Garcinia cambogia and Glucomannan reduce weight, change body composition and ameliorate lipid and glucose blood profiles in overweight/obese patients

Abstract

Background
Nowadays, overweight and obesity are worldwide epidemics associated with the development of diseases such as diabetes, dyslipidemias, hypertension and even cancer. Treatments for these conditions are not very successful and therefore looking for new strategies is imperative. Garcinia cambogia (GC) is used in Asia and Africa for hypolipidemic, antidiabetic and anti-obesity purposes while Glucomannan (GNN) is a diet supplement used to control weight in Japan and China. Here, the efficacy of GC and GNN in weight reduction and the impact on metabolic status of obese/overweight patients for 3 and 6 months was tested.

Material and Methods
This study was a pre-post test study. Adults> 18 years old (n = 136) with a body mass indexin excess of 25 were recruited for this study. These patients also suffered from diabetes mellitus type 2, dyslipidemias, hypertension and their combinations. They were treated with 1 g/day of both GC and GNN for 3 and 6 months

Results
The treatment reduced weight, visceral fat, fat mass, increased metabolic basal rate and was also effective reducing levels of triglycerides, glucose and cholesterol compared to baseline. There were not any adverse effects reported. Reduction in weight were independent of sex, age and previously reported condition.

Conclusions
It was concluded that treatment with GC and GNN is useful in the long term to reduce weight and improve the metabolic status of overweight/obese patients.

Full text

Journal of Herbal Medicine 26 (2021) 100424
Available online 8 January 2021
2210-8033/© 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Garcinia cambogia and Glucomannan reduce weight, change body
composition and ameliorate lipid and glucose blood proles in overweight/
obese patients
Andrea Maia-Landim
a
, Carolina Lancho
b
, María S. Poblador
a
, Jos´
e L. Lancho
a
,
*,
Juan M. Ramírez
a
a
Department of Morphological Sciences, School of Medicine, University of C´
ordoba, Avenida de Men´
endez Pidal s/n, 14071, C´
ordoba, Spain
b
Centro de par´
alisis cerebral Aspace, camino de Illarra s/n CP:20018, Donostia/San Sebasti´
an, Guipúzcoa, Spain
ARTICLE INFO
Keywords:
Garcinia cambogia
Glucomannan
Obesity
Overweight
Weight control
Lipid prole
ABSTRACT
Background: Nowadays, overweight and obesity are worldwide epidemics associated with the development of
diseases such as diabetes, dyslipidemias, hypertension and even cancer. Treatments for these conditions are not
very successful and therefore looking for new strategies is imperative. Garcinia cambogia (GC) is used in Asia and
Africa for hypolipidemic, antidiabetic and anti-obesity purposes while Glucomannan (GNN) is a diet supplement
used to control weight in Japan and China. Here, the efcacy of GC and GNN in weight reduction and the impact
on metabolic status of obese/overweight patients for 3 and 6 months was tested.
Material and methods: This study was a pre-post test study. Adults>18 years old (n =136) with a body mass
indexin excess of 25 were recruited for this study. These patients also suffered from diabetes mellitus type 2,
dyslipidemias, hypertension and their combinations. They were treated with 1 g/day of both GC and GNN for 3
and 6 months.
Results: The treatment reduced weight, visceral fat, fat mass, increased metabolic basal rate and was also effective
reducing levels of triglycerides, glucose and cholesterol compared to baseline. There were not any adverse effects
reported. Reduction in weight were independent of sex, age and previously reported condition.
Conclusions: It was concluded that treatment with GC and GNN is useful in the long term to reduce weight and
improve the metabolic status of overweight/obese patients.
1. Introduction
The number of people who are overweight or obese has reached
epidemic level not only in developed countries but across the world
(Caballero, 2007; James, 2008; OMS, 2012). The number of people
suffering from obesity has doubled since 1980 and it was estimated to be
around 1.4 billion in 2013 (Ng et al., 2014). In addition, some models
predict that half of the population in United States in 2030 will be obese
(Finkelstein et al., 2012).
These conditions have been associated with several metabolic dis-
orders such as diabetes, hypertension, dyslipidemias, cardiovascular
diseases, sleep apnea, osteoarthritis, osteoporosis and even increase the
risk of cancer (OMS, 2012; Pond, 1992; Tchernof and Despres, 2013).
Being overweight or obese reduces wellbeing, increases the risk of
mortality and reduces life expectancy (OMS, 2012). These conditions
show up when caloric intake exceeds caloric expenditure. This excess is
translated in an accumulation of fat in body fat deposit such as visceral
fat and changes in body composition (Pond, 1992). Different factors
such as people’s genetic background, bad nutritional habits, and
sedentary life style are related to overweight and obesity development
(Bowman et al., 2004; Kaur et al., 2017).
Obesity and being overweight are treated with a combination of
caloric restriction, a reduction in a 15–40 % of calories per day is usually
recommended, and exercise (preferably aerobic) aimed at reducing fat
Abbreviations: GC, Garcinia cambogia; GNN, Glucomannan; BMR, Basal metabolic rate; BMI, Body mass index; AHC, Hidroxicitric acid; DM2, Diabetes mellitus
type II.
* Corresponding author.
E-mail addresses: dea2929@hotmail.com (A. Maia-Landim), c.lancho@aspacegi.org (C. Lancho), cm1pofem@uco.es (M.S. Poblador), cm1laalj@uco.es
(J.L. Lancho), jmramirez@uco.es (J.M. Ramírez).
Contents lists available at ScienceDirect
Journal of Herbal Medicine
journal homepage: www.elsevier.com/locate/hermed
https://doi.org/10.1016/j.hermed.2021.100424
Received 9 November 2018; Received in revised form 21 March 2020; Accepted 6 January 2021

Journal of Herbal Medicine 26 (2021) 100424
2
accumulation and increasing energy expenditure (Iacobellis et al., 2008;
James, 2008; Kim et al., 2008; Kushner and Ryan, 2014). Cases of
morbid obesity are treated with bariatric surgery (Fried et al., 2014).
However, diets and exercise sometimes are unable to achieve their ob-
jectives for genetic reasons (Corella et al., 2005; Phares et al., 2004), low
diet/exercise compliance or because patients trend to regain the lost
weight in a short time after the diet (MacLean et al., 2015).
Pharmacotherapy has emerged as an alternative when changes in
lifestyle do not reduce weight, or may be a tool to improve the results of
diet and exercise to control weight or if bariatric surgery is not an option
(Apovian et al., 2015). Different drugs with different mechanisms of
action are available in the armamentarium to ght obesity (Patel, 2015).
However, pharmacotherapy has some disadvantages such safety con-
cerns or side effects. Thus fenuramine and dexfelnuramine, subitr-
amine and rimonobant were retired from the market for producing
pulmonary hypertension, cardiovascular or psychiatric effects, respec-
tively (Kang and Park, 2012).
Among different alternatives to control weight, the use of some
herbal extracts is gaining acceptance in recent years. These compounds
come from natural sources, have a low cost, and sometime have been
used for a long time in some Asiatic and Indic cultures as dietary sup-
plements without having negative effects which makes a good candidate
to use as weight control agents (Mopuri and Islam, 2017). Two of the
most common agents are Garcinia cambogia (GC) and glucomannan
(GNN). GC is an extract from a south Asian plant that has been used as a
nutritional supplement to control weight (Astell et al., 2013; Hasa-
ni-Ranjbar et al., 2009; Mopuri and Islam, 2017; Semwal et al., 2015;
Tomar et al., 2019). GC has a high content of hydroxycitric acid (AHC)
that is involved in blocking lipogenesis. This action is mediated through
the inhibition of the ATP-citrate liase, an enzyme that is required for the
rst step in the lipogenesis process (Ohia et al., 2002). AHC also seems to
act on serotonin levels reducing food intake (Preuss et al., 2004). Be-
sides, other metabolic actions of AHC on lipid metabolism have been
reported such as increase of fatty acid oxidation and regulation of genes
involved in lipid metabolism (Han et al., 2016; Hayamizu et al., 2003;
Kovacs and Westerterp-Plantenga, 2006; Roy et al., 2007). On the other
hand, GNN is a natural ber formed by β 1,4-linked D mannose and
D-glucose monomers extracted from a tuber called Amorphophallus
konjac (Lyon and Reichert, 2010). Its mechanism of action to reduce
weight might be based on its capacity of absorbing 50 times its weight in
water volume, which would produce a delayed gastric emptying
together with a satiety feeling (Cairella and Marchini, 1995; Shima
et al., 1983). The principal mechanism of action of both agents are
summarized in Fig. 1.
In this study, the aim was to evaluate the effects of a combined
treatment of GC and GNN in a population of overweight and obese pa-
tients who also suffered from diabetes mellitus type 2, dyslipidemias and
hypertension, upon body composition (weight, visceral and fat mass)
and metabolic status (metabolic basal rate, triglycerides, cholesterol and
glucose levels) at 3 and 6 months since study onset.
2. Material and methods
This study was designed as a multicentric, non-randomized pro-
spective trial, evaluating differences between two dependent means (a
pre-post test study). Consort checklist is in supplementary Table 1. Pa-
tients were recruited after they signed an informed consent in Scientics
Aesthetics Clinics of the Body in C´
ordoba, Spain. The minimum number
of patients required for obtaining signicant results was estimated by
power analysis running the following parameters in G*power (V3.1.9.2)
software. These parameters were type I and II errors of 5 and 95 %
respectively, and an effect size of 0.25. The result of this analysis
resulted in a minimum of 130 patients.
Inclusion criteria were patients with an BMI >25 from both sexes (61
male and 75 female) and an age ranging from 18 to 59 years old. These
patients also suffered from dyslipidemias, hypertension, DM2 or their
combinations. The patients’ main characteristics are summarized in
Table 1. We conrmed that patients were under treatment for hyper-
tension, DM2 or dyslipidemias for a range of 2 months to 4 years before
study onset. The exclusion criteria are related to avoid possible in-
terferences in the outcome with other diseases, surgical interventions or
other conditions that might inuence the metabolic status of the pa-
tients. For this reason we excluded patients with pregnancy or lactation,
with gastroplasty or gastrointestinal weight-reducing surgery, cessation
Fig. 1. Main GC and GNN mechanism of action on overweight control. AHC: hidroxicitric acid; GNN: Glucomannan; GH: Garcinia cambogia.
A. Maia-Landim et al.

Journal of Herbal Medicine 26 (2021) 100424
3
of smoking during the past 6 months, kidney disease, history of recur-
rent kidney stones, liver dysfunction, untreated high blood pressure,
history or symptoms of gallstones, cancer, history of endocrine disorders
(particularly hypothyroidism), history of bulimia and/or laxative abuse,
mental disorders with impaired independence, history of alcohol or
other drug abuse. All of them were evaluated at the start of the study
(baseline), 3 and 6 months from study onset in Scientics Aesthetics
Clinics of the Body in C´
ordoba, Spain. All of them completed previously
to study onset, a form to evaluate their medical history. All patients were
informed and signed the proper informed consent. This work was in
accordance with Helsinki declaration and was approved by Ethical
Boards of Hospital Universitario Reina Soa de C´
ordoba (Spain).
2.1. Pharmacological treatment
Patients were advised to have a balanced diet (Mediterranean diet),
regular meals and drink plenty of water. This diet has been generally
recognized for its metabolic benets (Fit´
o and Konstantinidou, 2016)
and it was also recommended to patients to practice physical exercise,
avoid smoking, and control alcohol intake as it is usual in the manage-
ment of these kinds of patients (De Sousa and Norman, 2016; Myers
et al., 2019; Sherling et al., 2017). Standardized extracts of GC (52.4 %
HCA) and A. konjac (94.9 %, glucomannan) were administered in cap-
sules of 500 mg each of them. The patients were treated with GC (500
mg), twice a day, half an hour before lunch and dinner and GNN (500
mg), twice a day, half an hour before lunch and dinner.
The GC and GNN compounds were obtained by patients by medical
prescription in pharmacies authorized by RD175/2001 for the formu-
lation of medical products. The RD175/2001 rule, is the Spanish law
that regulates the preparation of in situ drugs in pharmacies thus the
compounds prepared meet the highest quality and safety criteria.
This kind of treatment is based on the ranges reported by previous
studies that produced a safe reduction in weight although in short pe-
riods of time (Biancardi et al., 1989a; Birketvedt et al., 2005b; Cairella
and Marchini, 1995; Girola et al., 1996; Preuss et al., 2005; Sood et al.,
2008a; Thom, 2000; Toromanyan et al., 2007; Vasques et al., 2008; Vido
et al., 1993; Walsh et al., 1984).
2.2. Anthropometric measurements and estimation of body composition
Anthropometric measurements and body composition: Body mass
was measured on a digital balance (HD-305 TanitaTM) to the nearest 0.1
kg. Height was taken with a Seca Bodymeter 206 to the nearest 0.1 cm.
These data were used to calculate body mass (BM) and (BM) index (BMI)
kg/m
2
.
Bioelectrical impedance was performed with a BioScan Spectrum
operating at 50 KHz, measuring fat mass (Wid´
en et al., 1995). Briey,
two-compartment body composition, percentage fat mass (%FM) and
free fat mass (FFM) were measured by tetrapolar bioelectrical
impedance analysis in 12 h fasted subjects on a restricted
physical-activity schedule. FFM was assessed using the following equa-
tion (Deurenberg et al., 1991): FFM (kg) =0.340 (h
2
/R) +0.1534 (h)
+0.273 (BM) -0.127 (age) +4.56 (sex) -12.44 where: h is the height
(cm), R is the resistance (ohm) and female =0, male =1.
Basal Metabolic rate (BMR) was assessed by indirect calorimetry,
using a TEEM 100® (INBRASPORT) calorimeter: 12 h fasted subjects on
a restricted exercise schedule lay comfortably on their backs in a silent
room at a mean temperature of 24 ±1 ◦C, and VO2 and VCO2 were
recorded over a 15 min period; data obtained over the last 10 min were
used to calculate BMR. BMR estimation was based on Weir equation
(Weir, 1949): BMR (kcal/min) =[3.9(VO2) +1.1(VCO2)]. The value
obtained was multiplied by 1440 in order to estimate BMR for 24 h
(kcal/day). BMR was also calculated from the relationship with BM or
FFM (kcal/kg/24 h). Additionally, mean values for the respiratory
quotient (RQ), VO2 (L/min) and metabolic equivalent (MET) were also
obtained, taking 1 MET to be equal to an expenditure of 3.5 mL
O2/kg/min.
2.2.1. Blood analysis
Blood extraction was performed using a clinical routine laboratory
protocol after 12 h of patients fasting. Patients were advised to restrain
from performing exercise or consuming alcohol 24 h prior the test. Pa-
tients consumed food with lipid composition similar to that ingested
during the months the study took place. Glucose concentrations,
cholesterol and triglycerides levels were measured using a colorimetric
enzyme assay method (CEPA® kits – MBiolog Diagn´
osticos Ltda.) as
previously described (Vasques et al., 2008).
2.2.2. Statistic
Results are presented as mean ±SEM. SPSS© r22 was used to
perform an analysis of covariance to nd out if there were signicant
differences among measurements and the possible inuence of different
variables such as sex. Pearson correlation test was used to discard
possible inuence of age (that is a continuous variable) in the outcome.
A posteriori Tukey test was run to analyze differences as considered
appropriate. A p <0.05 was considered a as signicant.
3. Results
3.1. GC and GNN administration reduces weight and affects positively
body composition
The rst goal was to test if GC and GNN combined treatment was able
to reduce weight. The result conrmed that administration of GC and
GNN signicantly (p <0.01) reduced weight at 3 and 6 months since
study onset (Fig. 2A). Notably, there was a signicant (p <0.01)
reduction in weight at 6 months compared with 3 months (Fig. 3A).
Moreover, this reduction was effective in weight reduction indepen-
dently of sex or age by the patients as conrmed by analysis of covari-
ance for sex (p =0.62) and Pearson correlation for age at 3 months (p =
0.71; R
2
<0.001) and 6 months (p =0.47; R
2
<0.01) (Fig. 2B–D). Next,
analysis was carried out to see if visceral and fat mass were reduced
accordingly to weight loss. Indeed, both fat mass and visceral fat were
signicantly decreased at three months (p <0.01) and this reduction
was even higher (p <0.01) at 6 months compared with the previous
measurement (Fig. 3A, B). the authors also wanted to discover if BMR
was affected by GC and GNN administration. Indeed, BMR was increased
at 3 and 6 months p <0.05 and p <0.01 respectively vs study onset,
although in this case there was not a signicant difference between 3
and 6 months (Fig. 3C).
3.2. Treatment with GC and GNN improves metabolic status
In agreement with previous results (Vasques et al., 2008), it was
found that glucose, triglycerides and cholesterol levels were reduced in
Table 1
Patients description.
Variable Number (%)
Age 37.8 ±11.5
Sex
Male 61 (44.8)
Female 75 (55.2)
Disease
Hypertension (H) 27 (19.85)
Dyslipidemia (D) 28 (20.58)
Diabetes mellitus II (DM) 10 (7.35)
H+D 31 (22.80)
H+D+DM 40 (29.41)
Age (mean ±SD); H +D: Hypertension and Dyslipidemia;
H+D+M: hypertension and Dyslipidemia and Diabetes mellitus
type II.
A. Maia-Landim et al.

Journal of Herbal Medicine 26 (2021) 100424
4
obese patients under GC and GNN therapy. Cholesterol was reduced
signicantly (p <0.01) at 3 and 6 months since study onset (Fig. 4A)
without differences between 3 and 6 months. Triglycerides levels were
only found to be signicantly (p <0.05) reduced at 6 months (Fig. 4B),
in accordance with glucose levels which were signicantly reduced (p <
0.05) at 6 months since study onset (Fig. 4C). All the patients in this
study were evaluated periodically by their physician and they did not
report any adverse effects. Means and standard errors of each gure are
summarized in Table 2.
4. Discussion
It has been widely reported in the literature that GC and GNN
administration has a positive effect in weight and lipids control. How-
ever, many of these reports were hampered by a reduced number of
patients or follow-up (M´
arquez et al., 2012), which creates doubts about
the long-term effects of these treatments. Thus, Ramos and co-workers
reported that treatment with 1.5 g of GC daily for 8 weeks together
with caloric restriction reduce signicantly the weight in obese patients
(Ramos et al., 1995a). Accordingly Mates and Bormann in a study with
overweight patients (n =256) under caloric restriction and treated with
2.4 g of GC per day for 12 weeks also found a reduction in weight
(Mattes and Bormann, 2000). Other studies treated obese/overweight
patients with GC in combination with other plant extracts such as Chi-
tosan, Phaseolus vulgaris, Gymnema silvestra, Matricaria chamomilla,
Rosa damascena, Lavandula ofcinalis and Cananga odorata reporting
similar results. These studies included data no longer than 12 weeks and
Fig. 2. GC and GNN treatment effects in weight. A) GC and GNN reduce weight
in overweight/obese patients. B) Linear regression indicates that weight
reduction is independent of patient’s sex. C) Correlation test showing that there
is not association between age distribution and weight at 3 months. D) Corre-
lation test showing that there is not association between age distribution and
weight at 6 months. **p <0.01 vs study onset (0 months);
#
p <0.05 vs
3 months.
Fig. 3. GC and GNN treatment ameliorate and body composition. A) and B) Fat
mass (%) and visceral mass (%) were reduced at 3 and 6 months. C) Increase in
BMR upon treatment with GC and GNN. *p <0.05 and **p <0.01 vs study
onset (0 months);
##
p <0.01 vs 3 months.
A. Maia-Landim et al.

Journal of Herbal Medicine 26 (2021) 100424
5
with doses ranging from 0.055 g to 2.8 g per day (Girola et al., 1996;
Preuss et al., 2005; Thom, 2000; Toromanyan et al., 2007). On the other
hand, the benecial action of GNN treatment on weight control has also
been extensively reported. GNN treatment with doses from (1.24 to 3 g
per day) alone or with caloric restriction was able to reduce weight in
obese adult and children patients (Biancardi et al., 1989b; Birketvedt
et al., 2005a; Cairella and Marchini, 1995; Sood et al., 2008a; Vido et al.,
1993; Walsh et al., 1984). In addition, treatment with GC and GNN has
been reported to change lipid proles in overweight/obese patients.
Thus GC and GNN alone or in combination with another other plant
extract or with caloric restriction reduce the levels of cholesterol, tri-
glycerides and low density lipoproteins (Girola et al., 1996; Ramos et al.,
1995b; Sood et al., 2008b; Vuksan et al., 2000; Wardle et al., 2008;
Yoshida et al., 2006). On the other hand, the authors have recently re-
ported that the presence of different polymorphism in overweight/obese
patients may affect the effectiveness of GC and GNN treatment
(Maia-Landim et al., 2018).
In this study, the authors have included a large number of patients
and which have been followed up for 6 months. It was found that in
agreement with previously mentioned studies, this treatment was able to
reduce weight and this reduction was parallel to visceral fat and fat mass
and accordingly increased BMR. Besides, this treatment has a positive
effect on the lipid prole of patients, reducing cholesterol triglycerides
and glucose levels. Previously, it has been reported that combined
treatment of GC and GNN was able to reduce the levels of cholesterol but
without having any signicant effect upon weight, metabolic basal rate,
triglycerides and glucose. In this study, that was a double blind ran-
domized study (n =25 patients in control group and n =32 in study
group) that lasted for 12 weeks, the doses of GC was 2.5 g/day and GNN
1.5 g/day (Vasques et al., 2008). Here, the authors have increased the
number of patients up to 136 and the follow-up to 6 months reducing the
doses of each plant extract to a 1 g/day with the mentioned results.
Differences in the results between two studies might be related to the
number of patients recruited that regarding the present study increase
the possibility of nding signicant differences. Of note, signicant
differences in the lipid prole were only found when the results from 6
months to baseline were compared. These results can be attributable to a
decrease in administered doses and therefore more time is needed to
reduce triglycerides and glucose levels. It is true that our population is
heterogeneous regarding sex and age, which might be interpreted as a
limitation because factors such as hormonal levels are not controlled. It
was recognized that it should be addressed in further studies through
randomized controlled trials. However, it was necessary to test if our
combined treatment might work in different age ranges and in both
sexes as in fact the results would seem to demonstrate.
Others studies have failed to nd differences in weight or changes in
lipid prole in treated patients with GC and GNN (Onakpoya et al.,
2014, 2011; Ríos-Hoyo and Guti´
errez-Salme´
an, 2016; Semwal et al.,
2015; Zalewski et al., 2015). It is important to keep in mind that GC and
GNN are used in different concentrations and the quality of nal
extracted product sometimes is uncertain and vary among studies. Be-
sides, they are often used in combination with other plant extract which
make difcult to disclose the putative effects of both extracts.
GC and GNN safety have been screened and several studies have
reported that there is no increase in toxicity, side effects or mortality
associated with their use (Keithley et al., 2013; M´
arquez et al., 2012;
Ohia et al., 2002; Wells and Fewtrell, 2005). However, some concerns
have arisen regarding the treatment of GC and hepatic and pancreatic
toxicity (Crescioli et al., 2018; Iqbal et al., 2019; Lunsford et al., 2016).
These side effects might be related to previous pathologies of the pa-
tients, an uncontrolled dosage of the agent, other agents in the prepa-
ration or even that sometimes the preparations might be contaminated
with other substances with unpredictable results (Jamila et al., 2016).
Fig. 4. GC and GNN treatment ameliorate lipid and glucose blood levels. A)
Cholesterol levels at 3 and 6 months of treatment. B) Triglycerides levels at 3
and 6 months of treatment. C) Glucose levels at 3 and 6 months of treatment. *p
<0.05 and **p <0.01 vs study onset (0 months).
Table 2
Data from the graphics.
Parameter Time
Baseline (0) 3 months 6 months
Weight 85.96 ±
0.75
72.28 ±
0.67**
69.84 ±0.68**
,
#
Fat mass (%) 31.06 ±
0.35
38.52 ±
0.33**
26.04 ±0.31**
,
##
Visceral fat (%) 22.14 ±
0.23
20.10 ±0.24 18.26 ±0.26
Basal Metabolic rate (Kcal/
Kg/day)
1647 ±
28.70
1684 ±
29.45*
1714 ±29.80**
Cholesterol (mg/dL) 229.1 ±
4.11
209.4 ±
3.28**
198.7 ±2.85**
Tryglicerides (mg/dL) 159.8 ±4.9 148.3 ±3.7 142.9 ±2.9*
Glucose (mg/dL) 95.6 ±1.3 93.8 ±1 91.9 ±0.9*
Data are mean ±standard error of mean. (n =136). *p <0.05 and **p <0.01 vs
study onset (0 months);
#
p <0.05 and
##
p <0.01 vs 3 months.
A. Maia-Landim et al.

Journal of Herbal Medicine 26 (2021) 100424
6
For these reasons, it is of utmost importance to follow up and control the
preparation of the agents and the status of the patients. In this case, a
close follow up of the patients was performed certifying that all were in a
healthy situation given their comorbidities.
Looking at the results, one might think that it is also possible that the
co-treatment with GNN might counteract some of the adverse effects of
GC in these patients. However, to conrm this hypothesis, a new
experimental design must be explored in which a detailed study of liver,
renal and pancreatic function would be carried out.
The authors are aware that to extend the use of this kind of therapy to
treat obesity it is necessary to design more double-blinded randomized
trials, improving the characterization of the different extracts and using
homogenous doses to treat the patients. However, it is also mandatory to
expand our knowledge in the possible long-term effects of the supple-
mentation in obese patients. In this regard, in our study none of the
patients reported any side or adverse effects in the duration of the
treatment supporting the safety of this therapy. Another limitation of
this study is the difculty of differentiating the effects of the Mediter-
ranean diet from the effect of the administration of treatment. For this
reason, new studies would be necessary in which a population that did
not follow this type of diet was included to nd out if the effects of both
extracts are independent of the diet.
The authors consider that one important nding of this study is that
combined treatment was successful independent of age, sex, and pre-
vious associated comorbidity such hypertension, diabetes and dyslipi-
demias supporting that this treatment might be used in a wide variety of
patients.
5. Conclusions
This study demonstrated that combined treatment of GC and GNN on
overweight/obese patients, in the long-term reduced weight related to
decreasing visceral fat and fat mass and increasing BMR. This treatment
was also effective in ameliorating the lipid prole of these patients.
These effects were also independent of sex, age or suffering from hy-
pertension, diabetes mellitus type 2 or dyslipidemias. Even though it is
necessary to conduct further research with randomised controlled trials
to assess the long-term effects of these plant extracts, the authors
conclude that the combined treatment with GC and GNN might be a
good candidate to control weight in overweight/obese patients.
Transparency document
The Transparency document associated with this article can be found
in the online version.
CRediT authorship contribution statement
Andrea Maia-Landim: Methodology, Data curation, Writing - orig-
inal draft, Investigation. Carolina Lancho: . María S. Poblador: Su-
pervision, Validation, Writing - review & editing. Jos´
e L. Lancho:
Conceptualization, Supervision, Validation, Writing - review & editing.
Juan M. Ramírez: Conceptualization, Methodology, Investigation.
Declaration of Competing Interest
None to declare.
Acknowledgements
Non Applicable.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
online version, at https://doi.org/10.1016/j.hermed.2021.100424.
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