Bioactive Properties of Fermented Beverages: Wine and Beer

Abstract

In recent years, consumer demand has been increasingly oriented to fermented foods and/or beverages with functional properties. The functional beverage industry focused on producing a product that combines a peculiar aromatic taste with healthy properties. Today’s consumers are trying to reduce alcohol, gluten, sugar, and carbohydrates in beer and wine without reducing their native taste. Wine and beer are among the world’s most consumed beverages, and several studies confirm that fermented beverages could be associated with beneficial properties for human health. All beneficial properties derive both from the fermentation process and also from the characteristics of the raw materials used in the two beverages. This review was conducted to highlight the importance of the fermentative microorganisms in wine and beer and their relationship with functional foods, underlining their involvement in human health.

1. Introduction

Fermented beverages, in particular wine and beer as protagonists of the present review, are very complex products in terms of their ingredients. There are several parameters that affect their final quality, such as the quality of raw material: grapes for wine, which contain sugars (glucose and fructose) crucial for the alcohol content of the final wine, and malt for beer, the primary source of fermentable sugars. Hops are flowers that add bitterness, flavor, and aroma to beer. Yeast species: native yeasts found on the skins of grapes or added commercial strains of Saccharomyces cerevisiae used to ferment the sugar in grape juice into ethanol. Similar to wine, Saccharomyces cerevisiae is commonly used in beer fermentation, although Saccharomyces pastorianus (lager yeast) is used for lagers. Management of alcoholic fermentation (and malolactic in the case of red wine) and aging processes to develop complex flavors, among others [1]. Since the early 20th century, the composition of these two beverages during all the phases of production has been widely studied by many researchers. In recent years, research has shown growing interest in their bioactive ingredients. Nowadays, “functional food or beverage” refers to a non-alcoholic beverage product whose constituents include herbs, amino acids, vitamins, minerals, and raw vegetables or fruits that provide health benefits in addition to their nutritional value [2]. The beverage industry that produces “functional beverages” aims to enable consumers to enjoy a beverage with an added function. This function is commonly associated with health-enhancing properties and benefits for the entire body. The bioactive ingredients in both wine and beer contribute significantly to their health benefits and flavor profiles. These compounds are not just responsible for the taste and aroma but also have potential antioxidant, anti-inflammatory, and other health-promoting properties.

Wine, particularly red wine, is rich in polyphenols such as resveratrol, flavonoids, tannins, and anthocyanins. These compounds have antioxidant effects, which may help neutralize free radicals in the body, potentially reducing the risk of chronic diseases like cancer and heart disease; anti-inflammatory activity, important for preventing chronic diseases like arthritis and cardiovascular diseases or diabetes; and antimicrobial properties, which may help protect the body from harmful pathogens [3,4]. Polyphenolic compounds present in wine can modify the composition of the oral microbiota [5]. These compounds exhibit antimicrobial properties that can inhibit the growth of pathogenic bacteria associated with dental caries and periodontal diseases. By modulating the oral microbiome, wine polyphenols contribute to maintaining oral health and reducing the risk of tooth decay and gum inflammation. The polyphenols in red wine, especially resveratrol, are thought to improve blood vessel function and reduce cholesterol levels [4]. It also has a mild appetite-stimulating effect. On the other hand, beer contains polyphenols from malt and hops, which also contribute to its antioxidant properties. These compounds may help combat oxidative stress in the body [6]. Some studies suggest that moderate beer consumption might help increase bone density, particularly due to its polyphenol content. Red wine, in particular, has been associated with positive effects on bone health, though this needs further research [6]. Beer contains dietary fiber, which can aid in digestion and promote gut health. Additionally, certain compounds in beer may have prebiotic effects, supporting the growth of beneficial gut bacteria [7]. Also, the polyphenols in beer, particularly xanthohumol from hops, may help lower cholesterol levels and improve blood vessel function [6]. Melatonin found in wine and beer has raised great interest related to its health promotion effects. It has many functions, including enhancement of the antioxidant system, circadian rhythm regulation, sleep promotion, and immune regulation [8,9,10]. However, it is important to consider that while moderate consumption of wine or beer may help offer these potential benefits, it is important to remember that excessive alcohol consumption can have adverse effects on health. The key is moderation, as excessive intake may negate these benefits and lead to other health problems.

On the other hand, it can never be forgotten that both products are treated as fermented beverages; therefore, the protagonism of yeast strains in their final composition is crucial. Polyphenols’ functional activities are usually significantly changed during fermentation processes since there are considerable changes in their composition and content. Fermentation converts large-molecule polyphenols into small ones with stronger physiological activity. Therefore, fermented beverages such as wine and beer have higher bioactive value after fermentation [11]. Research studies have largely focused on Saccharomyces cerevisiae yeast, but now, non-Saccharomyces yeasts are being widely studied for their applicability in fermented beverage production. Some of the most promising yeasts for manufacturing functional wines and beers are the yeast species Wickerhamomyces anomalus and Torulaspora delbrueckii [12,13,14]. Regarding non-Saccharomyces applicability as probiotics, a significant number of species, such as Hanseniaspora osmophila, Lachancea thermotolerans, Metschnikowia pulcherrima, and T. delbrueckii, were evaluated from a functional health point of view [15,16]. Additionally, non-Saccharomyces yeasts are currently being used in agriculture as biological control mechanisms [17,18,19].

The objective of this paper is to review the raw material and the technological processes of elaboration of the two most popular beverages nowadays, wine and beer. The following section of the paper explores the impact of the raw material and the activity of yeasts during fermentation on the different natural health-promoting compounds of these beverages.

2. Winemaking and Brewing Process

2.1. Wine

2.1.1. Must Grape Composition

Grape must is the juice obtained after pressing freshly harvested grapes, and it includes the skins, seeds, and stems. This mixture is rich in a variety of compounds, such as sugars, acids, and phenolic and aromatic substances, which play a crucial role both in the fermentation process and in the final characteristics of wine [20]. The main components of grape must include:

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After water, which constitutes approximately 80–85% of the must, serving as the solvent for all other components [21], the most abundant substances in grapes at ripeness are sugars, in the form of fructose and glucose. These are found in almost equimolar amounts since they arise from hydrolysis of the disaccharide sucrose, produced through leaf photosynthesis. These fermentable sugars provide the primary substrate for yeast during fermentation [22]. Small amounts of pentoses and other sugars are also present alongside the primary sugars. Related to sugars are polysaccharides, which are long chains of sugar molecules that come from the cell walls of grape berries. These carbohydrate polymers are naturally present in the grape must. During winemaking, certain enzymatic treatments can hydrolyze some of these polysaccharides, causing them to be released into the must and ultimately into the wine. It can affect its texture, mouthfeel, and overall quality by making it feel fuller or smoother [23].

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Organic acids: Organic acids are a crucial group of compounds found in grape juices and wines. They play a key role in influencing the wine’s chemical and microbiological stability, impacting factors like appearance, pH, and titratable acidity. Additionally, these acids contribute significantly to the sensory characteristics of wine, such as its flavor [24,25,26]. Tartaric acid is typically the dominant acid in grape juice and serves as an important indicator of its composition. It plays a crucial role in preserving the chemical stability of wine, influencing factors like color and flavor [27]. Tartaric acid is produced during the early stages of berry cell development and continues to form as the berries mature [26]. Malic acid is produced early in the growing season, but its behavior during grape maturation and winemaking differs from that of tartaric acid. Initially, malic acid levels are gradually broken down as the berries ripen. The concentration of malic acid tends to be lower in warmer climates and in fully ripened grapes compared to cooler regions and less ripe grapes, depending on the specific growing conditions [25,26]. Malic acid will also contribute substantially to acidity and can be metabolized by lactic acid bacteria during malolactic fermentation, softening the wine’s taste. Minor acids in grapes include citric and ascorbic, although the former will also be produced through yeast metabolism, and traces of other acids have also been documented [28]. These acids are naturally found in grape juices. Other organic acids, such as succinic, lactic, and acetic acids, are also present in juice or wine, but they are primarily by-products of the winemaking process, including fermentation and microbial activity [25]. Succinic acid is produced early in the fermentation process, with its formation influenced by the yeast strain used and the specific nitrogen source available [26]. Citric acid plays a key role in metabolic processes, such as the Krebs cycle, and serves as an acidifying agent in food and beverages. In wine, an elevated concentration of citric acid may indicate adulteration [27]. Lactic acid bacteria can partially or completely metabolize citric acid, with acetic acid as a potential product. Additionally, citric acid metabolism contributes to the formation of diacetyl, acetoin, and 2,3-butanediol. The buttery aroma present in some wines arises from the diacetyl pathway. Higher acetic acid levels in wine typically result from spoilage by lactic acid or acetic acid bacteria [26].

Table 1. Main organic acids in grapes, must, and wine and their benefits.

Organic Acid	Presence/Location	Benefits
Tartaric Acid	Naturally occurring, unique to grapes	Stabilizes wine pH Adds freshness and structure Helps with preservation
Malic Acid	Natural, found in green grapes	Provides acidity and liveliness Adds freshness to young wines Converts to lactic acid during malolactic fermentation
Lactic Acid	Formed during malolactic fermentation	Softens acidity Adds creamy, rounded mouthfeel Enhances microbial stability
Acetic Acid	By-product of fermentation	In excess, causes vinegar-like off-flavors (a defect)
Citric Acid	Naturally present in small amounts in grapes	Increases acidity Enhances fruity flavor Acts as a natural antioxidant
Succinic Acid	Formed during alcoholic fermentation	Contributes to total acidity Adds pleasant salty and bitter notes in small doses

contains a summary of the main organic acids, their location, and their benefits.

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Phenolic compounds in grapes must play a crucial role in the flavor, color, mouthfeel, and overall quality of wine. These compounds are primarily derived from grape skins, seeds, and stems, and they can be extracted into the must during crushing and maceration. Phenolic compounds are naturally occurring substances consisting of one or more hydroxyl groups bonded to aromatic or benzene rings. Based on their benzene ring structure, they are classified as either flavonoids or nonflavonoids [29]. In wine, polyphenols play a crucial role in shaping various sensory characteristics, including appearance, color, astringency, bitterness, and flavor, while also contributing to the wine’s stability during oxidative processes [30]. These compounds originate from various parts of the grape: (1) the skins, which are rich in anthocyanins, flavan-3-ols, flavonols, dihydroflavonols, hydroxycinnamoyl tartaric acids, hydroxybenzoic acids, and hydroxystilbenes; (2) the seeds, where flavan-3-ols and gallic acid predominate; and (3) the juice, which primarily contains hydroxycinnamoyl tartaric acids [31]. The phenolic profile of a wine is shaped by the composition of the grape, the extent to which these compounds are extracted during juice processing, and the chemical reactions that occur during vinification, post-fermentation treatments, and aging [32].

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Nitrogen compounds, especially amino acids and ammonium, are the major nitrogenous compounds present in grapes and are critical for yeast growth and fermentation. In grape must, nitrogen compounds play a key role in fermentation. About half of the nitrogen compounds are α-amino acids, which are forms of nitrogen that yeast can use during fermentation [23]. These are referred to as yeast assimilable nitrogen (YAN), which is crucial because it helps yeast grow and complete fermentation properly. The remainder is proline and cannot be utilized. Environmental factors as well as grape variety can influence the amino acid content of the must [33]. That is why when the levels of NFA are low, the must is usually supplemented with nitrogen, such as di-ammonium phosphate, to avoid fermentation problems.

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The mineral content that can be present in must and wine refers to cations and their elements. These minerals are classified according to their electrical charge, as well as their abundance, into abundant cations (plant macronutrients): K⁺, Ca²⁺, Mg²⁺, Na⁺, and Si⁴⁺, and less abundant cations (micronutrients): Fe³⁺, Mn²⁺, Zn²⁺, Al³⁺, Cu²⁺, Ni²⁺, Li⁺, Mo⁴⁺, Co²⁺, and V³⁺. And in more abundant anions: PO₄³, SO₄²⁻, Cl⁻, and less abundant: Br⁻, I⁻ [22].

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The vitamin content of grapes is usually used up by yeasts during the fermentation process, but due to yeast metabolism, we find vitamins in the wine at levels similar to the beginning [34]. Vitamins generally found in fresh grapes are ascorbic acid, niacin, vitamin B6, riboflavin, thiamine, folate, and vitamin A (USDA nutritional analysis of fresh grapes) [35].

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Aromatic compounds: The precursors of C13-norisoprenoid aromatic compounds are carotenoids, which, although found in low concentrations in grapes, are present in all plants. On the other hand, isoprenoids will also contribute to the aroma of wine, and among these are monoterpenoids, sesquiterpenoids, and C13-norisoprenoids. The floral aroma of Muscat grapes is due on the one hand to the C13-norisoprenoids (they exist as non-volatile glycosides) and on the other hand to a free fraction of monoterpenoids [36]. Pyrazines are nitrogenous compounds derived from the metabolism of amino acids [37]. They are associated with typical vegetal aromas related to herbaceous character and are characteristic of Sauvignon Blanc [38,39] and Cabernet Franc varieties. They are mostly found in the skins and seeds, with a smaller proportion in the pulp [40]. Three main pyrazines have been identified in grapes: 3-isobutyl-2-methoxypyrazine (IBMP), 3-sec-butyl-2-methoxypyrazine (SBMP), and 3-isopropyl-2-methoxypyrazine (IPMP) [41].

2.1.2. Winemaking

Wine fermentation dates back thousands of years, evolving through different cultures and technological advancements. The earliest evidence of winemaking comes from Anatolia, around 6000 BCE [42]. Winemaking is deeply rooted in the traditions and lifestyles of many cultures. Each region has developed unique techniques and customs over thousands of years, influenced by geography, climate, and local heritage. Vinification, or winemaking, has evolved with scientific advancements in microbiology and chemistry. It was during the Scientific Revolution and Industrialization (1700–1900) that scientist Louis Pasteur discovered the role of yeast in fermentation, disproving the idea that it was a spontaneous process [43]. Winemakers began to control fermentation temperatures, which led to more predictable results. The control of the yeast strains used, as well as the use of stainless-steel tanks (in the 1950s and 1960s), revolutionized white wine fermentation by preserving fresh aromas, while malolactic fermentation became widely used to soften the acidity of red wines.

Because winemaking is an ancient tradition, it naturally gives rise to a wide range of wine styles, each of which can influence the microorganisms involved in the process. In the following section, we will delve into the essential stages of winemaking and the key transformations that take place during the production process. To provide a clearer understanding, we also present an overview of both white and red wine production, highlighting the specific differences between the two processes.

The production of white wine is a carefully controlled process designed to highlight the freshness and fruity flavors of the grapes. The grapes are typically harvested earlier than those for red wine to maintain acidity and freshness. The ideal harvest time depends on sugar content, acidity, and the desired flavor profile [44]. It is very important to select the best quality grapes, as any defects in the grapes will affect the final wine quality. Unlike red wines, which ferment with their skins to extract color and tannins, in the production of white wines in a conventional way, the grapes are pressed immediately after crushing to separate the must from the skins and seeds. The must will be clarified by settling or centrifugation to allow impurities and suspended solids to settle to the bottom of the tank, and the must will be moved to the fermentation tank where the alcoholic fermentation is carried out [45,46]. Ethanol fermentation is the enzymatic breakdown of sugars into ethanol and carbon dioxide through the action of the yeast under anaerobic conditions. The most commonly used yeasts belong to the Saccharomyces genus, especially strains like Saccharomyces cerevisiae ssp. cerevisiae and S. cerevisiae ssp. bayanus [47,48]. Fermentation will begin spontaneously by native yeasts or by adding commercial yeast into the must [49,50,51]. White wine fermentation usually takes place at lower temperatures (10 and 18 °C) [52]. Once the availability of the primary sugars in must (glucose and fructose) has been consumed, the wine is finished, and it is then separated from the yeast and grape lees (sediment).

Red wines are elaborated using a slightly different process compared to white wines. After harvesting, the grapes are destemmed. This step is important to prevent the release of herbaceous and bitter compounds from the stems into the wine. Unlike white wine, red wine fermentation takes place with the skins. This allows for the extraction of anthocyanins, which give the wine its color, and tannins, which provide structure and body. The must with skins is placed into a fermentation tank (stainless steel or wood), and the fermentation process starts through the action of indigenous yeasts or via direct inoculation [45,53]. Throughout fermentation, the grape solids rise to the top of the tank, forming a “cap”. To enhance the extraction of red pigments, influence the wine flavor, and maintain an even temperature throughout the must, winemakers use techniques to either punch down the cap or pump the juice from the bottom over the cap. Red wine fermentation usually occurs at higher temperatures (20–30 °C) [54,55] to promote the extraction of color and tannins. After fermentation, the resulting wine (with skins, seeds, and pulp) is pressed carefully to avoid extracting many bitter tannins from the seeds and to separate the liquid from the remaining solids. Red wine often is spontaneously, or purposely, taken through malolactic fermentation (MLF). This fermentation can occur naturally through the action of the wine’s native microorganisms, but it is an unpredictable process, as harsh environmental conditions can delay or even halt MLF entirely. Consequently, there has been ongoing advancement in selecting specific bacterial strains and developing starter cultures, allowing for more consistent and controlled management of the MLF process. In this fermentation, lactic acid bacteria (LAB) transform the harsher malate into softer lactate, resulting in a smoother and rounder wine. Currently, the strain Oenococcus oeni is recognized as the most effective and specific for ensuring the successful progression of MLF [56]. Unlike the alcoholic fermentation, the malolactic fermentation is a consideration by the winemaker, who may choose to prevent this fermentation from initiating through the use of antimicrobial additions or filtration [52]. After malolactic fermentation, the wine is racked and begins its aging process. Many red wines are aged in oak barrels, which adds complexity and imparts additional flavors such as vanilla, spices, and wood notes. Some lighter or fresher red wines are aged in stainless steel tanks to maintain their fruity aromas and freshness without the influence of oak. The aging time in barrels can vary depending on the style of wine and the winemaker [57,58,59]. White wines are typically not aged for long periods, whereas red wines are often aged, with aging times ranging from 6 months to several years [60].

2.1.3. Ecology During Wine Fermentation

The ecology during wine fermentation is a dynamic and crucial component of winemaking. The interactions between wild and cultured yeasts, lactic acid bacteria, temperature, oxygen levels, and available nutrients all contribute to the progression of fermentation and the final characteristics of the wine. By understanding and controlling these microbial dynamics, winemakers can influence flavor, aroma, texture, and overall wine quality, producing wines with unique and desired profiles. The complex interaction of microorganisms, particularly yeasts and bacteria, within the fermentation process plays a crucial role in shaping the characteristics of the wine, from fermentation dynamics to flavor profiles [61,62,63].

Grapes naturally carry microorganisms on their skins, including wild yeasts (mainly Saccharomyces and non-Saccharomyces sp.), bacteria, and molds. These microorganisms can begin fermentation when grapes are crushed and the must is exposed to oxygen. The composition of the microbial community can vary greatly depending on environmental factors such as the vineyard location, the harvest time, and weather conditions [63]. Research has demonstrated that grape-associated microbial communities are non-randomly associated with regional, varietal, and climatic factors across different viticulture zones. This suggests that environmental conditions play a significant role in shaping the microbial consortia on grape surfaces, which in turn can impact grapevine health and wine quality [64]. Studies have also shown that the size and diversity of cultivable microbial communities on grape berries are higher in vineyards with lower temperatures. Additionally, water activity (aw) has a positive effect on the cultivable population, metabolic activity, and microbial diversity, indicating that microclimate influences the microbial population associated with grape berries through the aw of grape skins [65]. Furthermore, the microbial community of the grape epidermis has been found to be closely associated with vineyard weather conditions. For instance, fungal diversity during grape maturation is mainly affected by relative humidity and precipitation, while bacterial diversity during certain stages is influenced by precipitation and relative humidity [66].

In the first stage of fermentation, wild yeasts (such as Kloeckera, Pichia, Candida, and Saccharomyces species) start consuming sugars, although they are less alcohol-tolerant than S. cerevisiae [67]. They typically thrive in the early stages, when alcohol levels are still low, and contribute to the development of aroma compounds, including esters and other volatile molecules. As fermentation progresses and alcohol levels rise, wild yeasts are often outcompeted by S. cerevisiae. In some cases, winemakers may choose to inoculate the must with selected S. cerevisiae to ensure predictable fermentation, but wild yeasts still play a role in the early stages because they can introduce a degree of unpredictability in the fermentation process. The timing and success of yeast inoculation can determine the final characteristics of the wine [68]. Currently, the implementation of mixed-culture inoculation protocols, incorporating diverse S. cerevisiae strains or the targeted introduction of non-Saccharomyces yeasts and/or lactic acid bacteria (LAB) through co-inoculation or sequential inoculation strategies, has been proposed as an optimized approach to harness the metabolic complexity of spontaneous fermentation while mitigating the risks associated with microbial spoilage, fermentation arrest, and stuck fermentations [69]. The advantages of mixed-culture fermentations lie in their ability to enhance wine complexity by increasing the diversity of volatile and non-volatile chemical compounds, enhancing the organoleptic properties of the wine, including more nuanced aroma and flavor profiles, which are generally preferred by consumers. Unlike pure fermentations using a single S. cerevisiae strain, mixed-culture fermentations foster synergistic metabolic interactions between yeasts, resulting in the production of distinct metabolites that cannot be achieved by monocultures alone [70]. Nevertheless, to achieve these desired outcomes, it is necessary to precisely control fermentation parameters, such as temperature, nutrient availability, and oxygen levels, since the metabolic activity and viability of Saccharomyces and non-Saccharomyces yeasts are very sensitive to environmental conditions [71]. Successful mixed-culture fermentations can be achieved by increasing the contribution of non-Saccharomyces yeasts through the enhancement of their metabolic activity and prolongation of their survival during fermentation [72]. Nevertheless, scientific studies have reported inconsistent results, even when examining the same yeast species [73,74]. Historically, it was assumed that non-Saccharomyces yeasts disappeared during the early phases of alcoholic fermentation due to their limited tolerance to challenging conditions, such as rising ethanol concentrations and nutrient depletion. However, recent in-depth research has revealed that the decline and survival patterns of these yeasts are influenced by various antagonistic microbial interactions, including competition, resource depletion, and biochemical inhibition [75].

In certain winemaking techniques, different species of yeast and even different strains of S. cerevisiae may be used together. Co-fermentation can lead to more complex aromas and flavors, as different yeast species produce different byproducts, such as acids, alcohols, and esters [76].

MLF occurs after alcoholic fermentation, but it can be influenced by the presence of other microorganisms. Wild bacteria, including strains of Lactobacillus and Pediococcus, may also compete with Oenococcus oeni. Winemakers often inoculate with specific bacterial strains to control the timing and success of MLF [56]. Oenococcus oeni is the dominant lactic acid bacteria (LAB) species associated with malolactic fermentation (MLF), primarily due to its ability to thrive under the harsh conditions typically found in wine, including high ethanol concentration, low pH, elevated SO₂ levels, and low temperatures [77]. However, global climate change is altering wine composition by increasing alcohol content and reducing acidity, which is driving changes in the bacterial ecosystem. Recent studies have shown that Lactobacillus and Pediococcus are also capable of surviving in different winemaking environments [78,79], with their metabolic pathways playing an increasingly important role in shaping wine aroma and flavor profiles [80]. Despite these findings, spontaneous MLF during winemaking remains unpredictable and difficult to control, which can result in delayed fermentation and pose risks to wine quality. Potential issues include an unstable bacterial environment, the production of unpleasant odors, elevated levels of biogenic amines (BAs), and excessive volatile acidity [81]. Therefore, achieving microbial stability and maintaining the sensory quality of wine depend on a reliable and well-managed MLF process.

Other factors that may influence microbial ecology: at the start of fermentation, some oxygen is beneficial for yeast growth and metabolism. However, excessive oxygen exposure can lead to the growth of spoilage microorganisms, such as acetic acid bacteria (Acetobacter) or molds (Botrytis or Penicillium), which may result in off-flavors or spoilage. As fermentation progresses and the yeast begins to consume sugars, the oxygen levels in the must decrease, and the environment moves toward anaerobic conditions. This encourages the activity of ethanol-producing yeasts and suppresses the growth of oxygen-dependent spoilage organisms. Yeast activity is highly temperature dependent. Optimal temperatures range between 25 and 30 °C, depending on the type of wine being elaborated. Higher temperatures can speed up fermentation but may cause excessive production of volatile compounds or even stress the yeast, while lower temperatures may slow fermentation and allow non-Saccharomyces yeasts to dominate for longer [82]. A deficiency in nutrients can lead to slowed or stuck fermentation, where the yeast fails to complete fermentation. Some winemakers add nutrients to ensure healthy fermentation and avoid stuck fermentations, which could result in the production of off-flavors [23].

The yeast and bacteria involved in fermentation play a significant role in the final flavor profile of the wine. Wild yeasts may introduce complexity, contributing unique aromatic compounds like fruity, floral, or spicy notes. In contrast, S. cerevisiae generally leads to a more predictable and cleaner fermentation, producing fewer off-flavors. Moreover, yeast and bacterial activity also influence the wine’s mouthfeel and tannin structure. During fermentation, yeast cells break down grape cell walls and release phenolic compounds, which contribute to the wine’s astringency and body. The choice of yeast and the length of fermentation can modify the extraction of tannins and influence the wine structure [83].

2.2. Beer

Beer is one of the most consumed alcoholic beverages in the world. The ingredients used are barley (Hordeum vulgare), hops (Humulus lupulus L.), water, and yeast [84,85]. The brewing process consists of malting, which is the transformation of barley or other cereals into malt, which is then added with water in the mashing phase to obtain wort. This substrate was fermented to transform the sugar into ethanol, carbon dioxide, and secondary metabolites. At the end of the fermentation process, the beer was subjected to a downstream process to obtain a final beer [86].

In recent years, there has been a trend among brewers to produce beers with different sensory profiles, especially “specialty beers”. The latter has experienced exponential growth in the last two decades, mainly driven by increasingly health-conscious consumers [87]. Specialty beers are low-calorie, low-alcohol, or non-alcoholic, gluten-free, and functional beers [88]. Beer contains some health-promoting substances that positively impact human health, including minerals, vitamins, polyphenols, fiber, and relatively low levels of ethanol. Functional beers are products obtained by adding a health-promoting value, intended as functional ingredients or functional fermentation yeasts [89]. Indeed, beer is rich in minerals, vitamins, and high nutritional value, and it could be considered a functional beverage from ancient times. Nowadays, “functional food or beverage” refers to a non-alcoholic beverage product whose constituents include herbs, amino acids, vitamins, minerals, and raw vegetables or fruits that provide health benefits in addition to their nutritional value [90,91,92,93]. The beverage industry that produces “functional beverages” aims to enable consumers to enjoy a beverage with an added function. This function is often related to properties that improve health and beneficial actions for the entire human body. Today’s consumers commonly seek to reduce alcohol, gluten, sugar, and carbohydrates in beer, but without reducing its native taste [94].

Beer possesses many functional ingredients, such as phenolic acids, polyphenols, quercetin, kaempferol, tyrosol, flavones, humulones, lupulones, vitamin B, vitamin B12, xanthohumol, minerals, and complex carbohydrates, except ethanol [95]. Functional ingredients in beer can mitigate the negative effects of alcohol. During the brewing process, the brewer could add other cereals or sources of sugars.

Malt beverages are considered functional and probiotic systems due to their nutritional and health properties. The beer industry has focused on research and development of new technologies and innovations to expand the craft beer offering in response to growing consumer demand. In this regard, craft beer is a product characterized by no pasteurization and produced in small breweries that use traditional methods in proving the process, focusing attention on the quality of the product. In craft breweries there is the tendency to brew gluten-free, low-calorie, low- and non-alcoholic, and functional and probiotic beer [96].

2.2.1. Wort Composition

Beer is obtained as a result of numerous metabolic and chemical reactions in which yeasts are involved. The brewer will always be looking for ways to optimize the use of yeasts to improve their fermentation performance, stress tolerance, and ethanol production. The goal is to produce a beer of satisfactory quality and consistent characteristics.

The quality of the beer is mainly defined by the flavor profile it presents, which is influenced throughout the entire brewing process. As a result of yeast metabolism, ethanol, glycerol, and carbon dioxide are produced. To this must be added the production of aromatic compounds, which determine the organoleptic characteristics of a beer (esters, higher alcohols, sulfur compounds, organic acids, and carbonyl compounds). The most remarkable ones are going to be the esters and higher alcohols, since they will bring fruity and floral aromas and a warm mouthfeel to the beer [97].

The sugar content of beer wort contains approximately 90% carbohydrates: glucose, fructose, sucrose, maltose, maltotriose, and dextrins. Its proportions will depend on the raw materials and process. The ingredient that will provide the sugars to the wort is malt; the most commonly used is malted barley, although other additives such as sorghum, wheat, and corn can provide sugars to the wort [98,99]. The studies carried out by Yorke et al. [100] determined the percentage of non-malted adjuncts that contributed the highest content of original extract, with wheat (60%) being the highest adjunct contributor of sugars to the wort. However, the final polyphenol content of the beer was higher in beers brewed with 30% adjuncts such as rice or wheat. One of the parameters to be taken into account when selecting a malt is its diastatic power, which indicates its capacity to convert starch into fermentable sugars [101]. The malting process consists of germinating cereals, drying them, and then roasting them. In this process, the starch available in the cereals is hydrolyzed by the action of enzymes that will later transform it into fermentable sugars during the mashing process. Depending on the roasting time and temperature, there are different types of malts: base malts (pale), specialty malts (caramel), and roasted malts (chocolate, coffee) [102]. Likewise, the sugar content varies depending on the malt used; dark malts contribute the least amount of fermentable sugars to the wort [103]. Similarly, the use of roasted malts provides a higher polyphenol content, as well as an increase in the antioxidant capacity of the wort [104]. Maltose is the most abundant sugar in beer wort, but yeasts start fermenting monosaccharides [105]. Therefore, the carbohydrate composition of the wort and its fermentation influence yeast metabolism and fermentation efficiency, modifying the organoleptic profile of the final product [106]. Variations in aromatic profiles have also been observed depending on sugar concentration; higher glucose and fructose concentrations produce more esters [107]. However, high sucrose concentrations cause stress in yeast cells, decreasing their viability as well as ester production [108]. Those sugars that are not fermented, such as dextrins or some maltotrioses, will add body, mouthfeel, and drinkability to the beer.

The individual amino acids in the must, ammonium ions, and small peptides are called assimilable nitrogen (FAN) by the yeasts. Its concentration may vary depending on malting and milling and/or raw materials. FAN is used as a general measure of yeast nutrients because they are necessary for their metabolism and, therefore, to obtain a quality beer. Worts with more FAN (12.0 °P at 115, 160, and 230 mg/L, respectively) showed higher production rates and final concentrations of isoamyl acetate [109], as it may affect the transcription of genes involved in the production of esters and higher alcohols (ATF1 and BAT1) [110,111]. Therefore, the concentration of FAN can influence the aromatic composition of beers. However, it can also be affected depending on the type of amino acids of which the wort is composed. Studies by Lei H. et al. [112] found that adding histidine to the wort increased the formation of higher alcohols and esters during fermentation. There is also a variation between ale and lager yeasts, as they take up the amino acids available in the wort in different orders [113]. Therefore, the quality and stability of a beer will depend on the content of different amino acids in the wort, but inefficiency in the utilization of nitrogen can affect the fermentative capacity of the yeast [113]. The use of unmalted cereals, such as barley from 50%, causes the protease activity to decrease and therefore the FAN content, so that in these cases the addition of enzymes would be necessary [114].

Lipids will come mainly from malt, but also from hops and yeasts, and their proportion can also influence the concentration of esters in the beer [115]. High concentrations of unsaturated fatty acids (UFA) in the wort, such as oleic, linoleic, and linolenic acid, may result in lower ester production [116]. Acetate esters, at higher levels of UFAs in the fermentation medium, generally decrease the production of ethyl ester by yeast [117]. Likewise, the lipid content will be influenced by maceration, since a higher concentration will be obtained with the infusion system [118].

In addition to the above compound, yeasts also need vitamins and a wide range of inorganic ions for proper metabolism and performance. Vitamins will allow the enzymes and coenzymes in yeast to work properly [119]. Their scarcity can affect the metabolic activity of the yeasts and thus the fermentation, and therefore the final taste of the beer. The content of vitamins such as thiamine and riboflavin is influenced by the malting process [120] as well as the wort production process [121]. Vitamins such as thiamine are found naturally in foods, especially in those ingredients rich in carbohydrates, so in beer the greatest contribution will come from barley [122]. Likewise, it has been observed that studies carried out among different beverages have not resulted in major differences between different beer styles such as ale (300.2 µg/L), lager (307.0 µg/L), stout/porter (322.0 µg/L), and wheat beer (326.9 µg/L). But if we compare wine and beer, higher concentrations were obtained in beer (307–326.9 µg/L) versus 58.2–162.7 µg/L in wine [123].

2.2.2. Brewing Process

The process of brewing wort begins with the grinding of the malted barley or cereal to be used [124]. The degree of milling must be considered in addition to removing from the endosperm as much malt as possible but leaving the shell intact to act as a filter layer during silage (the filter cake). This process is influenced by the type of roller used and the speed, being the hammer roller, in addition to an increase in the milling speed, with which more fermentable sugars are obtained in the wort [125]. It has also been found that wet milling increases the concentration of simple sugars such as glucose, but the polyphenol content is not affected [126]. Over-milling can cause very rapid clogging during filtration, as well as nutty flavors in the final beer [127].

Mashing allows the solubilization of malt components through physical, chemical, and enzymatic processes. The grain and brewing water are mixed to activate the enzymes present in the malt. The proteolytic decomposition must be controlled, so there must be sufficient assimilable nitrogen available in the wort for optimal fermentation, as well as influencing the stability of the foam. Cytolysis must be controlled to ensure filtration. Amylolysis provides the necessary fermentable extracts. During the maceration, temperatures must be considered, as higher temperatures will obtain sugars of longer chains and therefore less fermentable for the yeast. Temperatures typically range from 45 to 78 °C. Studies carried out by Montanari et al. [128] showed that the single decoction plus infusion mashing method yields more fermentable sugars than a double decoction. Current studies are focused on optimizing the maceration time, where it has been seen that by reducing the initial temperature, the enzymatic activity of α- and β-amylases increases and therefore the obtaining of fermentable sugars, since these enzymes are involved in starch hydrolysis [129].

The lautering consists of solid-liquid separation to separate the malt compounds dissolved during milling from the insoluble parts, such as shells. For this purpose, a filter bed is created with the grist from the maceration process and then washed with hot water to obtain the maximum possible fermentable sugars [130]. The lautering process is a time-consuming step in the brewing process, which is why studies focus on reducing this step. According to Karabín M. et al. [131], one of the options to reduce the time could be to add hop tannin extract during the mashing process, improving it by 20%. The hop tannin extract is rich in polyphenols, which increases the antioxidant capacity of the wort and thus prevents the formation of free thiol groups of cysteine-rich malt proteins, which cause gelatins to form at the bottom and slow down the lautering. The next step in the process would be to boil the wort. Boiling is divided into two processes: hot retention and evaporation. Hot retention involves chemical reactions such as isomerization of hops, development of aromas and color, and dissolution processes, as well as sterilization and inactivation of enzymes to prevent excessive fermentation. Protein coagulation also takes place to obtain a clarified must. During this phase, Maillard reactions occur at 80 °C that generate new aromatic substances [132]. The boiling temperature, which in many cases depends on the altitude, will influence the formation of foam in the beer. It has been seen that boiling temperatures of around 96 °C produce a greater amount of lipid transfer protein 1 (LPT1), involved in the formation of foam. But also, low LTP1 content due to boiling at a higher temperature (102 °C), together with low levels of free fatty acids, also favors foam stability [133]. Once the boiling has finished, clarification is carried out by means of a Whirlpool to separate the hot turbidity, giving rise to a fermentation wort. The wort is cooled to a temperature suitable for the growth of the yeast that will carry out fermentation (8–20 °C). Plate heat exchangers are used for this purpose. After cooling, sterile air or oxygen needed for yeast growth (6–8 ppm dissolved O₂) is injected into the wort through an aerator to generate very fine bubbles [134,135].

Once the wort has cooled and been transferred to the fermenter, yeast is added (“pitching”), and fermentation begins. Fermentation consists of metabolizing substrates into products through the activity of microorganisms and simultaneously obtaining energy. In the case of yeast, it transforms sugars into ethanol and CO₂ as well as by-products that have a considerable effect on the aroma profile and taste of the resulting beer [136].

3. Bioactive Compounds in Raw Materials

3.1. Wine

Grapes

Grapes possess antioxidant, anticarcinogenic, cardioprotective, and phytoestrogenic effects, as they are a source of bioactive compounds like polyphenols [137]. These compounds accumulate mainly in the grape skin, which is a residual by-product of winemaking. Among them we find stilbenes, with resveratrol being the most studied and known to reduce lipid accumulation in white adipose tissue [138]. The concentration of stilbenes found in grapes can be very variable, as it can be influenced by the state of ripening, the grape variety, or various external factors. Likewise, the maturation duration, yeast activity, or other stages within the winemaking process can contribute to the amounts that are finally found in wine [139].

Grape weight is made up of 2–5% seeds and 38–52% solid residues generated during the winemaking process. The seeds contain 40% fiber, 10% protein, 10–20% lipids, and another 30–40% carbohydrates, as well as phenolic compounds, vitamins, and minerals. Currently, what is being sought is to take advantage of these residues, such as the use of seeds or the press cake to obtain oil (up to 75%) that is subsequently used in food and cosmetics [140]. On the other hand, grape pomace also contains phenolic compounds, with approximately 0.3–9% total phenolic content, as well as 17–89% total dietary fiber, 16–64% insoluble fiber, 4–14% protein, 1–14% lipids, 12–40% carbohydrates, and another 2–9% ash [141,142,143,144,145,146].

The initial stage of grape development consists of cell division and expansion, followed by a phase of rapid growth during which the berry is formed and the seed embryos are produced. The compounds responsible for providing acidity to the wine, such as tartaric and malic acid, are incorporated during this phase. In addition, other compounds are produced in the pulp and skin, such as hydroxycinnamic acids, while in the tissues of the feet, tannins will accumulate, as well as minerals and amino acids. The next phase of growth corresponds to ripening, where there will be great changes, as the grapes change from being small, hard, and acidic berries to larger ones that are soft, sweet, less acidic, flavored, and colored. Most of the compounds produced during the first phase will continue in this phase; however, the malic acid is metabolized and used as an energy source, decreasing its proportion with respect to the concentration of tartaric acid. Tannins also decrease considerably after the harvest.

During the metabolic processes of grapes, various compounds are generated that offer the plant selective benefits when facing ecological stresses. The phenolic compounds found in wine, known as polyphenols, form a vast and varied group of secondary bioactive substances derived from grapes. Several studies suggest that polyphenols are secondary metabolites produced as a reaction of grapevines to unfavorable conditions throughout their normal development [147,148]. The biosynthesis and buildup of polyphenols occur during the ripening of the berries and are influenced by a range of factors. Among these factors are crop varieties (clones and rootstocks), environmental factors (agropedological, topographical, and climatic), and cultural practices (training systems, vine row spacing, pruning, bunch reduction, bud and leaf removal, as well as water, fertilizer, and pesticide management). Several studies determined that in the case of red grape varieties such as Cabernet Sauvignon and Pinot Noir, anthocyanins accumulate mainly in the skin of the grapes after veraison, but other varieties, such as Garnacha Tintorera, can also accumulate in the pulp [149,150]. In terms of climatic factors, studies conducted by Berli F. et al. [151] showed an increase in anthocyanin accumulation when grapes were subjected to solar UV-B radiation and abscisic acid was sprayed on the leaves and grapes, and these levels remained elevated until harvest. The use of other compounds such as benzothiadiazole, chitosan, and pectin-derived oligosaccharides has also been shown to influence the concentration of polyphenols and anthocyanins in grapes, increasing their concentration [152,153,154]. The profile of the different phenolic compounds produced in grapes will also depend mainly on the time of harvest. It can also vary depending on post-harvest handling protocols, as well as the application of specific treatments. Maturation studies on Cabernet Sauvignon and Tempranillo at three different periods showed an increase in proanthocyanins but a decrease in anthocyanins over time. Thus, ripening may have a different influence on the different polyphenolic compounds [155]. These processes are crucial in determining the polyphenolic composition of both grapes and wine. The primary polyphenols present in grapes include proanthocyanidins (monomers, oligomers, and polymers) and anthocyanins. To a lesser degree, other phenolic compounds such as phenolic acids, resveratrol and its derivatives, flavonols, flavanonols, and flavones can also be found [156].

Polyphenols are mainly found in the solid part of the grape (in the seed, skin, and stalks) [157]. Also, thanks to the antioxidant contributions of grape skins and seeds, these by-products are used as dietary fibers and cosmetic supplements [158]. Grape pomace can be processed into grape pomace flours (either whole or as separate skin/seed fractions), which can be utilized in the production of functional foods and dairy products [159,160]. This is aimed at enriching foods with dietary fiber and total polyphenols, boosting antioxidant activity, protecting against lipid oxidation, and, in some instances, enhancing the acceptability of the products [161].

Another compound that contributes to the antioxidant capacity of the grape is melatonin (MEL). Melatonin has been found in many organs of higher plants, such as seeds, leaves, and fruits, at concentrations between picograms and nanograms per gram of tissue [162]. Due to its similar structure to the auxin indole-3-acetic acid (IAA), researchers were led to test melatonin’s role as a growth factor for plants [163]. It has also been demonstrated that MEL promotes vegetative growth in etiolated Lupinus albus L. cotyledons [164] and its function in phyto-remediation [165]. A study by Xu et al. [166] reported the interplay between MEL and ethylene in regulating the salt tolerance in grapevines. Iriti et al. [167] observed that the treatment of grapevine with a plant defense activator (benzothiadiazole, BHT) ended in higher MEL concentration in berry skin extracts. Consistent with the antioxidant properties of MEL, higher levels may be anticipated in seeds, grapes, and final wines. The authors reported the initial detection of MEL in grape skins [167] and found that its content in eight grape varieties of Vitis vinifera L. ranged from 0.005 ng/g in Cabernet Franc to 0.965 ng/g in Nebbiolo. Similar results have been found for the same tissue of Malbec, Cabernet Sauvignon, and Chardonnay (0.6 ng/g, 1.2 ng/g, and 0.8 ng/g, respectively) in Argentina, indicating that there is hardly any difference between red and white varieties [168]. Another study presented much higher MEL content (9.3–17.5 ng/g) in grape skins, whereas the melatonin contents in seeds and flesh ranged from 3.5 to 10 ng/g and from 0.2 to 3.9 ng/g, respectively, during the transition from pre-véraison to véraison in Merlot cultivar from Italy [169]. Regarding whole berry, elevated MEL concentrations (100–150 mg/g), depending on the phenological stage, were detected in Merlot cultivars grown in Canada [170]; instead, only 1.2 and 1.5 ng/g of melatonin were observed in Sangiovese and Albana grapes, respectively [171]. Therefore, most studies reported that the MEL amount in grapes is around ng/g.

3.2. Beer

Beer is rich in functional ingredients (

Table 2. The average value of the main nutritive components in beer.

Nutritive Components	Range Value	Reference
Protein	0.2–6.6 g/L	[94,173]
Flavonoids	0.03–18.30 mg/L	[174]
Polyphenols	34–426 (mg/L)	[6]
Vitamins		[174,175]
Vitamin B1	0.0266 mg/L
Vitamin B2	0.26–4.03 mg/L
Vitamin B3	4.30–8.15 mg/L
Vitamin B5	0.033–1.065 mg/L
Vitamin B6	0.05–0.505 mg/L
Vitamin B7	0.008–0.022 mg/L
Vitamin B8	0–48,000 µg/L
Vitamin B9	0–6000 µg/L
Vitamin B12	23,000 µg/L
Vitamin C	Up to 30 mg/L
Elements		[94]
Potassium	200–600 mg/L
Calcium	20–160 mg/L
Magnesium	60–250 mg/L
Zinc	0.02–4.5 mg/L
Copper	0.02–0.4 mg/L
Selenium	<0.007 mg/L
Ethanol	3–9 (% v/v)	[94]
Energy	150–1100 kcal	[94,176]

). The content of nutrients and bioactive compounds, mainly polyphenolic compounds, is influenced by various ingredients: malted cereals such as barley, wheat, oats, and rice; hops; additives such as fruits and spices; and microorganisms such as Saccharomyces and non-Saccharomyces yeasts or bacteria such as lactic acid bacteria (LAB) [172] (Figure 1).

Here, a brief report of functional compounds present in the raw material is reported.

3.2.1. Hop and Barley

Hops (Humulus lupulus L.) are the main ingredient responsible for the bitterness of beer due to the iso-acids obtained from the isomerization of α-acids during the boiling of the wort. In addition to bitterness, hops also contribute to the aromas of beer, such as citrus, floral, herbal, and fruity. Hop varieties are rich in polyphenolic substances, especially proanthocyanidins (>55%), flavonoid glycosides (>28%), and polyphenols (40–140 mg/g) [177]. Barley is the ingredient that provides more functional components for beer.

Indeed, barley is rich in proteins, mineral salts (mainly selenium), polyphenols, and flavonoids. Generally, hops and barley produce the same functional contribution to beer with small differences. Obviously, the beer style and the brewing process determine the content of functional compounds present in the beer [178].

Phenolic compounds derived from hops and barley are caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, p-salicylic acid, syringic acid, gallic acid, proto-catechuic acids, catechin, kaempferol, naringenin, naringin, quercetin, and rutin [177,179,180].

The content of polyphenols in barley malt varies depending on the varieties used in the various styles of beer. In general, dark malts have a higher content of polyphenols than pale malts [103,104,105]. For this reason, the technical parameters used during the malting and mashing process are important [181].

One of the most important components for human health is xanthohumol, which is converted into isoxanthohumol during boiling. Beer can be enriched with xanthohumol through various products. Xanthohumol shows essentially anti-carcinogenic activity and a strong antioxidant effect [94,182].

3.2.2. Botanicals

Plants and plant extracts are traditionally used in beer production to improve their taste and aroma. Some plants, such as Artemisia vulgaris, Juniperus communis, Melissa offcinalis, Mentha spiata, Origanum vulgare, Pimpinella anisum, Rosmarinus offcinalis, Thymus serpyllum, Acorus calamus, Cinnamomum verum, Hypericum perforatum, Lupuli strobuli, Urticae radix, Brassica nigra, and Coriandrum sativum were used in beer production to produce a pleasant-tasting beverage [183].

The use of lemon balm and thyme also improved the functionality of the product by increasing the phenol content and therefore its antioxidant power.

The use of fruits in beer is traditionally used in Belgium to produce “Kriek” and “Framboise”, adding cherry and raspberry, respectively. The use of fruit during the maturation and refermentation phase imparts not only aromas but also bioactive compounds to beer. Fruits such as peach, apricot, grape, plum, orange, and apple also increased the content of bioactive compounds such as catechin, quercetin, myricetin, and resveratrol in final beers. They also significantly increased the antioxidant activity of beer and improved its phenolic profile qualitatively and quantitatively [184,185]. Fruits can be added to beer directly, as fruit extracts, and as fruit flavor additives. Fruit extracts usually include many bioactive compounds such as phenols and carotenoids. The introduction of these extracts adds functionality to the beer. Almost all types of fruits can be added to beer, such as peaches, mangoes, pears, apples, pineapples, bananas, strawberries, and blueberries.

Lemon juice, raspberry syrup, orange juice, and grapes are very popular as a supplement to beer, which broadens the consumer population to women and people who do not like the original bitterness of beer. The most common practice is the addition of grapes. Grapes combine the different bioactive compounds from wine, such as phenolic compounds and anthocyanins [186]. The addition of Prokupac and Muskat Hamburg, a variety of grape must, showed higher phenolic content by combining a product with improved functionality and pleasant sensory characteristics. Adding grape must from three different varieties to a pilsner beer containing up to seven times more phenolic compounds than the control pilsner beer. Drinking this beer had a beneficial effect on heart rate and blood pressure, keeping them within normal ranges. Although it is somewhat more expensive to produce, beers with added grape must could be of interest, especially for craft breweries looking for diversity and functionality.

3.2.3. Microorganisms

Brewer’s yeast cultures predominantly come from the genus Saccharomyces—a minority of non-Saccharomyces yeast. Among the genus Saccharomyces, the main characters in brewing fermentation are the species Saccharomyces cerevisiae (ale beer) and Saccharomyces pastorianus (lager beer) [187]. Generally, the study of new starter strains in the brewing sector has been finalized to a selection of yeast strains that exhibited a good fermentation performance and a distinctive aromatic taste. Recently, several investigations have been conducted to assess the functionality of different unconventional microbial starter cultures in craft beer.

Although most research has focused on the study of probiotic bacteria, mainly lactic acid bacteria, in recent years attention has turned to potential probiotic yeasts and their fermented products both in food and drinks [188,189,190,191]. Indeed, functional treatments of yeasts are related to the production of bioactive compounds [192], natural antioxidants [193], and the determination of anti-inflammatory effects [194].

Functional Yeasts

Currently, several studies have been conducted to evaluate the functionality of different unconventional probiotic starter cultures in craft beer production.

Saccharomyces cerevisiae var. boulardii, used in craft beer production, led to beers with lower alcohol content, higher antioxidant activity, similar sensory attributes to the S. cerevisiae commercial starter, much higher yeast viability after 45 days, and higher acidification, allowing for reduced contamination risks in large-scale production. Furthermore, the probiotic yeast showed faster growth and larger cell volumes than commercial yeast, increasing the probiotic mass of the final craft beer [195]. S. cerevisiae var. boulardii was also tested in mixed cultures during wort fermentation with different S. cerevisiae strains to produce craft beers with increased health benefits [196]. The use of these mixed fermentations did not negatively affect beer aroma. It promoted an increase in antioxidant activity and polyphenol content compared to beers produced with a single starter yeast, indicating the positive influence of the probiotic yeast strain on these parameters [196]. Moreover, S. cerevisiae var. boulardii was used in mixed fermentation with starter strains for lager beer, increasing the viability during 28 days of storage [197]. The research field of probiotic yeasts in craft beer has focused attention on non-conventional yeast. Forty-three non-Saccharomyces yeast strains belonging to the genera Rodosporidobolus, Candida, Lachancea, Rhodotorula, Torulaspora, Kazachstania, Brettanomyces, Pichia, Kluyveromyces, Metschnikowia, Hanseniaspora, and Saccharomyces, previously validated for their probiotic traits, were tested for craft beer production [198]. In this study, the wort used to brew the craft beer was added by hydrolyzed chickpea wort (PCW) or lentil wort (PLW) (20% wort replacement) to increase the protein content of the final beers. The selected strains Kazachstania unispora, Lachancea thermotolerans, and S. cerevisiae could be potential microbial candidates to obtain premium craft beer with highly nutritional and functional characteristics and a distinctive aroma character. The use of non-conventional yeast in brewing is related not only to probiotic traits or the impact on the aromatic profile but also to the elaboration of special, healthier beers, such as non-alcoholic/low-alcohol beers (NABLAB), low-calorie beers, and functional beers. These applications are possibly exploiting the metabolic differences found in various species of non-conventional yeasts. However, further investigation is necessary to understand the mechanisms that are related to the functional aspect of non-conventional yeasts.

The yeasts used to ferment the beer remain in the product afterwards, which is the reason they are pasteurized to give the product greater microbiological and compositional stability. However, craft beers, and more and more beers, are not sterilized, presenting a value as probiotics. Likewise, different yeast species are increasingly used, such as Saccharomyces cerevisiae var. boulardii, which can enhance the antioxidant capacity of beers, in addition to their polyphenol content [196].

Functional LAB

Live microorganisms beneficial to human health, mainly lactobacilli and bifidobacteria, are known as probiotics. They play a key role in boosting immunity and balancing the gut microflora. Probiotic craft beer with lactic acid bacteria (LAB) appeals to health-conscious consumers looking for flavorful beverages that support gut health, offering a refreshing alternative to traditional beers while promoting a holistic approach to wellness. LAB, known for their probiotic properties, are naturally present in fermented foods such as yogurt, kimchi, and kombucha. Their use in craft beer offers a new way to use and introduce them into the diet. Craft beer, unpasteurized and unfiltered, represents a new vehicle for the administration of probiotics. Studies on the use of LAB in craft beer production are still limited. Lactic acid bacteria are used as starter cultures in many animal- and plant-based foods [199]. The genera Enterococcus, Lacticaseibacillus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, and Weissella are naturally found on the surface of cereals [200]. Several works have shown that the fermentation of cereal-based beverages by LAB improves protein digestibility [199,201], enhances nutrient bioavailability (micro/macro) [202], prolongs shelf life [203], and, finally, improves organoleptic qualities [204]. In brewing, the use of LAB is linked to various stages of the production chain. In malting to control the endogenous microbial population that naturally colonizes the grain surface, the mild acidification resulting from lactic acid has a positive impact on malt quality and processing efficiency. LAB have also been recognized as a necessary agent to naturally acidify the wort and mash during brewing operations and to produce sour beers, such as Berliner Weisse or Lambic. Knowing which organoleptic active compounds are released during wort fermentation can help in the tailoring of new specialty “sour beers” inspired by European styles such as Belgian Lambic or German Berliner Weisse or by traditional fermented beverages [205].

One of the fundamental aspects of the probiotic concept is viability. For this reason, it is essential to evaluate the sensitivity of probiotic strains to the bitter acids of hops, which can inhibit the survival of Gram-positive lactic acid bacteria [206,207,208]. Indeed, a strain of Lactobacillus paracasei in co-fermentation with S. cerevisiae US-04 exhibited a significantly reduced vitality when hop was added in the wort, regarding its antimicrobial activity [209].

In this regard, several fermentation strategies have therefore been proposed to safeguard the vitality of LAB in beer, for example, the use of LAB in wort before the inoculum of yeast [210].

Elements

One of the most important trace elements for human health is selenium (Se). Its deficiency can cause severe immunodeficiency, cognitive decline, and even mortality [211,212].

Beer has been suggested to introduce Se into our body. The yeast S. cerevisiae used in fermentation is responsible for the biotransformation of inorganic Se into organic, bioactive, and easily absorbable compounds [213,214]. Enrichment of barley with Se in the field has given satisfactory results, but biofortification during malting has shown equally good results [215,216,217].

4. Nutritional Composition and Bioactive Compounds in the Fermentation Process

4.1. Nutritional Composition

4.1.1. Protein

The different stages in the brewing process affect the protein content in the final product, especially during the maturation and stabilization steps, where brewers try to remove part of the protein content. The protein and amino acid content of beer varies depending on the raw materials and the beer production technology [218].

Generally, the protein content in different beer styles is similar, although for some types, such as lager, ale, and wheat beer, the protein content is lower [219].

Wines contain nitrogenous substances in a concentration of between 15 and 230 mg/L; they do not provide nutritional value, but they do affect the clarity and stability of the wine. This must be taken into account in order to maintain the quality of the wine for the consumer. One of the most common defects in white wine that is not due to contamination by microorganisms is protein instability. Likewise, this instability will be influenced by storage conditions, since aggregates can form that produce turbidity in the bottle and depreciate its value [220].

4.1.2. Carbohydrates

Dextrins, monosaccharides, oligosaccharides, glucan, and arabinoxylans are the main carbohydrates in beer, with an average content of 3.3–4.4 g/100 mL [219]. Total carbohydrate content depends on the type of malt used and the fermentation process. Non-alcoholic beers such as non-alcoholic lager and non-alcoholic wheat beers (<0.25–<0.5% v/v) contain carbohydrates ranging from 4.5–14 g/100 mL, of which 1.3–11.4 g are sugars per 100 mL [221]. It is well established that carbohydrates provide energy, but they can affect blood sugar levels. For this reason, consumers need to be aware of the carbohydrate content in beer.

The carbohydrates present in wine will come from grapes, with the concentration of the main ones, according to Cibrario et al. [222], as follows: D-glucose and D-fructose (176 mg/L on average), L-arabinose (110 mg/L), D-sorbitol (120 mg/L), L-ramnosa (107 mg/L), trehalose (94 mg/L), and mannitol (83 mg/L). The other sugars that can be found are celobiose, galactose, lactose, maltose, melibiose, ribose, and xylose, whose concentrations are below 40 mg/L. Polysaccharides will influence the aroma of wine but also interact with tannins [223,224], decrease astringency [225], inhibit hydrogen tartrate crystallization, interact with other aromatic compounds in wine [226], prevent or limit aggregation and flocculation, and prevent protein haze formation in white wine [227,228]. The composition of polysaccharides can also influence the foaming of sparkling wines [229,230].

4.1.3. Energy Value

The energy value of beer is related to the alcohol content, total carbohydrates, total amino acids, and total organic acids. Typically, the energy value of craft beer is between 417 and 709 kcal/L [231]. Beers with 4% ABV contain 105 kcal/350 mL. Non-alcoholic beers have a lower alcohol content (<0.2%) and are therefore also more often characterized by lower energy values [232,233]. NAB, LAB, and CB contain small amounts of ethanol, which provides an energy intake of 7 kcal/g [234].

During the fermentation process, in addition to producing CO₂, ethanol, and aromatic compounds, yeast improves the nutritional value of wine by releasing amino acids and other nutrients from the yeast [154]. Fruit wines with an ethanol content of 8–11% and 2–3% sugar usually have a range of 70–90 kcal per 100 mL [235].

4.2. Bioactive Compounds in Fermented Beverages

The presence of bioactive compounds in fermented beverages has long been examined with great interest [236]. Alcoholic fermentation by yeasts transforms certain molecules into biological compounds with an impact on quality and human health [237].

4.2.1. Antioxidant Capacity

The measure of antioxidant capacity levels in biological samples and foods plays an essential role in the prevention and treatment of oxidative stress-associated diseases as well as for controlling variations within or between different products [238,239]. The term “total antioxidant capacity” refers to antioxidant properties of a complex material (such as a beverage, extract, or biological fluid) composed of many compounds in the analysis [240]. However, the complex matrix of foods and the lack of standardized quantification methods sometimes make it difficult to find a correlation between results to determine a foodstuff as “rich in antioxidants”.

The analytical methods employed for the study of antioxidant activity in wine are enormously important. The isolated antioxidant substances and their antioxidant power in functional food depend on the assay employed for their determination [241]. In wine and beer, the antioxidant activity is valued through chemical and enzymatic methods.

Regarding chemical tests, they involve a series of analytical techniques in which specific reagents or reactions are needed to detect and identify particular compounds in a sample [242]. Inside this group, the main methods used to quantify antioxidant activity in wines are ABTS and DPPH assays, where the ability of the antioxidant compound to scavenge reactive oxygen species (ROS) and free radicals is measured [243]. Two other methods frequently used to evaluate antioxidant activity are the ORAC (oxygen radical absorption capacity) assay that determines the ability of the sample to block the peroxyl radical. The radical chain reacts with a fluorescent probe [244]. Moreover, the FRAP (ferric reducing antioxidant power) is based on the antioxidant capacity to reduce ferric ions to the blue-colored ferrous complex in an acidic medium. It is simple and fast and does not necessitate special equipment [244]. A recent study showed a comparative analysis of the antioxidant activity by ABTS, DPPH, and FRAP tests and the content of individual phenolic compounds by HPLC in Cabernet Sauvignon and Merlot wines. Data exhibited clear differences in antioxidant activity measurements in the following order: FRAP > ABTS > DPPH. Cabernet Sauvignon wines had a slightly higher antioxidant capacity than Merlot varieties after DPPH (CS: 14.80–20.25 and M: 12.80–19.32 mm Trolox/L) and ABTS (CS: 21.15–36.30 and M: 18.40–35.10 mm Trolox/L) tests [245]. Instead, another study in white and red grapes, including Cabernet Sauvignon, showed the highest ranges of antioxidant capacity were shown when the ORAC assay was used (254.94–412.90 μmol Trolox/g dry weight for red grape varieties and 102.28–440.11 μmol Trolox/g dry weight for white grape varieties) [246]. These authors found that the different antioxidant capacities of the grapes, independent of the variety, were related directly to the total polyphenolic content, in agreement with other investigations [247]. In addition, different fractions of grapes presented different antioxidant abilities. The antioxidant capacity of thirty grape varieties was tested in different grape parts: pulp, peel, and seeds [248]. Grape seeds possessed the strongest antioxidant capacity in accordance with their highest respective total polyphenolic content, followed by peel and, finally, pulp. In accordance with Elejalde et al. [246] and Yang et al. [247], in grapes, a similar relationship between total antioxidant capacity and phenolics content was denoted in barley sprouts using ABTS, DPPH, and FRAP methods [249]. Moreover, the addition of dark malts can be useful for the increment of antioxidant ability of the wort, affecting the characteristics of the final beer [104]. Furthermore, different yeast species employed to ferment can influence this antioxidant ability. Wang et al. [250] observed that the presence of non-Saccharomyces (Hanseniaspora uvarum and Kurtmaniella quercitrusa) together with low-temperature fermentation conditions could be a viable strategy for improving the antioxidant capacity in fruit wines. Some authors have recently evaluated the potential release of antioxidant molecules during the beverage elaboration period. Thus, some non-Saccharomyces strains have good performance as glutathione (a natural antioxidant molecule) producers during the growth phase, after co-inoculations, as well as during the use of active dry yeasts as starters of the fermentation [251,252,253]. In craft beer fermented with wild yeast strains [254], there were no notable differences in the antioxidant capacity between different fermentation strategies: 9.50–13.67 mmol Trolox/L with native Saccharomyces, 11.18 mmol Trolox/L with commercial Saccharomyces, and 9.63–13.70 mmol Trolox/L in sequential cultures. However, it was noticed that the antioxidant capacity was lower when there was competition between species or when there were maltose non-fermenting strains. Other authors [255] have found lower values of antioxidant capacity in lager and ale beers between 424.77 and 10,508.47 μmol Trolox/L, but they have observed important changes in these values using the ORAC analysis method, ranging from 3.70 to 29.11 mmol Trolox/L.

The enzymatic method uses an enzyme as a biological catalyst for many reactions of interest, being used for extraction or for direct quantification of bioactive compounds [256]. Superoxide dismutase (SOD) assay is one of the more commonly used [239,243]. This enzyme neutralizes the effects of oxidative stress by reducing the free superoxide radicals into hydrogen peroxide and molecular oxygen. In a study by Tekos et al. 2021 [257] on Greek white and red wines, antioxidant capacity was studied by DPPH, ABTS, and SOD tests. These results showed that both wines contain compounds with potent antioxidant character, but notably higher in red wines. Another antioxidant enzyme usually employed for these analyses is catalase (CAT). This enzyme metabolizes H₂O₂ into water and oxygen. Some experiments tested the effects of wine intake on antioxidant enzyme activities. Wine consumption provoked a significant increase of CAT and glutathione peroxidase (GPx) and not for SOD in a trial in rats with renal damage [258]. The results of this work suggested that there is an improvement of the antioxidant defense potential in kidney and plasma because of ethanol and non-alcoholic antioxidant fraction after repeated red wine ingestion. In the same way, an extract of fermented barley improved the glutathione peroxidase and catalase in the livers of chronic ethanol-fed rats, but there were no differences in SOD activity in the liver [259].

Finally, electrochemical methods are emerging as a reliable, versatile, inexpensive, and fast way to measure the antioxidant activity in several foods, with the additional advantage of generating less waste compared to conventional methods [260]. They are divided into amperometry and voltametric methods [261]. Buenaventura et al. [262] carried out a systematic review of the role of voltametric analysis in wine. The authors found that cyclic voltammetry was most frequently used for determining the polyphenol content in wine. However, other authors [244,263] claimed that differential pulse voltammetry is a better method for polyphenol and antioxidant capacity analyses.

4.2.2. Polyphenols

Polyphenols encompass a broad group of compounds that are usually naturally occurring in vegetables and are known for their antioxidant and health properties. They are present in fruits, vegetables, cereals, and beverages. They can be classified into different groups, such as flavonoids, phenolic acids, stilbenes, and lignans [264]. These compounds, in addition to standing out for their beneficial properties for health, are responsible for the sensory characteristics of foods, such as color, hue, clarity, flavor, bitterness, and astringency [265]. They are responsible for defining the sensory characteristics and functionality of wine and beer. Recent studies have also shown that they have antibacterial capacity through different mechanisms, since they prevent the formation of bacterial biofilms, in addition to preventing the elimination of enzymes and bacterial substrates [97]. This can thus be used to reduce the use of SO₂ so that the physical and chemical characteristics of the wine or beer are not modified [266,267]. Moreover, polyphenols are related to the reduction of the risk of chronic diseases such as cardiovascular diseases, diabetes, and cancer [264]. They are able to activate the antioxidant system by up-regulating various endogenous antioxidants and scavenging excess free radicals [268]. In addition to being antioxidants, polyphenols are also referred to as prooxidants, since they induce apoptosis by activating caspases [269] and block cell proliferation [270,271]. In any case, the effects of polyphenols on health depend not only on their concentration but also on their absorption in the Mediterranean diet [272]. It should be noted that polyphenols have limited bioavailability, which may affect their absorption and utilization in the human body [11]. In the Mediterranean areas of Spain, Italy, Greece, and France, one of the main foods in the Mediterranean diet that provides different polyphenols (phenolic acids, flavonoids, stilbenes, and lignans) is wine [273,274,275,276].

If we focus first on the ingredients used to make wine (grapes) and beer (barley malt, hops) that naturally contain polyphenols, different concentrations can be observed depending on the varieties used, as well as on the parts of the fruit, cereal, or plant. In grapes, the pulp has 10% polyphenols, the seeds have 60–70% polyphenols (5–8% by weight), and the skin has 28–35% polyphenols [277,278]. The skin of white grapes is rich in catechins and proanthocyanidins. To prevent their oxidation, contact with oxygen is limited, and polyphenoloxidase is inhibited by the addition of SO₂. Oxidation causes the phenolic profile of the musts to show lower concentrations of hydroxycinnamic tartaric acid esters and flavanols, while those of 2-S-glutathionyl caffeyl tartaric acid are higher [277]. Therefore, as shown in

Table 3. Polyphenol content in different grape varieties.

Grape Varieties	Total Polyphenols (mg/L)	Seeds (mg/g)	Skins (mg/g)	References
White
Verdelho	319–2307	-	-	[289,291]
Chardonnay	649–2520	190	8.1	[289]
Malvasia	159–2958	63.9	9.1–27.6	[289,290,291,292,293,294]
Muscat	268–1321	102.2	10.4	[295,296,297]
Red
Pinot Nero	21–693	38.7	21.4	[289,298,299,300]
Merlot	590–3560	13.5–867	30–280	[289,295,301,302,303,304,305,306]
C. Sauvignon	38.39–2195	10.2–103.7	29.5–33.2	[289,295,301,303,306,307,308]
Tinto Fino	1578–2530	-	-	[307]
Syrah	66–4380	33–215.9	20.8–146.5	[309,310,311]

, the polyphenol content will depend on the grape (red or white), as well as the varieties within these. However, as can be seen in Table 3, differences in total polyphenols are not only found between varieties but also within varieties depending on certain external factors (location, environment, and management practices) [279]. The quality of the grapes and wine will be influenced by climatic and soil conditions [280,281]. Studies carried out by Ubalde et al. [282] in regions of Brazil determined that the ideal temperature for coloring is a maximum of 10 °C, while for ripening it is 15 °C, causing more anthocyanins to accumulate. Likewise, another parameter to take into account is the rain, since it can also prevent some fungal infections [283]. One way to protect the plant against this type of biological or even physical attack, such as solar radiation, is the production of polyphenols [284]. This is why areas with high rainfall influence the production of phenolic compounds in the grape skin [285,286]. The accumulation of hours of light during ripening also influences the accumulation of phenolic compounds such as anthocyanins [287]. Likewise, the incidence of solar radiation will activate the metabolism of certain compounds that provide quality to the wine, such as flavonols [288]. This is why grapes grown at higher altitudes will have these advantages [289]. On the other hand, practices such as single-spur pruned high-wire cordon and single-armed Guyot showed higher polyphenol content in the study conducted by Coletta et al. [290].

In beer, the two main ingredients that provide polyphenols are malt and hops. As mentioned above, they will influence the sensory characteristics of beer and therefore their quality. This is why the study of the polyphenol content of both ingredients has been extended to determine how it influences the beers especially over time [312,313]. Cereals such as barley, as well as rice, wheat and oats, which can be used as adjuncts in beer, are rich in phenolic acids, flavonoids, lignans, and tocols [314]. On the other hand, in hops we will find phenolic acids, flavan-3-ols and flavanols, prenylflavanoids (xanthogumol, 6-,8-prenylnaringenin) and stilbenes [315], as well as alpha- and iso-alpha acids. Although yeasts are also involved in the phenolic profile of beer, it is said that 70–80% corresponds to malt and 20–30% to hops. This phenolic profile will be composed of simple phenols, benzoic and cinnamic acid derivatives, coumarins, catechins, proanthocyanidins, chalcones and flavonoids [316]. During brewing, polyphenols in malt and hops optimized the reducing activity and thus reduced the carbonyl content during the fermentation process, i.e., the harshness of fresh beer. However, hop polyphenols may have a negative effect on turbidity stability [313]. In beer, the phenolic compounds found with respect to malt are lower, since only a small number are released in the wort, but the polyphenols of hops are more reactive compared to proteins. This is due to the polymerization rate of polyphenols, which are more active when associated with proteins [317]. The use of roasted malt also provides a higher polyphenol content to the beer [104,318]. However, other studies where bagasse has been analyzed after mashing have shown that the application of higher temperatures to obtain darker malts favors the degradation of these compounds, the values for pilsen malt being 31,403 µg/mL, while dark malt (for stout beer) was 23,516 µg/mL [319]. Therefore, polyphenols influence the composition and balance of beer both quantitatively and qualitatively, and this influence depends not only on the structure and properties of the compounds themselves, but also on external factors such as temperature, pH, presence of microorganisms and polar solvents [320]. Likewise, the concentration of polyphenols also depends on the mashing conditions applied, as well as the varieties of malt and hops used [321]. Juric A. et al. [321] indicate that a maceration step at 52 °C for 10 min increases the polyphenol content, while prolonging the time at this temperature decreases them.

Table 4. Polyphenol content in different malt and hop varieties.

Varieties	Total Polyphenols (µg/mL)	References
Hop
Cascade	2.8–19,600	[312,326,327]
Columbus	3.6–19,900	[312,327]
Hallertau	2.6–27,100	[312,328]
Saaz	229–37,900	[325,328]
Nugget	5200–16,700	[327,328]
Malt
Chateau Cristal	1.8	[312]
Chateau Munich	1	[312]
Pilsen	0.9	[312]

shows the concentrations that can be found in different varieties of malt and hops. There are several studies on the format in which the hops are used (cone, pellet or extract), where the hop extracts can have a higher concentration of polyphenols or, on the contrary, their content can be reduced [322,323,324,325].

Since ancient times, moderate wine consumption has been associated with certain health benefits [329]. Recent studies on the moderate consumption of some alcoholic beverages, such as wine or beer, have shown positive effects on antioxidant capacity, lipid profile, and the coagulation system [330], thus reducing cardiovascular disease [331,332]. These antioxidant and anti-inflammatory effects [333], in addition to anti-cancer [334], anti-inflammatory [335], hypotensive [336], or even anticoagulant [337] properties, can be attributed in part to the polyphenols contained in wine and beer. These health benefits have been observed mainly in red wine rather than in white wine due to its higher polyphenolic content. Likewise, the components of wine and grapes vary depending on the variety of grapes, geographical location, soil, weather conditions, and maceration, an additional process applied for making red wine, but similar beneficial effects have been observed. The greater health benefits of red wine may be related to its higher polyphenolic content due to the different production processes between red and white wine, since the maceration of red wine with the grape skin is one of its major contributions [338,339]. The maturation process is carried out in barrels, its purpose being to soften the astringent and bitter taste provided by the phenolic content. During the maturation process, the alcohol levels of the wine tend to increase, especially if the process is prolonged over time, consequently increasing the phenolic and flavonoid content as well as the concentration of trans- and cis-resveratrol and the lipid composition due to its greater exposure to skins and seeds [340]. Numerous chemical modifications and interactions with other molecules occur during this process [4]. Although white wine is not macerated with grape skins and seeds, several studies have shown relevant levels of antioxidant capacity, despite having low concentrations of polyphenols [341,342,343]. Likewise, it has been shown that if the maturation of white wine is prolonged with grape pomace, there is an increase in phenolic content, in addition to the development of unique organoleptic characteristics [344].

Beer is a beverage widely consumed throughout the world, consisting of carbohydrates, amino acids, minerals, vitamins, and other compounds such as polyphenols. As seen above, hops contribute many phenolic compounds. Among these compounds, we find polyphenols, where hops contribute 30% of those contained in a beer, while the other 70% are provided by the malt. Dried hop cones contain about 14.4% of polyphenols, including phenolic acids, prenylated chalcones, flavonoids, catechins, and proanthocyanidins [345]. The polyphenols most frequently found in beer are simple phenols, benzoic acid and cinnamic acid derivatives, coumarins, catechins, di- and tri-oligomeric proanthocyanidins, prenylated chalcones, and α- and iso-α-acids derived from hops.

Wine presents a great structural diversity of phenolic compounds due to the transformation of the chemical constituents of the grapes during vinification. These chemical processes have therefore been extensively studied [30,346]. Red wine polyphenols can be divided between flavonoids based on a common C6-C3-C6 skeleton (such as anthocyanins, flavonols, flavones, and proanthocyanidins in their aglycone or glycosylated form, and flavan-3-ols) and non-flavonoids, including C6-C1 hydroxybenzoic acids (protocatechuic acids, gallic, and syringic), C6-C3 hydroxycinnamic acids (coumaric and caffeic acids), and C6-C3-C6 stilbenes (such as resveratrol, cinnamates, and gallic acid) [347,348] (Figure 1). Most phenolic compounds (up to 50%) are formed by flavan-3-ols [349]. As mentioned, they possess a high antioxidant capacity, as they reduce oxidation of low-density lipoprotein (LDL) cholesterol, as well as modulate cell-signaling pathways and reduce platelet aggregation. Values between 1.2 and 3.0 g/L can be found in red wine. As for non-flavonoids, the stilbene resveratrol has been the most studied, as it has been shown that it can provide cardioprotective and chemopreventive effects, inhibiting LDL oxidation and platelet aggregation.

In the production of wine, different products can be obtained, the main one being wine, which can be white, red, or rosé. The main difference between white and red wines is the grape skins. In the case of white wine, the grapes are pressed, and the juice is fermented without skins or seeds. In the case of red wine, on the other hand, fermentation is carried out with the skins, which give the wine a reddish tone, tannins, and additional flavors, creating a more complex flavor profile. Finally, rosé wines are made by temporarily leaving the skins with the grape juice, which gives a red hue and a nuanced flavor profile that combines elements of red and white wines [243]. According to the study carried out by Pietro et al. [241], the highest content of total polyphenols found in red wine is 9.88 mg/mL, while in white wine it is 0.2 mg/mL. On the other hand, comparing ale (0.56 mg/mL) and lager beers (0.44 mg/mL), the differences in total polyphenols are more similar.

The fermentation process will influence the final polyphenol content of both beverages. In general, this content will increase in wine, especially in red wine, since fermentation and maceration take place in the presence of the grape skins, pulp, and seeds, which have the highest polyphenol content [350]. On the contrary, in beer this content will generally decrease, since the main source is the raw materials of hops and malt [351]. This decrease occurs because polyphenols precipitate with proteins and adsorb to hot and cold trub (protein, bitter substances, organic substances, and ash), yeast cells deposited at the bottom of the fermenter, and stabilizing agents [352]. The polyphenols that do not decrease after beer fermentation are catechin and ferulic acid [353,354]. In the case of prenylflavonoids in beer, they are always present after fermentation regardless of the type of beer, ale, or lager [355]. Xanthohumol is the most studied polyphenol in beer, whose concentration also decreases after fermentation. It is for this reason, and because of its health-promoting properties, that research has focused on the subsequent addition of this polyphenol to beer. Back et al. [356] patented a process in which they added a hop product rich in xanthohumol after boiling and cooling the beer wort, thus avoiding its isomerization and consequent reduction. However, there are several studies where polyphenols are also affected by the action of yeasts. It has been shown that the use of yeasts other than the usual ones in wine, as well as autochthonous yeasts, increases the overall polyphenol content in comparison with commercial yeasts in wine [357,358,359]. Increases have been seen in phenolic acids, certain flavonols such as quercetin and kaempferol, and in stilbenes. Studies have also focused on the study of Saccharomyces cerevisiae var. boulardii yeast strains, as they favor the increase of antioxidant capacity as well as polyphenol content in beers [195,196]. Likewise, the use of yeasts in sequential fermentation in wine, with Saccharomyces cerevisiae and Torulaspora delbrueckii and S. cerevisiae with Zigosaccharomyces bailii, can increase the resveratrol content by up to 4.5 times [360,361].

In the winemaking process, not only wine is obtained but also various by-products, such as grape pomace and grape seed [142,143]. These by-products were used as feed or fertilizer; however, they have also been found to have a high content of compounds such as dietary fiber, lipid bioactives, phenolics, and other natural antioxidants, which can be used in nutrition or the pharmaceutical industry [142,143]. More and more studies are being conducted to determine the bioactivity of grapes and their products and by-products, focusing mainly on their antioxidant activity, which is associated with a high content of polyphenols that act as free radical scavengers.

In brewing, we also have several by-products with high concentrations of polyphenols that can be used in biotechnological processes to obtain value-added compounds, as well as substrates for the cultivation of microorganisms or as raw material for the extraction of compounds such as antioxidants. The most common by-products obtained from brewing are spent grain, spent hops, and leftover yeast. The most abundant is malt bagasse, as 120–135 kg of malt bagasse is generated for every 100 kg of malt [362]. Bagasse contains between 15% and 26% protein, 70% fiber, and 3.9–10% lipids [363]. Their uses range from animal feeding to the production of biogas, protein concentrates, and fermentation products; however, more studies are looking for how to extract the fraction of polyphenols for greater use [364].

Table 5. Concentration of different polyphenols in wine and beer (mg/L).

Phenolic Compounds	Red Wine	Beer	Reference	Health Benefits
Flavonoids
Flavanols				Reduces the risk of diabetes Improves the intestinal microbiota
Catechin	6.98–91.99	0.03–5.4	[358,365,366,367,368]
Epicatechin	8.07–37.8	0.19–3.3	[358,365,367,368]
Flavonols				Reduces the risk of diabetes Inhibit the release of histamine Block UV radiation Has an anti-aging effect Prevents weight gain Inhibits the growth of bacteria associated with an obesity-inducing die Treatment in neurodegenerative disorders Treatment in coronary heart disease Antioxidant, antitumor and anti-inflammatory activity
Kaempferol	0.61–26.8	0.1–16.4	[358,365,368]
Quercetin	1.27–65.9	0.06–10	[358,365,368,369]
Myricetin	0.7–30.4	0.007–0.16	[358,365,368,370]
Non-Flavonoids
Hydroxycinnamic acids				Antioxidant, anti-inflammatory, anti-allergic and anti-epileptic properties Anticarcinogenic activity Precursors of bioactive molecules that can be used in food
p-Coumaric acid	0.02–8	0.003–55.8	[358,365,366,368,371,372,373]
Caffeic acid	0.02–644.5	0.3–23.5	[317,358,365,368,371,373,374,375]
Ferulic acid	0.05–10.43	0.01–6.5	[358,365,368,371]
Hydroxybenzoic acids
Syringic acid	0.27–2.7	≤0.5	[365,368,375,376]
Vanillic acid	0.2–3.2	0.75–3.6	[365,368,373,375,377,378]
Gallic acid	21.4–70	41.2–142.2	[349,372,379]

shows a summary of the main common polyphenols found in beer and wine and their concentrations.

If we look more specifically at the benefits of each of the different polyphenols or groups of polyphenols found in wine and beer, there are several studies on their health benefits. Nettleton et al. [380] found that the moderate consumption of wine and beer, due to their flavonoid content, reduces the risk of diabetes after menopause.

Red wine has a high content of flavanols, more specifically catechin and epicatechin. It has been shown that the consumption of foods with these polyphenols improves the intestinal microbiota, since it increases the populations of the Clostridium coccoides–Eubacterium rectale group, Bifidobacterium spp., and Escherichia coli [381]. Catechin is one of the most abundant compounds in beer, whose origin, like wine, comes from raw materials (malt and hop) [382].

Regarding flavonols, quercetin, whose daily intake in total food can be 16–25 mg/day, is worth mentioning. It has been seen that quercetin is able to inhibit the release of histamine. It can also block UV radiation and has an anti-aging effect [383]. It also prevents weight gain, reduces serum insulin, and inhibits the growth of bacteria associated with an obesity-inducing diet [384]. In wine and beer, it is one of the most abundant flavonols. Flavones are also used to treat some neurodegenerative disorders, as well as coronary heart disease, since they possess antioxidant, antitumor, and anti-inflammatory activity [385].

On the other hand, among the non-flavonoid polyphenols, the most abundant hydroxycinnamic acids found in wine and beer are coumaric acid, caffeic acid, and ferulic acid. Although in beer, the highest concentrations can be contributed by p-coumaric acid, the predominant acid in Chinese, European, and Chilean beers is ferulic acid [386,387]. In beer, they come from malt and hops and will bring antioxidant, anti-inflammatory, anti-allergic, and anti-epileptic properties to beers [373]. In grapes they are found mainly in the skin and pulp. As for hydroxybenzoic acids, the most predominant in both beverages are vanillic acid, gallic acid, and syringic acid. It has been shown that gallic acid can be used as an indicator of oxidation in beer during its production [374], while in wine it is the precursor of hydrolysable tannins [349]. It has been shown that these polyphenols are easily absorbed by the intestine and pass into the blood [388]. Non-flavonoid polyphenols also possess anticarcinogenic activity, as well as acting as precursors of bioactive molecules that can be used in food, cosmetics, and therapeutic industries [389].

Red wine generally has a higher polyphenol content than beer; however, xanthohumol, which is a prenylated chalcone, is only found in beer, as it comes from hops. It is usually found in concentrations of around 0.002 and 0.628 mg/L [369] and has anticarcinogenic properties [390,391].

4.3. Melatonin Production

Originally, melatonin (MEL) was recognized as a unique product of the pineal gland of vertebrates and considered a neurohormone (n-acetyl-5-methoxytyramine) that is rhythmically secreted into the bloodstream. Young people have higher MEL levels, but they diminish gradually with age [8]. In the last decades, it has been identified as a secondary metabolite in a broad range of invertebrates, plants, and microorganisms [392,393,394]. Regarding plants, melatonin has been found in different cereals [395]. In fruits, grapes, cherries, and strawberries presented the highest concentrations [396]. Moreover, in fermented beverages such as wine and beer, MEL concentration ranged from picograms to nanograms per milliliter. In winemaking, MEL content raised the highest value between the first and second days of fermentation by yeast activity. By contrast, a high level of MEL in beer is attributed to the content in barley [397].

Melatonin synthesis is well-described in vertebrates, but the synthetic route and enzymes seem to be similar in yeast. Melatonin has been shown to be synthesized from tryptophan (Trp) via 5-hydroxytryptophan, serotonin, and ultimately n-acetyl serotonin (Figure 2). Moreover, MEL can also be formed by O-serotonin methylation followed by n-methoxy tryptamine acetylation in yeast [398].

As expected, several studies found the presence of melatonin in wines (

Table 6. Melatonin content in wines elaborated in different locations.

Wine Variety	MEL Content (ng/mL)	Country	Reference
Sangiovese, Trebbiano, Albana	0.4–0.6	Italy	[171,402]
Chardonnay, Malbec, Cabernet Sauvignon	0.16–0.32	Argentina	[168]
Gropello, Merlot	8.1 and 5.2	Italy	[403]
Cabernet Sauvignon, Petit Verdot, Prieto Picudo, Syrah, Tempranillo	5.1–129.5	Spain	[404]
Cabernet Sauvignon, Merlot, Palomino Fino, Syrah, Tempranillo, Tintilla de Rota	74.13–423.01	Spain	[399]
Albana	0.6	Italy	[171]
Monovarietal red wines (Groppello DOC, Melag DOC, Nebbiolo IGT, Terre di Rubinoro DOCG and Syrah IGT)	0.14–0.62	Italy	[405]
Polyvaryetal red wines (Placido Rizzotto IGT and La Segreta IGT)	0.05–0.31	Italy	[405]
Monovarietal white wines (Chaudelune-Vin de glace DOC)	0.11–0.31	Italy	[405]
Nebbiolo	0.57–0.63	Italy	[406]
Monovarietal red wines (Cabernet Sauvignon, Merlot, Babeasca neagra, Seibel 1, Othello)	1.0–66.6	Romania	[407]
Polyvaryetal red wines (Cabernet Sauvignon and Merlot, Isabelle and Babeasca neagra)	11.6–23.0	Romania	[407]
Monovarietal rose wines (Cabernet Sauvignon, Lidia)	1.4–82.6	Romania	[407]
Polyvaryetal rose wines (Riesling and Chasselas)	2.0	Romania	[407]
Monovarietal white wines (Riesling, Noah)	11.8–35.4	Romania	[407]
Polyvaryetal rose wines (Riesling and Feteasca)	1.0	Romania	[407]

), many of them aimed at elucidating the origin of MEL in wines from the grape berries or the fermentation process of wine. Since the pioneering study by Sprenger et al. [398] that reported the presence of the MEL molecule in wine and its presence was related to the activity of the yeast implicated in the fermentation process, several works have confirmed the decisive role of yeasts in the final content of MEL in wines [237,399,400]. In a study by Gomez et al. [401], they monitored MEL during the entire winemaking process in the Malbec variety (Vitis vinifera L.). A quantity of 120–160 ng/g of MEL was detected in grape extract, but only its isomer was found in musts and wines in the range of 18–24 ng/mL, concluding that MEL from grape berries does not transfer to musts and enter into the winemaking process. Therefore, the MEL amount in wines is linked with yeast metabolism.

As previously mentioned, melatonin can be synthesized via tryptophan to n-acetyl serotonin as a direct precursor of MEL (Figure 2). Research articles reported the analysis of MEL and its precursors, especially tryptophan. Some results related that the addition of exogenous tryptophan considerably raises the MEL levels in wines [398,400,408]. The Trp was added to a synthetic medium before the fermentation in the study by Rodríguez-Naranjo et al. [400], while Xiang et al. [408] did a root application of Trp combined with spraying application during the véraison stage in the Marselan grape cultivar. Both works observed an increment of MEL in final products. Contrary to these results, there was no noticeable increase after Trp supplementation during the fermentation with S. cerevisiae in the work by Gomez et al. [401].

All previous studies have exclusively focused on melatonin production of S. cerevisiae without considering the action of non-Saccharomyces during alcoholic fermentation. Thus, recent studies focused attention on the possible relation of these non-conventional yeasts and the production of melatonin. Different S. cerevisiae strains and two non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) have been proven to be MEL producers during alcoholic fermentation in synthetic grape must [409]. On the other hand, Valera et al. [410] studied the influence of MEL supplementation in wine fermentations with different S. cerevisiae and non-Saccharomyces combinations and different YAN regimes. Non-Saccharomyces (Hanseniaspora uvarum, Starmerella bacillaris, T. delbrueckii, and M. pulcherrima) viability was increased by the addition of MEL in the first hours of fermentation with a higher YAN content (300 mg/L). In addition, they observed that MEL concentration in wine was increased when a mixed culture (S. cerevisiae + non-Saccharomyces strains) was performed. These results are in agreement with another recent work [411] where mixed cultures between S. cerevisiae and Lachancea thermotolerans generated higher values of MEL than the control in Aligoté + Fetească alba wines. In addition, they also observed when Pichia kluyveri (FROOTZEN^®, CHR Hansen, Hamburg, Germany) strain is inoculated, MEL is found in high amounts in Aligoté + Fetească albă and Sauvignon blanc wines. The presence of non-Saccharomyces in beer fermentation also enhances the MEL content. It has been found in beer elaborated with wild Saccharomyces and non-Saccharomyces yeast [14,254] that the proportion of MEL is double when non-Saccharomyces strains are present in the trials (6.69–102.98 ng/mL with non-Saccharomyces and 5.04–56.51 ng/mL with Saccharomyces strains). These results are coincident with another study [412] where the usage of sequential cultures favored the MEL quantity in almost all beers (33.63–66.57 ng/mL). In the study carried out by Fernandez-Cruz et al. [409], they observed that non-Saccharomyces strains T. delbrueckii and M. pulcherrima took longer to synthesize MEL than Saccharomyces. In the studies carried out by Fernandez-Cruz et al. [135] at the intracellular level with wine yeasts, melatonin was only detected in non-Saccharomyces yeasts.

The yeast S. cerevisiae can produce MEL in fermentation at high concentrations. Also, its content in the final product is influenced by multiple factors such as the length of fermentation, the Trp level, the composition of grapes, and the availability of reducing sugars [398,400,405] but the role of MEL in yeasts and other microorganisms seems to be far from being understood. It is worth mentioning that bacteria also play an important role in the MEL content in wines. The lactic acid bacteria Oenococcus oeni has been seen to produce MEL at laboratory and winery scales [413].

Regarding beer, the MEL content found in the final product comes from cereals used and from the yeast S. cerevisiae after the second fermentation. In a work by García-Moreno et al. [414], MEL was quantified during the brewing process, and they observed the highest level of this antioxidant in the barley wort (339 pg/mL) and in the second fermentation (333 pg/mL). Even so, the MEL content in beers is also influenced by factors such as the quality of the barley malts, the fermentation process, the elaboration system, and the alcohol strength of the beer [415]. Craft beers have higher levels than commercial ones (333 pg/mL and 113 pg/mL, respectively) [397]. In a study of commercial beers with different alcohol degrees, MEL content is directly proportional to alcohol concentration, ranging from 58 pg/mL in non-alcoholic beer to 169 pg/mL in beers with higher alcohol values. These results are in agreement with other previous work [416]. The presence of non-Saccharomyces in beer fermentation also enhances the MEL content. It has been found in beer elaborated with wild Saccharomyces and non-Saccharomyces yeast [14,254] that the proportion of MEL is double when non-Saccharomyces strains are present in the trials (6.69–102.98 ng/mL with non-Saccharomyces and 5.04–56.51 ng/mL with Saccharomyces strains). These results are coincident with another study [412] where the usage of sequential cultures favored the MEL quantity in almost all beers (33.63–66.57 ng/mL). In the study carried out by Fernandez-Cruz et al. [409], they observed that non-Saccharomyces strains T. delbrueckii and M. pulcherrima took longer to synthesize MEL than Saccharomyces. In the studies carried out by Fernandez-Cruz et al. [135] at the intracellular level with wine yeasts, melatonin was only detected in non-Saccharomyces yeasts.

Despite the fact that the presence of circadian behavior has been described in yeast [417,418,419,420], it was reported as a systematic circadian metabolism in response to cyclic environmental stimuli, but its relationship with the MEL is not clear. Instead, melatonin has antioxidant capacity, and it could contribute to preventing stresses inherent to wine and beer fermentations. In response to oxidative stress in yeasts, MEL acts by lowering intracellular reactive oxygen species (ROS) levels, improving the cell’s viability, and activating genes involved in the oxidative stress response related to antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase [421,422,423]. Moreover, Vázquez et al. [421] demonstrated that the presence of MEL produced by S. cerevisiae and non-Saccharomyces strains reduces lipid peroxidation by the modulation of the fatty acid composition, increasing oleic and palmitoleic acids, and leading to higher unsaturated fatty acids/saturated fatty acids ratios, which increases H₂O₂ tolerance. The protective character of MEL is extendable for other stresses like UV radiation (254 nm) [424]. On the other hand, MEL has been proposed as a growth signal molecule in yeasts that presents a zigzag pattern that appeared and disappeared during fermentation [425], and it binds a TEF1-A receptor involved in the glucose metabolism [426].

In humans, there are several beneficial effects for health associated with MEL, like antioxidant, anticancer, neuroprotective, and immunomodulatory action [162]. MEL is able to stimulate endogenous antioxidant enzymes and to counteract ROS such as ONOO⁻, NO˙, and H₂O₂ [427,428]. Furthermore, various investigations have already shown the protective actions of MEL linked to the preservation of cell viability through the protection of lipids, protein, and DNA from free radicals. Also, it was able to reduce the oxidative stress associated with aging in patients with fertility disorders [429], and it seems to reduce blood pressure in human males with chronic hypertension [430]. This molecule has been found in different locations of the cell, such as the cytosol, nucleus, membranes, and mitochondria, since its amphipathic character enables it to trespass physiological barriers [431]. It is quite important because the molecule can be at the places where it is needed, in contrast to other dietetic antioxidants. Regarding the neuroprotective activity of MEL, it has been very well-tested in sleep disorders, helping to reduce sleep latency and improving circadian rhythm. In this case, it was notably useful in patients with neurodegenerative diseases [432] as a treatment for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. There is also evidence about the efficacy of MEL in limiting tumor cell proliferation and regulating autophagy and apoptosis, and the MEL administration together with standard chemotherapies often makes patients’ quality of life better [432,433].

A notable characteristic of bioactive compounds is the low concentration necessary for their efficacy. Nevertheless, it is difficult to establish a direct correlation between dietary sources of melatonin, its bioavailability in humans after intake, and the establishment of one therapeutic dose. MEL levels detected in wine samples (Table 4) exceed their circulating concentrations in humans for the entire day (about 200 pg/mL at the maximum night peak and lower than 10 pg/mL during the day [434]), but the oral bioavailability of MEL after intake of a glass of wine needs further investigation [406]. Several works have aimed to study serum melatonin levels assessed after wine intake [397,435]. In a study, serum melatonin concentration rose from 10 to 12 pg/mL 60 min after a 100 mL glass of red wine was administered [435]. Varoni et al. [397] analyzed the levels of MEL in serum and saliva after the intake of a MEL-enriched red wine in healthy volunteers. The maximum concentration in serum was observed at 30 min and 60 min (8.6 pg/mL and 8.7 pg/mL, respectively), but it was no longer detectable at 90 min. Salivary levels slightly peaked at 45 min after MEL + wine administration, returning after 120 min to the control level. Similar results have been found before beer intake [416]; 45 min was the time necessary for the oral MEL to be absorbed and also detected in serum. The study employed seven healthy volunteers whose total MEL ingested was 112 ng for men and 56 ng for women at this time.

5. Bio Healthy Beverages

5.1. Low-Alcohol and Alcohol-Free Beer and Wine

Consumers’ attention to a healthier lifestyle has led to a selection of low-alcohol beverages. Affluent consumers also want variety in their products, which has led to a craft beverage revolution. The desire for low-alcohol and quality beers drives this so-called low-alcohol or no-alcohol revolution [436]. The absence of ethanol in low-alcohol and alcohol-free beers (AFBs) leads to a diminished sensory experience for the brewer. Indeed, ethanol enhanced the release of aroma compounds (specifically aldehydes and esters) and increased viscosity [437]. Brewers still face significant challenges in producing AFBs that provide a sensory experience comparable to regular alcoholic beers. Similarly, although a segment of wine consumers is looking for profiles with greater fruit intensity and flavor ripeness, which is achieved by harvesting with high maturity and therefore obtaining a greater volume of ethanol, other consumers are looking for softer wines with lower ethanol content. There are several strategies to produce wines with a reduced ethanol content, from the vineyard to the winery. In the winery, efforts have been made to find yeasts that, through carbon metabolism, remove ethanol and produce glycerol [13,438].

Non-Saccharomyces yeasts are an interesting alternative to produce reduced-alcohol beer. The exploration of non-Saccharomyces yeast species presents a promising opportunity to overcome these challenges. These yeasts, with their diverse metabolic capabilities and unique flavor profiles, offer the potential to create innovative and flavorful low-alcohol beers [198,439].

5.2. Gluten-Free Beer

Alternative grains such as rice, sorghum, corn, millet, oats, buckwheat, quinoa, and amaranth are used to produce gluten-free beers. These raw materials may negatively influence the quality of the beer. This approach led to the complete absence of gluten in the final beer, but the different composition and chemical structure of starch compared to barley also influenced the fermentation kinetics [440].

A recent paper reviewed new alternative solutions for the production of gluten-free beer. Some improvements in the malting of these alternative grains and reevaluating the starch-enzyme system to develop new mashing protocols have led to significant advancements in producing high-quality beers from non-barley grains [441]. A recent study brewing 40% of unmalted gluten-free cereals resulted in an acceptable final product from a physicochemical and sensorial point of view even if the target of 20 ppm has not been reached [442]. Gluten-free barley at pilot and industrial scale was reached using different brewhouse technologies and gluten-minimization treatments (tannins, prolyl-endopeptidase from Aspergillus niger, and silica gel) [443].

5.3. Healthier Beer and Wine

Beer and wine contain several healthy compounds such as antioxidants, phenolic products, traces of group B vitamins, minerals (selenium, silicon, potassium), soluble fibers, and microorganisms. Low or moderate beer/wine consumption showed positive effects on health by stimulating the development of healthy microbiota.

Polyphenols in beer derive from malt and hops [6], while in wine they are derived from grapes [444]. They have the ability to stimulate the growth of the gut microbiota, favoring anti-inflammatory and antioxidant effects [445]. Furthermore, their degradation products exhibit prebiotic properties, capable of counteracting intestinal dysbiosis. Several studies have shown that beer stimulates the gut microbiota through the growth of saccharolytic microorganisms that generate short-chain fatty acids [446,447].

The fibers contained in beer are essentially β-glucans, arabinoxylans, mannose, fructose polymers, etc., functioning as prebiotics for the intestinal gut [448,449].

Another type of substance that is often considered close to fiber because they have an extremely low digestibility is melanoidins (melanosaccharides), which possess antioxidant and antibacterial properties and interact with microbiota through a prebiotic type of action [450,451,452]. A recent review focused on health compounds responsible for interaction with gut microbiota with the perspectives of the development of fortified beers [453].

6. Conclusions

In conclusion, beverages such as wine and beer are made up of different bioactive compounds that give them not only sensory properties but also improve their functionality, in addition to providing health benefits under responsible consumption.

As we have seen throughout the review, both beverages contain vitamins, minerals, and other compounds that make them healthy. However, the compounds that will provide the most bio-healthy characteristics are the antioxidant compounds, such as polyphenols and melatonin. These compounds, derived from the metabolism of yeast in wine and ingredients such as malt and hops, in addition to the metabolism of yeast in beer, have antioxidant, anti-inflammatory, and cardioprotective effects and have been linked to reducing the risk of non-communicable diseases, such as cardiovascular disorders, certain types of cancer, and neurodegenerative diseases. As for polyphenols, their classification is complex, but they are divided into flavonoids and non-flavonoids, which will not only give bioactive characteristics to wine and beer but also modify their organoleptic profile. While it is true that moderate consumption of wine and beer, although associated with health benefits, is important to carry out responsible consumption because otherwise you could have negative health related to excessive alcohol consumption. As seen throughout the review, in terms of polyphenol concentration, red wine outperforms beer, possibly due to the presence of tannins; however, melatonin concentrations tend to be higher in beer than in wine.

On the other hand, the increasing demand for healthy drinks with a lower ethanol content makes it necessary to go deeper into this type of drink; it is therefore important that research continue in this direction with low-ethanol beer and wine.

Over the years, the sector of functional beer probably will grow, attracting people with healthy conditions but also different religious and cultural traditions. Functional beer and wine will see the birth of a health-conscious consumer without losing the taste of these traditional beverages. The ways to obtain a functional beer are possible by using herbs, spices, probiotic microorganisms, and functional compounds. In wine, these techniques would focus on the use of innovative wine-making techniques, new strains of yeasts and bacteria, as well as agricultural practices. Further investigations are necessary to give stability to the product and to confirm benefits to human health.