Scientific Papers

Diurnal differences in urine flow in healthy young men in a light-controlled environment: a randomized crossover design | Journal of Physiological Anthropology

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We observed clear diurnal differences in Qmax in healthy young men under both dim and bright daylight. Morning Qmax values were significantly lower than the bright daylight evening and the daytime, evening, and pre-sleep timepoints in dim daylight. The pre-sleep Qmax values in dim daylight were significantly higher than bright daylight, while late-night Qmax values in the fixed-time urination period were significantly lower than mDay under both the bright and dim daylight conditions.

Diurnal differences in Qmax values were observed in young, healthy men in a light-controlled environment, suggestive of a physiological phenomenon under control of the endogenous central clock system as well as local regulation by bladder-specific timing. The central clock, influenced by light exposure, is located in the supurachiasmatic nucleus and tunes peripheral clocks in organs such as the bladder to coordinate circadian rhythms of intraorgan activities [9]. Qmax is determined by both the contractility of the urinary bladder and resistance of the urethra; greater contractions with lower resistance generate a higher Qmax [25]. Thus, diurnal micturition rhythms are transduced from the circadian clock system [9] to the peripheral bladder clock to prevent urination at night for sound sleep [18]. This shift from voluntary “voiding” mode to “storage” mode at night can be reflected by decreases in bladder contractility.

In addition, we found that bright daylight significantly decreased before sleep Qmax versus dim daylight. This suggests that the pre-sleep bladder may have shifted to “storage” mode under bright daylight conditions, but “voiding” mode might have persisted under dim daylight conditions. In other words, bright daylight could regulate a phase-advancing shift in Qmax diurnal variation, similar to shifts of urinary Na+, Cl, uric acid excretion, and rectal temperature rhythms reported by Nakamoto et al. [13]. However, the mechanism of daylight exposure on Qmax pre-sleep is largely unknown. One possible explanation is the advancement of the master clock phase by bright compared with dim light [26]. In such cases, the mode shift of the bladder would have been advanced in line with the advanced master clock signals. Melatonin might precipitate this effect since onset time of melatonin secretion in the evening was reported to be earlier in bright daylight versus dim daylight conditions [27]. In addition to its role in chronobiologic regulation, melatonin also inhibits bladder contraction and is known to increase bladder capacity [28,29,30]; thus, the early initiation of nocturnal melatonin secretion by bright light exposure during the day may have downregulated Qmax pre-sleep. Given the reported high correlation between core body temperature and melatonin [31], the observed trend in the association between differences in core body temperature and Qmax could align with this hypothesis, despite the limited number of participants.

Psychological influence from the dim daylight condition may have also influenced our results [32, 33]. Since urination is also under voluntary control and this situation was unusual for some participants, it is possible that some participants willingly urinated more strongly than their normal level before going to bed.

In clinical settings, complaints about difficult nighttime urination are common. As a result, one of our objectives was to compare the Qmax at 4 a.m., a time in the middle of the sleep period that is unassociated with urination on demand, with daytime urination. This comparison was a subsidiary study to a previous experiment that focused on measuring urinary components [13]. The data in Supplementary Figure 4 show that, even when participants did not feel the need to urinate based on the fixed interval protocol, there was still a diurnal variation in Qmax, which was lowest in the early morning. Considering that the volume voided per micturition also decreased, it is challenging to determine whether the diurnal variation in Qmax is physiological from this fixed-time urination protocol. This is because Qmax is known to increase as the volume voided per micturition increases and there are significant individual differences in this relationship. Hence, for the statistical analysis of Qmax during scheduled urination, we compared the Qmax during forced urination at 04:00, the actual target time corresponding to sleep, with the value closest to the volume of daytime forced urination.

Diurnal rhythms of urination typically show a decrease in urinary frequency and an increase in volume voided per micturition upon waking or during nighttime [11]. In contrast, our study of healthy young participants revealed diurnal variations in frequency but no such pattern for volume voided per micturition. This could result from the adequate suppression of nocturnal urine production in these young individuals, leading to morning urination before complete filling of the bladder.

The present study has several limitations. First, the origin of diurnal Qmax differences in healthy young men is unreported. While bladder and urethral tension studies in healthy volunteers are possible, invasive catheter insertion is difficult to accomplish [25]. Thus, we could only speculate that melatonin or some psychological effect on bladder/urethral dynamics influenced our observed results. Second, the data obtained in the present study cannot easily be compared with the classical method of constant-routine protocols where participants are in fixed positions and experience sleep deprivation under conditions of constant dim light to determine individual circadian rhythms [34]. Since results from that method are not comparable to real-life situations that may influence circadian patterns, we opted for our novel method, standardizing whatever environmental variables we could; temperature and humidity were constant, while food and water were consumed in fixed quantities and at fixed times. Furthermore, strenuous exercise and napping were prohibited, but no constant positioning or sleep restrictions were imposed [13]. As for the potential masking effect of sleep, a study has shown that Qmax is not related to arousal conditions, as evidenced in newborn experiments [35]. Concerning diet, since elements like caffeine and alcohol are known to influence urination patterns [36], we standardized meal content to control for these dietary effects. Nonetheless, the precise influence of diet on Qmax is still not fully understood. While it remains a challenge to entirely offset the potential masking effects from sleep and diet, our protocol, we believe, effectively captures the variation in Qmax due to inherent diurnal rhythms. Third, the regular urination protocol did not accurately reflect the diurnal variation in Qmax, since it largely depends on bladder capacity and considerable individual differences exist. Therefore, we compared the Qmax at 4 a.m. to daytime values to ensure similar voided volumes. To study the diurnal rhythm of Qmax more precisely, one could monitor the amount of urine accumulating in the bladder continuously and induce urination once a certain volume is reached. However, this method also has limitations: the urination timing might be inconsistent, and there is a continuous need to monitor bladder capacity that could change voluntary voiding choice due to irritation or enhanced bladder focus during measuring. Fourth, concerning average flow rates, there were no diurnal differences observed in the free-urination protocol, nor in the comparison between 4 a.m. and mDay during the regular urination protocol. In light of this, Qmax might be more sensitive than average flow rate, as it more closely reflects the maximal detrusor pressure. We posit that variability in the somewhat lower detrusor pressure possibly remains low between day and night. Further research is required to elucidate this disparity between the diurnal differences of Qmax and average flow rates. Fifth, a standardized comparisons between Qmax and body clock with bright light exposure at night have not yet been reported. Next, only male participants were recruited since complaints of difficult urination at night/early in the morning are uncommon in older women. However, gender differences in circadian rhythms, including renal function, have been reported [37, 38], and we acknowledge that important diurnal Qmax variations may exist between the genders. Finally, the effect of the prostate peripheral clock on this phenomenon remains unknown and a topic for more detailed future studies [39]. In spite of these limitations, we are the first to report Qmax variations in healthy young men that can be used as a baseline to develop further gender-, condition-, and age-based studies.

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