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Functional Food Security and the Heart

Ram B Singh, Sergey Shastun, Sergey Chibisov, Arunporn Itharat, Fabien De Meester, Douglas W Wilson, Ghazi Halabi, Rie Horiuchi, Toru Takahashi

Ram B Singh, Arunporn Itharat, Halberg Hospital and Research Institute, Moradabad, India
Sergey Shastun, Sergey Chibisov, People’s Friendship University of Russia, Moscow, Russia
Arunporn Itharat, Thamasat University, Pathumthani, Thailand
Fabien De Meester, The TsimTsoum Institute, Krakow, Poland
Douglas W Wilson, Durham University, Durham, the United Kingdom
Ghazi Halabi, Medical 2000 Hospital, Choueifat, Labnon
Rie Horiuchi, Department of Food science and Nutrition, Faculty of human Environmental Sciences, Mukagawa Women's University, Japan
Toru Takahashi, Graduate School of human Environment Medicine, Fukuoka, Women's University, Fukuoka, Japan

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Ram B Singh, MD, FICC, Halberg Hospital and Research Institute, Moradabad(UP), 244001, India.
Email: rbs@tsimtsoum.net
Telephone: +91-9997794102

Received: October 1, 2016
Revised: October 25, 2016
Accepted: October 28, 2016
Published online: February 24, 2017

ABSTRACT

Increased demand for food security has made the world blind about the utility and necessity of functional food security characterized with food diversity and adequacy of nutrients. Food diversity may have been the major factor causing adequacy of nutrients in the Paleolithic diet 40,000 years ago. The increased prevalence of cardiovascular diseases (CVDs) and type 2 diabetes throughout the world, are closely linked to food security via westernized dietary patterns, physical inactivity, and rapid increase in the rate of obesity. The World Heart Federation and the World Health Organization are working hard to bring down the death rates due to CVDs, at least 25% by 2025.There is substantial evidence that increased intake of functional foods can bring about a significant decline in the epidemic of CVDs and type 2 diabetes, resulting in health promotion. It is possible that functional food security in conjunction with regular physical activity, can maintain the normal physiology and metabolism of our bodies, resulting into decline in CVDs and type 2 diabetes.

Key words: Foods; Dietary patterns; Western diet; Prudent diet

© 2017 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Singh RB, Shastun S, Chibisov S, Itharat A, De Meester F, Wilson DW, Halabi G, Horiuchi R, Takahashi T. Functional Food Security and the Heart. Journal of Cardiology and Therapy 2016; 3(6): 599-607 Available from: URL: http: //www.ghrnet.org/index.php/jct/article/view/1858

INTRODUCTION

High technology cardiac care and highly effective drug therapy have been responsible for causing a significant decline in deaths from cardiovascular diseases (CVDs), which could also be partly due to improved diet and lifestyle[1-3]. Reduction in the intake of saturated fat, salt and sugar, and increased consumption of functional foods; fruits, vegetables and whole grains, as well as some increase in physical activity and decrease in tobacco intake may have contributed to decline in CVDs in high income countries[1-6]. However, this decreasing trend in CVDs is partly offset by rising obesity and type 2 diabetes, and poor adherence to lifestyle changes[6-8]. Increased availability of statins for treatment of coronary artery disease(CAD) at affordable cost is the greatest single discovery which has improved the outcome among patients with CAD. The prevalence of high cholesterol, blood pressure and smoking have decreased in developed countries, with some impact in some middle-income countries[1-5].

The European Union agenda; “from farm to fork” approach involving organic farming initiatives, sustainable agriculture, and community-supported agriculture that is also promoted by some in the agriculture, food service, and restaurant communities, appears to be important to provide functional food security in European union countries. The global burden of diseases study has also emphasized on the role of diet and lifestyle factors to explain the causes of deaths due to CVDs and other chronic disease in 10 countries[7] (Figure 1). However, we are still ignorant about functional food security characterized by diversity and adequacy of nutrients that may have been beneficial and abundant in the Paleolithic diet 40,000 years ago because of food diversity[1-3]. The increased prevalence of CVDs and type 2 diabetes throughout the world has been closely linked to food security via westernized dietary patterns, physical inactivity, and rapid increase in the rate of obesity. In this mini review, we emphasize on the evidence for the role of functional foods security in the prevention of CVDs and type 2 diabetes[1-4].

Figure 1 Dietary factors and other risk factors in relation to mortality in the global burden of disease study (Reference 7).

THE EPIDEMIC OF HEART ATTACKS

The World Heart Federation pointed out on the heart of 25 by 25 for achieving the goal of reducing global and regional premature deaths from CVDs and published a modeling study in association with the American Heart Association[8]. The challenges of prevention of CVDs have also been addressed by a scientific statement of the International College of Cardiology who give greater emphasis on functional food security[9]. In South-West Asia, where undernutrition was common about 50 years ago, metabolic syndrome has become quite common, due to rapid economic development and food security[4]. In a cross-sectional survey from various corners of India among 6,940 subjects (3,433 women and 3,507 men) aged 25 years and above, the overall prevalence of obesity (BMI 25 kg/m2 and above) was 6.8% (7.8 vs 6.2%, p < 0.05) and overweight (BMI 23.0-24.9 kg/m2) 33.5% (35.0 vs 32.0%, p < 0.05) among women and men, respectively[10]. In South Asia, central obesity and insulin resistance develops rapidly after the body mass index goes beyond 23 Kg/M 2, which is considered a paradox because these populations turn highly susceptible to develop CAD and type 2 diabetes[4,11-13]. In a recent cohort study of 2.3 million adolescents, during 42,297,007 person-years of follow-up, 2,918 of 32,127 deaths (9.1%) were from CVDs, including 1,497 from heart attack, 528 from stroke, and 893 from sudden death. A BMI in the 50th to 74th percentiles, which is within the accepted normal range during adolescence, was associated with increased CVD and all-cause mortality after 40 years of follow-up[14]. Overweight and obesity among parents and offspring may be also associated with increased cardiovascular mortality via epigenetic inheritance in adulthood[15].

In the United Nations High Level Meeting (UN HLM), key targets were proposed to reach by 2025 to reduce the risk of premature death due to CVDs and other chronic diseases by 25% by 2025[8]. This proposal requires that CVDs and its risk factors be aggressively addressed because it is the largest contributor to global mortality, accounting for nearly half of the 36 million annual deaths[7]. Roth et al, reported estimates to indicate how reduction of selected risk factors would affect CVD mortality for different regions in 188 countries up to the year of 2025[16]. Risk factors were projected to 2025 assuming that current trends continue. If United Nations risk factor targets are achieved in the year 2025, counterfactual scenarios would be then constructed indicating CVD premature mortality, adjusting for joint effects of risk factors. It has been estimated that 7.8 million premature CVD deaths would occur in 2025 if current risk factor trends continue[16]. Premature CVD deaths would be reduced to 5.7 million if these risk factors targets are achieved as a result of a 26% reduction for men and a 23% reduction for women in the global risk of premature CVD death. The largest risk reduction would be achieved if the prevalence of hypertension is declined, followed by a reduction in tobacco smoking for men and obesity for women. Gender and region were important factors for meeting all risk factor targets on CVD mortality.

It is possible that United Nations target of a 25% reduction in premature CVD mortality by the year 2025 appears achievable for some countries. However, more aggressive risk factor targets may be required if all regions are to reach this goal. Many countries will see no change or even an increase in premature CVD mortality if there is no decrease in CVD risk factors. The Global Cardiovascular Disease Taskforce with the help from Institute for Health Metrics developed region specific estimates, showing that > 5 million premature CVD deaths among men and 2.8 million among women are projected worldwide by 2025[16]. These deaths may be decreased to 3.5 million and 2.2 million, respectively, if risk factor targets for blood pressure, diabetes mellitus, obesity and tobacco use, are achieved by various countries and regions because global risk factor targets have variable effects, depending on region. It is known that, United Nations targets for reducing systolic blood pressure and tobacco use have more substantial effects on future occurrence of CVDs, compared with maintaining current levels of body mass index and fasting plasma glucose. It seems that reductions in multiple risk factors has the largest impact for almost all regions and these goals can be accomplished only if all the health professionals and governments in each country set priorities, implement cost-effective population wide strategies, and collaborate in public-private partnerships across multiple sectors; including Ministry of health, Agriculture, Food and Nutrition, Sports and Housing.

FOOD SECURITY AND EMERGENCE OF CHRONIC DISEASES

The world population is currently (2016) growing at a rate of around 1.13% per year and the current average population change is estimated at around 80 million per year. The United Nations estimated that the world's population will increase from 7.4 billion in 2016 to 8.1 billion in 2025, with most growth in developing countries and more than half in Africa. By 2050, the world population will reach 9.6 billion. There is marked reduction in death rates due to undernutrition and an emergence of morbidity and mortality due to CVDs and other chronic diseases[7]. Nutrition in transition from poverty to affluence indicate that there is increased availability of Western foods resulting in food security for most populations of the world[1-4,7]. (Figure 1). However, as per IHME News, USA, Oct 2015,“The biggest cause of early death in the world is not smoking or alcohol - it's what you eat.” (Staufenberg J, Oct 2015). This observation is supported by intensive research because both undernutrition due to food scarcity and over-nutrition due to food security are associated with a significant increase in metabolic syndrome which is a risk factor of death due to CVDs, diabetes and cancer[6-9].

The world's population suffering from under-nourishment is around 12.5%, lower from almost half of the world’s population in 1947 as per records of FAO. However, 868 million people remain hungry, an estimated 2 billion people suffer from one or more micronutrient deficiencies and an estimated 1.4 billion people are overweight, of whom 500 million are obese, which predisposes to type 2 diabetes and CVDs. Therefore, food security has been the priority of most of the governments and health agencies, without much consideration for functional foods. The FAO and WHO were short of hard evidence that providing western type foods can enhance life expectancy for hardly 60 years or more. It may be associated with unhealthy diet, physical inactivity, tobacco use and alcohol consumption, which may cause emergence of obesity, metabolic syndrome, diabetes, hypertension, atherosclerosis, carcinogenesis, degenerative diseases of brain and osteoporosis[1,7-16]. The Western-type foods are: all refined, high-energy, salty, sugary and low-nutrient foods; red meat, preserved and processed meats, bread, biscuits, candies, cookies, white chocolate, high-sugar foods and syrups may have adverse effects on health, resulting in to hypertension, heart attack and stroke. All rapidly absorbed foods, deep fried foods, red meat, preserved, salted meats and snacks, plastic-containing foods, Chinese rice, trans-fat and too much of -6 and saturated fat and trans-fat-rich foods are also known to predispose to CVDs and other chronic diseases (Figure 2).

Figure 2 Transition from poverty to Food Security and Functional Food Security leading to health promotion and prevention of obesity.

FUNCTIONAL FOOD SECURITY AND THE HEART

Functional food security means increased availability of foods that are rich in protective nutrients and low in energy and nutrients having beneficial effects[17-20]. These foods can enhance life expectancy, to 68 years and more. The functional food security may be associated with other health behaviors; health education, no tobacco, moderate activity, moderation in alcohol intake and normal waist/hip ratio or normal waist circumference, they can lead to a reduction in chronic diseases mentioned above[4,7,17-20]. Functional foods and Functional Farming (4 F) may be defined as foods which contain certain nutrients that can address some physiological mechanisms in our bodies, thereby providing benefits[18-20]. Functional farming (FF) produces functional foods either by appropriate soil, or by genetic engineering or plant breeding[20]. Functional foods security in conjunction with increased physical activity are effective measures, and weight loss is the main predictor of the success in the prevention of diabetes and CVDs including heart attacks[1-4,17-20].

Some of the common functional foods are given in Table 1 and 2. The concept of functional foods may be easy to understand if we know about Paleolithic diet and changes in the diet that have occurred in the last 40,000 years during transition from Homo sapiens to modern men (Figure 3).

Table 1 Functional food package for prevention of metabolic syndrome.(For vegetarian, replace with soya bean, cottage cheese and yogurt).
Functional foodsAmount, g/dayFoodsNutrient/Mechanism
Fruits200-300Apple, grapes, guava, berriesFlavonoids, vit C, flavonoids
Vegetables200-300Green leaves, gourdsFlavonoids, carotenoids
Nuts30-50Walnuts, almond, peanutsAmino acids, w-3 in walnut, low glycemic index, MUFA
Whole grains400-500Gram, beans, peas, millets soybean, pulses, porridgeFlavonoids, amino acids, complex carbohydrates
Fish, sea foods50-100gSalmon, any oily fish, e g mackerelw-3, amino acids, selenium, CoQ10
Poultry50-100Egg-quail & hen, chicken, duckAmino acids,
Curd/yogurt100-200Prebiotic, probioticsImmunity, gut microbiome
Spices10-20Turmeric, fenugreek, cumin, corianderFlavonoids, minerals
Fats and oils30-100Olive, mustard/canolaFlavonoids, w-3, MUFA
Note. Olive and rape seed oil are known to decrease CVDs, diabetes and all-cause mortality.

Table 2 Blend of fats and oils with possible beneficial effects on health.
Oils, /100 gSaturated fat-6 fat-3 fatMUFAProtective nutrient
Olive oil (50%)77.50.7536Flavonoids, MUFA
Rape seed/canola oil (20%)1.44.11213w-3, MUFA
Rice bran oil (10%)2.53.40.213.8Oryzenol
Sesame oil(10%)1.540.14Phytosterol
Flex seed oil(10%)1.10.665.51.6w-3, 54%
Blended oil= total 100.13 g13.519.678.5658.4w-6/w-3 ratio = 2.29, resveratrol, oryzenol, phytosterol
Note. Olive oil and rape seed oil are known to decrease cardiovascular diseases, diabetes and all-cause mortality. No such evidence for other oils. MUFA=monounsaturated fatty acids.

Figure 3Changes in the nutrient content of evolutionary diet and emergence of chronic diseases.

Observational studies have also shown that diets rich in vegetables and low in red meat and whole-fat dairy products are associated with a decreased risk of diabetes and heart attacks, whereas dietary patterns rich in red meats, processed foods, refined grains, and sweets which are rich in bread, biscuits, pizza, candies and syrups, increase risk of diabetes and CVDs[1-7,21,22]. In a cohort study, 512,891 adults, aged 30-79 years, were recruited from China[22]. During 3.2 million person-years of follow-up, 5,173 deaths from CVDs, 2,551 incident major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3,523 intracerebral hemorrhages were recorded among the 451,665 participants without a history of CVDs or anti-hypertensive treatment at the outset. Those subjects who ate fresh fruit daily had lower systolic blood pressure (by 4.0 mmHg) and blood glucose concentrations [by 0.5 mmol/L (9.0 mg/dL)] (p < 0.001)[16]. The adjusted hazard ratios for daily consumption versus non-consumption were significant for CVD death, and for incident major coronary events, ischemic strokes, and intracerebral hemorrhages, respectively. Overall, 18.0% of participants reported consuming fresh fruit daily. A higher level of fruit consumption was associated with lower blood pressure and blood glucose concentrations and, largely independent of these and other dietary and non-dietary factors, with a significantly lower risk of major CVDs[22]. The traditional Mediterranean-style diet, characterized by high consumption of functional foods (vegetables, legumes, whole grains, fruits, nuts, and olive oil), moderate consumption of fish and wine, and low consumption of red and processed meat and whole-fat dairy products, is widely recognized as a healthy dietary pattern, rich in functional foods, which is similar to Paleolithic diet (Figure 3)[1,17,18-24]. Further cohort studies from Southern Europe also suggested a lower incidence of CVDs and diabetes with increasing adherence to the Mediterranean-style diet in previously healthy individuals[23] or myocardial infarction survivors[24].

In a case control study among 287 women, aged 22-69 years and 649 controls, the risk of acute myocardial infarction(AMI) was directly associated with frequency of consumption of meat (odds ratio 1.5 for upper v lower thirds of consumption), ham and salami (1.4), butter (2.3), total fat added to food (1.6), and coffee (2.8)[25]. Assessment of risk with functional food revealed significant inverse association for fish (0.6), carrots (0.4), green vegetables (0.6), and fresh fruit (0.4). The risk was below one for moderate alcohol consumption (0.7) and above one for heavier intake (1.2) indicating that alcoholism could be a risk factor of AMI. It is possible that frequency of consumption of functional foods and western type foods may provide useful indicators of the risk of AMI. It is likely that certain foods; fish, moderate alcohol, or vegetables and fruits may have an independent protective role against risk of AMI[25].

In another case study involving 342 subjects (171 patients with AMI and 171 matched controls) six food items were assessed that were considered protective; olive oil, fiber, fruits, vegetables, fish and alcohol[26]. The findings showed that the higher the score of food intakes, the lower the odds ratio of myocardial infarction. A significant linear trend was apparent after adjustment for the main cardiovascular risk factors. For each additional point in the a priori Mediterranean pattern (observed range: 9-38) the odds ratio (95 % confidence intervals) was 0.92 (0.86-0.98). This estimate was 0.55 (0.42-0.73) when we used the post hoc pattern (range: 0-8).The result indicated that a Mediterranean diet (that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products) can be an effective measure for reducing the risk of myocardial infarction. Our results support the exclusion of refined cereals with a high glycemic load as healthy elements of this pattern. In the further case study involving 760 patients, below age 79 years, have non-fatal AMI, and 682 patients have acute conditions unrelated to diet[27]. Increasing intake of anthocyanidins (OR = 0.45, 95% CI 0.26-0.78 for the highest vs the lowest quintile, (Ptrend = 0.003) and flavonols (OR = 0.65, 95% CI 0.41-1.02, (Ptrend = 0.02)) were significant protective factors against AMI[27]. It is possible that increased intake of anthocyanidins reduced the risk of AMI even after allowance for alcohol, fruit and vegetables, supporting a real inverse association between this class of flavonoids and AMI risk.

In a case study among 54 patients with AMI and 85 matched controls, the incidence of lipoprotein (a) excess (> 30 mg/dL; 42.6 vs 24.7%; p < 0.05) and mean concentration of lipoprotein (a) (Lp[a], 6.4 mg/dl, 95% confidence interval: 2.8-10.5; p < 0.05) was significantly greater in the AMI group compared with control subjects. Mean total cholesterol and triglycerides were significantly higher and mean nitrite level lower in the study group as compared with the control group. There was a significant greater incidence of cardiac events in the second quarter of the day compared with the fourth quarter. Lp (a), triglycerides, blood glucose, plasma insulin, malondialdehyde, diene conjugates, TBARS and TNF-alpha and IL-6 levels, which were significantly greater during the acute phase, showed a significant decline and serum nitrite and coenzyme Q demonstrated an increase at 4 weeks of follow-up when the acute reactions evoked by MI had been controlled. Large breakfasts were a predisposing factor for cardiac events in the second quarter of the day and it was significantly associated with metabolic reactions. The findings indicate that acute reactions as a result or as circadian rhythms appear to be important in the pathogenesis of AMI-associated complications and that a large breakfast in association with nitrite deficiency may further trigger the circadian rhythms[29].

In another case-control study involving 202 patients with AMI, there was a significant (p < 0.02) increase in cardiac events in the second quarter of the day compared to other quarters, respectively (16.8%, 41.0%, 13.8%, 28.2% per quarter) which was mostly after a heavy breakfast or dinner[30]. Neuropsychological mechanisms were observed as follows: emotional stress (45.5%), sleep deprivation (27.7%), cold climate (29.2%), hot climate (24.7%), large meals (47.5%) and physical exertion (31.2%). These triggering factors are known to enhance sympathetic activity and decrease vagal tone, resulting in an increased secretion of plasma cortisol, noradrenaline, aldosterone, angiotension-converting enzyme (ACE), interleukin (IL)-1, -2, -6, -18, and tumor necrosis factor-alpha (TNF-alpha), all of which are pro-inflammatory agents. There is also a deficiency in the serum levels of vitamin A, E, and C and magnesium, potassium, melatonin, and IL-10 (an anti-inflammatory agent). In our study, we found a decrease in magnesium, potassium, vitamin A, E, C and beta carotene combined with an increase in thiobarbituric acid-reactive substances (TBARS), MDA and diene conjugates, TNF-alpha and IL-6, all of which are indicators of oxidative damage and pro-inflammatory activity, respectively[29,30].

The relationship between dietary patterns and risk of acute coronary syndrome (ACS) was examined in a standardized case-control study INTERHEART, involving participants from 52 countries[31]. Using the principle-component analysis technique, the authors identified 3 major dietary patterns; Oriental (high intake of tofu and soy and other sauces), Western (high in fried foods, salty snacks, eggs, and meat), and prudent (high in fruit and vegetables). Consistent with previous studies in single within-population cohort studies, the authors found an inverse association between the prudent pattern score and risk of ACS and a significant positive association between the Western pattern score and increased risk of ACS. The Oriental pattern was not significantly associated with risk. The investigators constructed a dietary risk score based on 7 food items on the food-frequency questionnaire (meat, salty snacks, fried foods, fruits, green leafy vegetables, cooked vegetables, and other raw vegetables) and found that a higher score (indicating a poor diet) was strongly associated with ACS risk: Those in the highest quartile of the score had nearly 2-fold increased risk, even after adjustment for established coronary risk factors. In sensitivity analyses, the investigators found a consistent association for the composite diet score between men and women and across different regions of the world (North America, western Europe, Australia, central Europe, Middle East, Africa, south Asia, southeast Asia, China, and South America). On the basis of an arbitrary cut point of the score (top 3 quartiles versus the bottom quartile), the investigators estimated that 30% of MI could be explained by unhealthy diets worldwide. Although Western-style changes in food patterns are widely believed to adversely influence risk of chronic diseases, few epidemiological studies have directly linked dietary patterns and mortality from coronary heart disease. The INTERHEART study is the first large study to quantify eating patterns in all geographic regions of the world. It provides evidence that despite different food habits in various populations, reproducible patterns can be found in diverse regions of the world. These findings are important because there has been a concern that dietary patterns derived through a data-driven approach such as principle-component analysis may be highly unstable and non-reproducible because of very different eating habits in different populations.

In recent years, dietary-patterning analysis has been increasingly used as an alternative method to traditional single-nutrient analysis because it can assess cumulative effects of the overall nutrients in the diet. Habitual intake patterns are typically quantified by statistical methods such as factor or cluster analysis or diet-quality indexes based on prevailing dietary recommendations or healthful traditional diets eg, the Mediterranean diet, and Indo-Mediterranean diet. Principle-component analysis is commonly used to define dietary patterns using food consumption information to identify common underlying dimensions (factors or patterns) of food intake. The method aggregates specific food items based on the degree to which these food items are correlated with each other. A summary score for each pattern is then derived and can be used to examine relationships between various eating patterns and outcomes of interest such as coronary heart disease and other chronic diseases. Previous validation studies found that 2 major patterns (the prudent and Western patterns) identified through principle-component analysis of food consumption data assessed by food frequency questionnaires were reproducible over time and correlated reasonably well with the patterns identified from diet records. The consistent association observed between the Western or unhealthy dietary pattern (high in animal products, salty snacks, refined starches and sugar and fried foods and low in fruits and vegetables) and ACS risk in different regions of the world from the INTERHEART study and other studies[28-31] provides reliable evidence of the adverse effects of globalization on human nutrition and chronic disease risk, but the evidence is indirect because these studies did not specifically assess the impact of global trade and marketing on food consumption patterns, and their effects on inflammation, endothelial dysfunction, across different countries[28-31]. Despite this weakness, most recent studies suggest that the current trend of dietary convergence toward a typical Western diet is likely to play a role in the globalization of risk factors of CVDs including myocardial infarction[28-31].

INTERVENTION TRIALS WITH FUNCTION FOODS AND HEART ATTACK

Most trials with functional foods are conducted using Mediterranean-style diets in subjects with heart attack or those with high risk of CVDs[32-39]. Heart attack or AMI or acute coronary syndrome (ACS) is highly dynamic state associated with pro-inflammatory, severe neuro-endocrinological dysfunction, apart from myocardial damage[40-43]. There is marked increase in sympathetic activity, oxidative stress and inflammation, free fatty acids, dyslipidemia and deficiency of magnesium, potassium, coenzyme Q10 as well as in vitamin A, C, E and beta-carotine during the ACS event. These adverse effects are more common during second quarter of 24 hours. There is endothelial dysfunction due to rise in free fatty acids and endothelin 1 and reduction in bradykinin and nitric oxide which enhances the susceptibility for recurrent cardiovascular events after ACS but it could be prevented by Mediterranean style diet[40-43].

These syndromes usually occur when an acute thrombus forms in an atherosclerotic coronary artery. Atheromatous plaque sometimes becomes unstable or inflamed, causing it to rupture or split, exposing thrombogenic material, which activates platelets and the coagulation cascade and produces an acute thrombus. Platelet activation involves a conformational change in membrane glycoprotein (GP) IIb/IIIa receptors, allowing cross-linking (and thus aggregation) of platelets. Even atheromas causing minimal obstruction can rupture and result in thrombosis; in > 50% of cases, pre-event stenosis is < 40%. Thus, although the severity of stenosis helps predict symptoms, it does not always predict acute thrombotic events. The resultant thrombus abruptly interferes with blood flow to parts of the myocardium. Spontaneous thrombolysis occurs in about two thirds of patients; 24 h later, thrombotic obstruction is found in only about 30%. However, in virtually all cases, obstruction lasts long enough to cause tissue necrosis. In view of this pathophysiology of ACS, it is logical to administer functional foods in patients with AMI as soon as patient can tolerate a Mediterranean style soup developed from functional foods[32-34].

In randomized, controlled trial among 404 patients with ACS, intervention group was administered fruits, vegetable, whole grains, nuts and mustard oil initially as soup and later on as foods after few days compared to low fat diet[32-34]. After a follow up of 2 years, this study reported that the total mortality was 14.7% in the Paleolithic style diet group and 25.2% in the control group[34]. The differences in mortality are highly significant (p = 0.008). The findings of this study confirm that decreasing w-6/w-3 fatty acid ratio of the diet in the Paleolithic style diet group from 32.5 to 3.5 was associated with significant reduction in total cardiac mortality, total cardiovascular mortality and total mortality compared to control diet group.

In the Lyon Diet Heart Study, 605 patients who had a MI were randomly assigned to a Mediterranean-style diet of Crete or a prudent diet as per guidelines of the National cholesterol Education Program[35,36]. The experimental diet provide ratio of w-6 to w-3 of 4/1. This ratio was achieved by substituting olive oil and canola (oil) margarine for corn oil. In the Lyon Heart Study, the ratio of 4/1of w-6/w-3 fatty acids led to a 70%decrease in total mortality at the end of 27 months[35]. The risk of new AMI and episodes of unstable angina were reduced by ~ 70% by the modified Mediterranean diet. Long-term follow up for 4 years also showed that the beneficial effects of diet were continued[36]. Singh et al examined an Indo-Mediterranean diet in 1000 patients in India, with existing coronary disease or at high risk for coronary disease. Half of the patients (n = 499 vs 501) were administered a diet rich in fruits, vegetables, whole grains, walnuts, mustard oil and soy bean oil as a source for w-3 fat and rest 501 patients were advised to take prudent diet advised by the NCEP step 1 diet in 1988[37]. At the end of 2 year follow up, the mean intake of w-3 fatty acids was over two fold greater in the Indo-Mediterranean diet group compared to control group (1.8 ± 0.4 vs 0.8 ± 0.2 g/day, p < 0.001). The w-6/w-3 ratio of fatty acids was slightly higher at baseline in the intervention group than in the control group (39 ± 12 vs 34 ± 10) yet both these values are extremely high, reflecting a diet with a very high w-6 content yet low w-3[37]. At the end of two years follow up, this ratio of fatty acids, showed a marked decline in the intervention group, which was greater than that observed in the control group consuming control diet (9.1 ± 12 vs 21±10, p < 0.001). The study end points were; significant decline in the total cardiac events, sudden cardiac death and nonfatal MI in the Indo-Mediterranean diet group compared to the control group.

Burr et al[44] from United Kingdom reported 29% decline in total mortality including a decrease in sudden cardiac death in the group that received fish advice or took fish oil supplements relative to the group that did not among AMI patients. Singh et al[38] compared fish oil and mustard oil with control vegetable oils in patients with ACS. There was a significant decline in total cardiac events in the fish oil and mustard oil groups compared to control group patients with ACS during a follow up of one year[38]. The Lyon Heart Study was the first to attempt to modify the consumption of other fat components, and reduce the intake of omega-6 fatty acids despite the fact that there is convincing support for such studies. The differences in the w-6/w-3 ratio in the background diets and the dose of EPA and DHA could be an important factor in studies with conflicting results in intervention trials on the role of EPA and DHA in patients with ventricular arrhythmias in which a beneficial effect[45-51]. These mechanisms of action of functional foods and there beneficial effects on AMI pose the possibility that functional food and herb extract, such as cocoa, green tea, apple, black grapes, guava juice should be triad among patients undergoing angioplasty to prevent restenosis.

The findings from the PREDIMED Study indicate that there is no upper limit for fat intake because increased consumption of olive oil and other fatty acids (41% en from total fat) was associated with a significant decline in CVDs compared to control group receiving high saturated fat diet[39]. Hence, the US Department of Agriculture and International College of Cardiology have suggested no limit for total fat intake but limit the intake of saturated fat, trans-fat and possibly -6 fat which are known to have adverse effects. The best composition of fatty acid in the oil could be achieved by blending the oils as given in Table 2.

In brief, there is substantial evidence that increased consumption of functional foods can decrease cardiovascular events among patients with heart attack. Functional food security if foods are available at lower cost can enhance the consumption of these foods, resulting in to health promotion and global prevention of heart attack.

Acknowledgements

International College of Cardiology for providing logistic support to write this article.

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3 De Meester F. Wild-type land based foods in health promotion and disease prevention: the LDL-CC: HDL-CC model. In: De Meester F, Watson RR, eds. Wild Type Foods in Health Promotion and Disease Prevention. NJ: Humana Press, 2008. p. 3-20.

4 Shehab A, Elkilany G, Singh RB, Hristova K, Chaves H, Cornelissen G, Otsuka K. Coronary risk factors in Southwest Asia. Editorial, World Heart J 2015; 7: 21-23. (Novapublishers, NY)

5 Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després J-P, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 2016; 131: e38–e360. [PMID: 26673558]; [DOI: 10.1161/CIR. 0000000000000350]

6 Chauhan AK, Singh RB, Ozimek L, Basu TK. Saturated fatty acid and sugar; how much is too much for health? A scientific statement of the International College of Nutrition. Viewpoint, World Heart J 2016; 8: 71-78.(Novapublishers, NY)

7 GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet 2015; 385: 117-171. [DOI: 10.1016/S0140-6736(14)61682-2]

8 Sacco RL, Roth GA, Reddy KS, Arnett DK, Bonita R, Gaziano TA, Heidenreich PA, Huffman MD, Mayosi BM, Mendis S, Murray CJL, Perel P, Piñeiro DJ, Smith SC Jr, Taubert KA, Wood DA, Zhao D, Zoghbi WA. The heart of 25 by 25: achieving the goal of reducing global and regional premature deaths from cardiovascular diseases and stroke: a modeling study from the American Heart Association and World Heart Federation. Circulation 2016; 133. Published online before print May 9, 2016

9 Expert Group, International College of Cardiology; The challenges of prevention of cardiovascular diseases. A scientific statement of the international college of cardiology. World Heart J 2016.8 (4),in press (Novapublishers, NY)

10 Singh RB, Pella D, Mechirova V, Kartikey K, Demeester F, Tomar RS, Beegom R, Mehta AS, Gupta SB, De Amit K, Neki NS, Haque M, Nayse J, Singh S, Thakur AS, Rastogi SS, Singh K, Krishna A; The Five City Study Group. Prevalence of obesity, physical inactivity and undernutrition, a triple burden of diseases during transition in developing countries. Acta Cardiol 2007; 62: 119-127.

11 Singh RB, Bajaj S, Niaz MA, Rastogi SS, Moshiri M. Prevalence of type 2 diabetes mellitus and risk of hypertension and coronary artery disease in rural and urban population with low rates of obesity. Int J Cardiol 1998; 66(1): 65-72.

12 Pella D, Thomas N, Tomlinson B, Singh RB. Prevention of coronary artery disease: the South Asian paradox. Lancet 2003; 361: 79-80.

13 Janus ED, Postiglione A, Singh RB, Lewis B. on behalf of the council on arteriosclerosis of the International Society and Federation of Cardiology. The modernization of Asia: implications for coronary heart disease. Circulation 1996; 94: 2671-2673

14 Twig G, Yaniv G, Levine H, Leiba A, Goldberger N, Derazne E, Shor DB-A, Tzur D, Afek A, Shamiss A, Haklai Z, Kark JD. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. New Engl J Med 2016; April 13. [DOI: 10.1056/NEJMoa1503840]

15 Davey Smith, G, Sterne, JAC, Fraser, A, Tynelius, P, Lawlor, DA, and Rasmussen, F. The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study. BMJ 2009; 339: b5043

16 Roth GA, Nguyen G, Forouzanfar MH, Mokdad AH, Naghavi M, Murray CJ. Estimates of global and regional premature cardiovascular mortality in 2025. Circulation. 2015 Sep 29; 132(13): 1270-82.

17 Itharat A, Onsaard E, Singh RB, Chauhan AK, Shehab O. Flavonoids consumption and the heart. World Heart J 2016; 8: 103-108. (Novapublishers,NY)

18 The 2015-2020 Dietary Guidelines for Americans. [Link], accessed 01.07.2016

19 Singh RB, Takahashi T, Shastun S, Elkilany G, Hristova K, Shehab A, Onsaard E, Phomkong W, Chaves H, Singh M, Srivastava RK, Srivastav M, Singh RG. The Concept of Functional Foods and Functional Farming (4 F) in the Prevention of Cardiovascular Diseases: A Review of Goals from 18th World Congress of Clinical Nutrition. Journal of Cardiology and Therapy 2015; 2(4): 341-344. [Link]

20 Singh RB, Visen P, Sharma D, Sharma S, Mondol R, Sharma JP, Sharma M, Tokunaga M, Takahashi T, Mishra S, Sharma A, Jain M, Marinho F and Pal R. Study of functional foods consumption patterns among decedents dying due to various causes of death. The Open Nutra J 2015; 8: 16-28. (Bentham Science, USA)

21 Kastorini CM, Panagiotakos DB. Dietary patterns and prevention of type 2 diabetes; from research to clinical practice; a systematic review. Curr Diabetes Rev 2009; 5: 221–227.

22 Du H, Li L, Bennett D, Guo Y, Key TJ, Bian Z, Sherliker P, Gao H, Chen Y, Yang L, Chen J, Wang S, Du R, Su H, Collins R, Peto R, Chen Z; China Kadoorie Biobank Study. Fresh fruit consumption and major cardiovascular disease in China. N Engl J Med 2016; 374: 1332-1343. [DOI: 10.1056/NEJMoa1501451]

23 Martínez-González MA, de la Fuente-Arrillaga C, Nunez-Cordoba JM, Basterra-Gortari FJ, Beunza JJ, Vazquez Z, Benito S, Tortosa A, Bes-Rastrollo M. Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study. BMJ 2008; 336: 1348-1351.

24 Mozaffarian D, Marfisi R, Levantesi G, Silletta MG, Tavazzi L, Tognoni G, Valagussa F, Marchioli R. Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors. Lancet 2007; 370: 667-675.

25 Gramenzi A, Gentile A, Fasoli M,Negri E,Parazzini F.La Vecchia C. Association between certain foods and risk of acute myocardial infarction in women. BMJ 1990 ; 300: 771-773

26 Martínez-González MA, Fernández-Jarne E, Serrano-Martínez M, Marti A, Martinez JA, Martín-Moreno Mediterranean diet and reduction in the risk of a first acute myocardial infarction: an operational healthy dietary score. Eur J Nutr. 2002 Aug; 41(4): 153-60.

27 Tavani A, Spertini L, Bosetti C, Parpinel M, Gnagnarella P, Bravi F, Peterson J, Dwyer J, Lagiou P, Negri E, et al. Intake of specific flavonoids and risk of acute myocardial infarction in Italy. Public Health Nutr. 2006 May; 9(3): 369-74.

28 Singh RB, Fedacko J, Sharma JP, et al. Association of inflammation, heavy meals, magnesium, nitrite and coenzyme q10 deficiency and circadian rhythms with risk of acute coronary syndromes. World Heart J 2012; 2: 219-227.(Novapublishers,NY)

29 Singh RB, Pella D, Sharma JP, Rastogi S, Kartikey K, Goel VK, Sharma R, Neki NS, Kumar A, Otsuka K. Increased concentrations of lipoprotein(a), circadian rhythms and metabolic reactions evoked by acute myocardial infarction, associated with acute reactions in relation to large breakfasts. Biomed Pharmacother. 2004 Oct; 58 Suppl 1: S116-22.

30 Singh RB1, Pella D, Neki NS, Chandel JP, Rastogi S, Mori H, Otsuka K, Gupta P. Mechanisms of acute myocardial infarction study (MAMIS). Biomed Pharmacother. 2004 Oct; 58 Suppl 1: S111-5.

31 Iqbal R, Anand S, Ounpuu S, Islam S, Zhang X, Rangarajan S, Chifamba J, Al-Hinai A, Keltai M, Yusuf S, on behalf of the INTERHEART Study Investigators. Dietary patterns and the risk of acute myocardial infarction in 52 countries: results of the INTERHEART study. Circulation. 2008; 118: 1929–1937.

32 Singh RB, Rastogi SS, Verma R, Bolaki L, and Singh R. An Indian experiment with nutritional modulation in acute myocardial infarction. Am. J. Cardiol. 1992; 69: 879-885

33 Singh RB, Rastogi SS, Verma R, Laxmi B, Singh R, Ghosh S, Niaz MA. Randomized, controlled trial of cardioprotective diet in patients with acute myocardial infarction: results of one year follow up. BMJ 1992; 304: 1015-1019.

34 Singh RB, Fedacko J, Vargova V, Niaz MA, Rastogi SS, Ghosh S. Effect of low ω-6/ω-3 ratio fatty acid Paleolithic style diet in patients with acute coronary syndromes. A randomized, single blind, controlled trial. World Heart J 2012; 3: 71-84.(Novapublishers,NY)

35 de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994, 343(8911): 1454-9. Erratum in: Lancet 1995; 345(8951): 738.

36 De Logeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Diet Heart Study. Circulation 1999; 99: 779–785.

37 Singh RB, Dubnov G, Niaz MA, Ghosh S, Singh R, Rastogi SS, Manor O, Pella D, Berry EM. Effect of an Indo-Mediterranean diet on progression of coronary disease in high risk patients: a randomized single blind trial. Lancet 2002; 360: 1455-1461

38 Singh RB, Niaz MA, Sharma JP, Kumar R, Rastogi V, Moshiri M. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival—4. Cardiovasc Drugs Ther 1997; 11: 485-491.

39 Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368(14); 1279-1290.

40 Vogel RA. Eating vascular biology and atherosclerosis: a lot to chew on. Eur. Heart J. 2006; 27: 13-14.

41 Esposito K, Giugiliano D. Diet and inflammation: a link to metabolic and cardiovascular diseases. Eur. Heart J. 2006,27: 15-20.

42 Kelishadi R, Mirghaffari N, Poursafa P, Gidding SS. Lifestyle and environmental factors associated with inflammation, oxidative stress and insulin resistance in children. Atherosclerosis. 2009, 203: 311-319.

43 Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D'Armiento M, D'Andrea F, Giugliano D. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004; 292(12): 1440-1446.

44 Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, Deadman NM. Effect of changes in fat, fish and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989; 2: 757-76.

45 McCall DO, McGartland CP, McKinley MC, Patterson CP, Sharpe P, McCance CR, Young IS, Woodside JV. Dietary Intake of Fruits and Vegetables Improves Microvascular Function in Hypertensive Subjects in a Dose-Dependent Manner. Circulation. 2009; 119: 2153-2160.

46 Smith PJ, Blumenthal JA, Babyak MA, Georgiades A, Sherwood A, Sketch MH Jr, Watkins LL. Association between n-3 fatty acid consumption and ventricular ectopy after myocardial infarction. Am. J. Clin. Nutr. 2009; 89: 1315-20.

47 Campos H, Baylin A, Willett WC. Alpha-Linolenic acid and risk of nonfatal acute myocardial infarction. Circulation. 2008; 118: 339-345.

48 Harris WS, Reid KJ, Sands SA, Spertus JA. Blood omega-3 and trans fatty acids in middle aged acute coronary syndrome patients. Am. J. Cardiol. 2007; 99: 154-158.

49 Harper CR, Jacobson TA. Usefulness of omega-3 fatty acids and the prevention of coronary heart disease. Amer. J. Cardiol. 2005; 96: 1521-29.

50 Leaf A, Albert CM, Josephson M, Steinhaus D, Kluger J, Kang JX, Cox B, Zhang H, Schoenfeld D, Fatty Acid Antiarrhythmia Trial Investigators. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation 2005; 112: 2762–2768.

51 Zhao G, Etherton TD, Martin KR, Gillies PJ, West SG, Kris-Etherton PM. Dietary-linolenic acid inhibits pro-inflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am. J. Clin. Nutr. 2007; 85: 385–391

52 Singh RB, Rastogi SS, Singh R, Ghosh S, Niaz MA. Effects of guava intake on serum total and high density lipoprotein cholesterol levels and systemic blood pressures. Am J Cardiol 1992; 70: 1287-1291.

53 Sreeramulu D, Reddy CVK, Raghunath M. Antioxidant activity of commonly consumed cereals, millets, pulses and legumes in India. Indian J Biochem Biophys 2009; 46(1): 112-115. [PMID: 19374263]

Peer reviewer: IbrahimPietro Scicchitano

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