- Email: [email protected]
Mediterranean diet and physical activity: An intervention study. Does olive oil exercise the body through the mind?
4408
Letters to the Editor
one wonders if all of them were due to the lack of a true rise and/or fall of cTn. If not, why were they not categorized as AMI (either types 1 or 2 MI) given a cTn value NURL and presence of symptoms? Third, regarding outcomes measures, we question the implications of a delta cTn on clinical management. It is not entirely clear what percentage of patients were type 1 versus 2 MI. We stress that future studies should provide further detail into MI types, as clinical therapy might change. Finally, as noted by Cullen et al. in support of numerous other studies, it is important to understand that not all cTn assays are the same [5] and investigators cannot extrapolate findings from one study to another if using different cTn assays [2]. Studies should be required to define cTn kinetics across the different assays used, and the uniformity of this process will go a long way towards facilitating how clinical information is assimilated. In conclusion, the study by Cullen et al. provides important additional information to the ongoing research in the area of delta cTn in the early diagnosis of MI in the emergency department. Future studies looking at delta cTn should emphasize several points: 1) provide a detailed description of the study population and MI inclusion/exclusion
criteria; 2) harmonize adjudication process and analyze data along MI subtypes according to the Third Universal Definition of MI; and 3) harmonize the formulas utilized to calculate cTn delta values, with the goal of improving clinical specificity. These common practices will allow for a more global transparency of clinical and analytical data, paving the way for easier clinical implementation of cardiac troponin assays in routine practice.
References [1] Cullen L, Parsonage WA, Greenslade J, et al. Delta troponin for the early diagnosis of AMI in emergency patients with chest pain. Int J Cardiol 2013;168(3):2602–8. [2] Apple FS, Morrow DA. Delta cardiac troponin values in practice: are we ready to move absolutely forward to clinical routine? Clin Chem 2012;58(1):8–10. [3] Smith SW, Diercks DB, Nagurney JT, et al. Central versus local adjudication of myocardial infarction in a cardiac biomarker trial. Am Heart J 2013;165(3):273–9. [4] Thygesen K, Alpert JS, Jaffe AS, et al. Third Universal Definition of Myocardial Infarction. J Am Coll Cardiol 2012;60(16):1581–98. [5] Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574–81.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.035
Mediterranean diet and physical activity: An intervention study. Does olive oil exercise the body through the mind? Daniela Catalano, Guglielmo M. Trovato ⁎, Patrizia Pace, Giuseppe Fabio Martines, Francesca M. Trovato University of Catania, Department of Internal Medicine, Catania, Italy
a r t i c l e
i n f o
Article history: Received 4 April 2013 Accepted 4 May 2013 Available online 26 May 2013 Keywords: Mediterranean diet Physical activity Obesity Insulin resistance Cardiovascular risk
Sir, Several studies address how different features of unhealthy lifestyle and obesity are detrimental in cardiovascular disease [1–3]. The Mediterranean diet, assumed as a paradigm of healthy nutrition, is still studied, envisaging even pharmacological effects [4]. Other scientific contributions, without correct information, could be more negative than useful for the enhancement of healthier behavior: actually, in such studies, the successful counseling focused to secondary prevention-treatment should deserve more emphasis and dissemination. A recent investigation claims that an energyunrestricted Mediterranean diet supplemented with either extravirgin olive oil or nuts has a favorable role in cardiovascular death prevention [5]; nonetheless, no difference in the overall mortality
⁎ Corresponding author. Tel.: +39 0953781533; fax: +39 0953781549. E-mail address: [email protected] (G.M. Trovato).
among the three groups of treatment (with olive oil, mixed nuts and nothing) was demonstrated, and the slightly lower mortality for stroke and myocardial infarction is not so impressive facing with the identical all-cause mortality [5]. A missing information determines concerns [3], with the consequent question: toward which cause of mortality, apart from myocardial infarction and stroke, was there a shift in the subjects of the olive oil-nuts group? An elegant clinical intervention demonstrates an enhancement effect of olive oil on physical activity by a Mediterranean diet [6]. Beginning with the early clinical and epidemiological researches, the prominent role of olive oil in this nutritional pattern and its likely benefits are outlined [7,8]. Authors investigate also possible mood disturbance improvement that might explain changes in physical activity [6]. Since we currently manage our patients by lifestyle counseling and prescription of Mediterranean diet jointly with physical exercise [2,3], in this brief report we aim to display the changes of lifestyle, body weight and insulin resistance, assessed as HOMA-IR, and relationship, if any, among the effects of an intervention focused to the enhancement of healthier nutrition and of physical activity. The study included 92 (F 53, M 39) subjects, aged 49.86 ± 15.48 years, BMI 28.14 ± 5.53, referred for overweight-obesity assessment. Inclusion criteria were evidence of mild–moderate conditions associated with obesity (non-alcoholic-fatty-liver, i.e. NAFLD by ultrasound, arterial hypertension, dyslipidemia). Exclusion criteria were diabetes, renal insufficiency (GFR b 90 ml/min), cancer, heart failure N II NYHA class), chronic virus hepatitis and cirrhosis. A comprehensive clinical and laboratory assessment, including EKG, echocardiography, chest Xray, thyroid and abdomen ultrasound was provided. A counseling intervention (6 months) aimed at increasing adherence to Mediterranean diet score (AMDS; range 0–55) and at reducing sedentary habits, assessed by detailed physical activity reports (Baecke tool) was provided; both tools are described in detail elsewhere [9]. Suggestions
Letters to the Editor
and advice on individual “healthy” food purchase, storage and cooking were given. Reliable feedback and evidence of patients' adherence were obtained by scheduled dietician's interviews. Health psychology tools, i.e. GSE (General Self-Efficacy) and PSM (Psychological Stress Measure), validated in our population, were used. The use of organic certified olive oil was prescribed as a pivotal component of the diet and the olive oil intake (OOI g/day) was considered for the analysis of data. To find a predictive independent effect(s), if any, the modification of adherence to Mediterranean diet score (ΔAMDS), changes of olive oil intake (ΔOOI), level of instruction, Self-Efficacy (GSE) and Psychological Stress (PSM) were challenged by a multiple linear regression (MLR) model against the changes of physical activity, assessed by the Baecke tool (ΔBAECKE). A pre-intervention significant relationship between physical activity level, assessed by the Baecke questionnaire vs. AMDS (r = 0.615; p: b0.0001) but not vs. OOI (r = 0.087; p: 0.409) was observed. This relationship with physical activity level was maintained vs. AMDS (r = 0.456; p: b0.0001) but was not present vs. OOI (r = 0.131; p: 0.214) after the intervention. Changes of AMDS, OOI, BMI, Baecke and HOMA-IR show the benefits of the intervention (Table 1). The chosen model explains the variance (R2 0.134; p b 0.005) to the increase of physical activity: in greater detail, preintervention self-efficacy, the intervention increase of adherence to Mediterranean diet and of olive oil daily intake concur to explain independently the increase of physical activity (Table 2). These results suggest that the effectiveness of a dietary intervention is facilitated by a greater self-efficacy, that in this case encompasses the awareness of the benefits of the diet itself and its affordability in our population and in our Region. The prescribed diet was characterized also by the substitution of alimentary fat dressing with organic olive oil: independent relationship of the comprehensive Mediterranean diet profile and of olive oil intake with the increase of physical activity achieved by counseling is present. In this regard it must be stressed that several problems related to trading and use of olive oil are known: mostly important is the strong downward pressure on olive-oil quality using unscrupulous substances to remove sensory defects (extra-virgin olive oil cannot have undergone chemical manipulation) and contaminants. This is due mainly to aflatoxins, pesticide residuals and other pollutants. Similar problems are associated with alimentary nuts (almonds, walnuts, hazelnuts) [10]. For these reasons the use of organic certified olive oil should be warranted, always and also in clinical investigation, especially if it is easily and reliably available and at sustainable costs. The history of olive oil technology, culture and trade is ancient. Thales (624 BC–546 BC), the first Greek Philosopher and Scientist, was also involved in business. Aristotle explains that Thales reserved olive presses ahead of time at a discount only to rent them out at a high price when demand peaked, following his weather predictions of a particular good harvest.
Table 1 Comparison of BMI (body mass index), HOMA-IR (insulin resistance), adherence to Mediterranean diet score (AMDS), olive oil intake (OOI) g/da, and physical activity (assessed by the Baecke tool). Paired Student's t test: differences are all significant. 6 months lifestyle intervention changes. BMI AMDS OOI BAECKE HOMA
Before intervention
After intervention
t
p
28.14 ± 5.53 29.48 ± 4.61 26.00 ± 11.80 41.50 ± 4.98 2.47 ± 1.42
27.31 ± 5.02 31.95 ± 3.51 31.70 ± 12.70 43.97 ± 4.86 1.95 ± 1.14
3.213 − 9.798 − 6.465 − 7.813 5.109
0.002 b 0.0001 b 0.0001 b 0.0001 b 0.0001
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.034
4409
Table 2 Multiple regression model to explain physical activity changes, assessed by the Baecke tool (ΔBAECKE) by 6 months lifestyle counseling intervention. Changes of adherence to Mediterranean diet score (ΔAMDS), changes of olive oil intake (ΔOOI), GSE (general self-efficacy) and PSM (psychological stress measure), included as psychological preintervention measurements, explain independently and significantly the variance (R2 0.186; p b 0.003) to the increase of physical activity. The independent contribution of ΔAMDS to ΔBAECKE p b 0.043,of changes of olive oil intake (ΔOOI) p b 0.026 and, the contribution of GSE p b 0.016, are the three significant explaining independent variables. Multiple linear regression to ΔBAECKE Predictors Level of instruction GSE MSP ΔOOI ΔAMDS
R
R2
F
Sig.
0.431
0.186
3.932
0.003
β
p
−0.122 0.268 −0.082 − 0.230 0.203
0.237 0.016 0.444 0.026 0.043
Thales' objective in doing this was not to increase profits for himself but to prove to his citizens that science could be advantageous, contrary to what they thought. A well addressed intelligence boosts good business and health; differently, inactive body and mind slows down the hours and accelerates the years [3]. By our investigation links among behavior, diet, physical exercise and psychology are confirmed to be present, active and inter-related. This and other developed convincing evidence warrant the implementation of transferable and sustainable clinical strategies in human nutrition aimed at the prevention of cardiovascular risks. At last, hopefully, olive oil is like the truth: both always float on the top. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institution's Human Research Committee, according to: Shewan LG, Coats AJ. Adherence to ethical standards in publishing scientific articles: a statement from the International Journal of Cardiology. Int J Cardiol. 2012;161:124–5. This study has not received any funding resource. This report was in part presented at the 76th Scientific Sessions and Annual Meeting of the American Society for Nutrition, April 21–25, 2012. San Diego, CA. References [1] Carlsson AC, Wändell PE, Gigante B, Leander K, Hellenius ML, de Faire U. Seven modifiable lifestyle factors predict reduced risk for ischemic cardiovascular disease and all-cause mortality regardless of body mass index: a cohort study. Int J Cardiol 2013;168(2):946–52. [2] Trovato GM. Behavior, nutrition and lifestyle in a comprehensive health and disease paradigm: skills and knowledge for a predictive, preventive and personalized medicine. EPMA J 2012;3:8–21. [3] Gaglio M, Trovato GM, Vancheri F. True and false prevention of coronary disease. Recenti Prog Med 1981;71:207–34. [4] Siniorakis E, Arvanitakis S, Zarreas E, et al. Mediterranean diet: natural salicylates and other secrets of the pyramid. Int J Cardiol Jun 20 2013;166(2):538–9. [5] Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013;368:1279–90. [6] Kien CL, Bunn JY, Tompkins CL, et al. Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood. Am J Clin Nutr 2013;97:689–97. [7] Keys A, Menotti A, Karvonen MJ, et al. The diet and 15-year death rate in the seven countries study. Am J Epidemiol 1986;124:903–15. [8] Willett WC, Sacks F, Trichopoulou A, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 1995;61(6 Suppl):1402S–6S. [9] Trovato GM, Catalano D, Ragusa A, et al. Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy. Ren Fail 2013;35:615–23. [10] Moore JC, Spink J, Lipp M. Development and application of a database of food ingredient fraud and economically motivated adulteration from 1980 to 2010. J Food Sci 2012;77:R118–26.
Letters to the Editor
one wonders if all of them were due to the lack of a true rise and/or fall of cTn. If not, why were they not categorized as AMI (either types 1 or 2 MI) given a cTn value NURL and presence of symptoms? Third, regarding outcomes measures, we question the implications of a delta cTn on clinical management. It is not entirely clear what percentage of patients were type 1 versus 2 MI. We stress that future studies should provide further detail into MI types, as clinical therapy might change. Finally, as noted by Cullen et al. in support of numerous other studies, it is important to understand that not all cTn assays are the same [5] and investigators cannot extrapolate findings from one study to another if using different cTn assays [2]. Studies should be required to define cTn kinetics across the different assays used, and the uniformity of this process will go a long way towards facilitating how clinical information is assimilated. In conclusion, the study by Cullen et al. provides important additional information to the ongoing research in the area of delta cTn in the early diagnosis of MI in the emergency department. Future studies looking at delta cTn should emphasize several points: 1) provide a detailed description of the study population and MI inclusion/exclusion
criteria; 2) harmonize adjudication process and analyze data along MI subtypes according to the Third Universal Definition of MI; and 3) harmonize the formulas utilized to calculate cTn delta values, with the goal of improving clinical specificity. These common practices will allow for a more global transparency of clinical and analytical data, paving the way for easier clinical implementation of cardiac troponin assays in routine practice.
References [1] Cullen L, Parsonage WA, Greenslade J, et al. Delta troponin for the early diagnosis of AMI in emergency patients with chest pain. Int J Cardiol 2013;168(3):2602–8. [2] Apple FS, Morrow DA. Delta cardiac troponin values in practice: are we ready to move absolutely forward to clinical routine? Clin Chem 2012;58(1):8–10. [3] Smith SW, Diercks DB, Nagurney JT, et al. Central versus local adjudication of myocardial infarction in a cardiac biomarker trial. Am Heart J 2013;165(3):273–9. [4] Thygesen K, Alpert JS, Jaffe AS, et al. Third Universal Definition of Myocardial Infarction. J Am Coll Cardiol 2012;60(16):1581–98. [5] Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574–81.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.035
Mediterranean diet and physical activity: An intervention study. Does olive oil exercise the body through the mind? Daniela Catalano, Guglielmo M. Trovato ⁎, Patrizia Pace, Giuseppe Fabio Martines, Francesca M. Trovato University of Catania, Department of Internal Medicine, Catania, Italy
a r t i c l e
i n f o
Article history: Received 4 April 2013 Accepted 4 May 2013 Available online 26 May 2013 Keywords: Mediterranean diet Physical activity Obesity Insulin resistance Cardiovascular risk
Sir, Several studies address how different features of unhealthy lifestyle and obesity are detrimental in cardiovascular disease [1–3]. The Mediterranean diet, assumed as a paradigm of healthy nutrition, is still studied, envisaging even pharmacological effects [4]. Other scientific contributions, without correct information, could be more negative than useful for the enhancement of healthier behavior: actually, in such studies, the successful counseling focused to secondary prevention-treatment should deserve more emphasis and dissemination. A recent investigation claims that an energyunrestricted Mediterranean diet supplemented with either extravirgin olive oil or nuts has a favorable role in cardiovascular death prevention [5]; nonetheless, no difference in the overall mortality
⁎ Corresponding author. Tel.: +39 0953781533; fax: +39 0953781549. E-mail address: [email protected] (G.M. Trovato).
among the three groups of treatment (with olive oil, mixed nuts and nothing) was demonstrated, and the slightly lower mortality for stroke and myocardial infarction is not so impressive facing with the identical all-cause mortality [5]. A missing information determines concerns [3], with the consequent question: toward which cause of mortality, apart from myocardial infarction and stroke, was there a shift in the subjects of the olive oil-nuts group? An elegant clinical intervention demonstrates an enhancement effect of olive oil on physical activity by a Mediterranean diet [6]. Beginning with the early clinical and epidemiological researches, the prominent role of olive oil in this nutritional pattern and its likely benefits are outlined [7,8]. Authors investigate also possible mood disturbance improvement that might explain changes in physical activity [6]. Since we currently manage our patients by lifestyle counseling and prescription of Mediterranean diet jointly with physical exercise [2,3], in this brief report we aim to display the changes of lifestyle, body weight and insulin resistance, assessed as HOMA-IR, and relationship, if any, among the effects of an intervention focused to the enhancement of healthier nutrition and of physical activity. The study included 92 (F 53, M 39) subjects, aged 49.86 ± 15.48 years, BMI 28.14 ± 5.53, referred for overweight-obesity assessment. Inclusion criteria were evidence of mild–moderate conditions associated with obesity (non-alcoholic-fatty-liver, i.e. NAFLD by ultrasound, arterial hypertension, dyslipidemia). Exclusion criteria were diabetes, renal insufficiency (GFR b 90 ml/min), cancer, heart failure N II NYHA class), chronic virus hepatitis and cirrhosis. A comprehensive clinical and laboratory assessment, including EKG, echocardiography, chest Xray, thyroid and abdomen ultrasound was provided. A counseling intervention (6 months) aimed at increasing adherence to Mediterranean diet score (AMDS; range 0–55) and at reducing sedentary habits, assessed by detailed physical activity reports (Baecke tool) was provided; both tools are described in detail elsewhere [9]. Suggestions
Letters to the Editor
and advice on individual “healthy” food purchase, storage and cooking were given. Reliable feedback and evidence of patients' adherence were obtained by scheduled dietician's interviews. Health psychology tools, i.e. GSE (General Self-Efficacy) and PSM (Psychological Stress Measure), validated in our population, were used. The use of organic certified olive oil was prescribed as a pivotal component of the diet and the olive oil intake (OOI g/day) was considered for the analysis of data. To find a predictive independent effect(s), if any, the modification of adherence to Mediterranean diet score (ΔAMDS), changes of olive oil intake (ΔOOI), level of instruction, Self-Efficacy (GSE) and Psychological Stress (PSM) were challenged by a multiple linear regression (MLR) model against the changes of physical activity, assessed by the Baecke tool (ΔBAECKE). A pre-intervention significant relationship between physical activity level, assessed by the Baecke questionnaire vs. AMDS (r = 0.615; p: b0.0001) but not vs. OOI (r = 0.087; p: 0.409) was observed. This relationship with physical activity level was maintained vs. AMDS (r = 0.456; p: b0.0001) but was not present vs. OOI (r = 0.131; p: 0.214) after the intervention. Changes of AMDS, OOI, BMI, Baecke and HOMA-IR show the benefits of the intervention (Table 1). The chosen model explains the variance (R2 0.134; p b 0.005) to the increase of physical activity: in greater detail, preintervention self-efficacy, the intervention increase of adherence to Mediterranean diet and of olive oil daily intake concur to explain independently the increase of physical activity (Table 2). These results suggest that the effectiveness of a dietary intervention is facilitated by a greater self-efficacy, that in this case encompasses the awareness of the benefits of the diet itself and its affordability in our population and in our Region. The prescribed diet was characterized also by the substitution of alimentary fat dressing with organic olive oil: independent relationship of the comprehensive Mediterranean diet profile and of olive oil intake with the increase of physical activity achieved by counseling is present. In this regard it must be stressed that several problems related to trading and use of olive oil are known: mostly important is the strong downward pressure on olive-oil quality using unscrupulous substances to remove sensory defects (extra-virgin olive oil cannot have undergone chemical manipulation) and contaminants. This is due mainly to aflatoxins, pesticide residuals and other pollutants. Similar problems are associated with alimentary nuts (almonds, walnuts, hazelnuts) [10]. For these reasons the use of organic certified olive oil should be warranted, always and also in clinical investigation, especially if it is easily and reliably available and at sustainable costs. The history of olive oil technology, culture and trade is ancient. Thales (624 BC–546 BC), the first Greek Philosopher and Scientist, was also involved in business. Aristotle explains that Thales reserved olive presses ahead of time at a discount only to rent them out at a high price when demand peaked, following his weather predictions of a particular good harvest.
Table 1 Comparison of BMI (body mass index), HOMA-IR (insulin resistance), adherence to Mediterranean diet score (AMDS), olive oil intake (OOI) g/da, and physical activity (assessed by the Baecke tool). Paired Student's t test: differences are all significant. 6 months lifestyle intervention changes. BMI AMDS OOI BAECKE HOMA
Before intervention
After intervention
t
p
28.14 ± 5.53 29.48 ± 4.61 26.00 ± 11.80 41.50 ± 4.98 2.47 ± 1.42
27.31 ± 5.02 31.95 ± 3.51 31.70 ± 12.70 43.97 ± 4.86 1.95 ± 1.14
3.213 − 9.798 − 6.465 − 7.813 5.109
0.002 b 0.0001 b 0.0001 b 0.0001 b 0.0001
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.034
4409
Table 2 Multiple regression model to explain physical activity changes, assessed by the Baecke tool (ΔBAECKE) by 6 months lifestyle counseling intervention. Changes of adherence to Mediterranean diet score (ΔAMDS), changes of olive oil intake (ΔOOI), GSE (general self-efficacy) and PSM (psychological stress measure), included as psychological preintervention measurements, explain independently and significantly the variance (R2 0.186; p b 0.003) to the increase of physical activity. The independent contribution of ΔAMDS to ΔBAECKE p b 0.043,of changes of olive oil intake (ΔOOI) p b 0.026 and, the contribution of GSE p b 0.016, are the three significant explaining independent variables. Multiple linear regression to ΔBAECKE Predictors Level of instruction GSE MSP ΔOOI ΔAMDS
R
R2
F
Sig.
0.431
0.186
3.932
0.003
β
p
−0.122 0.268 −0.082 − 0.230 0.203
0.237 0.016 0.444 0.026 0.043
Thales' objective in doing this was not to increase profits for himself but to prove to his citizens that science could be advantageous, contrary to what they thought. A well addressed intelligence boosts good business and health; differently, inactive body and mind slows down the hours and accelerates the years [3]. By our investigation links among behavior, diet, physical exercise and psychology are confirmed to be present, active and inter-related. This and other developed convincing evidence warrant the implementation of transferable and sustainable clinical strategies in human nutrition aimed at the prevention of cardiovascular risks. At last, hopefully, olive oil is like the truth: both always float on the top. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institution's Human Research Committee, according to: Shewan LG, Coats AJ. Adherence to ethical standards in publishing scientific articles: a statement from the International Journal of Cardiology. Int J Cardiol. 2012;161:124–5. This study has not received any funding resource. This report was in part presented at the 76th Scientific Sessions and Annual Meeting of the American Society for Nutrition, April 21–25, 2012. San Diego, CA. References [1] Carlsson AC, Wändell PE, Gigante B, Leander K, Hellenius ML, de Faire U. Seven modifiable lifestyle factors predict reduced risk for ischemic cardiovascular disease and all-cause mortality regardless of body mass index: a cohort study. Int J Cardiol 2013;168(2):946–52. [2] Trovato GM. Behavior, nutrition and lifestyle in a comprehensive health and disease paradigm: skills and knowledge for a predictive, preventive and personalized medicine. EPMA J 2012;3:8–21. [3] Gaglio M, Trovato GM, Vancheri F. True and false prevention of coronary disease. Recenti Prog Med 1981;71:207–34. [4] Siniorakis E, Arvanitakis S, Zarreas E, et al. Mediterranean diet: natural salicylates and other secrets of the pyramid. Int J Cardiol Jun 20 2013;166(2):538–9. [5] Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013;368:1279–90. [6] Kien CL, Bunn JY, Tompkins CL, et al. Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood. Am J Clin Nutr 2013;97:689–97. [7] Keys A, Menotti A, Karvonen MJ, et al. The diet and 15-year death rate in the seven countries study. Am J Epidemiol 1986;124:903–15. [8] Willett WC, Sacks F, Trichopoulou A, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 1995;61(6 Suppl):1402S–6S. [9] Trovato GM, Catalano D, Ragusa A, et al. Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy. Ren Fail 2013;35:615–23. [10] Moore JC, Spink J, Lipp M. Development and application of a database of food ingredient fraud and economically motivated adulteration from 1980 to 2010. J Food Sci 2012;77:R118–26.