Clinical Medicine Insights Received 27 Mar 2021 | Revised 25 Apr 2021 | Accepted 20 May 2021 | Published Online 30 Jun 2021 DOI: https://doi.org/10.52845/CMI/2021-2-2-4 CMI JOURNAL 2 (2), 110−124 (2021) ISSN (O) 2694-4626 REVIEW ARTICLE Exercise and Non-Communicable Diseases: Part I Cardiovascular Diseases, Respiratory Diseases, Obesity, Depression, Liver Diseases Shashi K. Agarwal, MD ∗ 12227 US Highway 1, #309 North Brunswick, NJ 08902,USA Abstract Physical activity has established itself as a major risk factor for many chronic diseases. Individuals who lead a sedentary life have higher morbidity and mortality. Exercise, a subcategory of physical activity, is usually planned and structured involving large muscle groups. It is a major recommendation from all professional health associations to pre- vent and beneficially modulate the course of several chronic diseases. There are also emotional benefits and exercising individuals experience a better quality of life. This manuscript discusses the beneficial effects of exercise on five major non-communicable diseases, namely cardio- vascular diseases, respiratory diseases, obesity, depression, and liver diseases. Keywords: exercise, non-communicable diseases, cardiovascular dis- eases, COPD, obesity, depression, liver diseases Copyright : © 2021 The Authors. Published by Medical Editor and Educational Research Publishers Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 INTRODUCTION Physical activity (PA) is defined as any bod- ily movement produced by the contraction of skeletal muscles resulting in a substantial in- crease in resting energy expenditure1. Exercise is de- fined as ’any sport or activity that works large groups of muscles, is continually maintained and performed rhythmically2. Physical activity includes all move- ment that increases energy use, whereas exercise is planned, structured physical activity3. Exercises may be aerobic or resistance, butmay also involve stretch- ing, balance, and gait workouts and non-traditional activities such as tai chi and yoga4−6. Activities such as walking, cycling, jogging, and swimming are primarily aerobic exercises. They increasemitochon- drial density, insulin sensitivity, oxidative enzymes, blood vessel compliance and reactivity, lung func- tion, immune function, and cardiac output5. Resis- tance exercises include workouts with free weights, weight machines, bodyweight, or elastic resistance bands6. They result in improvements inmuscle mass, body composition, strength, physical function, bone mineral density, insulin sensitivity, blood pressure, CMI JOURNAL 2 (2), 110−124 MEERP LTD 110 Open Access Journal https://doi.org/10.52845/CMI/2021-2-3-11 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index EXERCISE AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, OBESITY, DEPRESSION, LIVER DISEASES lipid profiles, and cardiovascular health7. Stretching increases the range of motion around joints and en- hances flexibility8. Balance training can reduce falls risk by improving balance and gait9. Activities like Tai Chi and Yoga combine flexibility, balance, and resistance exercises10. Besides the physical benefits, all exercises benefit mental and emotional health11. The World Health Organization recommends that adult men and women should accumulate at least 150 min of moderate-intensity physical exercise per week and young people aged 5–17 years should accumulate at least 60 min of physical exercise of moderate to vigorous intensity daily12. The benefits of exercise for common chronicmedical conditions are discussed in this two-part manuscript. Part I discusses the role of exercise in cardiovascular diseases (CVD), chronic obstructive pulmonary dis- ease (COPD), obesity, depression, and liver diseases. Part II discusses its role in cancer, diabetes mellitus, kidney diseases, Alzheimer’s disease, and arthritis. 2 DISCUSSION The Centers for Disease Control and Prevention (CDC) defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”13. Chronic diseases are usually non-communicable dis- eases (NCDs) and inflict a heavy global health burden14. They include CVD (including hyperten- sion, coronary artery disease, stroke, and heart fail- ure), cancers, chronic respiratory diseases (chronic obstructive pulmonary disease, sleep apnea, and asthma), diabetes, Alzheimer’s disease, chronic kid- ney disease, arthritis, depression, obesity, and liver diseases (nonalcoholic and alcoholic hepatitis, vi- Supplementary information The online version of this article (10.52845/CMI/2021-2-2-4) contains supplementary material, which is available to autho- rized users. Corresponding Author: Shashi K. Agarwal, MD Shashi K. Agarwal, MD 2227 US Highway 1, #309 North Brunswick, NJ 08902,USA Email: usacardiologist@gmail.com ral hepatitis, cirrhosis of the liver)15. Cardiovascu- lar diseases are the leading NCDs worldwide and are the leading cause of loss of disability-adjusted life years and deaths globally16. Chronic respiratory diseases (such as asthma, chronic obstructive pul- monary disease (COPD), and lung cancer) contribute significantly to the rising burden of NCDs globally17. Overweight/obesity is a pandemic – its worldwide prevalence has doubled since 1980, and it is now affecting nearly a third of the world’s population18. Affected individuals face an increased risk of a mul- titude of comorbidities, including cardiovascular dis- ease, diabetes, and many cancers19. Depression is a common disease and is on the increase20. Depression cases worldwide registered an increase of 49.86% - incident cases increased from 172 million in 1990 to 25,8 million in 201720. Depression affects both mental and physical health and is often a potentially lethal disease21. The burden of liver diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, and hepatocellular carcinoma, contin- ues to rise worldwide22. Several personal factors play an important role in the genesis and progression of chronic NCDs – both modifiable and non-modifiable23. Non-modifiable risk factors include heredity, age, race, and gender24. Lifestyle behaviors are modifiable risk factors and include diet, obesity, smoking, and alcohol consumption24. Another modifiable risk factor is sedentary behavior and exercise24. The beneficial effects of increased physical activity, including structured activity such as exercise, on NCDs, are enormous25,26. Its effect on cardiovascular diseases, respiratory diseases, obesity, depression, and liver diseases is discussed in this manuscript. 2.1 CARDIOVASCULAR DISEASES A reduction in sedentary time and an increase in exercise time beneficially modulate CVDs27−29. Ex- ercise lowers CVD risk in a dose-dependent man- ner; moderate physical activity is associated with a 26% reduction in CVD risk, whereas high-intensity activities impart a 42% risk reduction30−32. Physical activity and pro-active physical exercise can even slow down or reverse CVD progression33−37. Reg- ular PA also reduces the risk of CVD mortality, both CMI JOURNAL 2 (2), 110−124 (2021) MEERP LTD 111 mailto:usacardiologist@gmail.com MEERP LTD SHASHI K. AGARWAL, MD in healthy individuals38 and in cardiac patients39,40. Moderate to high-intensity exercise has been shown to increase life expectancy by 1.3 to 3.7 years and active individuals remain free of CVD 1–3 years longer than their sedentary peers41. Aerobic exercise lowers blood pressure (BP) by 5- 7 mmHg42 while dynamic resistance training lowers BP by 2–3 mmHg43 in adults with hypertension (in both unmedicated and medicated patients). In- terestingly, the magnitude of these BP reductions rivals the magnitude of those obtained with first- line antihypertensive medications44. Exercising as little as one day per week is as effective as phar- macotherapy for reducing all-cause mortality among hypertensive patients45. In coronary artery disease patients, exercise reduces angina, myocardial infarc- tion, and sudden cardiac death46. Following a my- ocardial infarction, exercise reduces re-infarction, cardiac mortality, and all-cause mortality47. Physi- cal inactivity48 and low levels of fitness49 are also risk factors for stroke. Following a stroke, mod- erate to high-intensity aerobic exercise (of 20–40 min and 3–5 days per week) helps improve phys- ical fitness, maximal walking speed, and walking endurance50. Exercise is preventive for heart fail- ure (HF)51,52. Khan et al. demonstrated that men in the top quartile of longterm fitness levels had a 53% lower risk of developing HF52. In those with established heart failure53, exercise improves their quality of life54, reduces hospitalizations55, and low- ers mortality56. Physical activity has been noted to reduce the risk of atrial fibrillation57. Several studies have shown that exercise not only helps prevent peripheral artery disease (PAD)58 but also helps im- prove walking distance59 and the quality of life in these patients60,61. Physical activity often reduces the risk of erectile dysfunction (ED)62. It also helps improve function in men with established ED63. Ex- ercise also helps reduce several CVD risk factors, such as smoking64, obesity65, diabetes mellitus66, hyperlipidemia67, alcohol abuse68, chronic kidney disease69, depression70, loneliness71, psychosomatic stress71, sleep disturbances72, and illicit drug use73. Many mechanisms play a role in the beneficial ef- fects of exercise74. Regular exercise can help to reduce weight, reduce blood pressure, and improve lipid disorders, including raising HDL, decreasing LDL, and lowering triglycerides75. It also decreases insulin resistance, reduces blood coagulation and systemic inflammation76. Vigorous physical activ- ity reduces heart rate, increases myocardial oxygen supply, improves myocardial contraction and stroke volume, establishes electrical stability, and increases physiological cardiac hypertrophy77−79. However, older adults with chronic medical condi- tions must be careful about exercising vigorously, and stress testing may be required in people with known CVD80. Further, in certain conditions, such as decompensated congestive heart failure or se- vere aortic stenosis, exercise may be restricted or contraindicated81. 2.2 RESPIRATORY DISEASES Exercise, both aerobic and resistance, decreases res- piratory symptoms and leads to significant improve- ments in functional capacity in patients with res- piratory diseases82. The benefits of exercise train- ing in patients with COPD have been documented in several systematic review meta-analyses and in two Cochrane reviews83,84. Exercise training is an essential strategy in managing COPD, and re- sults in an improvement in 6-minute walk test (6MWT) distance84. Several studies using an in- cremental cycle ergometer test to measure maxi- mal exercise capacity also showed a significant im- provement in those patients allocated to pulmonary rehabilitation84. Besides a reduction in exercise- induced hyperinflation, there is an increase in muscle function, delaying the onset of peripheral muscle fatigue and resulting in less dyspnea and an increase in exercise tolerance84. People with COPD often have comorbidities that markedly affect their func- tional capacity85. These include chronic heart dis- ease, metabolic syndrome, musculoskeletal or neu- rological comorbidities, and many types of cancer86. Many of these chronic co-morbidities also improve with regular exercise in patients with respiratory diseases87. The role of exercise in the management of asthma is not well listed in professional organization guide- lines. Studies suggest that exercise improves asthma- related symptoms and cardiopulmonary fitness88,89. MEERP LTD CMI JOURNAL 2 (2), 110−124 (2021) 112 EXERCISE AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, OBESITY, DEPRESSION, LIVER DISEASES Exercise training may lower the ventilatory require- mentd of mild and moderate exercise thereby re- ducing the likelihood of provoking exercise-induced asthma90. In addition, a 12-week aerobic train- ing program demonstrated reductions in bronchial hyperresponsiveness and serum pro-inflammatory cytokines91. There was a decrease in asthma exacer- bations in adults with moderate to severe persistent asthma91. The quality of life (QOL) also improved in these patients91. Exercise training has an established role in cystic fibrosis (CF) management92. A Cochrane review (total number of 15 studies with 487 participants) examined the effects of exercise on CF93. Physical exercise in these patients improves exercise capac- ity, pulmonary function, and QOL93. There is an increase in sputum clearance through a combination of hyperventilation, mechanical vibration, coughing, and changes in sputum rheology, thereby improv- ing the much-needed bronchial hygiene in patients with CF94. Patients with interstitial lung disease also exhibit pulmonary benefits95−97. They experience less breathlessness95. Their walking distance (dur- ing the 6MWT) improves96. Similar benefits have been documented by several other studies97. These patients also report an improved QOL with exer- cise rehabilitation and training97. In patients with pulmonary arterial hypertension, exercise training improves right ventricular function98. Benefits have also been reported in patients with asbestosis and pulmonary fibrosis99. 2.3 OBESITY Sedentary behavior is also associated with obesity100. Regular exercise help prevent obesity, maintain weight or even lose weight101. A study of >4500 adults from the U.S. National Health and Nutrition Examination Survey showed that greater (moderate to vigorous intensity) physical activity was associated with a lower body mass index or BMI102. There is a significant body of evidence supporting the effect of physical activity in both short-term and long-term weight loss in adults103−105. Current recommendations from the American College of Sports Medicine state that PA between 150 and 250minutes per week helps prevent weight gain, PA between 150 and 250 minutes per week provides modest weight loss, while PA >250 minutes per week helps lose clinically significant weight loss101. However, recent work by Flack et al suggests that exercise closer to 300 minutes per week is needed for weight loss as there is an approximately 1000-kcal pe week compensatory response that accompanies exercise106. Jakicic et al reported that moderate to vigorous PA accumulated in bouts that were >10 min in duration was effective for weight loss at 18 months107. These bouts also helped maintain >10% weight loss from 6 to 18 months. Bouts of exercise of <10 min in duration were not effective. A study found that combining 5% to 7% (intentional) weight loss with regular physical activities, such as lifestyle activities or resistance training, resulted in improved mobility and lower extremity physical performance in overweight or obese older adults108. Resistance exercises are also effective, but data indi- cates they produce only minimal reductions in body weight. These exercises, however, help increase the loss of fat mass and help increase fat-free mass. The result is a reduction in the risk of several NCDs101. 2.4 DEPRESSION Depressed people have lower levels of PA109 and higher levels of sedentary behavior110. A recent analysis of data from the Brazilian National Health Survey, (59,399 individuals), found that a lack of PA for leisure was associated with depression in young males, middle aged, and older adults111. Several other studies have confirmed the protective effects of physical activity on depression112,113. Hamer et al noted that risk reduction for depression was noted at a minimal level of at least 20 min/week of any physical activity, with a greater risk reduction with activity at a higher volume and/or intensity114. In a systematic narrative review of 30 prospective cohort studies, Mammen and Faulkner reported that 25 of the 30 studies found that PA resulted in reduced inci- dent depression115. In a study of 49 studies (266,939 participants), Schuch and Stubbs found that PA low- ered the risk of depression by between 17% to 41%, across all ages and in all continents of the world116. CMI JOURNAL 2 (2), 110−124 (2021) MEERP LTD 113 MEERP LTD SHASHI K. AGARWAL, MD Exercise has recently also shown promise as an effective non-pharmaceutical treatment for depression117−120. Exercise of lower duration or lower intensity also imparts a reduction in depressive symptoms118,119. A Cochrane Review and meta- analysis of 35 randomized controlled trials (1356 individuals) found that exercise was moderately effective at reducing depressive symptoms in depressed adults117. Dunn et al. found that in patients with mild to moderate severity of major depressive disorder or MDD, a reduction in symptoms was noted in 47% of patients with exercise (17.5 kcal/kg/week) for 12 weeks120 . In their study, they found that rates of response and remission with ex- ercise were comparable to the rates reported in trials of cognitive-behavioral therapy and antidepressant medication. Schuch et al in a meta-analysis of 25 studies (757 individuals randomized to exercise and 730 to control conditions) found a significant antidepressant effect with exercise121. Patients with depression also have a higher risk of type II diabetes122 and cardiovascular disease123 and exercise helps reduce the risk of both. Exercise therapy also improves general physical health, body image, patients coping strategies with stress, and the quality of life in depressed individuals124. It also helps them become more independent in activities of daily living124. Evidence suggests that both exercise and antidepres- sant medication may alleviate depression through several processes, such as increased expression of neurotrophic factors125,126 and reduced systemic inflammation127. These influence neuronal growth and plasticity, leading to an increase in neurons, synaptic connections between neurons, and cerebral vasculature128−130. There is evidence that exercise induces increases in hippocampal, prefrontal cortex, and anterior cingulate cortex volume131. 2.5 LIVER DISEASES Physical inactivity and its related reduced cardiores- piratory fitness have been associated with increased nonalcoholic steatohepatitis (NASH) severity132. Among obese people, sedentary individuals have an increased risk of having a fatty liver in com- parison with weight-matched physically active individuals133. These data provide support for the hypothesis that increasing physical activity through exercise, defined as a planned, structured, and repetitive physical activity with a specific intensity, frequency, and duration, has beneficial effects on nonalcoholic fatty liver disease (NAFLD)134−136. The American Gastroenterological Association, the American Association for the Study of Liver Dis- eases, and theAmericanCollege ofGastroenterology all recommend physical exercise as a treatment for NAFLD137. Whitsett et al. conducted a systematic review of 18 studies and concluded that exercise significantly reduced hepatic fat content138. Wong et al demonstrated in a randomized trial of 145 NASH patients, aerobic and resistance exercise along with dietary restriction resulted in a 64% remission rate compared to a 20% remission rate in the non- intervention control group139. Several randomized trials provide evidence that aerobic exercise and resistance exercises are both effective in reducing liver fat140,141. This occurs even if there is no loss in body weight. Exercise in patients with NASH may also reduce progression to hepatocellular cancer142. Exercise has a direct effect on the liver. Aerobic and resistance training improve insulin resistance, liver fatty acid metabolism, and mitochondrial function143. Exercise also affects inflammation144. The result is a reduction in liver fat in these patients. Hepatitis C (HCV) patients are at an increased risk of CVD and have a lower QOL145. Studies have shown that HCV patients have lower physical activity than the general population146. Exercise in these patients not only reduces the CVD risk but also improves their QOL147. An improvement in the cognition function of these patients with exercise has also been noted148. In cirrhotic patients, exercise can improve en- durance and functional outcomes without any ad- verse effects149. In this systematic narrative review, moderate-intensity aerobic exercise or resistance training, 4 days/week, 20 minutes, for at least 8 weeks, helps cirrhotic patients to improve their car- diorespiratory system149. Pretransplant exercise helps to improve the physical and mental status of the patient while on the wait- list. An exercise and nutritional program appear to benefit their cardiopulmonary and musculoskeletal MEERP LTD CMI JOURNAL 2 (2), 110−124 (2021) 114 EXERCISE AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, OBESITY, DEPRESSION, LIVER DISEASES functions150. The patients notice an improved func- tional status and a sense of well-being. Following transplantation, exercise trainingwas associatedwith a shorter length of hospital stay and a reduced 90-day readmission rate151. 3 CONCLUSION Physicians often overlook exercise as a prophylactic measure or therapeutic modality for many common diseases and ailments. The evidence for the preven- tive and therapeutic effects of exercise on NCDs is strong. Even small amounts of exercise help most conditions, although the beneficial effect is greater with moderate to vigorous exercise. 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Transplant Proc. 2019 Dec;51(10):3330- 3337. doi: 10.1016/j.transproceed.2019.08.045. How to cite this article: Agarwal S.K, MD, Exer- cise and Non-Communicable Diseases: Part I Cardiovascular Diseases, Respiratory Dis-eases, Obesity, Depression, Liver Diseases. Clin-ical Medicine Insights. 2021; 110−124 . https://doi. org/10.52845/CMI/2021-2-2-4 MEERP LTD CMI JOURNAL 2 (2), 110−124 (2021) 124 Introduction Discussion CARDIOVASCULAR DISEASES RESPIRATORY DISEASES OBESITY DEPRESSION LIVER DISEASES CONCLUSION