Nutrition 79 80 (2020) 110991

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Nutrition
journal homepage: www.nutritionjrnl.com

Review

Mediterranean diet as tool to manage obesity in menopause:

A narrative review
Gabriella Pugliese Dr. M.D. a,b, Luigi Barrea Dr. M.D., Ph.D. a,b,*, Daniela Laudisio Dr. M.D. a,b,
Sara Aprano Dr. M.D. a,b, Bianca Castellucci Dr. M.D. a,b, Lydia Framondi Dr. R.N. a,b,
Rossana Di Matteo Dr. R.N. a,b, Silvia Savastano Prof. M.D., Ph.D. a,b, Annamaria Colao Prof. M.D., Ph.D. a,b,c,
Giovanna Muscogiuri Dr. M.D., Ph.D. a,b
a
Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Universita
"Federico II" di Napoli, Naples, Italy
b
(C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples,
Centro Italiano per la cura e il Benessere del paziente con Obesita
Naples, Italy
c
Cattedra Unesco “Educazione alla salute e allo sviluppo sostenibile”, University Federico II, Naples, Italy

A R T I C L E I N F O A B S T R A C T

Article History: Menopause is a physiological event in a woman’s life characterized by the cessation of spontaneous men-
Received 2 April 2020 strual cycles caused by a reduction in the sex hormones estrogen and progesterone and a consequent
Received in revised form 27 July 2020 increase of gonadotropins, which occurs when the stocks of ovarian follicles end. Weight gain is a common
Accepted 31 July 2020
phenomenon in menopause and age of onset is influenced by several factors. Among modifiable risk factors
Keywords: are sedentary lifestyle and unhealthy nutritional patterns, which often result in obesity that in turn contrib-
Menopause utes to an increase in cardiovascular risk in menopause, mostly through low-grade inflammation. The Medi-
Obesity terranean diet (MedD) is a healthy dietary pattern characterized by an adequate consumption of vegetables,
Woman’s health fruits, whole grains, and legumes with a reduction of saturated animal fats in favor of unsaturated vegetable
Mediterranean diet fats and a high intake of bioactive compounds including polyphenols and v-3 fatty acids with anti-inflamma-
Dietitian tory and antioxidant potency. Because of its palatability and long-term sustainability, the MedD, especially if
hypocaloric, combined with physical activity, has shown promising results in terms of weight loss in individ-
uals with obesity, as well as similar beneficial effects in menopause-related obesity. It has been observed that
greater adherence to the MedD in menopause is associated with reduced risk for becoming overweight/
obese, better cardiometabolic profile, and an improvement in menopausal symptoms. Although it is neces-
sary to confirm these data with future large intervention trials, the MedD can be considered a safe and
healthy approach in the management of menopause-related obesity and its cardiometabolic complications.
© 2020 Elsevier Inc. All rights reserved.

Introduction

Weight gain and consequently obesity are frequently encoun-

GP and LB contributed equally to this study, are co-first authors, and were respon-
sible for the conceptualization of the study. GM was responsible for the validation of
the study as well as the review and editing of the manuscript. SA, LF, RDM, DL, and
BC, were responsible for the investigation and data curation. GP, LB, and GM were
responsible for the writing and preparation of the original draft. AC and SS were
responsible for the visualization and supervision. The authors have no conflicts of
interest to declare.
*Corresponding author. Tel.: +39 081 7463779; Fax: +39 081 7463668.
E-mail addresses: robiniapugliese@gmail.com (G. Pugliese), luigi.barrea@unina.
it (L. Barrea), dani.laudisio@libero.it (D. Laudisio), saraaprano@hotmail.com
(S. Aprano), biancacastellucci1@gmail.com (B. Castellucci), lydiaframondi@gmail.
com (L. Framondi), rossanadimatteo96@hotmail.com (R. Di Matteo),
sisavast@unina.it (S. Savastano), colao@unina.it (A. Colao), giovanna.
muscogiuri@gmail.com (G. Muscogiuri).
tered conditions in menopause, which in addition to causing dis-
comfort for the woman and poor acceptance of her image also
entails an increased risk for cardiovascular events, type 2 diabetes
mellitus (T2DM), and metabolic alterations [1]. The pathogenesis
of obesity in menopause appears to be multifactorial and is the
result of several modifiable and non-modifiable factors (Fig. 1).
One of the non-modifiable factors is chronological aging. In fact
several reports showed an increase in weight with increasing age
and in particular an average weight gain of 0.5 kg/y in menopausal
women [2,3].
However, it seems that body changes strictly depend on the men-
opause state and not simply on aging. In a larger longitudinal study

https://doi.org/10.1016/j.nut.2020.110991
0899-9007/© 2020 Elsevier Inc. All rights reserved.
2 G. Pugliese et al. / Nutrition 79 80 (2020) 110991

Fig. 1. Non-modifiable and modifiable risk factors for obesity in menopause. Several risk factors including aging, hormonal imbalance, sedentary lifestyle, Western-style diet,
mood disorders, emotional eating, reduced satiety, energy expenditure and physical activity, increased consumption of high-calorie and processed foods contribute to pro-
moting weight gain and the onset of obesity in menopause, characterized by an android redistribution of body fat and which leads to an increase in systemic inflammation,
oxidative stress and overall cardiovascular risk. FSH, follicle-stimulating hormone; IL, interleukin; TNF, tumor necrosis factor.

from the Michigan site of SWAN (Study of Women’s Health Across
the Nation) with 543 premenopausal or early perimenopausal
women, a 6% increase in waist circumference (WC), a 10% increase in
fat mass, and a 1% decrease in skeletal muscle mass over a 6-y period
around the final menstrual period has been reported. These results
remained significant after adjusting for chronological age [4]. Life-
style has been identified as a modifiable risk factor that could con-
tribute to the onset of obesity in women after the reproductive life
span. In particular, in a study with 6079 Latin American women 40
to 59 y of age, it was observed that sedentary women, defined as
those who practice physical activity for <30-min periods three times
a week, had greater mean WC (86.2 12.3 versus 84.3 1.8 cm, P <
0.0001) and a higher prevalence of obesity (20.9% versus 14.3%, P <
0.0001) than non-sedentary women [5]. Moreover, sedentary
women, compared with non-sedentary women, had more severe
menopausal symptoms like hot flushes, sleep problems, psychologi-
cal disorders, and urogenital and sexual problems evaluated by men-
opause rating scale score [5].
As has been observed in the general population, greater adher-
ence to the Mediterranean diet (MedD) reduced morbidity from
cardiovascular diseases (CVDs) in menopause [6]. In a cross-sec-
tional study with 198 peri- and menopausal women participating
in the Flamenco (Fitness League Against Menopause Costs) project,
it was observed that women with a high adherence to the MedD,
evaluated by the Mediterranean Diet Score (MDS) [7] showed
lower plasma total cholesterol (P = 0.025), resting heart rate
(P = 0.005), low-density lipoprotein cholesterol (P = 0.019), triacyl-
glycerols (TGs; P = 0.046), and C-reactive protein (CRP; P = 0.009)
than those with a low adherence to the MedD, suggesting that a
high adherence to the MedD is associated with a cardioprotective
effect in peri- and menopausal women [8]. Furthermore, a pilot
study of a 12-wk Mediterranean-style diet intervention with post-
menopausal women who received counseling from a registered
dietitian was carried out. The intervention consisted of the follow-
ing dietary advice: increase sources of v-3 polyunsaturated fatty
acids (PUFAs), fruits, and vegetables; decrease saturated fats, v-6
PUFAs, and simple sugars; and substitute sources of saturated fat
and refined carbohydrates for extra virgin olive oil, walnuts, and
fatty fish, to maintain isocaloric conditions. After 12 wk, there was
greater adherence to the MedD, as evaluated with the MDS [7]
with an increase of 8.9 points (P < 0.001); an improvement in the
lipid profile, with a 3.8 mg/dL increase of serum high-density lipo-
protein cholesterol (P < 0.005); and a decrease of serum TGs by
11.6 mg/dL (P < 0.10) after the dietary intervention. These changes
 G. Pugliese et al. / Nutrition 79 80 (2020) 110991
consequently led to an improvement in the cardiovascular risk
profile [9].
In a study carried out with 15 sedentary postmenopausal
women randomized to exercise training or exercise plus the MedD
for 8 wk, it was demonstrated that regular moderate exercise
improved microcirculatory vascular function, as evaluated using
laser Doppler flowmetry and increased exercise tolerance as indi-
cated by ventilatory threshold [10].
Additionally, combining the MedD with exercise resulted in an
additional microvascular vasodilatory improvement, suggesting an
effective strategy for further cardiovascular risk reduction in post-
menopausal women [10].
Thus, the aim of this review was to examine the current evi-
dence on menopause and obesity, particularly focusing on the role
of the MedD as a tool to tackle obesity in menopause, highlighting
the potential beneficial effect of this nutritional pattern on health
in women after the reproductive age.
Menopause and obesity
Hormonal changes and in particular the reduction of estrogen
levels, a non-modifiable risk factor, lead to an alteration of the
energy homeostasis and of the regulation of hunger and satiety sig-
nals. Because the estrogens acting on the ERa receptors of the
pituitary hypothalamus circuit inhibit the sense of hunger, their
menopause-related deficiency causes an increase in the orexigenic
signals and an increased caloric intake that is accompanied by a
reduction in energy expenditure and physical activity leading to an
unfavorable energy balance [11]. The importance of sex hormones
on body composition has been reported in both animal and human
models with surgically induced menopause: Oophorectomized rats
had increased obesity, increased food intake, decreased physical
activity and energy expenditure; whereas hormone replacement
therapy with estrogens decreased the oophorectomy-induced
weight gain and abdominal adiposity deposition [12]. Even in
women, the drop in estrogens resulting from hysterectomy
resulted in a greater body mass index (BMI) and WC than controls
with normal ovarian function [13].
Menopause-related hyperandrogenism also promotes the
redistribution of body fat from the gluteal and femoral regions to
the abdominal region and from the subcutaneous to visceral adi-
pose tissue favoring the accumulation of perivisceral abdominal fat
[14]. The increased stimulus from follicle stimulating hormone
(FSH) also appears to play a role in weight gain. In fact, FSH recep-
tors are expressed not only in the gonads but also in visceral fat in
both men and women and it has been shown that the administra-
tion of FSH in mouse preadipocytes promoted lipid biosynthesis,
lipid droplet formation and redistribution of visceral fat mass [15].
Other etiologic factors of obesity in menopause are represented by
the decrease of basal metabolic rate and of lean body mass, partly
dependent on hypestrogenism and on the accentuated sedentary
lifestyle and reduced physical activity. Furthermore, in menopause
there was a greater consumption of high-calorie foods, processed
foods, and a low-fiber Western-type diet probably also to obtain
greater satisfaction and gratification as a consequence of psychic
conditions such as depression, anxiety, irritability, and mood disor-
ders that lead to emotional eating [16].
In menopausal women, there is a change in body composition
described as a transition from a gynoid to an android pattern of fat.
In an observational longitudinal study with 156 healthy perimen-
opausal women undergoing annual measurements of body compo-
sition and fat distribution by dual-energy x-ray absorptiometry
(DXA) for 4 y, it was observed that body fat and weight increased
significantly over time only in those women who became
3
postmenopausal. All women gained subcutaneous abdominal fat
over time; however, only those who became postmenopausal had
a significant increase in visceral abdominal fat, suggesting that
menopause per se was associated with a redistribution of body fat
mostly in the visceral compartment [17].
However, recent evidence suggests that achieving and adhering
to a healthful diet such as the MedD could attenuate the increase in
overall and abdominal adiposity in postmenopausal women [18]. In
a cross-sectional study with 176 perimenopausal women from the
Flamenco project, subjected to a food frequency questionnaire (the
MDS), and DXA to measure body composition, it was observed that
a higher intake of specific components of the MedD, such as whole
grain cereals, nuts, fruits, pulses, whole dairy products, and olive oil
as well as greater adherence to the MedD was associated with better
anthropometric parameters and body composition [19].
Abdominal fat can be considered an endocrine organ due to its
capacity to secrete adipokines, such as leptin and adiponectin, and
other substances including proinflammatory cytokines that are
closely associated with metabolic diseases like insulin resistance,
T2DM, and metabolic syndrome (MetS) [20]. In particular, it has
been demonstrated that women going through the menopausal
transition had deleterious changes in inflammatory markers and
adipokines that correlated with increased visceral adiposity [21]. It
has been shown that the state of estrogen deficiency typical of
menopause led to an increase in plasma proinflammatory cyto-
kines including tumor necrosis factor (TNF)-a, interleukin (IL)-4,
IL-10, and IL-12, whose increase especially in IL-6 is already known
to be associated with a higher energy intake from fat. This proin-
flammatory state, which led to an increased cardiovascular risk
and bone demineralization, was partially reversible through the
use of hormone replacement therapy, pointing out the importance
of estrogens in lowering systemic inflammation [22,23]. In addition
to the inflammatory mediators, during menopause there is an
increase in oxidative stress characterized by an overproduction of
free radicals such as reactive oxygen species (ROS) and by a weak-
ening of antioxidant levels, both related to aging and reduced
estrogen levels, depending on the concentration and chemical
structure of this hormone. In particular, estrogen at high concen-
trations inhibits the 8-hydroxylation of guanine DNA bases, pro-
tecting DNA from oxidative damage, while at low concentrations
this hormone seems to exert a pro-oxidant function, causing
breaks in genetic material, formation of DNA adducts, and oxida-
tion of bases [24]. In fact, by comparing pre- and postmenopausal
women, in the first group higher concentrations of inflammatory
cytokines and pro-oxidant biomarkers such as glutathione, 4-
hydroxynenal, and malonaldehyde were identified [25]. Further-
more, many traditional risk factors, including weight gain and
changes in body fat distribution from a gynoid to an android pat-
tern, the increase in circulating proinflammatory cytokines and
oxidative stress individually and synergistically increase the risk of
onset and progression of metabolic changes such as T2DM, dyslipi-
demia, hypertension, and MetS, as well as CVDs and osteoporosis
[22,26]. In the context of menopausal symptoms, sleep disturban-
ces are one of the most frequent symptoms, and are reported by
40% to 60% of menopausal women [27]. Because the physiologic
hormonal changes are non-modifiable factors, it is mandatory to
act on modifiable risk factors mostly through a targeted nutritional
approach to prevent menopausal-related weight gain and the con-
sequent cardiovascular detrimental effects.
MedD and Menopause-related obesity
As mentioned previously, obesity is a multifactorial and com-
plex disease defined by an excess of adipose tissue, an endocrine
4 G. Pugliese et al. / Nutrition 79 80 (2020) 110991
organ secreting a wide range of adipocytokines, including TNF-a,
IL-6, resistin, leptin, and adiponectin, which leads to low-grade
inflammation and metabolic disorders [28,29], including sleep dis-
turbance [30 32], hypovitaminosis D [33 37], intestinal micro-
biota changes [38], and some types of cancer [39 41].
Obesity-related low-grade inflammation linked to obesity can be
reversed with weight loss. Diet, in particular the high intake of foods
rich in bioactive compounds such as polyphenols and v-3 fatty
acids, have been reported to reduce low-grade chronic inflamma-
tion [28]. Beyond low-grade inflammation, obesity, and visceral fat
accumulation, diet can also stimulate pro-oxidant states [42]. On
one side, obesity per se can induce systemic oxidative stress through
several mechanisms that include superoxide generation, oxidative
phosphorylation, hexosamine pathways, and protein kinase C acti-
vation [43]. Additionlly, hyperleptinemia [44], postprandial ROS
generation [45], and tissue dysfunction [46] can contribute to oxida-
tive stress in obesity. On the other side, the oxidative stress can play
a role in the pathogenesis of obesity [43] causing an increase in pre-
adipocyte proliferation, adipocyte differentiation, and the size of
mature adipocytes [43,47]. It has been found that ROS are involved
in the control of body weight through several effects on hypotha-
lamic neurons, which control hunger and satiety behavior [48].
The MedD is a healthy dietary pattern characterized by a rich-
ness of plant-based foods, resulting in a high intake of phenolic
compounds (polyphenols) present in these foods, including extra
virgin olive oil, whole grain cereals, nuts, legumes, vegetables, red
wine, and fruits [49]. Due to their antioxidant and anti-inflamma-
tory properties, the synergistic consumption of these Mediterra-
nean foods could represent an ideal nutritional pattern in
menopause [50].
The MedD and its components can have beneficial effects by
reducing circulating concentrations of ceramides and certain
sphingomyelin species implicated in the development of chronic
health conditions [51 53]. In fact, clinical studies have reported
that a high adherence to the MedD was associated with the lowest
inflammatory indices in several chronic inflammatory diseases
including hidradenitis suppurativa [54], polycystic ovary syndrome
[55], non-alcoholic fatty liver disease [56], and T2DM [57].
Most of the studies reported that long-term health benefits of
the high adherence to the MedD are well established and, in particu-
lar, regarding weight gain and obesity, the MedD has been sug-
gested to be protective although its efficacy for weight loss at >12
mo in individuals with overweight or obesity remains controversial.
Regarding this topic, Mancini et al. [58] examined the effect of hypo-
caloric MedD on weight loss in individuals with overweight or obe-
sity compared with a low-fat diet, a low-carbohydrate diet, and the
American Diabetes Association (ADA) diet, which recommended
that carbohydrates and monounsaturated fatty acids together
should provide 60% to 70% of energy intake in a systematic review
of five randomized clinical trials (RCTs) [59]. This study showed that
the MedD intervention was associated with a greater weight loss at
12 mo than a low-fat diet ( 4.1 to 10.1 versus 2.9 to 5 kg,
respectively): No differences in terms of weight loss were detected
among the MedD, the low-carbohydrate, or the ADA diet group
( 4.1 to 10.1 versus 4.7 to 7.7 kg, respectively), concluding
that the MedD resulted in greater weight loss than the low-fat diet
and a similar weight loss compared with the low-carbohydrate and
the ADA diets in individuals with overweight or obesity [58].
In a meta-analysis of 16 RCTs, with a range of follow-up periods
between 1 and 24 mo, Esposito et al. reported that greater adher-
ence to the MedD is associated to more weight loss than a control
diet ( 1.75 kg; 95% confidence interval [CI], 2.86 to 0.64 kg).
Additionally, in none of these 16 RCTs was the MedD correlated
with weight gain. The authors of this meta-analysis concluded that
the MedD may be a useful tool in the reduction of body weight
[60]. Of interest, the effect of the MedD on body weight was greater
if it was hypocaloric ( 3.88 kg) or combined with physical activity
(-4.01 kg) [61]. Similar beneficial effects of the MedD detected in
obesity could be translated in menopause-related obesity. Indeed,
Papavagelis et al. explored the relationship between the adherence
to the MedD using the M.D.S. The authors reported that a high
adherence to the MedD was negatively associated with BMI, WC,
and waist-to-height ratio, whereas another dietary pattern, charac-
terized by high consumption of red meat and potatoes and low
consumption of nuts and coffee/tea, was positively associated with
the same parameters [62]. The same results have been highlighted
by a previous cross-sectional study carried out with 8954 Spanish
peri-/postmenopausal women showing that a high adherence to
the MedD, as assessed by a short screener valid questionnaire [63],
was associated with lower prevalence and lower odds of being
overweight/obesity [64]. Furthermore, in another study carried out
with postmenopausal women who followed different dietary pat-
terns, it was observed that although a low-fat diet was associated
with increased risk for weight gain in women who were normal
weight, overweight, or obese, high adherence to the MedD was not
associated with the aforementioned risk [65].
 n-Orea et al. also assessed the main symptoms of meno-
Sayo
pause such as vasomotor symptoms, insomnia, cognitive disorders,
and deterioration of quality of life using the Cervantes question-
naire and placing the participants into one of three groups: no
problems, severe problems, and an intermediate group [64]. Based
on severity and frequency of menopausal symptoms. they
observed that the odds ratio for being overweight/obese was 3.05
(95% CI, 1.98 4.71) for those in the severe problems group com-
pared with the women in the no problem arm, suggesting that the
occurrence of low to severe problems during peri- or postmeno-
pause is positively associated with overweight/obesity [64].
The MedD could also represent a promising approach to man-
age menopause-related symptoms. Indeed, dietary intake and
the presence of vasomotor symptoms at baseline and follow-up
at 3-y intervals over 9 y have been investigated in a prospective
cohort study of 6040 women with a natural menopause [66].
The authors found that better adherence to the MedD was nega-
tively associated with vasomotor symptoms and that a high-fat/
sugar dietary pattern increased the risk for vasomotor symp-
toms, while conversely the Western diet, characterized by high-
fat/sugar content, increased the risk for vasomotor symptoms
[66]. This could imply that the MedD, which prevents weight
gain, overweight, and obesity, could also be protective against
vasomotor symptoms. Additionally, some recent randomized
studies have highlighted that in postmenopausal women with
obesity assigned to either the MedD or the Central European
diet, which is moderate in carbohydrates and high in dietary
fiber, similar improvements in some anthropometric and meta-
bolic parameters such as in CRP, were found in both groups, thus
suggesting that the dietary fiber content is crucial to achieve
these benefits [67,68].
Conclusion
Taking into account the beneficial components of the MedD,
this healthy dietary pattern, especially if hypocaloric, could be a
suitable nutritional pattern for menopause-related obesity.
Furthermore, the antioxidants and anti-inflammatory properties
could potentially contribute to improvements in derangements of
glucose and lipid metabolism that often are associated with obesity.
Future large dietary intervention trials will be critical for elucidating
the beneficial effects of the MedD on menopause-related obesity.
 G. Pugliese et al. / Nutrition 79 80 (2020) 110991
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