Various foods are believed to affect autonomic nerve activity (Daly 1993, Fernstorm and Fernstorm 1984, Thelle 1993). Some herbal teas and coffee, for example, are consumed for their supposed ability to reduce stress or to energize. Coffee, in particular, is widely consumed both to induce wakefulness and to relax.

Many physiological variables have been considered for noninvasively detecting changes in autonomic nerve activity, e.g., body surface temperature, skin blood flow rate, blood pressure, response of the pupil to a flash of light and peripheral sweat measured by analyzing air sampled from the surface of the skin. However, few studies have reported the effects of foods on these variables, mainly because the signals of changes in autonomic functions following food intake are so small that it is difficult to measure them with high reproducibility. Moreover, the contributions of sympathetic and vagal activities to these variables have been difficult to evaluate separately.

To separately evaluate sympathetic nerve and vagal activity, an analysis of R-R intervals (the temporal durations between each heart beat) has been developed. The heart acts in a discrete fashion, with the successive heartbeats leading to a series of fluctuating values of R-R intervals and arterial systolic and diastolic pressures. In recent years, the possibility of quantifying these fluctuations or oscillations (particularly the variability of R-R intervals) by using computer techniques has been considered for human studies (Arai et al. 1989), deBoer et al. 1987, (Dixon et al. 1992, Moritani et al. 1993, Pagani et al. 1986, Pomeranz et al. 1985, Yamamoto et al. 1991). The time course of variability of R-R intervals is a wave form. A wave form can be considered to be constituted from some periodic frequency components by applying power spectral analysis (PSA),⁴ by which the relation between the frequency component included in wave forms and its magnitude is visualized as a spectral curve. Studies have demonstrated two major frequency components of heart rate variability (HRV): the high frequency, respiration-linked component (HC, >0.15 Hz) and the low frequency component (LC, <0.15 Hz). Pharmacological blockades of sympathetic or parasympathetic nerves and ganglionectomy experiments in animals indicate that the LC reflects mainly sympathetic activity and partly vagal activity. The HC generally is accepted as being modulated purely by vagal activity. Each magnitude is considered to be related to the degree of each autonomic activity (Akselrod et al. 1981 and 1985, Pagani et al. 1986, Pomeranz et al. 1985).

The present study was undertaken to investigate the possibility that PSA of HRV can be used to detect changes in autonomic nerve activity secondary to food intake. We used caffeine, which has many pharmacological properties, such as enhancing thermogenesis and the pressor effect, in this experiment.

SUBJECTS AND METHODS

Measurements were made in a quiet room with about 50% humidity and temperature of 21 ± 1°C. The subjects abstained from food, drink and exercise for the previous 3 h. Before measurements, the subjects were instructed to rest more than 15 min in the sitting position wearing an ear sensor in a quiet and relaxing atmosphere. Because respiration greatly influences HRV (Brown et al. 1993, Novak et al. 1993), subjects were instructed to breathe at a frequency of 1 breath/4 s (0.25 Hz) in synchrony with the sound of an electric metronome. The subjects breathed at comfortable tidal volume levels.

To avoid the influences of circadian rhythm, each measurement was taken between 1500 and 1600 h.

The R-R intervals were measured two to five times for each subject at rest (baseline values) and at timed intervals of 5-20 min after the test beverage was consumed. The subjects drank them within 2 min. Each measurement was made for 128 s in sitting subjects.

Sleepiness was estimated from the subjective report (5 = very wakeful, to 1 = very sleepy) of each volunteer in another test performed under the same conditions. Every 5 min, the subjects chose an appropriate grade that reflected their degree of sleepiness.

In addition to R-R intervals and subjective estimation of sleepiness, either blood pressure or surface body temperature was recorded. Either a blood pressure cuff or a thermometric probe was placed on the upper left arm. The subjects were instructed to drink the beverage within 4 min. The first minute of the following 5-min respiratory control period was for learning metronomic respiration. Following this 5-min period, the subjects rested for about 3 min with spontaneous breathing. Postural changes such as standing up were forbidden. This 8-min measurement cycle was repeated nine times.

In Experiment 2, measurements were made one to three times for each subject. The effects of time, treatment and time × treatment were evaluated by repeated measures ANOVA; for comparisons between the two groups at certain time points, Student's t test was used. When the scatter of the data was not equal, the nonparametric Mann-Whitney U test (Mann and Whitney 1947) was used. P < 0.05 was considered significant. Data obtained when the subjects estimated their sleepiness as grade 1 (very sleepy) were excluded.

RESULTS

DISCUSSION

Parasympathetic nerve activity is high when subjects are calm. The present increase in HC or PNS activity reflects calmness induced by coffee intake. An enhancement of sympathetic nerves was not detected in this experiment. Therefore, the present data suggest that only the relaxing effect of coffee was reflected in the power spectrum; the arousal effect was not seen.

Heart rate itself indirectly reflects autonomic nerve activity. However, it is apt to be influenced by too many other controlling mechanisms and physiologic phenomena and cannot be used as a reliable estimator of autonomic nerve activity and tone. The PSA of R-R intervals used in the present study is able to detect autonomic nerve activity more directly; however, PSA has some limitations.

The biggest limitation when we estimate the autonomic nerve activity by PSA is that the increase in spectral power does not directly correspond to the increase in the autonomic nerve activity itself; rather it corresponds directly to the modulation of sympathetic and vagal activities. (The magnitude of vagal activity is directly related to a specific physical situation, e.g., relaxation, but the modulation of the vagal activity shows only the rate of change in the vagal activity.) In potentially nonphysiologic conditions, such as when parasympathetic nerve activity is maximally stimulated [e.g., when blood pressure is increased by phenylephrine (Cerati and Schwartz 1991)], the modulation of vagal activity would disappear and consequently the HC would also disappear. Malik and Camm (1993) pointed out that only under standard physiologic conditions such as those in the present study can the modulation of vagal activity, which is measured as HC, be used to a certain degree as an estimator of that activity. Under potentially nonphysiologic conditions, however, the relation between the HC and the degree of vagal tone is too remote to have any practical value. The same limitation applies to the relation between the LC and mixed sympathetic and vagal influences.

The modulation of vagal activity is closely associated with respiration. In general, R-R intervals are short with inspiration and long with expiration. Accordingly, the HR shows fluctuations with a frequency at least equal to the respiratory rate. This spectral peak usually is observed in the high frequency region in the power spectrum. The peak is abolished by atropine or vagotomy, which means that it is parasympathetically mediated. Thus, the ventilatory pattern (respiratory rate, tidal volume) influences the HC of the power spectrum of R-R intervals.

In addition, caffeine stimulates respiration (Higgins and Means 1915) and significantly increases respiratory rate, with the degree of respiratory stimulation closely correlated with the plasma caffeine concentration (Robertson et al. 1978).

However, the influence of changes in respiratory rate was minimal in the present study, because the subjects were instructed to breathe at an indicated rate. There is, moreover, a report (Patwardhan et al. 1995) indicating that when subjects breathe metronomically at their own mean spontaneous breathing frequency, there is no difference in the HC of HRV from that in spontaneous breathing. Consequently, we can rule out the influences of change in respiratory frequency on the change in the HC in the present study.

In spite of subjects trying to breathe at a constant depth and rate, however, there remains the possibility of an indirect effect of caffeine on the HC. In fact, caffeine has a bronchodilatory effect, which may increase tidal volume and cause an increase in the HC. When the tidal volume is larger, the HC tends to be greater (Brown et al. 1993). Although this is not a very serious factor, the augmentation of the HC may in part be due to the bronchodilatory effect of caffeine.

Caffeine has many pharmacologic effects related to the sympathetic nervous system. Caffeine intake induces a transient rise in blood pressure in subjects who abstained from caffeine for a certain period of time (Martin 1988). High caffeine doses cause tachycardia (Starr et al. 1937), a substantial rise in plasma epinephrine (Izzo et al. 1983, Smits et al. 1983 and 1985) and an increase in plasma renin activity (Robertson et al. 1978). In addition, thermogenic (Acheson et al. 1980, Higgins and Means 1915) and lipolytic effects (Acheson et al. 1980) have been reported. In the present study, we did not detect a thermic effect, nor was sympathetic nerve activity significantly enhanced by caffeine-containing beverage intake. However, the involvement of the sympathetic nervous system in such pharmacological phenomena induced by caffeine is controversial. For example, the pressor effect of caffeine was observed even after treatment with a nonselective -blocker (Smits et al. 1983) and in subjects with autonomic dysfunction in whom sympathetic responsiveness is lacking (Robertson et al. 1978). Jung et al. (1981) found that a -adrenergic blocker did not reduce the thermogenic or lipolytic effect of caffeine. These reports suggest that the contribution of enhanced sympathetic tone to the caffeine-induced increase in these physiological variables may be relatively small. Further investigation is required to determine the effects of caffeine on the sympathetic nervous system.

We demonstrated that caffeine intake enhances autonomic nerve activities. Although a significant effect of caffeine on the increase in the LC or SNS activity was not observed, modulation of the vagal tone was markedly enhanced 20-30 min after consumption of the caffeine-containing beverages. We detected differences between beverages with and without caffeine by using a power spectral analysis of HRV. This method of analysis may not be useful for studying autonomic effects of all kinds of foods and nutrients because of its limited sensitivity. However, for some kinds of spices and herbs thought to have strong influences on autonomic nerves (Kawada et al. 1988, Watanabe et al. 1988), this method of analysis would provide novel clues in investigations of the effects of food on autonomic nerves. Although HRV measurement can be influenced by many factors such as respiratory rate and posture, with proper use the power spectral analysis method can be an effective means of noninvasively detecting changes in autonomic nerve activities following food intake.