Exercise and mortality: can there be too much of a good thing?

The health benefits of a physically active lifestyle are indisputable (1). Habitual physical activity and exercise training improve cardiovascular risk factors and reduce the risk for the development of chronic diseases, including cardiovascular diseases, metabolic diseases, various types of cancer, pulmonary, musculoskeletal, neurological and psychiatric diseases (2). Hence, the World Health Organization recommends adults to engage in at least 150 to 300 minutes of moderate-intensity aerobic physical activity or 75 to 150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination thereof throughout the week (3). As larger exercise volumes are believed to produce greater health benefits, adults may increase physical activity levels beyond the recommended dose (i.e. >300 min/week of moderate-intensity PA or >150 min/week of vigorous-intensity PA) for additional health benefits.

There is a debate, however, on the shape of the dose-response association of exercise volumes and health outcomes (4). The prevailing dogma suggests a curvilinear relationship, indicating that physically inactive individuals have the highest risk for adverse outcomes, while the most active individuals have the lowest risk. It is important to note that the health benefits of an increase in exercise volume depend on the initial activity status of the individual. For example, large risk reductions are expected when an inactive person starts to perform low volumes of physical activity, whereas a similar increase in exercise volume for a highly active person does not yield additional health benefits.

The alternative hypothesis is that extreme exercise volumes may be associated with partial loss of health benefits (5). The shape of such dose-response association would be J-shaped or U-shaped. There is only little data to support this alternative hypothesis, but an important study driving this debate is the Copenhagen City Heart Study. An initial publication from this cohort reported an increased mortality risk in ‘strenuous’ versus ‘light’ joggers (6). However, there were only two deaths in the ‘strenuous jogger’ group (n=36), causing a wide confidence interval (0.48–8.14), while the cause of death was not reported. Outcomes from this study were, therefore, unclear and vulnerable to (subjective) debate.

An updated analysis of the Copenhagen City Heart Study was recently published in Mayo Clinic Proceedings (7). Characteristics of leisure-time sports activities were collected in 8,697 healthy adults and mortality (cardiovascular) was assessed during a median follow-up of 25.6 years. The authors reported a U-shaped association between weekly exercise duration and outcomes. Mortality risks were the lowest for individuals performing 2.6 to 4.5 hrs/week of exercise, while a significantly higher mortality risk was observed in the most active group (>10 hrs/week, hazard ratio: 1.22, 95% confidence interval: 1.03 - 1.44). Outcomes from this study are contradictory to findings from other (larger) cohorts (8, 9) raising the question of how this is possible. Beyond differences in methodological considerations, follow-up time and correction for potential confounders and mediators, all studies relied on questionnaires to capture exercise characteristics. It is known that subjective data is vulnerable to various forms of bias, and where possible, the use of objectively collected data is preferred.

Accelerometers can be used to capture physical activity and exercise characteristics in daily life, and these devices are increasingly used in large epidemiological studies. Outcomes from a harmonised meta-analysis favour a curvilinear dose-response association between exercise volumes and mortality (10). Furthermore, the health benefits of objectively collected physical activity volumes were substantially larger compared to similar exercise volumes that were derived from studies using questionnaires (11), indicating that subjective data is likely to underestimate the true health benefits of exercise. Based on these insights, findings of the Copenhagen City Heart Study may not be as worrisome as they initially look. Until there is more evidence supporting the presence of a U-shaped association between exercise volumes and mortality, preferably from studies adopting objective measurement techniques, we believe that one should keep running, cycling, swimming, or perform any other type of sports to enhance or maintain cardiovascular health. After all, the benefits of exercise outweigh any potential risks for the large majority of the population.

Adapted from Eijsvogels et al. Curr Treat Options Cardio Med (2018) 20:84 Copyright 2018, The Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.