Time for precision exercise prescription: the same timing may not fit all

Precision medicine is a transformative approach to health care that addresses the inherent variability among individuals in terms of genetics, environment and lifestyle. It involves the customization of medical care to the unique characteristics of each individual, with the aim of optimizing treatment efficacy and minimizing adverse effects. This paradigm shift is made possible by the integration of comprehensive data, including multi-omics and clinical information, which allows for a more nuanced understanding of pathophysiological mechanisms and individual responses to interventions. One of them, also considered as medicine, is exercise. In the realm of exercise programmes for the prevention and treatment of a range of acute and chronic conditions, precision exercise prescription becomes particularly crucial. The variable nature of individual responses to exercise requires a tailored approach to maximize the benefits for each person, while reducing the risks of injury. Within the context of metabolic syndrome (MetS) acting as a crucial factor in the ongoing global cardiovascular crisis, and knowing the key role of exercise in the development and progression of MetS, the capability to forecast individual responses facilitates the development of personalized exercise strategies designed to address an individual's distinct risk profile.

A widely recognized approach for customizing and adjusting exercise programming to align with individual goals, lifestyle, preferences and progress is encapsulated in the FITT principle, which includes frequency, intensity, time and type of exercise. By manipulating FITT criteria, a nearly limitless number of combinations can be devised to suit specific objectives. There is increasing evidence on the potential need to include a new principle, which also starts with T, and stands for time of the day when the exercise is performed. A new study by Morales-Palomo and collaborators shows that morning high-intensity interval exercise is more effective on reducing systolic blood pressure and insulin levels that afternoon exercise in adults with MetS (Morales-Palomo et al., 2023). They conducted a 16-week exercise-based randomized controlled trial, in which 139 middle-aged adults (49 women, body mass index 30.6 ± 3.0 kg m⁻²) were allocated into morning exercise, afternoon exercise or a non-exercise control group. As expected, both exercise groups improved several cardiovascular disease risk factors, including total and central body fat, systolic blood pressure, insulin levels and cardiorespiratory fitness, compared with the control group. Interestingly, they showed that the morning exercise group improved their systolic blood pressure and insulin levels to a greater extent than those who exercised in the afternoon, yet no differences in fasting glucose levels were noted between the morning and afternoon exercise groups. Previous exercise interventions conducted on both healthy and metabolically compromised individuals showed either equivalent benefits between morning and afternoon exercise or a greater advantage for exercising in the afternoon (Brito et al., 2022; Galan-Lopez & Casuso, 2023). These mixed results emphasize the need for a thorough investigation into the dimension of exercise timing, shedding light on potential variations in outcomes across heterogeneous populations.

Physiological processes in humans, such as glycaemia and blood pressure homeostasis, are finely orchestrated by circadian rhythms, showing elevated levels in the morning compared with the evening. Certainly, healthy individuals manifest diminished insulin sensitivity and glucose tolerance during the evening as opposed to the morning. Therefore, it is plausible to believe that exercise exerts different physiological effects on the cardiovascular and endocrine systems depending on the time of the day when it is performed. However, we conducted a systematic review and meta-analysis and found no influence of the time of the day on the acute effect of exercise on blood glucose (n = 10 studies) or blood pressure (n = 11 studies) (Sevilla-Lorente et al., 2023). A comprehensive analysis of potential moderator variables (i.e. age, body mass index, sex, health status, the intensity and duration of exercise, and hour within the morning or evening) revealed no significant morning versus evening effect. More recently, a meta-analysis (Galan-Lopez & Casuso, 2023) focused on the metabolic adaptations to exercise training showed that afternoon exercise tended (standardized mean difference = 0.24, 95% CI = 0.478 to 0.004, I² = 0%, P = 0.0539) to be more effective than morning exercise training on reducing fasting blood glucose levels, with no differences being observed between morning versus afternoon in glycated haemoglobin, fasting insulin or homeostatic model assessment.

Importantly, previous studies have focused on glucose levels during fasting conditions, despite the fact that individuals spend the majority of their day in a postprandial state, which might not fully reflect real-world daily glycaemic control. Therefore, the utilization of continuous glucose monitoring devices becomes indispensable in the assessment of glycaemic control, as they provide detailed information on 24 h mean glucose levels, enabling a more precise analysis. Another relevant aspect to consider is that most prior investigations have either centred predominantly on men or have combined both men and women in their analyses, although women generally exhibit greater insulin sensitivity than men. This underscores the significance of considering sex-specific differences when exercise interventions are implemented and emphasizes the necessity to conduct separate analyses for men and women. Moreover, there is a recent emphasis on considering sex as a biological variable in research, because there is a lack of comprehensive examination of sex differences in the effects of exercise on health outcomes.

Descriptors outlining exercise interventions in trials often fall short in terms of optimal detailing in study reports. To address this issue, the Consensus on Exercise Reporting Template (CERT) was developed to offer guidance regarding a fundamental set of key elements deemed crucial for reporting replicable exercise programmes (Slade et al., 2016). In this CERT list, the time of day when the exercise is performed was not included. Although conclusive evidence on the optimal timing for exercise is lacking, documenting this aspect will enhance our understanding of whether the benefits of exercise can be maximized by individually adjusting the time of day when it is performed.

As we learn more about individual health, personalized exercise prescription is becoming a leading way to improve well-being and lower the risk of disease.