Flavonoids, flavones, catechins, polyphenols, anthocyanins, lignans, and phytoestrogens are all types of antioxidants and phytonutrients, and they are all found in plant-based foods [19,20]. There are more than 4000 known flavonoids, which are just one class of antioxidants. Diets rich in berries such as blackberries, cranberries, strawberries, or blueberries are the richest sources of antioxidant nutrients, in particular anthocyanins [15]. Anthocyanins are also from the flavonoids group, which are pigments widely distributed in fruits and vegetables [19]. Anthocyanins are responsible for red, blue, purple, and yellow colors in fruits, flowers, and vegetables and protect plant cells from the stresses of the environment such as high sunlight and pollutants [20]. In a recent study on the flavonoid content of foods, lingonberries, and blueberries, they were found to contain a greater amount of flavonoids (1100 mg/100 g dry weight) than raspberries and strawberries (500 mg/100 g dry weight). Anthocyanins were the dominant flavonoids in all berries [21]. This analysis reported compounds contributing varying amounts of the total flavonoid content in various types of strawberries (18%), lingonberries (29%), raspberries (^1%), and blueberries (67%). In eastern and western societies, tea, coffee, cocoa, and wine are the primary dietary sources of flavonoids. In addition, leafy vegetables, berries, apples, cherries, soybeans, onions, and citrus fruits are considered important sources of dietary flavonoids [15,20,21,22,23,24,25,26,27,28,29,30].

The USDA was the first to release a database on the flavonoid content of foods in 2003, which was updated using new data on 20 different flavonoids from a nationwide sampling of 59 fruits, nuts, and vegetables and 102 scientific papers [22]. The new database contains data on flavonoids for 395 food items and data from the National Health and Nutrition Examination Survey to ascertain the intake of five classes of flavonoids: anthocyanidins, flavanones, flavonols, flavones, and flavan-3-ols on a population basis (www.ars.usda.gov/nutrientdata). Interestingly, black tea provided the largest amount of flavonols to the diet (32%), followed by onions (25%), and parsley was the largest contributor of flavones. Dried parsley leaves contain a large amount of 13.53 g/100 g, though rarely is 100 g consumed at one time, and a teaspoon weighs 0.5 g. Among fruits, oranges (53%) and grapefruit juice (16%) contributed significant amounts of flavanones. Brewed tea provides the largest quantities of flavan-3-ols to the diet. Blueberries contributed the largest amount of anthocyanidins (31%), followed by bananas (21%) and strawberries (14%). Although bananas contain a lower amount of anthocyanidins than any of the berries, the intake of bananas is much higher than that of individual berries. This database provides worldwide researchers with new values on the flavonoid content of many more foods in order to better ascertain the impact of flavonoid consumption in various diseases [22]. Daily per capita intake of flavonoids in the United States using these data was: anthocyanidins, 5 mg; flavanones, 4 mg; flavones, 1 mg; flavonols, 10 mg; flavan-3-ols, 112 mg; total intake 132 mg/day. This is too low compared to the estimated flavonoid intake in European (250–900 mg/day), Asian (200–650 mg/day), and Middle Eastern countries (1650 mg/day) [15]. The higher intake of flavonoids in these countries is mainly because of black tea [22,23,24]. In the Indo-Mediterranean diet, the flavonoid intake was 1800 mg/day [7,9,10]. Despite the high intake of fruits, vegetables, and red wine in Mediterranean countries, the intake of total flavonoids in these countries (250–400 mg/day) is lower than in other European countries (350–900 mg/day), which is due to the much higher consumption of tea in non-Mediterranean countries [24]. In Japan, the mean intake of total flavonoids flavan-3-ols, isoflavones, flavonols, flavanones, and flavones was approximately 1500 mg/day, mainly from green tea, soya foods, onion, leafy vegetables, and fruits [25]. Thus, the total flavonoids in the Japanese diet are comparable with flavonoid contents in the Indo-Mediterranean diet (1500 versus 1800 mg/day, respectively), which makes these diets potential sources of flavonoid consumption for cardiometabolic protection [7,25].

Flavonoids are polyphenolic plant metabolites that have biologically relevant protective effects in a number of cardiometabolic disorders (CMDs) [26]. Some epidemiological studies have underscored a negative association between dietary flavonoid consumption and the propensity to develop CMDs, indicating that the contribution of the gut microbiota may be crucial for metabolizing dietary intake, as it is related to CVDs [26]. The Seven Countries Study reported that the consumption of flavonoids at baseline in the year 1960 was estimated by flavonoid content analysis of equivalent food composites of the diets in the 16 cohorts [2]. After follow up of 25 years, mortality from CAD, cancer in various organs, and all causes in the 16 cohorts revealed that average consumption of antioxidant flavonoids was inversely associated with CAD mortality. The study also explained about 25% of the variance in the rates of CAD in all the 16 cohorts. The consumption of saturated fat (73%; p = 0.0001), flavonoids (8%, p = 0.01), and percentage of smokers per cohort (9%; p = 0.03) together explained the independent consumption of alcohol and antioxidant vitamins, 90% of the variance in the rates of CAD. Interestingly, consumption of flavonoids was not independently associated with mortality from other causes. It is clear from this study that average flavonoid consumption may partly contribute to differences in mortality due to CAD across populations, but it did not seem to be an important determinant of cancer mortality in this study [2]. In a systematic review, a total of 39 prospective cohort studies were included, comprising 1,501,645 subjects and a total of 33,637 cases of CVD, 23,664 of CAD, and 11,860 of stroke [27]. Increased intake of total dietary flavonoids was linearly associated with a lower risk of CVD. Among the main classes of flavonoids, increasing intake of anthocyanins and flavan-3-ols is inversely associated with risk of CVD and flavonols and flavones with CAD. Only increasing flavanones showed a linear inverse association with stroke risk. Catechins showed a favorable effect on all outcomes of CVDs [27]. The intake of quercetin and kaempferol was also linearly associated with a lower risk of CAD and CVD, respectively. However, higher intake of all the aforementioned compounds was associated, to varying degrees, with a lower risk of CVD when comparing extreme categories of consumption. It seems that a flavonoid-rich diet may have potential cardiovascular benefits [27].

In another systematic review, at least 27 prospective cohorts (in 44 publications) evaluated the association between estimated habitual flavonoid intake and CVD risk [28]. The totality of evidence suggested that a long-term intake of flavonoid-rich foods may be associated with a lower risk of fatal and non-fatal CAD, CVD, and total CVD outcomes. The types of flavonoid subclasses more often included diets rich in anthocyanins, flavan-3-ols, and flavonols in lowering the risk of CVDs [28]. In the Nurses’ Health Study (1990–2018), including 60,582 women, and the Health Professional follow-up study (1990–2018), including 31,801 men, the follow-up period was 28 years [29]. After follow up, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among participants who had the highest consumption of olive oil (>0.5 tablespoons/day or >7 g/day) was 0.81 (95% CI: 0.78–0.84) compared with those who never or rarely consumed olive oil. The consumption of a greater amount of olive oil was associated with a 19% lower risk of CVDs mortality (HR: 0.81; 95% CI: 0.75–0.87), 17% lower risk of cancer mortality (HR: 0.83; 95% CI: 0.78–0.89), 29% lower risk of neurodegenerative disease mortality (HR: 0.71; 95% CI: 0.64–0.78), and 18% lower risk of respiratory disease mortality (HR: 0.82; 95% CI: 0.72–0.93). Replacement of 10 g/day of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with an 8–34% lower risk of total and cause-specific mortality [29]. Interestingly, no significant associations were observed when olive oil was compared with other vegetable oils combined, indicating that it is the flavonoid content of olive oil that provided the benefits.

In a previous systematic review, total polyphenol consumption for the total population was assessed to be approximately 900 mg/day, which varied as per variations in the target groups of populations [23]. The main sources of polyphenols in the foods were vegetables, fruits, tea, coffee, and red wine. The intake of total flavonoids with specific subclasses, but without total polyphenols, was associated with a low risk of diabetes, CVDs, and all-cause mortality. Despite several variations in the data available, it seems that the concept of the beneficial effect of a dietary pattern, rich in polyphenol needs further studies in order to define specific therapy [23]. Interestingly, this review reported a higher intake of flavonoids compared to other studies [15,19,20,21,22,23,24,26,27,28,29]. Twelve studies found an inverse association between polyphenol intake and CV events [23]. A significant decline in CV risk was observed at the highest quartile of total polyphenol consumption in a few studies (1170 mg/day for Spain and 2632 mg/day for Poland) [23,30,31]. However, more research conducted in Spain and Iran (1248 mg/day and 2459 mg/day, respectively) found no benefits, which may be due to no substantial differences in the interindividual intake of flavonoids [32,33]. Other studies (n = 10) evaluating the association with intake of total polyphenol showed that only three of them had a significant inverse relation with CV events [32,34,35], with intake in the range of 115 to 944 mg/day. In the USA, an inverse association was observed for both CV and T2D, with the highest quartile of total flavonoids (585 mg/day) [34]. In Poland, total polyphenol intake of 2632 mg/day showed an inverse association with risk of T2DM [36]. In a population-based study in Brazil, an inverse association between polyphenol intake and hypertension was reported [30]. Interestingly, both diets, the Mediterranean and Japanese, are considered healthy, hence the people of Mediterranean countries have a low risk of CVDs and diabetes, while those of Japan are known to have greater longevity.

However, there are both similarities and discrepancies in intake of foods and beverages between the two diets. The Mediterranean diet is rich in cereals (wheat), fruits, vegetables, nuts, fish, and olive oil [4]. The Japanese diet consists of a large quantity of grains (rice), fish, raw fish, vegetables, and fruit and lower consumption of energy and total fats [1,2,3].

Mediterranean populations consume high amounts of total fats, mainly olive oil (approximately 100 g/day in males and 80 g in females) and polyunsaturated fatty acids [4]. In contrast, the traditional Japanese diet contains a lower amount of fat, However, the recent past has seen a change from 20% energy from fats to 30%, whereas the ratio of n-6 PUFAs/n-3 PUFAs has increased from 2–3 to 4–5, with no significant increase in CVDs [3]. It seems that the healthiest diet should have all the ten qualities of the diets and it should also involve mastication [8] (Table 1).