exercise

Introduction

see exercise prescribing for exercise testing

see exercise & blood pressure for effects of exercise on blood pressure

Biochemistry

irisin may play a role in benefits of exercise

• PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved & secreted as the hormone, irisin
• irisin acts on white adipose cells to stimulate UCP1 expression & a broad program of brown-fat-like development
• irisin is induced with exercise in humans
• mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake
• this results in improvements in obesity & glucose homeostasis

exercise-induced euphoria & anxiolysis are mediated via endocannabinoids & their receptors & not via endorphins

exercise may improve cognition through enhanced expression of plasma Gpld1

Genetics

• elderly with the BDNF Val66Val polymorphism benefit greatly from physical activity

Physiology

• an increase in physical fitness through exercise via adaptation of skeletal muscle & the cardiovascular system
• regular exercise increases insulin sensitivity
  • moderate-intensity exercise >= 150 minutes/week
  • high-intensity exercise >=75 minutes/week
  • high-intensity interval training
• exercise stimulates glucose-transporter molecules to proliferate & move to the cell membrane, where they ferry glucose into the cell
• exercise also increases the formation of mitochondria
• levels of multiple metabolites associated with insulin resistance decrease, & metabolites linked to lipolysis, nitric oxide bioavailability, & brown fat metabolism increase in response to 12 minutes of exercise in adults
• regular exercise can have adverse metabolic consequences in some people

Indications

Benefits:

• has a protective effect in preventing or minimizing disability late in life
• decreases risk for type 2 diabetes
  • improves insulin sensitivity (see Physiology: below)
• strenous* (>= 75% VO2max) but not moderate (50% VO2max) associated with improved glycemic control in obese patients
• higher levels of physical activity (3000-4000 MET minutes/week)# associated with reduced risk of
  • diabetes mellitus (28%)
  • ischemic stroke (26%)
  • ischemic heart disease (25%)
  • colon cancer (21%)
  • breast cancer (14%)
• 30 minutes of moderate-to-vigorous physical activity at least 5 days a week associated with lower healthcare expenditures

* walking at a brisk pace can achieve 75% VO2max in obese patients

# editorialists note study did not examine activity intensity

exercise & cardiovascular disease

• regular exercise decreases cardiovascular & non-cardiovascular mortality in older adults (GRS9)
• may diminish risk for left ventricular diastolic dysfunction
• 1 hour of moderate exercise daily prevents weight gain in middle-aged women with BMI < 25, but not heavier women
• inverse dose-response relationship between vigorous exercise & mortality (RR minimum ~ 0.87)

exercise & cancer

• moderate to vigorous physical activity associated with
  • relative reduction in risk for 13 cancers
    • 42% lower risk for esophageal adenocarcinoma
    • 23% lower for renal carcinoma
    • 20% lower for myeloid leukemia
  • relative increase in risk for 2 cancers
    • 27% higher risk for malignant melanoma
    • 65% higher risk for prostate cancer
• exercise is cancer therapy

exercise & immunity

• risk for acute respiratory infections is lower in people who exercise regularly
  • Physically active people are also less likely to suffer severe outcomes from COVID.

exercise & mental health, cognition & neuropathology

• exercise improves mental health in adults
  • 45 minute session, 3-5 times per week, associated with the best mental health
  • exercise improves sleep quality & mood/anxiety in patients with depression & anxiety disorders
• effect of exercise on cognition is controversial
  • 24 meta-analyses report a positive overall effect of exercise on cognition
    • low statistical power in randomized control trials
    • small exercise-related benefits
  • exercise may improve cognition through enhanced expression of plasma Gpld1
• exercise may reduce neuroinflammation via increase in plasma clusterin
• greater midlife & late life moderate-to-vigorous physical activity may protect against late-life structural brain abnormalities, via cerebrovascular mechanisms

exercise & mortality

• life expectancy increases as aerobic fitness improves with no upper limit of benefit at any age
• exercise in men is associated with lower mortality
• light jogging associated with increased longevity
• physical activity may be increased as late as 50 years of age for full benefit; lower mortality becomes apparent after 10 years
• more vigorous physical activity associated with lower mortality
• bicycling to work associated with reduced all-cause mortality vs driving or public transportation (RR=0.59)
  • bicycling associated with reduced cardiovascular mortality & cancer mortality
  • walking associated only with reduced cardiovascular mortality
• physical activity & physical fitness during midlife associated with less disability & lower mortality in both genders
• 1 hour of moderate exercise daily prevents increase in mortality from sitting 8 hours/day
• 10 minutes of exercise a week for adults 40-85 years might be better than no physical activity in terms of mortality risk
• even small amounts of running associated with mortality benefit
• greater number of steps/day 8000 vs 4000 (> 40 years of age) associated with lower all-cause mortality
• middle-aged & older adults increasing moderate-to-vigorous exercise by 30 minutes/day could prevent 300,000 deaths annually

weekend warrior & mortality

• individuals who engage in active patterns of physical activity, whether "weekend warrior" or regularly active, experience lower all-cause & cause-specific mortality rates than inactive individuals
• "weekend warriors" have reduced risk in all-cause mortality (~30%), cardiovascular mortality (~40%) & cancer mortality (14-21%) (slighly less risk reduction than with regular exercise)
• "weekend warriors" concentrating exercise into 1-2 days/week may improve cardiovascular risk profiles

Adverse effects

• intensive exercise > 5 hours/week at age 30 increases risk of atrial fibrillation later in life, especially with quitting exercise later in life
• very vigorous activity > 9 MET hours/week (running at an 8 minute per mile pace or faster, high-intensity interval training, cross-country skiing uphill) is associated with progression in coronary artery calcification*
• increased risk of cardiovascular events & death in persons who exercise daily
  • exercise 2-4 days/week with lowest rates of cardiovascular events & death
  • risk for cardiac arrest during exercise for men age 35-65 years is low
    • 5% of all cardiac arrests in men age 35-65 years occur during exercise
    • 2/3 of exercise-associated cardiac arrests occur in men with prior cardiovascular symptoms or known cardiovascular disease
• heat stroke a greater risk in marathon runners than cardiac arrhythmia
• large breasts may discourage exercise & reduce intensity of exercise
• with extreme exercise, mitochondrial function - generation of ATP from glycolysis & glucose tolerance - declines
• strenuous jogging associated with increased mortality
• prolonged & highly intense exercise, may increase susceptibility to respiratory tract infection
  • athletes, firefighters, police officers, & military personnel at risk

* vigorous activity 6-9 MET hours/week is associated with attenuation of coronary artery calcification

Management

• recommendations for adults
  • aerobic exercise
    • 30 minutes of moderate intensity exercise at least 5 times/week, or 20 minutes of vigorous exercise at least 3 times a week
      • even a lesser amount of moderate intensity exercise can diminish mortality by as much as 22% in older adults (> 60 years)
      • >= 150 minutes of moderate intensity or >= 75 minutes of vigorous aerobic exercise weekly spread out over at least 4-5 days
      • 300-600 minutes of moderate intensity or 150-300 minutes of vigorous aerobic exercise weekly associated with lower mortality
    • 15 minutes of exercise/day minimum for mortality benefit
    • walking & running confer similar benefits given similar total energy expenditures
    • 20 minutes of moderate-intensity walking a day in high-risk patients can lower cardiovascular risk 10% over 6 years
    • 15 minutes of walking or 5 minutes of running (frequency not specified) reduces all-cause mortality by 30%
    • walking 1-2 days weekly or 3-7 days weekly lowers all-cause mortality 15% & 17%
    • even a lesser amount of moderately intensive exercise
    • running, even small amounts, is associated with a decrease in cardiovascular & all-cause mortality
    • brief bursts of vigorous intermittent lifestyle physical activity embedded into everyday life is associated with diminished mortality & lower cancer risk
    • maximal health benefits of running are achieved at small amounts of running, below those recommended by US physical activity guidelines
    • 54 minutes of vigorous exercise per week reduces all-cause mortality by 36%, risk of heart disease by 35% (optimal benefit/effort)
    • racquet sports, aerobics, & swimming associated with reduced all-cause mortality
      • assessed by participation in activity 4 weeks prior to survey in U.K.
      • no benefit for running or soccer
      • racquet sports associated with 47% reduction in mortality, swimming 28%, aerobics 27%, cycling 15%
      • racquet sports, swimming, & aerobics associated with reduced cardiovascular mortality;
        • no benefit for cycling, soccer, or running
    • 6 minute intervals of intensive cycling raises serum BDNF 4-5 times that of 90 minute low-intensity cycling
    • 9 additional minutes a day of moderate to vigorous physical activity improves cognition in middle-aged adults
    • smart watches & other devices are used to assess daily step counts
      • the CDC recommends 10,000 steps daily, < 5000 steps is sedentary
      • at only 2300 steps daily, cardiovascular mortality begins to diminish
      • at 4000 steps daily, all-cause mortality begins to diminish
      • at 10,000 steps daily, benefits begin to plateau, but continue to increase up to 20,000 steps daily
    • weekend warriors may improve cardiovascular risk profiles
  • strength training
    • exercise that maintains or increases muscle strength at least twice a week
    • 8-10 exercises on 2 or more non-consecutive days using the major muscles
    • choose a resistance (or weight) that results in substantial fatigue after 8-12 repetitions of each exercise
    • combination of aerobic exercise & weightlifting associated with 47-50% lower all-cause mortality risk in adults
      • regular weightlifting with or without moderate to vigorous aerobic activity reduces all-cause & cardiovascular disease mortality, albeit less than combination of aerobic exercise & weightlifting
      • leisure time muscle-strengthening exercise & moderate to vigorous aerobic exercise re independently associated with lower all-cause mortality US adults >= 65 years of age
  • WHO recommendations
    • 150-300 minutes of moderate physical activity, 75 to 150 minutes of vigorous activity, or an equivalent combination per week
    • muscle-strengthening activity involving all major muscle groups at least 2 days a week
  • balanced levels of aerobic physical activity (moderate & vigorous) combined with muscle strengthening activity may be associated with optimal reductions of mortality risk
  • workers in desk jobs
    • >= 2 hours of standing or light activity (light walking) during the workday, with an ultimate goal of 4 hours per workday
  • obesity: resistance training 3 days/week + 150 minutes of moderate- intensity aerobic activity [47}
  • coronary artery disease: prior to exercise, risk stratification (including exercise stress testing) is recommended
  • clearance by a physician not needed for asymptomatic adults prior to beginning exercise program at recommended level
  • vigorous exercise or competitive sports not recommended for
    • patients with ischemia or complex arrhythmias during exercisetress testing
    • severe aortic stenosis, aortic regurgitation with LVEF < 50%, mitral regurgitation with LVEF < 60%, or severe mitral stenosis
    • hypertrophic cardiomyopathy or arrhythmic cardiomyopathy
    • dilated cardiomyopathy
    • myocarditis prior to 6 months of recovery
    • long QT syndrome
    • cardiac arrest or arrhythmic syncope, regardless of ICD
• recommendations for children
  • school-aged children: at least 60 minutes of exercise/day (developmentally appropriate, moderate-vigorous activity)
  • children 3-5 years should be physically active throughout the day
  • children 6-17 should engage in moderate-to-vigorous activity for at least 1 hour each day
    • mostly aerobic activity, but strengthening should be included at least 3 days a week
• older adults should include balance training
  • increasing leisure time physical activity later in life associated with mortality benefit
• supplements not recommended
  • antioxidant supplementation of little or no benefit in combination with exercise:
    • vitamin E & vitamin C supplements may blunt exercise- induced increase in insulin-sensitivity
• recommendations for primary care providers
  • adovcating exercise in a primary care environment benefits patients in terms of compliance with exercise recommendations
    • number needed to treat = 12
  • further evaluation prior to embarking on an exercise program recommended only if:
    • heart disease or hypertension
    • musculoskeletal disease
    • chest pain or dizziness when trying to exercise in the past

More general terms

• physical therapy (PT)

More specific terms

• aerobic exercise (endurance exercise)
• exercise for seniors
• flexibility exercise (stretching)
• oropharyngeal exercises for sleep apnea
• resistance training (weight training)
• Tai chi
• therapeutic exercise
• triathlon

Additional terms

• exercise & Alzheimer's disease
• exercise & blood pressure
• exercise prescribing (counseling)
• exercise protocol
• exercise stress testing
• maximal oxygen consumption (VO2 max)
• physical conditioning (training)