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

A commentary by Thijs Eijsvogels and Sabiha Gati, Sports Cardiology and Exercise Section

Preventive Cardiology
Rehabilitation and Sports Cardiology

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.

Figure comment TE.JPG

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.


Thijs Eijsvogels and Sabiha Gati commented on this article:

7. Schnohr P, O'Keefe JH, Lavie CJ, Holtermann A, Lange P, Jensen GB and Marott JL. U-Shaped Association Between Duration of Sports Activities and Mortality: Copenhagen City Heart Study. Mayo Clin Proc. 2021.

other references:

1. Thompson PD and Eijsvogels TMH. New Physical Activity Guidelines A Call to Activity for Clinicians and Patients. Jama-Journal of the American Medical Association. 2018;320:1983-1984.
2. Pedersen BK and Saltin B. Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports. 2015;25 Suppl 3:1-72.
3. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, Carty C, Chaput JP, Chastin S, Chou R, Dempsey PC, DiPietro L, Ekelund U, Firth J, Friedenreich CM, Garcia L, Gichu M, Jago R, Katzmarzyk PT, Lambert E, Leitzmann M, Milton K, Ortega FB, Ranasinghe C, Stamatakis E, Tiedemann A, Troiano RP, van der Ploeg HP, Wari V and Willumsen JF. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54:1451-1462.
4. Eijsvogels TM and Thompson PD. Exercise Is Medicine: At Any Dose? JAMA. 2015;314:1915-6.
5. Franklin BA, Thompson PD, Al-Zaiti SS, Albert CM, Hivert MF, Levine BD, Lobelo F, Madan K, Sharrief AZ, Eijsvogels TMH, American Heart Association Physical Activity Committee of the Council on L, Cardiometabolic H, Council on C, Stroke N, Council on Clinical C and Stroke C. Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective-An Update: A Scientific Statement From the American Heart Association. Circulation. 2020;141:e705-e736.
6. Schnohr P, O'Keefe JH, Marott JL, Lange P and Jensen GB. Dose of jogging and long-term mortality: the Copenhagen City Heart Study. J Am Coll Cardiol. 2015;65:411-9.
8. Arem H, Moore SC, Patel A, Hartge P, Berrington de Gonzalez A, Visvanathan K, Campbell PT, Freedman M, Weiderpass E, Adami HO, Linet MS, Lee IM and Matthews CE. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern Med. 2015;175:959-67.
9. Lee DC, Pate RR, Lavie CJ, Sui X, Church TS and Blair SN. Leisure-time running reduces all-cause and cardiovascular mortality risk. J Am Coll Cardiol. 2014;64:472-81.
10. Ekelund U, Tarp J, Steene-Johannessen J, Hansen BH, Jefferis B, Fagerland MW, Whincup P, Diaz KM, Hooker SP, Chernofsky A, Larson MG, Spartano N, Vasan RS, Dohrn IM, Hagstromer M, Edwardson C, Yates T, Shiroma E, Anderssen SA and Lee IM. Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. BMJ. 2019;366:l4570.
11. Ekelund U, Dalene KE, Tarp J and Lee IM. Physical activity and mortality: what is the dose response and how big is the effect? Br J Sports Med. 2020;54:1125-1126.

Notes to editor

Note: The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.