Written by Steve Blechman
26 June 2020

 coronavirus 62620

 

   CORONAVIRUS PANDEMIC:

ANTI-INFLAMMATORY DIET

Fighting the Deadly Cytokine Storm and Stay Healthy!

By Steve Blechman

 

The cytokine storm is the major cause of death from the coronavirus! The cytokine storm is a severely dangerous hyperimmune reaction to infection of the coronavirus in the lungs, in which the immune system overproduces inflammatory cytokines, which can damage lungs and cause inflammation of the air sacs of the lung, which can inhibit oxygen in the body – causing pneumonia, respiratory failure and the requirement of a ventilator. Recent research has shown that the cytokine storm can also cause inflammation and cell damage to the heart, liver, brain, kidneys, intestines, as well as cause abnormal blood clots, which are causing lower body amputations and sudden cardiac thrombosis and death.

 

In those people infected with the COVID-19 virus, the coronavirus particles enter your body through your nose, mouth or eyes, into your lungs. The immune system recognizes the virus and sends immune-signaling molecules called cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Normally these cytokines play a beneficial role by activating our innate immune response and certain white blood cells called macrophages, neutrophils and natural killer cells that destroy and kill certain dangerous pathogens, bacteria and viruses. These white blood cells are like “killer, phagocytic Pac-Men” that release reactive oxygen species (ROS) free radicals and kill these bacteria and viruses. At the same time, these ROS free radical species damage normal tissues and cause inflammation and cell death. So these white blood cells in fact are a two-edged sword – they kill dangerous viruses and bacteria or they can go haywire, causing severe inflammation cell damage and organ failure!

 

The anti-inflammatory drugs approved for treating rheumatoid arthritis such as tocilizumab (Actemra) has great potential in treating COVID-19 patients with the deadly cytokine storm. Also, the inexpensive generic steroid drug dexamethasone reduces death rates by one-third with the most severe cases of infections. It is a major breakthrough treatment. These anti-inflammatory drugs reduce inflammation and tame down the cytokine storm and hyperactive immune response in some very ill patients. These drugs also have many side effects, but the benefits far outweigh the risks and can potentially save many lives!

 

 

Also, as early as 2005 “The FDA warned that taking non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen increase risk of having a heart attack or stroke.” (Sources: Harvard Health Publishing, July 13, 2015) Many people abuse these NSAIDs for pain and inflammation. It’s important to take these drugs under the supervision of a physician and take the lowest effective dose for the lowest length of time.

 

 

The Mediterranean diet, an anti-inflammatory diet, has great potential to naturally help tame down the uncontrolled hyperimmune response, which causes the potentially deadly cytokine storm and severe inflammation. The Mediterranean diet is the healthiest diet based on the latest scientific research. A healthy diet and lifestyle changes, such as following the anti-inflammatory Mediterranean diet along with exercise, has been shown to lower the risk of obesity, metabolic syndrome and high-risk ailments such as cardiovascular disease and diabetes. For the past two years, US News and World Report ranked the Mediterranean diet as the best overall diet for healthy eating, tied with the Dash Diet. The Mediterranean diet was also ranked #1 for the easiest diet to follow; best diet for diabetes; best heart-healthy diet, and best plant-based diet too. The Mediterranean diet is high in fish containing omega-3 fatty acids, in addition to antioxidant-rich vegetables, red wine and berries rich in polyphenols, beans, lentils, nuts, legumes and extra-virgin-olive oil that are rich in healthy monounsaturated polyunsaturated fats and low in saturated fats. A recent study by Harvard researchers and reported by the American Heart Association (March 5, 2020) and published in the Journal of the American College of Cardiology (March 2020) found that as little as half a tablespoon of olive oil a day was linked to significant decrease in cardiovascular disease. Research has shown that omega-3 fatty acids (primarily EPA and DHA) found in fatty fish such as salmon have potent anti-inflammatory properties and reduced inflammation and protect against heart disease. It was reported recently in the Wall Street Journal (June 3, 2020) that, “Amarin Corporation plans to test it’s fish oil derived drug Vascepa, can prevent and treat COVID-19 infection and reduce the risk of cardiovascular problems in patients who sustain heart damage during their illness.” This story added: “Amarin says Vascepa may help prevent or treat inflammation.”

 

 

Omega-3 fatty acids (EPA and DHA) both lower inflammation. Some research has shown that DHA is a more anti-inflammatory than EPA. These omega-3 fatty acids can lower inflammatory compounds called leukotrienes in the body. These leukotrienes are produced naturally from arachidonic acid, a polyunsaturated fat found in animal fats present in meat, poultry, eggs and cheese. High arachidonic acid levels in the body can increase inflammation and the inflammatory cascade, which can lead to the cytokine storm in susceptible individuals. That’s why it’s very important to limit animal fats and arachidonic acid in the anti-inflammatory Mediterranean diet and eat more omega-3 rich fish such as salmon.

 

 

Research has shown that inflammation is a major risk factor for cardiovascular disease. Research has shown that the traditional Mediterranean diet can reduce inflammation and improve cardiovascular health (Nutrients, August 9, 2020). Sixteen years ago the ATTICA Study (J Am Coll Cardiol, July 2004) found that the Mediterranean diet was associated with a 20% lower c-reactive protein (CRP) and 17% lower levels of interleukin-6 (IL-6.) CRP and IL-6 are elevated in systemic inflammation in the body. This was an observational study and demonstrated an association but not proof of cause and effect like a randomized, double-blind clinical trial; also, a similar study a year later called the Nurses’ Cohort in the USA (Am J Clin Nut, July 2005) was associated to a 24% lower c-reactive protein and 16% lower levels of interleukin-6 (IL-6). These very well conducted observational studies were later confirmed by a randomized clinical trial (PREDIMED pilot study). The Mediterranean diet supplemented with extra-virgin olive oil for three months that human adults followed reduced c-reactive protein. The Mediterranean diet, as I mentioned, was supplemented with extra-virgin oil containing monounsaturated fats and polyphenols and lowered low-grade inflammation implicated in the mechanism leading to atherosclerotic disease (Nutr Metab, September 2014). The PREDIMED trial later involving 1,139 high-risk cardiovascular adults further confirmed a dose-dependent anti-inflammatory of the Mediterranean diet rich in polyphenols based on measuring inflammatory biomarkers such as c-reactive protein and interleukin-6 (Br J Clin Pharmaca, January 2017). A later study (CANTOS trial) found that a monoclonal antibody that reduces c-reactive protein and interleukin-6, and inflammation, further confirmed the inflammatory hypothesis in atherosclerosis and cardiovascular disease without lowering blood lipids (N Engel J Med, Jan. 1999, Endocrinol Diabet Nutr, Nov. 2017). The Mediterranean diet containing extra-virgin olive oil, fruits, and red wine is rich in polyphenols with potent anti-inflammatory properties.

 

 

Recently, the Cleveland Clinic published a scientific review (June 2, 2020, Cleveland Clinic Journal of Medicine) entitled, What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? The review mentioned that zinc, vitamin D, and N-acetylcysteine (NAC) can lower proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF). The authors outline, “the biological plausibility, applicable clinical data and potential role of each of these agents.” The Cleveland Clinic Investigators continued to say that, “several agents intended to supplement dietary intake or indigenous molecules may have a theoretical role in preventing or treating COVID-19.” Based on their scientific review, the authors further acknowledge that ascorbic acid, zinc, vitamin D, and N-acetylcysteine have biologic plausibility for prevention and treatment of COVID-19 and are candidates for clinical trials evaluating patients with these indications.”

 

In conclusion, it is now reported that 1 in 5 people are at high risk of COVID-19. The coronavirus is not just going to disappear. It’s going to be with us for a while. We need to improve our health and lower our risks of getting COVID-19. We already know that people over 65 have higher systemic inflammation. Also, systemic inflammation is higher in overweight and the obese. Also, with pre-existing ailments such as metabolic syndrome, hypertension, diabetes, heart and cardiovascular disease increase systemic inflammation and risk of death from COVID-19. A healthy nutritional diet and lifestyle such as the anti-inflammatory Mediterranean diet may help lower inflammation. Clinical trials with the Mediterranean diet need to be done, and evaluated in people at high risk of COVID-19. Even though cases of coronavirus are going down and less people dying, we cannot take our foot off of the pedal! 40% of adults are obese in the United States. Many have metabolic syndrome and systemic inflammation. A simple blood test by your physician can measure your c-reactive protein levels. Eating healthy and improving our metabolic health and exercising more can help control our weight, lower inflammation, and improve our metabolic health.

 

 

DISCUSS ON OUR FORUMS

SUBSCRIBE TO MD TODAY!

 

GET OFFICIAL MD STUFF!

 

VISIT OUR STORE

 

FOLLOW MUSCULAR DEVELOPMENT ON:

 

FACEBOOK: MuscularDevelopment Magazine

 

TWITTER: @MuscularDevelop

 

INSTAGRAM: @MuscularDevelopment

 

YOUTUBE: http://bit.ly/2fvHgnZ

 

GET OUR NEWSLETTER

 

& STAY UP TO DATE!

 

SCROLL DOWN TO SIGN UP!

 

 

 

 

 

References:

1. Olive oil may lower heart disease risk. American Heart Association News. March 5, 2020. https://www.heart.org/en/news/2020/03/05/olive-oil-may-lower-heart-disease-risk

2. Olive Oil Consumption and Cardiovascular Risk in U.S. Adults. Journal of the American College of Cardiology. Marta Guasch-Ferré, Gang Liu, Yanping Li, Laura Sampson, JoAnn E. Manson, Jordi Salas-Salvadó, Miguel A. Martínez-González, Meir J. Stampfer, Walter C. Willett, Qi Sun, Frank B. Hu. Journal of the American College of Cardiology. April 2020. https://doi.org/10.1016/j.jacc.2020.02.036

3. FDA strengthens warning that NSAIDs increase heart attack and stroke risk. July 13, 2015. Harvard Health Publishing. Harvard Medical School. https://www.health.harvard.edu/blog/fda-strengthens-warning-that-nsaids-increase-heart-attack-and-stroke-risk-201507138138

4. Coronavirus breakthrough: dexamethasone is first drug shown to save lives. 16 June 2020. Nature. https://www.nature.com/articles/d41586-020-01824-5

5. Razquin C, Martinez-Gonzalez MA. A Traditional Mediterranean Diet Effectively Reduces Inflammation and Improves Cardiovascular Health. Nutrients. 2019;11(8):1842. Published 2019 Aug 9. doi:10.3390/nu11081842

6. Ying Chi, Yiyue Ge, Bin Wu, Wenshuai Zhang, Tao Wu, Tian Wen, Jingxian Liu, Xiling Guo, Chao Huang, Yongjun Jiao, Fengcai Zhu, Baoli Zhu, Lunbiao Cui, Serum Cytokine and Chemokine profile in Relation to the Severity of Coronavirus disease 2019 (COVID-19) in China, The Journal of Infectious Diseases, , jiaa363, https://doi.org/10.1093/infdis/jiaa363

7. 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.

8. COVID-19 cytokine storm: The anger of inflammation. Mehdi Mahmudpour, Jamshid Roozbeh, Mohsen Keshavarz, Shokrollah Farrokhi, Iraj Nabipour. Cytokine. https://doi.org/10.1016/j.cyto.2020.155151. September 2020

9. Wang, J, Jiang, M, Chen, X, Montaner, LJ. Cytokine storm and leukocyte changes in mild versus severe SARSCoV2 infection: Review of 3939 COVID19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. June 13, 2020; 1– 25. https://doi.org/10.1002/JLB.3COVR0520-272R

10. Roy AS, Matson M, Herlekar R. Response to 'Vitamin D concentrations and COVID-19 infection in UK Biobank' [published online ahead of print, 2020 Jun 4]. Diabetes Metab Syndr. 2020;14(5):777. doi:10.1016/j.dsx.2020.05.049

11. Quesada-Gomez JM, Castillo ME, 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 [published online ahead of print, 2020 Jun 11]. J Steroid Biochem Mol Biol. 2020;105719. doi:10.1016/j.jsbmb.2020.105719

12. Silberstein M. Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19? [published online ahead of print, 2020 Apr 23]. Med Hypotheses. 2020;140:109767. doi:10.1016/j.mehy.2020.109767

13. New Rules for Covid Summer: Be Flexible and Vigilant by Scott Gottleib, Yuval Levin, Monday June 15, 2020 https://www.wsj.com/articles/new-rules-for-covid-summer-be-flexible-and-vigilant-11592167772

14. Steroid drug hailed as 'breakthrough' in COVID-19 as trial shows it saves lives. June 16, 2020. Kate Kelland, Alistair Smout. Reuters. https://www.reuters.com/article/us-health-coronavirus-steroid/steroid-dexamethasone-reduces-deaths-among-patients-with-severe-covid-19-trial-shows-idUSKBN23N1VP 

15. What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? Seth R. Bauer, Aanchal Kapoor, Mary Rath, Suma A. Thomas, Cleveland Clinic Journal of Medicine Jun 2020, DOI: 10.3949/ccjm.87a.ccc046 

16. Risk of COVID19 for patients with obesity. Radwan Kassir. April 13, 2020. Obesity Reviews. https://doi.org/10.1111/obr.13034

17. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. Mandeep R. Mehra, M.D., Sapan S. Desai, M.D., Ph.D., SreyRam Kuy, M.D., M.H.S., Timothy D. Henry, M.D., and Amit N. Patel, M.D. May 1, 2020. DOI: 10.1056/NEJMoa2007621 

18. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. April 28, 2020
DOI: 10.1056/NEJMc2009787  

19. Fish Consumption in Healthy Adults Is Associated with Decreased Circulating Biomarkers of Endothelial Dysfunction and Inflammation during a 6-Year Follow-Up. Bas C. T. van Bussel, Ronald M. A. Henry, Casper G. Schalkwijk, Isabel Ferreira, Edith J. M. Feskens, Martinette T. Streppel, Yvo M. Smulders, Jos W. R. Twisk, Coen D. A. Stehouwer. The Journal of Nutrition, Volume 141, Issue 9, September 2011, Pages 1719-1725, https://doi.org/10.3945/jn.111.139733 

20. Ratih Wirapuspita Wisnuwardani, Stefaan De Henauw, Marika Ferrari, Maria Forsner, Frédéric Gottrand, Inge Huybrechts, Antonios G Kafatos, Mathilde Kersting, Viktoria Knaze, Yannis Manios, Ascensión Marcos, Dénes Molnár, Joseph A Rothwell, Azahara Iris Rupérez, Augustin Scalbert, Kurt Widhalm, Luis A Moreno, Nathalie Michels, Total Polyphenol Intake Is Inversely Associated with a Pro/Anti-Inflammatory Biomarker Ratio in European Adolescents of the HELENA Study, The Journal of Nutrition, nxaa064, https://doi.org/10.1093/jn/nxaa064  

21. Kate J Claycombe-Larson, Travis Alvine, Dayong Wu, Nishan S Kalupahana, Naima Moustaid-Moussa, James N Roemmich, Nutrients and Immunometabolism: Role of Macrophage NLRP3, The Journal of Nutrition, nxaa085, https://doi.org/10.1093/jn/nxaa085 

22. Calder, P.C.; Carr, A.C.; Gombart, A.F.; Eggersdorfer, M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181.  

23. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Author links open overlay panel. Richard I.Horowitz. Phyllis R.Freeman. James Bruzzesec. Respiratory Medicine Case Reports. Volume 30, 2020, 101063. https://doi.org/10.1016/j.rmcr.2020.101063 

24. Obesity Exacerbates the Cytokine Storm Elicited by Francisella tularensis Infection of Females and Is Associated with Increased Mortality. Mireya G. Ramos Muniz et al. June 26, 2018. Journal of Bio Med Rsch. https://doi.org/10.1155/2018/3412732

25. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1286  

26. Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1105  

27. Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1017  

28. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1286  

29. Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1105

30. Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients With Severe COVID-19 Pneumonia. March 23, 2020. AP News Wire https://apnews.com/Business%20Wire/9e97b7ad899e4bb4bcc80b0d5fc72c7d 

31. Obesity Exacerbates the Cytokine Storm Elicited by Francisella tularensis Infection of Females and Is Associated with Increased Mortality. Mireya G. Ramos Muniz, Matthew Palfreeman et al. Advances in Emerging and Neglected Infectious Diseases June 26, 2018. BioMed Research International. https://www.hindawi.com/journals/bmri/2018/3412732/ 

32. Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss. Nutrition Journal, 2008, Volume 7, Number 1, Page 1. Joaquín Pérez-Guisado, Andrés Muñoz-Serrano, Ángeles Alonso-Moraga 

33. Long-term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol. Paoli, A., Bianco, A., Grimaldi, K. A., Lodi, A., & Bosco, G. (2013). Nutrients, 5 (12), 5205-17. doi:10.3390/nu5125205  

34. Effect of ketogenic Mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees. Paoli, A., Cenci, L., & Grimaldi, K. A. (2011). Nutrition journal, 10, 112. doi:10.1186/1475-2891-10-112  

35. Mediterranean Diet Reduces Risk of Incident Stroke in a Population With Varying Cardiovascular Disease Risk Profiles. Paterson, K. E., Myint, P. K., Jennings, A., Bain, L., Lentjes, M., Khaw, K. T., & Welch, A. A. (Oct 2018). Stroke, 49 (10), 2415-2420. Advance online publication. doi:10.1161/STROKEAHA.117.020258 

36. Ahmad S, Moorthy MV, Demler OV, et al. Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet. JAMA Netw Open. Dec. 7, 2018;1(8):e185708. doi:10.1001/jamanetworkopen.2018.5708 

37. Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Mariarosaria Persichillo, Amalia De Curtis, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello. Interaction between Mediterranean diet and statins on mortality risk in patients with cardiovascular disease: Findings from the Moli-sani Study. International Journal of Cardiology, 2018; DOI: 10.1016/j.ijcard.2018.11.117

38. Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: The CENTRAL MRI Randomized Controlled Trial. Yftach Gepner, Ilan Shelef, Dan Schwarzfuchs, Hila Zelicha, Lilac Tene, Anat Yaskolka Meir, Gal Tsaban, Noa Cohen, Nitzan Bril, Michal Rein, Dana Serfaty, Shira Kenigsbuch, Oded Komy, Arik Wolak, Yoash Chassidim, Rachel Golan, Hilla Avni-Hassid, Avital Bilitzky, Benjamin Sarusi, Eyal Goshen, Elad Shemesh, Yaakov Henkin, Michael Stumvoll, Matthias Blüher, Joachim Thiery, Uta Ceglarek, Assaf Rudich, Meir J. Stampfer and Iris Shai. Circulation 2017;CIRCULATION AHA.117.030501, 2017. 

39. Zong, G., Li, Y., Wanders, A.J., Alssema, M., Zock, P.L., Willett, W.C., Hu, F.B., Sun, Q. Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies BMJ. 2016;355:i5796. 

40. Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study. European Journal of Nutrition, 2017, Page 1 Heinz Freisling, Hwayoung Noh, Nadia Slimani. 

41. Wiley. Fish consumption may prolong life. ScienceDaily, 18 July 2018. www.sciencedaily.com/releases/2018/07/180718082138.htm 

42. Zhang, P. Zhuang, W. He, J. N. Chen, W. Q. Wang, N. D. Freedman, C. C. Abnet, J. B. Wang, J. J. Jiao. Association of fish and long-chain omega-3 fatty acids intakes with total and cause-specific mortality: prospective analysis of 421 309 individuals. Journal of Internal Medicine, 2018; DOI: 10.1111/joim.12786 

43. Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association Frank M. Sacks, MD, FAHA, Chair, Alice H. Lichtenstein, DSc, FAHA, Jason H.Y. Wu, PhD, MSc, Lawrence J. Appel, MD, MPH, FAHA, Mark A. Creager, MD, FAHA, Penny M. Kris-Etherton, PhD, RD, FAHA, Michael Miller, MD, FAHA, Eric B. Rimm, ScD, FAHA, Lawrence L. Rudel, PhD, FAHA, Jennifer G. Robinson, MD, MPH, FAHA, Vice Chair, Neil J. Stone, MD, FAHA, and Linda V. Van Horn, PhD, RD, FAHA, Vice Chair On behalf of the American Heart Association.

44. Mediterranean Diet Reduces Risk of Incident Stroke in a Population With Varying Cardiovascular Disease Risk Profiles. Paterson, K. E., Myint, P.K., Jennings, A., Bain, L., Lentjes, M., Khaw, K.T., & Welch, A.A. (Oct 2018). Stroke, 49 (10), 2415-2420. Advance online publication. doi:10.1161/STROKEAHA.117.020258   

45. Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association Frank M. Sacks, MD, FAHA, Chair, Alice H. Lichtenstein, DSc, FAHA, Jason H.Y. Wu, PhD, MSc, Lawrence J. Appel, MD, MPH, FAHA, Mark A. Creager, MD, FAHA, Penny M. Kris-Etherton, PhD, RD, FAHA, Michael Miller, MD, FAHA, Eric B. Rimm, ScD, FAHA, Lawrence L. Rudel, PhD, FAHA, Jennifer G. Robinson, MD, MPH, FAHA, Vice Chair, Neil J. Stone, MD, FAHA, and Linda V. Van Horn, PhD, RD, FAHA, Vice Chair On behalf of the American Heart Association

46. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The Attica study. Journal of the American College of Cardiology. 2004. https://doi.org/10.1016/j.jacc.2004.03.039.

47. Teresa T Fung, Marjorie L McCullough, PK Newby, JoAnn E Manson, James B Meigs, Nader Rifai, Walter C Willett, Frank B Hu, Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction, The American Journal of Clinical Nutrition, Volume 82, Issue 1, July 2005, Pages 163–173, https://doi.org/10.1093/ajcn/82.1.163

48. Estruch R, Martínez-González MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial [published correction appears in Ann Intern Med. 2018 Aug 21;169(4):270-271]. Ann Intern Med. 2006;145(1):1-11. doi:10.7326/0003-4819-145-1-200607040-00004

49. Schwingshackl L, Christoph M, Hoffmann G. Effects of Olive Oil on Markers of Inflammation and Endothelial Function-A Systematic Review and Meta-Analysis. Nutrients. 2015;7(9):7651-7675. Published 2015 Sep 11. doi:10.3390/nu7095356

50. Medina-Remón A, Casas R, Tressserra-Rimbau A, et al. Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a substudy of the PREDIMED trial. Br J Clin Pharmacol. 2017;83(1):114-128. doi:10.1111/bcp.12986

51. Sureda A, Bibiloni MDM, Julibert A, et al. Adherence to the Mediterranean Diet and Inflammatory Markers. Nutrients. 2018;10(1):62. Published 2018 Jan 10. doi:10.3390/nu10010062

52. Ruiz-Canela M, Estruch R, Corella D, Salas-Salvadó J, Martínez-González MA. Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial [published correction appears in JAMA. 2018 Dec 4;320(21):2272]. JAMA. 2014;311(4):415-417. doi:10.1001/jama.2013.280618

53. Martínez-González MA, Salas-Salvadó J, Estruch R, et al. Benefits of the Mediterranean Diet: Insights From the PREDIMED Study. Prog Cardiovasc Dis. 2015;58(1):50-60. doi:10.1016/j.pcad.2015.04.003

54. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. Ramón Estruch, Emilio Ros, Jordi Salas-Salvadó, et al. The New England Journal of Medicine. Massachusetts Medical Society. Apr 4, 2013 https://www.nejm.org/doi/full/10.1056/NEJMoa1200303

55. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

56. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. Paul M Ridker, Brendan M. Everett, Tom Thuren. The New England Journal of Medicine

Date: Sep 21, 2017 https://www.nejm.org/doi/full/10.1056/NEJMoa1707914

57. Atherosclerosis - An Inflammatory Disease. Russell Ross. January 14, 1999https://www.nejm.org/doi/10.1056/NEJM199901143400207

58. Ruiz-Canela M, Martínez-González MA. Blocking inflammation: a new arsenal against atherosclerosis. Bloqueo de la inflamación: nuevo arsenal contra la arteriosclerosisEndocrinol Diabetes Nutr. 2017;64(10):515-516. doi:10.1016/j.endinu.2017.10.003