383

Introduction

Coffee is a widely consumed beverage world-

wide. In addition to its stimulating action on the

central nervous system, caffeine, a major compo-

nent of coffee, has been demonstrated to exhibit

some pharmacological actions on the cardiovas-

cular system.1, 2) For example, caffeine acts as a

non-selective blocker of adenosine A1 and A2 re-

ceptors. Blockade of the A1 receptors by caffeine

accelerates the release of catecholamines from

sympathetic nerve endings, and blockade of A2

receptors inhibits the vasodilatory effect of ade-

nosine.1, 2) This suggests that caffeinated coffee

and beverages containing caffeine may affect

＊ 2600-1, Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan

Jpn J Pharm Health Care Sci40(7) 383―388 (2014)

Acute Effects of Caffeine on Blood Pressure and Heart Rate in Habitual and Non-Habitual Coffee Consumers: A Randomized, Double-Blind,

Placebo-Controlled Study

Akiyoshi Hara,＊ Hiroko Ohide, Kazuya Miyagawa, Tomoko Takeuchi, Yoshihiko Nakatani, Hidekatsu Yokoyama and Taku Amano

Department of Pharmaceutical Science, International University of Health and Welfare

Received April 11, 2014Accepted May 21, 2014

　Caffeine, a major component of coffee, exhibits pharmacological actions on the cardiovascular system. In the present study, we examined the acute effects of caffeine on blood pressure (BP) and heart rate (HR) and the influence of habitual coffee intake on cardiovascular responses to caffeine. In this double-blind, placebo-controlled study, 136 young normotensive Japanese subjects were randomized. The subjects were first divided into 84 non-habitual and 52 habitual coffee consumers and further subdivided into placebo and caffeine groups; in the placebo group they had a cup of decaffeinated coffee, whereas in the caffeine group they had a cup of caffeinated coffee. In non-habitual coffee consumers, the systolic and diastolic BP at 30, 60, and 90 min after coffee intake were significantly higher in the caffeine group than in the placebo group. However, the pressor effect of caffeine disappeared in habitual coffee consumers. The changes in HR after coffee intake were similar between the placebo and the caffeine groups in both consumers of coffee. These results suggest that a single cup of caffeinated coffee is capable of increasing BP, and that the acute pressor effect of caffeine is diminished by habitual coffee consumption.

　Key words ―― coffee, caffeine, blood pressure, heart rate, habitual consumption, double-blind study

Regular Article

blood pressure (BP) and cardiac function. Indeed,

several reports show that the acute intake of caf-

feine increases BP in humans, although with little

effect on heart rate (HR).1, 3-6) Other studies show

that similar acute pressor effects are obtained

with caffeinated coffee but not with decaffeinated

coffee.7-9) The acute effects of caffeine were most-

ly evaluated in non-habitual or light habitual cof-

fee consumers or in subjects after prolonged ab-

stinence from caffeinated beverages, because

repeated caffeine intake could develop tolerance

to the pressor effect of caffeine.1, 10) A few studies

have been performed in the United States and

Europe, to determine whether the acute pressor

effect of caffeine is actually affected by the

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Jpn J Pharm Health Care Sci

amount and frequency of daily coffee drinking.

Nevertheless, the results are controversial;

Casiglia et al 7) and Corti et al 11) have reported that

habitual coffee consumption reduces the acute

pressor effect of caffeine, a �nding not supported

by Lane et al.5) In addition, such a study has never

been conducted in Japan, a country where coffee

is one of the most popular beverages. Therefore,

in the present study, the acute effects of caffeine

on BP and HR in habitual coffee consumers are

compared with those in non-habitual coffee con-

sumers, in young Japanese subjects, using a ran-

domized, double-blind, placebo-controlled study.

Materials and Methods

1. Subjects

The study was conducted on 136 healthy nor-

motensive Japanese 3rd-year students (20–22

years old) in the department of pharmaceutical

sciences, International University of Health and

Welfare. All the subjects who gave informed con-

sent were required to fill a questionnaire docu-

menting their weekly caffeinated coffee consump-

tion. According to the information obtained from

the questionnaire, the subjects were divided into

two groups: 1) the non-habitual coffee consumers

(who have two or less than two cups of caffeinat-

ed coffee per week), 2) the habitual coffee con-

sumers (who have three or more than three cups

of caffeinated coffee per week). The former group

comprised 84 individuals and the latter 52. The

average number of coffee cups for the non-habit-

ual consumers was 0.5 ∓ 0.1 (mean ∓ SEM) cups

per week, and it was 5.3 ∓ 0.2 (mean ∓ SEM)

cups per week for the habitual consumers.

2. Study design and protocol

All subjects abstained from caffeinated bever-

ages such as coffee, green tea, tea, and cola, for

12 hours before the study that began at 2:00 pm.

Each of the non-habitual and the habitual coffee

consumers were subdivided randomly into two

groups: placebo and caffeine groups. The subjects

in the placebo group had one cup of decaffeinated

instant coffee (Gold blend red label®, Nestle,

Kobe, Japan), and the subjects in the caffeine

group had one cup of caffeinated instant coffee

(Gold blend®, Nestle, Kobe, Japan). For the caf-

feinated drink, granules of caffeinated coffee (2.5

g) were dissolved in hot water (150 mL), while

for the decaffeinated drink, granules of decaffein-

ated coffee (2.5 g) were dissolved in hot water

(150 mL). All subjects were allowed to add sugar

and/or milk in their drinks. Before and 30, 60,

and 90 min after the decaffeinated or caffeinated

coffee intake, systolic blood pressure (SBP), dia-

stolic blood pressure (DBP), and HR were mea-

sured at the left upper arm, using a cuff-type au-

tomated oscillometric BP monitor (model HEM-

706, Omron, Kyoto, Japan), and a mean of three

readings was calculated.

3. Statistical analysis

Data of SBP, DBP, and HR were analyzed

blindly by the operator using a personal computer.

Statistical analysis was performed with an analysis

of variance, followed by unpaired Student’s t-test

for comparisons at each time point. A difference

was considered statistically signi�cant if P < 0.05.

All values are expressed as means ∓ SEM.

Results

1. Acute effects of caffeine in the non-ha-

bitual coffee consumers

Before the coffee intake, there were no signi�-

cant differences in the values of SBP, DBP, and

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Vol 40，No 7（2014）

HR between the placebo and caffeine groups in

the non-habitual coffee consumers (Table 1). The

changes in these parameters after decaffeinated or

caffeinated coffee intake are shown in Fig 1. In

the placebo group, all SBP, DBP and HR values

gradually decreased after decaffeinated coffee in-

take. In the caffeine group, however, BP did not

decrease after caffeinated coffee intake, and both

SBP and DBP were significantly higher when

compared with those in the placebo group, sug-

gesting that caffeine produces an acute pressor ef-

fect in the non-habitual coffee consumers. The

pressor effect appeared at 30 min and reached a

maximum at 90 min (at the end of the study),

when SBP and DBP in the caffeine group were

about 7 and 3 mmHg higher than those in the pla-

cebo group, respectively. Nevertheless, the change

in HR after coffee intake was not different be-

tween placebo and caffeine groups. These results

indicate that drinking caffeinated beverage in-

creases both SBP and DBP without changing HR

in the non-habitual caffeine consumers.

2. Acute effects of caffeine in the habitual

coffee consumers

In the habitual coffee consumers, there were no

signi�cant differences in the SBP, DBP, and HR

values between placebo and caffeine groups, be-

fore starting the experiment (Table 1). The

changes in these parameters after decaffeinated

and caffeinated coffee intake are shown in Fig 2.

In both placebo and caffeine groups, SBP, DBP,

and HR decreased after the coffee intake, the

same way as in the placebo group in the non-ha-

bitual coffee consumers. The SBP and DBP in the

caffeine group were not different from those in

the placebo group during the whole course of the

study after the coffee intake, suggesting that the

acute pressor effect of caffeine is diminished in

the habitual coffee consumers. The change in HR

after coffee intake in the caffeine group was simi-

lar to that of the placebo group, suggesting that

caffeine does not have any effect on HR regard-

less if the coffee consumer is habitual or non-ha-

bitual.

Discussion

The purpose of the present study is to examine

whether there is a difference in the acute effects

of caffeine intake on BP and HR between the ha-

bitual and the non-habitual caffeine consumers.

The randomized, double-blind, placebo-controlled

study was performed in young normotensive

Japanese, and was conducted in habitual and in

non-habitual caffeine consumers. The results

clearly show that SBP and DBP after intake of

caffeinated coffee are significantly higher than

Table 1　 Values of SBP, DBP and HR before intake of decaffeinated coffee (placebo group) and caffeinated coffee (caffeine group) in non-habitual and habitual consumers of coffee

Non-habitual consumers Habitual consumers

placebo group caffeine group placebo group caffeine group

No. of subjects 40 44 24 28

No. of Male/Female 12/28 21/23 17/7 18/10

SBP (mmHg) 109.3 ∓ 1.8 111.3 ∓ 2.1 115.5 ∓ 3.3 112.1 ∓ 2.3

DBP (mmHg) 65.8 ∓ 1.3 65.6 ∓ 1.2 68.3 ∓ 1.9 66.9 ∓ 1.3

HR (beats/min) 81.1 ∓ 1.8 85.8 ∓ 2.3 84.5 ∓ 3.5 84.5 ∓ 2.9

Each value represents the mean ∓ SEM. Numbers of male and female subjects are also shown.

386

Jpn J Pharm Health Care Sci

those after intake of decaffeinated coffee in the

non-habitual coffee consumers. We have previ-

ously observed that similar pressor effects are ob-

tained with caffeine-containing decaffeinated cof-

fee (which is obtained by the addition of caffeine

powder to decaffeinated instant coffee) but not

with caffeine-free decaffeinated coffee (Ohide H,

Miyagawa K, Nakatani Y, Takeuchi T, Yokoyama

H, Amano T, Hara A. Applied practice for mea-

surement of blood pressure in International Uni-

versity of Health and Welfare (4th Report): In�u-

ences of habitual drinking of coffee and teas on

the acute pressor effect of caffeine. Abstract of

the 132nd Annual Meeting of the Pharmaceutical

Society of Japan 2012, 4, 340.), supporting that

the pressor effects of coffee are primarily caused

by caffeine. Therefore, the above �ndings in the

present study suggest that caffeine intake acutely

increases SBP and DBP in the non-habitual cof-

fee consumers. In habitual coffee consumers,

however, caffeine intake increased neither SBP

nor DBP. These findings agree with the results

obtained by other investigators,7,11) and disagree

with a report in which habitual coffee consump-

tion does not attenuate the pressor effect of caf-

feine.5)

Similar studies have shown that acute caffeine

intake exerts a significant pressor action, with a

Fig 1　 Changes in SBP, DBP, and HR after decaffeinated coffee (placebo group ○) and caffeinated coffee (caffeine group ●) intake in non-habitual coffee consumers

Each value represents the mean ∓ SEM (n = 40 for the placebo group and 44 for the caffeine group). ＊P < 0.05 compared with the placebo group.

Fig 2　 Changes in SBP, DBP, and HR after decaffeinated coffee (placebo group ○) and caffeinated coffee (caffeine group ●) intake in habitual coffee consumers

Each value represents the mean ∓ SEM (n = 24 for the placebo group and 28 for the caffeine group). ＊P < 0.05 compared with the placebo group.

387

Vol 40，No 7（2014）

little or no effect on HR, in the non-habitual or

light habitual consumers of caffeine or after pro-

longed abstinence from caffeinated beverages.1,3-6)

These studies also show that BP usually rises

within 30 min, and the maximum increase occurs

60–120 min after the oral intake of caffeine.1, 3, 4)

The peak plasma concentrations of caffeine are

obtained within 60–90 min after oral intake of

caffeinated coffee or caffeine.4, 11, 12) These �ndings

are consistent with the time-course changes in BP

after acute intake of caffeinated coffee in the

present study, in which BP increased within 30

min and reached its maximum at 90 min (at the

end of the study) after the caffeinated coffee in-

take.

According to a review summarized by Nurminen

et al,1) 200–250 mg of caffeine increases SBP by

3–14 mmHg and DBP by 4–13 mmHg, and two

cups of caffeinated coffee increases SBP by 3–5

mmHg and DBP by 4–11 mmHg. The results of

the present study showed that even a smaller

amount of caffeine (one cup of instant coffee con-

tains about 70 mg of caffeine13)) causes a compa-

rable pressor effect in the non-habitual coffee

consumers; it increased SBP and DBP by a maxi-

mum of 7 and 3 mmHg, respectively. The pressor

effects of caffeine are more pronounced in older

subjects compared to young subjects,1, 3) and in

hypertensive subjects compared to normotensive

subjects.1, 6) However, our study shows that caf-

feine is effective in increasing BP even at small

amounts and even in young normotensive sub-

jects, when given to non-habitual coffee consum-

ers.

In the present study, 67％ of the habitual coffee

consumers were male subjects, and 61％ of the

non-habitual coffee consumers were female. It is

unlikely, however, that this sex disproportion in

the subjects is responsible for the differences in

BP responses to caffeine between non-habitual

and habitual coffee consumers, because no sex

difference were previously found for the pressor

effects of caffeine.1, 14) Alternatively, the disap-

pearance of the pressor effect in habitual coffee

consumers may be due to tolerance to caffeine, as

demonstrated by previous reports,1, 12) although the

underlying mechanism of tolerance remains un-

clear. According to the studies that targeted the

chronic (long-term) effects, repeated intake of

caffeine has either no effect or a decreasing effect

on BP.1,10) In addition, recent epidemiological

studies have demonstrated that regular intake of

coffee does not increase the risk of cardiovascular

events, such as hypertension, coronary heart dis-

ease and stroke, because of the development of

tolerance.15-18) Nevertheless, frequency and amount

of habitual caffeine consumption needed to devel-

op tolerance are not fully understand. Other

sources of caffeine, such as green tea, tea, or cola,

are also widely consumed in Japan, and it also re-

mains to be determined whether habitual con-

sumption of these beverages affects the pressor

response after caffeinated coffee intake. Further

studies are needed to understand the relationship

between the acute pressor effect and habitual caf-

feine consumption.

We conclude that a single cup of caffeinated

coffee is capable of increasing BP in young nor-

motensive Japanese subjects, and that the acute

pressor effect of caffeine is reduced by habitual

coffee consumption. Therefore, it should be noted

that intake of caffeinated beverages, including

coffee, may disturb the measurement of BP if the

measurement is made within a few hours after the

drinking, especially in the non-habitual caffeine

consumers.

388

Jpn J Pharm Health Care Sci

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