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The Modern Mediterranean Diet

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Manage episode 336668564 series 2422056
Contenido proporcionado por Terry Simpson. Todo el contenido del podcast, incluidos episodios, gráficos y descripciones de podcast, lo carga y proporciona directamente Terry Simpson o su socio de plataforma de podcast. Si cree que alguien está utilizando su trabajo protegido por derechos de autor sin su permiso, puede seguir el proceso descrito aquí https://es.player.fm/legal.

Scientists and dieticians consistently rank The Modern Mediterranean Diet (MED diet) as the diet most recommended. But often people don't know what the MED diet is. This post will define the Med diet.

Critics of the Med Diet

Critics argue that there is no uniform MED diet. They make these assertions based on one of these three arguments:

  1. That there is no uniform diet of the Mediterranean Region. There are over 20 countries on the 26,000 miles of coastline of the Mediterranean Sea. Each country with their own unique diets. Many of which have adopted a more modern American style diet.
  2. The diet is simply made up and therefore should be ignored.
  3. Finally some point out that there are many Med Diets as the literature.

Heart disease and Diet

Ancel Keys is the scientist most responsible for not only the Med diet but the relationship of heart disease to diet. In the 1950's, heart disease was thought to be a disease of aging, and smoking but not diet or lifestyle.

In the 1950's, much like today, heart disease was the number one cause of death among of middle aged executives. While there was a clear association between smoking and heart disease, there were far more deaths than could be explained from smoking. Then an Italian scientist told Dr. Keys about the low incidence of cardiovascular deaths of men in Naples.

Heart Disease and Diet in Europe

Keys confirmed this claim when he took a sabbatical in Oxford in 1952. Keys found there was a difference of heart disease between the poor and the executives of Italy. He developed the hypothesis that diet might explain difference between the two groups. To confirm this Keys, and his wife, then traveled throughout Europe catalog different diets and rates of heart disease.

In 1955 Keys presented his data to the World Health Organization, concluding that diet played a significant role in heart disease. Many members of the WHO mocked his "diet-heart theory." Keys then organized the seven countries study (click here).

Seven Countries Study

The seven countries study was an observational study looking at biomarkers, lifestyles and their relationship to heart disease. Those countries were Greece, Italy, former Yugoslavia, Finland, The Netherlands, Japan, and the United States. The cohorts were chosen because of diverse diets, lifestyle, and risk factors. Dietary and lifestyle influence on cardiovascular disease was unknown at the time.

The seven country study was to answer the question about dietary influence and heart disease.

The French Paradox

Low-carb bloggers accuse the seven country study of leaving out France. They cite the French Paradox, that the French eat a diet high in saturated fat but have a low incidence of heart disease.

However, France was not left out of the study. French investigators were present at the original pilot study in Nicotera Italy, but ultimately decided not to participate in the study. France was recovering from World War 2 and simply didn't have the resources to commit to such a study.

In fact, The French Paradox was "coined" in the 1980s, over twenty years after the start of the seven country study. The investigators didn't have access to that data, or the term. Low-carb bloggers didn't read the seven country study or the French paradox.

French Paradox Explained

Two factors explain the French Paradox.

The high fat diet was not widely adopted by the French prior to the mid 1970's. It takes time for a habit to have an effect on cardiovascular disease. For example, one doesn't develop heart disease after the first cigarette. The primary French diet in the 1950's through 70's was a Mediterranean Diet. Thus, the effect of the high fat diet would not be evident for twenty plus years after it was adopted.

The second explanation is that French physicians consistently underreported heart disease. Of note, Wine consumption has been the most studied aspect of the French Paradox. Red wine sales increased dramatically after the airing of the "French Paradox" on Sixty Minutes. Wine is an important component of the Med diet.

Seven Country Study and The Med Diet

From 1958 to 1970 over 12,000 men were tracked for diet, weight, smoking, physical activity, vital signs, cholesterol, and lung capacity. During that time there were about 2300 deaths, 27% from heart disease. Different countries had different rates of deaths from heart disease: USA 50%, Northern Europe 40%, Southern Europe 17%, Japan 5%. The dietary pattern that was identified in this study became the basis of what Keys would call The Mediterranean Diet. Key's book became a bestseller, describing not only the first version of the Mediterranean Diet, but providing healthy recipes for a country trying to fight the number one killer. Keys even wrote a best selling cookbook with his wife touting the benefit of the diet.

Adopting the Mediterranean Diet

Keys died shortly before his 101'st birthday. There are a number of great articles written about Keys, but the obituary here is one of the finest.

The Nine Point Scale

The first scoring system for the Med diet was proposed in 1995 (here). Other studies began to arise to determine the Med diet for cancer, autoimmune diseases, longevity, dementia, and other disease states.

One of the more famous was a meta analysis of twelve studies looking at longevity. Greater adherence in this scale also showed lower incidence of Parkinson's disease, Alzheimer's disease as well as cardiovascular mortality.

This scale gave points for increased consumption of vegetables, fruits, legumes, cereals, fish, and moderate red wine consumption. While those who had "above the median" of red and processed meats and dairy were given zero points. Ultimately this was refined further with the use of monounsaturated fatty acids (olive oil) as the primary fat (60% or greater).

EPIC Study

Trichopoulou, and her colleagues began the European Prospective Investigation into Cancer and Nutrition (EPIC) study in 1994 after the pilot study in 1991. The study enrolled more than 521,000 participants from 23 centers in 10 western European countries, detailing diet, lifestyle, medical history, and vital signs.

They used a validated food frequency questionnaire of over 150 foods commonly consumed in Greece. "For this analysis, we focused on nine nutritional variables: vegetables, legumes, fruits and nuts, dairy products, cereals, meat and meat products, fish and seafood, monounsaturated to saturated lipid ratio, and ethanol." (11).

Conclusions of the EPIC study

A two point increase in the Mediterranean diet score led to a decrease in mortality of 14%.

Diet Pyramids

Diet pyramids were common in the 1990's . One of the more famous was from Oldways where they developed a pyramid in 1994 to describe the Mediterranean Diet. (12). This pyramid was based primarily on the diet from the Island of Crete and southern Italy from the 1960's.

Diet pyramids are of little use in scientific studies, as they don't quantify the amounts of foods consumed. Some argue that diet pyramids are a useful way to display the data.

Lyon Heart Study

The Lyon heart study was a randomized secondary trial testing the Mediterranean Diet against the French Prudent diet. After 46 months there were 1.24 per one hundred patients who had either a cardiac death or nonfatal infarction. This compared to 4.07 per one hundred who had the standard cardiac diet. They also noted that most patients, after a few years, were still following the Mediterranean Diet, showing that adoption and compliance was not difficult.

Obesity and the Mediterranean Diet

The Mediterranean Diet is useful not only for disease, but for weight management. The latest drugs for obesity are GLP-1 agonists (Wegovy, Ozempic) there is a clear benefit from polyunsaturated fatty acids (PUFA) and raising GLP-1. While obese patients have lower GLP-1 response to glucose than non-obese, the PUFAs in the Mediterranean diet provide an increase in GLP-1.

Further the polyphenolic compounds of the Mediterranean Diet provide another benefit. People with the highest intake of polyphenols (especially the flavonoids) were associated with an 11 percent decrease risk of developing type 2 Diabetes.

Finally the antioxidant rich Mediterranean Diet has been seen as a potent tool against the inflammatory cascade seen in obese patients.

Closer adherence to the Mediterranean Diet has been shown to have decreased rates of obesity, as well as better lipid profiles.

Weight Loss Surgery Patients

We took over 180 patients who had various forms of weight loss surgery and calculated their Mediterranean Diet Score. We then compared those scores to their postoperative weight loss after five years. Those patients who had a score of 5 or more all were in the greater than 50% of weight loss regardless of the type of weight loss surgery. Those patients who had a score of 0-3 were in the lowest quarter of weight loss or even weight regain. The score of 4 seemed to be all over the scale.

Type 2 Diabetes Mellitus and the Mediterranean Diet

The Mediterranean Diet has been found to both decrease the risk of type 2 Diabetes, but a potent reversal of type 2 diabetes. This occurs through lifestyle intervention, and has been found best for long term weight loss.

Current Adoption of the Mediterranean Diet

Click the link below to see the modern Med Diet score card.

MedDietScoreCard

Most papers have discussed the 9 point system and this is consistent throughout the literature in the last fifteen years. The scoring is reasonably simple, or can be completed through a validated food frequency questionnaire.

The Mediterranean Diet continues to be the most studied diet on the planet, with the most reproducible results for chronic diseases from obesity, diabetes, heart disease, dementia and autoimmune diseases.

Closer adherence to the Mediterranean Diet is associated with longevity.

REFERENCES:

  1. My podcast and writing about The Mediterranean Diet: https://www.yourdoctorsorders.com/2018/09/the-mediterranean-diet/
  2. https://www.sevencountriesstudy.com/about-the-study/history/
  3. Keys A, Aravanis C, Blackburn HW, Van Buchem FS, Buzina R,
  4. Djordjević BD, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, Lekos D,
  5. Monti M, Puddu V, Taylor HL. Epidemiological studies related to coronary
  6. heart disease: characteristics of men aged 40-59 in seven countries.
  7. Acta Med Scand Suppl. 1966;460:1-392. PMID: 5226858.
  8. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French
  9. paradox for coronary heart disease. Lancet. 1992 Jun
  10. 20;339(8808):1523-6. doi: 10.1016/0140-6736(92)91277-f. PMID: 1351198.
  11. Burr ML. Explaining the French paradox. J R Soc Health. 1995 Aug;115(4):217-9. doi: 10.1177/146642409511500404. PMID: 7562866.
  12. Iwasaki M, Murakami M, Ijiri Y, Shimizu M, Yamamoto J. Are all wines
  13. made from various grape varieties beneficial in the prevention of
  14. myocardial infarction and stroke? Future Sci OA. 2020 Nov 9;7(2):FSO649.
  15. doi: 10.2144/fsoa-2020-0098. PMID: 33437515; PMCID: PMC7787155.
  16. Keys, Margaret, and Keys, Ancel. Eat Well & Stay Well. United Kingdom, Doubleday, 1959. Revised 1963.
  17. Aboul-Enein BH, Puddy WC, Bernstein J. Ancel Benjamin Keys
  18. (1904-2004): His early works and the legacy of the modern Mediterranean
  19. diet. J Med Biogr. 2020 Aug;28(3):139-147. doi:
  20. 10.1177/0967772017727696. Epub 2017 Nov 14. PMID: 29134858.
  21. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou
  22. P, Polychronopoulos E, Vassilakou T, Lipworth L, Trichopoulos D. Diet
  23. and overall survival in elderly people. BMJ. 1995 Dec
  24. 2;311(7018):1457-60. doi: 10.1136/bmj.311.7018.1457. PMID: 8520331;
  25. PMCID: PMC2543726.
  26. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects
  27. of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009
  28. Jun 23;338:b2337. doi: 10.1136/bmj.b2337. PMID: 19549997; PMCID:
  29. PMC3272659.000
  30. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to
  31. Mediterranean diet and health status: meta-analysis. BMJ. 2008 Sep
  32. 11;337:a1344. doi: 10.1136/bmj.a1344. PMID: 18786971; PMCID: PMC2533524.
  33. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects
  34. of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009
  35. Jun 23;338:b2337. doi: 10.1136/bmj.b2337. PMID: 19549997; PMCID:
  36. PMC3272659.
  37. Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A,
  38. Helsing E, Trichopoulos D. Mediterranean diet pyramid: a cultural model
  39. for healthy eating. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1402S-1406S.
  40. doi: 10.1093/ajcn/61.6.1402S. PMID: 7754995.
  41. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.
  42. Mediterranean diet, traditional risk factors, and the rate of
  43. cardiovascular complications after myocardial infarction: final report
  44. of the Lyon Diet Heart Study. Circulation. 1999 Feb 16;99(6):779-85.
  45. doi: 10.1161/01.cir.99.6.779. PMID: 9989963.
  46. Gioia C, Lucchino B, Tarsitano MG, Iannuccelli C, Di Franco M.
  47. Dietary Habits and Nutrition in Rheumatoid Arthritis: Can Diet Influence
  48. Disease Development and Clinical Manifestations? Nutrients. 2020 May
  49. 18;12(5):1456. doi: 10.3390/nu12051456. PMID: 32443535; PMCID:
  50. PMC7284442.
  51. Petersson SD, Philippou E. Mediterranean Diet, Cognitive Function,
  52. and Dementia: A Systematic Review of the Evidence. Adv Nutr. 2016 Sep
  53. 15;7(5):889-904. doi: 10.3945/an.116.012138. PMID: 27633105; PMCID:
  54. PMC5015034.
  55. Martín-Peláez S, Fito M, Castaner O. Mediterranean Diet Effects on
  56. Type 2 Diabetes Prevention, Disease Progression, and Related Mechanisms.
  57. A Review. Nutrients. 2020 Jul 27;12(8):2236. doi: 10.3390/nu12082236.
  58. PMID: 32726990; PMCID: PMC7468821.
  59. Schellenberg ES, Dryden DM, Vandermeer B, Ha C, Korownyk C.
  60. Lifestyle interventions for patients with and at risk for type 2
  61. diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013
  62. Oct 15;159(8):543-51. doi: 10.7326/0003-4819-159-8-201310150-00007.
  63. PMID: 24126648.
  64. Mancini JG, Filion KB, Atallah R, Eisenberg MJ. Systematic Review of
  65. the Mediterranean Diet for Long-Term Weight Loss. Am J Med. 2016
  66. Apr;129(4):407-415.e4. doi: 10.1016/j.amjmed.2015.11.028. Epub 2015 Dec
  67. 22. PMID: 26721635.
  68. Romagnolo DF, Selmin OI. Mediterranean Diet and Prevention of
  69. Chronic Diseases. Nutr Today. 2017 Sep;52(5):208-222. doi:
  70. 10.1097/NT.0000000000000228. Epub 2017 Aug 15. PMID: 29051674; PMCID:
  71. PMC5625964.
  72. Álvarez-Álvarez I, Martínez-González MÁ, Sánchez-Tainta A, Corella
  73. D, Díaz-López A, Fitó M, Vioque J, Romaguera D, Martínez JA, Wärnberg J,
  74. López-Miranda J, Estruch R, Bueno-Cavanillas A, Arós F, Tur JA,
  75. Tinahones FJ, Serra-Majem L, Martín V, Lapetra J, Más Fontao S, Pintó X,
  76. Vidal J, Daimiel L, Gaforio JJ, Matía P, Ros E, Ruiz-Canela M, Sorlí
  77. JV, Becerra-Tomás N, Castañer O, Schröder H, Navarrete-Muñoz EM, Zulet
  78. MÁ, García-Ríos A, Salas-Salvadó J, Díez-Espino J, Toledo E. Adherence
  79. to an Energy-restricted Mediterranean Diet Score and Prevalence of
  80. Cardiovascular Risk Factors in the PREDIMED-Plus: A Cross-sectional
  81. Study. Rev Esp Cardiol (Engl Ed). 2019 Nov;72(11):925-934. English,
  82. Spanish. doi: 10.1016/j.rec.2018.08.010. Epub 2018 Oct 2. PMID:
  83. 30287240.

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Manage episode 336668564 series 2422056
Contenido proporcionado por Terry Simpson. Todo el contenido del podcast, incluidos episodios, gráficos y descripciones de podcast, lo carga y proporciona directamente Terry Simpson o su socio de plataforma de podcast. Si cree que alguien está utilizando su trabajo protegido por derechos de autor sin su permiso, puede seguir el proceso descrito aquí https://es.player.fm/legal.

Scientists and dieticians consistently rank The Modern Mediterranean Diet (MED diet) as the diet most recommended. But often people don't know what the MED diet is. This post will define the Med diet.

Critics of the Med Diet

Critics argue that there is no uniform MED diet. They make these assertions based on one of these three arguments:

  1. That there is no uniform diet of the Mediterranean Region. There are over 20 countries on the 26,000 miles of coastline of the Mediterranean Sea. Each country with their own unique diets. Many of which have adopted a more modern American style diet.
  2. The diet is simply made up and therefore should be ignored.
  3. Finally some point out that there are many Med Diets as the literature.

Heart disease and Diet

Ancel Keys is the scientist most responsible for not only the Med diet but the relationship of heart disease to diet. In the 1950's, heart disease was thought to be a disease of aging, and smoking but not diet or lifestyle.

In the 1950's, much like today, heart disease was the number one cause of death among of middle aged executives. While there was a clear association between smoking and heart disease, there were far more deaths than could be explained from smoking. Then an Italian scientist told Dr. Keys about the low incidence of cardiovascular deaths of men in Naples.

Heart Disease and Diet in Europe

Keys confirmed this claim when he took a sabbatical in Oxford in 1952. Keys found there was a difference of heart disease between the poor and the executives of Italy. He developed the hypothesis that diet might explain difference between the two groups. To confirm this Keys, and his wife, then traveled throughout Europe catalog different diets and rates of heart disease.

In 1955 Keys presented his data to the World Health Organization, concluding that diet played a significant role in heart disease. Many members of the WHO mocked his "diet-heart theory." Keys then organized the seven countries study (click here).

Seven Countries Study

The seven countries study was an observational study looking at biomarkers, lifestyles and their relationship to heart disease. Those countries were Greece, Italy, former Yugoslavia, Finland, The Netherlands, Japan, and the United States. The cohorts were chosen because of diverse diets, lifestyle, and risk factors. Dietary and lifestyle influence on cardiovascular disease was unknown at the time.

The seven country study was to answer the question about dietary influence and heart disease.

The French Paradox

Low-carb bloggers accuse the seven country study of leaving out France. They cite the French Paradox, that the French eat a diet high in saturated fat but have a low incidence of heart disease.

However, France was not left out of the study. French investigators were present at the original pilot study in Nicotera Italy, but ultimately decided not to participate in the study. France was recovering from World War 2 and simply didn't have the resources to commit to such a study.

In fact, The French Paradox was "coined" in the 1980s, over twenty years after the start of the seven country study. The investigators didn't have access to that data, or the term. Low-carb bloggers didn't read the seven country study or the French paradox.

French Paradox Explained

Two factors explain the French Paradox.

The high fat diet was not widely adopted by the French prior to the mid 1970's. It takes time for a habit to have an effect on cardiovascular disease. For example, one doesn't develop heart disease after the first cigarette. The primary French diet in the 1950's through 70's was a Mediterranean Diet. Thus, the effect of the high fat diet would not be evident for twenty plus years after it was adopted.

The second explanation is that French physicians consistently underreported heart disease. Of note, Wine consumption has been the most studied aspect of the French Paradox. Red wine sales increased dramatically after the airing of the "French Paradox" on Sixty Minutes. Wine is an important component of the Med diet.

Seven Country Study and The Med Diet

From 1958 to 1970 over 12,000 men were tracked for diet, weight, smoking, physical activity, vital signs, cholesterol, and lung capacity. During that time there were about 2300 deaths, 27% from heart disease. Different countries had different rates of deaths from heart disease: USA 50%, Northern Europe 40%, Southern Europe 17%, Japan 5%. The dietary pattern that was identified in this study became the basis of what Keys would call The Mediterranean Diet. Key's book became a bestseller, describing not only the first version of the Mediterranean Diet, but providing healthy recipes for a country trying to fight the number one killer. Keys even wrote a best selling cookbook with his wife touting the benefit of the diet.

Adopting the Mediterranean Diet

Keys died shortly before his 101'st birthday. There are a number of great articles written about Keys, but the obituary here is one of the finest.

The Nine Point Scale

The first scoring system for the Med diet was proposed in 1995 (here). Other studies began to arise to determine the Med diet for cancer, autoimmune diseases, longevity, dementia, and other disease states.

One of the more famous was a meta analysis of twelve studies looking at longevity. Greater adherence in this scale also showed lower incidence of Parkinson's disease, Alzheimer's disease as well as cardiovascular mortality.

This scale gave points for increased consumption of vegetables, fruits, legumes, cereals, fish, and moderate red wine consumption. While those who had "above the median" of red and processed meats and dairy were given zero points. Ultimately this was refined further with the use of monounsaturated fatty acids (olive oil) as the primary fat (60% or greater).

EPIC Study

Trichopoulou, and her colleagues began the European Prospective Investigation into Cancer and Nutrition (EPIC) study in 1994 after the pilot study in 1991. The study enrolled more than 521,000 participants from 23 centers in 10 western European countries, detailing diet, lifestyle, medical history, and vital signs.

They used a validated food frequency questionnaire of over 150 foods commonly consumed in Greece. "For this analysis, we focused on nine nutritional variables: vegetables, legumes, fruits and nuts, dairy products, cereals, meat and meat products, fish and seafood, monounsaturated to saturated lipid ratio, and ethanol." (11).

Conclusions of the EPIC study

A two point increase in the Mediterranean diet score led to a decrease in mortality of 14%.

Diet Pyramids

Diet pyramids were common in the 1990's . One of the more famous was from Oldways where they developed a pyramid in 1994 to describe the Mediterranean Diet. (12). This pyramid was based primarily on the diet from the Island of Crete and southern Italy from the 1960's.

Diet pyramids are of little use in scientific studies, as they don't quantify the amounts of foods consumed. Some argue that diet pyramids are a useful way to display the data.

Lyon Heart Study

The Lyon heart study was a randomized secondary trial testing the Mediterranean Diet against the French Prudent diet. After 46 months there were 1.24 per one hundred patients who had either a cardiac death or nonfatal infarction. This compared to 4.07 per one hundred who had the standard cardiac diet. They also noted that most patients, after a few years, were still following the Mediterranean Diet, showing that adoption and compliance was not difficult.

Obesity and the Mediterranean Diet

The Mediterranean Diet is useful not only for disease, but for weight management. The latest drugs for obesity are GLP-1 agonists (Wegovy, Ozempic) there is a clear benefit from polyunsaturated fatty acids (PUFA) and raising GLP-1. While obese patients have lower GLP-1 response to glucose than non-obese, the PUFAs in the Mediterranean diet provide an increase in GLP-1.

Further the polyphenolic compounds of the Mediterranean Diet provide another benefit. People with the highest intake of polyphenols (especially the flavonoids) were associated with an 11 percent decrease risk of developing type 2 Diabetes.

Finally the antioxidant rich Mediterranean Diet has been seen as a potent tool against the inflammatory cascade seen in obese patients.

Closer adherence to the Mediterranean Diet has been shown to have decreased rates of obesity, as well as better lipid profiles.

Weight Loss Surgery Patients

We took over 180 patients who had various forms of weight loss surgery and calculated their Mediterranean Diet Score. We then compared those scores to their postoperative weight loss after five years. Those patients who had a score of 5 or more all were in the greater than 50% of weight loss regardless of the type of weight loss surgery. Those patients who had a score of 0-3 were in the lowest quarter of weight loss or even weight regain. The score of 4 seemed to be all over the scale.

Type 2 Diabetes Mellitus and the Mediterranean Diet

The Mediterranean Diet has been found to both decrease the risk of type 2 Diabetes, but a potent reversal of type 2 diabetes. This occurs through lifestyle intervention, and has been found best for long term weight loss.

Current Adoption of the Mediterranean Diet

Click the link below to see the modern Med Diet score card.

MedDietScoreCard

Most papers have discussed the 9 point system and this is consistent throughout the literature in the last fifteen years. The scoring is reasonably simple, or can be completed through a validated food frequency questionnaire.

The Mediterranean Diet continues to be the most studied diet on the planet, with the most reproducible results for chronic diseases from obesity, diabetes, heart disease, dementia and autoimmune diseases.

Closer adherence to the Mediterranean Diet is associated with longevity.

REFERENCES:

  1. My podcast and writing about The Mediterranean Diet: https://www.yourdoctorsorders.com/2018/09/the-mediterranean-diet/
  2. https://www.sevencountriesstudy.com/about-the-study/history/
  3. Keys A, Aravanis C, Blackburn HW, Van Buchem FS, Buzina R,
  4. Djordjević BD, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, Lekos D,
  5. Monti M, Puddu V, Taylor HL. Epidemiological studies related to coronary
  6. heart disease: characteristics of men aged 40-59 in seven countries.
  7. Acta Med Scand Suppl. 1966;460:1-392. PMID: 5226858.
  8. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French
  9. paradox for coronary heart disease. Lancet. 1992 Jun
  10. 20;339(8808):1523-6. doi: 10.1016/0140-6736(92)91277-f. PMID: 1351198.
  11. Burr ML. Explaining the French paradox. J R Soc Health. 1995 Aug;115(4):217-9. doi: 10.1177/146642409511500404. PMID: 7562866.
  12. Iwasaki M, Murakami M, Ijiri Y, Shimizu M, Yamamoto J. Are all wines
  13. made from various grape varieties beneficial in the prevention of
  14. myocardial infarction and stroke? Future Sci OA. 2020 Nov 9;7(2):FSO649.
  15. doi: 10.2144/fsoa-2020-0098. PMID: 33437515; PMCID: PMC7787155.
  16. Keys, Margaret, and Keys, Ancel. Eat Well & Stay Well. United Kingdom, Doubleday, 1959. Revised 1963.
  17. Aboul-Enein BH, Puddy WC, Bernstein J. Ancel Benjamin Keys
  18. (1904-2004): His early works and the legacy of the modern Mediterranean
  19. diet. J Med Biogr. 2020 Aug;28(3):139-147. doi:
  20. 10.1177/0967772017727696. Epub 2017 Nov 14. PMID: 29134858.
  21. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou
  22. P, Polychronopoulos E, Vassilakou T, Lipworth L, Trichopoulos D. Diet
  23. and overall survival in elderly people. BMJ. 1995 Dec
  24. 2;311(7018):1457-60. doi: 10.1136/bmj.311.7018.1457. PMID: 8520331;
  25. PMCID: PMC2543726.
  26. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects
  27. of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009
  28. Jun 23;338:b2337. doi: 10.1136/bmj.b2337. PMID: 19549997; PMCID:
  29. PMC3272659.000
  30. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to
  31. Mediterranean diet and health status: meta-analysis. BMJ. 2008 Sep
  32. 11;337:a1344. doi: 10.1136/bmj.a1344. PMID: 18786971; PMCID: PMC2533524.
  33. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects
  34. of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009
  35. Jun 23;338:b2337. doi: 10.1136/bmj.b2337. PMID: 19549997; PMCID:
  36. PMC3272659.
  37. Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A,
  38. Helsing E, Trichopoulos D. Mediterranean diet pyramid: a cultural model
  39. for healthy eating. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1402S-1406S.
  40. doi: 10.1093/ajcn/61.6.1402S. PMID: 7754995.
  41. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.
  42. Mediterranean diet, traditional risk factors, and the rate of
  43. cardiovascular complications after myocardial infarction: final report
  44. of the Lyon Diet Heart Study. Circulation. 1999 Feb 16;99(6):779-85.
  45. doi: 10.1161/01.cir.99.6.779. PMID: 9989963.
  46. Gioia C, Lucchino B, Tarsitano MG, Iannuccelli C, Di Franco M.
  47. Dietary Habits and Nutrition in Rheumatoid Arthritis: Can Diet Influence
  48. Disease Development and Clinical Manifestations? Nutrients. 2020 May
  49. 18;12(5):1456. doi: 10.3390/nu12051456. PMID: 32443535; PMCID:
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