Father of Medicine Hippocrates said ‘Walking is Man’s best medicine’.

Philosopher Plato (427–347 BC) said: ‘Lack of activity destroys the good condition of every human being while movement and methodical physical exercise saves and preserves it’.

Exercise has been extolled for its virtues since 3500 BC in China.

The first studies demonstrating a significant inverse relationship between physical activity and coronary heart disease (CHD) were those conducted by Morris et al. (1953b) in London early in the 1950s. These authors found that London bus conductors had only 73% the frequency of CHD as compared to the less active bus drivers. Their later comparison of London postmen and less active postal clerks produced much the same findings (Morris et al., 1953a). 

Physically inactive middle-aged women (engaging in less than 1 h of exercise per week) experience a 52% increase in all-cause mortality, a doubling of cardiovascular-related mortality, and a 29% increase in cancer-related mortality when compared with physically active ones.

Further, there is irrefutable evidence of the effectiveness of regular physical activity in the primary and secondary prevention of several chronic diseases (e.g., cardiovascular disease, diabetes, cancer, hypertension, obesity, depression and osteoporosis) and even premature death.

So, with this wide array of beneficial effects, if exercise could be packaged into a ‘PILL’ it would be the largest selling in the world.   

Yet, in this ‘modern’ world of household gadgets and ‘addictive’ electronic gizmos, exercise has plummeted even in the rural and low-income strata. The estimate is that only 50% of children and 8% of adolescents are active for the recommended 60 minutes per day. In the elderly, only 5% are active for the recommended 30 minutes of activity per day. Little wonder that lifestyle diseases (obesity, type 2 diabetes, heart ailments, paralytic attacks, osteoporosis and cancers) are overtaking infectious diseases as the number one killer. This is true even for the present Covid-19 pandemic where mortality is linked to lifestyle diseases.  

Exercise can be started at any age, even by those who live a sedentary life or in seniors. However, as with any medication the dose will depend on the individual’s capacity, fitness, presence of any comorbidities (like obesity, diabetes, high blood pressure, cardiovascular or cerebrovascular disorders etc.) and requirements. Like in most medications the principle is ‘start low, go slow’. Exercises are mainly of two types: physical training—aerobic and strength/resistance, and motor training—balance, coordination, and flexibility. The physical training is repetitive and automatic. These once learnt require high metabolic energy but not much neuromuscular effort.

The first of these is aerobic, popularly called cardio, (walking, jogging, running, swimming, dancing etc.) where the cardiorespiratory system is used. The other is resistance or strengthening exercises (weight-lifting, resistance bands etc.). The second are those requiring more neuromuscular effort including balance, flexibility and coordination. Thus, they require high neuromuscular effort but low metabolic energy (yoga, tai chi, etc.) And then there are the dual tasks that are composite of both (a combination of motor-cognitive tasks, such as standing on one foot and counting backwards by 3 from 100 or a combination of physical and cognitive activities, such as walking fast on a treadmill while performing various tasks presented on a screen; or a combination of two motor tasks, such as standing on one foot and throwing/catching a ball. Physical training depends on the intensity of the training while motor training depends on the complexity. Dual training, combining physical and motor tasks, leads to improved general health and better preserved cognition.

Exercise like any other medication should be prescribed or undertaken after evaluating all aspects of the present health, age and sex – the HIT formula –

H for How frequent,

I for Intensity and

T for Time duration of exercise

H – How frequent – 3 days per week

I – Intensity – walking at 2-3 miles per hour

T – Time period – 30-45 minutes per day

So, even if you are over 50-60 years you can start walking and improve your health.

Just a daily walk of 30 minutes can positively affect the following 10 things–

It’s the HIT MANTRA

1. Increases BMR and help you burn more calories
2. Improves blood viscosity
3. Increases growth of new blood vessels – angiogenesis
4. Increases oxygen flow from 8 litres a minute to 100 litres a minute, as also better cardiac and lung capacity.
5. Brain working improves – increased serotonin, endorphins, dopamine and brain-derived neurotrophic factor (BDNF). The last increases new brain cell (neuron) production.
6. Increased endorphins leading to feeling more energetic, reduced pain, less depression and anxiety and increased ability to overcome addiction.
7. Increased immunity
8. Faster and better digestion of carbohydrates and proteins, almost four times faster – this helps you lose weight
9. Increased muscle bulk and, because more muscles means more mitochondria, so more calories burnt
10. Better sleep

      How soon does this work? – even within a couple of hours and much, much better in a few weeks.

There is evidence for prescribing exercise in the primary and secondary prevention of pulmonary and cardiovascular diseases (coronary heart disease, chronic obstructive pulmonary disease, hypertension, intermittent claudication); metabolic disorders (type 2 diabetes, dyslipidemia, obesity, insulin resistance); muscle, bone and joint diseases (rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, osteoporosis); neurodegenerative diseases ( Alzheimer’s, Parkinson’s etc.), cancer; and depression (Pedersen and Saltin, 2006; Warburton et al., 2006a). Even if exercise is an effective therapeutic agent for all of these diseases, as with any other medicine, the dosage (volume and intensity of the exercise), frequency of administration (sessions per week), type (aerobic vs. resistance exercise), systemic and psychoactive effects and contraindications and side effects of the exercise must be taken into account to achieve the best clinical outcome. For instance, both resistance and aerobic training have been shown to be of benefit for the control of diabetes; however, resistance training may have greater benefits for glycaemic control than aerobic training.

REGULAR EXERCISE CAN

• Reduce abdominal adiposity
• Improve weight control
• Improve lipoprotein profiles (e.g. reduce triglyceride levels, increase high density lipoprotein – HDL and decrease low-density lipoprotein levels -LDL)
• Improve glucose homeostasis and insulin sensitivity
• Reduce blood pressure
• Improve autonomic tone
• Improve coronary blood flow
• Augment cardiac function
• Decrease blood coagulation
• Enhance endothelial function
• Reduce systemic inflammation

Signaling Pathways Regulated by Exercise in Skeletal Muscle

Let us now turn to the primary and secondary prevention of the above diseases.

Cardiovascular disorders

Some benefits of exercise include enhanced mitochondrial function, restoration and improvement of vasculature (Blood supply and angiogenesis), and the release of myokines from skeletal muscle that preserve or augment cardiovascular function and have long-term anti-inflammatory effect.

Exercise improves cardiovascular health by inducing changes in oxygen delivery, vasculature, peripheral tissues, and inflammation.

(A) Exercise improves oxygen delivery throughout the body through promotion of vasodilation and angiogenesis.

(B) Exercise increases mitochondrial biogenesis in adipocytes, skeletal muscle myotubes, and cardiomyocytes.

(C) Exercise causes a long-term anti-inflammatory effect (which is inversely related to the increased inflammation typically seen in CVD and obesity). Myokines released from skeletal muscle during physical exercise partially mediate these anti-inflammatory effects, and promote inter-tissue cross talk to mediate further cardiovascular benefits (Vina et al, 2012).

Exercise-induced myokines mediate organ cross-talk and improve cardiometabolic health.

(A) The myokine IL-6 inhibits TNF-a, reducing inflammation and protecting against the formation of atherosclerosis; stimulates GLP-1 secretion causing improved insulin secretion; increases lipolysis and fatty acid oxidation in adipose tissue and increases glucose uptake through the AMPK signaling pathway.

(B) Fstl1 decreases ischemic injury size through activation of the Akt/AMPK pathway (activating eNOS and enhancing revascularization) and early fibroblast stimulation (which aids in repair after ischemia-reperfusion).

(C) Myonectin (MyoN) increases fatty acid uptake in adipocytes and hepatocytes, and promotes protects against ischemic injury in the heart, possibly through Akt activation.

(D) NDNF improves survival after myocardial infarction (MI) by reducing apoptosis through stimulation of the Akt/AMPK/eNOS pathway (enhancing revascularization) (Pinckard et al, 2019).

The rate of obesity-related cardiovascular disease is rapidly increasing, and often associated with additional co-morbidities including type 2 diabetes. It is clear that exercise reduces cardiovascular risk factors, and this reduction in risk factors is independent of changes to body weight or incidence of type 2 diabetes. Exercise is also an important therapeutic treatment for patients who have cardiovascular diseases, further demonstrating the protective and restorative properties of exercise. In patients with CVD, exercise improved endothelium-dependent vasodilatation, increased ejection fraction and exercise tolerance, improved quality of life, and reduced CVD-related mortality. Exercise improves cardiovascular health by several mechanisms including increased mitochondrial biogenesis  fatty acid oxidation, dilation of blood vessels causing improved myocardial perfusion, and reduction of inflammation providing protection against the development of atherosclerosis (Pinckard et al, 2019).

Myokines released from skeletal muscle during exercise also mediate systemic and cardiovascular health benefits through an anti-inflammatory action, increased fatty acid oxidation, increased glucose uptake, and improved insulin secretion and sensitivity.

Importantly, several myokines (IL-6, Myonectin, Fstl1, and NDNF) have also been shown to have cardiovascular protective effects in response to ischemia-reperfusion injury (Pinckard et al, 2019).

Cognition and Brain

A large meta-analysis showed that in children lack of exercise adversely affects perceptual skills, creativity, concentration, academic readiness, achievement, IQ, math and verbal tests. On the other hand, studies have shown that regular exercise leads to definite improvement in speed of processing, attention span, executive functioning and global cognition. Exercise improves relational memory (hippocampus function) rather than item memory. An example is that remembering a face is an item memory but remembering the name where you have met them and what was the context of the meeting are part of relational memory. Also, you will agree that accuracy of memory is better than speed of memory and accuracy is improved by exercise (Mandoleesi et al 2018).

This is supported by neuroimaging findings, too. MRI shows larger volume in aerobically active children in critical brain areas connected to memory, namely, hippocampus and dorsal striatum. Functional MRI too supports this with larger P300 values. It has been found that these children are also able to monitor, regulate and correct their processing errors which is linked to the prefrontal and anterior cingulate cortices. Hippocampal volume is increased in elders as well (Mandoleesi et al 2018).

In adolescents and young adults the data is less certain though more active individuals have better brain functioning.

In older age groups the effects are more like in children, affecting not only cognition, but also overall brain function and even structure. For example, exercise improves preferentially executive functioning like multi-tasking, planning, regulation, inhibition and error-monitoring. These are controlled by the prefrontal and anterior cingulate cortices. Thus, in this age group we see more selective improvement rather than general brain function enhancement. Lack of exercise affects these functions selectively. This is why we see sedentary elders having less self-regulation in day-to-day activities and confusion with multi-tasking and planning (Mandoleesi et al 2018).         

Aerobic exercise thus has a wide range of actions on neuronal growth, synaptic plasticity and increase in blood supply through new blood vessel formation (angiogenesis). The effects on BDNF (brain-derived neurotrophic factor) are very important, as this controls neuronal growth and maintenance. Exercise also increases IGF-1. (see below) 

On the other hand, resistance training even with resistance bands of gradually higher intensity have a positive effect on IGF-1. IGF-1 in turn has a positive effect on neuronal growth, survival and differentiation and thus improves cognition. It also lowers homocysteine, a prime marker of inflammation, which is elevated in many with Alzheimer’s disease.

Improving cognition requires an hour per day five days a week exercises ranging from simple walking or jogging (aerobic) to resistance (strength) exercising. The level of exercise undertaken depends on the age, sex and co-existence of other morbidities.  However, regardless of the level of exercise similar benefits are seen. Combination exercises of mental exercise with above are better than simple aerobic exercise or resistance exercises alone. Example while running or walking try to subtract 100-3 till zero. Or, if mathematics is not your forte, then try remembering twenty names of birds or fruits or vegetables.     

World-wide 35 million have Alzheimer’s. Exercise results in more hippocampal volume, Also, through reducing stress, increasing endorphins and other chemicals, neurogenesis (increasing number of new brain cell) and improving blood flow to the brain dementia is prevented and can even be reversed (Rovio et al 2005).   

Detraining or stopping exercising can result in

• Blood vessels change in 2 weeks
• VO2 max reduced 20% lower – affects cardiac function – because there is a loss of mitochondria in 2 weeks
• High sugar levels
• Resting BMR lowered
• 5 weeks increases fat mass by 12%
• 1 week bed rest (injury etc) loses muscle mass with increased insulin and insulin resistance so more stored fat
• Higher BP

So what are you waiting for? Put on your walking shoes and hit the road.

References:

1. Morris JN, Heady JA, Raffle PA, Roberts CG, Parks JW. Coronary heart-disease and physical activity of work. Lancet. 1953b;265:1053–1057.
2. Morris JN, Heady JA, Raffle PA, Roberts CG, Parks JW. Coronary heart-disease and physical activity of work. Lancet. 1953a;265:1111–1120.
3. Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006;16(Suppl. 1):3–63
4. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ. 2006a;174:801–809.
5. Vina J, Sanchis-Gomar F, Martinez-Bello V, Gomez-Cabrera MC. Exercise acts as a drug; the pharmacological benefits of exercise. Br J Pharmacol. 2012;167(1):1‐12.
6. Pinckard K, Baskin KK and Stanford KI (2019) Effects of Exercise to Improve Cardiovascular Health. Front. Cardiovasc. Med. 2019 6:69
7. Mandolesi L, Polverino A, Montuori S, et al. Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits. Front Psychol. 2018;9:509.
8. S. Rovio, I. Kareholt, E.-L. Helkala et al., “Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease,” Lancet Neurology, 2005 vol. 4, no. 11, pp. 705–711.