Topical Review

Section Editors: Armin J. Grau, MD, PhD, and George Howard, DrPH

Coffee, Tea, and Cocoa and Risk of Stroke

Susanna C. Larsson, PhD

offee, tea, and cocoa are important dietary sources of

polyphenols and have received much attention during the
past years because of their potential beneficial effects on cardiovascular health. The polyphenols in these beverages and
cocoa may reduce the risk of stroke through multiple mechanisms, including antihypertensive, hypocholesterolemic,
antioxidant, and anti-inflammatory effects as well as through
improvements of vascular endothelial function and insulin
sensitivity. This review summarizes the available evidence
from experimental studies, prospective studies, and metaanalyses of the potential role of coffee, tea, and cocoa in the
prevention of stroke.

Methods
References for this review were identified through a literature search
of the PubMed database through October 2013 by using the following search terms: coffee, tea, cocoa, chocolate, prospective study, cohort study, randomized trial, meta-analysis, review, stroke, cerebral
infarction, and cerebrovascular disease. Moreover, the reference lists
of pertinent publications were searched manually for further relevant
articles. Priority was given to systematic reviews and meta-analyses
published during the past 5 years. When >1 meta-analysis on the
same topic was available, the most recent publication was included
in the present review.

Coffee
Coffee is a complex beverage with hundreds of bioactive components
with potential adverse or beneficial effects on the cardiovascular system. The most abundant bioactive compounds in coffee are caffeine,
diterpenes (present in the oil), and polyphenols. The cardiovascular
effects of coffee drinking depend in part on coffee preparation method and individual characteristics (eg, hypertension and hyperlipidemia).13 There are 2 main methods of coffee preparation: filtered and
unfiltered. Filtered coffee, also known as drip-brewed coffee, is the
most common mode of preparation in the United States and involves
brewing the coffee through a paper filter. Unfiltered coffee, often
known as boiled coffee, do not use a filter and includes Scandinavian
boiled, French press, Turkish/Greek, and espresso coffees. Espresso
is often the base for other drinks, such as latte, cappuccino, macchiato, and caff Americano.
Caffeine is a stimulant that induces a transient increase in blood
pressure (BP). Findings from a meta-analysis of 5 randomized controlled trials (RCTs) of the acute effects of caffeine on BP in individuals with hypertension showed that intake of 200300 mg caffeine
(equivalent to 1.52 cups of coffee) produced a mean rise of 8.1
mmHg in systolic blood pressure and of 5.8 mmHg in diastolic blood
pressure (Table1).1 The increase in BP was observed in the first hour

after caffeine ingestion and lasted for 3 hours. However, a metaanalysis of 10 RCTs of the long-term effect of coffee consumption in
mainly healthy, normotensive individuals found no significant changes in systolic blood pressure or diastolic blood pressure (Table1).2
Prospective studies of habitual coffee consumption and risk of hypertension have yielded inconsistent results, with a positive association
found in 2 out of 4 studies.2 Tolerance to the effects of caffeine on BP
in some individuals may in part explain why the long-term effects
of coffee consumption differ from the short-term effects. Moreover,
other compounds present in coffee may counteract the BP-raising effect of caffeine. A study of 6 habitual and 9 nonhabitual coffee drinkers found that intravenous caffeine raised BP in both groups, whereas
coffee consumption increased BP in nonhabitual drinkers only.4
The diterpenes cafestol and kahweol have cholesterol-raising
properties.5 The diterpenes are extracted from the coffee beans by
hot water but are retained by a paper filter.5 Hence, unfiltered coffee,
particularly Scandinavian boiled and Turkish coffees, contains much
higher concentrations of diterpenes than filtered coffee, which only
contains negligible amounts.6 Espresso coffee contains intermediate
amounts.6 In a meta-analysis of 12 RCTs, including 1017 subjects,
consumption of unfiltered coffee significantly increased total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride
concentrations, whereas filtered coffee consumption produced a small
change in total cholesterol concentrations only (Table1).3 The metaanalysis further showed that those who had hyperlipidemia seemed to
be more sensitive to the cholesterol-raising effect of coffee.3
Coffee is rich in various polyphenols, most notably chlorogenic
acid (CGA), which possesses antioxidant activities in vitro.7 Studies
in animals have demonstrated that coffee and caffeic acid, a primary
CGA metabolite, can decrease lipid peroxidation, thus indicating
also an in vivo antioxidant activity.7 However, there is controversy on
whether chlorogenic acid and other polyphenols in coffee could suppress the oxidative modification of LDL particles in humans. Among
3 available studies on this topic, 2 studies reported a protective effect
of 1 cup of boiled8 or filtered coffee9 on LDL oxidation, whereas 1
study found neither short-term nor long-term effects of filtered coffee
consumption on lipid peroxidation.10 As opposed to caffeine, CGA
have been demonstrated to have antihypertensive effects,11,12 possibly
via nitric oxidemediated vasodilation.12 Results from an RCT of 23
healthy adults showed that CGA ingestion significantly reduced systolic blood pressure by 2.41 mmHg and diastolic blood pressure by
1.53 mmHg.11

Epidemiological Studies on Coffee and Stroke

In the past, coffee was generally viewed as a risk factor for cardiovascular disease. However, recent evidence suggests that moderate
coffee consumption may reduce stroke risk. Results from a metaanalysis of 11 prospective studies (published through January 2011)
involving 479689 participants and 10003 stroke cases showed a
nonlinear relationship between coffee consumption and stroke risk

From the Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Correspondence to Susanna C. Larsson, PhD, Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210,
SE-17177 Stockholm, Sweden. E-mail Susanna.Larsson@ki.se
(Stroke. 2014;45:309-314.)
2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org

DOI: 10.1161/STROKEAHA.113.003131

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309

310StrokeJanuary 2014
Table 1. Summary of Recent Meta-Analyses of RCTs of the Effects of Coffee or Caffeine Intake on Cardiometabolic Biomarkers
References

Interventions

Duration

Mesas et al,
20111

Coffee or caffeine
(200300 mg)

<60180 min

Steffen et al,
20122

Filtered, boiled,
instant, or
decaffeinated
coffee

416 wk

Cai et al, 20123

Filtered coffee

1479 d

Cai et al, 20123

Boiled/unfiltered
coffee

No. of
Trials

1479 d

Outcomes

Effects

Mean Change
(95% CI)

Heterogeneity
P Value

I2, %

SBP (mmHg)

8.14 (5.68, 10.61)

0.99

DBP (mmHg)

5.75 (4.09, 7.41)

0.57

10

SBP (mmHg)

0.55 (2.46, 1.36)

<0.001

72

10

DBP (mmHg)

0.45 (1.52, 0.61)

0.07

41

10

Total cholesterol
(mmol/L)*

0.09 (0.02, 0.17)

0.52

LDL cholesterol
(mmol/L)*

0.06 (0.03, 0.15)

0.35

10

Triglycerides
(mmol/L)*

0.04 (0.05, 0.13)

0.43

12

Total cholesterol
(mmol/L)*

0.33 (0.18, 0.49)

<0.0010

79

LDL cholesterol
(mmol/L)*

0.31 (0.08, 0.53)

0.002

73

Triglycerides
(mg/dL)*

0.21 (0.05, 0.37)

0.001

77

CI indicates confidence interval; DBP; diastolic blood pressure; LDL, low-density lipoprotein; RCTs, randomized controlled trials; and SBP; systolic blood pressure.
*Values were converted from mg/dL to mmol/L by dividing the levels of cholesterol (total, LDL, and HDL) by 38.67; triglyceride levels by 88.57; and glucose levels
by 18.02.

(Figure1).13 Compared with no coffee consumption, the overall relative risks (RRs; 95% CI) of total stroke were 0.87 (0.810.93) for 2,
0.84 (0.770.91) for 34, 0.88 (0.790.97) for 6, and 0.94 (0.801.10)
for 8 cups/d of coffee.13 Risk estimates were similar for ischemic and
hemorrhagic stroke and for men and women at lower levels of coffee
consumption (2 cups/d).13
Three prospective studies on coffee consumption and stroke1416 were
published since the meta-analysis. Two of them confirmed an inverse
association of moderate coffee consumption with stroke incidence14 or
mortality.15 Findings from a large prospective cohort of 229119 US
men and 173141 US women showed an inverse association between
moderate coffee consumption and stroke mortality.15 In men, the multivariable RRs (95% CI) of total stroke death were 0.99 (0.791.24) for
<1, 0.92 (0.731.15) for 1, 0.84 (0.681.02) for 23, 0.65 (0.510.84)
for 45, and 0.83 (0.611.14) for 6 cups/d compared with no coffee consumption (P for trend=0.003).15 In women, compared with no
coffee consumption, the RRs (95% CI) were 1.15 (0.911.45) for <1,
0.89 (0.701.13) for 1, 0.93 (0.751.15) for 23, 0.82 (0.621.09) for
45, and 0.84 (0.561.25) for 6 cups/d (P for trend=0.05).15 A prospective study of 82369 Japanese adults also observed an inverse association between moderate coffee consumption and stroke risk (RR,

Relative Risk (95% CI)

1.1

1.00 (ref.)
0.94

0.92

0.9

0.91
0.88

0.87
0.84

0.85

0.84

0.8

0.7

Coffee Consumption, cups/day

Figure 1. Relative risks of stroke by coffee consumption in prospective studies. The relative risks were extracted from the metaanalysis by Larsson and Orsini.13

0.81; 95% CI [0.720.91], for 2 cups/d versus none).14 No association

between caffeinated or decaffeinated coffee consumption and stroke
risk was observed in a prospective study of 42659 German adults, but
the number of cases was small (n=310).16 Coffee consumption is usually associated with a less health conscious diet and lifestyle. Although
most studies controlled for other dietary and lifestyle factors, residual
confounding may in part explain the inconsistent results. Furthermore,
because the relative composition of bioactive compounds in coffee varies by coffee preparation method, this could contribute to the heterogeneity among studies in different populations.

Green and Black Tea

Tea is the most frequently consumed beverage in the world after water. Tea is produced from the leaves of the plant Camellia sinensis and
can be classified by degree of fermentation: black tea (fermented),
predominantly consumed in Western countries; oolong tea (partially
fermented), primarily consumed in Southern China and Taiwan; and
green tea (unfermented), mainly consumed in Asia. All types of tea
are rich in various flavonoids. Catechins are the main flavonoids in
green tea, whereas black tea mainly contains condensed flavonoids,
such as theaflavins and thearubigins.17 Tea and tea-derived flavonoids
have been demonstrated to have a hypocholesterolemic effect and to
reduce the development of atherosclerosis in animal models.17,18 Tea
flavonoids can enhance nitric oxide status and improve endothelial
function, which could at least partly be responsible for the benefits of
tea on cardiovascular health.17,18
Studies in humans also indicate potential beneficial effects of consumption of green and black tea on cardiometabolic risk factors, including endothelial function (measured by flow-mediated dilatation),
blood pressure, and cholesterol and blood glucose concentrations
(Table2). The most consistent findings are for endothelial function.
In a meta-analysis of 9 RCTs (2 on green tea, 6 on black tea, and 1 on
both types of tea), involving 213 participants, the overall absolute increase in FMD of tea consumption (median daily dose of 500 mL tea,
equivalent to 23 cups) versus placebo was 2.6% of the arterial diameter.19 This is a relative improvement of 40% compared with the average FMD of 6.3% measured under placebo or baseline conditions.19
Results from a meta-analysis of 14 short-term (3 months) RCTs
showed that green tea consumption lowered total and LDL cholesterol

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Larsson Coffee, Tea, Cocoa, and Stroke 311

Table 2. Summary of Recent Meta-Analyses of RCTs of the Effects of Green and Black Tea Consumption on Cardiometabolic
Biomarkers
Interventions

Duration

No. of
Trials

Outcomes

Effects

Ras et al, 2011

Green or black tea

as a beverage

120 min4 wk

FMD (%)

Zheng et al,
201120

Green tea as a
beverage or green
tea extract

3 wk3 mo

14

Total cholesterol
(mmol/L)*

11

LDL cholesterol
(mmol/L)*

12

References
19

Hartley et al,
201321

Hartley et al,
201321

Liu et al, 201322

Zheng et al,
201323

Green tea as a
beverage or green
tea extract

Black tea extracts,

in tablet form or
as a drink

Green tea extract

or decaffeinated
green tea extract

Green tea extract

or decaffeinated
green tea extract

36 mo

36 mo

4 wk3 mo

324 wk

Mean Change
(95% CI)

Heterogeneity
P Value

I2, %

<0.001

75.8

0.19 (0.21,
0.16)

0.35

0.06 (0.08,
0.03)

0.20

25

HDL cholesterol
(mmol/L)*

0.006 (0.02,
0.03)

0.27

18

SBP (mmHg)

3.18 (5.25,
1.11)

0.72

DBP (mmHg)

3.42 (4.54,
2.30)

0.39

Total cholesterol
(mmol/L)

0.62 (0.77,
0.46)

0.28

21

LDL cholesterol
(mmol/L)

0.64 (0.77,
0.52)

0.33

13

HDL cholesterol
(mmol/L)

0.01 (0.08, 0.11)

0.18

39

Triglycerides
(mmol/L)

0.08 (0.24,
0.07)

0.41

SBP (mmHg)

1.85 (3.21,
0.48)

0.49

DBP (mmHg)

1.27 (3.06,
0.53)

0.53

Total cholesterol
(mmol/L)

NA

NA*

NA

84

LDL cholesterol
(mmol/L)

0.43 (0.56,
0.31)

0.22

33

HDL cholesterol
(mmol/L)

0.01 (0.06,
0.04)

0.20

36

Triglycerides
(mmol/L)

NA

NA*

NA

64

17

Fasting glucose
(mmol/L)

0.09 (0.15,
0.03)

0.73

13

Fasting insulin
(IU/mL)

1.16 (1.91,
0.40)

0.01

57

Hb A1c (%)

0.30 (0.37,
0.22)

0.10

44

HOMA-IR (units)

0.04 (0.67,
0.59)

0.13

44

22

Fasting glucose
(mmol/L)

0.08 (0.14,
0.02)

0.92

16

Fasting insulin
(U/mL)

0.04 (0.36, 0.45)

0.35

Hb A1c (%)

0.04 (0.15,
0.08)

0.12

40

HOMA-IR (units)

0.05 (0.37,
0.26)

0.31

16

2.6 (1.8, 3.3)

CI indicates confidence interval; DBP; diastolic blood pressure; FMD, flow-mediated dilation; Hb A1c, glycohemoglobin; HDL, high-density lipoprotein; HOMA-IR,
homeostatic model assessment index for insulin resistance; LDL, low-density lipoprotein; NA, not available; RCTs, randomized controlled trials; and SBP; systolic blood
pressure.
*Meta-analysis was not performed because of significant heterogeneity between the trials.
Values were converted from mg/dL to mmol/L by dividing by 38.67 for total cholesterol, LDL cholesterol, and HDL cholesterol; by 88.57 for triglycerides; and by
18.02 for glucose.

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312StrokeJanuary 2014
Table 3. Summary of Recent Meta-Analyses of RCTs of the Effects of Cocoa or Chocolate Consumption on Cardiometabolic
Biomarkers
References
Ried et al, 2012

Hooper et al,
201228

27

Interventions

Duration

No. of
Trials

Outcomes

Effects

Dark or milk
chocolate or
flavanol-rich
cocoa powder

28 wk*

20

SBP (mmHg)

19

DBP (mmHg)

Dark or milk
chocolate, cocoa
drinks, or cocoa
supplements

18 wk

Mean Change
(95% CI)

Heterogeneity
P Value

I2, %

2.77 (4.72,
0.82)

<0.001

83

2.20 (3.46,
0.93)

<0.001

70

SBP (mmHg),
acute

1.75 (6.27,
2.77)

NA

85

23

SBP (mmHg),
chronic

1.50 (3.43,
0.43)

NA

NA

DBP (mmHg),
acute

1.38 (4.14,
1.38)

NA

79

22

DBP (mmHg),
chronic

1.60 (2.77,
0.43)

NA

52

MAP (mmHg),
chronic

1.64 (3.27,
0.01)

NA

11

FMD (%), acute

3.19 (2.04, 4.33)

<0.001

84

11

FMD (%), chronic

1.34 (1.00, 1.68)

0.58

11

Fasting glucose
(mmol/L)

0.02 (0.22,
0.17)

0.02

54

Fasting insulin
(U/mL)

2.65 (4.65,
0.65)

0.50

Hb A1c (%)

0.02 (0.09, 0.14)

NA

NA

HOMA-IR (units)

0.67 (0.98,
0.36)

0.61

21

Total cholesterol
(mmol/L)

0.04 (0.11,
0.03)

NA

NA

21

LDL cholesterol
(mmol/L)

0.07 (0.13,
0.00)

NA

NA

21

HDL cholesterol
(mmol/L)

0.03 (0.00, 0.06)

NA

NA

22

Triglycerides
(mmol/L)

0.05 (0.09,
0.01)

NA

NA

10

C-reactive protein
(mg/L)

0.12 (0.42, 0.66)

NA

NA

CI indicates confidence interval; DBP; diastolic blood pressure; FMD, flow-mediated dilation; Hb A1c, glycohemoglobin; HDL, high-density lipoprotein; HOMA-IR,
homeostatic model assessment index for insulin resistance; LDL, low-density lipoprotein; MAP, mean arterial pressure; NA, not available; RCTs, randomized controlled
trials; and SBP; systolic blood pressure.
*One trial was 18 wk.
Acute effect: studies of 90150 min duration; chronic effect: studies of <3, 36, or 726 wk duration.

concentrations but had no effect on high-density lipoprotein cholesterol.20 In another meta-analysis of RCTs of 3 months duration, both
green and black tea consumption reduced LDL cholesterol concentrations as well as BP.21 With regard to glucose and insulin, 2 metaanalyses of several RCTs found that green tea consumption decreased
fasting blood glucose concentrations, whereas results for insulin and
hemoglobin A1c concentrations were inconsistent.22,23

Epidemiological Studies on Tea and Stroke

In a meta-analysis of 14 prospective studies of green or black tea
consumption, the overall RR of total stroke for a 3-cup/d increment
in tea consumption was 0.87 (95% CI, 0.810.94), with heterogeneity
among studies (P=0.006).24 There was no evidence of publication bias
(Egger test: P=0.85).24 The association was similar in men and women and among most subgroups, but was slightly stronger for green
tea (RR=0.83; 95% CI [0.720.96]; Pheterogeneity<0.01; n=5 studies)
than for black tea (RR=0.91; 95% CI [0.830.98]; Pheterogeneity=0.17;

n=13 studies).24 The heterogeneity may be because of differences in

types of tea, tea preparation methods (amounts of tea leaves, cup size,
brewing time, water temperatures, addition of milk or sugar, etc),
stroke measures, and analysis strategies.24
Two recent large prospective studies of green14 or black tea25 consumption confirmed a reduction in stroke risk associated with high
tea consumption. Results from a cohort of 82369 Japanese men and
women showed a significant 20% reduced risk of total stroke among
those who consumed 4 cups/d of green tea.14 In a cohort of 74961
Swedish men and women, consumption of 4 cups/d of black tea,
compared with no consumption, was associated with a significant
21% lower risk of total stroke.25 In both studies, the association was
similar for ischemic stroke and intracerebral hemorrhage.

Cacao Products
Cacao products, such as chocolate, are rich sources of flavonoids,
mainly flavan-3-ols (also referred to as flavanols), which are potent

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Larsson Coffee, Tea, Cocoa, and Stroke 313

Figure 2. Relative risks (RRs) of stroke for the highest versus lowest category of chocolate consumption in prospective studies. Squares represent the
study-specific RRs (size of the square indicates the
study-specific statistical weight, that is, the inverse
of the variance); the horizontal lines represent
95% confidence intervals (CIs); and the diamond
represents the overall RR estimate with its 95%
CI. Study-specific RRs were combined by using
a random effects model. The RRs were extracted
from the meta-analysis by Larsson et al.33 Heterogeneity test: I2=0%; P=0.47. COSM indicates Cohort
of Swedish Men33; EPIC, European Prospective
Investigation into Cancer31; IWHS, Iowa Womens
Health Study34; SHEEP, Stockholm Heart Epidemiology Program35; and SMC, Swedish Mammography
Cohort.32

antioxidant and anti-inflammatory compounds. Both the flavan-3-ol

content and the total antioxidant capacity in plasma increase after
cocoa consumption.26 Whether these effects are reduced when cocoa
is ingested with milk or when cocoa is consumed as milk chocolate
is controversial.26 Flavanols found in cocoa have also been shown to
increase the formation of endothelial nitric oxide, which promotes
vasodilation and thus blood pressure reduction.27
The potential benefits of cacao products on cardiovascular health
have been examined in several short-term RCTs, and results from
those trials have been summarized in meta-analyses. The overall results from 2 meta-analyses indicate that cocoa or chocolate intake
may modestly reduce systolic blood pressure27 and diastolic blood
pressure,27,28 but findings from individual trials were inconsistent
(Table3). A recent meta-analysis of 42 acute or short-term chronic
(18 weeks) RCTs found that cocoa or chocolate interventions significantly reduced fasting insulin concentrations, insulin resistance,
and mean arterial pressure as well as improved endothelial function
measured by FMD (Table3).28 Cocoa or chocolate consumption had
only marginally significant or no effects on blood concentrations of
cholesterol (total, LDL, and high-density lipoprotein), triglycerides,
glucose, hemoglobin A1c, and C-reactive protein.28 In a recent 1-year
trial comprising 93 postmenopausal women with type 2 diabetes mellitus, a combination of flavan-3-ols and isoflavones reduced LDL
cholesterol (0.1 mmol/L; P=0.04) and insulin (0.8 mU/L; P=0.02)
concentrations and the homeostatic model assessment index for insulin resistance (0.3; P=0.004).29
Several controlled intervention studies have found that flavanols
present in cocoa may improve platelet function. Based on data from
5 trials, Ostertag etal30 estimated that intake of 100 mg of flavanols
induces a 3% to 11% reduction in platelet aggregation.

Epidemiological Studies on Chocolate and Stroke

The few prospective studies of chocolate consumption in relation to
stroke risk have reported either a statistically significant3133 or a nonsignificant inverse association34,35 (Figure2). Results from a metaanalysis of those 5 studies (4 from Europe and 1 from the United
States) showed a significant 19% lower risk of stroke when comparing the highest with the lowest category of chocolate consumption
(Figure2) and a significant 14% reduction in stroke risk for a 50-g/
week increment in chocolate consumption, without heterogeneity
among studies.33 There was indication of potential publication bias in
the meta-analysis for the highest versus lowest category of chocolate
consumption (Egger test: P=0.03) but not in the doseresponse metaanalysis (Egger test: P=0.26).33

Summary
Current evidence from experimental studies in animals and
humans along with findings from prospective studies indicates
beneficial effects of green and black tea as well as chocolate

on cardiovascular health, and that tea and chocolate consumption may reduce the risk of stroke. The strongest evidence
exists for beneficial effects of tea and cocoa on endothelial
function, total and LDL cholesterol (tea only), and insulin
sensitivity (cocoa only). The majority of prospective studies
have reported a weak inverse association between moderate
consumption of coffee and risk of stroke. However, there are
yet no clear biological mechanisms whereby coffee might provide cardiovascular health benefits. Awaiting the results from
further long-term RCTs and prospective studies, moderate
consumption of filtered coffee, tea, and dark chocolate seems
prudent.

Disclosures
None.

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Key Words: cacao coffee diet flavonoids polyphenols risk
factors stroke tea

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Coffee, Tea, and Cocoa and Risk of Stroke

Susanna C. Larsson
Stroke. 2014;45:309-314; originally published online December 10, 2013;
doi: 10.1161/STROKEAHA.113.003131
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