The physiological benefits of sitting less and moving more: opportunities for future research

Introduction

Being physically active is one of the important health components of health. Current physical activity (PA) guidelines for Americans recommend that adults should perform an equivalent of moderate-intensity aerobic activities for at least 150 minutes and muscle-strengthening activities for at least 2 days, on a weekly basis.¹ In addition, the guidelines recommend that adults should reduce sedentary behavior. Previously, excessive sedentary behavior was considered as one end of the continuum of PA, and “sedentary behavior” and “physical inactivity” were used interchangeably. While physical inactivity is defined as no moderate- or vigorous intensity PA beyond basic movement from daily life activities,¹ sedentary behavior refers to any waking activity characterized by little energy expenditure above rest [≤1.5 metabolic equivalents (METs)].² These activities are usually performed while in a sitting, reclining, or lying posture, such as TV viewing, computer work, and other screen time.²

Sedentary behavior is highly prevalent in the United States (US) and is a public health issue. Data from the National Health and Nutrition Examination Survey indicates that US adults spent 7.7 hours per day on being sedentary.² The time in sedentary behavior has further increased during the coronavirus disease 2019 (COVID-19) pandemic.³ Accumulating epidemiological evidence indicates that sedentary behavior or prolonged sitting is a risk factor for all-cause and cardiovascular disease (CVD) mortality.² The risks related to sedentary behavior are more pronounced in adults who are physically inactive, a risk that is decreased even by replacing sedentary time with light-intensity PA,⁴ such as desk pedaling or walking around the house. In addition to total amount of sedentary time, prolonged, repetitive bouts in sedentary activities is also associated with a greater risk of mortality.⁵ Prolonged sedentary behavior, such as prolonged sitting, should be broken up by standing or moving. While mounting evidence has focused on moderate-to-vigorous physical activities due to its substantial health benefits, little is known about the effect of sedentary behaviors on health. Such knowledge is important, given that the majority of the US population perform insufficient or no moderate-to-vigorous physical activities and are at high risk of being negatively influenced by sedentary behavior.⁶ Interventions targeting sedentary time, such as breaking up sedentary behavior by standing and moving, may be safe, feasible, and applicable to execute daily for a wider range of the population.

Therefore, this review discusses the pathophysiological effects of sedentary behavior and the potential physiological benefits of reducing/breaking sedentary behaviors at levels below the current guidelines for PA. This review also discusses the importance of monitoring sedentary behaviors in the era of the COVID-19 pandemic and the clinical implications of sitting less and moving more.

Sedentary Behaviors and Physiological Effects

Cardiorespiratory fitness

Cardiorespiratory fitness (CRF) is an important predictor of health outcomes and has been associated with premature mortality and chronic diseases.⁷ Every 1 MET increase in CRF is associated with a 19% decrease in risk of CVD mortality.⁸ Recent studies suggest that sedentary behavior is associated with reduced CRF.^{9, 10} More specifically, using accelerometer data, Kulinski et al. showed that each additional hour of daily sedentary time was associated with a decrease in CRF by 0.12 METs in men and by 0.24 METs in women.¹⁰ Other studies, using self-reported time in sedentary behaviors (e.g., sitting or TV viewing), also found that similar negative associations between sedentary time and CRF.^11–13 On the other hand, Eriksen et al. found that the associations of higher total daily sitting time with lower CRF existed in individuals who were sedentary or lightly physically active, but not in those moderately or vigorously physically active.¹¹ Barlow et al. found that sitting time was negatively associated with CRF in women, but not in men.¹³ Their findings may be explained by the difference in PA between men and women; compared to men, women generally are more sedentary as well as participate in less daily moderate and vigorous PA.¹⁰

Taken together, the evidence suggests that persons who participate in long periods of sedentary behavior, particularly in combination with low PA levels, are at high risk of low CRF, and are therefore at greater risk for CVD mortality.^{7, 8} Although there is no clinical trials examining the effects of reducing sedentary time on CRF, such interventions targeting sedentary behaviors may have considerable implications for CRF, especially for individuals who do not engage regular moderate-to-vigorous PA.^{10, 14}

Cardiac function

Cardiac function maintains blood supply to the body and is one of the determining factors of CRF. PA or regular exercise is known to be associated with structural and functional adaptations in the heart, including changes in systolic and diastolic function. Cardiac systolic function describes the contractility of the heart and can be measured by cardiac output, a product of stroke volume and heart rate, while diastolic function refers to cardiac relaxation and ventricular filling rate. At rest, compared to untrained individuals, athletes have higher stroke volume but lower heart rate,¹⁵ and thus similar cardiac output.¹⁶ During exercise, athletes have higher maximal cardiac output, as a result of higher maximal stroke volume,^16–18 which may contribute to higher CRF than untrained individuals.¹⁷ Highly trained individuals have higher resting diastolic function^{19, 20} and tend to have higher ventricular filling and emptying rate during exercise.^{21, 22} These functional adaptations are also associated with structural adaptations in response to PA, such as increased left ventricular wall thickness.²³ On the other hand, lack of PA or cessation of regular exercise results in loss of these adaptations.²⁴ While evidence is based on either the comparison between athletes and untrained individuals or the effect of exercise training or moderate-to-vigorous physical activity,^{25, 26} there is no study targeting the effect of sedentary behavior on cardiac function. In this context, studies are needed to determine whether reducing sedentary time is sufficient to induce positive cardiac adaptations.

Vascular function

Vascular function, measured as endothelial function and arterial stiffness, plays an important role in cardiovascular health. Endothelial cells form a single layer and lie on the interior surface of all blood vessels. Endothelial cells maintain vascular homeostasis by regulating the balance between vasoconstriction and vasodilation.²⁷ Impaired endothelium-dependent vasodilation is the signature feature of endothelial dysfunction; endothelial dysfunction is the critical step of developing atherosclerosis.²⁸ Arteriosclerosis is also associated with the stiffening of large arteries. Increased arterial stiffness causes hemodynamic changes,²⁹ including excess transmission of pressure pulsatility to the microcirculation, and is associated with target organ damage and an increased incident of CVD.³⁰ Individuals at risk of CVD, such obesity, diabetes, or hypertension, commonly have endothelial dysfunction and increased arterial stiffness, compared to healthy controls.^{31, 32}

There is sufficient evidence to indicate that sedentary behavior is associated with vascular dysfunction. Flow-mediated dilation (FMD) is the gold standard, non-invasive assessment of endothelial function.^{33, 34} A meta-analysis of 17 experimental studies found that a single bout of prolonged sitting for 1.5–6 hours decreased FMD by ~2% in the lower limbs.³⁵ A decrease in FMD by 1% is associated with an increased risk for future cardiovascular events by 13%.³⁶ Carotid to femoral pulse wave velocity (cfPWV) is the gold standard measure of arterial stiffness.³⁷ Another meta-analysis of 12 studies found that higher time spent in sedentary behaviors was associated with increased cfPWV.³⁸ Experimental study also showed that a 3-hr bout of prolonged sitting acutely increased cfPWV.³⁹ Increased cfPWV is associated with a 48% increased risk for a first cardiovascular event.⁴⁰ Other studies have also shown that a single bout of prolonged sitting for 3–4 hours reduces cerebral blood flow,^{41, 42} as well as increases blood pressure and cerebral vascular resistance.⁴³ These adverse alterations in cerebral hemodynamics may negatively impact brain health and cognitive function in a long term.

Interrupting prolonged sedentary behavior may prevent the related adverse changes in vascular function. A meta-analysis showed that a single bout of prolonged sitting with interruptions was associated with higher FMD than uninterrupted sitting.³⁵ Hartman et al. found that 2-minute walking breaks at light intensity PA every 30 minutes prevented a decline in FMD and cerebral blood flow following a 3-hour bout of prolonged sitting.⁴² The authors further found that a 16- week intervention on preventing prolonged sitting (>30 min) resulted in an increase in FMD and cerebral blood flow.⁴² In agreement with these findings, Carter et al. found that 2-minute walking breaks at light intensity PA every 30 minutes prevented a reduction in cerebral blood flow following a four hour bout of prolonged sitting.⁴¹ On the other hand, 8-minute walking breaks at light intensity PA every 2 hours did not protect cerebral blood flow from being reduced by prolonged sitting.⁴¹ Kruse et al. found that declines in FMD following a four hour bout of prolonged sitting were not reversed by using 10-minute standing or desk pedaling breaks every hour.⁴⁴ Graves et al. also found that increasing standing time and decreasing sitting time by using a standing desk during workdays for 8 weeks did not change FMD.⁴⁵ In terms of cfPWV, there was no difference between workers who were long-term seated vs. standing desk users.⁴⁶ In addition, seated calf raises ten times every 10 minutes during a three hour bout of prolonged sitting did not prevent an increase in cfPWV.³⁹ To prevent adverse changes related to sedentary behavior in vascular function, interruption of prolonged sedentary behaviors should be frequent (e.g., every 30 minutes) and with sufficient intensity (e.g., sitting to standing or breaks with short durations of light walking).

Skeletal muscle function

Skeletal muscle generates physical movements, and the integrity of the skeletal muscle system plays a major role in functional capacity and the ability to perform activities in daily life. Moreover, skeletal muscle regulates insulin sensitivity and participates in glucose metabolism. While muscle mass and strength can predict levels of PA,⁴⁷ the amount and intensity of PA also influence muscle health. Studies found that lifelong or elevated PA during adulthood was positively related to higher muscle mass and strength at older age.^48–51 On the other hand, reduced or insufficient PA is associated with loss of muscle mass,^{52, 53} lower insulin sensitivity, and increased risks of physical dysfunction.⁵⁴ The underlying mechanisms of PA on muscle function are with multiple facets from the organelle in muscle cells to muscle fiber-types. PA has been shown to enhance mitochondrial function,^55–57 increase anti-oxidant components,⁴⁸ increase blood flow and oxygenation,⁵⁸ and maintain appropriate type of muscle fiber proportions in skeletal muscle.⁵⁶

Time spent in sedentary behavior may also contribute to decreased skeletal muscle function. Cross-sectional studies indicated that longer sedentary time such as television viewing was associated with lower muscle strength, muscle power, and muscle mechanical quality.^59–63 Reducing sedentary time by increasing PA, regardless of intensity, may prevent the adverse effects of being sedentary on muscle function.⁶⁴ Studies have shown that a greater amount of PA, even at light intensity, was associated with higher muscle strength and lean mass.^{59, 60} However, the adverse effects of sedentary behavior and benefits of light PA on muscle function may exist in men, but not in women.^{62, 65} These effects may also be influenced by age and disease status, such as diabetes.^{66, 67} Some studies even suggested that time spent on moderate-to-vigorous PA, instead of sedentary behavior and light PA, is a key to determine the improvements in muscle function.^{65, 68} While more studies are needed to decipher the relationships between sedentary behavior/PA with muscle function, decreasing sedentary time and increasing PA should still be encouraged to prevent the adverse effect of sedentary behaviors/physical inactivity on muscle function.

Fatigue

Fatigue is a symptom commonly seen in work settings and often found in older populations or individuals with chronic diseases.^{69, 70} Fatigue is caused by multiple factors, at physical and/or mental levels, and is usually quantified through examining perceived and performance fatigabilities. While performance fatigability describes an objective functional reduction, such as in muscle strength or walking speed, during a period of PA, perceived fatigability represents a subjective and perceived state of changes in the integrity of performing an activity.⁷¹ Studies have shown that perceived fatigability can interfere with quality of life and is associated with a higher risk of mortality.^{70, 72}

While the associations of perceived fatigability with PA have been reported,^{73, 74} less has focused on its relationship to sedentary time. A sedentary lifestyle may be a compensatory strategy to minimize a level of fatigue. It may also increase severity of fatigue, associated with pathophysiological changes induced by sedentary behaviors as described in the previous sections. The relationships between perceived fatigability and sedentary behaviors may be influenced by the domains of fatigue measured, subject characteristics, such as disease statues, and levels of PA. Engberg et al. found that in the general population, longer sitting time was associated with a higher level of general fatigue, physical fatigue, and reduced activity, but not with mental fatigue.⁷⁵ On the other hand, in cancer survivors, a systematic review did not find a clear relationship of fatigue with sedentary behaviors.⁷⁶ Ellingson et al. found that a higher level of perceived fatigue was associated with higher sedentary time, but the association was only observed in those who did not meet the current PA guidelines.⁷⁷ Breaking up sedentary behavior by sitting less and moving more might abolish the association with fatigue in sedentary populations.

Although a causal relationship of fatigue and sedentary time remains to be determined, it is presumable that sedentary behaviors and fatigue together form a vicious cycle. To break the cycle, it is necessary to break up prolonged sedentary time as much as one can. Zaslavsky et al. used an isotemporal substitution model to estimate the associations between substituting sedentary time for other types of PA and perceived fatigability.⁷⁸ Their findings suggested that perceived fatigability can be improved even by decreasing sedentary time with low light physical activities (e.g., washing and drying dishes).⁷⁸ A single bout of 10-min mild exercise has also been found to acutely increase the brain activity in the dorsal-lateral prefrontal cortex,⁷⁹ the same area deemed as an important neural substrate for regulating fatigue feedback and adjusting central drive.⁸⁰ For adults who are sedentary, repeated light PA or mild exercise may be an initial approach of decreasing sedentary time and improving fatigue.

Increasing Sedentary Behaviors in the Era of COVID-19 Pandemic

The COVID-19 pandemic has dramatically changed health behaviors, including a decline in PA and an increase in sedentary behaviors.³ These may be potentially due to stay at home orders and social distancing policies that restrict the access and ability to perform physical activities and increase the risk of being sedentary. Even though stay at home orders have been lifted in the US at this time, many people may still have safety concerns regarding going to public gatherings while others remain working from home. Our group conducted an online survey in adults 18 years or older in the US, between May 27, 2020 and June 26, 2020. We found that adults who always worked from home reported ~9 hours daily spent on sitting (n=283; unpublished data). Compared to the time prior to the COVID-19 pandemic, this equated to an hour increase in sedentary time, which may lead to significant negative health impacts, as described in the previous sections. While a flexible approach to moderate-to-vigorous PA is necessary, targeting sedentary time is also important and may be safer, more feasible, and applicable to execute daily for a wider range of the population in a home setting. There are no apparent guidelines focusing on sedentary behavior and increased movement in the new at home environment. Future recommendations for sedentary behavior disruption in the era of a pandemic prevention and mitigation appear critically important. Opportunities do exist; for instance, one can easily setup reminders on a computer or mobile phone to take regular breaks during prolonged sitting (i.e., > 30min),⁵ by standing or by performing some low-intensity activities, such as desk pedaling or walking around the house for 1–2 minutes.

Summary

Sedentary behaviors, such as sitting or TV viewing, may be associated with several pathophysiological changes, including decreased CRF, reduced vascular or skeletal muscle function, and increased fatigue (Figure 1). These adverse effects of sedentary behavior may impact those who do not meet the current PA recommendations, which account for most of the US population. During the COVID-19 pandemic, the increases in sedentary behavior and the related pathophysiological effects have emerged as an important public health problem. This necessitates the development of an intervention strategy focusing on reducing/breaking up sedentary time or sitting less and moving more. Such interventions may be practical for people who currently do not meet the current PA recommendations, prior to attempting to adopt a more active lifestyle that approaches/meets/exceeds ideal PA recommendations. Additional studies are needed to identify the associations between sedentary behavior and health outcomes, as well as to determine the optimum strategies of reducing sedentary time. This information provides important clinical implications and will help improve current PA guidelines.

Figure 1.

Summary of physiologic responses to prolonged sedentary behavior.

List of Abbreviations

cfPWV

Carotid to femoral pulse wave velocity

CVD

Cardiovascular disease

COVID-19

Coronavirus disease 2019

CRF

Cardiorespiratory fitness

FMD

Flow-mediated dilation

METs

Metabolic equivalents

PA

Physical activity

US

United States