Chronic Fatigue: Why You're So Tired, and What to Do About It
- The Bioregulatory Medicine Institute
- 2 days ago
- 9 min read
Join Dr. James Odell for Season 2 of the Science of Self-Healing Podcast! He's the medical and executive director for BRMI, as well as a practicing naturopathic doctor for over 35 years, and he's here to share with you his extensive knowledge of medicine from a different perspective.
Fatigue isn’t just a side effect of modern life—it can be a sign of something far deeper. In this episode, Dr. Odell uncovers the complex world of Chronic Fatigue Syndrome (ME/CFS) and its surprising link to the powerhouses of our cells: the mitochondria. You’ll discover how mitochondrial dysfunction may lie at the heart of the brain fog, muscle pain, and post-exertional crashes that define this debilitating condition.
We explore the latest science behind energy production, how viruses and inflammation disrupt mitochondrial function, and why fatigue often lingers long after an illness. More importantly, we offer practical, evidence-based strategies for supporting your mitochondrial health—from targeted nutrients and antioxidants to lifestyle therapies and cutting-edge emerging treatments.
Whether you live with chronic fatigue or are just curious about how your body makes—and loses—energy, this episode will transform the way you think about fatigue and healing.
Transcript for: Chronic Fatigue: Why You're So Tired, and What to Do About It
Hello and welcome to the Science of Self-Healing podcast, produced by the Bioregulatory Medicine Institute (BRMI). We provide unique insights into how you can naturally support your body’s ability to regulate, adapt, regenerate, and self-heal. I’m Dr. James Odell, your host and BRMI’s medical and executive director, with over 35 years as a naturopathic doctor. Please remember, this podcast is for informational purposes only and not a substitute for personalized care from a qualified health professional.
Before we begin, I’d like to invite you to our upcoming conference and retreat aboard Celebrity Cruise’s ship Beyond. We’ll depart from Miami for a 7-night Caribbean cruise, visiting St. Kitts, St. Thomas, and the Dominican Republic. We’ve reserved Aqua Class Staterooms with exclusive amenities, starting at $2,284.50 per person (double occupancy), plus $295 for the conference with promo code BEYOND. Our conference, held on sea days, features a range of engaging talks AND is open to practitioners and anyone interested in health. Space is limited—visit https://www.brmi.online/vitalityandbeyond for details and registration. We hope to see you aboard!
Fatigue is a universal human experience, often brushed off as the cost of modern life. However, for millions of individuals across the globe, fatigue goes far beyond mere tiredness—it becomes a chronic, debilitating condition that profoundly disrupts daily living. Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME/CFS), affects an estimated 17–24 million people worldwide and remains one of the most misunderstood and under-researched conditions in medicine.
A growing body of scientific evidence suggests that a key player in the manifestation of chronic fatigue is mitochondrial dysfunction. Mitochondria—often referred to as the powerhouses of the cell—are responsible for producing the energy necessary for almost all physiological processes. When these tiny organelles falter, the body's energy systems crash, contributing to the persistent fatigue, brain fog, and physical malaise experienced by those with ME/CFS.
This podcast provides an in-depth exploration of the relationship between chronic fatigue and mitochondrial health. It delves into the science behind mitochondrial function, examines the underlying causes of mitochondrial dysfunction in chronic fatigue, and offers actionable strategies for supporting mitochondrial health through nutrition, lifestyle interventions, and emerging therapies. We'll also touch on how mitochondrial dysfunction manifests in related disorders and the implications for long-term disease prevention and management.
Understanding Chronic Fatigue Syndrome (CFS/ME)
ME/CFS is a complex, multi-system disorder that affects the nervous, immune, and endocrine systems. The hallmark symptom is profound, unexplained fatigue that lasts for more than six months and is not alleviated by rest. Other core symptoms include:
Post-exertional malaise (PEM): A worsening of symptoms following physical or mental activity
Unrefreshing sleep
Cognitive impairment (“brain fog”)
Orthostatic intolerance (difficulty standing upright)
Muscle and joint pain
Headaches
Sensitivity to light, sound, and temperature
Diagnosis is primarily clinical, based on patient history and symptom criteria, as there are currently no definitive lab tests for ME/CFS. The Institute of Medicine (now the National Academy of Medicine) proposed the term "Systemic Exertion Intolerance Disease" (SEID) in 2015 to better reflect the biological and debilitating nature of the condition.
While the precise cause remains elusive, numerous hypotheses have been proposed, including viral infections, immune system abnormalities, neuroinflammation, and—as this podcast emphasizes—mitochondrial dysfunction.
Additionally, ME/CFS often overlaps with other syndromes such as fibromyalgia, postural orthostatic tachycardia syndrome (POTS), and multiple chemical sensitivity (MCS), suggesting shared pathological mechanisms including autonomic dysfunction, inflammation, and impaired cellular energy metabolism.
Mitochondria: The Cellular Engines of Life
Mitochondria are dynamic, double-membraned organelles found in nearly every human cell. They play a vital role in generating adenosine triphosphate (ATP), the primary molecule that stores and transfers energy within cells. This energy powers everything from heartbeats to hormone production to mental focus.
Beyond energy production, mitochondria are involved in other critical functions, including:
Calcium signaling
Regulation of cell death (apoptosis)
Reactive oxygen species (ROS) management
Steroid synthesis
Cell signaling and differentiation
Innate immunity and inflammation modulation
The energy-generation process—known as oxidative phosphorylation—takes place within the inner mitochondrial membrane. Nutrients such as glucose and fatty acids are converted into ATP through a complex series of biochemical reactions, including the citric acid cycle and electron transport chain.
Any disruption in this tightly regulated system can lead to energy deficits, accumulation of metabolic waste, and cellular stress—all of which are implicated in chronic fatigue.
Mitochondrial Dysfunction in ME/CFS
Multiple studies have identified mitochondrial abnormalities in individuals with ME/CFS. These include:
Reduced ATP production: Patients often exhibit lower levels of ATP synthesis, particularly in response to exertion.
Altered mitochondrial morphology: Structural changes in mitochondria, such as swelling or fragmentation, can impair their function.
Impaired oxidative phosphorylation: Dysregulation of the electron transport chain reduces energy efficiency.
Increased oxidative stress: Excessive production of ROS damages mitochondrial membranes and DNA.
Abnormal lactate levels: Accumulation of lactic acid in tissues, even with minimal exertion, indicates a shift toward anaerobic metabolism.
Decreased mitochondrial DNA (mtDNA) copy number: This may be associated with impaired mitochondrial replication and repair.
This mitochondrial dysfunction likely contributes to the core symptoms of ME/CFS, including fatigue, muscle pain, and post-exertional malaise. Some researchers propose that the body may down-regulate energy production as a protective mechanism in response to infection or stress, akin to a state of "cellular hibernation."
Potential Causes of Mitochondrial Impairment in Chronic Fatigue
Understanding the root causes of mitochondrial dysfunction in ME/CFS can guide more effective treatment strategies. Several factors have been implicated:
1. Viral and Bacterial Infections
Many patients report a viral illness—such as Epstein-Barr virus, cytomegalovirus, or SARS-CoV-2—as the trigger for their fatigue. Pathogens can directly damage mitochondria or alter immune responses that disrupt mitochondrial activity.
2. Immune Dysregulation
Chronic immune activation and inflammation can interfere with mitochondrial signaling and ATP production. Elevated cytokines such as TNF-alpha and interleukin-6 are commonly found in ME/CFS patients.
3. Oxidative and Nitrosative Stress
An imbalance between ROS and antioxidants leads to mitochondrial damage. In ME/CFS, oxidative stress is both a cause and consequence of energy dysregulation. Chronic inflammation exacerbates this oxidative burden.
4. Nutrient Deficiencies
Mitochondria require a host of vitamins, minerals, and amino acids to function optimally. Deficiencies in magnesium, B vitamins, coenzyme Q10, carnitine, zinc, selenium, and other cofactors can impair energy metabolism.
5. Environmental Toxins
Exposure to pesticides, heavy metals, and mold toxins has been linked to mitochondrial dysfunction. These toxins can inhibit mitochondrial enzymes and damage cellular membranes. Chronic exposure may also alter epigenetic regulation of mitochondrial genes.
6. Genetic and Epigenetic Factors
Mitochondrial DNA mutations or polymorphisms in nuclear genes involved in energy metabolism may predispose certain individuals to fatigue syndromes. Epigenetic changes due to stress or environmental influences may silence key mitochondrial genes.
Strategies for Supporting Mitochondrial Function
Although mitochondrial dysfunction in ME/CFS is complex, a multi-pronged therapeutic approach may help restore function and improve symptoms. These strategies include:
1. Targeted Nutritional Support
Coenzyme Q10 (Ubiquinone/Ubiquinol): Supports the electron transport chain and acts as an antioxidant. Doses of 100–300 mg/day may improve fatigue.
L-Carnitine: Facilitates the transport of fatty acids into mitochondria. Acetyl-L-carnitine may cross the blood-brain barrier and benefit cognitive fatigue.
Magnesium: Essential for ATP production. Magnesium malate or glycinate are preferred for better absorption and gastrointestinal tolerance.
B Vitamins: B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), and B12 (methylcobalamin) are crucial for mitochondrial enzyme function.
Alpha-Lipoic Acid (ALA): Regenerates other antioxidants and enhances glucose metabolism.
NAD+ Precursors: Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) help boost cellular NAD+ levels, supporting mitochondrial function.
Creatine Monohydrate: May help buffer ATP and provide short bursts of cellular energy.
2. Antioxidant Therapy
Glutathione: Intravenous or liposomal glutathione may reduce oxidative stress and improve mitochondrial resilience.
N-acetyl cysteine (NAC): A precursor to glutathione with direct antioxidant effects.
PQQ (Pyrroloquinoline quinone): Stimulates mitochondrial biogenesis and protects existing mitochondria from oxidative damage.
Resveratrol and Curcumin: Polyphenols that modulate inflammation and support mitochondrial pathways.
MitoQ: A mitochondria-targeted antioxidant that may improve energy output and reduce oxidative stress.
3. Lifestyle Interventions
Pacing: Managing activity levels to stay within the “energy envelope” is essential to avoid post-exertional malaise. Tools such as heart rate monitoring can help avoid energy crashes.
Sleep Optimization: Maintaining consistent sleep-wake cycles and minimizing disruptions enhances mitochondrial repair.
Stress Management: Chronic stress impairs mitochondrial efficiency. Techniques like meditation, gentle yoga, and biofeedback can be restorative.
Mild Movement: When tolerated, light physical activity (stretching, tai chi) can stimulate mitochondrial biogenesis.
Clean Environment: Reducing exposure to environmental toxins and allergens supports detoxification and mitochondrial recovery.
4. Emerging Therapies
Elamipretide (SS-31): A mitochondrial-targeting peptide under investigation for its ability to improve energy production and reduce fatigue.
Hyperbaric Oxygen Therapy (HBOT): May enhance mitochondrial oxygenation and energy metabolism.
Red/Near-Infrared Light Therapy (Photobiomodulation): Supports mitochondrial function by stimulating cytochrome c oxidase.
Peptide Therapies: Experimental treatments targeting mitochondrial biogenesis and immune modulation are being explored.
Exosome Therapy: Investigated for its role in cellular repair and mitochondrial signaling.
Integrative and Functional Medicine Approaches
Functional medicine practitioners often take a systems-biology approach to ME/CFS, seeking to identify and correct underlying imbalances. This may involve comprehensive lab testing for:
Nutrient levels
Mitochondrial markers (e.g., organic acid tests)
Hormonal imbalances
Toxic exposures
Inflammatory cytokines
Gut microbiome composition
Mitochondrial DNA integrity and function
Customized protocols often include dietary changes (e.g., anti-inflammatory or ketogenic diets), detoxification strategies, adaptogenic herbs, and mitochondrial-targeted supplements. Many patients also benefit from working with practitioners who understand the nuances of post-viral fatigue, environmental sensitivities, and neuroimmune dysfunction.
Conclusion: A Path Toward Healing
Chronic Fatigue Syndrome is a devastating condition that demands greater understanding, research, and compassionate care. Mitochondrial dysfunction provides a unifying framework to understand the energy deficits at the core of ME/CFS. By supporting mitochondrial health through nutrition, lifestyle interventions, and emerging therapeutics, many individuals may find meaningful relief and a renewed sense of vitality.
While recovery can be slow and nonlinear, advancements in mitochondrial medicine offer hope. The future may hold more precise diagnostics and individualized treatments that address fatigue not as a vague complaint, but as a biologically rooted imbalance—one that can be understood, addressed, and ultimately healed. With continued research and advocacy, the silence surrounding chronic fatigue may give way to clarity, compassion, and comprehensive care.
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This article is for informational purposes only and is not intended to be a substitute for the direct care of a qualified health practitioner who oversees and provides unique and individualized care. The information provided here is to broaden our different perspectives and should not be construed as medical advice, diagnosis, or treatment.
