SummaryCircadian rhythms, metabolism, and nutrition are intimately linked [1, 2], although effects of meal timing on the human circadian system are poorly understood. We investigated the effect of a 5-hr delay in meals on markers of the human master clock and multiple peripheral circadian rhythms. Ten healthy young men undertook a 13-day laboratory protocol. Three meals (breakfast, lunch, dinner) were given at 5-hr intervals, beginning either 0.5 (early) or 5.5 (late) hr after wake. Participants were acclimated to early meals and then switched to late meals for 6 days. After each meal schedule, participants’ circadian rhythms were measured in a 37-hr constant routine that removes sleep and environmental rhythms while replacing meals with hourly isocaloric snacks. Meal timing did not alter actigraphic sleep parameters before circadian rhythm measurement. In constant routines, meal timing did not affect rhythms of subjective hunger and sleepiness, master clock markers (plasma melatonin and cortisol), plasma triglycerides, or clock gene expression in whole blood. Following late meals, however, plasma glucose rhythms were delayed by 5.69 ± 1.29 hr (p < 0.001), and average glucose concentration decreased by 0.27 ± 0.05 mM (p < 0.001). In adipose tissue, PER2 mRNA rhythms were delayed by 0.97 ± 0.29 hr (p < 0.01), indicating that human molecular clocks may be regulated by feeding time and could underpin plasma glucose changes. Timed meals therefore play a role in synchronizing peripheral circadian rhythms in humans and may have particular relevance for patients with circadian rhythm disorders, shift workers, and transmeridian travelers.
Time-dependent variations in the hormonal and metabolic responses to food are of importance to human health, as postprandial metabolic responses have been implicated as risk factors in a number of major diseases, including cardiovascular disease. Early work reported decreasing glucose tolerance in the evening and at night with evidence for insulin resistance at night. Subsequently an endogenous circadian component, assessed in constant routine (CR), as well as an influence of sleep time, was described for glucose and insulin. Plasma triacylglycerol (TAG), the major lipid component of dietary fat circulating after a meal, also appears to be influenced by both the circadian clock and sleep time with higher levels during biological night (defined as the time between the onset and offset of melatonin secretion) despite identical hourly nutrient intake. These time-dependent differences in postprandial responses have implications for shiftworkers. In the case of an unadapted night shift worker, meals during work time will be taken during biological night. In simulated night shift conditions the TAG response to a standard meal, preceded by either a low-fat or a high-fat premeal, was higher after a nighttime meal than during a daytime meal, and the day/night difference was larger in men than in women. In real night shift workers in Antarctica, insulin, glucose, and TAG all showed an increased response after a nighttime meal (second day of night shift) compared to a daytime meal. Night shift workers are reported to have an approximately 1.5 times higher incidence of heart disease risk and also demonstrate higher TAG levels compared with matched dayworkers. As both insulin resistance and elevated circulating TAG are independent risk factors for heart disease, it is possible that meals at night may contribute to this risk.
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