Do Thin People Need to Exercise?

Exercise is universally accepted as an aid for weight loss. Striving for an ideal weight is done both for the purpose of seeking lifelong health and for simple vanity. Whatever the case may be, weight loss is a desirable pursuit.

But what of those who are naturally average weight or even svelte? Is exercise a waste of time or simply a means to allow for greater calorie consumption?
As it turns out, there is a panoply of benefits to be experienced that are independent of weight.

Improved HDL (‘Good Cholesterol’)

Heart disease, a synonym of low cardiovascular fitness, does not spare the thin, and as a matter of fact, greater mortality from cardiovascular disease observed in the obese is also seen in the underweight.
Low HDL cholesterol can be found in the normal-weight, and even if the level of HDL appears normal, they may very well be dysfunctional. Exercise, including strength training, increases HDL and improves HDL functionality independent of weight . In fact, those with lower BMI reveal a larger increase in HDL cholesterol in response to aerobic exercise. HDL function is a reflective of mitochondrial oxidative function and dysfunction of the mitochondria underlies adverse cardiovascular changes. Pharmaceutical inventions that result in HDL elevation alone do not share the same clinical benefits. Therefore, improving HDL cholesterol through exercise at any weight can help protect against CVD.

Lower Blood Pressure

Age and weight are the main risk factors for high blood pressure. That doesn’t mean there aren’t plenty of average to low weight individuals with the condition. Furthermore, low fitness in the average weight raises the risk for high blood pressure above the that of the general population. Combining low fitness with genetic predisposition and subclinically elevated stress levels that are becoming ‘normal’ in modern living, it becomes very easy for those of normal or low weight to develop high blood pressure. Low to moderate intensity exercise decreases blood pressure levels rapidly and markedly. Aerobic training specifically is the recommended form of exercise for reducing hypertension. By lowering blood pressure with exercise, the risks for cardiovascular-related diseases (e.g., stroke) and kidney disease will sharply decline.

Better Learning

Immediate cognitive benefits such as reaction time(i.e., processing speed) and executive function i.e., planning, attention, working memory) are reaped from moderate exercise (e.g., stationary cycling, brisk walking) and ‘high-dose exercise’ (~40min daily training) in the young and in the old likely by improving circulation, neutral activation, and neutral growth in the brain. Such gains are similar to those experienced with ADD/ADHD medication. In a separate study, motor memory as measured by long-term skill acquisition was benefitted in healthy young volunteers between the ages of 18 to 35 from brief bouts of cycling after learning a new skill compared with a healthy age-matched control group fared worse on learning retention.
Slightly more intense aerobic exercise such as running, jumping rope, and sports (e.g., basketball, soccer) will lead to even greater impacts in these various cognitive measures.

Lowered Stress and Anxiety

Exercise (aerobic and anaerobic) is so efficacious in alleviating anxiety that it is now viewed as an adjunct to standard theory for anxiety disorders including social phobias, panic attacks. Exercise seems to allay the physical responses to perceived stressors which involve hyper-reactivity of the lower sympathetic nervous system and hypothalamic-pituitary-adrenal axis (HPA) and increase neurotropic factors (e.g., BDNF) which likely possess an anxiety-lowering effect. Additionally, the thermogenic effect of exercise influences a state of relaxation and release of tension. Exercise-induced BDNF increases also help explain its powerful therapeutic effect in obsessive compulsive disorder (OCD). A less technical addition benefit from exercise is its allowance of the individual to ‘time-out’ and engage in a health-promoting distracting activity with farer reaching anxiolytic effects than other means of distraction.

A Boost in Mood and Self-Esteem

A ‘runner’s high’ is a real phenomenon that describes the state of euphoria that is experienced from the endorphins produced by exercise. With this exercise-induced euphoria is an altered perception of pain, or in other words, an increased pain tolerance. This is not only a perceived but a clear physiological response due to the release of natural opiates with prolonged exercise. This effect is known to linger up to around half an hour following exercise, but new evidence points to a higher and long-lasting pain threshold in normal healthy individuals who improved their fitness with chronic exercise.
Another part of mood improvements as a result of exercise are increased self-esteem and a higher sense of self-worth that develops. This additional positive effect is seen in the very young as well as in the old and were seen to take place even when changes in body weight and composition were minute. Whether thin or overweight, an improved fitness allow an individual to feel more strong and thus more capable of facing challenges in life.

Nature’s Treatment for Depression

Physical activity’s role in overcoming depression is profound. Its mode of action goes beyond that of a simple distraction. By potently inducing hippocampal neurogenesis, exercise can help treat depression. While a lack of adult neurogenesis does not directly cause depression per say, reduced hippocampal neurogenesis (i.e., neuron content in the hippocampus) – usually resulting from chronic stress (also a major cause of depression) – decreases the ability to cope with stressors, hence causing adverse behavioral effects. With stimulating neurogenesis, exercise becomes a crucial factor in overcoming depression.

In many studies exercise works equally well as psychotherapy and anti-depressant medications in treating depressive symptoms in mild to severe depression, and in some studies, it works even better. It is also very successful as an adjunct to therapy, particularly when remission is incomplete, with occurs very often with anti-depressants alone. Whereas typical SSRIs treat depression by inciting neurogenesis through elevating the levels of serotonin, exercise prompts neurogenesis through multiple mechanisms including increases in BDNF, endorphins, vascular endothelial growth factor (VEGF), and serotonin. Additionally, exercise protects the brain from exposure to kynurenine – a stress-related metabolite associated with stress-mediated depression – by facilitating its breakdown Other than this, exercising has the added benefit of providing the individual with distraction and an increased sense of self-efficacy. Also important to consider is that side effects such as insomnia, sexual dysfunction, hair loss, weight gain, and withdrawal syndrome (e.g., nausea, dizziness, headaches, anxiety, fatigue, etc.) have been reported with drug therapy while exercise is strongly associated with opposite effects on these parameters.

By the same token, exercise can strongly reduce the risk of developing depression by maintaining neurogenesis and thus nurturing a healthy stress response. It is no surprise that adults who exercise are less likely to develop depression than inactive adults.

Based on the comparing different types of exercise (e.g., low-intensity aerobic exercise, flexibility exercise)and their effects on mitigating major depressive disorder, moderate aerobic exercise is considered to be most effective, however other studies utilizing resistance training have found high efficacy with this type of activity as well. A dose-dependent effect is implied.

A Natural Sleep Aid

It might be believed that exercise can have adverse effects on sleep due to over-stimulation when in actuality the opposite is true with the exception of highly vigorous exercise immediately before bedtime. Increasing physical activity to at least 150 minutes per week in inactive sufferers of insomnia can ameliorate the severity of the condition. Older adults with insomnia also report improved sleep quality as measured by sleep latency, sleep duration, daytime dysfunction, and sleep efficiency with aerobic exercise. In a study with postmenopausal woman – a vulnerable group to sleep disruption – the implementation of aerobic exercise seemed to be dose-responsive and weight-independent in decreasing sleep disturbances. Even the perception of adequate excretion before sleeptime is positively related to all around objectively-assessed better sleep (e.g., shortened sleep onset, fewer nightly awakenings, more deep sleep, etc.) in young adults who engage in evening exercise. Other sleep-related conditions including sleep disordered breathing and sleep apnea improve with increasing fitness without significant effects on body weight. Resistance training and its relationship to sleep has been less studied, although current findings similar benefit.

Combined mechanisms including increases in body temperature, energy expenditure, anti-anxiety effects, and entrainment of circadian rhythm are theorized to be responsible for the role of physical activity in promoting sleep initiation and sleep quality.

Stronger Immune System

Many who may appear healthy suffer from frequent bouts of colds and viruses due a weak immune system. Moderate exercise instantly upregulates immunity. Studies show a risk reduction of 23% for respiratory tract infections in the regularly physical active and a significant decrease in the duration of cold symptoms in frequent walkers. Part of exercise’s immunoprotection can be attributed to lowering common suppressors of immunity – stress hormones and pro-inflammatory cytokines (i.e., inflammation). As a bonus, 90 minutes of exercise (e.g., jogging, bicycle-riding) can notably intensify the potency of vaccinations, lowering the possibility for resistance.

On the other hand, note that severe training will raise stress hormones, generate inflammation, and suppress the immune system.

More Creativity

For the writers, artists, musicians, inventors, entrepreneurs, and even those in need of drafting a fresh and new business plan, exercise is the boon to creativity. It has been shown that aerobic exercise gets the creative juices flowing immediately during a moderate workout with even stronger effects lasting up to two hours later. Exercising for this purpose would probably be done most effectively in an isolated environment such as in one’s own home or in a natural setting as opposed to an urban environment where a conscious vigilance may be needed.

Overcoming Addictions

Exercise can help conquer addictions by more than just substituting time spent on the addictive behavior on a workout session. Given its success in alcohol recovery, smoking cessation, and general substance abuse, convincing neurological effects have been hypothesized in explaining its efficacy in different phases of addiction. Exercise stimulates the same ‘pleasure circuit’ (i.e. ,dopamine release) that is activated with drug use and other addictive behaviors (e.g., video games, gambling, junk food, etc.). Using exercise to act on the reward pathway that re-direct the vulnerability to drug use in the initial stages towards a health-promoting activity. In fact, multiple studies have found drug-use to be much less prevalent among active adolescents versus their inactive counterparts. In the progression stage where initiation has already been started, beginning an exercise regime can prevent the progression into addiction as demonstrated by studies on the already using. Besides enhancing dopaminergic signaling to mimic addiction-related benefits, exercise also affects glutamatergic signaling which is noted to be dysregulated in the addicted. By acting through these pathways, exercise can similarly be highly successful in this stage by interrupting the progression into established addiction. After addiction, exercise has shown to positively influence withdrawal and discourage relapses by masking the period of withdrawal where dopamine activity is reduced and returning the upregulation of glutamatergic neurotransmission to normal. Other uncomfortable withdrawal symptoms like insomnia that occur frequently with alcohol withdrawal that can also be bypassed by using exercise to normalize the circadian rhythms. Moreover, the abilities of exercise to reduce depressive states and heighten coping ability to stress can prevent the desire to gravitate towards dangerous additions and enhance the suppression of adverse reactions in the difficult withdrawal stage in the currently addicted to help transition to total remission.

Helps Digestion

Constipation is not very significantly correlated to obesity or overweight status. Some studies find constipation to be more prevalence in the overweight subjects while others find normal BMI most associated with the condition. In any case, constipation may strike anyone and inactivity can be a major cause. Understanding why inactivity can cause constipation is rather simple. Without being upright and in motion, bowel movement ceases to be regular as the activity in the intestinal tract is put in ‘park’, so to speak. Apparently physical activity promotes better mineral absorption by enhancing the efficiency of intestinal absorption. There is also the strengthening of the abdominals that occurs with certain exercises which can help break down food for better nutrient utilization and less constipation. Exercise can also help nutritional status indirectly. Rising up to exercise at the onset of constipation can help improve digestion immediately and replace the need to self-medicate with laxatives that are likely to induce nutrient loss.

Mild to moderate intensity exercise is best for gastrointestinal health, although minimizing the risk for more serious gastrointestinal complaints such as diverticulitis may require more intense physical activity. On the contrary, overly vigorous training with dehydration can cause heartburn, nausea, diarrhea, constipation, and/or gastrointestinal bleeding.

• Maximized Sexual Health

In men, exercisers are more likely to be protected from erectile dysfunction likely as a result of elevated circulation. In women, frequent exercise increases genital arousal by increasing activity of the sympathetic nervous system. Moreover, the boosts in energy and mood that exercise provides benefits sexual desire in both sexes. Fitness in particular can enhance sexual performance by increasing endurance.

Asthma Relief

It may be thought that asthma and exercise go together like water and oil. The truth is, physical activity and physical fitness is protective against asthma. Exercise promotes cardiopulmonary fitness and relieves asthma synonyms. Nonsteroidal anti-inflammatory drugs (NSAIDs) are rightfully used in place of corticosteroids to control asthma, but they are not without their own possible side effects. Exercises can decrease asthma flare-ups the same way NSAIDs are used – by lowering inflammation, specifically airway inflammation. Exercise might also act against asthma by clearing the bronchioles to prevent mucous build-up and airway edema. Moreover, exercise can inhibit smooth muscle latching and subsequent asthma symptoms through improving the sigh rate which is abnormally slowed with prolonged inactivity. Asthma is no longer an excuse to withhold vital exercise; the key is engaging in non-severe training. With proper exercise, medication can be reduced and quality of life can improve.

Stronger Bones

Thinness and low muscle tone are established risk factors for osteoporosis. Exercise, namely weight-bearing exercise, is just about the most important protective factor in osteoporosis. While less prominent in risk reduction, even non-impact exercise works to preserve bone mass, particularly at the lumbar spine and the femoral neck. Not only does exercise (weight-bearing) stimulate osteoblast activity (i.e., bone building) to increase bone mass but gains in muscle content can provide critical fracture protection in smaller skeletons. Non-impact aerobic training might positively affect bone mass by decreasing inflammation, including stress-induced, bone loss (weight-bearing exercise is capable of this too) with a positive net effect on bone health, at least in the short-term. Aerobic exercise, like resistance exercises, can improve balance which also can mitigate fracture risk, albeit indirectly. Non-weight bearing aerobic activity alone over time, especially with low weight, can lead to more bone loss and fracture susceptibility due to the loss of lean body mass. Chronic cycling without any weight-loading training has shown to decrease bone density. Therefore, weight-bearing training is the cornerstone of bone mass and bone strength. The most propitious time to maximize bone mineral density is when one is young because bone remodeling is a slow process and more importantly, reported skeletal ‘gains’ from exercise are highest at this time.

Blood Sugar Control

Diabetes has been unfairly recognized as an obesity-related disease. In fact, diabetes is prevalent enough in normal and low BMIs to be a serious concern that warrants protective measures in all body types. Somewhat unexpectedly, underweight status has recently been declared at a risk factor for diabetes.

Exercise as aerobic or resistance-based activity provides from the best defenses against poor glucose tolerance and the development of diabetes. Interestingly, one clinical trial found participants given a moderate exercise intervention of at least 150 minutes per week were better protected against diabetes than those given metformin.

Exercise, especially high-intensity and ‘high-dose’ exercise, is reported to increase insulin sensitivity – independent of weight loss – in the obese as well as in those of normal weight. By enhancing insulin sensitivity in skeletal muscle, glucose is effectively forced out of the bloodstream and used as an energy supply to feed muscle cells. Besides improving insulin resistance, long-term exercises helps to correct impaired insulin secretion – a distinct diabetes-related defect – by increasing beta cell insulin secretion capacity. This method of correction is particularly important considering non-overweight diabetics usually suffer from insufficient insulin secretion as opposed to insulin resistance. Contrary to some beliefs, exercise, as long as it is low intensity, decreases cortisol (i.e., stress) levels. This is primarily considered to be an anti-anxiety benefit, but cortisol relates directly to glucose levels as it increases insulin resistance and leads to decreased insulin secretion. Furthermore, increasing levels of perceived stress are correlated with increasing rates of diabetes. Acquired fitness from long-term exercise also results in less activation of cortisol to common triggers. Fitter – not thinner – individuals are consistently seen with lower cortisol levels. Exercise also indirectly lowers cortisol levels and protects against insulin resistance by encouraging a higher quality sleep. Sleep loss, which is established as a risk factor for diabetes, causes a rise in cortisol levels and a decrease in glucose control the following day. Finally, as inflammation is yet another mechanism that harms glucose control and provokes the development of diabetes, exercise comes in handy against another prominent risk factor of the disease through lowering stress-induced and general inflammation. Ideally, exercising to sufficiently mitigate diabetes susceptibility in a high risk profile should be at least ‘sweat-producing’.

Reduces chronic inflammation

Suffering from inflammation does not have to equate to being in pain or suffering from a medical condition. Today many unknowingly are experiencing what’s called ‘chronic systemic inflammation’ where pro-inflammatory cells are constantly active in the body. This syndrome is an epidemic in the obese, but a surprising number (nearly 30%) of average weight individuals are plagued with ‘SI’. Normal weight individual with high body fat (i.e., ‘skinny fat’) are reported to have subclinical vascular inflammation paired with an unfortunate metabolic recipe of high glucose, elevated blood pressure, and a poor lipid profile, otherwise known as ‘metabolic obesity’. Another study looked at young women with a normal BMI with a body fat percentage greater than 30% and found these women to be highly inflammatory according to their blood samples despite no alcohol abuse and no smoking.

Exercise (aerobic and resistance) works notoriously well in combating inflammation. When there is weight to be lost, only exercise and not diet-induced weight loss produces a lessening in inflammation. Resistance is the more important of the two for it helps to replace adipose tissue (i.e., fatty tissue), which generates inflammation, with muscle.
By limiting inflammation, a host of inflammatory conditions and degenerative diseases can be prevented. Inflammation precedes all disease which some notable examples being atherosclerosis, diabetes, arthritis, Alzheimer’s disease, osteoporosis, sarcopenia, inflammatory skin diseases, digestive disorders, and even cancer. Current studies strong independent inverse associations between high levels of physical activity and risks of psoriasis, arthritis, and inflammatory bowel disease (IBD).

Starves Off Cognitive Decline (I.E., Dementia, Alzheimer’s Disease)

Younger adults may be tempted to ignore this benefit, at least in the present time, and studies deem increasing physical activity during midlife to have protective effects later in life, certain individuals – about one quarter of the population to be exact – are especially susceptible to Alzheimer’s disease if they are carriers of the Apoe4 gene. Startling research has found early and significant brain shrinkage in seemingly healthy E4 carriers as young as in their 20s compared to those without the high-risk gene. Encouragingly, other studies have indicated an even stronger risk-reduction effect from exercise in this group to the extent where daily aerobic activity could lower risk to that of the normal population.

Compared to widely reported risks for Alzheimer’s including diabetes, smoking, and obesity, a lack of physical activity was shown to be the strongest risk factor after reviewing large sample sizes in population-based data. Continuous physical activity throughout the lifetime can prevent and even begin to reverse brain aging by offsetting age-dependent decreases in neurogenesis, which translates to a preservation in brain volume. It does this by stimulating BDNF, also known as brain-derived neurotrophic factor, to an extent far greater than any conventional commercially-available health supplement. Simple training interventions (e.g., 40 minutes of daily walking) in older adults even benefit neural connectivity, restoring it almost that of younger healthy people.

Committing a lifestyle to exercising as little as 20 minutes three times a week can lower the risk for age-related cognitive decline. Similarly, significant improvements in memory have been noted in mildly cognitively-impaired aging adults with just 40 minutes of aerobic exercise twice a week. Resistance training is also useful in reducing these age-associated deficits.

Increases Longevity

Exercise consistently reduces all-cause mortality, including that of cancer. Conversely, a lack of energy expenditure is associated with markedly increased mortality. For example, all-cause mortality is increases as much as 52% in physically inactive middle-aged women.

Vigorous (but not physically exhausting) exercise may even extend lifespan. Endurance training promotes mitochondriogenesis (i.e., the production of new mitochondria/mitochondrial content) and preserves the function of the mitochondria which in turn increases an organism’s defense against biological assault and damage that accumulates during the aging process. This effect is enhanced by resistance training, so a balanced exercise regime is advised for optimal mitochondrial function. Essentially, organ function is preserved with the preservation of mitochondrial function. After healthspan (i.e., the delaying of major diseases), the lifespan ‘maxes out’ with organ reserve capacity, and that is profoundly delayed with increased fitness.

The minimal amount of exercise needed for any beneficial effect on life extension is 15 minutes daily(or 92 minutes per weekly), which equates to 3 year longer lifespan. Concerning the relationship with exercise and life extension: ‘the more the better’.

Decreases Risk of Cancer

Possibly the most crucial reason to engage in exercise is for the prevention of cancer. Exercise seems to have the greatest protective effect over two very relevant cancers – breast cancer and colon cancer. Increased BMI is a noteworthy risk for cancer, but physical activity is independently associated with risk reduction. Up to a 60% risk reduction for breast cancer was observed in women with only mild physical activity consisting of mostly housework-related and occupational-related physical exertion. The strong benefits of recreational physical activity in breast cancer reduction is reported in multiple studies with most attention being stressed on the duration (e.g., 10 hours or more of brisk walking weekly), not the intensity of such activity. In those who already contracted breast cancer survival is significantly better among the physically active. Effects are encouragingly similar for colon cancer with longer weekly hours of walking correlating with decreased risk. For those who exercised over 4 hours a week, a 40% lowered risk was found compared to those who exercised less than one hour a week. Exercise’s prophylactic value for these cancers specifically can most likely be attributed to decreased exposure to oestrogen for breast cancer and reduced bowel transit time for colon cancer. Inverse statistically significant relationships between exercise and other cancers such as pancreatic, prostate, endometrial, ovarian, and lung have been found as well. The mechanisms responsible for the protection against general cancer are inflammation downregulation, improved insulin sensitivity, IGF-I (insulin-like growth factor) restriction, decreases in adiposity (i.e., fat), and immunomodulation.

Conclusions

It is blatantly evident that maintaining or increasing high levels of physical activity is vital to us all. For complete risk mitigation, frequent (e.g., 3+ days a week) cardio-based and strength training exercises are required. The sum of all physical activity should expend a minimum of 1000 calories a week, preferably over 2000, however. Such measures should not be put off until midlife or old age but should begin in the young for lifelong benefit. Importantly, the level of vigor in exercise should be commensurate to the current fitness level. In other words, the unfit should not delve into vigorous activity without first building up that level of intensity or else adverse rather than beneficial effects can occur. On the other hand, fitter individuals should progress to more intensive exercises to achieve further benefit. As the saying goes ‘If you don’t use it, you lose it”, and that applies not only to specific organs but to life itself.

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WILLIAMS PT. Incident Diverticular Disease Is Inversely Related to Vigorous Physical Activity. Medicine and science in sports and exercise. 2009;41(5):1042-1047. doi:10.1249/MSS.0b013e318192d02d.
(Sexual Health):

Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003 Aug 5;139(3):161-8.
Lorenz TA, Harte CB, Hamilton LD, et al.. Evidence for a curvilinear relationship between sympathetic nervous system activation and women’s physiological sexual arousal. Psychophysiology. 2012;49(1):111-117. doi:10.1111/j.1469-8986.2011.01285.x.
Cormie P, Newton RU, Taaffe DR, et al. Exercise maintains sexual activity in men undergoing androgen suppression for prostate cancer: a randomized controlled trial.
Prostate Cancer Prostatic Dis. 2013 Jun;16(2):170-5. doi: 10.1038/pcan.2012.52. Epub 2013 Jan 15.

(Asthma):

Eijkemans M, Mommers M, Draaisma JMT, et al. Physical Activity and Asthma: A Systematic Review and Meta-Analysis. Hernandez AV, ed.PLoS ONE. 2012;7(12):e50775. doi:10.1371/journal.pone.0050775.
Fanelli A, Cabral AL, Neder JA, et al. Exercise training on disease control and quality of life in asthmatic children. Med Sci Sports Exerc. 2007 Sep;39(9):1474-80.

(Osteoporosis):

Diehl JJ, Choi H. Exercise: the data on its role in health, mental health, disease prevention, and productivity. Prim Care. 2008 Dec;35(4):803-16. doi: 10.1016/j.pop.2008.07.014.
Raab DM, Crenshaw TD, Kimmel DB, et al. A histomorphometric study of cortical bone activity during increased weight-bearing exercise. J Bone Miner Res. 1991 Jul;6(7):741-9.
Lertsinthai P, Charoenphandhu J, Suntornsaratoon P, et al. Voluntary wheel running mitigates the stress-induced bone loss in ovariectomized rats. J Bone Miner Metab. 2015 May;33(3):261-9. doi: 10.1007/s00774-014-0597-3. Epub 2014 Jul 11.
Sherk VD, Barry DW, Villalon KL, et al. Bone loss over 1 year of training and competition in female cyclists. Clin J Sport Med. 2014 Jul;24(4):331-6. doi: 10.1097/JSM.0000000000000050.
Suominen H. Muscle training for bone strength. Aging Clin Exp Res. 2006 Apr;18(2):85-93.

(Diabetes):

Taylor R, Holman RR. Normal weight individuals who develop type 2 diabetes: the personal fat threshold. Clin Sci (Lond). 2015 Apr;128(7):405-10. doi: 10.1042/CS20140553.
Sairenchi T, Iso H, Irie F, et al. Underweight as a predictor of diabetes in older adults: a large cohort study. Diabetes Care. 2008 Mar;31(3):583-4. Epub 2007 Dec 10.
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403.
Dubé JJ, Fleishman K, Rousson V, et al. Exercise Dose and Insulin Sensitivity: Relevance for Diabetes Prevention. Medicine and Science in Sports and Exercise. 2012;44(5):793-799. doi:10.1249/MSS.0b013e31823f679f.

Tsuchiya M, Manabe Y, Yamada K, et al. Chronic exercise enhances insulin secretion ability of pancreatic islets without change in insulin content in non-diabetic rats. Biochem Biophys Res Commun. 2013 Jan 11;430(2):676-82. doi: 10.1016/j.bbrc.2012.11.092. Epub 2012 Dec 2.
Hill EE, Zack E, Battaglini C, et al. Exercise and circulating cortisol levels: the intensity threshold effect. J Endocrinol Invest. 2008 Jul;31(7):587-91.
Traustadóttir T, Bosch PR, Matt KS. The HPA axis response to stress in women: effects of aging and fitness. Psychoneuroendocrinology. 2005 May;30(4):392-402. Epub 2005 Jan 11.
Zschucke E, Renneberg B, Dimeo F, et al. The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback. Psychoneuroendocrinology. 2015 Jan;51:414-25. doi: 10.1016/j.psyneuen.2014.10.019. Epub 2014 Oct 25.
Jang Y-M, Lee EJ, Kim DL, et al. The Association between Midnight Salivary Cortisol and Metabolic Syndrome in Korean Adults. Diabetes & Metabolism Journal. 2012;36(3):245-250. doi:10.4093/dmj.2012.36.3.245.
Kato M, Noda M, Inoue M, et al. Psychological factors, coffee and risk of diabetes mellitus among middle-aged Japanese: a population-based prospective study in the JPHC study cohort. Endocr J. 2009;56(3):459-68. Epub 2009 Mar 7.
Leproult R, Copinschi G, Buxton O, et al. Sleep loss results in an elevation of cortisol levels the next evening.
Sleep. 1997 Oct;20(10):865-70.
AlDabal L, BaHammam AS. Metabolic, Endocrine, and Immune Consequences of Sleep Deprivation. The Open Respiratory Medicine Journal. 2011;5:31-43. doi:10.2174/1874306401105010031.
Wang X, Bao W, Liu J, et al. Inflammatory Markers and Risk of Type 2 Diabetes: A systematic review and meta-analysis. Diabetes Care. 2013;36(1):166-175. doi:10.2337/dc12-0702.
Manson JE, Nathan DM, Krolewski AS, et al. A prospective study of exercise and incidence of diabetes among US male physicians. JAMA1992;268:63-7.

(Inflammation):

Gómez-Ambrosi J, Silva C, Galofré JC, et al. Body mass index classification misses subjects with increased cardiometabolic risk factors related to elevated adiposity. International Journal of Obesity (2012) 36, 286–294; doi:10.1038/ijo.2011.100; published online 17 May 2011
Kang S, Kyung C, Park JS, et al. Subclinical vascular inflammation in subjects with normal weight obesity and its association with body Fat: an 18 F-FDG-PET/CT study. Cardiovascular Diabetology. 2014;13:70. doi:10.1186/1475-2840-13-70.
De Lorenzo A, Del Gobbo V, Premrov MG, et al. Normal-weight obese syndrome: early inflammation? Am J Clin Nutr. 2007 Jan;85(1):40-5.
Lambert CP, Wright NR, Finck BN, et al. Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons. Journal of Applied Physiology. 2008;105(2):473-478. doi:10.1152/japplphysiol.00006.2008.
Frankel HC, Han J, Li T, et al. The Association Between Physical Activity and the Risk of Incident Psoriasis. Archives of dermatology. 2012;148(8):918-924. doi:10.1001/archdermatol.2012.943.
Di Giuseppe D, Bottai M, Askling J, et al. Physical activity and risk of rheumatoid arthritis in women: a population-based prospective study. Arthritis Research & Therapy. 2015;17(1):40. doi:10.1186/s13075-015-0560-2.
Khalili H, Ananthakrishnan AN, Konijeti GG, et al. Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses’ Health Study cohorts. BMJ : British Medical Journal. 2013;347:f6633. doi:10.1136/bmj.f6633.

(Cognitive Decline):

Norton S, Matthews FE, Barnes DE, et al. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 2014 Aug;13(8):788-94. doi: 10.1016/S1474-4422(14)70136-X.

Lautenschlager NT, Cox K, Cyarto EV. The influence of exercise on brain aging and dementia. Biochim Biophys Acta. 2012 Mar;1822(3):474-81. doi: 10.1016/j.bbadis.2011.07.010. Epub 2011 Jul 24.
O’Dwyer L, Lamberton F, Matura S, et al. Reduced Hippocampal Volume in Healthy Young ApoE4 Carriers: An MRI Study. Stamatakis EA, ed. PLoS ONE. 2012;7(11):e48895. doi:10.1371/journal.pone.0048895.
Nagamatsu LS, Chan A, Davis JC, et al. Physical Activity Improves Verbal and Spatial Memory in Older Adults with Probable Mild Cognitive Impairment: A 6-Month Randomized Controlled Trial. Journal of Aging Research. 2013;2013:861893. doi:10.1155/2013/861893.

(Longevity):

Vina J, Sanchis-Gomar F, Martinez-Bello V, et al. Exercise acts as a drug; the pharmacological benefits of exercise. British Journal of Pharmacology. 2012;167(1):1-12. doi:10.1111/j.1476-5381.2012.01970.x.
Dai D-F, Chiao YA, Marcinek DJ, Szeto HH, Rabinovitch PS. Mitochondrial oxidative stress in aging and healthspan. Longevity & Healthspan. 2014;3:6. doi:10.1186/2046-2395-3-6.
Wang L, Mascher H, Psilander N, et al. Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle. J Appl Physiol (1985). 2011 Nov;111(5):1335-44. doi: 10.1152/japplphysiol.00086.2011. Epub 2011 Aug 11.
Andersen SL, Sebastiani P, Dworkis DA, Feldman L, Perls TT. Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2012;67A(4):395-405. doi:10.1093/gerona/glr223.
Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet. 2011 Oct 1;378(9798):1244-53. doi: 10.1016/S0140-6736(11)60749-6. Epub 2011 Aug 16.

(Cancer):

Diehl JJ, Choi H. Exercise: the data on its role in health, mental health, disease prevention, and productivity. Prim Care. 2008 Dec;35(4):803-16. doi: 10.1016/j.pop.2008.07.014.
Hou N, Ndom P, Jombwe J, et al. An epidemiologic investigation of physical activity and breast cancer risk in Africa. Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2748-56. doi: 10.1158/1055-9965.EPI-14-0675. Epub 2014 Sep 21.
McTiernan A, Kooperberg C, White E, et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women’s Health Initiative Cohort Study. JAMA. 2003 Sep 10;290(10):1331-6.
Ibrahim EM, Al-Homaidh A. Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. 2011 Sep;28(3):753-65. doi: 10.1007/s12032-010-9536-x. Epub 2010 Apr 22.
Wolin KY, Lee IM, Colditz GA, et al. Leisure-time physical activity patterns and risk of colon cancer in women. Int J Cancer. 2007 Dec 15;121(12):2776-81.
Hardman AE. Physical activity and cancer risk. Proc Nutr Soc. 2001 Feb;60(1):107-13.
Slattery ML. Physical activity and colorectal cancer. Sports Med. 2004;34(4):239-52.
Brown JC, Winters-Stone K, Lee A, et al. Cancer, Physical Activity, and Exercise. Comprehensive Physiology. 2012;2(4):2775-2809. doi:10.1002/cphy.c120005.

(Conclusions):

Warburton DER, Nicol CW, Bredin SSD. Health benefits of physical activity: the evidence. CMAJ : Canadian Medical Association Journal. 2006;174(6):801-809. doi:10.1503/cmaj.051351.

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