Take the Stairs: Inactivity Physiology and Chronic Disease
Written by: Greg Potter
The importance of exercise in promoting good health has been recognised for aeons. There is now sufficient scientific evidence to support public health guidelines that promote at least 150 minutes of moderate-vigorous physical activity per week with the intention of reducing risk for chronic diseases (e.g. Niebauer et al., 1997). National Health and Nutrition Examination Survey data suggest that less than a third of American citizens meet this recommendation, and less-educated people and minority racial groups are even more sedentary (Kruger et al., 2007). For the purpose of this post, sedentary (from the Latin ‘sedere’, to sit) behaviour is defined by engaging mostly in sitting and lying behaviours while awake, and partaking in less than 150 minutes of moderate exercise per week, in keeping with the existing physical activity literature (Bennett et al., 2006).
In already sedentary individuals, it is unlikely that further reductions in exercise could contribute more to higher rates of chronic diseases in the coming years. What could contribute to continued declines in health, however, is a reduction in non-exercise activity. An important realisation that has gained public awareness of late is that the amount of time (and, for most, energy expended) during non-exercise activity including activities of daily living is more than that during exercise. Indeed, running 35 miles per week or walking several miles daily 5 days per week entails both less energy expenditure, and fewer muscle contractions, than intermediate amounts of non-exercise activity.
Non-exercise Activity Energy Expenditure
Environmental changes accompanying technological advances continue to produce ever more sedentary lifestyles. Data from the 2003–2004 National Health and Nutrition Examination Survey suggest that American citizens spend an average of 55% of their waking lives in sedentary pursuits (Matthews et al., 2008). As disheartening as it may be, it is unlikely that we’ve reached the pinnacle of our inactivity. Indeed, there’s still room for further declines in activity as even individuals that labelled themselves as ‘couch potatoes’ (engaging in no exercise) stand and ambulate roughly 9 hours per day (Levine et al., 2005). Those engaged in active lifestyles such as houseworkers are believed to perform low-intensity activities while standing for around 12 hours per day (Black et al., 1996).
Using accelerometry to estimate distance covered walking in a day, relatively sedentary young adults were found to cover around 9 miles per day (Harris et al., 2007). Moreover, even obese, sedentary adults stand and ambulate for an average of roughly 6.5 hours per day (Levine et al., 2005).
From such observations, it is apparent that there is great intra- and inter-individual variability regarding non-exercise activity, and non-exercise activity thermogenesis seems to be the most variable component of total daily energy expenditure. This component typically ranges from approximately 300 to 2,000 kcals per day, when comparing the mean values of estimates of individuals’ energy expenditure among the lowest and highest quartiles of total energy expenditure (Black et al., 1996, and Brooks et al., 2004). Higher values still have been reported for particularly strenuous occupations, such as lumberjacks (Karvonen et al., 1961).
Early Epidemiological Research on Inactivity and Disease
One of the first people to systematically document the association between inactivity and disease risk was Dr. Jerry Morris, who has been dubbed the founding father of inactivity physiology. Through a survey conducted in 1949, Dr. Morris found that the sedentary occupations of London’s bus drivers, which entailed sitting throughout the majority of 5.5 hour shifts, contributed to higher rates of cardiovascular disease (CVD) in these individuals than in the bus conductors, who climbed and descended the stairs over the course of the working day.
The medical orthodoxy retained considerable scepticism as to these findings, but Dr. Morris subsequently reinforced this preliminary finding by examining postmen who delivered mail by bicycle or on foot, and workers seated behind counters, including clerks and telephonists. Once again, the more active postmen suffered a lower incidence of myocardial infarctions. Moreover, among the more active workers, those with CVD suffered less severely than those with CVD in the more sedentary workers (Morris et al., 1953).
In a subsequent study using data from 206 hospitals, among 3,800, 45-70 year old men who died of causes other than coronary heart disease, Dr. Morris and his colleague found that when disregarding age and cause of death, prevalence of ischaemic myocardial infarction was twice as high in occupations involving only ‘light’ exertion than those requiring ‘heavy’ exertion (13.4% versus 6.8%), as classified by two experts in industrial medicine (Morris & Crawford, 1958).
Hypertension prevalence was lower in ‘heavy’ workers than in those performing less strenuous work, and, within the hypertensive group, myocardial fibrosis in the form of multiple, small ‘scars’ was also about two-fold higher in those performing ‘light’ work than those engaged in ‘heavy’ work. As per Dr. Morris’s previous work, ischaemic fibrosis prevalence was lower in ‘heavy’ workers, and relatively more of it took the form of smaller scars, suggesting that the ischaemic myocardial fibrosis was not so severe in ‘heavy’ workers.
Complete or near-complete coronary occlusion was nearly twice as high in workers in ‘light’ (5.8%) versus ‘heavy’ (3.4%) occupations. There was, however, no indication that physical activity at work affected coronary atheroma. Of those individuals who passed away from coronary heart disease, there were 482 deaths in ‘light’ workers, and 230 in ‘heavy’ workers, a ratio of over 2:1, and the authors suggested that if the London area had been fully represented the ratio would have been greater still, based on previous enquiries.
To summarise their findings, there was no relationship between occupational physical activity and atheroma of coronary walls, a moderate relationship with occlusion of the coronary lumen, and a strong relationship with ischaemic myocardial fibrosis. Workers in more active occupations were likely to experience more benign forms of these conditions and were also more likely to develop them later. These light-heavy trends were relatively consistent when analysed within the context of a given social class (the expected trend of ischaemic myocardial fibrosis with social class was found, the rate falling from 13.3% in the lowest class to 7.8% in the highest), lending credence to their findings.
Such early work laid the foundations for subsequent research, but was not without flaws. The possibility that individuals may have performed ‘lighter’ work secondary to pre-existing health problems was not explored, confounding the possibility that sedentary work produced adverse cardiovascular effects.
More Recent Epidemiological Research on Inactivity and Health
Fast-forward to the present day, and new research linking inactivity to declines in health is being published by the week. Several nuances to the effects of inactivity on health are also beginning to emerge.
It is first worth noting that, as per Dr. Morris’s early research, the studies mentioned herein were observational, and as of yet there have been insufficient interventional studies in humans to provide support for a causal role of inactivity in CVD or all-cause mortality. This being said, the evidence to date has yielded few anomalies. For example:
• Weller & Corey (1998) found that the relative risk for CVD mortality was 2.7-fold higher in the most sedentary individuals than the least.
• Manson et al. (2002) found that sitting time was associated with CVD risk in women, independent of age or recreational energy expenditure.
• Manini et al. (2006) found a dose-response decrease in mortality across three tertiles of non-exercise activity energy expenditure in the elderly.
• Matthews et al. (2007) reported that there was a progressive inverse relationship between risk for all-cause mortality and non-exercise activity in Chinese women. Their findings also indicated a benefit of non-exercise activity independent of exercise.
• Katzmarzyk et al. (2009) found a 54% higher risk of all-cause mortality in the most versus least sedentary quintile of 18-90 year olds and also a 54% higher risk of CVD in the most versus least sedentary quintile. Interestingly, there was no significant association between sedentary behaviour and cancer. Similar trends were evident when stratified by age, body mass index, sex, and smoking status, suggesting an independent effect of sitting per se. Sitting time did not include leisure time sitting, particularly among younger participants, however, and was assessed by self-report.
While there therefore appears to be a role of inactivity in CVD and all-cause mortality, inactivity also seems to predispose individuals to other issues such as metabolic syndrome and diabetes:
• During 6 years of follow-up among women from the Nurses’ Health Study, sitting in front of the television, sitting while driving, sitting at work, and other sitting at home were all associated with type 2 diabetes (Hu et al., 2003).
• Using television and computer viewing time as proxies for sedentary behaviour, Dunstan and colleagues (2005) came to the conclusion that those spending the most time in these activities had over twice the risk of developing metabolic syndrome. For every 1 hour increase in television viewing per day, there was a 26% rise in metabolic syndrome prevalence among women. Moreover, the magnitude of this negative effect was roughly equal to the positive effect of 30 minutes of additional physical activity. I would note, however, that television viewing time may not be an accurate representation of total sedentary time, especially in men (Sugiyama et al., 2008).
• Healy et al., (2008) also reported an independent effect of television viewing hours on metabolic risk factors in adults exceeding physical activity guidelines for physical activity.
• Healy et al., (2008) used accelerometry to assess time in sedentary behaviour in adults, finding that it was related to metabolic risk factor clustering and waist circumference, independent of moderate-to-vigorous physical activity.
There have now been multiple meta-analyses regarding the role of inactivity in disease, but a particularly strong one has recently been published. Wilmot et al., (2012) performed a meta-analysis of 18 studies (16 prospective and 2 cross-sectional), totalling 794,577 participants. The mean age of participants in the studies ranged from 38 to 63. Two studies included men only, 3 women only and the other studies included mixed groups. In prospective studies, mean follow-up ranged from 3 to 21 years and all studies used self-reported measures of physical activity.
The most sedentary had a 112% increase in the Relative Risk (RR) of diabetes versus the most active, a 147% increase in the RR of cardiovascular events, a 90% increase in the risk of cardiovascular mortality and a 49% increase in the risk of all-cause mortality. These associations were largely independent of physical activity, lending credence to the harmful effects of sedentary behaviour per se. These findings were all significant based on pooled estimates but the association with diabetes was strongest based on the Bayesian predictive effect.
It should be noted that the negative effects of physical inactivity have frequently been demonstrated to be independent of body composition measurements, and even within individuals engaging in regular exercise, there were often strong associations between sitting and risk of mortality. In a correlational analysis, Bertrais et al. (2005) found that an insignificant amount of variance in exercise could be explained by indices of sedentary time. These findings are important to note as it suggests that sedentary behaviour probably cannot be entirely compensated for with exercise, even when meeting the current physical activity recommendations.
Physiological Mechanisms Underlying the Negative Effects of Inactivity
As hypothesised by Dr. Morris and colleagues, it appears that inactivity exerts its negative impact on health via metabolic aberrations. The central premise of inactivity physiology is that cellular and molecular processes explaining responses during inactivity are qualitatively different from those during exercise (Hamilton et al., 2007). That is to say, signals producing negative effects from inactivity are often different from those that exercise signals that promote health when the exercise is performed consistently.
In comparison to typical daily non-exercise activity, brief periods of immobility repress or stimulate the expression of dozens of genes, subsequent to declines in energy expenditure that thousands of daily muscle actions produce (Bey et al., 2003). Such non-exercise activity has been found to be one of the strongest determinants of disease risk factors such as triacylglycerol and high-density lipoprotein levels during a single day, through detrimental changes in fast-acting cellular processes (Bey & Hamilton, 2003).
Accepted Conditions Related to Inactivity
Deep venous thrombosis (DVT) is a potentially fatal condition where blood clots develop in leg muscle veins during inactivity; intermittent muscle actions produce the ‘muscle pump’, which serves to return blood to the heart. This condition is therefore an example for how too much sitting per se can induce medical problems.
Bed-rest as a Model of Human Inactivity
Within the same group of healthy men, three weeks of bed rest (Saltin et al., 1968) had a greater impact on physical work capacity, as assessed via maximal Oxygen consumption, than three decades of aging (McGuire et al., 2001). Declines in function during bed rest were secondary to reduced cardiac output (Saltin et al., 1968), whereas aging was characterised by impaired maximal oxygen extraction (McGuire et al., 2001). These findings are highly intriguing, but bed rest is not entirely representative of sedentary behaviour. This being said, some of the metabolic aberrations induced by human bed-rest studies, including insulin resistance and dysglycaemia, are shared by other models of reductions in non-exercise activity (Hamburg et al., 2007).
Inactivity and Lipoprotein Lipase
Lipoprotein Lipase (LPL) was perhaps the first protein regulating lipoproteins at the cellular level studied during physical inactivity (Bey & Hamilton, 2003). In a rodent model of enforced immobility induced via hindlimb suspension, LPL activity started to decline after 4 hours of inactivity, and beyond 18 hours no further decline was evident. While exercise training has been shown to increase skeletal muscle LPL (Seip et al., 1997), inactivity decreases LPL activity, suggesting that there is some overlap in the physiological processes affected by exercise and inactivity. Low LPL secondary to inactivity is associated with diminished plasma triacylglycerol uptake and after 1 and 11 days alike, plasma HDL levels had decreased by roughly 20% (Bey & Hamilton, 2003).
The influence of inactivity on LPL activity is dependent upon muscle fibre type. The slow-twitch motor units are therefore affected the most in relative terms, as the higher threshold, fast-twitch fibres are only recruited when more strenuous activity is performed, in keeping with Henneman’s size principle (Henneman et al., 1965). Indeed, LPL activity decreased to only 10% of that of controls after 12 hours of unloading in rats in muscle fibres recruited most frequently in everyday life (Hennig & Lømo, 1985).
In a model of inactivity where one leg was prevented from bearing the rodent’s body mass, LPL activity decreased to 5% of that in controls in the most oxidative muscle fibres in the unloaded leg (Bey & Hamilton, 2003). The contralateral leg that still bore the rodent’s body mass did not show such a decline. These findings therefore highlight that a decline in LPL activity is a local phenomenon.
The health implications of these alterations in LPL activity are vast. Impaired LPL function may contribute to diabetes-induced dyslipidemia (Shimada et al., 1995), coronary artery disease incidence and severity (Wittrup et al., 1999), metabolic problems in aging (Hamilton et al., 2001), hypertension (Stump et al., 2006) and metabolic syndrome (Komurcu-Bayrak et al., 2007). Some evidence points to positive effects of LPL on attenuating diet-induced obesity and insulin resistance (Koike et al., 2004), but this is equivocal (Kim et al., 2001).
As this research is in its infancy, it is likely that numerous other proteins are also affected.
Inactivity, Insulin Sensitivity and Glucose Disposal
Skeletal muscle accounts for roughly 80% of insulin-stimulated glucose disposal. In rodents, enforced immobility rapidly engenders peripheral insulin resistance (Seider et al., 1982). Dunstan and colleagues (2012) demonstrated that, in overweight and obese adults, interspersing sitting with 2 minute bouts of low-intensity physical activity every 20 minutes produced a 23% decrease in insulin area under the curve and a 24% reduction in postprandial glucose area under the curve compared with a group that did not perform the low-intensity activity.
Genetic Influences on Responses to Inactivity
It appears that a specific genotype may predispose individuals to the adverse effects of inactivity. More specifically, when carriers of a select T allele of the TCF7L2 gene (the most significant type 2 diabetes mellitus susceptibility gene) are exposed to bed-rest, they fail to augment their insulin secretion to mitigate the insulin resistance that results from reduced muscular activity (Alibegovic et al., 2010).
Inactivity and Body Composition
Multiple lines of evidence converge to support the contention that inter-individual differences in non-exercise activity may have effects on body composition. For example, lean and obese people stand and ambulate around 9 and 6.5 hours per day, respectively (Levine et al., 2005). Simply supporting the body and engaging in spontaneous movement raises whole-body energy expenditure around 2.5-fold above sitting (Levine et al., 2000).
Non-exercise activity also declines significantly as people age (Harris et al., 2007) and there is a tendency towards increased adiposity with age up to a point. Therefore, given the small differences in daily energy balance that could explain weight gain over many years (Hill, 2005) it is possible that non-exercise activity plays a role in modulating adiposity.
Strategies to Circumvent Inactivity
If you’re job entails prolonged periods of relative inactivity, fear not. There are numerous, easy ways to incorporate more movement into your daily life, without necessitating any unwarranted neuroticism over avoiding sitting still.
Some of these suggestions will be more socially ‘acceptable’ (ergo commonplace) than others, but the trick is simply to incorporate those that you feel you can include in your life.
• Walk. If you feel you can make the time to do so, take a stroll, whether to work or the shops. Being outdoors can, of course, confer other benefits related to factors such as sun exposure.
• Cycle. If your destination is beyond walking distance, or you’re pressed for time, hop on your bike.
• Park further from your destination. This is a simple way to naturally include more walking in your daily activities.
• If you’re on the train or on a plane, take advantage of the aisle to stretch your legs.
• If you’re on a busy train, offer your seat to another passenger.
• If you’re on a boat, get out on the deck and enjoy the sea breeze.
The feasibility of implementing these recommendations will depend upon how forward-thinking your employer is (or on your own desire, if you’re self-employed).
• Consider a standing desk or, better yet, a stepping, bicycle or treadmill desk. Energy expenditure studies suggest that if an individual in energy balance replaced 2 hours of workplace sitting per day at a stepping desk, a body mass loss of roughly 20kg could ensue over the course of 1 year, if all else remained equal (McAlpine et al., 2007). I don’t think this would pan out in the real world given how fiercely the body defends its body fat mass, but I think it could only benefit health, nonetheless.
• During sitting, rhythmically tense and relax the muscles of your legs from time-to-time.
• Take a break from the screen. If applicable, offer to make your colleagues a tea and coffee round and you can kill two birds with one stone by helping to foster good relationships and promoting your own metabolic health. If you’re self-employed, punctuate your work with some gentle calisthenics. Good options include those that help counter the posture which you hold. For example, if you sit, include exercises that counteract hip flexion and an anterior head carriage (not that this necessarily accompanies sitting) such as straight leg glute bridges with the back of your head resting on a bench. One way to ensure that you adhere to this is to set some sort of timer to remind you get up every 20 minutes or so. Such activity has been shown to improve insulin and blood glucose metabolism (Dunstan et al., 2012).
• If you sit during working hours, use your lunch break to move around. Go elsewhere to eat. If you aren’t eating, go for a walk.
• If you have a mini-fridge at your desk, get rid of it. Not only will this reduce the likelihood of you engaging in mindless eating, it will also require you to be more active in procuring your food.
In the Home
• If you watch TV, move around intermittently while doing so. This could entail doing some self-myofascial release work in the form of foam rolling or some static stretching.
• Do the housework. This might entail washing up the dishes, vacuuming the house or hanging out the washing to dry.
• Growing your own fruit and vegetables can be deeply satisfying, healthy, and an easy way to increase your non-exercise activity energy expenditure.
There are numerous other ways by which to incorporate more activity into your life, including something as simple as choosing the stairs over the escalator. If you feel it would help you commit to being more active, a pedometer can be a useful means by which to monitor your movement, and you can set target step counts, gradually increasing your activity until you reach a point which you feel is both sustainable and beneficial. As an approximation, 10,000 steps daily seems to be a reasonable target that can confer health benefits among people who are otherwise sedentary. Better yet, an accelerometer will also let you track the intensity of your activity.
I hope this post has shed some light on the specifics of why staying active is important, and provided easily implemented ways to increase activity.
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Greg Potter is a Coach, Personal Trainer and Sports Massage Therapist in the U.K. Check out his blog at http://gdmpotter.blogspot.co.uk/ and find him on Twitter @GDMPotter