietary goals): trends, regional disparities and socioeconomic determinants, Eur J Clin Nutr,
doi:10.1038/sj.ejcn.1602852Rosella, Fu, Buajitti, Goel, Death and chronic disease risk associated with poor life satisfaction: a population-based cohort study, Am J Epidemiol,
doi:10.1093/aje/kwy245Ruggiero, Castelnuovo, Costanzo, Persichillo, Bracone et al., Socioeconomic and psychosocial determinants of adherence to the Mediterranean diet in a general adult Italian population, Eur J Public Health,
doi:10.1093/eurpub/cky127Salas-Salvadó, Becerra-Tomás, Papandreou, Bulló, Dietary patterns emphasizing the consumption of plant foods in the management of type 2 diabetes: a narrative review, Adv Nutr,
doi:10.1093/advances/nmy102Shivappa, Bonaccio, Hebert, Castelnuovo, Costanzo et al., Association of proinflammatory diet with low-grade inflammation: results from the moli-sani study, Nutrition,
doi:10.1016/j.nut.2018.04.004Shivappa, Steck, Hurley, Hussey, Hébert, Designing and developing a literature-derived, populationbased dietary inflammatory index, Public Health Nutr,
doi:10.1017/S1368980013002115Singh, Gillies, Singh, Singh, Chudasama et al., Prevalence of co-morbidities and their association with mortality in patients with COVID-19: a systematic review and meta-analysis, Diabetes Obes Metab,
doi:10.1111/dom.14124Sofi, Abbate, Gensini, Casini, Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis, Am J Clin Nutr,
doi:10.3945/ajcn.2010.29673Stefan, Birkenfeld, Schulze, Ludwig, Obesity and impaired metabolic health in patients with COVID-19, Nat Rev Endocrinol,
doi:10.1038/s41574-020-0364-6Sánchez-Sánchez, García-Vigara, Hidalgo-Mora, García-Pérez, Tarín et al., Mediterranean diet and health: a systematic review of epidemiological studies and intervention trials, Maturitas,
doi:10.1016/j.maturitas.2020.03.008Tian, Jiang, Yao, Nicholson, Li et al., Predictors of mortality in hospitalized COVID-19 patients: a systematic review and meta-analysis, J Med Virol,
doi:10.1002/jmv.26050Tong, Imamura, Monsivais, Brage, Griffin et al., Dietary cost associated with adherence to the Mediterranean diet, and its variation by socio-economic factors in the UK Fenland Study, Br J Nutr,
doi:10.1017/S0007114517003993Tosti, Bertozzi, Fontana, Health benefits of the Mediterranean diet: metabolic and molecular mechanisms, J Gerontol A Biol Sci Med Sci,
doi:10.1093/gerona/glx227Turner-Mcgrievy, Davidson, Wingard, Wilcox, Frongillo, Comparative effectiveness of plant-based diets for weight loss: a randomized controlled trial of five different diets, Nutrition,
doi:10.1016/j.nut.2014.09.002Vilarnau, Stracker, Funtikov, Da Silva, Estruch et al., Worldwide adherence to mediterranean diet between 1960 and 2011, Eur J Clin Nutr,
doi:10.1038/s41430-018-0313-9Wirth, Robinson, Murphy, Shivappa, Hébert, The dietary inflammatory index is associated with gastrointestinal infection symptoms in the national health and nutrition examination survey, Int J Food Sci Nutr,
doi:10.1080/09637486.2019.1614539Wong, Yang, Thach, Chau, Chan et al., Modification by influenza on health effects of air pollution in Hong Kong, Environ Health Perspect,
doi:10.1289/ehp.11605Wood, Shivappa, Berthon, Gibson, Hebert, Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma, Clin Exp Allergy,
doi:10.1111/cea.12323Wright, Wilson, Smith, Duncan, Mchugh, The BROAD study: a randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes, Nutr Diabetes,
doi:10.1038/nutd.2017.3
