Review Article
Beer Polyphenols and Menopause: Effects and Mechanisms—A
Review of Current Knowledge
Berner Andrée Sandoval-Ramírez,1 Rosa M. Lamuela-Raventós,1,2 Ramon Estruch,2,3
Gemma Sasot,1,2 Monica Doménech,2,3 and Anna Tresserra-Rimbau1,2
1Department of Nutrition, Food Science and Gastronomy, XaRTA, INSA, School of Pharmacy and Food Sciences, University of
Barcelona, Barcelona, Spain
2CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
3Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
Correspondence should be addressed to Anna Tresserra-Rimbau; annatresserra@ub.edu
Received 4 April 2017; Revised 26 June 2017; Accepted 10 July 2017; Published 17 August 2017
Academic Editor: Giuseppe Cirillo
Copyright © 2017 Berner Andrée Sandoval-Ramírez et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Beer is one of the most frequently consumed fermented beverages in the world, and it has been part of the human diet for thousands
of years. Scientific evidence obtained from the development of new techniques of food analysis over the last two decades suggests
that polyphenol intake derived from moderate beer consumption may play a positive role in different health outcomes including
osteoporosis and cardiovascular risk and the relief of vasomotor symptoms, which are commonly experienced during
menopause and are an important reason why women seek medical care during this period; here, we review the current
knowledge regarding moderate beer consumption and its possible effects on menopausal symptoms. The effect of polyphenol
intake on vasomotor symptoms in menopause may be driven by the direct interaction of the phenolic compounds present in
beer, such as 8-prenylnaringenin, 6-prenylnaringenin, and isoxanthohumol, with intracellular estrogen receptors that leads to
the modulation of gene expression, increase in sex hormone plasma concentrations, and thus modulation of physiological
hormone imbalance in menopausal women. Since traditional hormone replacement therapies increase health risks, alternative,
safer treatment options are needed to alleviate menopausal symptoms in women. The present work aims to review the current
data on this subject.
1. Introduction
Beer is one of the most frequently consumed alcoholic bever-
ages in the world. Beer consumption ranks first in Europe,
slightly above wine consumption, according to the World
Health Organization [1] and third amongst alcoholic bever-
age preferences in North America [2]. Archaeological
findings show that Chinese villagers brewed fermented alco-
holic drinks as far back as 7000 BC on a small individual
scale, with a production process and methods similar to those
of ancient Egypt and Mesopotamia [3]. Throughout human
history, products, ingredients, procedures, and techniques
have evolved due to technological advances and the imple-
mentation of industrialized processes [4] further enhancing
the long history of beer as a part of the human diet.
During the last two decades, scientific evidence has sug-
gested that moderate consumption of alcoholic beverages
has positive outcomes on different aspects of cardiovascular
risk, as evidenced by Nogueira et al. who correlated regular
daily intake of 330ml of beer with positive changes in insulin
sensitivity and lipid profiles [5]. Fermented beverages have
also shown positive associations with different cardiovascular
disease endpoints such as coronary heart disease, peripheral
arterial disease, chronic heart failure, and stroke in which
regular moderate consumption of alcohol reduced the preva-
lence of adverse events [6], and fermented beverages have
shown anti-inflammatory properties [7]; these findings may
explain the benefits of regular and moderate alcohol intake
on cardiovascular disease risk [8–11]. In the last decade, the
development of new techniques for food analysis has allowed
Hindawi
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 4749131, 9 pages
https://doi.org/10.1155/2017/4749131
the quantification of phenolic profiles [12], which, in turn,
has led to new studies suggesting that regular polyphenol
consumption might provide health benefits for menopausal
and postmenopausal women, reducing vasomotor symptoms
[13, 14] and osteoporosis [15].
Hop (Humulus lupulus L) is the ingredient used for beer
making and is rich in phenolic compounds. Mass spectrome-
try analysis show that it contains around 14.4% of phenolic
acids, flavonoids, proanthocyanidins, prenylated chalcones,
and catechins [16]. Furthermore, malt provides 70%–80% of
the total polyphenolic compounds found in beer [17]. It has
been shown through high-performance liquid chromatogra-
phy and posterior ultrasound separation that fermentation,
boiling, and the amount of hop used to manufacture beer sig-
nificantly influence the final polyphenol concentrations [18].
Menopause is induced by the permanent cessation of
menstruation due to the end of ovarian follicular activity.
This affects the physiology of women [19] and leads to a
diminished production of estradiol which is correlated with
the night sweats and hot flushes experienced by many
menopausal women [20]. According to the Menopause Epi-
demiology Study, in which 4402 women were surveyed, these
symptoms are one of the main reasons for women to seek
medical care and over-the-counter treatments that provide
some relief and improve the quality of life [21]. For the pres-
ent work, we review the current knowledge found through
online scientific libraries, PubMed and Scopus, regarding
moderate beer consumption, polyphenol intake from beer,
and their possible benefits for menopausal women.
2. Polyphenolic Compounds in Beer
Beer contains amino acids, carbohydrates, vitamins, min-
erals, and polyphenols. As mentioned above, beer contains
a diversity of polyphenols mainly derived from hops and
malt [16, 22]. Moreover, during the beer fermentation
process, a resin produced by hops that contains monoacyl-
phlorogucinols is converted into bitter acids such as humu-
lones and isohumulones. These molecules act as bioactive
antioxidants and provide additional beneficial effects [23].
Table 1: Flavonoids contained in different types of beer.
Molecule
Mean content (mg/100ml)
Alcohol-free Ale Dark Regular
Chalcones
Xanthohumol 0.0003 0.0100 0.0300 0.0014
Flavanols
Catechin 0.1000 0.3300 0.0200 0.1100
Epicatechin 0.0056 0.0500 0.0100 0.0600
Procyanidin dimer B3 0.1600
Procyanidin trimer C2 0.0300
Prodelphinidin trimer C-GC-C 0.0200
Prodelphinidin trimer GC-C-C 0.0100
Prodelphinidin trimer GC-GC-C 0.0400
Prodelphinin dimer B3 0.1800
Flavanones
6-Geranylnaringenin 0.0011 0.0027 0.0004
6-Prenylaringenin 0.0007 0.0200 0.0200 0.0026
8-Prenylaringenin 0.0003 0.0044 0.0092 0.0010
Isoxanthohumol 0.0100 0.2100 0.1200 0.0400
Naringin 0.0008
Flavones
Apigenin 0.0042
Flavonols
3,7-Dimethylquercetin 0.0003
Myricetin 0.0007
Quercetin 0.0067
Quercetin 3-O-arabinoside 0.0006
Quercetin 3-O-rutinoside 0.0900
Isoflavonoids
Biochanin A 0.0005 0.0015
Daidzein 0.0005
Genistein 0.0010
Data from the Phenol-Explorer database [12].
2 Oxidative Medicine and Cellular Longevity
Tables 1–3 show the polyphenols found in different types of
beer. Malt contains many free and total (bound) polypheno-
lic compounds; according to composition analysis using a
liquid chromatography-antioxidant technique before and
after fermentation, the concentrations of polyphenolic com-
pounds may be increased by up to threefold after the fermen-
tation process [24]. The main polyphenolic compounds
present in beer are sinapic, ferulic, and caffeic acids. Vanillic
acids are present in bound and unbound forms while 4-
hydroxyphenylacetic and p-coumaric acids are present as
free forms [17]. The main phenolic acids found in beer are
shown in Figure 1.
3. Polyphenol Metabolites in Plasma
Analysis of polyphenol concentrations in plasma reveals that
after ingestion, beer goes through the gastrointestinal tract.
An estimated amount of between 5–10% of beer is absorbed
in the small intestine, with the remaining 90–95% continuing
on to the colon where it is further fermented by the gut
microbiota [25], increasing the amount of polyphenols
such as 4-hydroxyphenylacetic and vanillic acids absorbed
[26–28]. After being absorbed, polyphenols undergo hepatic
conjugation reactions with S-adenosyl methionine, sulfates,
glucuronates, or a combination of them [29]. After 30
minutes, the plasma levels of nonconjugated hydroxypheny-
lacetic acid significantly increase. Vanillic, caffeic, and ferulic
acid levels raise equally as conjugated and nonconjugated
forms, with a slight prevalence of sulfate over glucuronate
isoforms [30]. Composition analysis carried out in human
urine samples after ingestion of wine, tea, beer, or coffee
has shown that polyphenol compounds and metabolites such
as resveratrol [31], 4-O-methylgallic acid, isoferulic acid [32],
and isoxanthohumol [33] are excreted through renal filtra-
tion. Table 4 provides detailed information about the plasma
levels of polyphenol metabolites after the ingestion of beer.
4. Menopause: Physiology, Symptoms, and
Current Treatment
Menopause is defined as the permanent cessation of men-
struation as a direct result of the end of ovarian follicular
activity [35]. Follicular development is a cyclical process that
occurs on average every 28 days during reproductive life.
However, with age, these cycles become irregular and then
stop completely. This cessation causes abnormal fluctuations
of sex hormones, such as the follicle-stimulating hormone
(FSH), anti-Müllerian hormone, estrogen, and insulin-like
growth factors-I (ILGF-I), which eventually lead to physio-
logical and morphological changes in many organs and
systems in women [36].
These physiological changes induce different symptoms
and signs which are characteristic of menopausal women,
such as irregular bleeding, night sweats, hot flashes, tachycar-
dia, breast pain, lack of energy, dyspareunia, joint soreness,
atrophic vaginitis, interrupted sleeping patterns, anxiety,
mood swings, dry skin, and loss of libido [37, 38]. Moreover,
menopause may also predispose women to a series of risks,
such as an increased risk of atherosclerosis [39–43], osteope-
nia, and osteoporosis [44, 45] (Figure 2).
Hot flashes are one of the most frequent symptoms
presented by women undergoing menopause. They have a
profound impact on the quality of life and increase health
costs [46]. Vasomotor symptoms represent one of the main
reasons why menopausal women seek medical care and
treatments in the hope of relieving their discomfort [47].
Hot flashes are the result of the brain’s response to dimin-
ished and fluctuating sex hormone concentrations that
occur in menopause [48, 49]. Mechanisms of temperature
homeostasis on the hypothalamus and peripheral vascula-
ture are influenced by different hormones such as ovarian
hormones, norepinephrine, and serotonin. Kronenberg
described the links between vasomotor symptoms and
different thermal, hormonal, and autonomic parameters,
demonstrating the relevance of hormones in the deregula-
tion of core body temperature that leads to hot flashes in
menopause [50].
Current menopausal treatment includes estrogen
hormone replacement therapy (HRT); selective estrogen
Table 2: Phenolic acids contained in different types of beer.
Molecule
Mean content (mg/100ml)
Alcohol-
free
Ale Dark Regular
Hydroxybenzoic acids
2,6-Dihydroxybenzoic
acid
0.0900
2-Hydroxybenzoic acid 0.0011 0.2000
3,5-Dihydroxybenzoic
acid
0.0300
3-Hydroxybenzoic acid 0.0300
4-Hydroxybenzoic acid 0.0073 0.1100 0.0700 0.9600
Gallic acid 0.1100 0.0300 0.0700
Gallic 3-O-gallate 0.2600
Gentisic acid 0.0300
Protocatechuic acid 0.2700 0.0600 0.0400 0.0500
Syringic acid 0.1100 0.0200
Vanillic acid 0.0300 0.2900 0.1700 0.0700
Hydroxycinnamic acids
4-Caffeoylquinic acid 0.0100
5-Caffeoylquinic acid 0.0800
Caffeic acid 0.0100 0.0075 0.0300 0.0300
Ferulic acid 0.1200 0.3300 0.0900 0.2600
m-Coumaric acid 0.0200
o-Coumaric acid 0.1500
p-Coumaric acid 0.4000 0.1200 0.0500 0.1000
Sinapic acid 0.0073 0.0700 0.0300 0.0200
Hydroxyphenylacetic acids
4-Hydroxyphenylacetic
acid
0.0300
Homovanillic acid 0.0500
Data from the Phenol-Explorer database [12].
3Oxidative Medicine and Cellular Longevity
receptor modulators, such as tamoxifen and raloxifene
[51]; and other medications such as selective serotonin
reuptake inhibitors that alleviate vasomotor symptoms
[52]. However, in different studies carried out in human
patients, it has been suggested that HRT has no benefit
in preventing cardiovascular disease and may even lead
to an increased risk of arterial and venous thrombotic
events [53], ovarian cancer [54], nonalcoholic steatohepati-
tis [55], and other diseases. These reports have encouraged
scientists to find alternative and safer treatment options for
menopausal symptoms.
5. Moderate Beer Intake and Health
Although it is well known that ethanol is a carcinogenic
substance for humans [56], several studies have shown that
regular and moderate intake of fermented beverages, such
as wine and beer, may be associated with different positive
Table 3: Other phenolic compounds contained in beer.
Molecule
Mean content (mg/100ml)
Alcohol-free Ale Dark Regular
2,3-Dihydroxy-1-guaiacylpropanone 0.0025 0.0034
3-Methylcatechol 0.0029 0.0001
4-Ethylcatechol 0.0010 0.0006
4-Hydroxycoumarin 0.1100
4-Methylcatechol 0.0022
4-Vinylguaiacol 0.0100 0.0300 0.1500
4-Vinylphenol 0.0300 0.0045
Catechol 0.0100 0.0011
Esculin 0.0200
Pyrogallol 0.0300 0.0047
Tyrosol 0.2700 0.3200
Umbelliferone 0.0017
Vanillin 0.0048 0.0200
Data from the Phenol-Explorer database [12].
32%
22%
22%
24%
p-Coumaric
Protocatechuic
Tyrosol
Others
(a)
18%
16%
18%
48%
Ferulic
Vanillic
Catechin
Others
(b)
11%
21%
15%
53%
Ferulic
Vanillic
Isoxanthohumol
Others
(c)
8%
24%
7%
61%
Tyrosol
4-Hydroxybenzoic
Ferulic
Others
(d)
Figure 1: Main polyphenol content in different types of beer presented in percentages: (a) alcohol-free beer; (b) ale beer; (c) dark beer;
(d) regular beer.
4 Oxidative Medicine and Cellular Longevity
health effects, such as the reduction in the risk of cardio-
vascular disease as evidenced by the J-shaped relation
found in wine [57] and beer [58] intake on cardiovascular
risk, the reduction in atheroma plaque formation [59],
prevention on different cancer types [23, 60, 61], and the
reduction in bone mineral loss that leads to osteoporosis
and osteopenia [15, 62]. The lack of evidence attributing
the same effects to spirit intake suggests that polyphenolic
compounds might play an important role in the beneficial
effects of moderate alcoholic beverage intake on several
health outcomes [63–66].
6. Beer and Menopause
Several intervention studies have evaluated the effects of beer
and menopause. An 8-week, randomized, double-blind,
cross-over trial showed that consuming 8-prenylnaringenin
(8-PN), a characteristic polyphenol from hops and beer,
resulted in a significant reduction in menopause symptoms
[14] and discomforts [67]. Vasomotor symptoms are
believed to be caused by a slight increase in body temperature
in conjunction with a smaller thermo-neutral zone [68].
These processes are controlled by a region of the anterior
Table 4: Mean plasmatic levels of polyphenolic metabolites after beer intake.
Polyphenolic metabolite Dose per day Mean concentration (plasma) T-Max (h) Ref.
Ferulic acid 500ml 0.11μmol/l 0.5 [34]
4-Hydroxyphenylacetic acid 500ml 1.4 μmol/l 0.5 [30]
Vanillic acid 500ml 0.11μmol/l 0.5 [30]
p-Coumaric acid 500ml 0.05–0.07 μmol/l 0.5 [30]
Caffeic acid 500ml 0.05–0.07 μmol/l 0.5 [30]
T-Max: time when maximal concentration is achieved.
(i) Anxiety
(ii) Mood swings
(iii) Diminished libido
(ii) Night sweats
(i) Bone mineral loss
(i) Joint soreness
Estrogen
Inhibin
ILGF-I
AMH
FSH
(i) Dyspareunia 
(ii) Atrophic vaginitis
(i) Tachycardia
(i) Hot flashes
Figure 2: Sexual hormone status and common clinical manifestations in menopause. Insulin-like growth factor I (ILGF-I); anti-Müllerian
hormone (AMH); follicle-stimulating hormone (FSH).
5Oxidative Medicine and Cellular Longevity
hypothalamus called the thermoregulatory nucleus. This area
responds to sex hormones as shown by experimental models
with ovariectomized rats. These rats presented significant
differences in body temperature compared to a unovariecto-
mized control group, and the differences reversed when the
rats were treated with estrogens or clonidine, an alpha-
adrenoceptor used for vasomotor symptom treatment, sug-
gesting that temperature irregularities in menopause may
be due to changes in the sex hormone regulatory system
[69]. In the same animal model, low doses of approximately
400μg/kg/day of 8-prenylnaringenin were also able to allevi-
ate menopausal vasomotor symptoms [70].
The effect of 8-prenylnaringenin may be explained by its
strong affinity for both alpha and beta estrogen receptors
(ER). The binding of 8-PN and the consequent activation of
ERs lead to the stimulation of alkaline phosphatase activity
and upregulate the activity of progesterone receptors and
presenelin-2 [14], both of which are estrogen-stimulated genes
(Figure 3). In addition, low doses of 8-prenylnaringenin
increase the libido of menopausal women [71].
The absorption of hop phenolic acid and the pharmaco-
kinetics and possible health benefits of hops have been
studied in women [72]; however, at present, no clinical trial
has assessed the effects of moderate beer consumption on
menopausal women.
7. Summary
Menopause is a physiological condition that causes signifi-
cant discomfort in many women around the world with the
presentation of a myriad of symptoms related to an imbal-
ance in sex hormone levels. Hot flashes and night sweats
are two of the most common clinical findings in menopausal
women that lead them to seek medical care. Since traditional
hormone replacement therapies increase health risks, alter-
native, safer treatment options are needed. Hop and beer
polyphenols seem to be an alternative to alleviate the
menopausal symptoms presented by women.
There is evidence that regular and moderate intake of the
polyphenols commonly found in hop and beer may help to
relieve many common symptoms presented by women
undergoing menopause. Said benefits can also be obtained
by menopausal women from regular alcohol-free beer con-
sumption, since ingredients used and most processes are
Promoter
Prolactin
FSH
LH
Gene
(DNA)
17-
훽-Estrogen
Prolactin
FSH
LH
8-Prenylnaringenin
6-Prenylnaringenin
Isoxanthohumol
Estrogen receptor
Figure 3: Mechanism of phytoestrogens. Like estrogen, phytoestrogen molecules travel through plasma and diffuse into the target cells, where
they bind to cytoplasmatic estrogen receptors (ER). The newmolecule-ER complex then dimerizes and is translocated into the nucleus, where
it binds to specific promoters that decrease the expression of genes translating hormones such as follicle-stimulating hormone (FSH) and
luteinizing hormone (LH) and promote the translation of prolactin. The use of estrogen receptors by 17-b-estrogen and molecules such as
8-prenylaringenin, 6-prenylaringenin, and isoxanthohumol explains why these molecules can be used to decrease the intensity of many
classical symptoms of menopause.
6 Oxidative Medicine and Cellular Longevity
shared between alcohol-free and regular beer. Alcohol-free
beer could provide women with all the same possible benefits,
without the risk of gastrointestinal pathologies and cancer
that frequent alcohol consumption represents to health.
Nonetheless, randomized intervention clinical trials are
needed to confirm their efficacy.
Disclosure
No foundation or institution was involved in the writing of
the manuscript or the decision to submit the manuscript
for publication.
Conflicts of Interest
Anna Tresserra-Rimbau, Rosa M. Lamuela-Raventós, and
Ramon Estruch have received funding from The European
Foundation for Alcohol Research (ERAB). Rosa M.
Lamuela-Raventós and Ramon Estruch report serving on
the board of and receiving lecture fees from Research
Foundation on Wine and Nutrition (FIVIN) and Cerveceros
de España. Rosa M. Lamuela-Raventós has received lecture
fees and travel support from PepsiCo, and Ramon Estruch
reports serving on the boards of the Mediterranean Diet
Foundation, receiving lecture fees from Sanofi-Aventis, and
receiving grant support through his institution fromNovartis.
Acknowledgments
This work was supported by the European Foundation for
Alcohol Research (ERAB) (EA 1324, EA 1514, EA 1515,
and EA 1517), the CICYT (AGL2016-79113-R), and the
Instituto de Salud Carlos III (ISCIII) (CIBEROBN) from
the Ministerio de Economía, Industria y Competitividad
(MEIC) (AEI/FEDER, UE) and Generalitat de Catalunya
(GC) (2014 SGR 773).
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