Journal of Human Hypertension (2014), 1–5

& 2014 Macmillan Publishers Limited All rights reserved 0950-9240/14

www.nature.com/jhh

REVIEW
The effect of chlorogenic acid on blood pressure: a systematic
review and meta-analysis of randomized clinical trials
IJ Onakpoya1, EA Spencer1, MJ Thompson1,2 and CJ Heneghan1

Several dietary supplements are currently marketed for management of hypertension, but the evidence for effectiveness is
conflicting. Our objective was to critically appraise and evaluate the evidence for the effectiveness of chlorogenic acids (CGAs) on
blood pressure, using data from published randomized clinical trials (RCTs). Electronic searches were conducted in Medline,
Embase, Amed, Cinahl and The Cochrane Library. We also hand-searched the bibliographies of all retrieved articles. Two reviewers
independently determined the eligibility of studies and extracted the data. The reporting quality of all included studies was
assessed by the use of a quality assessment checklist adapted from the Consolidated Standard of Reporting Trials Statement.
Disagreements were resolved through discussion. Seven eligible studies were identified, and five including 364 participants were
included. There were variations in the reporting quality of the included RCTs. Meta-analysis revealed a statistically significant
reduction in systolic blood pressure in favour of CGA (mean difference (MD):  4.31 mm Hg; 95% confidence interval (CI):  5.60 to
 3.01; I2 ¼ 65%; Po0.00001). Meta-analysis also showed a significant reduction in diastolic blood pressure favouring CGA (MD:
 3.68 mm Hg; 95% CI:  3.91 to  3.45; I2 ¼ 97%; Po0.00001). All studies reported no adverse events. In conclusion, the evidence
from published RCTs suggests that CGA intake causes statistically significant reductions in systolic and diastolic blood pressures.
The size of the effect is moderate. Few clinical trials have been conducted; they vary in design and methodology and are confined
to Asian populations and funded by CGA manufacturers. Large independent trials evaluating the effects of CGA on blood pressure
are warranted.

Journal of Human Hypertension advance online publication, 19 June 2014; doi:10.1038/jhh.2014.46

INTRODUCTION extract is marketed as a weight loss supplement under a variety of

Hypertension is a leading cause of death and a major risk factor
for cardiovascular disease.1 Although more than 90% of
hypertensive cases are idiopathic,2 dietary and lifestyle factors
are major risk factors associated with its increasing incidence.3,4
Several dietary supplements are currently marketed for the
management of hypertension, but the evidence for effectiveness
is conflicting.5 One such supplement thought to have an
antihypertensive effect is chlorogenic acid (CGA).
CGAs are naturally occurring compounds, which are found in
green coffee extracts, that is, unroasted coffee beans.6 The
traditional method of extracting green coffee from green coffee
bean involves the use of alcohol as a solvent.7 Green coffee
extracts are rich in CGA, and this group of polyphenols are
believed to be responsible for the biological actions of green
coffee. There are four main classes of CGA in green coffee namely:
3-, 4- and 5-caffeoylquinic acids (3-, 4- and 5-CQA), 3,4-, 3,5- and
4,5-dicaffeoylquinic acids (3,4-, 3,5- and 4,5-diCQA), 3-, 4-,
and 5-feruloylquinic acids (3-, 4- and 5-FQA), and 3-, 4- and
5-p-coumaroylqunic acids (3-, 4- and 5-p-CoQA).8
CGAs have been postulated to decrease glucose absorption
in the intestines through inhibition of glucose 6 phosphatase
and decreasing the sodium gradient of apical cells.9 In vitro and
animal studies have shown that CGA modulates the activities
of hepatic and pancreatic lipases,10,11 actions which could
lead to an inhibition of fat accumulation and stimulation of
lipid metabolism.12,13 Thus extracted CGA-enriched green coffee
brand names such as ‘Coffee Slender’ and ‘Svetol’.
CGAs are also thought to possess properties beneficial for blood
pressure control. They have been hypothesized to have antiox-
idant activity, demonstrated by their ability to scavenge free
radicals in vitro, and increase the antioxidant capacity of plasma
in vivo.14,15 Animal studies have demonstrated that CGAs improve
endothelial function and reduce blood pressure by enhancing
acetylcholine-induced endothelium-dependent vasodilation,16,17
and randomized studies in healthy human volunteers have shown
that CGA could modulate blood pressure possibly by promoting
the effects of nitric oxide and by reducing blood homocysteine
levels.18,19
Clinical trials examining the effects of CGAs on blood pressure
have been conducted, and a recent traditional review concluded
that dietary intake of CGA could be beneficial for blood pressure
management.20 Our objective in this review was to critically
appraise and evaluate the evidence for the effectiveness of CGA
on blood pressure, using data from published randomized clinical
trials (RCTs).
MATERIALS AND METHODS
We conducted electronic searches in five major English databases:
Medline, Embase, Amed, Cinahl and The Cochrane Library. Each database
was searched from inception to October 2013. The MeSH terms used
included hypertension, hypertens*, antihypertens*, antihypertens*, blood

1
University of Oxford, Nuffield Department of Primary Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, UK and 2Department of Family Medicine,
University of Washington, Seattle, WA, USA. Correspondence: Dr IJ Onakpoya, University of Oxford, Nuffield Department of Primary Care Health Sciences, New Radcliffe House,
Radcliffe Observatory Quarter, Oxford, Oxfordshire OX2 6GG, UK.
E-mail: igho.onakpoya@phc.ox.ac.uk
Received 7 February 2014; revised 15 April 2014; accepted 12 May 2014
 Onakpoya et al./chlorogenic acids and blood pressure
IJ Onakpoya et al
2
pressure, green coffee, green coffee extract, CGA, caffeic acid, ferulic acid,
and derivatives of these (a Medline search strategy has been included as a
web supplement; Supplementary Appendix 1). We also searched Google
Scholar for relevant conference proceedings using the search terms
‘chlorogenic acid’ and ‘conference’, and hand-searched the bibliographies
of all retrieved articles. No age, gender or language restrictions were
imposed.
Only double-blinded RCTs were included in this review. To be
considered for inclusion, RCTs had to test the effectiveness of orally
administered CGA supplement against placebos or identical controls for
blood pressure reduction in participants with or without hypertension.
Studies had to report blood pressure as outcome measures, and must have
had at least four weeks of intervention because the study findings may
have implications for public health.21 Studies were included irrespective of
lifestyle modification incorporated into the trial. Studies in which CGA was
combined with other supplements for blood pressure management were
excluded from the review.
Two reviewers (IJO and EAS) independently determined the eligibility of
studies. Data extracted by two reviewers (IJO and EAS) included patient
characteristics, interventions and results. The reporting quality of all
included studies was assessed by the use of a quality assessment checklist
(Supplementary Appendix 2) of the Consolidated Standard of Reporting
Trials Statement.22 Disagreements were resolved through discussion.
The data were presented as means with standard deviations. Mean
changes in systolic and diastolic blood pressures were used as primary
endpoints to assess the differences between the CGA and placebo or
control groups. Using standard meta-analysis software (RevMan 5.0),23 we
generated a risk of bias graph, and computed mean differences (MDs) and
95% confidence intervals (CIs) for studies with sufficient data for statistical
pooling. The random-effects model was used for meta-analyses.24
Sensitivity analyses (analysing trials based on study design) were used to
test the robustness of overall analyses using the I2 statistic; values of 25, 50
and 75% indicated low, medium and high statistical heterogeneity,
respectively. Dose-effect correlations were used to examine the
relationship between the dosage of CGA and changes in blood pressure.
RESULTS
Our searches identified 83 non-duplicate citations from which
seven eligible studies were identified (Figure 1). Two trials were
excluded because their duration was less than 4 weeks.19,25 Five
trials18,26–29 including a total of 364 participants were included in
the review.
Four trials were of parallel design, whereas one27 was crossover.
There were variations in the reporting quality of the included RCTs
# of records # of additional records
identified through identified through other
database sources (n=0)
searching (n=107)
# of records after duplicates
removed (n= 83)
# of records # of records
screened (n=83) excluded (n=76)
# of full-text articles
excluded. with reasons
(n=2)
# of full-text articles Studies with duration
assessed for eligibility
less than four weeks: 2
(n=7)
# of studies included in
qualitative synthesis (n=5)
# of studies included in quantitative
synthesis (meta-analysis) (n=5)
Figure 1. Flow diagram showing the process for inclusion of studies
in the review.
Journal of Human Hypertension (2014) 1 – 5
(Figure 2). No RCT adequately reported randomization and
allocation techniques, but three RCTs (60%) reported adequate
blinding of study investigators and participants. No RCT clearly
reported how outcome assessments were blinded. There was no
evidence of selective outcome reporting across the RCTs, but only
two RCTs (40%) showed low risk of other biases. All RCTs were
conducted in two Asian countries (four in Japan, and one in India;
Table 1). Participants in three RCTs26,28,29 had mild hypertension,
whereas those in two18,27 were reported to have normal blood
pressure; one of which18 included participants with reduced
vasodilatory responses. The age of participants in these studies
ranged between 22 and 65 years, and the study duration ranged
from 4 to 26 weeks, with daily dosages of CGA varying from 25 to
1050 mg (Table 1).
Meta-analysis of the five RCTs (n ¼ 507; Figure 3) showed
a statistically significant reduction in systolic blood pressure in
the CGA group compared with placebo or controls (MD:
 4.31 mm Hg; 95% CI:  5.60 to  3.01; I2 ¼ 65%; Po0.00001).
A dose-effect plot showed a significant correlation between CGA
dose and reduction in systolic blood pressure (P ¼ 0.005; Figure 4).
Meta-analysis of three RCTs (n ¼ 415) with good evidence of
blinding of participants and personnel showed a significant
reduction in systolic blood pressure in favour of CGA (MD:
 3.20 mm Hg; 95% CI:  4.01 to  2.36; I2 ¼ 0%; Po0.00001).
Meta-analysis excluding the crossover study and participants with
normal blood pressure (n ¼ 423) also revealed a significant
reduction in systolic blood pressure favouring CGA (MD: 
3.71 mm Hg; 95% CI:  5.06 to  2.36; I2 ¼ 63%; Po0.00001).
Meta-analysis of the two RCTs with larger sample sizes (n ¼ 395)
showed a statistically significant reduction in systolic blood
pressure favouring CGA over placebo/controls (MD:  3.12; 95%
CI:  3.98 to  2.27; I2 ¼ 0%; Po0.00001).
Meta-analysis of the five RCTs (n ¼ 507; Figure 5) showed a
significant reduction in diastolic blood pressure favouring CGA
over placebo or controls (MD:  3.68 mm Hg; 95% CI:  3.91 to
 3.45; I2 ¼ 97%; Po0.00001). A dose-effect plot excluding two
outliers failed to show a significant association between CGA dose
and diastolic blood pressure reduction (r ¼ 0.6; P ¼ 0.1). Meta-
analysis of the RCTs excluding participants with normal blood
pressure (n ¼ 487) revealed a significant reduction in diastolic
blood pressure in favour of CGA (MD:  2.45 mm Hg; 95% CI:
 2.72 to  2.17; I2 ¼ 51%; Po0.00001). Meta-analysis of three
RCTs with parallel group design and excluding participants with
normal blood pressure (n ¼ 423) revealed a significant reduction in
diastolic blood pressure favouring CGA over placebo or controls
(MD:  2.51 mm Hg; 95% CI:  2.79 to  2.23; I2 ¼ 44%;
Po0.00001). Meta-analysis of the RCTs with larger sample sizes
(n ¼ 395) also showed a significant reduction in diastolic blood
pressure in favour of CGA (MD:  2.18 mm Hg; 95% CI:  2.54 to
 1.82; I2 ¼ 0%; Po0.00001).
No adverse events were observed in all the included studies,
and the compliance rate was at least 90%. In total, six drop-outs
were reported. Three studies26,28,29 were wholly funded by
manufacturers; one was part-funded by the manufacturer,27
whereas the funding source in one study was not specified.18
Participants in three RCTs18,26,29 did not change their lifestyle,
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias
0% 25% 50% 75% 100%
Low risk of bias Unclear risk of bias High risk of bias
Figure 2. Risk of bias graph.
& 2014 Macmillan Publishers Limited
 Onakpoya et al./chlorogenic acids and blood pressure
IJ Onakpoya et al
3
a
Table 1. Study characteristics of RCTs evaluating the effects of chlorogenic acid on blood pressure

Study Year Relevant Type of subjects Age Study Intervention Comparator Baseline BP Adverse Lifestyle Funding
Country outcome and sample size (years) duration and daily dose (mm Hg): events modification source
(weeks) of CGA CGA/control

Kozuma et al.b Blood Mildly 30–50 4 25, 50 and Soy soup SBP: 146±5/ None No change Manufacturer
(2005)26 pressure hypertensive 100 mg in soy 145.4±5.5 in dietary sponsored
Japan (117) soup DBP: lifestyle
92.5±2.7/
91.7±2.5
Ochiai et al. Blood Normotensive 34.8–37.2 26 125 ml drink Placebo SBP: None No change Not specified
(2004)18 pressure males (20) containing drink free of 115.1±15.5/ in dietary
Japan CGA 140 mg GCE 118.9±6.9 lifestyle
DBP:
69.5±7.9/
66.9±6.6
Vinson et al.c Blood Normotensive 22–46 22 700 and 700 mg of SBP: None Dietary and Part
(2012)27 pressure and 1050 mg green inert capsule 125.38±5.10 exercise sponsored by
India overweight coffee with DBP: counselling manufacturer
(16) CGA 45.9% 81.88±2.68
Watanabe Blood Mild essential 43–63 12 125 ml fruit 125 ml fruit SBP: 145±6/ None Weight Manufacturer
et al. (2006)28 pressure hypertension and vegetable and 147±5 reduction, sponsored
Japan (28) juice vegetable DBP: 91±2/ sodium
containing juice 90±4 reduction,
CGA 140 mg physical
activity
Yamaguchi Blood Mild essential 30–65 4 Test coffee Test coffee SBP: None No change Manufacturer
et al.b (2008)29 pressure hypertension containing 82, 143.6±8.3/ in dietary sponsored
Japan (183) 172 and 143.6±8.7 lifestyle
299 mg CGA DBP:
91.0±2.8/
91.6±2.8

Abbreviations: CGA, chlorogenic acid; DBP, diastolic blood pressure; GCE, green coffee extract; RCT, randomized clinical trial; SBP, systolic blood pressure.
a
Unless otherwise stated, blood pressure values have been reported as means with s.d. bStudies had three CGA intervention groups. cStudy had two CGA
intervention groups.

Chlorogenic acid Placebo Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Kozuma 2005 -3.2 4.6 29 -1.3 3 29 11.6% -1.90 [-3.90, 0.10]
Kozuma 2005 [1] -4.7 4.5 28 -1.3 3 29 11.6% -3.40 [-5.39, -1.41]
Kozuma 2005 [2] -5.6 4.2 31 -1.3 3 29 12.1% -4.30 [-6.14, -2.46]
Ochiai 2004 -4.6 4.9 10 -0.5 1.6 10 8.1% -4.10 [-7.29, -0.91]
Vinson 2012 -2.6 4.25 16 6 5.6 16 7.5% -8.50 [-11.94, -5.06]
Vinson 2012 [1] -0.5 4.9 16 6 5.6 16 7.1% -6.50 [-10.15, -2.85]
Watanabe 2006 -10 1.3 14 -2 4.6 14 10.0% -8.00 [-10.50, -5.50]
Yamaguchi 2008 -2.7 2.5 37 0 6.2 37 11.1% -2.70 [-4.85, -0.55]
Yamaguchi 2008 [1] -2.8 4.2 35 0 6.2 37 10.2% -2.80 [-5.23, -0.37]
Yamaguchi 2008 [2] -3.3 3.6 37 0 6.2 37 10.6% -3.30 [-5.61, -0.99]

Total (95% CI) 253 254 100.0% -4.31 [-5.60, -3.01]

Heterogeneity: Tau2 = 2.73; Chi2 = 25.54, df = 9 (P = 0.002); I2 = 65%
-10 -5 0 5 10
Test for overall effect: Z = 6.51 (P < 0.00001)
Favours chlorogenic acid Favours placebo/control

Figure 3. Effect of chlorogenic acid on systolic blood pressure (mm Hg).

whereas those in two RCTs27,28 had dietary and exercise
modifications.
DISCUSSION
Main findings
The results of our meta-analyses reveal that supplementation
with CGA results in a statistically significant reduction in systolic
blood pressure. Our results also show that CGA administration
causes small, statistically significant reductions in diastolic
blood pressure. The sizes of the effects appear moderate, and
the clinical relevance is modest at best. The results of the meta-
analysis should be interpreted with caution because of the
moderate-to-large statistical heterogeneity observed in the overall
analyses and the variation in the study designs and reporting
quality of the included studies. To our knowledge, this is the first
systematic review evaluating the effects of CGA on blood
pressure.
CGAs are involved in the suppression of macrophage infiltra-
tion, and thus may be involved in blood vessel remodelling.30 A
short-term RCT in humans demonstrated that acute ingestion of
CGA-enriched coffee resulted in significant reductions in both
systolic and diastolic blood pressures.25 There was evidence of
greater flow-mediated dilation and increase in plasma nitric oxide
concentration in the CGA group compared with controls, but
these did not reach statistical significance. Although it is unclear if
the effects could have reached significant levels with longer-term
consumption, our results corroborate the study findings on the
effects of CGA on blood pressure.

& 2014 Macmillan Publishers Limited Journal of Human Hypertension (2014) 1 – 5

 Onakpoya et al./chlorogenic acids and blood pressure
IJ Onakpoya et al
4
The reduction in systolic blood pressure of 4.1 mm Hg translates
to a 3.1% reduction from the baseline across studies, and the
decrease in diastolic blood pressure of 3.93 mm Hg equates to
4.6% reduction in these participants; 60% of whom had mild
hypertension. Although such reductions appear moderate, they
could prove a potentially useful tool in prevention of hypertension
if sustained over a longer period. However, due to the variation in
the methods applied to the different studies, the trueness of the
observed effect is debatable.
A majority of the studies had small sample sizes, which may
have biased the study results.31 A lack of clear reporting of
randomization and allocation concealment methods compromises
the internal validity of the included studies, and consequently
limits the firmness of the conclusions that can be drawn on the
effects of CGA on blood pressure.32 Similarly, the external validity
of the results is also limited as the results may apply only to
participants of Asian ethnicity.
The blood pressure reducing properties of CGA constituents—
caffeic or ferulic acid—have been studied in animals.33
Intravenous injections of these acids at concentrations of 2.5, 5
and 10 mmol kg  1 revealed that ferulic acid possessed the
stronger depressor effect. Human studies have demonstrated
that although there is inter-individual variability in the absorption
and pharmacokinetics, CGAs have a high bioavailability when
consumed orally.8,34,35 Though our dose-effect plots suggested
some association between daily CGA dosage and blood pressure
reduction, there is no established dosage at which CGAs generate
reductions in blood pressure.
9 replicated in individuals who are not of Asian descent. Finally, the
8
pressure reduction (mmHg)
The extent to which concomitant lifestyle adjustments influ-
enced the results seen in the meta-analyses is uncertain. Apart
from coffee, CGA is available in a wide variety of foods including
potatoes, fruits and peanuts; on the average, humans are thought
to consume approximately 1 g of CGA daily via food intake.16
Whether the extra amount of CGA consumed by trial participants
led to an enhancement of its effect on blood pressure is not clear.
The adverse event reports from the included studies suggest
that CGA is generally safe. In a previous report, CGA consumption
has been reported to increase plasma total homocysteine
concentration, which is a risk factor for coronary heart disease.19
Due to the small number of studies conducted in humans, and the
short duration of the interventions, we cannot be sure whether
consumption of CGA is entirely risk-free and more research is
needed.
Strength and limitations
This review has some strength. We used a comprehensive search
strategy to identify relevant studies. The results of all the
sensitivity analyses undertaken were in the same direction as
our overall analysis; analyses of only the large trials resulted in a
reduction in the observed heterogeneity, with no change in the
direction of the study results. However, we recognize several
limitations. We may not have found all RCTs evaluating the effects
of CGA on blood pressure, especially unpublished studies. Due to
the small number of studies included in the review, we could not
use a funnel plot to test for publication bias, and we could not
perform subgroup analyses. Furthermore, because all studies took
place in Asia, it is unclear whether the effects seen can be
studies identified in our review were largely funded by CGA

manufacturers, and this could also have biased the reporting of

7 outcomes.
Systolic blood

6
5 Research implications
4 Well-designed, independently-funded and adequately powered
3 RCTs and including participants of non-Asian descent evaluating
the effects of CGA on systolic and diastolic blood pressures are
2 needed. These trials should be of longer-term duration to allow for
1 monitoring of any adverse events associated with the ingestion of
CGA. Future investigators should adhere to standardized guide-
0
0 100 200 300 400 500 600 lines when reporting clinical trials results so as to minimize the risk
of bias in their studies. To better understand the biologic
Daily dose of CGA (mg)
mechanisms of CGA on blood pressure, well-designed studies
Figure 4. Scatter plot showing the relationship between daily CGA with longer duration examining the effects of CGA on flow-
dose and systolic blood pressure reduction. mediated dilatation and nitric oxide status in blood vessels are

Chlorogenic acid Placebo Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Kozuma 2005 -2.9 2.9 29 -0.8 3.1 29 9.8% -2.10 [-3.64, -0.56]
Kozuma 2005 [1] -3.2 3.2 28 -0.8 3.1 29 9.7% -2.40 [-4.04, -0.76]
Kozuma 2005 [2] -3.9 2.8 31 -0.8 3.1 29 9.9% -3.10 [-4.60, -1.60]
Ochiai 2004 -3.2 0.6 10 3.3 0.3 10 11.0% -6.50 [-6.92, -6.08]
Vinson 2012 1.38 6.73 16 0.88 2.73 16 6.4% 0.50 [-3.06, 4.06]
Vinson 2012 [1] -0.13 2.01 16 0.88 2.73 16 9.6% -1.01 [-2.67, 0.65]
Watanabe 2006 -7 0.6 14 -4 0.6 14 11.0% -3.00 [-3.44, -2.56]
Yamaguchi 2008 -2.7 1.52 37 -0.5 1.55 37 10.8% -2.20 [-2.90, -1.50]
Yamaguchi 2008 [1] -2.3 1.5 35 -0.5 1.55 37 10.8% -1.80 [-2.50, -1.10]
Yamaguchi 2008 [2] -2.8 1.24 37 -0.5 1.55 37 10.9% -2.30 [-2.94, -1.66]

Total (95% CI) 253 254 100.0% -2.54 [-3.93, -1.15]

Heterogeneity: Tau2 = 4.49; Chi2 = 270.31, df = 9 (P < 0.00001); I2 = 97%
Test for overall effect: Z = 3.59 (P = 0.0003) -10 -5 0 5 10
Favours chlorogenic acid Favours placebo/control

Figure 5. Effect of chlorogenic acid on diastolic blood pressure (mm Hg).

Journal of Human Hypertension (2014) 1 – 5 & 2014 Macmillan Publishers Limited


required. Research into the minimum effective dose of CGA, which
can generate reductions in blood pressure is also imperative.
CONCLUSION
The evidence from published RCTs suggests that CGA intake
causes statistically significant reductions in systolic and diastolic
blood pressures. The size of the effect of CGA is moderate and the
clinical relevance is uncertain. Few clinical trials have been
conducted; they vary in design and methodology and are all
confined to Asian population. Large independent trials evaluating
the effects of CGA on blood pressure are warranted.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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