Editing Health and safety

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During [[beer production]], large quantities of hot liquids are handled, especially during [[mashing]] and wort [[boiling]]. Brewers should be careful. All vessels and auxiliary equipment (e.g. hoses) should be checked for stability before they are used. Wearing heat-resistant gloves and suitable work clothing is recommended. Remember to close appropriate valves before filling a vessel with hot liquid.

The harmful effects of heavy drinking have been well described; beverages with high alcohol content are not good for human health.<ref name=yangao>Yang D, Gao X. [https://www.sciencedirect.com/science/article/abs/pii/S0924224421001552 Research progress on the antioxidant biological activity of beer and strategy for applications.] ''Trends Food Sci Technol.'' 2021;110:754-764.</ref> However, the effect of an intermediate amount of drinking is more complex and needs further study. This issue involves the possible probiotic effects associated with non-alcoholic ingredients in beverages such as beer. Some clinical trials have suggested that moderate consumption of beer is good for human health, mainly due to antioxidants, anti-inflammatory effects, and reduced risk of cardiovascular disease. Increasing anti oxidant activities (AOX) of foods and beverages consumed by people is an effective way to improve human health.

In general, the evidence suggests a J-shaped curve relationship between alcohol consumption and cardiovascular disease (CVD) morbidity and mortality, indicating that moderate drinkers are at lower risk than abstainers and heavy drinkers [2].<ref name=borsol>Boronat A, Soldevila-Domenech N, Rodríguez-Morató J, Martínez-Huélamo M, Lamuela-Raventós RM, de la Torre R. [https://www.mdpi.com/1420-3049/25/11/2582 Beer phenolic composition of simple phenols, prenylated flavonoids and alkylresorcinols.] ''Molecules.'' 2020;25(11):2582.</ref> Other more specific studies observed that cardiovascular protection was only observed with moderate consumption of fermented alcoholic beverages containing [[phenolic compounds]] such as wine or beer. The protective effect was not observed following moderate consumption of spirits. In the specific case of beer, low-to-moderate consumption (up to one drink/day in women and two drinks/day in men) reduces the risk of CVD and represents no harm in relation to major chronic conditions [3,4]. Evidence suggests that beer’s beneficial health effects result from an additive effect between beer’s alcohol content and beer’s phenolic compounds [5]. its alcohol content is lower compared to other popular alcoholic drinks. Therefore, its low alcohol content together with its phenolic composition suggest beer to be a potential trigger of positive health effects while minimizing the detrimental effects associated with alcohol consumption. The phenolic compounds have been associated with relevant biological activities such as antioxidant, anti-inflammatory, antidiabetic and estrogenic activities.

beer can also be a source of compounds with potential toxic and pro-carcinogenic properties at higher concentrations such as carbonyl compounds and furan derivates [18].<ref name=borsol/>

Moderate beer consumption has been shown to have beneficial effects on human health, many of which are based on the redox properties of the antioxidant compounds present in beer [5,16,17]. It is known that antioxidants present in beer help to improve certain diseases, for example, moderate beer consumption is associated with an increase in bone density, cardiovascular [18] and immunological benefits and is also associated with anti-inflammatory and antioxidant properties [19]. Moderate beer intake may also exert higher protection against coronary heart disease than spirits; it has been reported that systolic blood pressure, homocysteine, and several biomarkers of inflammation decreased only after the non-alcoholic beer intervention, and these effects are likely to be attributed to the non-alcoholic fraction of the beer, mainly polyphenols [20].<ref name=marcab>Martinez-Gomez A, Caballero I, Blanco CA. [https://www.mdpi.com/2218-273X/10/3/400 Phenols and melanoidins as natural antioxidants in beer. Structure, reactivity and antioxidant activity.] ''Biomolecules.'' 2020;10(3):400.</ref>

Small-scale commercial beers tend to have higher levels of phenolic compounds than and large scale (macro) beers.<ref name=cargui>Carvalho DO, Guido LF. [https://www.sciencedirect.com/science/article/abs/pii/S0308814621020999 A review on the fate of phenolic compounds during malting and brewing: technological strategies and beer styles.] ''Food Chem.'' 2022;372:131093.</ref> This is partly because [[pasteurization]] and [[filtration]] are not employed in small-scale beers. Also, macro beers are usually produced using cereal [[adjuncts]] like [[maize]], which generally contribute lower levels of phenolics. Lastly, the amount and variety of hops often used for small scale "craft" beers tend to provide higher phenolic content.<ref name=sibpla>Šibalić D, Planinić M, Jurić A, Bucić-Kojić A, Tišma M. [https://link.springer.com/article/10.1007/s11696-020-01276-1 Analysis of phenolic compounds in beer: from raw materials to the final product.] ''Chem Zvesti.'' 2021;75(1):67–76.</ref> Presumably all these factors apply to home brew beer as well, although phenolic levels still vary depending on ingredients and brewing process.

Alcohol intake in the form of liquor can lead to an increase in serum homocysteine, a heart-related disease that promotes the production of oxygen free radicals and hydrogen peroxide, which can cause vascular endothelial cell damage, platelet adhesion and aggregation and promote low-density lipoprotein oxidation, leading to atherosclerosis and embolism.<ref name=yangao/> In contrast, moderate consumption of beer has not been found to increase serum homocyste ine, probably because beer contains vitamin B6, which can promote the catabolism of homocysteine.

The selenium contents range from 0.59 to 10 μ g/L (Rodrigo et al., 2015).<ref name=yangao/>


'''Health Benefits of Polyphenols'''<br />
In regard to polyphenols, these are characterized by the presence in their structure of one or several phenolic groups, capable of reducing reactive oxygen species and various organic substrates and minerals. These redox properties explain the considerable interest in their role in the prevention of several major chronic diseases associated with oxidative stress, such as cardiovascular diseases, cancers, type II diabetes, neurodegenerative diseases or osteoporosis [21]. Phenols present in beer help lower blood pressure and increase the concentration of nitric oxide in the plasma, reducing the risk of cardiovascular disease [18].
These healthy properties are, in part, due to a specific type of phenolic compounds present in beer, the flavonoids. These compounds also possess anti-inflammatory, antioxidant and hypocholesterolemic properties [22]. In addition, polyphenols prevent oxidation of low-density lipoproteins [22] as they block free radicals that can oxidize fats in the body [23]. Polyphenols are recognized as preventers of colon cancer [24,25,26]. They are also able to cause positive changes in the gut microbiota, for example, flavonols induce an increase in the growth of Lactobacillus spp. and Bifidobacterium spp [24]. Polyphenols are also associated with improvements experienced by women in menopause [27] and improvements observed in people suffering from arthritis [28], but the bioavailability of polyphenol associated with this benefit, resveratrol, is low [29].
More specifically, some antioxidants have been studied such as xanthohumol (flavonoid present in beer and found only in hops [30]) and its cyclization product, isoxanthohumol, which have been studied previously by us [31] both present anti-cancer properties. Xanthohumol displays many bioactive effects such as antioxidant, anti-inflammatory, anti-microbial, hypoglycemic, and anti-obesity [32,33]. In particular, this compound is effective against different types of cancer [30] among which are: breast [34], ovarian [34], prostate [35], of colon [36] and pancreas [37] as well as being effective against leukemia [38] and protecting DNA against oxidative damage [39]. With a xanthohumol content of around 200 mg/L, beer is the principal source of this molecule in the human diet [33,40].<ref name=marcab/>

'''Health Benefits of Melanoidins'''<br />
Regarding melanoidins, several works have shown that in addition to their ability to affect the color, flavor, and body of beer, these compounds can exert a certain effect on health. Difficulties in ascribing definite properties to individual melanoidins are caused by their diversity, complexity, drawbacks with purification and identification, and poor solubility in water and organic solvents. Additionally, other low molecular weight compounds are usually linked with melanoidins and may influence their properties. Furthermore, the degree of digestibility and bioavailability of melanoidins in organisms is often low [41].
Nonetheless, some studies have shown that melanoidins exert antioxidant, antimicrobial, antihypertensive, antiallergenic, and prebiotic properties [42]. Melanoidins also demonstrate the ability to bind metal ions such as Fe+2 [43] and are considered as antimutagenic and tumor growth-inhibiting compounds [44,45]. Melanoidins protect against damage caused by ROS to DNA and a more intense effect was found for dark beers than for blond beers due to dark beers are richer in melanoidins [41].
There is evidence that melanoidins behave as dietary fiber, being indigestible by humans and fermented in the gut, dietary melanoidins are not digested in the upper gastrointestinal tract and they are mainly recovered in the faeces [46]. Consequently, food melanoidins, as part of the food indigestible material that reaches the lower gut, can be metabolized by the gut microorganisms and have to be considered as a potential prebiotic material.<ref name=marcab/>

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Recent studies correlate the consumption of polyphenols-rich foods with the prevention of many modern diseases associated with oxidative stress [11–14]. Even though ethanol has been regarded as carcinogenic to humans (WHO IARC group 1) [15] a mild or moderate ethanol consumption in the form of beer or wine can contribute to the overall positive status of human health [16–20].<ref name=hablon>Habschied K, Lončarić A, Mastanjević K. [https://www.mdpi.com/2304-8158/9/2/238 Screening of polyphenols and antioxidative activity in industrial beers.] ''Foods.'' 2020;9(2):238.</ref>

light and moderate drinking has been associated with lower mortality rates compared to heavy drinking and abstaining (Denke, 2000; Yen et al., 2012). Especially red wine consumption has been associated with a lower risk of mortality (Klatsky, Friedman, Armstrong, & Kipp, 2003), even though confounding factors such as diet, exercise and social class have been found to be favorable in wine drinkers (Klatsky et al., 2003; Wannamathee & Shaper, 1999). However, the role of alcohol as a toxin, which has deleterious effects on human health, should not be underestimated (Fernandez-Sola, 2015; Gerhauser, 2005).<ref name=wangas>Wannenmacher J, Gastl M, Becker T. [https://ift.onlinelibrary.wiley.com/doi/abs/10.1111/1541-4337.12352 Phenolic substances in beer: Structural diversity, reactive potential and relevance for brewing process and beer quality.] ''Compr Rev Food Sci Food Saf.'' 2018;17(4):953–988.</ref>

[[Lipid transfer protein|LTP]] and [[protein Z]] have been identified as the main beer allergens.<ref>Gorjanović S, Sužnjević D, Beljanski M, et al. [https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2050-0416.2004.tb00624.x Effects of lipid-transfer protein from malting barley grain on brewers yeast fermentation.] ''J Inst Brew.'' 2004;110(4):297–302.</ref>

Reactions to LTP appear to be more common in the Mediterranean area [44], with clinical cross-reactivity being described between foods and pollens. However, although less common in birch-endemic areas, clinical reactivity to LTP is still important in some patients, for example, Flinterman et al. [45]. Clinically, there are thus similarities with the North European pollen/fruit syndrome, but this Southern Europe variant is clinically more severe, not prevented by cooking, and due to different protein cross-reactivities.<ref>Unsworth DJ, Lock RJ. [https://www.sciencedirect.com/science/article/abs/pii/B9780128001417000061 Chapter 6: Food Allergy Testing.] In: Makowski GS, ed. ''Advances in Clinical Chemistry.'' Vol 65. Elsevier; 2014:173–198.</ref>

Beer proteins positively affect the plasma lipid level in rats decreasing the total cholesterol, LDL-cholesterol and triglyceride levels57. The hypolipidemic effect of beer proteins might be one of the reasons why moderate consumption of beer is associated with lower rates of cardiovascular diseases33.<ref name=stanislava>Stanislava G. [https://onlinelibrary.wiley.com/doi/epdf/10.1002/j.2050-0416.2007.tb00291.x Barley grain non-specific lipid-transfer proteins (ns-LTPs) in beer production and quality]. ''J Inst Brew''. 2007;113(3):310–324.</ref>

Beer has been implicated as the causative agent of urticaria and severe IgE-modified anaphylaxis. Despite the large worldwide beer consumption, allergic reactions to beer have been very rarely reported.<ref name=stanislava/>

Since [[Low alcohol beer|non-alcoholic beers]] have significantly lower calorie content than normal beers, they are becoming more attractive to a health-conscious consumer.<ref>Krebs G, Müller M, Becker T, Gastl M. [https://www.sciencedirect.com/science/article/abs/pii/S0963996918306872 Characterization of the macromolecular and sensory profile of non-alcoholic beers produced with various methods.] ''Food Res Int.'' 2019;116:508–517.</ref>

Although ethanol is recognised as a major contributor to cancer diseases, moderate consumption of red wine is known to have some health benefits. The decrease in coronary heart disease observed among wine drinkers despite a diet very rich in saturated fat is known as the “French paradox”.(234) Wine polyphenols and alcohol most probably contribute to this protective effect.(235,236) Beer contains much less polyphenols than wine, although one of its raw materials, hop, is much richer than grapes. The two beverages also show very different polyphenol distributions (e.g., no anthocyanidins in beer but more prenylchalcones).<ref name=calcol>Callemien D, Collin S. [https://www.tandfonline.com/doi/abs/10.1080/87559120903157954 Structure, organoleptic properties, quantification methods, and stability of phenolic compounds in beer—a review.] ''Food Rev Int.'' 2009;26(1), 1–84.</ref>

In conclusion, our data suggest that beer can supply molecules with potential antioxidant activity, as well as micronutrients containing part of the active site of superoxide dismutase and glutathione peroxidase, both potentially contributing to the overall antioxidant activity in vivo.<ref name=fanmon>Fantozzi P, Montanari L, Mancini F, et al. [https://www.sciencedirect.com/science/article/abs/pii/S0023643897903418 ''In vitro'' antioxidant capacity from wort to beer.] ''LWT - Food Sci Technol.'' 1998;31(3):221–227.</ref>

Production of reactive oxygen species (ROS) in tissue contributes to the development of various chronic diseases such as cancer, neurodegenerative diseases, and cardiovascular diseases (Benzie, 2000; Stocker, 1999). Administration of antioxidants to patients may therefore help in removing ROS and thus improve the clinical outcome. Dietary antioxidants can enhance cellular defence and help to prevent oxidation damage to cellular components. There has been considerable public and scientific interest in therapeutic use of natural antioxidants. Among the natural antioxidants, polyphenols play a very important role. Dietary polyphenols are thought to be beneficial to human health by exerting various biological effects such as free radical scavenging, metal chelation, modulation of enzymatic activity, and alteration of signal transduction pathways.<ref name=itakur>Itagaki S, Kurokawa T, Nakata C, et al. [https://www.sciencedirect.com/science/article/abs/pii/S030881460801162X ''In vitro'' and ''in vivo'' antioxidant properties of ferulic acid: A comparative study with other natural oxidation inhibitors.] ''Food Chem.'' 2009;114(2):466–471.</ref> Epidemiological studies have shown relationships between consumption of polyphenol-rich foods and prevention of diseases such as cancer, coronary heart disease, and osteoporosis, and results of these studies have promoted interest in polyphenols. This study in rats provides a scientific background of the usefulness of ferulic acid as a functional food ingredient that helps prevent pathological oxidation.

*'''Cardiovascular protection.''' Flavonols and flavan-3-ols induce cardioprotective effects, including antioxidant effects (protection against LDL oxidation) and inhibition of platelet activity and vasodilatation.(205,237) trans-Resveratrol shows an impact on platelet aggregation and vasodilatation, and through its effect on the antioxidant status, regulates gene expression and decreases the total lipid concentration (cholesterol and triglycerides).(238) Although less potent, cis-resveratrol, trans- and cis-piceid also improve the antioxidant activity (239,240). Piceid absorption is enhanced by the presence of its sugar.(241)<ref name=calcol/>
*'''Anticancer activity.''' Xanthohumol is a “broad-spectrum” cancer chemopreventive agent acting on all three stages of carcinogenesis. Xanthohumol and isoxanthohumol are both active ROS scavengers, while only the former is active in superoxide scavenging assays. Isoxanthohumol, 8-prenylnaringenin, and xanthogalenol may also exert chemopreventive effects.(55,71,79,242,243) trans-Resveratrol inhibits the initiation and growth of tumors. It inhibits cyclooxygenase, ornithine decarboxylase, and angiogenesis.(244,245) trans-Piceid is a weaker inhibitor of ROS production.(246) Very little information is available on potential anticancer effects of flavonols and flavan-3-ols. Flavonoids might reduce the risk of cancer, although some procarcinogenic activities have also been reported.(115,205)<ref name=calcol/>
*'''Anti-inflammatory activity.''' Flavonoids alter the synthesis of eicosanoids (mediators of inflammation). They decrease the leukotriene/prostacyclin ratio by modifying lipoxygenase activity.(247,248) Immune regulation has also been observed.(249) trans-Resveratrol shows similar effects.<ref name=calcol/>
*'''Estrogenic activity.''' Prenylflavanones have mainly been studied for their estrogenic activity. Hopein is a very potent phytoestrogen. The authors recommend its application in prevention or treatment of (post)menopausal symptoms and osteoporosis.(71,134,242) Weak estrogenic activity has been observed for close analogs like 6-prenylnaringenin, 8-geranylnaringenin, 6,8-diprenylnaringenin, and isoxanthohumol. Prenylchalcones like xanthohumol and xanthogalenol also show low activity.(135) Estrogenic activity has recently been reported for some stilbenes, especially transresveratrol. cis-Resveratrol appears less potent.(245,251)<ref name=calcol/>
*'''Impact on neurodegenerative diseases.''' Hop proanthocyanidins can help prevent nitric-oxide-related disorders such as Alzheimer’s and Parkinson’s diseases.(49)<ref name=calcol/>

Phenolic compounds in food are of particular interest due to the potential health benefits associated with them. The biological activity of phenolic compounds is partly linked to their antioxidant activity, which enables them to protect human cells from oxidative stress. In fact, light and moderate drinking has been associated with lower mortality rates compared to heavy drinking and abstaining.<ref name=wangas/> Especially red wine consumption has been associated with a lower risk of mortality, even though confounding factors such as diet, exercise and social class have been found to be favorable in wine drinkers. This controversial phenomenon that light and moderate drinking is associated with a decrease in coronary heart
disease events has been associated with the high polyphenol content of red wine. Especially resveratrol has been linked to the beneficial health effects of red wine.

xanthohumol has been identified as one of the most potent cancer-chemopreventive compounds in beer (Gerhauser et al., 2002). Xanthohumol and other prenylated hop flavonoids are still a field of active research due to their biological activity with phytoestrogenic, antioxidant and cancer-chemopreventive activities (Stevens & Page, 2004; van Hoyweghen, Biendl, & Heyerick, 2010; Venturelli et al., 2016). However, the efficiency of xanthohumol as a pharmacologically effective food compound might be limited due to its low bioavailability (Venturelli et al., 2016). Cancer-chemopreventive substances in beer and their potential modes of action were reviewed by Gerhauser (2005). The bioavailablity of phenolic compounds is affected by their chemical structure, especially glycosylation. Glycosylation adversely affects gut absorption of phenolic compounds as it inhibits passive diffusion through biological membranes. However, removal of the sugar moiety might be achieved by human β-glucosidases and enzymes of the gut microflora (Scalbert & Williamson, 2000). However, other food constituents like lipids, proteins or carbohydrates also interact with polyphenols by noncovalent bonds (hydrophobic and hydrogen bonding). These interactions have an impact on polyphenol bioavailability and bioaccessibility as recently summarized by (Jakobek, 2015). Polyphenol intake from foods is observed by the increase of plasma antioxidant activity and by measuring phenolic compound levels in urine after the ingestion of polyphenol-rich foods (Bourne, Paganga, Baxter, Hughes, & Rice-Evans, 2009; Ghiselli et al., 2000; Scalbert & Williamson, 2000). Polyphenol intake after beer ingestion has been found to depend on the alcohol content of beer, with dealcoholization resulting in lower bioavailability (Ghiselli et al., 2000). In order to evaluate the potential health benefits of beer polyphenols, further studies concerning metabolism of phenolic compounds and the specific biological effects of phenolic metabolites are needed.<ref name=wangas/>

Resveratrol is reportedly an anti-inflammatory and anticancer agent, and also acts preventively on cardiovascular diseases development [55,56]. Cosmetic industry acknowledges it as an anti-aging agent [49].<ref name=habkos>Habschied K, Košir IJ, Krstanović V, Kumrić G, Mastanjević K. [https://www.mdpi.com/2306-5710/7/2/38 Beer polyphenols—bitterness, astringency, and off-flavors.] ''Beverages.'' 2021;7(2):38.</ref>

Phenolic acids are potent antioxidants and are absorbed by humans after beer ingestion.<ref name=wangas/>

Amount of phenolics in beer and wine is comparable (10). Recent claims suggest that the in vivo AO capacity of beer and red wine are similar despite different concentrations of total polyphenols, possibly due to superior absorption of the beer phenolics as compared with those in red wine (2, 10,11). Although beer per drink (of equivalent alcohol content) contains more than twice as many of the AOs as white wine and only half the amount in red wine (12), the red wine AOs may be larger molecules that are not as readily absorbed as the smaller AOs in beer (13,14).<ref name=gornov>Gorjanović SŽ, Novaković MM, Potkonjak NI, LeskoŠek-Čukalović I, Sužnjević DŽ. [https://pubs.acs.org/doi/abs/10.1021/jf903091n Application of a novel antioxidative assay in beer analysis and brewing process monitoring.] ''J Agric Food Chem.'' 2010;58(2):744–751.</ref>

The health benefits of barley β-glucans include reduction of blood cholesterol and glucose and weight loss by increased satiety, and therefore, the control of heart disease and type-2 diabetes (Baik & Ullrich 2008). However, new findings revealed that cereal grains also contain many health-promoting components such as vitamins, minerals, essential fatty acids, phytochemicals and other bioactive food components, which include phenolic compounds (Dykes & Rooney 2007).<ref name=simhor>Šimić G, Horvat D, Dvojković K, et al. [https://www.agriculturejournals.cz/web/cjfs.htm?type=article&id=144_2016-CJFS Evaluation of total phenolic content and antioxidant activity of malting and hulless barley grain and malt extracts.] ''Czech J Food Sci.'' 2017;35(1):73–78.</ref>

Beer has a higher nutritional value than other alcoholic beverages, because of its minerals and essential nutrients such as potassium, magnesium, calcium and sodium.<ref name=soliva>Solgajová M, Ivanišová E, Nôžková J, Frančáková H, Tóth Ž, Dráb Š. [https://www.proquest.com/openview/0a0ccd3ae387c2d4a4db31f29bec1614/1 Antioxidant activity and polyphenol content of malt beverages enriched with bee pollen.] ''J Microbiol Biotech Food Sci.'' 2014;3(3):281–284.</ref>

Among dietary antioxidants, phenolics are by far the most abundant in common human diets. Epidemiological studies have suggested associations between the consumption of phenolics-rich food and the prevention of many human diseases associated with oxidative stress (2-5). On the basis of their daily intake, which greatly exceeds that of other antioxidants (i.e., vitamin E, vitamin C, β-carotene), phenolic compounds may be a major factor in assuring the antioxidant potential of the diet and may contribute to maintaining the endogeneous redox balance in humans.<ref name=piafor>Piazzon A, Forte M, Nardini M. [https://pubs.acs.org/doi/abs/10.1021/jf101975q Characterization of phenolics content and antioxidant activity of different beer types.] ''J Agric Food Chem.'' 2010;58(19):10677–10683.</ref>

For individuals regularly consuming wine, coffee, beer, and tea, these beverages will likely be the major sources of phenolics. Beer is a very popular beverage consumed in large amount all over the world and is a source of natural antioxidants, particularly phenolic acids, originating from barley and hop (9-12). The antioxidant activity of beer coupled with low ethanol content is a relevant factor in determining the nutritive characteristics of beer. Recently, phenolic acids from beer have been described as being quickly absorbed and extensively metabolized in humans (13, 14). Beer drinking has been reported to increase plasma antioxidant and anticoagulant activities and to positively affect plasma lipid levels in humans (13-18). In animal models beer drinking also decreases susceptibility to oxidation of low-density lipoproteins (19, 20). Moreover, beer consumption seems to have no effect or even an inverse effect on total homocysteine concentration (21-23).<ref name=piafor/>

Mild to moderate alcohol consumption is associated with beneficial healthy effects on the cardiovascular system (57, 58). Population-based studies have observed that moderate drinking in the range of one to three drinks daily is associated with a rate of coronary disease 30-40% lower compared with that in the nondrinking population. The association between alcohol consumption and cardiovascular disease is not linear but "U-shaped", with higher death rates found among those who abstain as well as those who drink an excess of six drinks a day (57).<ref name=piafor/>

Vitamins and selenium are derived from grains used for brewing.<ref name=yangao/>

Large breweries usually apply more cost-effective processes to produce beer, such as the use of cheaper raw materials including supplementary grains. Craft breweries, on the other hand, use only barley malt as a raw material in beer production, the use of which may be related to the existence of different or richer phenolic compounds in craft beers (Cheiran, Manfroi, Kahmann, & Frazzon, 2019). During storage, phenolic compounds in beer cause turbidity by reacting with proteins. Large breweries usually utilize clarification process by removing these phenolic compounds. After the clarification, the beer has to be stabilized by exogenous antioxidants to enhance the flavor. While craft beer is not filtered and do not use additives, hence has higher contents of phenolic compounds than that in final commercial beer (Marques, Quelhas, Visentainer, & Monteiro, 2017).<ref name=yangao/>

There is growing evidence that melanoidins have beneficial health properties, such as chemical prophylaxis, AOX, anti bacterial activity, and the ability to chelate different minerals (Adebayo et al., 2018; Delgado-Andrade & Morales, 2005; Morales et al., 2005). Barley malt melanoidins have been found to increase the activity of preventive enzymes in kidney and liver and reduce the level of oxidative stress in rodent plasma.<ref name=yangao/>

As recently presented, MRPs have exhibited important beneficial health effects, such as antiradical, antimutagenic, antimicrobial, antihypertensive, antiallergenic, antioxidant, and cytotoxic properties (Rufian-Henares and Morales 2007; Wang and others ´ 2011; Echavarr´ıa and others 2012; Langner and Rzeski 2014; Pastoriza and Rufian-Henares 2014).<ref name=cargon>Carvalho DO, Gonçalves LM, Guido LF. [https://ift.onlinelibrary.wiley.com/doi/abs/10.1111/1541-4337.12218 Overall antioxidant properties of malt and how they are influenced by the individual constituents of barley and the malting process.] ''Compr Rev Food Sci Food Saf.'' 2016;15(5):927–943.</ref>

Phenolic acids, among all classes of phenolic compounds in foodstuffs (including barley and beer), are the most easily absorbed from the intestinal tract41,45. Phenolic acids from foods have been detected in urine9  and are present in blood in considerable concentrations13. Even when the consumption of more complex phenolic compounds is high, they are degraded and simple phenolic acids are excreted.<ref name=szw>Szwajgier D. [https://onlinelibrary.wiley.com/doi/10.1002/j.2050-0416.2009.tb00376.x Content of individual phenolic acids in worts and beers and their possible contribution to the antiradical activity of beer.] ''J Inst Brew.'' 2009;115(3):243–252.</ref> ferulic acid, the main phenolic acid in barley and beer, is present in the esterified form, but an esterase activity of bacterial origin is present in the human gastrointestinal tract.

Oxidative stress is involved in the pathology of several human diseases, such as atherosclerosis, diabetes, neurodegenerative diseases, ageing, and cancer [1]. Dietary antioxidants can counteract the negative effects of oxidative stress. Polyphenols are the most abundant dietary antioxidants, due to their presence in all fruits and vegetables [1]. Polyphenol intake can be several hundreds of milligrams per day, up to 1 g/day, depending on dietary habits [2] and, in particular, in wine, coffee, beer, chocolate, and tea consumption; and it largely exceeds that of other antioxidants, such as vitamin E, vitamin C, and β-carotene [3]. Among polyphenols, phenolic acids account for about one-third of the total intake, while flavonoids account for the remaining two-thirds of the total intake [2]. Epidemiological studies have suggested associations between long-term consumption of polyphenols-rich foods and prevention of oxidative stress-related diseases such as cancer, cardiovascular diseases, diabetes, inflammation, and degenerative diseases [1,4–6].<ref>Nardini M, Foddai MS. [https://www.mdpi.com/1420-3049/25/11/2466 Phenolics Profile and Antioxidant Activity of Special Beers.] ''Molecules.'' 2020;25(11):2466.</ref> In addition to the most familiar products, special beers produced with the addition of fruits, spices, or natural food during the fermentation process, have been becoming very popular throughout the world, responding to requests for new gustatory, olfactory, and visual stimuli from consumers. During re-fermentation and maturation of special beers, flavors and bioactive compounds, such as carotenoids and polyphenols, are extracted from fruits, spices, and natural food added to beer. Recently, the addition of fruits during the fermentation process has been reported to significantly increase the content of bioactive compounds and the antioxidant activity of beer [13]. Despite many studies describing the raw materials and the effects of technological processes, little is known about the healthy compounds and nutritional quality of commercially available beers [14–16].

Catechins: Flavanol (+)-catechin is the third most abundant compound in hop cones possessing antioxidative and vasodilative features [43]. Flavanols catechin and epicatechin show antioxidative and anti-inflammatory properties [47]. A mixture of hop proanthocyanidins shows more pronounced antioxidative properties than individual flavanols and proanthocyanidins [43].<ref name=habkos/>

[[Styrene]], present in weissbier and other phenolic beers, is possibly carcinogenic.<ref name=langra>Langos D, Granvogl M. [https://pubs.acs.org/doi/abs/10.1021/acs.jafc.5b05606 Studies on the simultaneous formation of aroma-active and toxicologically relevant vinyl aromatics from free phenolic acids during wheat beer brewing.] ''J Agric Food Chem.'' 2016;64(11):2325–2332.</ref>

Xanthohumol is a well-known compound [40]. It has been studied as an anticancer agent, but poses many other positive properties against pathogenic fungi, malaria, and HIV-1 viruses [43]. It has chemopreventive, sedative, anti-inflammatory, and antimicrobial properties. Even though the isomer of xanthohumol—isoxanthohumol is proven to be a bit less potent than xanthohumol, it too has anti-mutagenic and antiangiogenic activity [43,44]. Another chemical compound with anticarcinogenic properties belonging to this group is 8-prenylnaringenin [45].<ref name=habkos/>

Both tyrosol (TYR) supplementation and its biotransformation into hydroxytyrosol (HT) are capable of triggering relevant beneficial effects on the cardiovascular system [30]. HT is considered one of the strongest dietary antioxidants, with anti-inflammatory, antiproliferative, antiplatelet and proapoptotic activities [32]. Therefore, beer would represent an indirect source of HT via TYR hydroxylation. Consequently, beer should also be considered a relevant source of TYR and HT, together with the traditional dietary sources of extra virgin olive oil and wine.<ref name=borsol/> Belgian strong ale, the beer with the highest concentration in TYR and HT, uses a specific and traditional yeast that could produce higher proportions of TYR [43].

despite the interesting beer antioxidant profiles described in the present paper and in the literature, it is important to highlight the importance of a moderate consumption of beer in the context of a healthy dietary pattern, such as the Mediterranean diet [23]. Excessive beer consumption can lead to an excessive body weight, hamper pancreatic function and increase the risk of cancer due to its ethanol content and also due to the low levels of toxic compounds [17].<ref name=borsol/>

Flavonoids are commonly referred to as antioxidants because of their redox properties, which allow them to act as reducing agents, hydrogen donators and singlet oxygen quenchers. Therefore they may prevent diseases associated to cell oxidative stress, such as cancer, cardiovascular diseases, autoimmune diseases and other age-related diseases (for a comprehensive overview on polyphenols and health, see Vassallo, 2008).<ref name=fumgal>Fumi MD, Galli R, Lambri M, Donadini G, De Faveri DM. [https://www.sciencedirect.com/science/article/abs/pii/S0889157511000238 Effect of full-scale brewing process on polyphenols in Italian all-malt and maize adjunct lager beers.] ''J Food Compos Anal.'' 2011;24(4–5):568–573.</ref> Tannin molecules have been reported to have anticarcinogenic, antimutagenic and antioxidant activities. They were also reported to inhibit the growth of fungi, bacteria, and viruses (Chung et al., 1998; Khanbabaee and Van Ree, 2001). However, the ingestion of large quantities of tannins results in adverse health effects as they precipitate proteins, inhibit digestive enzymes and affect the utilization of vitamins and minerals (Szajdek and Borowska, 2008).

In moderate beer drinkers, studies showed a 20–25% reduction in fatality rate from coronary diseases and a reduction by 50% of death factor risk (Bamforth, 2002; Walzl, 2005). These beneficial effects of beer on human health is mainly related to phenolic compounds, particularly to their antioxidant activity and their bioavailability (for a comprehensive overview see Preedy, 2009). Fantozzi et al. (1998) outlined that beer contains a quantity of phenols that supply molecules which play a role in antioxidant activity in vivo. Ghiselli et al. (2000) pointed out that polyphenols in beer induced a significant increase in plasma antioxidant capacity, that the phenolic acids in plasma increase after beer intake, and that the alcohol level plays an important indirect role in the absorption of phenols. Bourne et al. (2000) observed that ferulic acid (belong to nonflavonoid group) in beer is readily assimilated by the body. Gorinstein et al. (2007) found that the antioxidant potential of beer was well correlated to flavanols and flavonoids but slightly lower referred to total polyphenols, and that beer polyphenols improve lipid metabolism and increase antioxidant and anticoagulant activities.<ref name=fumgal/>

Beer is a source of many compounds not only for human nutrition but also for human health [3]. The polyphenols in beer due to their antioxidative features could contribute together with other dietary sources of polyphenols to protection from degenerative changes in the human body and so protect from diseases by moderate beer consummation. They have anticarcinogenic and antifungicide activities [3]. There is also a group of isofl avonoids in beers whose phytoestrogenic effects are now studied [4, 5].<ref name=keljur>Kellner V, Jurková M, Čulík J, Horák T, Čejka P. [https://www.researchgate.net/profile/Vladimir-Kellner/publication/236144996_January_February_2007_32/links/00b7d5165784fc0249000000/January-February-2007-32.pdf Some phenolic compounds in Czech hops and beer of Pilsner type.] ''Brew Sci.'' 2007;60:31–37.</ref>

Many biological effects and health benefits have been associated with flavonoid consumption, although these effects may be related to their ability to modulate cell-signaling rather than their antioxidant activity (Williams, Spencer, & Rice-Evans, 2004).<ref name=quival>Quifer-Rada P, Vallverdú-Queralt A, Martínez-Huélamo M, Chiva-Blanch G, Jáuregui O, Estruch R, Lamuela-Raventós R. [https://www.sciencedirect.com/science/article/abs/pii/S0308814614012205 A comprehensive characterisation of beer polyphenols by high resolution mass spectrometry (LC–ESI-LTQ-Orbitrap-MS).] ''Food chem.'' 2015;169:336–343.</ref>

Xanthohumol is a “broad-spectrum” cancer chemopreventive agent acting on all three stages of carcinogenesis. Xanthohumol and isoxanthohumol are both active ROS scavengers, while only the former is active in superoxide scavenging assays. Isoxanthohumol, 8-prenylnaringenin, and xanthogalenol may also exert chemopreventive effects [18, 61–64].<ref name=coljer>Collin S, Jerković V, Bröhan M, Callemien D. [https://link.springer.com/referenceworkentry/10.1007/978-3-642-22144-6_78 Polyphenols and beer quality.] In: Ramawat KG, Mérillon J-M, eds. ''Natural Products.'' 1<sup>st</sup> ed. Springer; 2013:2334–2353.</ref>

Prenylflavanones have mainly been studied for their estrogenic activity. Hopein is a very potent phytoestrogen. The authors recommend its application in prevention or treatment of (post)menopausal symptoms and osteoporosis [61, 63, 65]. Weak estrogenic activity has been observed for close analogs like 6-prenylnaringenin, 8-geranylnaringenin, 6,8-diprenylnaringenin, and isoxanthohumol. Prenylchalcones like xanthohumol and xanthogalenol also show low activity [66].<ref name=coljer/>

Flavonols induce cardioprotective effects, including antioxidant effects (protection against LDL oxidation) and inhibition of platelet activity and vasodilatation [48, 69], while very little information is available on their potential anticancer effects.<ref name=coljer/>

trans-Resveratrol shows an impact on platelet aggregation and vasodilatation, and through its effect on the antioxidant status, regulates gene expression and decreases the total lipid concentration (cholesterol and triglycerides) [115]. Although less potent, cis-resveratrol, trans-, and cis-piceid also improve the antioxidant activity [116, 117]. Piceid absorption is enhanced by the presence of its sugar [118]. trans-Resveratrol inhibits the initiation and growth of tumors. It inhibits cyclooxygenase, ornithine decarboxylase, and angiogenesis [119, 120]. trans-Piceid is a weaker inhibitor of ROS production [121]. As flavonoids, trans-resveratrol alters the synthesis of eicosanoids (mediators of inflammation) and decreases the leukotriene/prostacyclin ratio by modifying lipoxygenase activity [120–122]. Estrogenic activity has recently been reported for some stilbenes, especially trans-resveratrol. cis-Resveratrol appears less potent [120, 123].<ref name=coljer/>

The relationship between alcohol consumption and cardiovascular events or all-cause mortality is described as a J-shaped curve, whereby maximum benefit is achieved at a moderate consumption level (Roerecke & Rehm, 2012; Sierksma & Kok, 2012).<ref name=zapmar>Zapata PJ, Martínez-Esplá A, Gironés-Vilaplana A, Santos-Lax D, Noguera-Artiaga L, Carbonell-Barrachina ÁA. [https://www.sciencedirect.com/science/article/pii/S0023643819300039 Phenolic, volatile, and sensory profiles of beer enriched by macerating quince fruits.] ''Lwt.'' 2019;103:139–146.</ref> These benefits are additive to the beneficial effects of other healthy lifestyle factors such as non-smoking, physical activity and a healthy diet (Mukamal, Chiuve, & Rimm, 2006).

Oxidative stress reflects an imbalance between an organism’s excessive production of oxygen radicals and its reduced capacity to detoxify. Oxidative intermediates, such as OH•, O•2−, and NO•, attack cell components and cause inflammation, cancer, ageing, and metabolic diseases [1,2]. It has been commonly accepted that the prevention of oxidative stress benefits human health [3,4]. For example, the ingestion of natural plants such as vegetables, fruits, and tea [5–10] has been well identified to counteract the amount of oxidative stress that cells encounter and to reduce the incidence of diseases related to oxidative damage [11–14]. The positive effect of a phytogenic diet on human health can be mainly attributed to the abundance of bioactive flavonols with pharmaceutical properties.<ref name=gaofan>Gao Y, Fang L, Wang X, et al. [https://www.mdpi.com/416306 Antioxidant activity evaluation of dietary flavonoid hyperoside using ''Saccharomyces cerevisiae'' as a model.] ''Molecules.'' 2019;24(4):788.</ref>

it was found that the degree of the positive effects of drinking beer on health are directly associated with the content of phenolic compounds in beer, after analyzing beers with different levels of phenolics (3). Gasowski, B., Leontowicz, M., Leontowicz, H., Katrich, E., Lojek, A., Číž, M., Trakhtenberg, S., and Gorinstein, S. The influence of beer with different antioxidant potential on plasmalipids, plasma antioxidant capacity, and bile excretion of rats fed cholesterol-containing and cholesterol-free diets. J. Nutr. Biochem. 15(9):527–533, 2004. 

One area that others in the brewing industry have been less than comfortable in me pursuing is that of beer (in moderation) as a component of a healthful lifestyle. The issue was not that they did not believe it to be true, but rather that the perception would be that a scientist working within the industry could not take a dispassionate approach to the matter. I have been assiduous in not using industry funds in any of this work and I have always been at pains to emphasise negatives as well as positives as I sought to (at the least) illustrate how beer is more than the equal of wine, for which beverage there seems not to have been the same reluctance to hold back 127-137. We have highlighted how wine is (incorrectly) perceived as a healthier option 138, 139. We have also highlighted the ignorance concerning matters of beer and brewing that many people have 140. There should be no let-up in the education of the drinking public. In terms of specific research on health-related issues concerning beer, then we have included studies on antioxidants 141, folate 142, minerals 143 especially silicate 144, as well as soluble fibre and prebiotics as referred to earlier. Furthermore, we have explored the gliadin content of commercial beers 145 and highlighted the merit of the enzyme prolylendoproteinase in producing gluten free beer 146. We employed an ELISA-based procedure to measure gliadin. There are those who insist that it is insufficiently sensitive and are critical of its use in beer. This area needs extensive gluten free research, including studies in conjunction with those in the medical profession. We also did not fight shy of the matter of carbohydrates in beer in relation to health, discussing the nonsense of the beer belly and the glycaemic index as it pertains to beer 147.<ref>https://onlinelibrary.wiley.com/doi/full/10.1002/jib.594</ref>

Commercial lager beer contains lower amounts of THMs than the water used for brewing.<ref>Wu QJ, Lin H, Fan W, Dong JJ, Chen HL. [https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2050-0416.2006.tb00733.x Investigation into benzene, trihalomethanes and formaldehyde in Chinese lager beers.] ''J Inst Brew.'' 2006;112(4):291–294.</ref> Could be a result of filtering?

THMs are not removed by agents used for dechlorination, only by carbon filtration.<ref>Moore N, Ebrahimi S, Zhu Y, Wang C, Hofmann R, Andrews S. [https://iwaponline.com/ws/article/21/5/2313/80665/A-comparison-of-sodium-sulfite-ammonium-chloride A comparison of sodium sulfite, ammonium chloride, and ascorbic acid for quenching chlorine prior to disinfection byproduct analysis.] ''Water Supply.'' 2021;21(5):2313–2323.</ref>

Consuming beverages with high magnesium content can help reduce risk of coronary heart disease,<ref>https://www.sciencedirect.com/science/article/pii/S0306987713004763</ref> and beer is relatively high in [[magnesium]]...

There is a well-balanced amount of minerals contained in beer. Being relatively high in potassium and low in sodium it is an ideal drink to include in diets for hypertensive patients (De Stefano and Montanari, 1996). It is low in calcium and rich in magnesium which may help protect against gall stone and kidney stone formation.<ref name=monmay>Montanari L, Mayer H, Marconi O, Fantozzi P. [https://www.sciencedirect.com/science/article/abs/pii/B9780123738912000341 Chapter 34: Minerals in beer.] In: Preedy VR, ed. [[Library|''Beer in Health and Disease Prevention.'']] Academic Press; 2009:359–365.</ref>

A large amount of potassium (500–600 mg/L) is particularly interesting for the nutritional importance of beer. Due to an osmotic effect, a high potassium content promotes the elimination of [[sodium]] and [[chloride]]s and therefore helps body dehydration and demineralization (De Stefano and Montanari, 1996). It remains in the final product and accounts for 30% of the recommended daily amount, considering 1 L of medium alcoholic beer as an acceptable daily intake.<ref name=monmay/>

{| class="wikitable"
|+ Mineral composition of beer<ref name=monmay/>
!Inorganic substances !! Amount in beer (mg/L) !! Recommended daily intake (mg/day) !! Physiological effects in humans
|-
| Phosphates || 300–400 || 1,250–1,500 ||Important constituent of bones and teeth; responsible for energy storage and transmission
|-
| Sulfate || 150–200 || – || No important effect
|-
| Nitrate || 10–80 || – || Nitrate can be converted to nitrite which is harmful to health. The amount of nitrate in beer is usually below the legal limit of 50 mg/l for drinking water and is harmless
|-
| Chloride || 150–200 || 2,500 || –
|-
| Potassium || 500–600 || 2,500 || Good for prophylaxis against heart attack; a high potassium content is diuretic
|-
| Sodium || 30–32 || 550 || Low sodium content desirable
|-
| Calcium || 35–40 || 800–1,000 || Can prevent heart diseases
|-
| Magnesium || 100–110 || 300–350 || Lowers the cholesterol level, beneficial effect on cardiac activity
|}

From a nutritional point of view, beer contains significant amounts of B vitamins, mainly folates and riboflavin, and selenium.<ref name="Siqueira">Siqueira, PB, et al. [https://www.researchgate.net/publication/49599952_O_PROCESSO_DE_FABRICACAO_DA_CERVEJA_E_SEUS_EFEITOS_NA_PRESENCA_DE_POLIFENOIS "O Processo De Fabricação Da Cerveja E Seus Efeitos Na Presença De Polifenóis (The Beer Manufacturing Process And Its Effects On The Presence Of Polyphenols)"] ''Alimentos e Nutrição Araraquara'', vol. 19, no. 4, 2008, pp. 491-498.</ref>

Due to its antioxidant capacity and low alcohol content, beer is able to improve plasma antioxidant activity, reducing the risk of coronary artery diseases without presenting the negative aspects produced by high doses of ethanol. Therefore, due to beer has a high concentration of antioxidant compounds, its moderate consumption is capable of positively influencing the plasma lipid level and its anticoagulant capacity.<ref name="Siqueira"/>

Beer is considered a source of folates and otherB vitamins, such as [[niacin]], pyridoxine and cyanidesnocobalamin, in addition to being cited as an important sourceselenium and have a diuretic effect, due to the high ratiopotassium / sodium. 6Hops are considered an herb with propertiesmedicinal products, used as an antibiotic and anti-inflammatory. Ostudy of the properties of some compounds present in thehops revealed bioactive effects in a large part of theirmetabolites. 23The antioxidant properties of phenolic acidsgives them the ability to prevent cancer due to theirability to scavenge free radicals, which cause oxidationthe DNA of cells. Arimoto-Kobayashi 4 reviewed liver and lungs of rats, revealing which componentspresent in beer are able to protect the body againstagainst the genotoxic effects of heterocyclic amines.Several compounds were isolated from beer andsubmitted to in vivo tests , with the objective of studying theirability to prevent the occurrence of degenerative diseasessuch as cancer, and cardiovascular disease. Amongthe isolated compounds, prenylflavonoids andalpha acids. The xanthohumol chalcone, together withits isoxanthohumol isomer, formed during processingare prenylflavonoids found in greater con-focusing on beer. Xanthohumol has been identified asthe main agent in cancer prevention, due to itshigh antioxidant capacity, besides presenting propertiesanti-estrogenic, anti-inflammatory, anti-angiogenic activities,inhibition of DNA polymerase and the ability to controlproliferation of cancer cells. 17Epidemiological studies indicate that consumptionmoderate alcohol consumption is inversely related to thecardiovascular diseases, presenting a lowermortality rate among those who consume beveragesmoderately alcoholic, mainly wine and beer,compared to individuals who do not consume these drinksor those who consume too much. Epidemic studiessuggest a relationship between foods rich inpolyphenols and the prevention of some diseases, like cancer,cardiovascular disease and inflammation.<ref name="Siqueira"/>

On average, beer contains 2–6 g/L peptide, which mainly originates from the cereal grains.<ref>Han Y, Wang J, Li Y, Hang Y, Yin X, Li Q. [https://www.sciencedirect.com/science/article/abs/pii/S0308814615005993 Circular dichroism and infrared spectroscopic characterization of secondary structure components of protein Z during mashing and boiling processes.] ''Food Chem.'' 2015;188:201–209.</ref>

Beer contains about 500 mg/L of proteinaceous material.<ref name=steiner>Steiner E, Gastl M, Becker T. [https://www.researchgate.net/profile/Elisabeth_Wiesen/publication/226773564_Protein_changes_during_malting_and_brewing_with_focus_on_haze_and_foam_formation_A_review/links/56bc4bc508ae2481ab6aeeba.pdf Protein changes during malting and brewing with focus on haze and foam formation: a review.] ''Eur Food Res Technol.'' 2011;232:191–204.</ref>



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*[https://www.academia.edu/48356644/Functionality_of_Special_Beer_Processes_and_Potential_Health_Benefits Functionality of Special Beer Processes and Potential Health Benefits]
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*https://www.academia.edu/56514472/New_type_of_beer_beer_with_improved_functionality_and_defined_pharmacodynamic_properties
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*https://pubs.acs.org/doi/abs/10.1021/jf104421q Fate of pesticides during beer brewing

==References==