Human circadian phase–response curves for exercise

Abstract

Key points Exercise elicits circadian phase‐shifting effects, but additional information is needed. The phase–response curve describing the magnitude and direction of circadian rhythm phase shifts, depending on the time of the zeigeber (time cue) stimulus, is the most fundamental chronobiological tool for alleviating circadian misalignment and related morbidity. Fifty‐one older and 48 young adults followed a circadian rhythms measurement protocol for up to 5.5 days, and performed 1 h of moderate treadmill exercise for 3 consecutive days at one of eight times of the day/night. Temporal changes in the phase of 6‐sulphatoxymelatonin (aMT6s) were measured from evening onset, cosine acrophase, morning offset and duration of excretion. Significant phase–response curves were established for aMT6 onset and acrophase with large phase delays from 7:00 pm to 10:00 pm and large phase advances at both 7:00 am and from 1:00 pm to 4:00 pm. Delays or advances would be desired, for example, for adjustment to westward or eastward air travel, respectively. Along with known synergism with bright light, the above PRCs with a second phase advance region (afternoon) could support both practical and clinical applications. Abstract Although bright light is regarded as the primary circadian zeitgeber, its limitations support exploring alternative zeitgebers. Exercise elicits significant circadian phase‐shifting effects, but fundamental information regarding these effects is needed. The primary aim of the present study was to establish phase–response curves (PRCs) documenting the size and direction of phase shifts in relation to the circadian time of exercise. Aerobically fit older ( n = 51; 59–75 years) and young adults ( n = 48; 18–30 years) followed a 90 min laboratory ultrashort sleep–wake cycle (60 min wake/30 min sleep) for up to 5½ days. At the same clock time on three consecutive days, each participant performed 60 min of moderate treadmill exercise (65–75% of heart rate reserve) at one of eight times of day/night. To describe PRCs, phase shifts were measured for the cosine‐fitted acrophase of urinary 6‐sulphatoxymelatonin (aMT6s), as well as for the evening rise, morning decline and change in duration of aMT6s excretion. Significant PRCs were found for aMT6s acrophase, onset and duration, with peak phase advances corresponding to clock times of 7:00 am and from 1:00 pm to 4:00 pm, delays from 7:00 pm to 10:00 pm, and minimal shifts around 4:00 pm and 2:00 am. There were no significant age or sex differences. The amplitudes of the aMT6s onset and acrophase PRCs are comparable to expectations for bright light of equal duration. The phase advance to afternoon exercise and the exercise‐induced PRC for change in aMT6s duration are novel findings. The results support further research exploring additive phase‐shifting effects of bright light ...

Circadian rhythm phase shifts caused by timed exercise vary with chronotype

“…We chose morning and evening exercise for 2 reasons. First, morning exercise has been shown, in some studies, to cause significant phase advances, which could alleviate circadian misalignment in late chronotypes and others whose internal rhythms are delayed relative to the environment (21,33,34). Second, morning and evening are the most common times when people exercise on weekdays, so exercise at these times could be implemented as feasible behavioral interventions for circadian disruption in free-living individuals (46).…”

“…Recent studies in mice showed that exercise performance, gene transcription, and energy utilization depend on the time of day of exercise (31,32). Clinical studies have conflicting results, but some have shown that morning or early afternoon exercise phase advances, while evening exercise phase delays the internal circadian rhythm (21,(33)(34)(35)(36). However, most of these prior studies were performed in controlled lab conditions, and many studies included physically active adults such that the results may have been confounded by recent nonlaboratory exercise regimens.…”

Time-of-Day-Dependent Physiological Responses to Meal and Exercise

“…Based on this research, it is expected that the evening exercise has beneficial effects in non-dipping hypertensive men. However, in a recent human study, exercise at the evening and nighttime (from 1900 to 2200 h) delays the phase of melatonin metabolites (14), thus it is possible that evening exercise progress the circadian disturbance of blood pressure via a phase-delay of circadian rhythm. Further studies are required to evaluate the effect of exercise both in terms of hypotensive effect and circadian rhythm is required for the control of circadian blood pressure in hypertensive subjects.…”

“…Further evidence is expected to lead to a clearer understanding of the molecular mechanisms leading to the interaction between circadian clock and time-of-day effects. Finally, exercise also has the potential for a timekeeper of circadian clock, especially exercise at night-time induces phase-delay in humans (14). Thus, further evidence is needed to discuss the effects of exercise timing in the context of therapeutic effects and its circadian rhythms.…”

“…Likewise, exercise entrains the circadian clocks in the peripheral tissues such as muscle, liver and lung via the sympathetic nervous system and glucocorticoid signaling (11,12). These effects of nutrient and exercise on circadian clock are observed not only in rodents, but also in humans (13,14).…”