Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013

Because of the limits of the search for studies and the natural attention beig naturally paid to the good studies mostly done in affluent countries, this review does not include older studies of the mortality of people working in very heavy manual jobs. These studies found that mortality is very high in these people, despite the self-selection of the participants.

Of course, on the one hand, the high mortality of the people involved in these jobs is explainable in part by their harsh living conditions. But, on the other hand, it would be naive to draw the line far to the right in the region of very high physical activity. The authors of this review do not do this, but it is worth remembering the harm of very hard physical activity.

We thank Bauman and colleagues[1] for their response to our work and appreciate the opportunity to clarify our results. We hope this will open discussions on this important topic.

The World Health Organization (WHO)[2] and the World Cancer Research Fund[3] consistently suggest that all forms of physical activity (leisure-time, occupational, transport-related, and household) are protective against certain chronic diseases. However, Bauman and colleagues argued that global physical activity recommendations were based on studies focusing on leisure-time and transport-related activity only (no citation provided for this argument). Bauman et al. also claimed that occupational activities are unreliably recalled, but their claim is not supported by the study that they cited (in fact, the study they cited did not even examine occupational activities). Bauman et al. downgrade domestic and occupational activities as “low level moving about”, but the health benefits of activities in these two domains have been shown in empirical studies,[4] and the fact that these activities could reach the threshold of moderate to vigorous-intensity is well acknowledged.[2, 3] According to WHO, levels of participation in leisure-time activity “may be limited” in many low- and middle-income countries, but “moderate to vigorous physical activity may be performed in the context of transport and/or occupational and/or domestic activities”.[2]

Bauman et al. cited an unpublished study and stated that “population studies that have objectively assessed total PA with accelerometers in relation to health outcomes have consistently supported the current PA recommended levels”. However, published systematic reviews and meta-analyses have shown that the minimum recommended activity level is not the optimal level for health. For example, Wu et al., 2013[5] have reported based on the findings from their dose-response meta-analysis that activity levels several times higher than the current recommended minimum levels were more protective against breast cancer.

Bauman et al. stated that “a recent meta-analysis[6] of leisure time and transport-related PA showed a clear risk reduction in mortality of 30-40% when people achieved the recommended 30-60 minutes of moderate intensity PA per/day, and doing 10-fold more than this conferred no greater benefit”. However, the meta-analysis[6] did not examine transport-related physical activity as Bauman et al. stated. The study focused on leisure-time activity only; comparing their levels of leisure-time activity with the levels of total activity from our study is completely misleading. Moreover, considering only a single domain of physical activity such as leisure-time activity ignores the activity undertaken in other domains, which could result in biased estimates.[7] Furthermore, comparing the results of our meta-analysis, which studies the impact of physical activity on the incidence of 5 diseases, with results from a study that examines physical activity’s effect on all-cause mortality is not valid since it involves comparing separate outcomes of interest.

Bauman et al. commented that one of the reasons we found a higher level of physical activity for significant reduction in risk of diseases is that we used an activity level below 600 MET-minutes/week as a reference category for our continuous dose-response analyses. It is clear from the graphs that the dose response curves start from 0 MET-minutes/week, and we also mentioned in the paper that no activity (i.e., 0 MET-minutes/wk) was used as the reference category for assessing the continuous dose-response relationships.

Inclusion of all daily activities is an important aspect of our study. We disagree with Bauman et al. that achieving the total activity of 3000-4000 MET-minutes/week is unrealistic. Bauman et al. stated that only 1% of the population meet the activity level of 3000 to 4000 MET-minutes/week. No citation for this statement was provided, but it seems likely that this is again based on the assumption that only leisure time and transport-related activity counts. We have provided empirical evidence of the distribution of total activity based on nationally representative surveys in multiple countries (Figure 1), which clearly shows that a non-trivial proportion of people have reached the level of 3000-4000 MET-minutes/week. Indeed, Bauman et al’s own citation[8] refutes their argument that even Pennsylvanian Amish men couldn’t reach the maximum level of activity shown in the graphs: with an average of 18,000 MET-minutes per week and a standard deviation of 7340, the 97.5th percentile among Amish men would just about reach the 32,500 MET-minutes per week that forms the upper boundary of our graphs.

We agree with Autier and Pizot[9] and Baumann et al. that evaluating activity by MET has limitations which we discussed in the paper, but is by far the most objective method to standardize physical activity measured heterogeneously across different epidemiological studies. It is noteworthy that we mapped studies that measured physical activity qualitatively to the GBD 2013 exposure distribution to generate estimates of total physical activity. While this enabled us to standardize physical activity measures and include the maximum possible number of studies, it added some measurement errors which might underestimate our estimations (regression dilution bias). It means that the true health benefits are probably higher but our sensitivity analysis showed that this is unlikely to affect the shape of the curve, meaning that the activity level of 3000 to 4000 MET-minutes/week where most health gains occurred is still valid.

Bauman et al. stated that “the conclusion that PA needs to be several times higher than the levels recommended in current guidelines (30-60 minutes per day, above activities of daily living) for meaningful reduction in the risk of NCDs is misleading.” We are not saying that the minimum recommended level is not beneficial for health; we merely pointed out that additional activity is associated with further reductions in risk, which seems an entirely unsurprising finding for recommended minimum levels of physical activity. Bauman et al. define "normal daily activities" as “everyday domestic and most occupational activities” and they are suggesting that one should not count activity in these two domains. This contradicts the WHO recommendation which says that moderate-to-vigorous intensity activities could be accumulated across all domains of life. Bauman and colleagues’ suggestion could not only confuse policymakers but also de-motivate people who are trying to be more active at home and work. In addition to a lack of scientific and biological evidence to support their claim, another issue with their suggestion is that different people have exerted different levels energy in the process of going about their “activities of daily living”. If household and occupational activity is not taken into consideration, physical activity measures are incomparable across studies. In our study, we attempted to make physical activities in the different domains of life comparable by standardizing them into total activity in MET-minutes/week; accordingly, our results showed higher activity levels for more significant reduction in risk. The key message based on the findings of our study is that incorporating physical activity into daily life through being more physically active at work and during leisure time, turning household chores into exercise, and engaging in active transportation such as walking or cycling can have immense health benefits.

Hmwe H Kyu, Institute for Health Metrics and Evaluation, University of Washington, USA;
John Everett Mumford, Institute for Health Metrics and Evaluation, University of Washington, USA;
J. Lennert Veerman, School of Public Health, Faculty of Medicine and Biomedical Sciences, University of Queensland, Australia;
Mohammad H Forouzanfar, Institute for Health Metrics and Evaluation, University of Washington, USA

References

1. Bauman A, Brown W, Plotnikoff R. Re: Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. Re-setting the physical activity threshold – a flawed and potentially harmful approach? Available from: http://www.bmj.com/content/354/bmj.i3857/rr-3.
2. World Health Organization. Global recommendations on physical activity for health. Geneva: World Health Organization: 2010.
3. World Cancer Research Fund AIfCR. Food, Nutrition, and Physical Activity, and the Prevention of Cancer. A Global Perspective. Washington D.C: 2007.
4. Boyle T, Keegel T, Bull F, et al. Physical Activity and Risks of Proximal and Distal Colon Cancers: A Systematic Review and Meta-analysis. J Natl Cancer Inst. 2012;104(20):1548-61.
5. Wu Y, Zhang D, Kang S. Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2013;137(3):869-82.
6. Arem H, Moore SC, Patel A, et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA internal medicine. 2015;175(6):959-67.
7. Bull FC, Armstrong TP, Dixon T, et al. Physical inactivity. In: Ezzati M, Lopez AD, Rodgers A, Murray CJL, editors. Comparative Quantification of Health Risks: Global and Regional Burden of Diseases Attributable to Selected Major Risk Factors. Geneva: World Health Organization; 2004. p. 847.
8. Bassett DR, Schneider PL, Huntington GE. Physical activity in an Old Order Amish community. Med Sci Sports Exerc. 2004;36(1):79-85.
9. Autier P, Pizot C. Meaningless METS: studying the link between physical activity and health. British Medical Journal Publishing Group; 2016.

Re-setting the physical activity threshold – a flawed and potentially harmful approach?

Widely accepted global recommendations regarding the amount of physical activity (PA) required for chronic disease prevention (150-300 minutes/week; [1,2]) were challenged in a recent meta-analysis, which showed insignificant reductions in risk of NCDs at conventionally recommended levels of PA [3]. The inconsistency is likely explained by the fact that global recommendations are based on evidence for PA in leisure/recreational 'exercise' and transport that are reliably recalled, and are over and above the low level 'moving about' which is part of everyday domestic and most occupational activities. In contrast, the meta-analysis by Kyu et al focused on the health consequences of total physical activity, including occupational and domestic activities that show more tenuous relationships with health outcomes; these activities are unreliably recalled (and significantly over-estimated) and the intensity of these activities is usually low [4].

The new meta-analysis included data from generic surveys, in which PA is reported across various domains; these surveys often demonstrate 2-3 times the prevalence of “sufficient activity”, compared with contemporaneous leisure time physical activity surveys in the same countries [5]. Inclusion of all activities, including occupational and domestic activities, resulted in a range of activity reported in the first five figures from 0-32,500 MET.mins/week [3]. At moderate intensity of 4 METs, the upper end of this range is equivalent to 19.3 hours per day of exercise or activity, which is clearly unrealistic. Indeed, this is more than the weekly energy expenditure of contemporary Pennsylvanian Amish men who live without motorised or electrical assistance [6]. Even in their summary figure 7, Kyu et al indicate an upper limit of 10,000 MET.mins/week, which is approximately 6 hours per day of moderate intensity activity. The pattern of the dose-response relations between PA and risk of cardiovascular disease, diabetes and cancers are similar to those in previous consensus documents [1,7], with the maximal decline in risk observed in moving from inactive to currently recommended levels (around 500-600 MET.mins/week). However, the estimated PA required for significant risk reduction is higher in the Kyu paper, because of the dilution effects of inaccurately reported occupational and domestic activities and over-estimation of their MET values, and because values based on all physical activity below 600 MET.mins/day are used as the reference categories. Since low level activities are likely to have some benefit [8], the amount of activity required for significant risk reduction, in comparison with this reference category, is further inflated.

A recent meta-analysis of leisure time and transport-related PA showed a clear risk reduction in mortality of 30-40% when people achieved the recommended 30-60 minutes of moderate intensity PA per/day, and doing 10-fold more than this conferred no greater benefit [9]. Another recent meta-analysis highlighted the importance of the upper range of current PA recommendations (ie 60 minutes per day) to fully offset the health consequences of prolonged occupational/transit sitting time [10]. Both these meta-analyses used METs as a common metric of PA intensity.

In the editorial that accompanied the Kyu paper, Autier and Pizot (12) claim the use of METs for measuring PA is meaningless, because they do not 'tell us whether risk reductions would be different with short duration intense activity or longer duration light activity'. While this is true, METs remain important as the unit of exposure that has provided information on the volume of PA required to mitigate the health consequences of inactivity, as evidenced through hundreds of cohort studies. When METS accrued through self-reported occupational and domestic activity are included, there is likely to be significant measurement error, and if estimates of total daily are required, these should be measured objectively.

The conclusion that PA needs to be several times higher than the levels recommended in current guidelines (30-60 minutes per day, above activities of daily living) for meaningful reduction in the risk of NCDs is misleading. Population studies that have objectively assessed total PA with accelerometers in relation to health outcomes have consistently supported the current PA recommended levels, further suggesting methodological limitations in the Kyu et al study [13].

Unfortunately the public and the media are easily misled, as many media reports have now reported on the Kyu paper, indicating people “need between two and five times as much exercise as was previously recommended for health”. Potential adverse consequences of these media reports will be to: [i] de-motivate people who are trying to increase their PA, [ii] provide an unachievable target for most people (fewer than 1% of adults reach the amount recommended by Kyu et al [14] [iii] confuse policymakers and [iv] obfuscate the work of PA advocates. Kyu describes nine potential sources of error in the results, but do not mention the key issue of differential measurement error across self-reported domains of PA. Public debate to prevent these unintended consequences is essential.

Adrian Bauman, University of Sydney
Wendy Brown, University of Queensland
Ronald Plotnikoff, University of Newcastle, Australia

References

[1] World Health Organization. Global recommendations on Physical activity for health. 2010. WHO, Geneva whqlibdoc.who.int/publications/2010/9789241599979_eng.pdf {accessed August 2016]
[2] Australian Physical activity guidelines 2014.[ accessed August 2016]. http://www.health.gov.au/internet/main/publishing.nsf/content/health-pub...
[3] Kyu H, Bachman V, Alexander L, et al. Physical activity and risks of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ 2016;354:i3857.
[4] Peeters GMEE, van Gellecum Y, van Uffelen JGZ, Burton NW, Brown WJ. (2014). Contribution of house and garden work to the association between physical activity and wellbeing in younger, mid-age and older women. British Journal of Sports Medicine, 48(12), 996-1001.
[5] Macniven R, Bauman A, Abouzeid M. A review of population-based prevalence studies of physical activity in adults in the Asia-Pacific region. BMC Public Health. 2012 Jan 17;12(1):1.
[6] Bassett DR, Schneider PL, Huntington GE. Physical activity in an Old Order Amish community. Medicine and Science in Sports and Exercise. 2004; 36(1):79-85.
[7] Haskell, W.L., Lee, I.M., Pate, R.R., Powell, K.E., Blair, S.N., Franklin, B.A., Macera, C.A., Heath, G.W., Thompson, P.D. and Bauman, A., 2007. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation, 116(9), 1081.
[8] Hupin D, Roche F, Gremeaux V, Chatard JC, Oriol M, Gaspoz JM, Barthélémy JC, Edouard P. Even a low-dose of moderate-to-vigorous physical activity reduces mortality by 22% in adults aged≥ 60 years: a systematic review and meta-analysis. British journal of sports medicine. 2015 Oct 1;49(19):1262-7.
[9] Arem H, Moore SC, Patel A, Hartge P, de Gonzalez AB, Visvanathan K, Campbell PT, Freedman M, Weiderpass E, Adami HO, Linet MS. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA internal medicine. 2015 Jun 1;175(6):959-67.
[10] Ekelund, U., Steene-Johannessen, J., Brown, W.J., Fagerland, M.W., Owen, N., Powell, K.E., Bauman, A., Lee, I.M. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. The Lancet. Jul 27, 2016. pii: S0140-6736(16)30370-1
[11] Autier P and Pizio C. Meaningless METS: studying the link between physical activity and health. BMJ 2016;354:i4200 doi:10.1136/bmj.i4200
[12] Fishman, EI., Steeves JA, Zipunnikov V, Koster A, Berrigan D, Harris TA, Murphy R. (2016). Association between Objectively Measured Physical Activity and Mortality in NHANES. Medicine and Science in Sports and Exercise 48(7): 1303-1311
[13] ABS NHS Australian health survey 2014-2015 [unpublished re-analysis of weighted CURF data, August 2016]