Could Mitochondrial Dysfunction Be Responsible for Your Chronic Fatigue, Pain, and Brain Fog? Part 1
YOU NEED TO SUPPORT YOUR MITOCHONDRIA!
We all want to have more energy, be pain free, and have a clear, sharp mind. Those living with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) or fibromyalgia (FM) know that mitochondrial dysfunction is one of the major reasons for their illnesses, but did you know that mitochondrial dysfunction underlies most chronic diseases? It’s now recognized as an important factor in ADD/ADHD, Autism Spectrum Disorder (ASD), Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, cancer, liver and kidney disease, and metabolic syndrome, and has even been implicated in immune system dysfunction and mood disorders.
This series will dive into the essentials you need to know about mitochondria’s role in your body. I’m going to help you to understand when it’s time for a “mitochondrial reboot” so you’re more likely to have a strong, healthy body and mind, functioning at peak performance. Or if you now suffer from a chronic fatiguing, musculoskeletal, cardiovascular, neuropsychiatric condition like CFS/ME, FM, mycotoxin illness, or Chronic Lyme Disease (CLD/PTLDS), you’ll see that supporting your mitochondrial function will help you live a healthier and more productive life. This is truly an exciting area of medical research.
MITOCHONDIAL BASICS
Mitochondria are the energy powerhouse inside all your cells (except red blood cells). They are responsible for making ATP, the fuel essential for all of your organs to function properly. If you remember Biology 101, you may recall that the Krebs cycle is the biochemical pathway that helps to make energy and ATP. My biology teacher taught us the acronym “On Cozy City Island Our Aunt Suzie Saw Funny Men” to help us remember the steps of the energy pathway and the Krebs cycle, as seen here:
Each mitochondrion has 4 main compartments: the outer membrane, the inner membrane, the matrix, and the intermembranous space. Any abnormal functioning in any of them will directly impact the mitochondria. The outer membrane contains the enzymes that help to transport fat into the matrix, where it can be converted into energy. The inner membrane contains the cristae, which are complex folds and tubules containing the enzymes responsible for making ATP. If you lose cristae, you lose your ability to produce ATP. The matrix is enclosed by the inner membrane and contains mitochondrial DNA and a number of important enzymes, such as ATP synthase, the enzyme that is responsible for the production of ATP.
What Causes Mitochondrial Damage?
Mitochondrial damage occurs naturally during ATP production, as free radicals are released. These free radicals cause oxidative stress when electrons are transferred from one molecule to the next. As each oxygen molecule is converted into water, an unpaired oxygen molecule is released as a free radical. This can be harmful to the mitochondria if produced in excess. Free radicals damage DNA, proteins, lipids, and DNA polymerase, the enzyme responsible for mitochondrial replication, leading to mitochondrial structural and functional damage. Although cellular DNA is protected against damaging free radicals by histones, mitochondrial DNA lacks this protective barrier. Since mitochondria are exquisitely sensitive to increased free radical/oxidative stress--part of normal cellular processes--multiple infections, toxins, or any inflammatory factors on the 16-point MSIDS map can potentially affect their performance. This might be one of the reasons you are chronically ill or not functioning at your best if you have addressed other medical problems but still are searching for answers.
DISEASES RELATED TO MITOCHONDRIAL DYSFUNCTION
Mitochondrial dysfunction is a great imitator; it can underlie a wide variety of symptoms. Apart from fatigue, there is a link between mitochondrial dysfunction and many other diseases. Mitochondria are particularly abundant in organs that need active and abundant sources of energy, such as the skeletal muscle, heart muscle, liver, kidneys, and brain.
Mitochondrial dysfunction in the heart can lead to various cardiac conditions, including conduction defects, cardiovascular disease, cardiomyopathy (an enlargement of the heart that leads to poor cardiac output and congestive heart failure), and atherosclerosis.
Mitochondrial dysfunction in skeletal muscles leads to weakness, low muscle tone, exercise intolerance, and myofascial pain.
Mitochondrial dysfunction in the liver can cause hypoglycemia, with low blood sugars secondary to defects in glucose production, nonalcoholic fatty liver failure (also known as non-alcoholic fatty liver disease (NAFLD), or Metabolic Associated Steato-hepatitis). NAFLD is a silent and potentially deadly medical condition in epidemic proportions worldwide, and it can potentially lead to cirrhosis of the liver and liver cancer. Read more here:
Mitochondrial dysfunction in the kidneys can cause proximal tubular dysfunction (Fanconi’s syndrome) as well as a loss of essential amino acids, electrolytes, and minerals such as magnesium.
Mitochondrial dysfunction in the brain sets the stage for a host of neurological diseases, including Huntington’s disease, Alzheimer’s disease, and Parkinson’s disease, as well as psychiatric disorders such as schizophrenia, bipolar, and anxiety disorders:
Mitochondrial dysfunction has also been linked to cancer, such as in hepatitis C–associated hepatocellular carcinoma:
Mitochondrial dysfunction can also manifest as various dysfunctions of the central and peripheral nervous system. For example, when the optic nerve and visual systems are affected, it can lead to optic neuritis and visual loss. This can be seen in acute and chronic Lyme disease and Bartonella, where free radical/oxidative stress affects the second cranial nerve. When the eighth cranial nerve, which sends signals from the inner ear to the brain, is affected, it can cause hearing loss. When the peripheral nerves are affected, you can experience neuropathic pain, chronic inflammatory demyelinating polyneuropathy, and problems with the autonomic nervous system. One such problem is postural orthostatic tachycardia syndrome (POTS), causing low blood pressure, chronic fatigue, palpitations, brain fog, and in severe cases fainting. Some with POTS also have absent or excessive sweating, and problems with temperature regulation:
POTS/dysautonomia is a common manifestation of chronic Lyme, Bartonella, mold toxicity, and Long Covid. Although the primary factor causing the autonomic dysfunction may initially be a bacterial infection, viral infection, or toxin (many times it’s all of the above), the final pathway leading to the neurological dysfunction is mitochondrial damage. That is why it is so important to address mitochondrial health during and after acute and chronic illness.
Can You Avoid Mitochondrial Damage?
The answer is no. Not when we are living through epidemics of infections like Lyme, Bartonella, Covid, and other viruses, with massive amounts of environmental toxins constantly getting into our bodies. These toxins not only damage the fragile mitochondrial cell membranes, but also adversely affect the health of the gut microbiome, further contributing to inflammation. The different diseases listed above are worsened with oxidative stress, after free radicals damage mitochondrial cell membranes. Since you can’t avoid environmental toxins, these can all increase oxidative stress leading to end stage mitochondrial damage, as discussed in these previous Substacks:
Mitochondrial Damage Underlies Many Neurological Conditions
The resulting increased free radicals from infections, toxins, microbiome abnormalities, leaky gut and mast cell activation, vitamin and mineral deficiencies, or sleep disorders (the 6 primary rivers of inflammation) adversely affect many neurological conditions. In Alzheimer’s disease, for example, amyloid plaques and intraneuronal neurofibrillary tangles are affected by free radicals. To make matters worse, once the amyloid plaques have formed and start to accumulate, they can further increase oxidative stress, leading to a vicious downward cycle.
Patients with Alzheimer’s disease (AD) are known to have increased levels of oxidative stress, reflected by the increased levels of iron and copper in the brain, as well as an increase in lipid, protein, and DNA oxidation. That adversely affects the mitochondria in AD neurons, so cell communication starts to fail. Part of the neurological damage also comes from sugar molecules binding to proteins and lipids, creating advanced glycation end products (AGEs), which damage cells. AGEs are molecules formed when proteins or fats combine with sugars in the bloodstream, in a process called glycation. AGEs then accumulate in the body over time, and their formation is accelerated by high blood sugar levels, as seen in diabetes. But AGEs also increase with insulin spikes when you eat too many simple sugars--which is why avoiding simple carbohydrates is so important for your long-term health! AGEs bind to specific receptors in the body called RAGEs (Receptors for Advanced Glycation End Products), triggering inflammatory and oxidative stress pathways. That is one of the reasons why diabetes and insulin resistance (also associated with NAFLD) are known risk factors for AD.
The same situation exists for Parkinson’s disease, where there is oxidative damage to an area of the brain known as the substantia nigra, which produces the neurotransmitter dopamine. Without enough dopamine, Parkinsonian tremors and difficulties with initiating movements appear. Markers of oxidative stress have been well documented in Parkinson’s patients. Researchers have found that their mitochondria are much less efficient at generating ATP. Research is now looking into mitochondrial regeneration in AD and PD, and we are seeing some encouraging results.
How Does Oxidative Stress Increase Inflammation?
Oxidative stress has been implicated in a wide variety of central nervous system disorders, including Lyme disease and MSIDS. Free radicals are produced in Lyme disease patients infected with Borrelia burgdorferi, and these not only damage mitochondrial cell membranes, but also activate microglia in the brain, the cells that act as the main form of active immune defense in the central nervous system. This stimulates the production of proinflammatory cytokines, such as IL-1, IL-6, and TNF-α, which cause symptoms of fatigue, muscle and joint pain, neuropathy, headaches, mood disorders, and cognitive difficulties. There is a switch inside a nucleus called NF Kappa B. When free radicals are present, they turn on this switch, and subsequently increase inflammation, with one of the downstream effects being mitochondrial damage.
I frequently see many of the signs and symptoms of mitochondrial dysfunction in my Lyme/MSIDS patients. Many experience episodes of optic neuritis and visual and hearing loss, neuropathy (present in up to 70 percent of persistent Lyme disease patients), and CIDP (chronic inflammatory demyelinating polyneuropathy), as well as POTS and autonomic nervous system dysfunction. Neuropathy is common in all of these diseases, ones in which there is a loss of myelin sheathing that protects nerve fibers. This may be the result of multiple infections, immune damage, environmental toxins, or problems with proper detoxification, all of which can produce free radicals and damage fragile mitochondrial membranes.
Coming up next, much, much more about mitochondrial dysfunction and lifestyle interventions to improve mitochondrial health. Stay tuned!