The beneficial biochemistry of physiological changes brought about high-intensity exercise has been well reported throughout biomedical literature. Now, this exercise biochemistry can be very beneficial in relieving some of the symptoms of chronic Lyme Disease. This was shown clearly by a study in 2015 published by D’Adamo et al who introduced resistance-exercise training that lasted up to three times a week to patients living with Lyme Disease.

These patients reported relief and better management of the symptoms because of their exercise routine. Musculoskeletal pain, many kinds of neurological dysfunction, fatigue, low-health related quality of life, and fibromyalgia-like symptoms are common with patients living with chronic Lyme Disease. The biochemical changes that come from high-intensity exercise can relieve many of these symptoms.

A case report of a 14-year-old girl that had persistent symptoms after a year of diagnosis of Lyme Disease and antibiotic therapy was published by Moser et al in 2011. A simple intervention of physical therapy and resistance training markedly improved the patient’s pain, fatigue, and quality of life. In this particular case, the girl started out with significant impairments in strength, endurance, and gait, displayed severe fatigue, pain, and total body tremor.

After this simple intervention, she was able to regain her normal gait mechanics and even returned to playing high school sports. Her body tremor was minimal and her fatigue and daily pain reduced to very low levels that enabled her to return to school and church activities.

What is it about exercise training that is so effective against Lyme symptoms?

The answer is there is no single effect. It is the sum total of many beneficial physiological effects that we are saying as a culmination of health in Lyme disease patients. Here I will discuss some of the different benefits that have been shown with exercise therapy.

Exercise therapy is very effective in people with chronic pain.  Studies involving a wide variety of clinical populations that suffer from chronic pain including those with arthritis, peripheral neuropathies (pain associated with damage of nerves), Parkinson's' Disease, chronic neck and back pain, etc have shown an effective reduction in pain after exercise intervention.

Exercise is said to have a “hypoalgesic” response or a “reduction in pain” response. While we may not know the exact mechanisms by which exercise achieves this, one way is by activating the endogenous opioid system in our bodies.

Sleep quality improves with exercise. Research has shown that patients with chronic fatigue, insomnia, arthritis, have better quality sleep when offered exercise intervention. It is well-known that regular exercise will enhance skeletal muscle structure and function effectively.

This is true for both healthy populations as well as patients with various ailments including COPD (chronic obstructive pulmonary disease), sarcopenia, osteoporosis, aged people, and even those with heart failure. This is an increase in skeletal muscle function is so important for many who suffer from fatigue and exercise intolerance.

Exercise has plenty of mental health benefits including a marked reduction in stress, anxiety, and depression. It is thought to achieve this by changing our hormonal status, neurotransmitter levels (chemical messengers used for communication by the nervous system) as well as modulating both sympathetic and parasympathetic nervous systems (the two arms of our nervous system that help us focus and relax respectively).

Exercise reduces the activity of chemicals of a group called mono-amines such as serotonin and norepinephrine, both neurotransmitter molecules associated with depression. Stress is caused by a hyper-activation of a central axis called the hypothalamic-pituitary-adrenal axis. This axis is involved with the flow of information from the hypothalamic gland to the pituitary gland to the adrenal gland which releases the stress hormones.

Chronic activation leads to unfavorable stress in the system. Exercise will reduce the levels of these stress hormones including cortisol and corticotrophin-releasing factor.

Exercise therapy is one of the primary modes of treatment and management of the disease fibromyalgia. Fibromyalgia mimics Lyme Disease in many different ways and plenty of biomedical research points towards a positive benefit of exercise toward the treatment of this disease. Exercise has shown to effectively reduce stress, pain, anxiety, depression, and insomnia in fibromyalgia.

Regular exercise training also leads to marked improvements in the immunity of the patients. Some of the studies show an increase in neutrophil concentration immediately following exercise. These cells form part of the host defense and are involved in the pathology of many diseases.

Lymphocyte count (another immune cell) increases as a result of exercise as well. Natural Killer Cell activity improves after exercise. These are the cells that form the primary defense against viruses and tumor cells.

Defense against microbes and even cancer cells improves drastically with exercise training. All of this is important to chronic Lyme patients who sometimes suffer from reduced immunity.

Finally, exercise has a profound effect on the release of growth hormones. Plasma levels of human growth hormones have been shown to markedly higher after exercise and proportional to the duration as well as intensity.  The growth hormone is the anti-aging hormone that makes us look and feel younger and at the same time induce a lipolytic activity (fat destroying activity) in the body.

Thus exercise therapy in combination with multiple modalities is important for increasing the health of Lyme patients and better equips their bodies to fight the disease.

1. Pain and Exercise:

Some forms of chronic pain are receptive to exercise therapy for the maintenance of pain relief. It is also commonly used in the management of musculoskeletal pain with demonstrated benefits in terms of pain reduction and improved function in people with arthritis.

Toth et al published a randomized, single-blind control study in 2014 that compared management of human peripheral neuropathic pain with an educational intervention. Peripheral neuropathy is a common symptom of chronic Lyme Disease. They showed effective management of pain using exercise modalities. A transient increase in pain threshold is seen in healthy individuals after one bout of resistance exercise.

Knutzen et al showed in 2007 that this resistance to pain may be achieved with progressive exercise training. A randomized trial on 90 individuals with mild-to-moderate Parkinson’s Disease showed a decreased intensity of pain after exercising for three weeks. Chronic neck and back pain has been shown to be ameliorated after regular exercise.

In healthy individuals, the reduction in sensitivity to painful stimuli following exercise is called a hypoalgesic response. Exercise-induced hypoalgesia shows tremendous benefits in fibromyalgia, chronic fatigue syndrome, low back pain, musculoskeletal pain, and shoulder myalgia. Many of these syndromes have plenty in common with Lyme’s Disease.

The exact molecular mechanisms by which exercise promotes pain relief is unknown. The most widely considered mechanism is the activation of the endogenous opioid system. Intense exercise can also release peripheral and central beta-endorphins that are associated with a reduction in pain intensity.

Animal studies have also shown that non-opioid systems such as endocannabinoid systems of neurotransmitters such as serotonin and norepinephrine can also be activated. Some people have hypothesized a cross-talk between cardiovascular and pain modulatory systems. For example, pain regulation and blood pressure control involve the same brain stem nuclei, neurotransmitters (eg: monoamines), and neuropeptides (opioids).

Increased blood pressure and heart rate are in conjunction with alterations in sensitivity to painful stimuli. The increased heart rate and blood pressure are thought to activate the arterial baroreceptors which are associated with the release of pain-relieving neurotransmitters and peptides and the activation of the pain modulatory regions of the brain.

The hormonal system is also thought to play a role. During exercise, the sympathetic part of the nervous system and the HPA (hypothalamus-pituitary-adrenal) axis is activated. Noradrenaline and cortisol are direct products of this activation and both hormones have strong analgesic effects on the central nervous system.

Aerobic exercise is also shown to release adrenocorticotrophic hormone (ACTH) and this is associated with increased dental pain thresholds.  The HPA-axis is also activated during recovery from exercise that leads to increased post-exercise cortisol production and enhanced vagal activity.

2. Sleep Quality

Exercise in general is thought to improve sleep quality in healthy individuals as well as many patient populations. Here I’ve summarized a few studies that bear resemblance to our Lyme population because of commonalities in cognitive defects, chronic fatigue, arthritis symptoms, etc.

Carla et al published a study in 2016 showing the effectiveness of exercise on improving sleep quality and muscle strength in patients with Parkinson’s disease. They showed that a resistance training intervention can improve sleep quality to healthy controls in patients suffering from Parkinson’s disease.

Another disease that can affect sleep and finds relevance to our Lyme patients is rheumatoid arthritis. Many chronic Lyme Disease patients suffer from arthritis, chronic fatigue, and sleep disturbance.  Durcan et al showed that even in patients with rheumatoid arthritis, this was effective in inducing better quality sleep that is so vital for healing.

3. Skeletal Muscle Structure and Function

The improvements in physical ability in various disorders that come from enhanced skeletal muscle function have been reported in various studies.

Exercise develops muscle mass not only in healthy individuals, but also in people with several chronic diseases such as chronic obstructive pulmonary disease (COPD), sarcopenia, osteoporosis, in elderly aged people, and even people with chronic heart failure.

In chronic heart failure loss of muscle strength is the cause of many symptoms such as fatigue, dyspnea, and exercise intolerance – symptoms often seen in Lyme patients as well. An increase in muscle strength by exercise has been shown to alleviate these symptoms.

4. Stress, Anxiety, and Depression

Decreased anxiety, depression, and insomnia associated with clinical depression were shown with exercise training (Brosse, 2002; Dunn 2001; King 1997, Singh 1997). Exercise can have profound effects on the hormonal milieu, neurotransmitter levels, and sympathetic and parasympathetic nervous system activity and is thought to improve depression by these mechanisms.

The predominant mechanism of depression is the reduction in the activity of mono-amines, namely reductions in serotonin and norepinephrine. Alternatively, hyperactivity of the hypothalamic-pituitary-adrenal axis due to increased release of cortisol and corticotropin-releasing factor has also been associated with depression.

Long-term resistance training leads to decreased cortisol response to stress as shown by Braith et al, 2006. Many studies and clinical trials have found strong evidence of a positive correlation between regular physical exercise and a reduction in depressive symptoms.

Both strength training and aerobic training have positive effects on depression. These effects are thought to be mediated by the stimulation of negative feedback mechanisms in response to the acute stressor of exercise that stimulates the HPA axis. These include enhanced density and efficiency of mineralocorticoid receptors, lower cortisol levels, and inhibition of cortisol synthesis.

Increased vasopressin to corticotrophin-releasing hormone ratio has positive effects on the negative feedback through a reduction in pituitary stimulation. All of this also increases immunity.

Exercise modulates major central nervous system neurotransmitters associated with an individual's state of alertness (norepinephrine), pleasure (dopamine), and level of anxiety (serotonin).

Other neurochemicals that are released during physical activities include opioids and endocannabinoids which promote a sense of euphoria and well-being, anxiolytic effects, sedation, and decreased sensitivity to pain in humans.

Expression levels of neurotrophic factors like BDNF (brain-derived neurotrophic factor), insulin-like growth factor (IGF-1), vascular endothelial growth factor (VEGF), neurotrophin-3 (NT-3), fibroblast growth factor (FGF-2), glial cell line-derived neurotrophic factor (GDNF), epidermal growth factor (EGF) and nerve growth factor (NGF) increase after exercise.

All of these factors are important for survival, proliferation, and maturation of nerve cells.  They also inhibit apoptotic signals and play a substantial role in the individual’s cognition and behaviors.

5. Treatment of Fibromyalgia

Fibromyalgia mimics Lyme Disease in many different ways and there are many studies that show exercise to be an effective treatment for this condition. Exercise is now a standard protocol of treatment in clinics for patients with fibromyalgia.

This is important as people with fibromyalgia (and chronic Lyme disease) often present with reduced muscle strength and endurance that is accompanied by greater levels of muscle fatigue compared to sedentary women. This leads to a substantial reporting of physical disability. Exercise can normalize response to stress, reduce pain perception, anxiety, depression, and insomnia and thus can be of immense value to patients with fibromyalgia (and chronic Lyme disease).

A review of five of these studies showed clearly that women (with fibromyalgia) who did resistance training rated their well-being 25 units better than women who did not do any resistance training.  They reported having a better physical function (ability to do normal activities), reduced pain, reduced tenderness (estimated as a number of points perceived as painful with 4 kilograms of pressure), etc.

Remarkably women who went through resistance training could lift as much as 28 kg more than before, whereas the control group could barely lift 1 kg more showing a marked increase in muscle strength.  This improved muscular performance can enhance many things in a patient suffering from fibromyalgia including their ability to perform daily tasks and counteract disability.

Researchers have also described metabolic conditions in muscle tissue suffering from fibromyalgia that is consistent with physical deconditioning. Deconditioning is linked to the etiology of fibromyalgia by increasing an individual’s vulnerability to microtrauma during mechanical strain related to posture and physical activity. The metabolic adaptations that happen in normal healthy individuals after exercise can normalize some of these findings and may lead to improvements in pain. So by increasing resilience to the process of microtrauma, and repair, exercise improves response to pain.

6. Increase in immunity from regular, moderate exercise.

There are many studies that show how regular moderate exercise can improve our immune cell function

1. Neutrophil concentration increases during and after exercise. Neutrophils are part of the innate immune system and are essential for host defense and are involved in the pathology of many diseases. Moderate exercise also boosts neutrophil functions including chemotaxis, phagocytosis, and oxidative burst. Lymphocyte cell count also increases during exercise.
2. Natural Killer cell activity increases during and after exercise. NK cells mediate non-major histocompatibility complex (MHC) restricted cytotoxicity, with potential resistance to viral infections and cytolysis of some malignant cells.
3. During exercise, epinephrine is a release from adrenal medulla and norepinephrine from the sympathetic nerve terminals. Arterial plasma concentrations of epinephrine and norepinephrine increase linearly with dynamic exercise. These hormones have a direct effect on immune cell response. For example, T, B, and natural killer cells all have beta-adrenoreceptors that modulate the activity of these hormones. These receptors are thought to mediate their effects through the activation of adenylyl cyclase and cAMP. Epinephrine is responsible for the recruitment of natural killer cells to the blood.
4. Studies show that defense against many disease-causing microbes is improved remarkably after exercise. For example, in 1922 it was reported that 80% of the sedentary guinea pigs died after exposure to type I pneumococcus but animals that were given acute exercise showed only a 20% fatality rate. Similarly, mice trained on running wheels and injected with Salmonella typhimurium had a significantly higher survival rate than sedentary mice, and this was directly correlated to the increased levels of IL-1. Comparable results were observed in trained mice that were infected by the influenza virus.
5. Studies have also shown a protective effect of exercise against cancers, such as breast cancer mediated by its effects on the immune system.

       7. Effect on Growth Hormone.

Growth hormone is released from the anterior pituitary is increased during exercise.  Plasma levels of growth hormone increase in response to exercise both with duration and intensity.

Correlations in the response of exercise-induced norepinephrine and hGH levels suggest that the catecholamines drive the hGH response to exercise. The hGH levels increase seem to be a direct response to the increasing energy demands of the exercise as well as repair of skeletal muscle damage.

The growth hormone is thought to exert its primary effects by stimulating IGF-1 secretion from the liver. The growth hormone augments adipose tissue lipolysis and increases net protein synthesis by facilitating amino acid transportation and availability via both endocrine and locally produced IGF-1.  It also has direct effects on muscle synthesis.

The lipolytic effects of hGH are mediated by potentiating the sensitivity (by activating of beta-adrenergic receptors) of adipose tissue to other lipolytic hormones like catecholamines, stimulating the fat breakdown enzyme (hormone-sensitive lipase) and inhibiting fat storage enzymes (fatty acid synthase and acetyl-CoA carboxylase).

The growth hormone is also widely purported to have anti-aging effects. hGH and IGF-1 also impact connective tissue. The synthesis of collagen is stimulated by exercise. Many studies demonstrate strong relationships between collagen synthesis and tendon and muscle synthesis and plasma growth hormone levels. It has been shown to increase cell proliferation, protein synthesis in the rabbit tendon, and also recovery from anterior cruciate ligament (ACL) injuries in rats.

8. Cognitive Function

Lyme disease patients often report brain fog and a drop in their cognitive abilities. Exercise is well known to increase cognitive functions in healthy and diseased individuals.

Many studies have shown that throughout their lifespan from younger children to the elderly higher levels of fitness are associated with better performance on cognitive tasks.

For example children, 9-10 years of age with higher levels of aerobic fitness completed cognitive tests comparable to 18-30-year-olds. Lower levels of fitness corresponded to lower accuracy and slower response speed.

The more fit children also demonstrated different brain activation patterns, as measured by functional MRI, compared with less fit children. Exercise is thus a potent modulator of brain structure and function. Children that exercise also have greater executive control.

During exercise, brain blood flow increases and is shown to delay the negative effects of advancing age. A systemic vascular dysfunction that alters blood flow to the brain often presents as cognitive impairment. Alzheimer's Disease patients for example also display lower cerebrovascular activity compared to healthy age-matched controls.

Exercising animals show increased cerebral blood flow even when they were not exercising compared to sedentary animals. In humans, this increase in cerebral blood flow is as much as 17% at rest. Brain vasculature also increases as a result of regular exercise.

Capillary growth in the motor cortex is detected as early as thirty days of training. An increase in cerebral blood flow can decrease the neurotoxicity that Lyme patients may display as a result of the Borrelia infection.

Another area that develops with exercise is the hippocampus associated with memory and learning. Animals that were placed in a stimulating environment but with limited locomotor activity did not demonstrate hippocampus neurogenesis. Animals with access to running wheels performed better both on learning and memory tests.

Davenport and colleagues reported that exercise not only increases cerebral blood flow but also the cerebrovascular reserve by increasing neurotrophic factors, angiogenesis, vascular function, and neurovascular coupling. This would result in greater neurogenesis, cognitive performance, and cognitive reserve.

Thus, increases in cerebral blood flow, the expression of a number of trophic factors (BDNF, IGF-1, VEGF, NT3, FGF-2, GDNF, EGF, and NGF) and the induction of proinflammatory processes promote neurogenesis, angiogenesis and synaptogenesis: all of which help with cognition.

9. Fatigue

Fatigue is the most common symptom displayed across the spectrum of many individuals suffering from chronic Lyme disease.  Fatigue is different from just tiredness, as it is an enduring sensation of weakness, lack of energy, tiredness, and exhaustion.

It is chronic and not related to any over-exertion and cannot be relieved by rest.  Fatigue affects people with Lyme disease and overlaps with individuals suffering from fibromyalgia, rheumatoid arthritis, or peripheral neuropathy.

Neurobiological changes that are related to fatigue include metabolic changes in the brain, particularly levels of serotonin, dopamine, and norepinephrine.

For example, high levels of serotonin are associated with negative behaviors: lethargy and sleepiness. Both physical and mental exhaustion can be related to dopamine deficiencies in specific brain areas such as the ventral tegmental area of the midbrain, the substantial nigra pars compact, and the infundibular nucleus of the hypothalamus.

Dopamine deficiencies in these brain areas in conjunction with exhaustion support the hypothesis that low levels of dopamine could reduce motivation and motor co-ordination and could lead to lethargy and fatigue.