Healthy Drinks with Lovely Colors: Phenolic Compounds as Constituents of Functional Beverages

: Consumers increasingly prefer and seek food and beverages, which, due to their natural characteristics, bring health beneﬁts, both in the prevention of diseases and in their curative power. In this way, the production of nutraceutical foods and beverages gains more and more importance in the market. On the other hand, and because the eyes also eat, producing attractive foods due to their color, texture, appearance, and sensory characteristics is a permanent challenge in the food industry. Being able to gather healthy and attractive items in a single food is an even greater challenge. The long list of beneﬁts associated with phenolic compounds, such as antioxidant, anticancer, anti-inﬂammatory, and antiaging properties, among others, fully justiﬁes their use in the enrichment of various food products. Thus, in this review, we propose to summarize the potential use of phenolic compounds used as ingredients of pleasant and functional beverages. thearubigins, theasinensins, polyhydroxylated ﬂavan-3-ols. Potential for use of EGCG in human cancer prevention and treatment. Induction of the suppression of tumor cell proliferation, stimulation of apoptosis, promotion of progestogen, and changes in testosterone release. Reduce the risk of Parkinson’s disease. Gallic acid, protocatechuic acid, (+)-catechin, vanillic acid, caffeic acid, syringic acid, ( − )-epicatechin, p-coumaric acid, and ferulic acid. The major free phenolic acids in beers are m -, p - and o -coumaric and ferulic. Sinapic, vanillic, chlorogenic, homovanillic, p -hydroxybenzoic, 2,6- and 3,5-dihydroxybenzoic, syringic, gallic, protocatechuic, and caffeic acids. Positive effect on plasma lipid proﬁle and plasma antioxidant capacity. Increase


Introduction
As many researchers state, color is an important product-intrinsic sensory cue when it comes to establishing people's anticipations regarding the likely taste and flavor of a food or a drink. Several researchers now suggest that our experience of taste and flavor is determined by the expectations that we generate before tasting, especially when we can inspect a drink visually before deciding on whether, or not, to buy or taste it [1,2]. Brain and visual system development are intimately linked to the acquisition of food and drink, and contemporary neuroscience demonstrates that the sight of appealing food or drink is a powerful cue for the brain, especially the brain of a hungry person [3].
Consequently, many of us often have our sense of taste tricked by the sense of sight. We expect the food and drink to taste like what we see. When the color of a drink is different from what was expected, our brain tells us that it will taste different. Scientific studies proved that we frequently judge food quality based on colors to identify the taste, which ultimately affects our purchase decision. Taste buds play a significant role in determining the six basic tastes-sweet, salty, sour, bitter, umami, and fat [4]. Signals will be sent from taste buds to the brain that will interpret taste and flavor. The taste transduction mechanism is schematized in Figure 1. The apical surface of the taste receptor cell contains channels and G protein-coupled receptors that are activated by chemical stimuli. The basolateral surface contains voltage-gated Na + , K + , and Ca 2+ channels, as well as all the mechanisms for synaptic transmission mediated by serotonin. The ion Ca 2+ acts as a 2nd messenger and the increase in cytoplasmatic Ca 2+ occurs due to the activation of voltage-gated Ca 2+ channels or due to their release from intracellular stores. This second messenger causes  [5] and Vera and Wooding [6].
However, before we eat or drink, we will look at the food or drink first, and signals are sent to the brain which interprets the taste of the food or beverage before we consume it, predetermining the expected taste and flavor. The detection of shape and color is done by the eyes. Light enters the eye through the cornea, passing through the pupil at the center of the iris (Figure 2). The lens adjusts to focus the light on the retina, where it appears upside down and backward. Receptor cells on the retina send information via the optic nerve to the visual cortex. When light falls on the retina, it creates a photochemical reaction in the rods and cones at the back of the retina. The reactions then continue to the bipolar cells, the ganglion cells, and eventually to the optic nerve [7], which sends the information to the brain ( Figure 2).
Beverages 2021, 7, x FOR PEER REVIEW 2 of 23 age-gated Ca 2+ channels or due to their release from intracellular stores. This second messenger causes synaptic vesicles to fuse and release their transmitter onto receptors on primary sensory neurons, directly to the gustatory cortex, in the brain [5,6]. Figure 1. Transduction mechanisms in a generic taste cell. Adapted from Purves et al. [5] and Vera and Wooding [6].
However, before we eat or drink, we will look at the food or drink first, and signals are sent to the brain which interprets the taste of the food or beverage before we consume it, predetermining the expected taste and flavor. The detection of shape and color is done by the eyes. Light enters the eye through the cornea, passing through the pupil at the center of the iris (Figure 2). The lens adjusts to focus the light on the retina, where it appears upside down and backward. Receptor cells on the retina send information via the optic nerve to the visual cortex. When light falls on the retina, it creates a photochemical reaction in the rods and cones at the back of the retina. The reactions then continue to the bipolar cells, the ganglion cells, and eventually to the optic nerve [7], which sends the information to the brain ( Figure 2). Black columns are solutions where fruit acids had been added; white columns are solutions without fruit acids. Adapted from Zampini et al. [11].
Thus, humans tend to associate colors with food and connect these colors to certain tastes and flavors. For example, black-colored food is usually perceived as bitter or having a burnt flavor. Bright colors, like yellow, are perceived as sweet or sour; red can be perceived as spicy. Several studies, conducted over the last thirty-five years, show that the majority of us do indeed match basic tastes to colors in a nonrandom way that is regular across individuals and consistent over time [12][13][14][15].
The phenolic compounds, which naturally occur in many fruit-based beverages, may positively or negatively affect their sensory traits, with important impacts on color, perceived taste and flavor, and astringency. Polyphenols originate from plants due to their secondary metabolism and accumulate in plant organs like leaves, fruits, roots, and stems. They are essential to plant life as they provide defense against harmful microorganisms and make plants unpalatable to predators [16,17]. They also present different color palettes, that may influence, as has been mentioned before, our taste and flavor perception ( Figure 4). Thus, humans tend to associate colors with food and connect these colors to certain tastes and flavors. For example, black-colored food is usually perceived as bitter or having a burnt flavor. Bright colors, like yellow, are perceived as sweet or sour; red can be perceived as spicy. Several studies, conducted over the last thirty-five years, show that the majority of us do indeed match basic tastes to colors in a nonrandom way that is regular across individuals and consistent over time [12][13][14][15].
The phenolic compounds, which naturally occur in many fruit-based beverages, may positively or negatively affect their sensory traits, with important impacts on color, perceived taste and flavor, and astringency. Polyphenols originate from plants due to their secondary metabolism and accumulate in plant organs like leaves, fruits, roots, and stems. They are essential to plant life as they provide defense against harmful microorganisms and make plants unpalatable to predators [16,17]. They also present different color palettes, that may influence, as has been mentioned before, our taste and flavor perception ( Figure 4).  Adequate consumption of phenolic compounds may offer health benefits [19]. The consumption of fruit-based beverages, fermented or not, and rich in phenolic compounds and presenting a lovely color, has also been related to healthy diets, such as the Mediterranean diet, and to the prevention of chronic diseases since they present antioxidant properties [19]. After the consumption of a fruit beverage rich in phenolic compounds, only a select number of phenolic compounds is absorbed into the circulatory system via the small intestine [20]. The absorptive process is dependent on molecular complexity, size, charge, food matrix, and the presence of other drugs [21]. A huge amount of the ingested phenolics is metabolized by the gut microbiota, generating small molecules (phenolic acids or lactone structures) that may be absorbed and exercise physiological effects [22][23][24]. Evidence suggests that these metabolites have health benefits for humans [25]. Phenolic compounds act as reducing or metal-chelating agents, hydrogen donors, and singlet oxygen quenchers [26]. Moreover, phenolic compounds can prevent disease through mechanisms that differ from the antioxidant function, such as cellular signaling, gene expression, and modulation of enzymatic activity [27]. Furthermore, the consumption of diets rich in phenolic compounds may also modulate human gut microbiota [28].
However, which beverages can be considered beneficial to health by consumers? Do they associate the colors of food and beverages with the presence of beneficial compounds? Most of the research on the psychological influence of color on judgments of taste/flavor intensity has been conducted with beverages because it is easier to manipulate the level of color in solutions than in solid foods [28] and there is a motivation to produce red fruit beverages like grape juice or grape nectar for their important nutritional properties [29,30]. Red coloring in beverages and foods also appears to be a particularly good inducer of sweetness. It seems that humans may have internalized the environmental association between sweetness and redness in ripe fruits [31].
Therefore, taking all this into account, in this review, we aim to overview the potential use of phenolic compounds, natural or man-made, as ingredients of joyful and functional beverages.

The Traditional Mediterranean Diet
Before the mid-1960s, the common diet pattern in countries in the Mediterranean Sea basin, such as Italy and Greece, was recognized as a "Mediterranean diet" [32]. However, providing an accurate definition of this type of diet is not easy, as it varies with the cultural, social, and religious habits of each country, and with time [33,34].
Recognized as Intangible Cultural Heritage by the United Nations Educational, Scientific and Cultural Organization (UNESCO) in 2013 (UN), the Mediterranean diet is traditionally recognized for its varied palette of colors, rich in aromas and memories, but mainly because it is an extremely healthy cuisine given its complete nutritional composition of essential macronutrients and micronutrients [35][36][37]. Indeed, several studies report that the inhabitants of the Mediterranean region with a Mediterranean dietary pattern had Adequate consumption of phenolic compounds may offer health benefits [19]. The consumption of fruit-based beverages, fermented or not, and rich in phenolic compounds and presenting a lovely color, has also been related to healthy diets, such as the Mediterranean diet, and to the prevention of chronic diseases since they present antioxidant properties [19]. After the consumption of a fruit beverage rich in phenolic compounds, only a select number of phenolic compounds is absorbed into the circulatory system via the small intestine [20]. The absorptive process is dependent on molecular complexity, size, charge, food matrix, and the presence of other drugs [21]. A huge amount of the ingested phenolics is metabolized by the gut microbiota, generating small molecules (phenolic acids or lactone structures) that may be absorbed and exercise physiological effects [22][23][24]. Evidence suggests that these metabolites have health benefits for humans [25]. Phenolic compounds act as reducing or metal-chelating agents, hydrogen donors, and singlet oxygen quenchers [26]. Moreover, phenolic compounds can prevent disease through mechanisms that differ from the antioxidant function, such as cellular signaling, gene expression, and modulation of enzymatic activity [27]. Furthermore, the consumption of diets rich in phenolic compounds may also modulate human gut microbiota [28].
However, which beverages can be considered beneficial to health by consumers? Do they associate the colors of food and beverages with the presence of beneficial compounds? Most of the research on the psychological influence of color on judgments of taste/flavor intensity has been conducted with beverages because it is easier to manipulate the level of color in solutions than in solid foods [28] and there is a motivation to produce red fruit beverages like grape juice or grape nectar for their important nutritional properties [29,30]. Red coloring in beverages and foods also appears to be a particularly good inducer of sweetness. It seems that humans may have internalized the environmental association between sweetness and redness in ripe fruits [31].
Therefore, taking all this into account, in this review, we aim to overview the potential use of phenolic compounds, natural or man-made, as ingredients of joyful and functional beverages.

The Traditional Mediterranean Diet
Before the mid-1960s, the common diet pattern in countries in the Mediterranean Sea basin, such as Italy and Greece, was recognized as a "Mediterranean diet" [32]. However, providing an accurate definition of this type of diet is not easy, as it varies with the cultural, social, and religious habits of each country, and with time [33,34].
Recognized as Intangible Cultural Heritage by the United Nations Educational, Scientific and Cultural Organization (UNESCO) in 2013 (UN), the Mediterranean diet is traditionally recognized for its varied palette of colors, rich in aromas and memories, but mainly because it is an extremely healthy cuisine given its complete nutritional composition of essential macronutrients and micronutrients [35][36][37]. Indeed, several studies report that the inhabitants of the Mediterranean region with a Mediterranean dietary pattern had a low incidence of lifestyle diseases, namely, cardiovascular disease, when compared to the American population [32,[38][39][40][41]. Consequently, what is so special about the Mediterranean diet? It should be noted that this diet pattern has evolved, as mentioned by Radd-Vagenas et al. [33], who defined the historical timeline of Mediterranean diets: ancient, "traditional", and modern. Thus, considered the cradle of civilization, the Mediterranean basin was influenced by ancient civilizations, and the food and food patterns of the time were shaped by the culture of each people, the historical period, the economy, and the climatic conditions, among other factors [42]. Two important influences should be mentioned in the model of ancient Mediterranean cuisine: the influence of Arabic/Islamic culture, as it includes a greater variety of fruits and vegetables (pomegranate, almonds, spinach, eggplant, citrus fruits), barley, wheat, rice, and spices; as well as Cristóvão Colombo's voyages to America, from which various vegetables, tomatoes, potatoes, corn, and pepper emerged [36,43].
However, a healthy diet would always be based on meats (in moderation), fish, fruits, vegetables, cereals, without forgetting the role of drinks, where the base would be water, but, in moderate quantities, it would also include the consumption of wine [43]. Figure 5 shows the food and beverage groups consumed in the Mediterranean dietary pattern.
Beverages 2021, 7, x FOR PEER REVIEW 5 of 23 a low incidence of lifestyle diseases, namely, cardiovascular disease, when compared to the American population [32,[38][39][40][41]. Consequently, what is so special about the Mediterranean diet? It should be noted that this diet pattern has evolved, as mentioned by Radd-Vagenas et al. [33], who defined the historical timeline of Mediterranean diets: ancient, "traditional", and modern. Thus, considered the cradle of civilization, the Mediterranean basin was influenced by ancient civilizations, and the food and food patterns of the time were shaped by the culture of each people, the historical period, the economy, and the climatic conditions, among other factors [42]. Two important influences should be mentioned in the model of ancient Mediterranean cuisine: the influence of Arabic/Islamic culture, as it includes a greater variety of fruits and vegetables (pomegranate, almonds, spinach, eggplant, citrus fruits), barley, wheat, rice, and spices; as well as Cristóvão Colombo's voyages to America, from which various vegetables, tomatoes, potatoes, corn, and pepper emerged [36,43].
However, a healthy diet would always be based on meats (in moderation), fish, fruits, vegetables, cereals, without forgetting the role of drinks, where the base would be water, but, in moderate quantities, it would also include the consumption of wine [43]. Figure 5 shows the food and beverage groups consumed in the Mediterranean dietary pattern. The "traditional" Mediterranean diet can be referred to as belonging to a time before the globalization of ultra-processed foods and the modern era of industrial agriculture [44]. It is based on plants that grow in the Mediterranean region, including olives [45][46][47].
In the different patterns of the Mediterranean diet, olive oil is a common factor, either for its beneficial properties or for being associated with the seasoning of various raw dishes, such as salads that allow the consumption of large quantities of vegetables and legumes, or for its use in cooked food. The use of spices and herbs is recommended, avoiding the excessive use of salt. Thus, the basic Mediterranean diet includes the daily consumption of vegetables, fruit, beans, bread, cereals, potatoes, nuts, seeds, dairy products, and olive oil, and the weekly consumption of fish, shellfish, poultry, and eggs and, once a week or less, meat. Regarding drinks, water is the base that should be consumed daily. The consumption of tea (infusion of Camellia sinensis) and infusions of aromatic herbs (sage, siderites, lemon, verbena, chamomile, mint) is recommended. Infusions of several The "traditional" Mediterranean diet can be referred to as belonging to a time before the globalization of ultra-processed foods and the modern era of industrial agriculture [44]. It is based on plants that grow in the Mediterranean region, including olives [45][46][47].
In the different patterns of the Mediterranean diet, olive oil is a common factor, either for its beneficial properties or for being associated with the seasoning of various raw dishes, such as salads that allow the consumption of large quantities of vegetables and legumes, or for its use in cooked food. The use of spices and herbs is recommended, avoiding the excessive use of salt. Thus, the basic Mediterranean diet includes the daily consumption of vegetables, fruit, beans, bread, cereals, potatoes, nuts, seeds, dairy products, and olive oil, and the weekly consumption of fish, shellfish, poultry, and eggs and, once a week or less, meat. Regarding drinks, water is the base that should be consumed daily. The consumption of tea (infusion of Camellia sinensis) and infusions of aromatic herbs (sage, siderites, lemon, verbena, chamomile, mint) is recommended. Infusions of several herbs present a huge source of phenolic compounds, as can be seen in Table 1. For instance, lemon balm (Melissa officinalis) presents a total phenolic concentration of 133 mg GAE/g DW and it can be used to ease the negative mood effects of laboratory-induced psychological stress [48]. Table 1. Total phenolic content expressed in mg of gallic acid equivalents per g of dry weight (mg GAE/DW), and total flavonoid content in milligrams of chlorogenic acid equivalents per gram of leaf dry weight (mg CAE/g DW) of herbal infusions. Adapted from Herrera et al. [49]. Other beverages, like coffee, and fermented beverages, such as wine, should be consumed in moderation, and, particularly wine, preferably with meals [45,50]. Thus, the Mediterranean diet is a plant-based diet particularly rich in phytochemicals named polyphenols and flavonoids (Table 2) [51][52][53][54], and also full of color, from the yellow-green of olive oil to the dark red of fruit, fruit juices, and wine, as can be seen in Table 3 that exemplifies a one-day summer menu based on the "traditional" Mediterranean diet.    Table 3. One-day menu sample of the Mediterranean diet. Adapted from Radd-Vagenas et al. [33].

Meal Foods
Breakfast Bread topped with grated fresh tomato, crumbled feta, dried oregano, and drizzled with extra virgin olive oil Herbal tea or boiled Greek coffee  Cherry, raspberry, strawberry, grapes Delphinium and pelargonidin Dark fruits Table 3. One-day menu sample of the Mediterranean diet. Adapted from Radd-Vagenas et al. [33].

Meal Foods
Breakfast Bread topped with grated fresh tomato, crumbled feta, dried oregano, and drizzled with extra virgin olive oil Herbal tea or boiled Greek coffee Lunch (main meal) Mediterranean penne with courgettes and eggplant, mozzarella cheese, olives, basil leaves. Seasoned with olive oil, and accompanied with red wine Dinner Ratatouille with tomato sauce or kale risotto with pumpkin or fish, rice, olive oil, and natural spices White wine Snacks Water Fresh fruit in season or fruit juices Nuts Dried fruit, e.g., figs, raisins Many of the polyphenol-rich elements of the Mediterranean diet are fruits, where the total phenol concentration may range between 158.8 (μmol/g) in cranberry to 7.5 (μmol/g) in grapefruit ( Table 4). Several of these fruits can be eaten in their natural form, or in the form of multi-fruit juices which present a high total phenol antioxidant index (PAOXI).  Cherry, raspberry, strawberry, grapes Delphinium and pelargonidin Dark fruits Table 3. One-day menu sample of the Mediterranean diet. Adapted from Radd-Vagenas et al. [33].

Breakfast
Bread topped with grated fresh tomato, crumbled feta, dried oregano, and drizzled with extra virgin olive oil Herbal tea or boiled Greek coffee Lunch (main meal) Mediterranean penne with courgettes and eggplant, mozzarella cheese, olives, basil leaves. Seasoned with olive oil, and accompanied with red wine Dinner Ratatouille with tomato sauce or kale risotto with pumpkin or fish, rice, olive oil, and natural spices White wine Snacks Water Fresh fruit in season or fruit juices Nuts Dried fruit, e.g., figs, raisins Many of the polyphenol-rich elements of the Mediterranean diet are fruits, where the total phenol concentration may range between 158.8 (μmol/g) in cranberry to 7.5 (μmol/g) in grapefruit ( Table 4). Several of these fruits can be eaten in their natural form, or in the form of multi-fruit juices which present a high total phenol antioxidant index (PAOXI).  Many of the polyphenol-rich elements of the Mediterranean diet are fruits, where the total phenol concentration may range between 158.8 (μmol/g) in cranberry to 7.5 (μmol/g) in grapefruit ( Table 4). Several of these fruits can be eaten in their natural form, or in the form of multi-fruit juices which present a high total phenol antioxidant index (PAOXI).  Many of the polyphenol-rich elements of the Mediterranean diet are fruits, where the total phenol concentration may range between 158.8 (μmol/g) in cranberry to 7.5 (μmol/g) in grapefruit ( Table 4). Several of these fruits can be eaten in their natural form, or in the form of multi-fruit juices which present a high total phenol antioxidant index (PAOXI). Many of the polyphenol-rich elements of the Mediterranean diet are fruits, where the total phenol concentration may range between 158.8 (µmol/g) in cranberry to 7.5 (µmol/g) in grapefruit ( Table 4). Several of these fruits can be eaten in their natural form, or in the form of multi-fruit juices which present a high total phenol antioxidant index (PAOXI).  Despite having observed a change in eating habits in countries that were the basis for the Mediterranean diet, due to economic development, high rates of urbanization, and the influence of American fast-food culture [33,52], nowadays, more and more of the world's population tries to practice a healthy diet, but with a great concern for the sustainability of the planet. Thus, the Mediterranean diet, favoring the consumption of fresh food, produced locally and according to a sustained production system, and consumed in a pleasant and familiar environment with associated physical activity, is associated with a healthy lifestyle.

Classification of Phenolic Antioxidants
Phenolic compounds are classified as primary antioxidants [53] and originate from one of the main classes of secondary metabolites in plants. They have antioxidant properties through several mechanisms: (i) the ability to remove free radicals and inhibit the formation of reactive species during the normal course of metabolism; (ii) preventing the occurrence of damage to lipids, proteins, and nucleic acids; and (iii) preventing consequent cell damage and death [56]. Thus, they are commonly associated with preventing the development of cardiovascular diseases, neurodegenerative diseases, autoimmune diseases, diabetes, and cancer [57][58][59][60][61][62].
Depending on their origin, phenolic antioxidants can be classified as natural or artificial. Figure 6 shows the classification of phenolic antioxidants. Antioxidants used in foods and beverages are intended to prevent their deterioration and to increase shelf life. However, the appearance and characteristics of each food or drink, such as color and sensory proprieties, must be kept unchanged [63]. Furthermore, they must be easy to apply and economical. The safety of food additives is verified through the application of standard methodologies by regulatory authorities, namely, the Antioxidants used in foods and beverages are intended to prevent their deterioration and to increase shelf life. However, the appearance and characteristics of each food or drink, such as color and sensory proprieties, must be kept unchanged [63]. Furthermore, they must be easy to apply and economical. The safety of food additives is verified through the application of standard methodologies by regulatory authorities, namely, the European Food Safety Authority (EFSA) or the United States Food and Drug Administration (FDA), which validate the use of substances and in which concentrations [64].
In recent years, there has been a growing preference for natural phenolic antioxidants over artificial ones, fundamentally due to the increasing demand by consumers for functional foods and beverages with the addition of natural additives, which maintain their nutritional properties and flavor [68]. Besides, this trend results, according to the same authors, from the preference currently given to natural phenolic antioxidants in food stabilization, and the restrictions applied by the responsible entities on the use of synthetic phenolic antioxidants [69,70].
Natural phenolic antioxidants have a great diversity of structures, in which the basic monomer of polyphenols is the phenolic ring [71]. They are divided into several classes, the most representative of which are flavonoids and phenolic acids. For their part, flavonoids are further divided into flavones, flavanones, flavonols, flavanols, isoflavones, and phenolic acids and are generally classified into hydroxybenzoic and hydroxycinnamic acids [72].
Stilbenes are a group of phenolic compounds that share a similar chemical structure to flavonoids ( Figure 6). Trans-resveratrol is one of the most recognized stilbenes, present mostly in glycosylated forms. Red wine, as well as the red grapes that originate this fermented drink, are rich in resveratrol. Several studies show that moderate consumption of red wine leads to a reduction in the development of cardiovascular diseases and atherosclerotic plaques, and provides neuroprotective, antidiabetic, anti-inflammatory, antioxidant, anticarcinogenic, and antiviral activity [73][74][75].
When analyzing different types of wines, namely, whites, rosés, and reds, Paixão et al. [76] showed that red wine had significantly higher phenolic levels than the rosé and white wines, and consequently exhibited the highest antioxidant power. According to Fiori et al. [77], the highest concentration of resveratrol is higher in red wine than in white wine because it is present in the skin and seeds of grapes. Thus, the different phenolic composition of wines is related to the grape variety, as well as the edaphoclimatic conditions of the region where the grapes are produced, cultural practices, the stage of ripeness [78,79], maceration [80,81], yeasts used in the vinification process [82], and other winemaking conditions [83].
Cordova and Sumpio [84] also concluded that red wine has more health-promoting activity than beer or spirits due to its richer content of phenolic compounds, hence the increased interest in the nutraceutical value of wines.
Additionally, herbal teas and infusions are rich in natural antioxidants, mainly flavonoids: theaflavins, bis-flavanols, and fulvic acids. Their consumption has increased because they are recognized as having anticariogenic properties and antimicrobial and anticancer activity [85,86]. McCarthy et al. [87] studied the antioxidant potential of plant extracts and compared them with synthetic antioxidants and vitamin E, incorporating them in pork. The catechins present in tea were shown to be more effective in terms of their antioxidant power, compared to butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), and antioxidant activity was evaluated through the thiobarbituric acid reactive substance assay (TBARS assay-reactive species of thiobarbituric acid).
The market for natural antioxidants is growing and new products have appeared on the market with a healthy image, namely, smoothies, functional drinks, and yogurts with green tea, grape seed, lemon balm, and aloe vera, among others [68].
It is important to note that there are natural antioxidants that have lower antioxidant activity than their synthetic equivalents, which can lead to the use of a higher dosage, causing toxicity reactions [88]. Thus, the intensification of toxicity studies of these compounds is necessary to know the limits of their use.

Synthetic Phenolic Antioxidants in Beverages
Several synthetic phenolic antioxidants (SPAs) are widely used in industrial and commercial products, but only a few can legally be added to food products [89]. Thus, with a common molecular structure in which the phenolic rings are replaced by alkyls hindered in the ortho position [70], butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate (PG), and tertiary-butylhydroquinone (TBHQ) are commonly used as food antioxidants [90]. However, BHA and BHT are the antioxidants most used as additives in food products [91,92].
The poor stability of natural antioxidants has increased the number of SPAs that are preferred for use in food and beverages to prevent and delay lipid oxidation reactions, preventing the formation of foreign flavors and undesirable chemical compounds, such as aldehydes, ketones, and organic acids, and prolong the shelf life of products [93].
SPAs can be used alone or in combination. Thus, BHA is commonly found in dry cereals, derived from potatoes, in cooked foods (boiled or fried and desserts), and in drinks [90,94]. In food supplements, condiments, spices, chewing gum, and oils, BHT can be used alone or in combination with BHA or TBHQ [95]. As a preservative, TBHQ is used in edible animal fats, meat products, and unsaturated vegetable oils [96]. Propyl gallate has been used in the food industry as a stabilizer in fatty foods and as an additive in mayonnaise, fats, edible fats, and baked goods [97].
The presence of a wide range of undesirable compounds in foods and beverages has made the area of food safety increasingly relevant, to provide the population with the necessary high-quality food. Therefore, the growing concern about using safe and environmentally friendly food products has recently led to the realization of several studies to find out if the use of SPAs in food and beverages is safe for health. Their conclusions are contradictory. In some studies, SPAs revealed antimutagenic and antitumor properties [98][99][100][101][102] but, in others, allergic reactions, including asthma and hives [103], toxic effects in some animal tissues [104], liver toxicity, endocrine-disrupting effects, and even carcinogenicity [93,[105][106][107] were reported, questioning their use [70,108].
This issue generated concern on the part of the governments of the European Union and most countries to create legislation that regulates the use of SPAs, either individually or in mixtures, as the market for combined natural or synthetic phenolic antioxidants is expected to have a growth rate of around 5% by 2023 [109]. In the European Union, the use of certain SPAs has been restricted and has even been banned in soft drinks [89].

Phenolic Antioxidants and Human Health
Although, in the present day, the main world health concern is COVID-19, the global pandemic caused by the SARS-COV-2 virus, other diseases also kill millions of people every year. Globally, the number of deaths due to cardiovascular diseases (CVDs) between 1990 and 2017 increased from 12.3 to 17.79 million ( Figure 7A) [110]. The World Health Organization (WHO) estimates that 60% of all CVDs occur now in developing nations ( Figure 7B) [110], where a recent increase in the incidence of CVDs has been driven by higher obesity rates. The global economic burden of these diseases is projected to rise from an estimated USD 863 billion in 2010 to an estimated USD 1044 billion by 2030 [111]. This increase is expected to be most acutely felt in nations such as India, Egypt, and the republics of the former Soviet Union ( Figure 7C) [110]. To allow comparisons between countries and over time, this metric is age standardized. Data retrieved from Our World in Data [110] and World Heart Federation [111].
Longevity is considered by the United Nations as one of the biggest achievements of this century, and a major social transformation [112]. Evidence supports that diets rich in plant-based foods can be associated with a lessened risk of cardiovascular disease (CVD) [113], thus promoting longevity. The current nutritional guidelines for the prevention of CVDs include a diet high in fruits, vegetables, whole grains, nuts, legumes, and non-tropical vegetable oils, and are based on the Mediterranean diet, which is rich in phenolic compounds [114]. Various phenolic compounds may exercise beneficial effects by reducing risk factors for the onset of CVDs and age-related disease (ARD) that involves the socalled "inflamm-aging" process [115,116]. The association of phenolic compounds with the reduced incidence of CVDs was studied by Lutz et al. [117] who state that these compounds can promote a healthy aging process, retarding or even inhibiting the risk factors involved in CVDs, mainly high cholesterol levels, high blood pressure, diabetes, urinary . The death rate from cancer (C). Annual number of deaths per 100,000 people (data from 2017). To allow comparisons between countries and over time, this metric is age standardized. Data retrieved from Our World in Data [110] and World Heart Federation [111].
Longevity is considered by the United Nations as one of the biggest achievements of this century, and a major social transformation [112]. Evidence supports that diets rich in plant-based foods can be associated with a lessened risk of cardiovascular disease (CVD) [113], thus promoting longevity. The current nutritional guidelines for the prevention of CVDs include a diet high in fruits, vegetables, whole grains, nuts, legumes, and non-tropical vegetable oils, and are based on the Mediterranean diet, which is rich in phenolic compounds [114]. Various phenolic compounds may exercise beneficial effects by reducing risk factors for the onset of CVDs and age-related disease (ARD) that involves the so-called "inflamm-aging" process [115,116]. The association of phenolic compounds with the reduced incidence of CVDs was studied by Lutz et al. [117] who state that these compounds can promote a healthy aging process, retarding or even inhibiting the risk factors involved in CVDs, mainly high cholesterol levels, high blood pressure, diabetes, urinary isoprostanes, low-density lipoprotein (LDL) oxidation, platelet aggregation, and inflammatory status, among others [118][119][120][121]. All these health-related issues contribute to atherothrombosis and the consequent occurrence of CVDs [122]. Table 5 summarizes some of the main beverages that possess polyphenolic compounds, their structures, and bioactivities. isoprostanes, low-density lipoprotein (LDL) oxidation, platelet aggregation, and inflammatory status, among others [118][119][120][121]. All these health-related issues contribute to atherothrombosis and the consequent occurrence of CVDs [122]. Table 5 summarizes some of the main beverages that possess polyphenolic compounds, their structures, and bioactivities.

Beverages Main Phenolics Indicated Bioactivities
Ref. Potential for use of EGCG in human cancer prevention and treatment. Induction of the suppression of tumor cell proliferation, stimulation of apoptosis, promotion of progestogen, and changes in testosterone release. Reduce the risk of Parkinson's disease. [53,86,123,124] Fruit juices (Tree fruits, citrus fruits, and dark fruits)

Tea and infusions
Polyphenols, most of which are flavonoids, present mainly in the ester and glycoside forms.

Beverages Main Phenolics Indicated Bioactivities
Ref. Potential for use of EGCG in human cancer prevention and treatment. Induction of the suppression of tumor cell proliferation, stimulation of apoptosis, promotion of progestogen, and changes in testosterone release. Reduce the risk of Parkinson's disease. [53,86,123,124] Fruit juices (Tree fruits, citrus fruits, and dark fruits)

Tea and infusions
Polyphenols, most of which are flavonoids, present mainly in the ester and glycoside forms.
Chlorogenic acid has potential cardiovascular benefits related to the lowering of blood pressure, endothelial function improvement, low-density lipoprotein cholesterol oxidation, and nitric oxide bioavailability prevention of metabolic syndrome, including vascular endothelial function impairment, obesity, and diabetes. [53,[129][130][131] Polyphenols, most of which are flavonoids, present mainly in the ester and glycoside forms.
Lower the incidence of degenerative diseases such as cancer, arthritis, arteriosclerosis, heart disease, inflammation, brain dysfunction, and acceleration of the aging process. [53,125] Plant-based milk substitutes (Oilseed and nut milk substitutes) (1) of the main beverages that possess polyphenolic compounds, their structures, and bioactivities.  Potential for use of EGCG in human cancer prevention and treatment. Induction of the suppression of tumor cell proliferation, stimulation of apoptosis, promotion of progestogen, and changes in testosterone release. Reduce the risk of Parkinson's disease. [53,86,123,124] Fruit juices (Tree fruits, citrus fruits, and dark fruits) Polyphenols, most of which are flavonoids, present mainly in the ester and glycoside forms.
Help to support the cardiovascular system. Lowers cholesterol levels and can reduce menopause symptoms due to their elevated content of isoflavones, which are a class of chemical known as "phytoestrogens". Their high antioxidant content makes them preventative agents against ovarian, breast, stomach, prostate, and lung cancer. [53,126-128]
Help to support the cardiovascular system. Lowers cholesterol levels and can reduce menopause symptoms due to their elevated content of isoflavones, which are a class of chemical known as "phytoestrogens". Their high antioxidant content makes them preventative agents against ovarian, breast, stomach, prostate, and lung cancer. [53,[126][127][128] Coffee (Coffea arabica and Coffea canephora) tivities.  Potential for use of EGCG in human cancer prevention and treatment. Induction of the suppression of tumor cell proliferation, stimulation of apoptosis, promotion of progestogen, and changes in testosterone release. Reduce the risk of Parkinson's disease. [53,86,123,124] Fruit juices (Tree fruits, citrus fruits, and dark fruits) Polyphenols, most of which are flavonoids, present mainly in the ester and glycoside forms.
Help to support the cardiovascular system. Lowers cholesterol levels and can reduce menopause symptoms due to their elevated content of isoflavones, which are a class of chemical known as "phytoestrogens". Their high antioxidant content makes them preventative agents against ovarian, breast, stomach, prostate, and lung cancer. [53,126-128]
Chlorogenic acid has potential cardiovascular benefits related to the lowering of blood pressure, endothelial function improvement, low-density lipoprotein cholesterol oxidation, and nitric oxide bioavailability prevention of metabolic syndrome, including vascular endothelial function impairment, obesity, and diabetes. [53,[129][130][131]  Consumption of cocoa reduces the risk of cardiovascular disease.
Extracts prepared from cocoa powder and cocoa beans were shown to exhibit antihyperglycemic effects.
Consumption of cocoa reduces the risk of cardiovascular disease. Extracts prepared from cocoa powder and cocoa beans were shown to exhibit antihyperglycemic effects.
Consumption of cocoa reduces the risk of cardiovascular disease.
Cancer is also a worldwide menace; it is the second leading cause of death in developed countries ( Figure 7A) and is increasing in developing countries. Humanity has been trying to find better and cheaper treatments with fewer side effects, to reduce the incidence of the disease and its consequent mortality [140].
Cancer is also a worldwide menace; it is the second leading cause of death in developed countries ( Figure 7A) and is increasing in developing countries. Humanity has been trying to find better and cheaper treatments with fewer side effects, to reduce the incidence of the disease and its consequent mortality [140].
Phenolic compounds have been described as exhibiting anticancer activity in vitro and in vivo [53,[141][142][143][144] (Table 5). Their efficacy varies from one compound to another, which is due to the variations in their structures as well as their molecular targets [145]. Structure vs. activity relationship studies have identified the involvement of aromatic rings and hydroxylic groups in antitumor activity [146,147]. Additionally, reports suggest that molecules with a larger number of hydroxylic groups displayed better anticancer activity compared to others with no hydroxylic groups or compounds with -OCH3 fractions The most common flavonoids in wine are flavonols (quercetin, kaempferol, and myricetin), flavan-3-ols (catechin and epicatechin), tannins, and anthocyanins (cyanin). Nonflavonoids comprise stilbenes, hydroxycinnamic acids, and benzoic acids.
Decrease the levels of lipid peroxidation and a lower the incidence of certain types of cancer. The moderate consumption of red wine has a relatively higher benefit in the prevention of atherosclerosis and coronary heart disease (CHD).
Cancer is also a worldwide menace; it is the second leading cause of death in developed countries ( Figure 7A) and is increasing in developing countries. Humanity has been trying to find better and cheaper treatments with fewer side effects, to reduce the incidence of the disease and its consequent mortality [140].
Phenolic compounds have been described as exhibiting anticancer activity in vitro and in vivo [53,[141][142][143][144] (Table 5). Their efficacy varies from one compound to another, which is due to the variations in their structures as well as their molecular targets [145]. Structure vs. activity relationship studies have identified the involvement of aromatic rings and hydroxylic groups in antitumor activity [146,147]. Additionally, reports suggest that molecules with a larger number of hydroxylic groups displayed better anticancer activity compared to others with no hydroxylic groups or compounds with -OCH3 fractions [145]. In addition, studies comparing the efficacy of cinnamic and benzoic acids in inhibiting cancer cell growth showed that cinnamic acids that contain an unsaturated propionic acid side chain are superior anticancer agents [146,147]. Therefore, benzoic and cinnamic acid derivatives possessing hydroxyl substitutions could be used naturally or in pharmaceutical formulas to prevent cancer cell proliferation [145].
Another concern, in terms of wellbeing, especially in the 21st century, as life expectancy, according to the WHO, is projected to reach 73 years by 2025 [151], is neurodegenerative diseases such as Alzheimer's and Parkinson's. Many thousands of people born at the end of the 20th century will live through the 21st century and see the advent of the 22nd century. People will live longer, but will they really have "quality of life"? Evidence supports that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis [152].
The pathogenesis of diseases such as Alzheimer's or Parkinson's is multifactorial, with a complex combination of genetic and nongenetic components [53,125,152]. Most of these cases are nongenetic or sporadic. According to the World Health Report [152], inflammation, glutamatergic toxicity, dysfunction of mitochondrial activity and the ubiquitin/proteasome system, activation of apoptosis pathways, elevation of iron and nitric oxide, and alteration of the homeostasis of antioxidants/oxidation are the main mechanisms involved in neurodegenerative pathologies. Green tea, which is particularly rich in flavonoids [86], including catechins and their derivatives, could have a beneficial role in reducing the risk of Parkinson's disease [53,153]. The catechol-like structure of catechins competitively inhibits uptake by the presynaptic or vesicular transporters of the metabolite product of 1-methyl-4-phenylpyridinium ions (MPP+), also presenting a catechol-like structure. This competition protects dopaminergic neurons against MPTP/MPP+-induced injury [154].
Alzheimer's disease pathology progresses gradually via anatomically connected brain regions. The progressive pathology is due to the direct transfer of amyloid-β1-42 oligomers (oAβ) between connected neurons [155]. Concerning Alzheimer's disease, there are several in vitro studies demonstrating that green tea extract may protect neurons from amyloid β-induced damage [156,157].
Oxidative stress or inflammation can also be the cause of chronic diseases such as diabetes, insulin resistance, urinary tract infections, chronic obstructive pulmonary disease, and rheumatoid arthritis [53,158,159]. These chronic diseases, like arthritis (also considered an autoimmune disease with unknown etiology), may accelerate cardiovascular complications [147].
Phenolic compounds have been described as able to promote a decrease in hyperglycemia, improve acute insulin secretion and insulin sensitivity [160], prevent rheumatoid arthritis [161], and have antiadhesive activity against uropathogenic bacteria, preventing urinary tract infections [162].
So, all the health menaces described above have a huge impact, not only on personal health, but also in terms of people's productivity, wellbeing, and, ultimately, quality of life and happiness.

Digestion, Catabolism, and Bioaccessibility of Beverage Phenolic Compounds
The absorption, transportation, bioavailability, and bioactivity of polyphenols and related metabolites after food or beverage intake have been research topics of increasing interest in recent decades. The absorption and metabolism of polyphenols in the digestive tract regulate their biological properties and bioavailability, and only those released from the food/beverage matrix are digested in the small and large intestine [163]. Polyphenols occur in beverages mainly as large polymers (esters, glycosides) which cannot be absorbed in these forms and require hydrolysis by digestive enzymes or intestinal microbiota. Only 5-10% of the phenolic compounds from different fruits are bioaccessible in the small intestine, while 90% of phenolic compounds reach the large intestine, where they are catabolized by gut microbiota [164,165].
Gut microbiota convert complex polyphenols into low molecular weight compounds that can be absorbed [24] and thus are accountable for the beneficial effects of polyphenol consumption [166,167]. Additionally, clinical studies indicate that polyphenols are also able to express prebiotic properties, by modulating the growth of beneficial bacteria such as Bifidobacterium and Lactobacillus [167,168]. New products containing probiotic strains as well as polyphenol compounds as antioxidants have been launched in the market, particularly beverages based on fruits, vegetables, cereals, and soybeans [169,170]. Additionally, nanoencapsulation-based approaches can be used to develop beverages, which may com-bine the benefits of natural products with the known biological properties of phenolic compounds, without resulting in a loss of sensory or nutritional quality and increasing bioaccessibility [171].
However, as stated by Teng and Chen [172], bioaccessibility values of polyphenolic compounds should be strongly reconsidered, considering the recently identified circulating and excreted metabolites, keeping in mind the colonic metabolic products which contribute largely to their absorption, making them able to travel around the human body in the circulatory system or reach body tissues to elicit bioactive effects.

Final Remarks
Phenolic compounds may affect the sensory characteristics of food with impact on color, flavor, and astringency. This impact is important and needs to be evaluated so that health-promoting compounds are also pleasant and generally consumed. Moreover, more projects and the implementation of more research, especially for human trials, are needed to confirm the efficacy of polyphenols at the gut level.
The Mediterranean diet based on dietary patterns in the countries of the Mediterranean basin is considered healthy because it is centered on the consumption of fruits, vegetables, cereals, olive oil, fish, eggs, and meats (in moderation). Fruit juices, tea, herbal infusions, coffee, nondairy beverages, beer, and red wine are included in the diet, directly or as a by-product of vegetal origin that is processed, possibly fermented, and also may contain probiotic microorganisms valuable for gut microbiota equilibrium and polyphenol bioavailability and absorption.
The demand for this type of diet by consumers has increased, as it is associated with the prevention of cardiovascular disease, cancer, and neurodegenerative diseases, and longevity. The pharmaceutical industry has been discovering medicines that diminish some of the symptoms of these diseases. Many are still incurable, and prevention is still the best action. Prevention requires a change in lifestyle habits, especially in food and beverage consumption. Strong and already confirmed evidence suggests that a diet of food and beverages rich in polyphenols may help to prevent and control the abovementioned health issues, reducing multimorbidity and leading to a healthier and happier life.