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Frontiers in Nutrition 01 frontiersin.org
Eects of green coee aqueous
extract supplementation on
glycemic indices, lipid profile, CRP,
and malondialdehyde in patients
with type 2 diabetes: a
randomized, double-blind,
placebo-controlled trial
SajadKhalili-Moghadam
1, MehdiHedayati
2, MahdiehGolzarand
3*
and ParvinMirmiran
1,3*
1 Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National
Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences,
Tehran, Iran, 2 Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine
Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 3 Nutrition and Endocrine
Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
Background/objectives: Studies have reported the health benefits of green
coee extract (GCE) in experimental models. In the current study, we aimed
to determine whether supplementation with GCE improves glycemic indices,
inflammation, and oxidative stress in patients with type 2 diabetes (T2D).
Methods and study design: This randomized, double-blind, placebo-controlled
trial included 44 patients (26 male and 18 female) with T2D and overweight/obesity.
After blocked randomization, patients received either capsules containing 400 mg
GCE twice per day (n = 22) or a placebo (n = 22) and were followed for 10 weeks.
In this study, glycemic indices, lipid profiles, anthropometric examinations, blood
pressure, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde
(MDA) were measured twice; at baseline and at the end of the study.
Results: After 10 weeks of supplementation, GCE supplementation significantly
reduced body weight (p = 0.04) and body mass index (BMI) (p = 0.03) compared
to the placebo. The intention-to-treat (ITT) analysis indicated patients in the GCE
group had a lower fasting blood glucose (FBG) concentration compared to the
placebo group; however, this decreasing was marginally significant (8.48 ± 8.41 vs.
1.70 ± 5.82 mg/dL, p = 0.05). There was no significant dierence in insulin levels
and HOMA-IR between the groups. At the end of the study, significant changes
in systolic blood pressure (SBP) (p = 0.01), triglyceride (TG) level (p = 0.02), high-
density lipoprotein (HDL) (p = 0.001), and TG-to-HDL ratio (p = 0.001) were
found between the intervention and placebo groups. Our trial indicated GCE
supplementation had no eect on diastolic blood pressure (DBP), low-density
lipoprotein (LDL), or total cholesterol. During the supplementation period, the
hs-CRP level significantly decreased in the GCE group compared to the placebo
group (p = 0.02). No significant changes were observed in the MDA level between
the two groups at the end of the study (p = 0.54).
OPEN ACCESS
EDITED BY
Kenji Watanabe,
Yokohama College of Pharmacy, Japan
REVIEWED BY
Vali Musazadeh,
Tabriz University of Medical Sciences, Iran
Niloufar Rasaei,
Tehran University of Medical Sciences, Iran
Naheed Aryaeian,
Iran University of Medical Sciences, Iran
*CORRESPONDENCE
Mahdieh Golzarand
mahdieh_golzarand@yahoo.com
Parvin Mirmiran
mirmiran@endocrine.ac.ir
RECEIVED 17 June 2023
ACCEPTED 03 November 2023
PUBLISHED 16 November 2023
CITATION
Khalili-Moghadam S, Hedayati M,
Golzarand M and Mirmiran P (2023) Eects of
green coee aqueous extract supplementation
on glycemic indices, lipid profile, CRP, and
malondialdehyde in patients with type 2
diabetes: a randomized, double-blind,
placebo-controlled trial.
Front. Nutr. 10:1241844.
doi: 10.3389/fnut.2023.1241844
COPYRIGHT
© 2023 Khalili-Moghadam, Hedayati,
Golzarand and Mirmiran. This is an open-
access article distributed under the terms of
the Creative Commons Attribution License
(CC BY). The use, distribution or reproduction
in other forums is permitted, provided the
original author(s) and the copyright owner(s)
are credited and that the original publication in
this journal is cited, in accordance with
accepted academic practice. No use,
distribution or reproduction is permitted which
does not comply with these terms.
TYPE Clinical Trial
PUBLISHED 16 November 2023
DOI 10.3389/fnut.2023.1241844
Khalili-Moghadam et al. 10.3389/fnut.2023.1241844
Frontiers in Nutrition 02 frontiersin.org
Conclusion: Our findings showed beneficial eects of GCE on SBP, TG, hs-CRP,
and HDL levels in patients with T2D and overweight/obesity over a 10-week
period of supplementation.
Clinical trial registration: https://en.irct.ir/trial/48549, identifier
[IRCT20090203001640N18].
KEYWORDS
type 2 diabetes, Hs-CRP, Malondialdehyde, Insulin, lipid profile, green coee
Introduction
Generally, patients with type 2 diabetes mellitus (T2D) are at
increased risk for various cardiovascular and renal diseases. ese
patients have several comorbidities, such as fatty liver disease,
atherogenic dyslipidemia, and hypertension, which are associated
with an increased risk of disability and mortality (1). A total of 425
million adults suer from diabetes globally, which is anticipated to rise
to 629 million by 2040 (2). So, pharmacotherapy and lifestyle changes
are necessary to control T2D in the long term (3). Dietary modication
is also recommended to reduce the complications of T2D, and
currently, most studies have focused on the eects of nutraceuticals
on treating or preventing diabetes complications (4).
e green coee bean is an unroasted coee fruit that is rich in
bioactive phytochemical compounds (5). e main bioactive
ingredient of green coee is chlorogenic acid (CGA), which has
benecial eects on blood pressure, inammatory markers, oxidative
stress, and diabetes in experiments (6). Several mechanisms have
been proposed by which CGA exerts its eects, such as inhibiting the
cytochrome P450 1A enzymes that increase the pro-inammatory
response (7), increasing the expression of genes that reduce oxidative
stress (8), decreasing insulin resistance by activating the hepatic
proliferation-activated receptor α (PPAR-α) (9), or improving blood
glucose by activating AMP-activated protein kinase (AMPK) (10).
However, the health benets of green coee for humans are
inconsistent. Several randomized controlled trials (RCTs) have
evaluated the eects of green coee extract (GCE) supplementation
on cardiometabolic risk factors. Some studies have found that GCE
has favorable eects on cardiometabolic risk factors, while others
have not (11–15). In addition, most studies have been conducted on
healthy adults or subjects with overweight or obesity, and there is a
lack of individual studies on patients with T2D (11, 16, 17). Results
of a recent meta-analysis on 27 RCTs showed an advantageous
inuence of GCE on glycemic markers, triglycerides (TG), and high-
density lipoprotein (HDL); however, due to the high heterogeneity
between studies, the results should beinterpreted with caution (18).
In regards to inammatory markers, there are also contradictory
results (19).
Despite the protective eects of GCE on chronic diseases (20),
research regarding the eects of GCE on T2D is scarce. Moreover,
most of the previous studies assessed the eects of CGA rather than
GCE in animal models. Besides, ndings concerning the eects of
GCE are rather inconsistence. us, wedesigned a clinical trial study
to assess the eects of GCE supplementation on glycemic indices, lipid
prole, hs-CRP, and malondialdehyde (MDA) in patients with T2D
and overweight/obesity.
Methods
Study design
e present study was a parallel randomized, double-blind,
placebo-controlled trial. e National Nutrition and Food Technology
Research Institute of Shahid Beheshti University of Medical Sciences’
ethics committee approved this study. It is also registered on the
Iranian Registry of Clinical Trials (registration number:
IRCT20090203001640N18). At the beginning, the participants signed
a “written informed consent form.”
In this study, 44 patients with T2D and overweight/obesity who
were referred to the Taleghani Hospital, Tehran, between June 2022
and December 2022 participated. Inclusion criteria were as follows:
being aged 30–70 years old, suering from T2D [fasting blood glucose
(FBG) ≥ 126 mg/dL, measured twice, 2-h plasma glucose ≥200 mg/dL,
or HbA1C ≥ 6.5%, or taking oral hypoglycemic medicines] (21),
having a history of diabetes between 1 and 10 years, and having a body
mass index (BMI) of 25–35 kg/m2. Exclusion criteria were as follows:
receiving insulin therapy, pregnancy or lactation, going on diet during
the past 3 months, taking any dietary supplements at least once a week
in the past 3 months, and having severe hepatic, renal, and
inammatory diseases. Wealso removed patients who took less than
80% of their capsules or changed the type or dosage of medications
during the intervention. At baseline, patients were asked to complete
a questionnaire regarding socio-demographic characteristics, diet and
drug histories, and medical history through a comprehensive face-to-
face interview.
Intervention
In this study, the sample size was calculated based on the primary
outcome with a power of 80% and an alpha of 0.05. en, participants
were randomly assigned into two groups of 22 patients that received
either oral capsules of a GCE or a homologated placebo (starch). Both
GCE and placebo capsules were produced by Bonyan Salamat Kasra
Co., Tehran, Iran, and were similar in size, shape, and smell. GCE
contains 0–2% caeine and 45–50% CGA by weight. Randomization
was conducted using the permuted block method based on sex.
Blocked randomization was done with block sizes of four concealed
in a container by one of the researchers. e blocks were composed of
A and B characters, representing bottles of capsules coded with A or
B to ensure concealment. e other investigator randomly assigned
the participants to one of the two groups. Subjects were recommended
to consume two capsules (each capsule contains 400 mg GCE or
Khalili-Moghadam et al. 10.3389/fnut.2023.1241844
Frontiers in Nutrition 03 frontiersin.org
placebo) aer their main meals to reduce gastrointestinal
complications for 10 weeks. All participants were contacted every two
weeks to ensure that they complied with the supplementation protocol
(adherence of at least 80% was considered good) and to evaluate the
side eects. Subjects who reported severe side eects or consumed less
than 80% of the capsules were excluded from the study. e
participants and researchers were blinded by the intervention.
Nutritional recommendations (based on the food guide pyramid)
were given to the subjects during the study period, and they were
requested to maintain their usual physical activity.
Dietary assessment
In order to assess dietary changes during the trial period, all the
patients were asked to provide two three-day food records (1 weekend
day and 2 weekdays) at the beginning and end of the intervention.
Food records consisted of the serving size of consumed foods and
ingredients. Also, the subjects were interviewed to report their intake
based on household measures. e Household Measures and food
model booklet with pictures of household items was used to better
estimation of portion size of the food and beverages. ese measures
were used to obtain the grams of food consumed. Nutritionist IV
soware (First Databank, San Bruno, CA, UnitedStates), which is
adapted for the national composition food tables, was used to perform
nutrient analysis.
Outcomes assessment
At baseline and at the end of the study, all physical, clinical, and
biochemical factors were measured. Weight was measured using a
Seca digital scale (Germany) while the subjects were minimally
clothed and without shoes, with a precision of 100 g. Also, height was
measured using a tape meter attached to the wall to the nearest 0.5 cm.
In addition, BMI was calculated by dividing weight (kg) by the square
of height (m
2
) at baseline and 10 weeks later. Aer 10 min of rest,
systolic blood pressure (SBP) and diastolic blood pressure (DBP) were
measured twice using a digital sphygmomanometer (Citizen, Japan)
with a precision of 1 mmHg. Finally, the average of the two
measurements was considered the subject’s blood pressure. Physical
activity level was assessed using a short form of the International
Physical Activity Questionnaire (IPAQ) (22). e physical activity
data were reported as metabolic equivalent minutes per week
(MET-minutes/wk).
At the beginning and aer 10 weeks of intervention, 10 mL of
venous blood was drawn from participants aer a 12-h fasting period.
e blood serum was obtained by centrifugation at a rate of 3,500
rounds per minute. Aerwards, the serum samples were frozen and
stored at −70°C until the time of the experiments at the research
institute for endocrine sciences, Shaid Beheshti University of Medical
Sciences, Tehran, Iran. e serum concentrations of FBG, TG, total
cholesterol, and HDL were assessed using an enzymatic colorimetric
method (Delta Darman, Iran). Also, the serum insulin levels were
measured using the enzyme-linked immunosorbent assay (ELISA)
technique (Monobind, Austria). To estimate insulin resistance, the
homoeostasis model assessment of insulin resistance (HOMA-IR) was
calculated according to the equation by Matthews et al. (23):
HOMA-IR = [insulin (Mu/L) × glucose (mg/dL)]/405. e low-density
lipoprotein (LDL) levels were calculated using the Friedewald formula:
LDL = TC – HDL – (TG/5) (24). e serum hs-CRP levels were
assessed using turbidimetry (Delta Darman, Iran). e serum
concentration of MDA was measured using a colorimetric method
using a commercial kit (Karmania Pars Gene, Iran). e intra-assay
coecients of variation (CVs) for serum FBG, insulin, TG, cholesterol,
LDL, HDL, and CRP were 0.92, 6.1, 0.97, 2.8, 1.63, and 7.3,
respectively.
Statistical analysis
e statistical tests were performed using SPSS soware (version
20.0; Chicago, IL, UnitedStates). e Kolmogorov–Smirnov test was
used to test the normality of variable distributions. Quantitative
variables are expressed as the mean ± standard deviation (SD), and
categorized variables are reported as counts (percent). Baseline
characteristics and biochemical variables of the subjects were
compared using the student’s t-test and the chi-squared test for
quantitative and qualitative variables, respectively. A student’s paired
t-test was used to compare baseline and 10-week values of outcomes
within each group. To examine the eect of supplementation on
outcomes of interest, an analysis of covariance (ANCOVA) with
adjustment for the baseline value, age, sex, smoking, physical activity,
medications, and baseline BMI was used. All analyses were conducted
using the intention-to-treat (ITT) method. Missing values were
replaced by the single imputation method. Two-sided p values < 0.05
were considered statistically signicant.
Results
Participants flow
In this RCT, a total of 44 patients with T2D and overweight/
obesity were enrolled into two groups: the GCE supplementation
group (n = 22) and the placebo group (n = 22). During the 10-week
follow-up, four subjects in the placebo group and one subject in the
intervention group dropped out due to poor adherence to the
supplementation, side eects such as stomachaches, or being unwilling
to continue the study (Figure1). Finally, 39 subjects completed study,
but weanalyzed 44 patients using the ITT method. Patients had a
compliance rate of 88.6%. Wefound no major intervention-related
adverse eects in either groups during the study.
e baseline characteristics of the participants are shown in
Table1. e mean age of participants was 56.1 ± 6.20 years. Also, 41%
of participants were women. No signicant dierences were found
between the GCE and placebo groups in terms of age, BMI, smoking
status, or physical activity at baseline.
e dietary intake of participants is shown in Table 2. No
signicant dierences were observed in the dietary intake between the
GCE and placebo groups at the baseline of the trial. Also, no signicant
changes were observed in the dietary intakes between the two groups
aer 10 weeks, except for the percent of energy from saturated fatty
acid (SFA) consumption. Aer 10 weeks, subjects in the placebo group
consumed less SFA compared to the GCE group (8.22 ± 1.85 vs.
9.55 ± 1.54% of energ y).
Khalili-Moghadam et al. 10.3389/fnut.2023.1241844
Frontiers in Nutrition 04 frontiersin.org
Anthropometric and glycemic induces
Anthropometric and glycemic induces at baseline and aer
10 weeks of supplementation are reported in Table 3. Body weight
(p = 0.04) and BMI (p = 0.03) signicantly decreased in the GCE group
compared to the placebo group aer 10 weeks of supplementation. e
ITT analysis indicated patients in the GCE group had a lower FBG
concentration compared to the placebo group; however, this
decreasing was marginally signicant (8.48 ± 8.41 vs. 1.70 ± 5.82 mg/
dL, p = 0.05) than the placebo group. During the intervention, no
signicant dierence in insulin level (−6.23 ± 13.2 vs. −3.59 ± 6.28
μIU/dL, p = 0.20) and HOMA-IR (−2.84 ± 5.72 vs. −1.07 ± 2.46,
p = 0.08) was found between the two groups.
Blood pressure and lipid profile
Blood pressure and lipid prole at baseline and aer 10 weeks of
supplementation are reported in Table4. At the end of the study, GCE
signicantly reduced SBP (−5.56 ± 3.41 vs. −0.90 ± 2.67 mmHg,
p = 0.01), TG level (−49.7 ± 72.5 vs. −4.40 ± 98.6 mg/dL, p = 0.02), and
TG-to-HDL ratio (−1.40 ± 1.83 vs. 0.13 ± 2.12, p = 0.001), and
increased HDL level (3.22 ± 5.10 vs. 1.73 ± 6.10 mg/dL, p = 0.001)
compared to the placebo. Our trial indicated no eect of GCE on DBP,
LDL, or total cholesterol aer 10 weeks of supplementation.
Hs-CRP and MDA levels
Table5 shows hs-CRP and MDA concentrations at baseline and
end of the study in the GCE and placebo groups. During the
supplementation period, the hs-CRP level signicantly decreased in
the GCE group compared to the placebo group (p = 0.02). No
signicant changes were observed in the MDA level between the two
groups at the end of the study.
Discussion
In this RCT among participants with T2D and overweight/
obesity, GCE supplementation with doses of 800 mg/d for 10 weeks
led to a significant decrease in weight, BMI, SBP, HOMA-IR,
serum TG, and CRP levels, and a significant increase in serum
HDL levels. Our results did not show beneficial effects of GCE
supplementation on SBP and serum concentrations of insulin,
FIGURE1
Flow chart of study.
TABLE1 Baseline characteristics of the participants.
Variables Green
coee
group
(n = 22)
Placebo
group
(n = 22)
p-value
Age (year) 55.4 ± 6.68 56.7 ± 5.74 0.47
Female (%) 10 (45.5) 8 (36.4) 0.54
Smoking (yes) 6 (27.3) 4 (18.2) 0.47
Education level (%)
Under diploma 16 (72.7) 14 (63.6) 0.51
Diploma and over 6 (27.3) 8 (36.4)
Oral drugs (%)
Metformin 16 (72.7) 19 (86.4) 0.26
Glybencelamid 6 (27.3) 7 (31.8) 0.74
Statins 6 (27.3) 5 (22.3) 0.72
Physical activity
(MET-h/wk)
34.3 ± 3.95 35.3 ± 3.64 0.41
Data are presented as percent and mean ± standard deviation. p value is reported based on
independent t-test for continuous variables and chi-square for non-continuous variable.
Khalili-Moghadam et al. 10.3389/fnut.2023.1241844
Frontiers in Nutrition 05 frontiersin.org
total cholesterol, LDL, and MDA. Evidence has verified the safety
of the dose and duration of the GCE intervention. According to
the previous studies, which used a dosage of 400–1,000 mg/d with
a duration of 8–12 weeks, wechose this dose and duration in the
current study (25).
Anthropometric and lipid profile
Our results regarding body weight and BMI were in line with
ndings from previous studies (12, 26). In a trial of the eect of GCE
on body composition in women with obesity, GCE supplementation
(400 mg/d for 8 weeks) reduced body weight and BMI (12). Also, a
meta-analysis has reported that consumption of GCE with a dosage of
180–200 mg/d can lead to a weight loss of 2.5 kg. However, there was
a high heterogeneity (I
2
= 97%) between studies that made conclusions
with diculty (26) Green coee is a rich source of a natural
antioxidant known as CGA. erefore, the weight-lowering eect of
green coee may bedue to the CGA (27). CGA can contribute to body
weight loss through its anti-hyperlipidemia eects. In an animal
model, CGA can reduce cholesterol synthesis and increase fatty acid
oxidation by inhibiting β-hydroxy-β-methyl glutaric acyl-coenzyme
A reductase (28). ese mechanisms can explain the reduced eects
of GCE supplementation on lipid prole in this trial. Also, CGA has a
reducing eect on the deposition of fatty acids in the adipose tissue by
decreasing the serum insulin level, which leads to body weight loss
(12). In the current trial, GCE consumption caused a signicant
reduction and increase in TG and HDL levels, respectively. A trial on
subjects with obesity who consumed 1,000 mg/d of green coee for 6
weeks reported a signicant improvement in their lipid prole (15).
Similar to our ndings, in a RCT on patients with nonalcoholic fatty
liver disease (NAFLD) who consumed 400 mg of GCE for 8 weeks,
they observed a signicant increase in HDL levels (16). But this trial
did not detect any signicant eect of GCE on TG, LDL, or total
cholesterol compared to the placebo. However, in another trial on
subjects with metabolic syndrome, consumption of 400 mg GCE for
8 weeks had no improvement eect on lipid prole parameters (11).
Several mechanisms were proposed for the anti-lipogenic eect of
CGA. is phytochemical component has an inhibitory eect on
pancreatic lipase activity, which decreases fat absorption. In addition,
CGA has an increasing and decreasing eect on fatty acid oxidation
and fatty acid biosynthesis, respectively (8, 29, 30).
Glycemic indices
Our trial showed that GCE could decrease FBG compared to
the placebo; however this reduction was marginally signicant. But
this study did not detect any signicant eect of GCE on insulin
and HOMA-IR. Some of previous studies have reported dierent
results (11, 31). Roshan etal. (11) found that the subjects in the
GCE group (dosage of 800 mg/d and duration of 8 weeks) had
signicantly greater decreases in blood glucose and insulin
resistance compared to the placebo. In an animal study, GCE
treatment eectively reduced the FBG (dosage of 100 mg/kg and
duration of 6 weeks) compared to the placebo group in high-fat
diet (HFD)-induced obese mice (31). Also, in another animal
study, GCE (80 mg/d) resulted in attenuation of HFD-induced
insulin resistance aer 14 weeks (32). But, in line with our ndings
an HFD diet plus 0.5% w/w GCE in mice with metabolic syndrome
did not improve insulin resistance aer 12 weeks (33). A meta-
analysis that summarized the results from six interventional
studies reported that GCE has a reducing eect on blood glucose
(34). Also, this meta-analysis concluded that GCE has no eect on
insulin or HOMA-IR (34). Some reason can explain these slight
TABLE2 Dietary intake of participants at the baseline and after 10 weeks
supplementation.
Dietary
factors
Time Green
coee
group
(n = 22)
Placebo
group
(n = 22)
p-
valuea
Energy (kcal/d) Baseline 2,266 ± 232 2,186 ± 174 0.20
10 weeks 2,123 ± 243 2,109 ± 220 0.19
Carbohydrate
(% of energy)
Baseline 61.3 ± 4.55 58.2 ± 7.52 0.11
10 weeks 58.1 ± 3.81 59.9 ± 5.74 0.28
Protein (% of
energy)
Baseline 15.3 ± 1.61 14.9 ± 1.71 0.38
10 weeks 15.1 ± 2.71 15.7 ± 1.68 0.65
Fat (% of
energy)
Baseline 26.8 ± 4.77 30.3 ± 6.90 0.07
10 weeks 29.6 ± 5.44 27.5 ± 5.45 0.21
SFA (% of
energy)
Baseline 8.99 ± 2.93 9.58 ± 2.85 0.50
10 weeks 9.55 ± 1.54 8.22 ± 1.85 0.009
MUFA (% of
energy)
Baseline 9.91 ± 2.08 9.45 ± 2.48 0.51
10 weeks 10.3 ± 2.67 9.42 ± 2.31 0.21
PUFA (% of
energy)
Baseline 6.25 ± 2.09 5.67 ± 1.60 0.30
10 weeks 6.06 ± 2.43 6.15 ± 2.21 0.99
Fiber (g/d) Baseline 41.3 ± 12.07 39.1 ± 6.01 0.44
10 weeks 40.5 ± 12.3 39.3 ± 8.23 0.65
Cholesterol
(mg/d)
Baseline 200 ± 84.7 188 ± 66.9 0.59
10 weeks 198 ± 72.8 182 ± 86.5 0.43
Sodium (mg/d) Baseline 3,256 ± 1,021 3,358 ± 1,113 0.75
10 weeks 3,342 ± 1,284 2,885 ± 633 0.09
Magnesium
(mg/d)
Baseline 483 ± 95.9 446 ± 75.9 0.16
10 weeks 434 ± 98.1 455 ± 77.6 0.41
Potassium
(mg/d)
Baseline 4,534 ± 1,045 4,373 ± 840 0.57
10 weeks 4,183 ± 1,120 795 ± 193 0.93
Calcium (mg/d) Baseline 1,395 ± 402 1,331 ± 284 0.54
10 weeks 1,318 ± 512 1,245 ± 279 0.60
Selenium
(μg/d)
Baseline 111 ± 24.2 121 ± 29.6 0.22
10 weeks 105 ± 6.1 117 ± 6.7 0.18
Vitamin C
(mg/d)
Baseline 173 ± 55.4 146 ± 66.3 0.15
10 weeks 134 ± 12.2 142 ± 13.5 0.67
Vitamin E
(mg/d)
Baseline 10.3 ± 2.9 12.6 ± 7.7 0.20
10 weeks 10.6 ± 0.8 10.1 ± 0.8 0.68
Data are presented as mean ± standard deviation.
ap value is reported based on independent t-test for baseline values and ANCOVA test for
nal values.MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; SFA,
saturated fatty acids.
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TABLE3 Anthropometric and glycemic indices at baseline and after 10 weeks supplementation.
Variable Time Green coee group (n = 22) Placebo group (n = 22) p-valuea
Weight (kg) Baseline 75.8 ± 4.49 73.7 ± 4.40 0.04
10 weeks 73.3 ± 3.50c72.9 ± 3.75
Mean changes −2.62 ± 2.23 −0.72 ± 2.13
BMI (kg/m2)Baseline 27.9 ± 1.39 27.4 ± 1.25 0.03
10 weeks 26.9 ± 1.37c27.0 ± 1.15
Mean changes −1.01 ± 0.94 −0.3 ± 0.83
FBG (mg/dL) Baseline 141 ± 18.4 141 ± 12.9 0.05
10 weeks 132 ± 13.5c138 ± 11.8
Mean changes −8.48 ± 8.41 −1.70 ± 5.82
Insulin (μIU/dL) Baseline 17.7 ± 18.9 16.2 ± 9.27 0.20
10 weeks 11.5 ± 8.2b12.6 ± 4.12b
Mean changes −6.23 ± 13.2 −3.59 ± 6.28
HOMA-IR Baseline 6.76 ± 7.89 5.47 ± 3.98 0.08
10 weeks 3.92 ± 2.97b4.40 ± 1.80
Mean changes −2.84 ± 5.72 −1.07 ± 2.46
Data are presented as mean ± standard deviation.
ap value is reported based on ANCOVA test with adjustment for baseline values, age, sex, smoking, physical activity, medications, and baseline BMI.
bp value is reported based on paired t-test (p < 0.05).
cp value is reported based on paired t-test (p < 0.01).BMI, body mass index; FBG, fasting blood glucose; HOMA-IR, homeostatic model assessment for insulin resistance.
TABLE4 Blood pressure and lipid profile at baseline and after 10 weeks supplementation.
Variable Time Green coee group (n = 22) Placebo group (n = 22) p-valuea
SBP (mmHg) Baseline 130 ± 6.27 124 ± 5.67b0.01
10 weeks 125 ± 4.31d123 ± 4.41
Mean changes −5.56 ± 3.41 −0.90 ± 2.67
DBP (mmHg) Baseline 80.5 ± 6.37 78.4 ± 5.25 0.51
10 weeks 80.2 ± 5.13 77.8 ± 4.35
Mean changes −0.33 ± 2.77 −0.61 ± 2.58
Triglyceride (mg/dL) Baseline 187 ± 86.4 172 ± 109 0.02
10 weeks 138 ± 45.9 d168 ± 47.4
Mean changes −49.7 ± 72.5 −4.40 ± 98.6
Cholesterol (mg/dL) Baseline 176 ± 36.2 172 ± 40.9 0.34
10 weeks 173 ± 42.2 16 ± 45.5
Mean changes −3.93 ± 29.9 −10.6 ± 28.0
LDL (mg/dL) Baseline 171 ± 34.4 172 ± 40.9 0.50
10 weeks 154 ± 35.1c163 ± 45.6
Mean changes −17.1 ± 28.2 −9.78 ± 33.8
HDL (mg/dL) Baseline 42.5 ± 11.8 40.7 ± 7.83 0.001
10 weeks 45.7 ± 12.1d39.0 ± 5.39
Mean changes 3.22 ± 5.10 −1.73 ± 6.10
TG/HDL ratio Baseline 4.64 ± 2.31 4.29 ± 2.32 0.001
10 weeks 3.23 ± 1.34d4.42 ± 1.44
Mean changes −1.40 ± 1.83 0.13 ± 2.12
Data are presented as mean ± standard deviation.
ap value is reported based on ANCOVA test with adjustment for baseline values, age, sex, smoking, physical activity, medications, and baseline BMI.
bp value is reported based on independent t-test (p < 0.05).
cp value is reported based on paired t-test (p < 0.05).
dp value is reported based on paired t-test (p < 0.01).BMI, body mass index; DBP, diastolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; SBP, systolic blood
pressure.
Khalili-Moghadam et al. 10.3389/fnut.2023.1241844
Frontiers in Nutrition 07 frontiersin.org
contradictory results; the dierence in population study can beone
of the reasons for the inconsistency in the results. In current study,
weassessed the eects of GCE on diabetic patients, but previous
studies assessed the eects of GCE on dierent population. Also,
the dierence in the baseline FBG and insulin levels can beanother
reason for the inconsistency in the results. It is suggested that CGA
could improve FBG by activating AMP-activated protein kinase
(AMPK), and activation of this kinase consequently increased
glucose uptake in the cells by glucose transporter 4 (GLU4) fusion
with the plasma membrane (10). Also, CGA can inhibit the key
enzymes linked to the absorption of glucose (including pancreatic
amylase isoenzymes I and II, α-glucosidase, and α-amylase),
leading to postprandial blood glucose improvement (10).
Furthermore, CGA can decrease glucose production
(glycogenolysis and gluconeogenesis) by inhibiting the glucose-6-
phosphatase enzyme (35). It is thought that GCE lowers insulin
resistance by the activation of insulin receptor substrate-1 via
inhibiting c-Jun N-terminal kinase phosphorylation. is causes
GLUT4 translocation to the adipocyte membrane (36). Also, GCA
can decrease insulin resistance by activating the hepatic
proliferation-activated receptor α (PPAR-α), which facilitates the
clearing of lipids from the liver (9).
Hs-CRP and MDA levels
Our trial demonstrated that GCE administration for 10 weeks in
patients with T2D signicantly decreased CRP. Our results were in
agreement with a double-blind, placebo-controlled, randomized trial of
the eect of GCE on adult patients with non-alcoholic fatty liver disease
conducted by Shahmohammadi etal. (17). ey reported that GCE
supplementation has an improving eect on hs-CRP levels. But, in a
placebo-controlled double-blind pilot study on healthy men, GCE had
no eect on CRP compared to the placebo group (14). e inconsistent
results can bedue to dierences in the duration and dosage of the
intervention, sample size, and population. e main reason for this
inconsistency in the result can bedue to the dierence in population
study. In comparison with the previous study that has assessed the eects
Of GCE on healthy subjects, but weassessed the eects of GCE on
diabetic population, that these subjects have more inammation than
healthy subjects. is study was conducted only on men subjects, which
can beanother reason of inconsistency in the results. Also, all subjects in
the current study have higher BMI and age compared to the subjects of
previous study. A recent meta-analysis of eight trials found that GCE
supplementation (dosage 50–1,200 mg/d, duration of 8–12 weeks) has no
eect on CRP (19). However, based on the results of this meta-analysis,
GCE supplementation has a decreasing eect on tumor necrosis factor
alpha (TNF-α) as an inammatory biomarker (37). CGA, by increasing
the expression of genes encoding enzymes, including glutathione
peroxidase and superoxide dismutase, exerts reducing eects on
oxidative stress (8). Also, CGA has improved eects on inammation by
inhibiting the cytochrome P450 1A enzymes that increase the
pro-inammatory response in peripheral blood mononuclear cells (7).
Our ndings did not show a signicant eect of GCE on MDA levels
aer 10 weeks.
Study strengths and limitations
e randomized, placebo-controlled design was the main strength
of our study. However, using a xed dose of GCE and a short period
of intervention were the limitations of the current study. erefore,
additional studies with a large sample size, dierent dosages, and
longer durations are required to demonstrate the potential eects of
GCE in patients with T2D.
Conclusion
Based on the ndings of our study, GCE administration at a
dosage of 800 mg/d for 10 weeks in patients with T2D decreased SBP,
TG, and CRP and increased HDL compared to placebo. Moreover,
FBG reduction in GCE group was marginally signicant compared to
the placebo group. erefore, GCE may have a benecial eect on
lipid prole and inammation in patients with T2D.
Data availability statement
e original contributions presented in the study are included in
the article/supplementary material, further inquiries can bedirected
to the corresponding authors.
Ethics statement
e studies involving humans were approved by Faculty of
Nutrition and Food Technology, National Nutrition and Food
TABLE5 CRP and MDA at baseline and after 10 weeks supplementation.
Variable Green coee group (n = 22) Placebo group (n = 22) p-valuea
CRP (mg/L) Baseline 3.31 ± 2.41 2.69 ± 2.13 0.02
10 weeks 2.28 ± 1.46b2.88 ± 1.84
Mean changes −1.04 ± 1.21 0.18 ± 1.85
MDA (μmol/L) Baseline 1.44 ± 0.96 1.15 ± 0.59 0.18
10 weeks 1.19 ± 0.78 1.25 ± 0.59
Mean changes −0.25 ± 1.06 0.09 ± 0.67
Data are presented as mean ± standard deviation.
ap value is reported based on ANCOVA test with adjustment for baseline values, age, sex, smoking, physical activity, medications, and baseline BMI.
bp value is reported based on paired t-test (p < 0.01).BMI, body mass index; CRP, C-reactive protein; MDA, malondialdehyde.
Khalili-Moghadam et al. 10.3389/fnut.2023.1241844
Frontiers in Nutrition 08 frontiersin.org
Technology, Research Institute, Shahid Beheshti University of
Medical Sciences, Tehran, Iran. e studies were conducted in
accordance with the local legislation and institutional requirements.
e participants provided their written informed consent to
participate in this study.
Author contributions
SK-M and PM conceived and designed the study. SK-M, PM, and
MH contribute to data collection. SK-M and MG analyzed the data
and draed the initial manuscript. All authors contributed to the
article and approved the nal manuscript.
Acknowledgments
The authors gratefully wish to thank the National Nutrition
and Food Technology Research Institute, Shahid Beheshti
University of Medical Sciences, Tehran, Iran, for their study
funding and financial support. Wethank the laboratory section of
the Research Institute for Endocrine Science, Shahid Beheshti
University of Medical Sciences. Wealso thank all the patients who
participated in the study.
Conflict of interest
e authors declare that the research was conducted in the
absence of any commercial or nancial relationships that could
beconstrued as a potential conict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their aliated organizations,
or those of the publisher, the editors and the reviewers. Any product
that may be evaluated in this article, or claim that may be made by its
manufacturer, is not guaranteed or endorsed by the publisher.
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