Expresso coffee increases parasympathetic activity in young, healthy people

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Expresso coffee increases parasympathetic activity in young, healthy people M. Monda, An. Viggiano, C. Vicidomini, Al. Viggiano, T. Iannaccone, D. Tafuri, B. De Luca Department of Experimental Medicine, Section of Human Physiology, Clinical Dietetic Service, Second University of Naples, Naples, Italy

Caffeine induces modifications of activity of the autonomic nervous system. This study analyzed the effect of a cup of espresso coffee on the heart rate variability (HRV) power spectral analysis, which is a method providing evaluation of the sympathetic and parasympathetic discharge. In young, healthy sedentary subjects (10 male, 10 female; aged 25–30 years), the HRV-power spectrum was evaluated over a period of 150 min after the administration of espresso coffee (caffeine, 75 mg) or decaffeinated coffee (caffeine, < 18 mg) in supine and seated position. Absolute values of the spectrum were summed in low (LF) and high frequencies (HF). The LF and HF spectra were used to estimate the sympathetic and parasympathetic activity, respectively. In the supine position, coffee increases HF, while decaffeinated coffee causes little modifications of HF. In the seated position, HF is not modified by coffee or decaffeinated coffee. Coffee and decaffeinated coffee do not induce any modification of LF in both positions. This experiment indicates that espresso coffee influences parasympathetic activity in the supine position. Keywords: autonomic nervous system, caffeine, heart rate

Introduction The activity of the autonomic nervous system is influenced by food intake,1–3 indicating that there is an important relationship between eating behavior and vegetative asset.4–6 Heart rate variability (HRV) power spectral analysis is a well-accepted, useful, and noninvasive method, and has provided a comprehensive quantitative and qualitative evaluation of neuroautonomic function under various research and clinical settings.7–10 In general, power spectral analysis of HRV has shown at least two distinct regions of periodicity in electrocardiogram R-R intervals. The high-frequency (HF) component (> 0.15 Hz) is a major contributor to reflecting parasympathetic Correspondence to: Prof. Marcellino Monda, Dipartimento di Medicina Sperimentale, Fisiologia Umana, Servizio di Dietetica, Seconda Università di Napoli, Via Costantinopoli 16, 80138 Napoli, Italy. Tel: +39 815665804; Fax: +39 815667500; E-mail: [email protected] Received 18 April 2008, revised manuscript accepted 3 October 2008

© W. S. Maney & Son Ltd 2009 DOI 10.1179/147683009X388841

nervous system activity, and the low-frequency (LF) component (< 0.15 Hz) is associated with both sympathetic and parasympathetic activities.11,12 Unlike invasive measurements such as plasma catecholamine concentration, catecholamine turnover, and muscle sympathetic nerve activity, the HRV power spectral analysis lightens the burden imposed on subjects during an experiment and is a suitable and valuable approach to evaluate vegetative activity in large-scale of research. Caffeine is the most widely consumed drug in the world; it is found in foods such as coffee, tea, cocoa and cola. The caffeine content of a cup of coffee ranges from 58 mg to 259 mg, while the caffeine content of a cup of decaffeinated coffee is less than 18 mg.13 The main pharmacological effects of caffeine include a variety of stimulatory effects upon the central nervous system; caffeine increases respiratory rate, bronchodilatation, lipolysis, and diuresis. It can cause gastrointestinal disturbances, tremor, headache,

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insomnia, palpitations and, sometimes, even cardiac arrhythmias;14–16 it has been suggested that caffeine may be potentially hypertensive.17 Caffeine is a natural alkaloid methylxanthine. Some 99% is absorbed after oral ingestion, the blood concentration peaks 1–1.5 h after ingestion, and its half-life in adults is 3–6 h. Caffeine is metabolized by the cytochrome P450 hepatic enzyme system. Espresso is the main type of coffee drunk in most of southern Europe. It is also popular throughout much of the rest of Europe and in Argentina, Brazil, and Cuba, and urban centers in North America, Australia, and New Zealand. Espresso is a coffee beverage brewed by forcing steam or very hot water under high pressure through finely ground, darkly roasted, coffee beans. Caffeine ingestion, in a beverage at a dose of 240 mg, enhances modulation of parasympathetic nerve activity.18 Pills containing 400 mg of caffeine increases LF/HF ratios during sleep.19 Capsules of caffeine (300 mg) induce an increment of LF during endurance exercise in healthy subjects,20 while caffeine consumption (capsules of 250 mg twice daily for 2 weeks) modifies HRV, as a consequence of enhanced parasympathetic activity with a concomitant reduction in sympathetic activity.21 Although the above mentioned investigations indicate that caffeine ingestion at a dose of 240–400 mg (as beverage, pills or capsules) causes modifications in the HRV, there are no scientific papers regarding the effects on HRV exerted by a cup of espresso coffee, which has a lower dose of caffeine (about 75 mg).13,22 The aim of this study was to test the modification induced by this beverage on the autonomic nervous system.

Subjects and methods Subjects Sedentary subjects (10 male and 10 female; 25–30 years of age) were enrolled at the Clinical Dietetic Service at Second University of Naples, Italy, with height and weight ranging from 1.60–1.65 m and 58–62 kg, respectively, so that the sample was homogeneous. Volunteers were defined as ‘sedentary’ when they had not performed sport or intense physical activity for the last 3 years. Informed consent was provided by all participants. The study was approved by the Human Ethical Review Committee of the Second University of Naples. The subjects in this study were healthy and weight stable during the last 3 months. All individuals were non-smokers, non-alcohol-drinkers and moderate coffee drinkers (2–3 cups of espresso coffee for day).

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Each subject had a normal physical examination with regular blood pressure. Participants fasted overnight for at least 12 h. Measurements were conducted between 8 am and 10 am. Before commencement of the measurements, subjects rested quietly for 30 min. The respiratory frequency was constant at 12–14 breaths/min. Each subject was asked to avoid consumption of coffee, tea, chocolate and cola and to report all foods on a food diary for 2 days before the experiment. Analysis of diaries revealed that the foods affecting the metabolism of caffeine had been excluded. Experimental HRV-power spectral analysis was evaluated first in the supine and then in the seated position before (baseline period) and for 150 min after drinking an espresso coffee (about 75 mg caffeine; Tris Caffè, Italy) or a decaffeinated espresso coffee (< 18 mg caffeine; Tris Caffè, Italy). The constitution of two types of beverage is the same, except for the concentration of caffeine. Decaffeination drastically reduces only the concentration of caffeine, leaving other substances intact, as reported in the manu facturer’s label. Subjects remained seated during the 5 min pause between the recording sessions. Blood pressure was also measured before and every 30 min for 150 min after drinking the appropriate beverage. Each subject repeated the experiment on two different days, at least 7 days apart, using coffee on one day and decaffeinated coffee on the other day. The subjects were unaware of which of the two drinks was used in each session. The HRV-power spectrum analysis was evaluated on 5-min long ECG recording. The ECG signal was acquired on a PC (at sampling frequency of 100 samples/s) with an electrocardiograph (Cardioline, delta1 plus, Italy) connected to the serial port of a PC; a custom software written with LabView (National Instruments, Texas) was used for data acquisition and analysis. All the R-waves were automatically recognized and all the R-R intervals were calculated. The R-Rintervals sequence was re-sampled to obtain a constanttime based signal (10 samples/s). The Fast Fourier Transform was then applied to this signal and visualized in the form of power spectrum. The absolute values of this spectrum were, finally, summed in the low frequency (LF) range (0.04–0.15 Hz), and in the high frequency (HF) range (0.15–0.40) range. LF and HF were the values used to estimate the sympathetic and parasympathetic activity.23,24 Statistical analysis Experimental values are presented as mean with 95% confidence intervals. Statistical analysis was performed

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with the analysis of variance with two factors and repeated measures on both factors; factors were treatment (2 levels) and time (13 levels). The analysis was computed with Systat software. Multiple comparisons were performed by Sceffe post hoc test.

Results Figure 1 reports values of HF in subjects after the administration of coffee or decaffeinated coffee. In the supine position, coffee induces an increase in HF values with a peak at 105 min, while decaffeinated coffee causes little modifications of HF. In the seated position, HF is not modified by the administration of coffee or decaffeinated coffee. The analysis of variance showed a significant effects for treatment [F(1,19) = 507; P < 0.01], for time [F(2,228) = 89; P < 0.01], and for treatment × time [F(12,228) = 24; P < 0.01]. The post hoc test showed that the ‘coffee supine-group’ was different from the ‘decaffeinated coffee supine group’ at 30–120 min.

Figure 2 Low-frequency (LF) power in supine or seated subjects after administration of a cup of espresso coffee or decaffeinated coffee at time 0

Figure 1 High-frequency (HF) power in supine or seated subjects after administration of a cup of espresso coffee or decaffeinated coffee at time 0. *Post-hoc test statistical difference (P < 0.05) between coffeegroup and decaffeinated-group in supine position

Figure 2 shows the values of LF in subjects after the administration of coffee or decaffeinated coffee. Coffee and decaffeinated coffee did not induce any modification of either supine or seated position. No statistical difference was noted. Examples of power spectra for a supine subject with pre- and post-ingestion of espresso coffee are reported in Figure 3, showing an increase of the black dark area (high frequency range, as expression of parasympathetic activity) after coffee administration. Examples of the power spectra for a supine subject with ingestion of decaffeinated coffee or for a seated subject with ingestion of coffee and decaffeinated coffee are not reported in the figures, because there were not differences between pre-ingestive and postingestive conditions. Figure 4 shows values of systolic blood pressure in subjects after the administration of coffee or decaffeinated coffee. Coffee and decaffeinated coffee did not induce any modification in either the supine or seated position. No statistical difference was noted. The values of diastolic blood pressure in subjects after the administration of coffee or decaffeinated

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Figure 3 Examples of power spectra for a supine subject with pre- and post-injection of espresso coffee. Pale grey area, low frequency (0.04–0.15 Hz); dark grey area, high frequency (0.15–0.40 Hz)

coffee are reported in Figure 5. Coffee and decaffeinated coffee did not induce any modification in either supine or seated position. No statistical difference was noted.

Discussion This study is the first to demonstrate that a cup of espresso coffee increases parasympathetic activity in young, healthy people in a supine position. In a seated position, the coffee does not cause any modification in parasympathetic discharge. This indicates that the seated position exerts an influence on the activity of the autonomic nervous system, which is not modified by a cup of coffee with about 75 mg of caffeine. Therefore, part of the observed effects derive from the position. The results of this investigation are consistent with findings obtained by Rauh et al.,23 who did not detect significant difference in HRV parameters up to 90 min after ingestion of 100 mg or 200 mg of caffeine. The novel finding of our experiment is the fact that the supine position can reveal the effects induced by a low

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Figure 4 Systolic blood pressure power in supine or seated subjects after administration of a cup of espresso coffee or decaffeinated coffee at time 0

dose of caffeine, which are masked in the seated position. On the other hand, the influence of caffeine on cardiac vagal activity could be an indirect effect, namely via baroreceptorial reflex, and this effect is more evident in the supine position. Hibino et al.18 demonstrated that there is a small change in the HRV-power spectral analysis after the intake of 240 mg of caffeine. In that work, the HRVpower spectral analysis was performed at regular intervals only in the supine position before and after caffeine or vehicle intake; the results were statistically significant only at a few points in the time series. Our result is consistent with that reported by Hibino et al.;18 moreover, we have shown that it is possible to improve the sensitivity of the method and to reveal the autonomic modifications induced by a very small dose of caffeine. The main differences in the protocol used here are: (i) the use of sedentary subjects; (ii) the exclusion of caffeine-containing foods for 2 days before the experimental session; (iii) the use of the Task Force24 recommendations for the HRV-power

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more than in the diastolic, blood pressure after caffeine administration,27 showing that caffeine influences not only the HRV,28 but also the blood pressure. Further experiments are needed to extend this non-hypertensive influence on blood pressure to older, healthy individuals or subjects with hypertension. On the other hand, the results of the present experiment are useful in the management of subjects with bradycardia. Although direct evidence is needed to demonstrate that a cup of espresso coffee can induce hypokinetic arrhythmia in susceptible people, this experiment suggests some caution in the use of espresso coffee for subjects with alteration of cardiac rhythm. Since subjects with vagal hyper-tone are more susceptible to alterations of cardiac rhythm,29 an increase in vagal tone induced by coffee could induce an arrhythmia. The findings of the present study demonstrate that the analysis of HRV is a useful method, which is also able to reveal small modifications in the autonomic nervous system activity. Indeed, a dose of 75 mg of caffeine induces parasympathetic changes that are revealed by the analysis of HRV, but not by other non-invasive methods such as blood pressure measurement. Figure 5 Diastolic blood pressure in supine or seated subjects after administration of a cup of espresso coffee or decaffeinated coffee at time 0

spectral analysis; and (iv) the study of HRV in both the supine and seated positions. The last point is probably the most relevant to reveal a prevalent sympathetic alteration (enhanced in the seated position) and/or parasympathetic alteration (enhanced in the supine position). The model presented in the present work is the closest to the habitual way and dose of daily caffeine intake (i.e. espresso coffee) in Southern Europe. Further studies are needed to describe the molecular mechanisms of these effects. Furthermore, this experiment shows that a cup of espresso coffee (75 mg of caffeine) does not modify blood pressure in young, healthy people, suggesting that this drink does not induce hypertensive effects. Our findings are in agreement with other literature data showing that habitual coffee consumption is unrelated to blood pressure.25 Conversely, Waring et al.26 showed that caffeine (300 mg) influences blood pressure in young adults under resting conditions. Exercise induces a significant elevation in the systolic,

Conclusions This study sheds further light on a complex issue regarding the effects of caffeine, a used and abused substance in human nutrition, on the activity of the autonomic nervous system.

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