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SYSTEMATIC REVIEWS AND META-ANALYSES
The effects of green coffee bean extract supplementation on lipid
profile in humans: A systematic review and meta-analysis of
randomized controlled trials
Feng Ding
a
, Baoping Ma
b
, Ali Nazary-Vannani
c
, Hamed Kord-Varkaneh
d
,
Somaye Fatahi
e
, Maria Papageorgiou
f
, Jamal Rahmani
d
, Faezeh Poursoleiman
d
,
Israel Júnior Borges do Nascimento
g
, Hui Li
b
, Dongyang Han
b
, Dongmei Wang
b,
*
a
Emergency Department, Harbin fifth hospital, Harbin, Heilongjiang, 150040, China
b
Cardiovascular Medicine Department, Harbin Fifth Hospital, Harbin, Heilongjiang, 150040, China
c
Department of Cellular and Molecular Nutrition, Students’Scientific Research Center (SSRC) School of Nutritional Sciences and Dietetics, Tehran
University of Medical Sciences, Iran
d
Department of Clinical Nutrition and Dietetics, Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of
Medical Sciences, Tehran, Iran
e
Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
f
Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, Geneva 14, Switzerland
g
University Hospital and School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Received 27 July 2019; received in revised form 30 September 2019; accepted 2 October 2019
Handling Editor: M. Pirro
Available online ---
KEYWORDS
Meta-analysis;
Green-coffee;
Lipid profile;
HDL;
LDL;
Triglyceride
Abstract Background and aim: This systematic review and meta-analysis aimed to assess the ef-
fects of green coffee bean extract (GCBE) supplementation on lipid profile in adults.
Methods and results: The PubMed/Medline, Scopus, Web of sciences, and Google Scholar were
systematically searched for randomized controlled trials available in English and published
before February 2019. The meta-analysis was conducted using fixed effects models, and
between-study heterogeneity was assessed by Cochran’s Q test and I
2
. A total of 17 effect sizes
were included in the meta-analysis. Combined effect sizes on serum total cholesterol concentra-
tions revealed significant effects of GCBE supplementation on serum total cholesterol [weighted
mean difference (WMD): 4.51 mg/dL, 95% confidence interval (CI): 6.89, 2.12, p<0.001],
low density lipoprotein-cholesterol (LDL-C) (WMD: 4.38 mg/dL, 95% CI: 6.44, 2.31,
p<0.001), and high density lipoprotein-cholesterol (HDL-C) (WMD: 2.63 mg/dL, 95% CI: 2.20,
3.07, p<0.001) compared to controls. Nevertheless, no significant changes were observed in
serum triglycerides levels (WMD: 4.34 mg/dL, 95% CI: 9.00, 0.32, pZ0.068).
Conclusion: The evidence from available studies suggests that the GCBE supplementation leads to
significant reductions in total cholesterol, HDL-C, and LDL-C levels, and has modest, but, non-
significant effects on triglycerides levels.
ª2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the
Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Feder-
ico II University. Published by Elsevier B.V. All rights reserved.
* Corresponding author.
E-mail address: dongmei_7683@sina.com (D. Wang).
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
https://doi.org/10.1016/j.numecd.2019.10.002
0939-4753/ª2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical
Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Nutrition, Metabolism & Cardiovascular Diseases (xxxx) xxx, xxx
Available online at www.sciencedirect.com
Nutrition, Metabolism & Cardiovascular Diseases
journal homepage: www.elsevier.com/locate/nmcd
Introduction
Dyslipidemia is characterized by elevated levels of total or
low-density lipoprotein cholesterol (LDL-C), triglycerides,
and/or low levels of high-density lipoprotein cholesterol
(HDL-C). Lipid profile is influenced by several factors
including genetics, lifestyle and dietary factors [1] and
although modifiable, dyslipidemia remains a leading risk
factor for metabolic syndrome and cardiovascular disease
such as coronary heart disease (CHD) [2,3]. According to
World Health Organization (WHO), 4 million deaths are
attributed to CHD worldwide per year [4], and 70% of pa-
tients with premature CHD symptoms demonstrate
abnormal lipid metabolism. Earlier work has demon-
strated that for every 10% reduction in serum total
cholesterol (TC) levels, there is a 15% decline in CHD-linked
mortality risk [5], highlighting the importance of dyslipi-
demia in CHD progression and the need to improve serum
lipids in patients with dyslipidaemia.
Currently, the prevention and first-line treatment of
dyslipidemia include dietary and lifestyle changes, along-
side pharmacotherapy [6]. For example, physical activity
and smoking cessation have well-established, beneficial
effects on the lipid profile of patients with dyslipidemia
[7,8] and were, therefore, cornerstones in the development
of international guidelines and recommendations for pa-
tients with abnormal lipid profile [9]. Moreover, in addi-
tion to dietary recommendations relevant to diet
composition, the use of several nutraceuticals is explored
as potential lipid-lowering strategies. Some nutraceutical
supplements have also been shown to exert positive ef-
fects on vascular function and cardiovascular disease risk
[10e14].
Green coffee bean extract (GCBE) is a supplement
extracted from raw coffee beans prior to fermentation and
roasting and has been suggested to have several health
benefits [15e17]. GSBE includes chlorogenic acid and
caffeine, which may explain at least some of its therapeutic
effects [18]. The efficacy of the effect of GCBE supple-
mentation on lipid profile is still inconclusive. Recent
clinical trial demonstrated that GCBE supplementation
decreased serum total cholesterol (TC), low density
lipoprotein-cholesterol (LDL-C) levels and plasma free
fatty acids in obese women [19 ]. In contrast, other in-
vestigations have failed to show an improvement in lipid
parameter measured in blood after supplementation of
GCBE [20,21].
As such, this systematic review and meta-analysis
aimed to review available randomized controlled trials
(RCTs) to assess the efficacy and doseeresponse relation-
ship of GCBE supplementation on parameters of lipid
profile.
Methods
This systematic review protocol has been established ac-
cording to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses Protocol (PRISMA-P) 2015
guidelines [22].
Search strategy
Four independent databases (PubMed/Medline, Scopus,
Web of Sciences and Google Scholar) were used to perform
literature search for identifying randomized clinical trials
which investigated the effects of GCBE supplements on
lipid profile and were published before February 2019.
Medical subject heading (MeSH) and non-MeSH terms
were used with the following keywords: “chlorogenic
acid”OR “green coffee”OR “green coffee extract”AND
“clinical trials”OR “cross-over Studies”OR “double-blind
method”OR “single-blind method”OR “random alloca-
tion”OR “RCT”OR “intervention studies”OR “interven-
tion”OR “controlled trial”OR “randomized”OR
“randomized”OR “random”OR “randomly”OR “placebo”
OR “assignment”. Furthermore, a manual search was
conducted on the reference lists to identify eligible articles
that may have been missed.
Eligibility criteria
Inclusion criteria were: (1) RCTs with crossover or parallel
study designs, (2) studies that were carried out in in-
dividuals aged 18 years old, (3) studies that reported
sufficient TC, and/or LDL-C, and/or TG, and/or HDL-C data
at baseline and follow-up in both GCBE supplementation
and control groups, and (4) studies that conducted an
intervention with any green coffee species.
Exclusion criteria were: (1) studies that were carried
out in children, pregnant women or animals, (2) studies
that were not RCTs, (3) studies that did not provide suffi-
cient information for the outcomes in GCBE or control
groups, (4) studies that evaluated the effects of GCBE
alongside other components, and (5) grey literature such
as conference papers, dissertations, and patents.
Data extraction
Two authors (A.N and H.K) selected studies independently
without being blinded to authors, institutions, journal name,
as well as trial results. Disagreements between authors
concerning study selection were solved through a third in-
dependent author (Y.Z). If there was an absence in data
reporting, the corresponding author was contacted via email
to obtain the required data. The following data was extracted
from each study: first author’s name, year of publication, age
and gender of subjects, trial duration, study location, type
and dosage of GCBE supplementation, study design, health
status of participants, number of participants in each group,
mean and standard deviation (SD) of outcome measures at
baseline, post-trial follow-up and/or changes in outcome
measures from baseline to the end of the study. If a study
reported multiple follow-ups throughout the study dura-
tion, only the most recent data was included.
Quality assessment
The Cochrane scoring system [22] was used to determine
the methodological quality and risk of bias in each of the
2 F. Ding et al.
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
Table 1 Characteristics of eligible studies.
Author, Country,
year
Clinical trial design Population Sex (percentage of
men)
Treatment
duration
Outcome n Study groups
Shekoufeh Salamat
et al. Iran, 2019
randomised double-
blind clinical trial/
parallel
patient with
dyslipidemia
Men 8 weeks TC,HDL-C, LDL-C, TG 34 Placebo
36 800 mg of decaffeinated GCBE with 50%
chlorogenic acid
Atsushi Suzuki et al.,
Japan, 2019
double-blinded,
placebo-controlled
pilot study
healthy Japanese men Men 2 weeks TC,HDL-C, LDL-C, TG 8 Placebo
8 100-mL of beverage contain (300 mg/
d CGA)
Hanieh Roshan et al.,
Iran, 2018
randomised double-
blind clinical trial/
parallel
patients with the
metabolic syndrome
Both (men:81%) 8 weeks TC,HDL-C, LDL-C, TG 22 Placebo
21 800 mg/d GCBE
Sara
Martínez_López
et al., Spain, 2018
randomized single-
blind clinical trial/
cross-over r
Hypercholesterolemic
subjects
Both (men:37%) 8 weeks TC,HDL-C, LDL-C, TG 27 Placebo
27 6 g/d coffee contain (445 mg CGA &
121 mg caffeine)
normocholesterolemic
subjects
Both (men:40%) 8 weeks TC,HDL-C, LDL-C, TG 25 Placebo
25 6 g/d coffee contain (445 mg CGA &
121 mg caffeine)
Satoko Fukagawa
et al., Japan, 2017
randomized single-
blind clinical trial/
cross-over
healthy women with
xerotic skin
Women 8 week TC,HDL-C, LDL-C, TG 26 Placebo
23 270 mg/d GCBE
Fatemeh Haidari
et al., Iran, 2017
randomised double-
blind clinical trial/
parallel
obese women Women 8 weeks TC,HDL-C, LDL-C, TG 34 Placebo
30 400 mg/d GCBE
Hedayat Allah
Shahmohammadi
et al., Iran, 2017
randomised double-
blind clinical trial/
parallel
Non-Alcoholic Fatty
Liver Disease
Both (NR) 8 weeks TC,HDL-C, LDL-C, TG 22 Placebo
22 1000 mg/d GCBE
Gloria M Agudelo-
Ochoa et al.
Colombia, 2016
controlled clinical
trial was single-
blinded
Healthy Adults Both (men:50%) 8 weeks TC,HDL-C, LDL-C, TG 25 Placebo
25 400 mL coffee/d contain (420 mg CGA)
25 400 mL coffee/d contain
(780 mg mg CGA)
Tae-Su Kim et al.
Korea, 2012
randomised double-
blind clinical trial/
parallel
Mildly Obese Women Women 8 weeks TC 10 Placebo
10 210 mg/d dextrin þ100 mg/
d GCBE(Chlorogenic acids Z29.4%,
Caffeine Z13.6%)
Park Ju Yeon et al.,
south Korea, 2008
randomised double-
blind clinical trial/
parallel
Overweight women women 8 weeks TC,HDL-C, LDL-C, TG 20 Placebo
23 200 mg/d GCBE
Ryuji OCHIAI et al.,
Japan, 2008
randomized,
placebo-controlled,
cross-over study
patients with essential
hypertension
Both (men:87%) 4 weeks TC,HDL-C, LDL-C, TG 15 Placebo
16 368 ml GCBE drink contain 598 mg/
d CGAs
Takuya Watanabe
et al., Japan, 2006
randomised double-
blind clinical trial/
parallel
adults with mild
hypertension
Both (men:39%) 12 weeks TC,HDL-C, LDL-C, TG 14 Placebo
14 125 mL/day fruit and vegetable juice
mixed with GCBE contain 140 mg/d CGA
Kazuya KOZUMA
et al., Japan,2005
randomised double-
blind clinical trial/
parallel
Mildly hypertensive
patient
Men 4 weeks TC,HDL-C, LDL-C, TG 29 Placebo
31 185 mg/d GCBE
28 93 mg/d GCBE
29 46 mg/d GCBE
GCBE: green coffee bean extract, CGA: Chlorogenic acids, TC: Total cholesterol, HDL-C: High-density lipoprotein cholesterol, LDL-C: Low-density lipoprotein cholesterol, TG: total glycerides, NR: not
reported.
Green coffee bean extract and lipid profile 3
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
included studies. Possible sources of bias in randomized
trials were assessed, including the random sequence
generation, the allocation concealment, the blinding of
study participants and personnel, the blinding of outcome
assessment, the incomplete outcome data, the selective
reporting, and other biases. Three scores of yes, no, and
unclear could be given to each before mentioned item,
which are referred as high risk, low risk, and unknown risk
respectively (Supplemental Table 1).
Data synthesis and statistical analysis
Mean change and standard deviation (SD) of the outcome
measures were used to estimate the mean difference be-
tween the intervention group and the control group at
follow-up. If data was reported in a different format,
standard calculations were performed to derive the mean
and SD [23,24]. For example, if the SD of the mean dif-
ference was not reported in the studies, it was calculated
using the following formula: SD
change
Zsquare root
[(SDbaseline2þSDfinal 2)-(2RSD
baseline
SD
final
)]. In
order to estimate effect sizes, the fixed effects model was
used and results were provided across weighted mean
difference (WMD) and 95% confidence intervals (CI). Sub-
group analyses were conducted to discover potential
sources of heterogeneity among the studies. Sensitivity
analysis was performed to discover the impact of each
study on the overall effect size by using the one-study
exclusion (leave-one-out) method. Publication bias were
assessed by means of visual calculation of funnel plots and
Egger’s tests [25]. If any publication bias was detected, it
was tested via the ‘trim and fill’approach [26]. All statis-
tical analyses were implemented using Stata software
(Stata Corp. College Station, Texas, USA).
Results
Study selection
The electronic search strategy retrieved a total of 1224
records, 806 of which were unique. After screening of the
title and abstract, 25 publications met our selection criteria
and underwent full-text review. After full-text assessment,
13 publications [17,19,20,27e35,38] with 17 studies were
included in this meta-analysis (Supplemental Fig. 1).
Characteristics of the included studies
The characteristics of the included studies are detailed in
Table 1. These studies were published between 2005 and
Overall (I-squared = 3.6%, p = 0.412)
Martínez-López et al.(b) (2018)
Suzuki et al. (2019)
M Agudelo-Ochoa et al.(a) (2016)
KOZUMA et al.(b) (2005)
ID
Watanabe et al. (2006)
Fukagawa et al. (2017)
Kim et al. (2012)
Shahmohammadi et al. (2017)
salamat et al. (2018)
Martínez-López et al.(a) (2018)
M Agudelo-Ochoa et al.(b) (2016)
KOZUMA et al.(c) (2005)
Yeon et al. (2008)
OCHIAI et al. (2004)
Haidari et al. (2017)
KOZUMA et al.(a) (2005)
Study
Roshan et al. (2017)
-4.51 (-6.90, -2.13)
-6.70 (-15.09, 1.69)
5.80 (-12.76, 24.36)
-2.00 (-14.49, 10.49)
-5.50 (-15.75, 4.75)
WMD (95% CI)
-15.00 (-33.67, 3.67)
-5.50 (-15.60, 4.60)
-0.10 (-21.61, 21.41)
-17.51 (-29.62, -5.40)
1.41 (-10.83, 13.65)
1.00 (-6.94, 8.94)
-4.00 (-15.95, 7.95)
-5.70 (-15.07, 3.67)
-0.05 (-13.74, 13.64)
-6.00 (-29.68, 17.68)
-7.00 (-11.12, -2.88)
5.90 (-4.08, 15.88)
0.02 (-16.05, 16.09)
100.00
8.09
1.65
3.65
5.42
Weight
1.63
5.58
1.23
3.88
3.80
9.02
3.99
6.48
3.04
1.02
33.59
5.71
%
2.21
-4.51 (-6.90, -2.13)
-6.70 (-15.09, 1.69)
5.80 (-12.76, 24.36)
-2.00 (-14.49, 10.49)
-5.50 (-15.75, 4.75)
WMD (95% CI)
-15.00 (-33.67, 3.67)
-5.50 (-15.60, 4.60)
-0.10 (-21.61, 21.41)
-17.51 (-29.62, -5.40)
1.41 (-10.83, 13.65)
1.00 (-6.94, 8.94)
-4.00 (-15.95, 7.95)
-5.70 (-15.07, 3.67)
-0.05 (-13.74, 13.64)
-6.00 (-29.68, 17.68)
-7.00 (-11.12, -2.88)
5.90 (-4.08, 15.88)
0.02 (-16.05, 16.09)
100.00
8.09
1.65
3.65
5.42
Weight
1.63
5.58
1.23
3.88
3.80
9.02
3.99
6.48
3.04
1.02
33.59
5.71
%
2.21
0-33.7 0 33.7
Figure 1 Forest plot of randomized controlled trials investigating the effects of green coffee administration on Total Cholesterol (TC).
4 F. Ding et al.
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
2019 (February) and were conducted in Iran [17,20,29,19],
South Korea [32,33], Spain [28], Colombia [31], and Japan
[27,30,34,35,36]. The follow-up period ranged from 2 to 12
weeks. The daily supplementation dose of green coffee
varied between 46 and 6000 mg. Apart from studies which
included both sexes, four trials were conducted in women
only [19,30,32,33] and six studies were performed in men
only [17,27,36]. The sample size of the RCTs ranged from 16
[27]to70[17,27]. Participants in the included studies were
healthy [27,28,31], obese/overweight individuals
[19,32,33] or patients with various comorbidities including
metabolic syndrome [20], non-alcoholic fatty liver disease
[29] and women with xerotic eczema [30], dyslipidemia
[17,28], and hypertension [35,36].
Meta-analysis results
Effect of GCBE supplementation on TC levels
In total, 776 participants were assessed across 17 studies
(cases Z387, controls Z389), which reported serum TC
levels as an outcome measure. Overall results from the
fixed effects model indicated that GCBE supplementation
administration resulted in significant change in TC levels
after GCBE supplementation (weight mean difference
(WMD): 4.51 mg/dL, 95% CI: 6.89, 2.12, p<0.001),
without significant heterogeneity among the studies
(I
2
Z3.6%, pZ0.412) (Fig. 1). In the subgroup analyses,
studies that explored GCBE supplementation dosages
400 mg (WMD: 5.27 mg/dL, 95% CI: 8.13, 2.41,
p<0.001), and had an intervention duration between 8
and 11 (WMD: 5.086 mg/dL, 95% CI: 7.787, 2.386,
p<0.001) resulted in a greater reduction in TC levels
(Supplementary Table 2).
Effect of GCBE supplementation on HDL-C levels
Serum HDL-C levels was assessed in 16 studies with a total
of 755 participants (case Z376 and control Z379).
Combined results from the fixed effects model indicated
that HDL-C levels did change significantly following GCBE
administration (WMD: 2.63 mg/dL, 95% CI: 2.20, 3.07,
p<0.001). The heterogeneity among the studies
(I
2
Z46.2%, pZ0.022) was moderate (Fig. 2) and could be
explained by intervention duration, GCBE dosage and
participants’characteristics (i.e., sex). Interestingly, in-
creases in HLD-C levels after green coffee consumption
was significant when GCBE supplementation dose was
400 mg (WMD: 2.76 mg/dL, 95% CI: 2.32, 3.21, p<0.001)
compared to lower supplementation doses (<400 mg)
(WMD: 0.663 mg/dL, 95% CI: 1.07, 2.39, pZ0.454).
Furthermore, interventions with longer supplementations
durations (8e11 weeks) (WMD: 2.75 mg/dL, 95% CI: 2.31,
3.19; p<0.001) and studies conducted in women green
Overall (I-squared = 46.2%, p = 0.022)
salamat et al. (2018)
Study
M Agudelo-Ochoa et al.(b) (2016)
M Agudelo-Ochoa et al.(a) (2016)
KOZUMA et al. (2005)
Martínez-López et al.(a) (2018)
KOZUMA et al. (2005)
Yeon et al. (2008)
Suzuki et al. (2019)
Fukagawa et al. (2017)
Shahmohammadi et al. (2017)
Haidari et al. (2017)
ID
KOZUMA et al. (2005)
Watanabe et al. (2006)
Martínez-López et al.(b) (2018)
OCHIAI et al. (2004)
Roshan et al. (2017)
2.64 (2.21, 3.07)
2.61 (-0.03, 5.25)
-1.30 (-5.54, 2.94)
-1.40 (-6.06, 3.26)
0.00 (-4.17, 4.17)
1.50 (-3.38, 6.38)
0.00 (-4.90, 4.90)
4.30 (0.86, 7.74)
1.20 (-4.67, 7.07)
-3.00 (-8.39, 2.39)
-0.67 (-4.23, 2.89)
3.00 (2.53, 3.47)
WMD (95% CI)
0.00 (-4.12, 4.12)
-5.00 (-15.14, 5.14)
3.30 (-1.92, 8.52)
-1.60 (-9.37, 6.17)
-0.05 (-3.13, 3.03)
100.00
2.67
%
1.04
0.86
1.08
0.78
0.78
1.58
0.54
0.64
1.47
84.29
Weight
1.10
0.18
0.69
0.31
1.98
2.64 (2.21, 3.07)
2.61 (-0.03, 5.25)
-1.30 (-5.54, 2.94)
-1.40 (-6.06, 3.26)
0.00 (-4.17, 4.17)
1.50 (-3.38, 6.38)
0.00 (-4.90, 4.90)
4.30 (0.86, 7.74)
1.20 (-4.67, 7.07)
-3.00 (-8.39, 2.39)
-0.67 (-4.23, 2.89)
3.00 (2.53, 3.47)
WMD (95% CI)
0.00 (-4.12, 4.12)
-5.00 (-15.14, 5.14)
3.30 (-1.92, 8.52)
-1.60 (-9.37, 6.17)
-0.05 (-3.13, 3.03)
100.00
2.67
%
1.04
0.86
1.08
0.78
0.78
1.58
0.54
0.64
1.47
84.29
Weight
1.10
0.18
0.69
0.31
1.98
0-15.1 0 15.1
Figure 2 Forest plot of randomized controlled trials investigating the effects of green coffee administration on HDL.
Green coffee bean extract and lipid profile 5
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
coffee administration resulted in a greater increasing in
HDL (WMD: 2.97 mg/dL, 95% CI: 2.51, 3.44, p<0.001).
Effect of GCBE supplementation on LDL-C levels
LDL-C levels were assessed in 16 studies with a total of 727
participants (cases Z363 and control Z364). Pooled re-
sults from the fixed effects model indicated that LDL-C
levels did change significantly after green coffee con-
sumption (WMD: 4.38 mg/dL, 95% CI: 6.44, 2.31,
p<0.001). There was moderate heterogeneity among
studies (I
2
Z38.3%, pZ0.060) (Fig. 3). In the subgroup
analyses, we found that intervention duration, GCBE sup-
plementation dosage and participants’sex largely
explained the observed heterogeneity. Similar to the TC
results, studies which i) used GCBE supplementation doses
400 mg (WMD: 4.89 mg/dL, 95% CI: 7.24, 2.53,
p<0.001), ii) had an intervention duration 12 weeks
(WMD: 11.931 mg/dL, 95% CI: 22.54, 1.32, pZ0.028),
and iii) were conducted in women (WMD: 8.026 mg/dL,
95% CI: 11.187, 4.866, p<0.001) resulted in greater
reduction in LDL-C levels.
Effect of GCBE supplementation on TG
A total of 16 studies, including 756 participants
(case Z377 and control Z379), investigated the effects of
GCBE on TG levels. Pooled results from the fixed effects
model indicated that TG levels did not change significantly
after GCBE consumption (WMD: 4.34 mg/dL, 95% CI:
9.00, 0.32, pZ0.068) and there was no significant het-
erogeneity among studies (I
2
Z1.3% %, pZ0.437) (Fig. 4).
Non-linear doseeresponse relationships between dose
and duration of GCBE supplementation and outcomes
Evaluation of the doseeresponse relationships between
dose and duration of GCBE supplementation and markers
of lipid metabolism, did not indicate significant associa-
tions based on treatment duration and GCBE dosage
(Fig. 5).
Sensitivity analysis
To assess the impact of each single study on the combined
effect size, we removed each trial from the analysis, step
by step and accounted for their individuality. We observed
no significant effects of any individual study on the com-
bined effect sizes of TC, LDL-C, TG or HDL-C levels.
Publication bias
Visual inspection of funnel plot demonstrated no evidence
of publication bias in the meta-analysis of GCBE supple-
mentation on TC, LDL-C and TG levels (Supplemental
Fig. 2). Egger’s linear regression test confirmed this
finding (TC: pZ0.331, LDL: pZ0.140 and TG: pZ0.424).
Overall (I-squared = 38.3%, p = 0.060)
Roshan et al. (2017)
ID
Study
Gloria M Agudelo-Ochoa (2016)
shekoufeh salamat (2018)
OCHIAI et al. (2004)
Sara Martínez-López (2018)
Watanabe et al. (2006)
KOZUMA et al.(b) (2005)
Fukagawa et al. (2017)
Yeon et al. (2008)
Atsushi Suzuki (2019)
Haidari et al. (2017)
KOZUMA et al.(c) (2005)
Gloria M Agudelo-Ochoa (2016)
Shahmohammadi et al. (2017)
Sara Martínez-López (2018)
KOZUMA et al.(a) (2005)
-4.38 (-6.45, -2.32)
0.00 (-11.00, 11.00)
WMD (95% CI)
-1.00 (-9.41, 7.41)
-8.28 (-18.46, 1.90)
-8.40 (-23.96, 7.16)
-3.50 (-11.45, 4.45)
-15.00 (-29.51, -0.49)
7.50 (-2.26, 17.26)
-3.30 (-12.93, 6.33)
-2.30 (-15.94, 11.34)
4.10 (-11.66, 19.86)
-9.00 (-12.45, -5.55)
-3.70 (-13.56, 6.16)
-3.00 (-11.55, 5.55)
3.31 (-4.65, 11.27)
0.70 (-6.61, 8.01)
-11.00 (-25.74, 3.74)
100.00
3.53
Weight
%
6.03
4.11
1.76
6.75
2.03
4.48
4.60
2.29
1.72
35.80
4.39
5.84
6.73
7.99
1.96
-4.38 (-6.45, -2.32)
0.00 (-11.00, 11.00)
WMD (95% CI)
-1.00 (-9.41, 7.41)
-8.28 (-18.46, 1.90)
-8.40 (-23.96, 7.16)
-3.50 (-11.45, 4.45)
-15.00 (-29.51, -0.49)
7.50 (-2.26, 17.26)
-3.30 (-12.93, 6.33)
-2.30 (-15.94, 11.34)
4.10 (-11.66, 19.86)
-9.00 (-12.45, -5.55)
-3.70 (-13.56, 6.16)
-3.00 (-11.55, 5.55)
3.31 (-4.65, 11.27)
0.70 (-6.61, 8.01)
-11.00 (-25.74, 3.74)
100.00
3.53
Weight
%
6.03
4.11
1.76
6.75
2.03
4.48
4.60
2.29
1.72
35.80
4.39
5.84
6.73
7.99
1.96
0-29.5 0 29.5
Figure 3 Forest plot of randomized controlled trials investigating the effects of green coffee extract supplementation on LDL-C.
6 F. Ding et al.
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
However, there was a significant publication bias in the
meta-analysis of GCBE supplementation on HDL-C levels
(Egger’s test: pZ0.000). The ‘trim and fill’sensitivity
method did not show any negative unpublished studies
that assessed HDL-C levels.
Discussion
In this meta-analysis of 17 randomized controlled trials,
subjects who received GCBE supplementation had signifi-
cantly lower total cholesterol (4.51 mg/dL), HDL-C
(2.63 mg/dL), and LDL-C (4.38 mg/dL) levels compared
to controls. We also observed modest improvements in TG
levels following GCBE administration, which, however, did
not reach statistical significance. Between-group compar-
isons by sex revealed that the lowering effects of GCBE
supplementation on LDL-C and TG levels and its positive
impact on HDL-C levels were significantly greater in
women. Greater lipid-lowering effects were also seen in
GCBE interventions which had a duration 8e11 weeks and
tested higher supplementation doses (400 mg/day).
Taken together, these findings suggest that GCBE supple-
mentation exerts some beneficial effects on lipid profile,
however, these effects appear to be dependent on partic-
ipants’characteristics and featured of the
supplementation.
The effect of green coffee on lipid profile may be
mediated by several possible mechanisms. GCBE contains
a significant amount of chlorogenic acid, which has been
shown to decrease total cholesterol levels in the serum/
liver by inhibiting the intestinal absorption, transfer, and
hepatic biosynthesis of lipids and cholesterol [37,38]. In
addition to these actions of chlorogenic acid on lipid
metabolism, experimental studies have shown that
chlorogenic acid may upregulate the expression of PPAR-a,
which, in turn, regulates the expression of major genes for
lipid and lipoprotein metabolism [38,39,40].
Indeed, the effects of chlorogenic acid on serum lipids
shown in previous clinical and preclinical studies appear
to be similar to those observed in the current meta-
analysis. For example, consumption of food enriched
with chlorogenic acid resulted in significant improvements
in lipids assessed in blood [20]. Another investigation
demonstrated that supplementation with chlorogenic acid
caused a significant reduction in serum free fatty acid, total
cholesterol, triglyceride, and a significant increase in HDL-
C levels in a rat model of dyslipidemia [29].
The moderate statistical heterogeneity estimated in the
analyses for HDL cholesterol may have been due to varia-
tions in participants’characteristics in the various RCTs.
The intervention duration, GCBE dosage and gender of
study participants could explain the heterogeneity. In
Overall (I-squared = 1.3%, p = 0.437)
Haidari et al. (2017)
KOZUMA et al.(b) (2005)
Watanabe et al. (2006)
Suzuki et al. (2019)
OCHIAI et al. (2004)
Martínez-López et al.(a) (2018)
salamat et al. (2018)
M Agudelo-Ochoa et al.(b) (2016)
M Agudelo-Ochoa et al.(a) (2016)
Shahmohammadi et al. (2017)
KOZUMA et al.(a) (2005)
ID
Roshan et al. (2017)
Fukagawa et al. (2017)
Martínez-López et al.(b) (2018)
KOZUMA et al.(c) (2005)
Yeon et al. (2008)
Study
-4.34 (-9.00, 0.32)
1.00 (-8.29, 10.29)
-2.40 (-24.71, 19.91)
8.00 (-59.04, 75.04)
-0.80 (-25.32, 23.72)
13.00 (-84.48, 110.48)
1.00 (-10.85, 12.85)
-9.25 (-30.49, 11.99)
-10.00 (-39.24, 19.24)
5.00 (-25.48, 35.48)
-35.36 (-55.02, -15.70)
-3.40 (-23.67, 16.87)
WMD (95% CI)
-15.94 (-44.32, 12.44)
-6.30 (-38.98, 26.38)
-3.70 (-16.21, 8.81)
1.50 (-18.06, 21.06)
-16.50 (-35.99, 2.99)
100.00
25.19
4.37
0.48
3.62
0.23
15.49
4.82
2.54
2.34
5.62
5.29
Weight
2.70
2.04
13.88
5.68
5.72
%
-4.34 (-9.00, 0.32)
1.00 (-8.29, 10.29)
-2.40 (-24.71, 19.91)
8.00 (-59.04, 75.04)
-0.80 (-25.32, 23.72)
13.00 (-84.48, 110.48)
1.00 (-10.85, 12.85)
-9.25 (-30.49, 11.99)
-10.00 (-39.24, 19.24)
5.00 (-25.48, 35.48)
-35.36 (-55.02, -15.70)
-3.40 (-23.67, 16.87)
WMD (95% CI)
-15.94 (-44.32, 12.44)
-6.30 (-38.98, 26.38)
-3.70 (-16.21, 8.81)
1.50 (-18.06, 21.06)
-16.50 (-35.99, 2.99)
100.00
25.19
4.37
0.48
3.62
0.23
15.49
4.82
2.54
2.34
5.62
5.29
Weight
2.70
2.04
13.88
5.68
5.72
%
0-110 0110
Figure 4 Forest plot of randomized controlled trials investigating the effects of green coffee extract supplementation on TG.
Green coffee bean extract and lipid profile 7
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
Coef.= -0.075 p= 0.135 Coef.= -0.397 p= 0.831
Coef.= -0.021 p= 0.061 Coef.= -4.468 p= 0.118
-30 -20 -10
010
0200 400 600 800 1000
Green coffee dosage (mg/day)
95% CI Predicted mean difference (mg/dl)
Mean difference (mg/dl)
TC
-20 -10
010 20
0 5 10 15
Treatment duration (weeks)
95% CI Predicted mean difference (mg/dl)
Mean difference (mg/dl)
TC
-4 -2 024
0200 400 600 800 1000
Green coffee dosage (mg/day)
95% CI Predicted mean diffe rence (mg/dl)
Mean difference (mg/dl)
HDL
-6 -4 -2 024
0 5 10 15
Treatment duration (weeks)
95% CI Pre dicted mean difference (mg/dl)
Mean difference (mg/ dl)
HDL
Coef.= -4.013 p= 0.201 Coef.= -2.61 p= 0.342
Coef.= -0.029 p= 0.686 Coef.= -7.13 p= 0.128
-20 -10
010 20
0200 400 600 800 1000
Green coffee dosage (mg/day)
95% CI Predicted mean difference (mg/dl)
Mean difference (mg/dl)
LDL
-
20
-
10
010 20
0 5 10 15
Treatment duration (weeks)
95% CI Predicted mean difference (mg/dl)
Mean difference (mg/ dl)
LDL
-
60
-
40
-
20
020
0200 400 600 800 1000
Green coffee dosage (mg/day)
95% CI Predicted mean difference (mg/dl)
Mean difference (mg/ dl)
TG
-
40
-
20
020 40
0 5 10 15
Treatment duration (weeks)
95% CI Predicted mean difference (mg/dl)
Mean difference (mg/dl)
TG
Figure 5 Non-linear dose-responses between green coffee extract supplementation and unstandardized mean difference in TC, HDL, LDL and TG.
The 95% CI is depicted in the shaded regions.
8 F. Ding et al.
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
addition, a small sample size in some of studies may have
contributed to this heterogeneity. Other studies have
already shown decreases in blood pressure in essential
hypertension [30,36,37], improvements in glycaemic con-
trol [20], and now significant decreases in total cholesterol.
It is worth mentioning that despite the overall benefi-
cial effects of GCBE on markers of lipid metabolism, an
elevation in LDL-C and reduction in HDL-C levels were
observed in three RCTs [30,36,37].The investigators in the
mentioned RCTs suggested that the adverse effects of GSBE
on serum lipids were probably related to the differences in
the coffee roasting methods and requires further research
[41,42]. Another explanation may be that chlorogenic acid
is subject to structural changes, such as oxidation, and,
degradation of this compound may differentially affect
serum markers of lipid metabolism [43]. Conversely, there
are some concerns about potential hepatotoxic effects of
green coffee extracts. In an earlier investigation, 2 g of
chlorogenic acid/day increased homocysteine concentra-
tions (risk factor for cardiovascular disease) in coffee
drinkers [34]. In that study, adverse events appeared,
when concentrated green coffee was consumed over a
week. Therefore, the potential risk for cardiovascular dis-
ease in humans may be due to the acute ingestion of
higher levels of chlorogenic acid for a short-term period.
A major strength of this meta-analysis is that multiple
subgroup analyses were performed to examine the po-
tential impact of supplementation (i.e, dose and inter-
vention duration) and participants’characteristics (i.e,sex,
baseline lipid profile) in the relationship between GCBE
supplementation and lipid profile. The presence of mod-
erate heterogeneity and the low numbers of RCTs in some
subgroup analyses are the main limitations of the present
study. Furthermore, the median study duration of 8 weeks
prevents authors from making conclusions about the
effectiveness of green coffee extracts in the longer-term.
Conclusion
The available evidence from studies suggests that supple-
mentation with green coffee extracts results in significant
reductions in total cholesterol, HDL-C, and LDL-C levels
and in modest, but non-significant, improvements in TG
levels.
Funding
No Funding.
Declaration of Competing Interest
The authors declare no conflict of interest.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.numecd.2019.10.002.
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10 F. Ding et al.
Please cite this article as: Ding F et al., The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic
review and meta-analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/
j.numecd.2019.10.002
