fatigue - Page 3

Exercise to Alleviate Fatigue

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We all know that exercise is good for us, but few know how truly important it really is. I work with a woman who was injured by Gardasil. Prior to her vaccination, she was healthy and active, but after the vaccination, immediately, and in the years that followed, she has endured a complex array of symptoms that included intense and unremitting fatigue, regular bouts of dizziness and syncope, hypersomnia, muscle pain, neuropathies, intense salt and water cravings, and excessive weight loss.

As we have worked to identify various possible culprits, and we have identified a few, one thing that struck me as absolutely fascinating is how she managed her ordeal, how she managed her dizziness, syncope and hypersomnia before knowing what was wrong. She managed with exercise (and salt, water, and now some medications). She told me, that although it was excruciatingly difficult at first, exercising reduced her dizziness. More specifically, aerobic exercise provided her with 4-6 hours of non-dizzy, non-blackout functioning, while weight-lifting could provide her with as much as 24 hours of functioning. This was intriguing, to say the least. What biochemical factors were altered by exercise that allowed her periods of functioning and how did the type of exercise moderate the duration of functioning?

Before I tell you what I think may be the answer, let me backtrack a bit and tell you about something else I have been pondering as of late, the nature of fatigue. Fatigue is one of those symptoms that is ubiquitous across so many syndromes that it is often overlooked as a clinically important indicator of anything. This is a shame because fatigue can tell us so much. Even with the syndrome that bears its name – chronic fatigue syndrome – the debates about the reality of fatigue as a meaningful physiological attribute of disease are rampant. What is fatigue? Where does it come from? Does chronic fatigue even exist?

What is Fatigue?

At its most basic level, fatigue is a lack of energy. And while there may be a myriad of environmental or outside sources of fatigue, like stress, workload, exercise, lack of sleep, poor nutrition, and even an array of disease states whose core symptoms include fatigue, the internal components of fatigue all point to a change in biochemistry that reduces cellular energy production and usage. Something in our external or internal environments flips an energy switch. What is that switch?

Mitochondria and Fatigue

Yes, I said mitochondria. Harken back to your high school biology, remember those energy powerhouses inside the cell, responsible for generating ATP – adenosine triphosphate – the cell’s chemical energy – without which, the cell dies. Even if you don’t remember, trust me on this, we need working mitochondria to survive. Mitochondrial disease can be devastating because it affects the most basic functioning of the cell, its energy usage. From a cellular perspective, damaged or deficient mitochondria impair all the major metabolic pathways necessary for building, breaking down or recycling the cell’s molecular machinery, even down to preventing DNA and RNA synthesis. And as logic would have it, organs that require the greatest energy are affected most by mitochondrial disease or injury; think heart, lungs, brain, liver, GI tract and muscles.

Mitochondrial injury or dysfunction can occur by a number of mechanisms, by an inherited mutation, a spontaneous mutation or by environmental factors. Mitochondria are particularly sensitive to all the toxic insults of modern living, bad food, sedentary lifestyle, stress, environmental chemicals, medications and vaccines. Over time, and after repeated exposures, these insults reduce mitochondrial functioning through a process called oxidative stress. All those ‘anti-oxidant’ concoctions on the market are to reduce oxidative stress.

Long story short, and by way of a gross over-simplification, low or dysfunctioning mitochondria create a myriad of complicated symptoms. Depending upon the organ(s) where the dysfunction occurs, that’s where disease develops. No matter where the mitochondrial insults take place, the loss of energy will lead not only the dysfunction of that organ system, but also, to an overall sense of fatigue. Thus, fatigue, at its most basic level, means some sort of mitochondrial loss of function. When fatigue is severe, unremitting and presents with what seems like a cluster of unrelated symptoms, it is very clinically relevant. Indeed, fatigue may be the key clinical indicator.

Exercise and Mitochondrial Biogenesis

What does all this have to do with exercise and our post Gardasil patient with symptoms that included fatigue, dizziness, hypersomnia, muscle pain, among others?  Well, it turns out, a lot. Let’s begin with exercise.

Exercise increases mitochondria, in number and in size. The act of exercising tells our cells to produce more mitochondria. It’s called mitochondrial biogenesis. On the most obvious level, this makes perfect sense. When we exercise our demands for energy increase and to meet those needs our cells respond by birthing more of the machinery that produces this energy.

Not knowing any of this, or that post vaccine injuries could be attributable to mitochondrial insults (see our article about thiamine deficiency post Gardasil and oxidative stress), somehow, intuitively, our Gardasil injured woman felt she needed to exercise to survive and, unlike so many of us, she listened to her body. By exercising, she increased the number of mitochondria, effectively compensating for their deficits in functioning. Think about it, if you can’t have optimum energy production in the machinery you have, but you still need a certain amount of energy output to survive, increase the number of machines producing that energy. The exercise didn’t fix what was broken, but it may have helped her body to function and survive. She increased her cellular energy by exercising. And the increase in energy reduced her dizziness and blackouts.*

The fact that exercise may alleviate fatigue and do so by changing the most fundamental aspect of cellular functioning, points to the possibility of a wonderfully simple and elegant, non-medication based, therapeutic option for folks suffering with fatigue – related symptoms. Some physician/researchers suggest that exercise, under the guidance of trained experts, also improves symptoms associated with some mitochondrial related conditions.

I have not yet figured out why the different types of exercise yielded different levels of functioning, perhaps an exercise physiologist can weigh in and clarify that for us, but it is clear from this case and from the research materials on the subject of exercise and mitochondrial disease and injury that exercise is a critical component of maintaining or managing cellular energy requirements. Sometimes it is the most simple solutions that alleviate the most complicated of problems.

*Post Script

I should mention that exercise is in no way a ‘cure’ for the serious injuries and illnesses that she and others sustain. There is quite a bit of controversy regarding whether exercise is safe or effective for individuals with chronic fatigue and other conditions. Individuals with health issues should not begin an exercise program without consulting their healthcare provider. It should also be noted that the case presented here represents a particular history of symptoms and in no way reflects a prescription or recommendation for salt or water loading or even exercise.

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Guts and Brains and Hormones, Oh My!

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When a woman experiences fatigue, brain clouding, flat mood, PMS, and constipation, we call it anxiety or stress and we stick her on an antidepressant that she will likely take for the rest of her life. Where in this protocol have we investigated why she is feeling that way?  How have we personalized the treatment to her unique biochemistry?  What is the plan for side effects including new and different psychiatric symptoms resulting from this prescription?  We haven’t.  We’ve applied a one-size-fits all treatment to mask symptoms without consideration for the cause.

The Immune System and Depression

Psychiatry has known about the role of the immune system in certain presentations of depression for the better part of the last century, and more recently, pioneering thinkers like Maes, Raison, and Miller have written about the role of altered immune set points and inflammation in models of depression. Our immune systems are largely housed in the gut and the interplay between the gut and the brain is a complex and profoundly important relationship to appreciate.

We all recognize that anxiety or nervousness can impact our guts – most of us have had butterflies before a date or even diarrhea with extreme performance anxiety?  We are just learning that this relationship is bidirectional; however, and that the gut can also communicate its state of calm or alarm to the nervous system.  We think that the vagus nerve is a primary conduit of information and that inflammatory markers are the vehicles traveling this highway. Scientists have studied the “protective effects” of severing this nerve when animals are exposed to gut-related toxins that normally cause depressive symptoms.  We are getting ahead of ourselves; however, because we need to better elucidate why inflammation matters, where it comes from, and why it is the universal driver of chronic illness.

How Does Inflammation Start?

When a woman feels foggy, run-down, easily overwhelmed, and flat, we know that  her hormones as messengers between her gut and brain are out of balance. From my perspective; however, hormone derailment is a downstream effect of cellular dysfunction from oxidative stress and inflammation. Inflammation stems from many sources, including, hallmarks of the modern American lifestyle:

  • Sugar. Sugar, particularly in the form of fructose and sucrose, spikes insulin and triggers release of inflammatory cytokines. It forms advanced glycation endproducts when it binds to proteins, and oxidizes lipids which form cell and mitochondrial membranes.
  • Chemicals. Pesticides, environmental pollution from industrial waste, hormonally-modulating plastics, fire retardants, and cosmetic additives all stimulate our immune systems to varying extents and disrupt optimal production of energy on a cellular level, particularly in vulnerable tissues like the thyroid.
  • Pathogens. The aforementioned culprits, and notably herbicides, gluten grains, and genetically modified foods, promote intestinal permeability, changes in our intestinal flora that facilitate growth of pathogenic bacteria, yeast, and fungus which keep our immune systems in a state of alarm,
  • Stress. This catch-all term, broadly defined, represents the ultimate link between hormones and inflammation, because stress, whether it’s psychological or physiologic, triggers the release of cortisol. Cortisol helps to mobilize blood sugar so that you can run effectively and efficiently from that tiger chasing you. It also acts as a systemic immune suppressant, lowering levels of secretory IgA, an important body guard of the gut mucosa.

Cortisol and insulin are like stress-response sisters, and high cortisol states will also contribute to insulin resistance, or high insulin and high sugar while the cells, themselves, are starving.  Insulin protects fat storage (inhibits lypolisis), and fat cells secrete their own inflammatory signals in addition to aromatizing testosterone to estradiol contributing to states of estrogen dominance, while also increasing DHEA and androgens to fuel that process (as well as acne, hair growth, and agitation).

Cortisol also inhibits the conversion of storage thyroid hormone to active hormone leading to states of hypothyroidism even with normal-looking labs.

What Does Inflammation Do?

Once inflammation is active, it is highly self-perpetuating. These inflammatory cytokines travel throughout the body causing oxidating stress to the fragile machinery of the tissues and mitochondria, specifically.  In the brain, inflammation serves to shunt the use of tryptophan toward production of anxiety-provoking chemicals like quinolinate, instead of toward serotonin and melatonin. They produce a replicable collection of symptoms called “sickness syndrome”, noted for it’s overlap with “depressive” symptoms: lethargy, sleep disturbance, decreased social activity, mobility, libido, learning, anorexia, and andhedonia. Psychiatric researchers have observed that patients with higher levels of inflammatory markers (like CRP) are less likely to respond to antidepressants, and more likely to respond to anti-inflammatories.

Where Do We Begin to Heal?

How is any of this good news? This approach to chronic illnesses like depression views it as a complex, non-specific symptom reflecting a state of bodily disharmony.  It isn’t that you were born with bad genes or low serotonin.  It is far more likely that you are experiencing an unhealthy inflammatory balance, driven by cortisol dysfunction, and stemming from a sick gut.  We can come at modifying your system from many angles, but here is a basic starter kit:

  • Exercise – Burst exercise is my primary recommendation.  It is the most bang for your buck in terms of cardiovascular benefit and specifically enhancing mitochondrial health because it puts a special kind of stress on the body when you move to your max for 30 seconds that then recover for 90.  I recommend 8 intervals 1-3x/week.
  • Meditation – The effects of stimulating the relaxation nervous system, even through listening to a 20 minute guided meditation, can be far-reaching.  Enhanced genomic expression of anti-inflammatory genes and suppression of inflammatory ones was demonstrated in this study.
  • Diet – I recommend a diet that controls for glycemic fluctuations through elimination of refines carbs and grains, and through high levels of natural fats to push the body to relearn how to use fats for fuel.  This is the brain’s preferred source.  I discuss some therapeutic foods here.
  • Strategic supplementation – Natural anti-inflammatories like polyunsaturated fats (evening primrose oil and fish oil), curcumin (the active component of turmeric), and probiotics to name a few, can help promote a synergy of beneficial effects from the above interventions.

In my practice, despite some suggestion that antidepressants may actually be having their effect through an anti-inflammatory mechanism, these medications have become obsolete.  An appreciation of the role of inflammation and immunity in driving hormonal imbalance which directly impacts mood, energy, and wellness, is at the core of personalizing the definition of “depression”. Don’t be lured into the simplicity of a one disease-one drug model.  There’s no room for you in that equation.

About the author. Dr. Brogan is an M.I.T/Cornell/Bellevue-trained psychiatrist specialized in holistic women’s health. She is a mother of two and has a busy practice in Manhattan. A passion for understanding the intersection between health, nutrition, and the environment are the bedrock of her wellness approach with patients and at home. Visit her site at: Kelly Brogan, MD, Holistic Women’s Health Psychiatry.

References

Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Miller et al Biol Psychiatry. 2009 May 1; 65(9): 732–741.

Cytokines and cognition – The case for a head to toe inflammatory paradigm. Wilson et al. JAGS 50:2041–2056, 2002.

A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70:31–41.