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Lack of Exercise Is a Major Cause of Chronic Diseases

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Abstract

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene‐environment interaction (including aerobic training adaptations, personalized medicine, and co‐twin physical activity); and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [accelerated biological aging/premature death, low cardiorespiratory fitness (Vo2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, pre‐eclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer‐term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life. © 2012 American Physiological Society. Compr Physiol 2:1143‐1211, 2012.

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Figure 1. Figure 1.

Physical activity produces primary and tertiary preventive health benefits for chronic diseases. Left panel. Physical inactivity is an actual initiating cause of a chronic disease/condition. Restoration of physical activity (primary prevention) removes the actual cause (physical inactivity) that produced the health deficiency. Right panel. Physical inactivity is not the cause of lung cancer. Smoking is an actual cause of lung cancer. Addition of aerobic exercise training compensates (tertiary prevention) for loss of lung function after surgical removal of a portion of lung by strengthening respiratory skeletal muscles for remaining lung 179. Exercise does not cure lung cancer.

Figure 2. Figure 2.

Changes in artery function and structure (remodeling) show differential time courses in response to increasing or decreasing human physical activity as hypothesized by Thijssen et al. 506. Exercise training (right side) produces early, rapid increases of arterial function (blue line), which is followed weeks later by arterial remodeling (red line and larger diameter vessel) that returns arterial function to pre‐exercise training levels. Physical inactivity (left side) is associated with immediate, rapid decreases in arterial diameter after spinal cord injury (decreased size in top far left blood vessels and red line). Function immediately decreases and then returns to preinjury value.

Reproduced, with permission, from Figure 2 in reference 506.
Figure 3. Figure 3.

Health deficiencies accelerated by decreasing physical activity from higher to lower levels. Gheorghe Constantinescu generously made original drawing.

Reproduced, with permission, from reference 52.
Figure 4. Figure 4.

Best‐fit linear lines are shown for aerobic capacities of two cross‐sectional groups (aerobic trained and sedentary) as a function of their increasing chronological age. At the chronological age of 80 years, a horizontal line is extended from the endurance‐trained line to the left where it intersects the sedentary line at age 50 years. Subjects were women who had been aerobically trained for at least 2 years with road‐racing competition (closed circles) versus women who were sedentary (open squares) who performed no regular exercise and had body mass indexes (BMIs) more than 35 kg/m2 (aerobic‐trained women were matched across the entire age range for age‐adjusted world‐best 10‐km running times to ensure homogeneity relative competitiveness).

Reproduced, with permission, from reference 503.
Figure 5. Figure 5.

Relative risk of death as a function of cardiorespiratory fitness (CRF) or change in CRF. Relative risks of all‐cause mortality by (CRF) quintiles for 12,831 women aged 20 to 100 years without cardiovascular disease (CVD) or cancer in the Aerobics Center Longitudinal Study. Relative risks were adjusted for age, year of examination, body mass index, smoking status, abnormal electrocardiogram, hypertension, diabetes, hypercholesterolemia, and family history of CVD.

Reproduced, with permission, from reference 312.
Figure 6. Figure 6.

Best‐fit linear lines are shown for power of two cross‐sectional groups (strength trained and sedentary) as a function of their increasing chronological age. At the chronological age of 80 years, a horizontal line is extended from the power‐trained line to the left where it intersects the sedentary line at age 56 years. The cross‐sectional strength‐trained subjects are shown in closed circles and sedentary in open circles.

Reproduced, with permission, from reference 402.
Figure 7. Figure 7.

Mortality risk at different exercise capacities. Significant reductions in mortality do not occur less than 4 metabolic equivalents of resting metabolism (METs), become less at approximately 4 to 6 METs and an asymptote occurring at approximately 10 METs in 15,000 US veterans of wars.

Reproduced, with permission, from reference 278,280.
Figure 8. Figure 8.

Physical inactivity is an actual cause of premature death by interacting with other environmental factors to increase risk factors for metabolic syndrome, which, in turn produces two “leading causes” of “premature death” (type 2 diabetes and atherosclerosis). Primary prevention of physical inactivity is shown by physical activity inhibiting physical inactivity.

Figure 9. Figure 9.

Overweight and obese, by age from 1960 to 2006. Modified, with permission, from CDC website (86).

Figure 10. Figure 10.

Human caloric expenditure for physical activity in nonathletes is much lower than physically active populations. The y axis is the ratio of activity energy expenditure (AEE)/resting energy expenditure (REE). AEE = free‐living energy expenditure – (diet‐induced energy expenditure + REE). Data are presented for various human groups (nonathletes living in developed nations, military trainees, individuals from rural areas engaged in high levels of physical activity, and athletes in training) on the x axis. Each bar is a single subject. Nonathletes in developed nations have AEE/REE ratio of approximately 0.5, which is equivalent to physical activity levels (PAL) of approximately 1.67.

Reproduced, with permission, from reference 225].
Figure 11. Figure 11.

Gain by visceral and abdominal fat depots in nonexercising group while 6 months of exercise training produced loss in these fat depots. Data are presented as change in (A) visceral abdominal fat, (B) subcutaneous abdominal fat, and (C) total abdominal fat on the y axis. Four exercise levels are given on the x axis; they are (i) control (no exercise); (ii) low‐amount, moderate‐intensity exercise (caloric equivalent of walking ∼ 12 miles/week at 40% to 55% of peak oxygen consumption); (iii) low‐amount, vigorous‐intensity exercise (same amount of exercise as group 2, but at 65% to 80% of peak oxygen consumption); and (iv) high‐amount, vigorous‐intensity exercise (caloric equivalent of jogging ∼20 miles/week at 65% to 80% of oxygen consumption).

Reproduced, with permission, from reference 479.
Figure 12. Figure 12.

Insulin secretion is presented as a function of insulin sensitivity. Insulin secretion rises as insulin sensitivity falls when physically active individual (Point A) becomes sedentary (Point B). A failure of insulin secretion to compensate for fall in insulin sensitivity is noted when both insulin secretion and insulin sensitivity decline from Points B‐C, indicating prediabetes. The upper axis for increased and decreased levels of physical activity implies bidirectionality of the two arrows for glucose intolerance and insulin resistance. The leftward enlarging two arrows illustrate increasing glucose intolerance and insulin resistance with 2 to 3 days of decreased physical activity. The clinical significant is that low levels of physical activity produce a permissive environment for prediabetes. In opposite direction, high levels of daily physical activity markedly diminish the permission state to develop prediabetes. The distinction between the two arrows is based upon variability in Masters athlete's responses to stopping training as shown in Figure 2 of reference 443 in which four subjects had lesser increases in blood insulin (insulin resistance arrow) at 30 min into an oral glucose tolerance test as compared to ten other subjects (glucose intolerance arrow). A continued decline in both insulin secretion and insulin sensitivity at Point D is where overt type 2 diabetes is present.

Reproduced, with permission, from Bergman's original figure in reference 36.
Figure 13. Figure 13.

Peak value for bone mineral density (BMD) in third decade of life contributes to the age in later life at which threshold for osteoporosis is passed. The higher the peak value for BMD, the later age in life delays age at which BMD reaches the osteoporosis threshold, below which osteoporosis is diagnosed. The upper line reflects a population that had high bone‐loading physical activities throughout lifespan with genes predisposing to high bone strength in contrast to the lower line reflecting low lifetime bone loading with genes predisposing to low bone strength. Adapted, with permission, from Rizzoli et al. 438 who modified original figure of Hernandez et al. 235.

Reproduced, with permission, from reference 438.
Figure 14. Figure 14.

Rise in childhood and adolescent obesity in United States From 1980s through 2007 to 2008 obesity in 2 to 5, 6 to 11, and 12 to 19‐year‐old US females increased 3‐ to 5‐fold. [Tabular data is converted from graphic, with permission, from references 386, 387].



Figure 1.

Physical activity produces primary and tertiary preventive health benefits for chronic diseases. Left panel. Physical inactivity is an actual initiating cause of a chronic disease/condition. Restoration of physical activity (primary prevention) removes the actual cause (physical inactivity) that produced the health deficiency. Right panel. Physical inactivity is not the cause of lung cancer. Smoking is an actual cause of lung cancer. Addition of aerobic exercise training compensates (tertiary prevention) for loss of lung function after surgical removal of a portion of lung by strengthening respiratory skeletal muscles for remaining lung 179. Exercise does not cure lung cancer.



Figure 2.

Changes in artery function and structure (remodeling) show differential time courses in response to increasing or decreasing human physical activity as hypothesized by Thijssen et al. 506. Exercise training (right side) produces early, rapid increases of arterial function (blue line), which is followed weeks later by arterial remodeling (red line and larger diameter vessel) that returns arterial function to pre‐exercise training levels. Physical inactivity (left side) is associated with immediate, rapid decreases in arterial diameter after spinal cord injury (decreased size in top far left blood vessels and red line). Function immediately decreases and then returns to preinjury value.

Reproduced, with permission, from Figure 2 in reference 506.


Figure 3.

Health deficiencies accelerated by decreasing physical activity from higher to lower levels. Gheorghe Constantinescu generously made original drawing.

Reproduced, with permission, from reference 52.


Figure 4.

Best‐fit linear lines are shown for aerobic capacities of two cross‐sectional groups (aerobic trained and sedentary) as a function of their increasing chronological age. At the chronological age of 80 years, a horizontal line is extended from the endurance‐trained line to the left where it intersects the sedentary line at age 50 years. Subjects were women who had been aerobically trained for at least 2 years with road‐racing competition (closed circles) versus women who were sedentary (open squares) who performed no regular exercise and had body mass indexes (BMIs) more than 35 kg/m2 (aerobic‐trained women were matched across the entire age range for age‐adjusted world‐best 10‐km running times to ensure homogeneity relative competitiveness).

Reproduced, with permission, from reference 503.


Figure 5.

Relative risk of death as a function of cardiorespiratory fitness (CRF) or change in CRF. Relative risks of all‐cause mortality by (CRF) quintiles for 12,831 women aged 20 to 100 years without cardiovascular disease (CVD) or cancer in the Aerobics Center Longitudinal Study. Relative risks were adjusted for age, year of examination, body mass index, smoking status, abnormal electrocardiogram, hypertension, diabetes, hypercholesterolemia, and family history of CVD.

Reproduced, with permission, from reference 312.


Figure 6.

Best‐fit linear lines are shown for power of two cross‐sectional groups (strength trained and sedentary) as a function of their increasing chronological age. At the chronological age of 80 years, a horizontal line is extended from the power‐trained line to the left where it intersects the sedentary line at age 56 years. The cross‐sectional strength‐trained subjects are shown in closed circles and sedentary in open circles.

Reproduced, with permission, from reference 402.


Figure 7.

Mortality risk at different exercise capacities. Significant reductions in mortality do not occur less than 4 metabolic equivalents of resting metabolism (METs), become less at approximately 4 to 6 METs and an asymptote occurring at approximately 10 METs in 15,000 US veterans of wars.

Reproduced, with permission, from reference 278,280.


Figure 8.

Physical inactivity is an actual cause of premature death by interacting with other environmental factors to increase risk factors for metabolic syndrome, which, in turn produces two “leading causes” of “premature death” (type 2 diabetes and atherosclerosis). Primary prevention of physical inactivity is shown by physical activity inhibiting physical inactivity.



Figure 9.

Overweight and obese, by age from 1960 to 2006. Modified, with permission, from CDC website (86).



Figure 10.

Human caloric expenditure for physical activity in nonathletes is much lower than physically active populations. The y axis is the ratio of activity energy expenditure (AEE)/resting energy expenditure (REE). AEE = free‐living energy expenditure – (diet‐induced energy expenditure + REE). Data are presented for various human groups (nonathletes living in developed nations, military trainees, individuals from rural areas engaged in high levels of physical activity, and athletes in training) on the x axis. Each bar is a single subject. Nonathletes in developed nations have AEE/REE ratio of approximately 0.5, which is equivalent to physical activity levels (PAL) of approximately 1.67.

Reproduced, with permission, from reference 225].


Figure 11.

Gain by visceral and abdominal fat depots in nonexercising group while 6 months of exercise training produced loss in these fat depots. Data are presented as change in (A) visceral abdominal fat, (B) subcutaneous abdominal fat, and (C) total abdominal fat on the y axis. Four exercise levels are given on the x axis; they are (i) control (no exercise); (ii) low‐amount, moderate‐intensity exercise (caloric equivalent of walking ∼ 12 miles/week at 40% to 55% of peak oxygen consumption); (iii) low‐amount, vigorous‐intensity exercise (same amount of exercise as group 2, but at 65% to 80% of peak oxygen consumption); and (iv) high‐amount, vigorous‐intensity exercise (caloric equivalent of jogging ∼20 miles/week at 65% to 80% of oxygen consumption).

Reproduced, with permission, from reference 479.


Figure 12.

Insulin secretion is presented as a function of insulin sensitivity. Insulin secretion rises as insulin sensitivity falls when physically active individual (Point A) becomes sedentary (Point B). A failure of insulin secretion to compensate for fall in insulin sensitivity is noted when both insulin secretion and insulin sensitivity decline from Points B‐C, indicating prediabetes. The upper axis for increased and decreased levels of physical activity implies bidirectionality of the two arrows for glucose intolerance and insulin resistance. The leftward enlarging two arrows illustrate increasing glucose intolerance and insulin resistance with 2 to 3 days of decreased physical activity. The clinical significant is that low levels of physical activity produce a permissive environment for prediabetes. In opposite direction, high levels of daily physical activity markedly diminish the permission state to develop prediabetes. The distinction between the two arrows is based upon variability in Masters athlete's responses to stopping training as shown in Figure 2 of reference 443 in which four subjects had lesser increases in blood insulin (insulin resistance arrow) at 30 min into an oral glucose tolerance test as compared to ten other subjects (glucose intolerance arrow). A continued decline in both insulin secretion and insulin sensitivity at Point D is where overt type 2 diabetes is present.

Reproduced, with permission, from Bergman's original figure in reference 36.


Figure 13.

Peak value for bone mineral density (BMD) in third decade of life contributes to the age in later life at which threshold for osteoporosis is passed. The higher the peak value for BMD, the later age in life delays age at which BMD reaches the osteoporosis threshold, below which osteoporosis is diagnosed. The upper line reflects a population that had high bone‐loading physical activities throughout lifespan with genes predisposing to high bone strength in contrast to the lower line reflecting low lifetime bone loading with genes predisposing to low bone strength. Adapted, with permission, from Rizzoli et al. 438 who modified original figure of Hernandez et al. 235.

Reproduced, with permission, from reference 438.


Figure 14.

Rise in childhood and adolescent obesity in United States From 1980s through 2007 to 2008 obesity in 2 to 5, 6 to 11, and 12 to 19‐year‐old US females increased 3‐ to 5‐fold. [Tabular data is converted from graphic, with permission, from references 386, 387].

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Frank W. Booth, Christian K. Roberts, Matthew J. Laye. Lack of Exercise Is a Major Cause of Chronic Diseases. Compr Physiol 2012, 2: 1143-1211. doi: 10.1002/cphy.c110025