Exercise reduces cardiovascular inflammation by modulating the immune system

Exercise reduces cardiovascular inflammation by modulating the immune system

OVERVIEW

  • Voluntary and regular exercise in mice decreases the number of inflammatory leukocytes (white blood cells) in the bloodstream.
  • Exercise causes a decrease in leptin (a digestive hormone) secreted by fat cells, which decreases the production of leukocytes by hematopoietic stem and progenitor cells in the bone marrow.
  • Cardiac patients who exercised four or more times a week had lower leptin and leukocyte blood levels.
  • These results suggest that a sedentary lifestyle contributes to cardiovascular risk through increased production of inflammatory leukocytes.

It is well established that regular exercise has many benefits for cardiovascular health, but the underlying mechanisms have not yet been fully identified and understood. A recent study published in Nature Medicine shows that in mice, voluntary exercise reduces the proliferation of hematopoietic stem and progenitor cells (HSPC), which has the effect of reducing the number of inflammatory leukocytes in the bloodstream. Remember that HSPC cells have the ability to transform into different types of cells that are involved in the immune response (leukocytes, lymphocytes, macrophages, etc.).

A sedentary lifestyle, chronic inflammation and abnormally high white blood cell count (leukocytosis) promote atherosclerosis, which can potentially cause myocardial infarction, stroke or heart failure.

To test whether regular exercise can modulate hematopoiesis, the researchers put mice in cages in the presence (or not for the control group) of an exercise wheel, where they could exercise at their will. Mice use these exercise wheels readily and with great zeal and are therefore not subjected to stress as when they are forced to exercise such as, for example, forced swimming that has already been used in other studies. After six weeks, mice that exercised voluntarily (doing about 20 times more physical activity than sedentary mice) reduced their body weight and increased their food intake.

Analyses have shown that exercise reduced the proliferation of hematopoietic stem and progenitor cells by 34%. The decrease in HSPC through exercise had the effect of reducing the number of inflammatory leukocytes (white blood cells) in the bloodstream. In addition, the mononuclear cells in the bone marrow of mice that exercised were less able to differentiate into granulocytes, macrophages, and pre-B cells. The researchers showed that the mechanism involves a decrease in the production of leptin (a hormone secreted during digestion to regulate fat stores and control the feeling of satiety) in fat tissues. The decrease in leptin in the bloodstream of mice had the effect of increasing the production of factors of quiescence and retention of hematopoietic stem cells in the bone marrow, and consequently of decreasing the number of leukocytes in the bloodstream (see figure below).

Figure. Schematic summary of the effects of exercise on leukocyte levels and the risk of cardiovascular disease. LepR+: expressing the leptin receptor. Adapted from Frodermann et al., 2019.

Leptin supplementation in mice that exercised (using subcutaneous micropumps) reversed the exercise-induced effects on hematopoiesis, proving that this digestive hormone is involved in this phenomenon.

The exercise wheel was removed from the mouse cage after six weeks. Three weeks later, the effect on leptin production faded, but the effects of exercise on hematopoiesis persisted, i.e. the leukocyte levels of exercise mice were still lower than that of sedentary mice. There is therefore a “memory” of the exercise, which was related to epigenetic changes, i.e. to a difference in the expression of certain genes without alteration of their DNA sequence.

A reduction in leukocyte levels in the blood can lead to an increased risk of infection, as has already been observed for high-intensity exercise. The researchers wanted to see if this was the case with the mice in their study. A component of the cell wall of bacteria (lipopolysaccharide) was injected into the stomachs of mice to induce an inflammatory response. The mice responded quickly by increasing the number of HSPC and defence cells (neutrophils, monocytes, B lymphocytes, T-cells) in the blood and at the site of infection. Mice who exercised reacted more than sedentary mice to lipopolysaccharide injection and had a lower mortality rate when real sepsis was provoked. It is therefore clear that regular voluntary exercise in mice does not decrease the emergency immune response to infection.

The researchers then wanted to find out if the decrease in leukocytes caused by exercise could reduce atherosclerosis and inflammation of atherosclerotic plaques. To do this they used a “knockout” mouse line in which the gene encoding apolipoprotein E was inactivated (Apoe–/–­­­­­). This protein carries lipids into the blood and is essential for their elimination. Inactivation of the Apoe gene causes hypercholesterolemia and atherosclerosis in mice. Apoe–/–­­­­­ mice that developed atherosclerosis were placed in cages containing an exercise wheel, which led to a decrease in leptin levels, a decrease in leukocytes, and a decrease in plaque size. The same beneficial effects of exercise on atherosclerosis were observed in a mouse line in which the gene encoding the leptin receptor was inactivated specifically at the level of stromal cells.

The researchers finally wanted to know if exercise could have beneficial effects on hematopoiesis in patients with cardiovascular disease. To do this, they checked whether there was an association between the amount of exercise and the blood levels of leptin or the number of leukocytes in 4,892 participants of the CANTOS study, who were all recruited after having a heart attack. Participants who exercised four or more times a week had significantly lower leptin blood levels. Another study (Athero-Express Study) also showed a favourable relationship between the amount of exercise and levels of leptin and leukocytes. The results of these two clinical studies, combined with those obtained in mice, indicate that physical activity has beneficial effects on leptin levels and leukocytosis in patients with cardiovascular disease.

This new study suggests that a sedentary lifestyle contributes to cardiovascular risk through an increased production of inflammatory leukocytes, and confirms the idea that physical activity reduces chronic inflammation. Let us recall the main recommendations of the World Health Organization’s (WHO) regarding physical activity for health:

“In order to improve cardiorespiratory and muscular fitness, bone health, reduce the risk of noncommunicable diseases and depression,

  1. Adults aged 18–64 should do at least 150 minutes of moderate-intensity aerobic physical activity throughout the week or do at least 75 minutes of vigorous-intensity aerobic physical activity throughout the week or an equivalent combination of moderate- and vigorous-intensity activity.
  2. Aerobic activity should be performed in bouts of at least 10 minutes duration.
  3. For additional health benefits, adults should increase their moderate-intensity aerobic physical activity to 300 minutes per week, or engage in 150 minutes of vigorous-intensity aerobic physical activity per week, or an equivalent combination of moderate- and vigorous-intensity activity.
  4. Muscle-strengthening activities should be done involving major muscle groups on 2 or more days a week.”

To learn more about the benefits, quantity and types of exercise, check out these articles:

How much exercise to live longer?

Exercise on an empty stomach to burn more fat

Can regular exercise compensate for long periods spent sitting?

Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors

Exercise on an empty stomach to burn more fat

Exercise on an empty stomach to burn more fat

OVERVIEW

  • Sedentary men did supervised exercise 3 times a week for 6 weeks after ingesting either a sugary drink or a sugar-free placebo drink.
  • Participants who exercised on an empty stomach “burned” twice as much fat as those who consumed a sugary drink before exercise sessions.
  • Participants who exercised on an empty stomach also saw their insulin sensitivity improve more than those who ingested calories before the exercise sessions.

It is now well established that exercise in all its forms improves overall health. In addition to increasing cardiorespiratory capacity, regular exercise improves insulin sensitivity and reduces insulin secretion after meals. However, each individual’s response to similar exercises is very variable: some people become fitter or lose more weight or stabilize their blood sugar more than others. One of the factors that could be important is the timing of meals and exercise sessions. Muscles use energy in the form of sugars and fats, which can come from the last meal or from reserves in the body when fasting. The accumulation of too much fat in the muscles is problematic for health, because the fat-engorged muscles do not respond well to insulin, a hormone that stimulates the absorption of glucose by muscle, adipose and liver cells. Therefore, excess fat in the muscles can contribute to insulin resistance, hyperglycemia and increased risks of type 2 diabetes and other metabolic imbalances.

In a randomized controlled study, an international team tested the effect of the timing of meals on the metabolic benefits associated with exercise. Thirty sedentary and overweight or obese men were divided into three groups (see figure below): a control group that continued to live normally and two other groups that did supervised exercise in the morning (treadmill running), three times a week for six weeks, without breakfast; the second group ingested a vanilla-flavoured drink containing 20% sugar two hours before each exercise session, whereas the third group ingested a vanilla-flavoured placebo beverage containing water and no calories. After each morning exercise session, participants in both groups drank the beverage they had not received prior to the session. This means that all the runners ingested the same number of calories and did the same amount of exercise, only the timing of calorie consumption differed, i.e. before or after the exercise session.

Figure. Protocol schematic for the training study.  Adapted from Edinburgh et al., 2019.

The study was randomized and controlled, so participants did not know what type of drink they ingested before and after exercising. 83% of participants reported that they could not detect differences between the sugary and placebo drinks or were unable to identify which beverage contained sugar. It should be noted that the sugar used here, maltodextrin (partially hydrolyzed starch), has a very low sweetening power and is therefore difficult to detect.

Blood samples and biopsies of a muscle located in the thigh (vastus lateralis) were taken before and after the intervention in order to measure different metabolites and proteins of interest. Glucose, glycerol, triglycerides, HDL and LDL cholesterol, insulin, C-peptide, and fatty acids were measured in the blood, and phospholipid composition, protein content involved in glucose transport, insulin signalling and lipid metabolism were measured in the vastus lateralis muscle samples.

Not surprisingly, the control group did not improve their physical fitness or insulin sensitivity during these six weeks. On the contrary, the other two groups who exercised saw their fitness improved and their waistline decreased, although only a few of the participants lost weight.

The most striking finding of the study was that participants who exercised on an empty stomach “burned” twice as much fat as those who consumed a sugary drink before the exercise session. Yet participants in both groups who exercised expended the same number of calories.

Participants who ran on an empty stomach also saw their insulin sensitivity improve further and their muscles synthesized greater amounts of certain proteins (AMP-activated protein kinase, an energy sensor, and the glucose transporter GLUT4) involved in the response of muscle cells to insulin and the use of sugars.

Studies on exercise and metabolic health will need to consider the timing of meals in the future. Since it is not possible for everyone to exercise in the morning after the night fasting period, it will be interesting to check if it is possible to obtain the same metabolic benefits after a shorter daytime fasting period, for example, when exercising in the early evening after skipping lunch. However, it should not be forgotten that any physical activity (walking, housework, etc.), performed at any time of the day, is beneficial for health.

How much exercise to live longer?

How much exercise to live longer?

OVERVIEW

  • A meta-analysis published in October 2019 confirms that exercising reduces the risk of all-cause or cardiovascular mortality.
  • The decrease in risk is directly proportional to the amount of exercise up to about 2 hours of running per week. More than 4 hours of running per week or the equivalent do little to reduce the risk further.
  • Very high amounts of exercise (up to 8 times the amount of exercise recommended in public guidelines) do not reduce longevity, contrary to what some previous studies have suggested.

Exercise to live longer
Physical activity has many and varied beneficial effects on cardiovascular risk factors, including lower blood pressure and resting heart rate, improved blood sugar and lipidemia, normalizing body mass index, improved sleep and reduced stress. According to several long-term epidemiological studies, regular physical activity is one of the most effective lifestyle habits to increase life expectancy, up to 6 years.

Can too much exercise be detrimental to longevity?
This is an issue that is the subject of debate due to the conflicting data published to date. A meta-analysis published in October 2019 concludes that high amounts of exercise (up to 8 times the amount of exercise recommended by public guidelines) do not reduce longevity. This meta-analysis included 48 prospective studies, one of which included 6 distinct cohorts and another 9 distinct cohorts. Compared to the recommended level of physical activity (150 minutes of moderate to intense exercise per week), the mortality risk was lower for people who exercised more, at least up to 10 hours of running per week (Figure 1). This applies to all-cause mortality, and even more so to mortality from cardiovascular disease, including coronary heart disease. It should be noted that the reduction in mortality risk appears to be directly proportional to the amount of exercise up to about 2 hours of running per week and that more than 4 hours of running or the equivalent does little to reduce the risk further.

Figure 1. Dose-effect relationship between the amount of exercise and mortality from all causes, or mortality from cardiovascular disease, or mortality from coronary heart disease. The amount of exercise recommended in the public guidelines was used as a reference. Adapted from Blond et al., Br. J. Sports Med. 2019.

Some studies have suggested that a very large amount of exercise can decrease longevity. For example, a 15-year study of 55,137 participants (including 13,016 joggers) indicated that running reduced the risk of death from all causes by about 30% and the risk of cardiovascular mortality by 45%, with an increase in life expectancy of 3 years. A more detailed analysis of the results was made by the authors in an attempt to answer the question, “Is more exercise better for life expectancy?” The results show a so-called U-shaped curve (Figure 2) where hard runners (>49 MET-h/wk) appeared to have less benefit than light or moderate runners, but this difference was not statistically significant (P>0.05). One MET (Metabolic Equivalent of Task) corresponds to the amount of energy expended at rest, for walking it is 3.5 MET and for running it is approximately 7–8 MET.

Figure 2. Risk of mortality depending on the amount of running.
Adapted from Lee et al., Mayo Clinic Proc, 2016.

It should be noted that this is a single study, that the people who did >49 MET-h/wk represented only 1.6% of the study participants, and that the variation in the data collected was high. In contrast, the study described above, where very large amounts of exercise had no adverse effect on longevity, is a meta-analysis of 48 studies with a much higher total number of participants. This example illustrates why meta-analyses are so useful in epidemiology: they provide more accurate results (greater statistical power) and make it possible to draw global conclusions from a large number of studies and data.

Cardiorespiratory capacity and mortality risk
A recent study evaluated the association between cardiorespiratory capacity and all-cause mortality. The study population consisted of 122,007 patients who were followed for 8.4 years on average, during which time 13,637 patients died. At the beginning of the study, all patients did a treadmill stress test (limited by symptoms) to assess their cardiorespiratory capacity (CRC). For the analysis, participants were divided into 5 groups, according to the level of their CRC: low (<25th percentile), below average (25th–49th percentile), above average (50th–74th percentile), high (75th–97.6th percentile) and “Elite” (≥97.7th percentile). The results (Figure 3) clearly indicate that a greater CRC is associated with a decrease in mortality and that patients with very high CRC (Elite group) had the lowest risk of mortality.

Figure 3. Risk of all-cause mortality as a function of cardiorespiratory capacity.
Adapted from Mandsager et al., JAMA Network Open, 2018.

There is no U-curve in this study, but it must be noted that patients in the “Elite” group are not athletes and that it is not known whether or not they exercised regularly. The maximum cardiorespiratory capacity of the “Elite” group averaged 13.8 MET, which is considered excellent functional capacity, but slightly below the level of elite athletes (marathon runners, triathletes, cyclists) whose maximum cardiorespiratory capacity is about 17 to 20 MET. The fact remains thatcardiorespiratory capacity is a modifiable indicator of long-term mortality and that health care professionals should encourage their patients to achieve and maintain a high level of physical fitness.

Running a marathon puts a significant strain on the hearts of amateur runners
According to a Spanish study published in Circulation, amateur runners who complete a marathon event (42.2 km) see their levels of cardiac damage markers increase significantly. Cardiac markers [cardiac troponins I and T (TnIc and TnTc), the N-terminal truncated form of natriuretic brain peptide (NT-proBNP), creatine kinases (CK-MB and CK-MM), myoglobin] are proteins that are released into the blood when the heart muscle is damaged. In contrast, in half-marathon runners (21.1 km) and 10 km races there was no significant increase in markers of heart damage. A sudden increase in cardiac markers after exercise is generally considered benign because the normal values of these markers are restored after a few days. The authors of the study note that although the release of cardiac troponins into the blood is not an indicator of heart malfunction, higher concentrations after a marathon reflect greater cardiac stress than for shorter runs. The incidence of cardiac arrest during marathons is a fairly rare phenomenon, i.e. 1 in 50,000 runners who complete the race, but these accidents are highly publicized. Cardiorespiratory arrests during marathons occur especially in men aged 35 and over and are caused by coronary artery disease (obstruction of one of the coronary arteries that irrigates the heart muscle). When cardiorespiratory arrest occurs in a young person under the age of 35, the cause is usually congenital heart disease. Given the growing popularity of marathons and the lack of experience and adequate preparation of some amateur runners, this study suggests that shorter races (e.g. half marathons) would be more suited to reduce the stress placed on the hearts of these runners.

No U-curves for light to moderate intensity exercise
The Copenhagen City Heart Study recently reported that leisure time physical activity reduces both all-cause mortality and mortality from coronary heart disease. Compared to sedentary participants, the gains in life expectancy were: 2.8 years for those who did light physical activity, 4.5 years for moderate-intensity physical activity, and 5.5 years for high-intensity physical activity. There is no U-curve in this study, but it should be noted that participants who exercised intensely (4 hours per week or several hours per week of a competitive sport) in this study still did less than those of the other studies cited above. In several other studies of light to moderate intensity exercise during leisure time, a U-shaped relationship was not observed. In other words, it does not seem possible to do too much light to moderate physical activity, such as walking, housework, gardening, baseball or softball, bowling, volleyball, golf, doubles tennis (and other racket sports) and dance.

Humans have adapted to do a lot of physical activity during life. A recent study of the Hazda hunter-gatherer modern tribe in northern Tanzania shows that, on average, these people do 14 times more light-to-moderate physical activity than North Americans. Members of the Hazda tribe have few cardiovascular risk factors (low prevalence of hypertension throughout life, optimal levels for cardiovascular health biomarkers). The Chimanes, an indigenous people in the Bolivian Amazon who have a subsistence lifestyle based on hunting, fishing, gathering, and farming, also has excellent cardiovascular health. Chimanes are very active, travelling up to 18 km per day and it is estimated that less than 10% of waking hours are spent on sedentary activities, compared to more than 60% in North America.

On the contrary, North American adults today sit an average of about 10 hours a day out of 16 waking hours. Physical exercise on a regular basis is therefore necessary to maintain good cardiorespiratory capacity as well as good cardiovascular health and to be able to live longer in good health.

Aerobic fitness is associated with levels of blood metabolites that are good for your health

Aerobic fitness is associated with levels of blood metabolites that are good for your health

A large number of studies indicate that there is a positive association between exercise and good health, particularly good cardiovascular health. Researchers are now focusing their efforts on identifying the physiological and molecular mechanisms underlying these beneficial effects.

A study conducted among 580 young Finnish men shows that aerobic fitness (also known as cardiorespiratory capacity) is associated with levels of several metabolites that are beneficial to health. The approach used in this study is referred to as “metabolomics”, i.e. an approach that aims to identify metabolic differences, for example in the blood of people with a disease (diabetes, cancer) compared to people in good health. Most of the metabolomic studies conducted to date have focused on diseases, but this approach has also been applied recently to determine which metabolites are indicative of good health, particularly with regard to exercise.

Of the 66 metabolites selected in the Finnish study, 48 were at different levels between the group of participants who had the highest aerobic fitness and the one with the lowest aerobic fitness (see Figure 2 and Figure 3 of the original article). These differences include a 44% lower concentration of low-density lipoprotein (LDL, the “bad cholesterol”), an 81% higher concentration of high-density lipoprotein (HDL, the “good” cholesterol), a 52% lower total of triglycerides (Figure 1 below, orange bars). On the other hand, greater muscular strength of the participants was not associated with favourable levels for these same metabolites (Figure 1 below, blue bars).

Figure 1. Main differences in blood metabolites between the participants who had the highest aerobic fitness and those who had the lowest (orange bars) or between the participants who had the highest muscular strength and those who had the lowest (blue bars). * Significant difference (P <0.001 or P <0.002); NS: Not significant difference. From Kujala et al., 2019.

Cholesterol
The more detailed analysis (see Figure 2 in the original article) shows that all LDL and VLDL particles of different sizes (small, medium, large, very large, extremely large) are present in lower concentrations in the blood of participants who have a good aerobic capacity than in participants who have a lower aerobic capacity. On the contrary, all HDL particles (very large, large, or medium-sized), except for small ones, are present in higher concentrations in the group with the highest aerobic fitness. Large-size HDLs are particularly beneficial for good cardiovascular health.

Participants with good cardiorespiratory capacity had 80% less apolipoprotein B (ApoB) in their blood than those who were less fit. ApoB is a protein found in very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The measurement of the ApoB makes it possible to estimate the number of particles of cholesterol, which is a good indication of the risk of developing cardiovascular disease. High blood levels of ApoB are therefore a risk marker for cardiovascular disease, independently of the level of LDL-cholesterol.

Triglycerides
A high concentration of triglycerides in the blood is a risk marker for coronary heart disease and is associated with obesity and type 2 diabetes. Excessive consumption of sugars and alcohol (not fat) is generally the cause of a high level of triglycerides in the blood.

Other metabolites
Other important metabolites that are present in lower concentrations in individuals with good aerobic capacity include total fatty acids (-60%), glycerol (-64%), lactate (-34%), pyruvate (-36%), branched-chain amino acids (BCAA) isoleucine (-37%) and leucine (-55%), and amino acids phenylalanine (-54%) and tyrosine (-55%). Interestingly, theunsaturation degree of fatty acid of participants in better aerobic fitness was 59% higher than in less fit participants; asituation conducive to good cardiovascular health knowing that it is saturated fatty acids that, in excess, increase theconcentration of LDL-cholesterol and are atherogenic.

High levels of BCAA, phenylalanine and tyrosine are found in obese people and they have been associated with a 5-fold increased risk of developing type 2 diabetes in two separate cohorts. Lower levels of glycerol and ketone bodies (acetylacetate, 3-hydroxybutyrate) in individuals with a high aerobic capacity suggest an increase in fat degradation.

Several metabolites (19) remain associated with a high aerobic fitness after adjustments to account for age and percentageof body fat. After making the same adjustments, muscular strength was associated with only 8 measures of the “metabolome” and none of these associations related to cholesterol or other blood lipids.

This study found more favourable associations between aerobic fitness and certain metabolites that are risk factors for cardiovascular disease than for high muscular strength. It should not be concluded, however, that muscular endurance exercises are useless, quite the contrary. Indeed, muscle training increases aerobic fitness and is an important component of maintaining and improving the condition of people with chronic diseases and the elderly. It is therefore necessary to combine aerobic and muscular exercises to optimize the benefits for cardiovascular health and overall well-being.

Active transportation, a great way to balance work and health

Active transportation, a great way to balance work and health

Although regular physical activity is associated with a marked decrease in the risk of several chronic diseases and premature mortality, the proportion of sedentary people, i.e. who do not reach the minimum of 150 minutes of physical activity recommended per week, continues to increase worldwide. According to recent estimates, a sedentary lifestyle is directly responsible for about 10% of premature deaths worldwide, a negative impact similar to that of smoking and obesity. Several factors contribute to this decline in the level of physical activity, the most important of which are probably the major social transformations that accompanied industrialization and, more recently, the technological revolution: motorized transport modes make it possible to travel great distances easily, computing is at the centre of many professions, and the constant arrival of new electronic devices continues to reduce the energy costs of most of our activities, both at work and at home. While this progress can generally be viewed as positive in terms of improving quality of life, it is important to remain aware that the resulting decrease in physical activity can be detrimental to health.

Canada is not immune to this trend, as studies that have measured physical activity levels accurately (using an accelerometer) show that only 15% of adults are active enough to reach the minimum of 150 minutes of physical activity per week. This is very little, and although lack of time is the main reason given by sedentary people for their low participation in physical activity, this excuse does not really hold up: 29% of Canadian adults spend 15 hours or more per week (more than two hours a day) in front of the TV and 15% are frequent computer users (11 hours or more per week) during leisure time. There is therefore a window of time available to reduce the sedentary lifestyle, especially since it is possible to be more active without having to dedicate a specific period of the day to exercise: several studies show that the simple fact of integrating light or moderate physical activities in our daily routine, whether walking, gardening or doing housework, is enough to enjoy the benefits of exercise on health (see our article on this subject).

Active transportation
The time spent commuting to and from work represents another interesting opportunity to increase the level of physical activity. In Canada, the use of motorized means of transportation to get to work is widespread, with 8 out of 10 workers using a motor vehicle for daily commuting (75% as drivers, 5% as passengers) (Figure 1). Conversely, active modes of transport such as walking and cycling are used by only 8% of workers, a proportion that is much lower than in most European countries: in Holland for example, no less than 50% of all daily trips are made by walking and cycling, while in all Nordic countries (Denmark, Sweden, Norway and Finland) this proportion is around 30%.


Figure 1. Distribution of the modes of transportation used by Canadians to get to work. From Statistics Canada (2013).

This low use of active transportation in North America likely contributes to the negative impacts of a sedentary lifestyle, particularly with respect to the high proportion of people who are overweight. It has been estimated that each hour spent in a car is associated with a 6% increase in the risk of obesity, while every kilometre walked is associated with a 5% reduction in the risk of being overweight. For example, an Australian study that followed 822 people over 4 years found that those who travelled every day by car tended to have greater weight gain (2.18 kg) than those who did not use a car (0.46 kg). This is in agreement with the results of a British study showing that people who stopped using their car to get to work and replaced it with active transportation or public transit lost weight (- 0.30 kg/m2). Conversely, those who stopped using active modes of transportation and instead opted for the car saw their body mass index significantly increase (+ 0.32 kg/m2).

In addition to promoting the maintenance of a healthy weight, several studies have shown that active transportation also has several positive effects on health, particularly in terms of prevention of cardiovascular disease, type 2 diabetes and premature mortality. One of the best examples is a large study of 263,540 participants living in 22 communities in the United Kingdom. By analyzing the modes of transportation used by this population to get to work, the researchers found that cyclists had a 41% lower risk of premature mortality than those who used motorized transport (public or cars). A positive effect was also observed for walkers, with a 27% reduction in the risk of myocardial infarction and a 36% reduction in the risk of dying from a cardiovascular event. Overall, a meta-analysis of 23 prospective studies that examined this issue (531,333 participants in total) shows that commuters who use active transportation (cycling, walking) have a significantly lower risk of cardiovascular disease (9%), type 2 diabetes (30%), and premature mortality (8%). As with any form of physical activity, these benefits associated with active transportation come from the many positive effects of this type of exercise on all cardiovascular risk factors, including hypertension, dyslipidemia, diabetes and obesity (Table 1).

Table 1. Major cardiovascular risk factors influenced by active transportation.

Cardiovascular risk factors mitigated by active transportationReferences
HypertensionZwald et al. (2018)
Hayashi et al. (1999)
Furie and Desai (2012)
Gordon-Larsen et al. (2009)
Berger et al. (2017)
Laverty et al. (2013)
Grøntved et al. (2016)
Murtagh et al. (2015)
High cholesterolZwald et al. (2018)
Furie and Desai (2012)
Low HDL cholesterolZwald et al. (2018)
High triglyceride levelsGordon-Larsen et al. (2009)
Berger et al. (2017)
Grøntved et al. (2016)
Diabetes
(including glucose intolerance and insulin resistance)
Zwald et al. (2018)
Hu et al. (2003)
Furie and Desai (2012)
Gordon-Larsen et al. (2009)
Blond et al. (2019)
Laverty et al. (2013)
Grøntved et al. (2016)
High body mass indexZwald et al. (2018)
Furie and Desai (2012)
Gordon-Larsen et al. (2009)
Berger et al. (2017)
Laverty et al. (2013)
Flint et al. (2014)
Grøntved et al. (2016)
Murtagh et al. (2015)
Luan et al. (2019)
High waist circumferenceFurie and Desai (2012)
Murtagh et al. (2015)

The benefits of cycling
The positive impacts of active transportation are particularly striking for those who travel by bicycle, with higher reductions in the risk of several chronic diseases and premature mortality than those who walk (Figure 2). These benefits associated with regular cycling are in line with Danish and British studies indicating that premature mortality rates are about 30% lower for cyclists compared to non-cyclists. This superiority of cycling over walking is probably due to the fact that cyclists in these studies showed a higher level of overall physical activity than walkers, with 90% of the people travelling by bicycle who reached the minimum recommended activity against 54% for those who travel on foot.


Figure 2. Reduced risk of several chronic diseases depending on the mode of active transportation. Adapted from Dinu et al. (2019).

Intervention studies carried out among sedentary people show that the positive effects of active bicycle transportation on health can be observed in the first six months following the adoption of this mode of transport. For example, people who cycle 20 minutes daily to commute to work for 8 weeks already show a noticeable improvement in their maximum aerobic fitness (VO2max), one of the best markers of good health. More recently, a British study showed that only 6 months of active bicycle transportation resulted in abdominal fat loss and significant improvement in insulin sensitivity in a group of sedentary people who were overweight or obese. The positive impact of active transportation is therefore very rapid, and these modes of transport can really contribute to improving the health of sedentary people.

It is also interesting to note that the benefits of active bicycle transportation on the reduction of all-cause mortality and type 2 diabetes are similar to those observed among people who cycle in their leisure time (Figure 3). For people who lack the time to exercise during the week or the weekend, riding a bike to work compensates for this lack of time by integrating physical activity into their daily routine. Not to mention that some studies suggest that the bicycle is the mode of transport that makes you happiest!


Figure 3. Risk of premature death for people who use bicycles in leisure time or as an active means of transportation. Adapted from Østergaard et al. (2018).

 

Fragmented transport
Walking or cycling to work is obviously not within everyone’s reach, especially for people who have to travel long distances from home to their workplace (in Canada, for example, over half of workers live more than 8 km from their work). On the other hand, even without completely replacing the use of motorized vehicles, it is still possible to be more physically active by walking or cycling for a portion of the journey (using bicycle-sharing systems), for example by parking the car at a certain distance from work or by getting off the bus or the metro a few stops earlier. For commuters using motorized transportation, the mere fact of walking the last kilometre (about 10 minutes) to and from work is equivalent to 100 minutes of physical activity per work week, a good proportion of the minimum recommended exercise. This is a worthwhile investment of time: in the British study mentioned earlier, even if the maximum protection (41%) is observed among commuters who make the entire trip by bike, people who used this mode of transportation for only part of the journey still had a 24% lower risk of premature mortality compared to those who travelled exclusively by motorized transport.

Built environment
In North America, land use planning is unfortunately not very favourable to active transportation. In most cases, the cities developed after the invention of the automobile, which resulted in the construction of infrastructure focused mainly on the use of the car as a means of transport and therefore favoured urban sprawl. In Europe, the cities are older and were built before the advent of motorized transport, leaving in place infrastructure more conducive to non-motorized travel. For example, the proportion of workers who use bicycles as a means of transportation to work is 10 times higher in some European cities such as Copenhagen and Amsterdam than in North America (Figure 4).

Figure 4. Comparison of active bicycle transportation in various international cities. Adapted from Buehler and Pucher (2012). It should be noted that the data for Montréal are from 2006, so before the implementation of the bike-sharing system (Bixi). The proportion of bike users has increased since then to 3.2% in 2011, and Montréal is now ranked 18th cycling metropolis in the world.

To promote active transportation, we must therefore rethink what is called the “built environment”, i.e. the overall infrastructure that is part of our daily life, such as buildings, parks, schools, the road network, food sources (grocery stores, restaurants) or recreational facilities. Several studies have shown that people who live in cities where distances are reduced, streets are well connected, shops easily accessible and where areas for walking and cycling are well demarcated and safe are more physically active and in better cardiovascular health. It is therefore to be hoped that this type of built environment will become the norm in the near future.

Can regular exercise compensate for long periods spent sitting?

Can regular exercise compensate for long periods spent sitting?

It is well established that regular physical exercise improves lipid levels, glucose tolerance, and insulin sensitivity, all of which are cardiovascular risk factors. One question researchers have been asking in recent years is whether a single exercise session can, after a period of prolonged physical inactivity, have a positive impact on the risk factors associated with a sedentary lifestyle. This is an important issue as more and more workers are sitting for long hours at the office or in their car, and many of them do not have time to exercise more than once a week.

In a randomized controlled trial published in 2019 in the Journal of Applied Physiology, participants (n = 10) first spent four days without exercise, sitting for much of the day (≈13.5 hours/day). At the end of the fourth day, half of the participants did one hour of intense treadmill exercise (60–65% VO2max) and the other half remained inactive. On the morning of the fifth day, after fasting for 12 hours, all participants consumed a meal high in fat and glucose. Blood samples were taken before and every hour (up to 6 h) after the meal, and triglycerides, glucose and insulin were measured. After a rest period of several days, the experiment was repeated by swapping the groups (crossover study design).

No significant differences in plasma levels of triglycerides, glucose or insulin were found between the two groups. The authors conclude that prolonged physical inactivity (e.g., sitting about 13.5 hours/day and walking fewer than 4,000 steps/day) creates conditions where people become “resistant” to the metabolic improvements that are normally achieved after an aerobic exercise session. It is therefore important to develop good habits at work and at home (take active breaks, work standing, etc.), in order to fully benefit from the positive effects of exercise during leisure time.

A similar study published in 2016 came to comparable conclusions. The researchers randomized the participants into three groups: 1) sitting >14 h/day and a high-calorie diet; 2) sitting >14 h/day and a balanced diet; 3) active: standing, walking, sitting 8.4 h/day and a balanced diet. In addition to being randomized, the study had a crossover design, i.e., subjects participated in three five-day interventions (one week of rest between each intervention), changing groups each time. On the evening of the fourth day, the participants did treadmill running for 1 hour (67% VO2max). On the third and fifth day, participants consumed a high-fat meal (high-fat tolerance test) and blood tests were taken before and every hour (up to 6 hours) after the meal. Triglycerides, free fatty acids, glucose, and insulin were subsequently assayed in the plasma of the various samples collected.

After two days of sitting for long hours, participants had 27% higher triglyceride levels after consuming a high-fat meal, compared to participants who were more active. In participants who spent four days sitting for more than 14 hours, the 1-hour aerobic exercise did not decrease triglyceride levels in the blood or increase fat oxidation. On the other hand, in participants who were active during the previous four days, aerobic exercise decreased triglycerides by 14% (a non-significant decrease, p = 0.079) and significantly increased fat oxidation (p <0.05). The authors concluded that sitting for a good part of the day for 2 to 4 days was sufficient to increase postprandial triglyceride levels (after a meal) and that this increase cannot be reduced by sustained exercise.

A meta-analysis of 13 population studies assessed the ability of physical activity to eliminate or reduce the association between sitting time and all-cause mortality. These studies were conducted with more than 1 million people who were followed from 2 to 18.1 years. The results (Figure 1) show a very clear dose-effect relationship between the amount of exercise and the reduction in the relative risk of mortality associated with sitting or watching television. High levels of moderate physical activity (i.e., approximately 60–75 min/day) appear to eliminate the increased risk of mortality associated with long periods of sitting (Figure 1A). However, high levels of physical activity significantly alleviate, but do not eliminate the risk of mortality associated with long periods (> 5 h) spent watching television (Figure 1B).

Figure 1. Meta-analyses of joint associations of sitting time and amount of physical activity with all-cause mortality (A) and television-viewing time and amount of physical activity with all-cause mortality (B). 2.5 MET-h/week is equivalent to about 5 minutes of moderate activity per day; 16 MET-h/week is equivalent to 25–35 minutes of moderate activity per day; 30 MET-h/week is equivalent to 50–65 minutes of moderate activity per day, and 35.5 MET-h/week is equivalent to 60–75 minutes of moderate activity per day. From Ekelund et al., 2016.

 

The amount of physical activity in the highest quartile (> 35.5 MET-h/week) is equivalent to approximately 60–75 minutes of moderate-intensity exercise per day. This is much more than the minimum recommended by public health organizations (150 min/week). However, among those who do 16 MET-h/week, which is equivalent to 25–35 minutes of moderate-intensity physical activity, the increased risk of mortality associated with long periods of sitting (> 8 h/day) is less marked than for people in the least active group (<2.5 MET-h/week, equivalent to about 5 min of exercise per day). The increased risk of mortality (58%) for those who are less active and who sit more than 8 hours a day is similar to that associated with other risk factors such as smoking and obesity.

Why are the results for sitting time and television-viewing time different? This may be due in part to differences in the accuracy with which these behaviours are reported, but the authors of the study propose other plausible explanations: 1) people usually watch television in the evening, normally after dinner, and a prolonged sedentary episode after a meal could be particularly harmful to the metabolism of lipids and glucose; 2) people likely take more active breaks during work than during the viewing of TV programs, and it appears that these breaks are beneficial in reducing several cardiometabolic risk factors; 3) It is also plausible that people who watch television consume more “snacks” or obesogenic food.

Spending long periods of time in a sitting position is very common in our modern societies and this will only increase with future technological and social innovations. In addition to promoting regular physical exercise, public health organizations will likely also need to include a reduction in sedentary time in their guidelines and emphasize the importance of taking “active” breaks. Taking short active breaks may mean walking for a minute, drinking water, and getting up when talking on the phone. We must develop strategies to avoid sitting for long periods of time. In addition, we need to find the time to do at least 150 minutes of moderate exercise a week, up to 300 minutes a week to get maximum health benefits.