Information

Can mitochondria become cancerous?


Given that mitochondria have their own DNA and can replicate independently, can they ever become cancerous? For example, could a mutation in their DNA cause them to rapidly replicate, ultimately killing the cell it's in?


Interesting question.

As a prelude, I should probably mention that single celled organisms cannot get cancer as we understand and define it. Mitochondria are not, of course, single celled organisms, they are organelles, but this interesting question involves treating them as if they were autonomous. We'll come back to that later. First, single-celled organisms and cancer…

Of all the hallmarks of cancer, unregulated replication is probably the most fundamental, but all the same, cancer is necessarily a disease of multicellular organisms with differentiated tissues. Bacteria do not get cancer. Protozoa do not get cancer. Yeast do not get cancer. I'm spending too much space on my prelude here, but let's pretend like this isn't an issue and just address unregulated replication. Incidentally, the review I linked is an updated version of the classic review of cancer biology. If you're interested in cancer biology, I highly recommend reading it, and perhaps the original 2000 review.

Ok, now to the question. Let's put aside the problem of a single organelle or single celled organism getting cancer, and consider whether mitochondria can develop mutations in their DNA that cause them to replicate in an unregulated fashion.

Yes, mitochondria do have their own DNA, but they are not fully autonomous. They do "replicate independently", but what is meant by this is that mitochondria replication (via fission) is a process that occurs independent from the replication (via mitosis) of its enclosing cell. The process is regulated by proteins encoded in the nuclear genome (not the mitochondrial genome)

Both fission and fusion are regulated by dynamin related proteins, which you can read about in this, fairly dense review. The mitochondrial genome encodes very few genes, 14 at last count, and while problems with those genes and proteins are implicated in a few diseases, uncontrolled replication is not one of them.


The Mitochondria: Key to Health and Longevity

ARTICLE SUMMARY
• Mitochondria generate 90 percent of the body’s energy, powering the cells to perform vital functions.
• Mitochondria burn two main fuels: glucose and ketones. Because the standard American diet has given rise to a widespread sugar addiction, most people tend to burn glucose.
• When the mitochondria are healthy, a person is generally healthy.
• Mitochondrial deficiency can give rise to symptoms in virtually any organ or tissue.
• Many factors—chemicals, foods, modern lifestyle habits and electromagnetic fields—have been implicated as causes of mitochondrial dysfunction.
• In cancer, the mitochondria change first—before any gene coding changes—which undermines the “gene theory” premise of conventional cancer explanations.
• Dysfunctional mitochondria can trigger a series of cellular processes that result in insulin resistance (diabetes).
• Feeding and nourishing mitochondria with wholesome ketones—which do not require insulin—can help restore mitochondrial health and relieve brain starvation in individuals with cognitive impairment.
• AMPK is an enzyme responsible for multiple metabolic functions. AMPK and mitochondrial imbalances can initiate a cascade of inflammatory changes related to disorders such as obesity and diabetes.
• As key elements for cellular energy production, AMPK and mitochondria require nutrient and lifestyle changes when imbalanced.
• Supporting mitochondrial health can help control the aging process as well improve overall health.

For most of my professional life as an alternative family physician, I’ve understood that the frontier in medicine and health is a place where diseases without cures remain unsolved mysteries—awaiting the breakthroughs of discovery, connection, coincidence and evidence that will unravel and explain them. It is impossible to overstate the importance of unraveling these mysteries. Unfortunately, most family doctors and internists are unlikely to recognize or have prior knowledge about these troubling conditions and thus cannot guide their patients to proper medical treatment.

Sir Arthur Conan Doyle’s creation of one of the best-known fictional detectives, the iconic Sherlock Holmes, introduced a logical method for solving mysteries: “Once you eliminate the impossible, whatever remains, however improbable, must be the truth.” Ten years ago, I heard about a strange health condition—mitochondrial dysfunction—with documented links to other conditions such as autism and attention-deficit/hyperactivity disorder (ADHD), which may result from severe and damaging changes within the cells. Inspired by Doyle to retain my suspicions, my story begins with whatever remains, however improbable. Applying an understanding of mitochondria, I suspected the origins of and pursued the missing but probable explanation for this widespread health and medical problem.

WHAT ARE MITOCHONDRIA?
A brief course in cell biology is crucial to understanding the breakdown that leads to illness. Just as the body has vital organs—such as the heart, stomach and liver—the cell has similar critically functioning components. In the cell, these parts are called “organelles” and include the nucleus, Golgi complex, centrioles and mitochondria. Not confined to humans, mitochondria exist in all forms of life. Having unique DNA similar to the DNA of bacteria, mitochondria are actually a kind of parasite that lives in all organisms. By scientific estimate, eight to two thousand mitochondrial hitchhikers live in every cell of the human body.

The essential role of the mitochondria is to produce energy. Mitochondria generate 90 percent of the body’s energy and power the cells to perform vital functions that include breathing, thinking, talking and walking. How does this work? Inside the mitochondria, carbohydrates, fats and proteins are metabolized by utilizing oxygen to produce energy, which converts ADP (adenosine diphosphate) to the energy-packed ATP (adenosine triphosphate). Called the Krebs’s cycle, this process is a marvel of cellular biology, producing thirty-eight ATPs per molecule of glucose burned.

When the mitochondria are healthy, a person is generally fit and healthy. Moreover, under the influence of a positive cascade of effects, the more mitochondria that individuals have, the healthier they are, which increases their ability to create energy. Children brimming with energy, for instance, are loaded with mitochondria, whereas the less energetic elderly have fewer mitochondria at the cellular level. 1 Recognizing that the mitochondria are essential to human health also leads to another conclusion, namely that health and disease processes are interrelated. According to a researcher writing in the Journal of Inherited Metabolic Disease, mitochondrial deficiency “can theoretically give rise to any symptom, in any organ or tissue, at any age, and with any mode of inheritance.” 2

MITOCHONDRIA IN THE NEWS
Since the discovery of genes in 1954, a “gene theory” has become the most likely explanation for cancer, with researchers positing that humans develop cancer as a result of genetic changes in the cell. According to this theory, when the immune system does not identify or destroy a deformed cell, the altered cell continues to multiply, becoming a tumor, and the person eventually is diagnosed with cancer.

In 2003, the Human Genome Project completed its mapping of the entire human gene sequence, a thirteen-year undertaking that required the collaboration of twenty universities in seven countries. Scientists are now working on a new project—mapping the cancer genome to discover treatments—a task one thousand times greater than the original mapping of the human genome.

These dedicated cancer researchers have produced two remarkable discoveries. First, the genetic pattern of cancer is verifiably random. Second, the genetic changes often occur after the onset of cancer, indicating that some cellular changes are occurring well before genes are ever affected. As scientists were investigating both plausible and “improbable” explanations, I asked myself: what is changing that disables the body’s immune system? After critical inquiry and researching scientific sources, I reached the conclusion that the most likely, science-based explanation is that the mitochondria are changing and become impaired.

MITOCHONDRIAL DYSFUNCTION AND CANCER
Scientists point to mitochondrial dysfunction as the genesis of a number of diseases, including cancer. Mitochondrial changes and their relationship to cancer have been proven in a simple experiment. When scientists transfer the nucleus of a cell with cancer genes into a normal cell, the genes revert to normal genes—the cell does not become cancerous. However, when scientists do the reverse, transferring the nucleus of a normal cell to a cancer cell, the cell remains cancerous, suggesting that genes are not driving the cancer. Those engaged in this work have concluded that the driver of cancer is not genetic but dysfunctional mitochondria in cells.

Since food is consumed by mitochondria in the metabolic process, diet is an additional factor involved in mitochondrial dysfunction. Researchers have rediscovered the 1923 conclusions of scientist-physician Otto Warburg, who observed that cancer was caused by a metabolic change—a discovery for which he received a Nobel Prize in 1931. Warburg described how cancer cells stop using oxygen to make energy and shift to non-oxygenated, inefficient metabolism that uses fermentation to produce energy.

Fermentation metabolism causes mitochondria to produce only two ATPs per glucose molecule metabolized, while also forming acidic byproducts. The cell nucleus then changes the gene code to support this impaired metabolism. The fact that the mitochondria change first—before any gene coding changes—undermines the “gene theory” premise of conventional cancer explanations. Most doctors are unaware that the build-up of lactic acid is a result of the cancer, not the originating cause, and so they try to de-acidify the cancer patient’s body by recommending that patients eat an alkaline diet.

MITOCHONDRIAL DYSFUNCTION, DIABETES AND OBESITY
Overconsumption of fructose, the sweetest of the sugars principally found in fruits, is a commonly known cause of diabetes. Whereas table sugar (sucrose) is half glucose and half fructose, high-fructose corn syrup is commonly formulated as 42 percent glucose and 58 percent fructose. Because fructose is a unique sugar metabolized only by the mitochondria in the liver, the culprit that causes diabetes is uric acid, which (as already discussed) is a metabolite of fructose. Though uric acid is a strong antioxidant outside the cell, inside the cell it has the opposite action, producing ROS. In the presence of uric acid, the mitochondria, which should be making the energy-packed ATP, instead produce the energy-depleted ADP.

Once dysfunctional mitochondria stop metabolizing food—and especially thermal-producing fats—the fats accumulate inside the cell and its membrane. The result is twofold: tissues become fat (i.e., fatty liver disease) and fat-laden cell membranes lose permeability, preventing water-soluble sugar from entering the cell. Insulin, which ordinarily allows sugar to enter cells, fails because the accumulated fat prevents sugar’s passage. This condition is called insulin resistance or diabetes. Simultaneously, the liver (fatty liver disease) and body (obesity) begin to store fat. Establishing the etiology of these conditions, a seminal 2013 article in Diabetes stated, “An elevated serum uric acid is. . . one of the best independent predictors of diabetes and commonly precedes the development of both insulin resistance and diabetes. An elevated uric acid also independently predicts the development of fatty liver, obesity, [and] hypertension.”. 9 Other researchers have noted that “[f]ewer and smaller-sized mitochondria are found in skeletal muscle of insulin-resistant, obese, or T2DM [type 2 diabetes mellitus] subjects.” 10

People who remain thin while eating vast quantities of food often baffle observers. “How can they eat all that food and be so skinny?” A common explanation for what appears to be inexplicable is “high metabolism.” However, scientific understanding of the importance of healthy mitochondria offers a more plausible explanation: overweight people who eat one meal a day but continue to gain weight likely have fewer healthy mitochondria, following injury of the mitochondria by some combination of the factors described earlier. People who remain thin even though they eat a lot likely have high amounts of healthy mitochondria.

MITOCHONDRIAL DYSFUNCTION AND NEUROLOGICAL DISORDERS
Alzheimer’s disease, branded as type 3 diabetes (insulin resistance) by many medical experts, is a condition whereby the “diabetic brain” cannot use sugar and therefore is starved. Magnetic resonance imaging (MRI) of Alzheimer’s patients displays brain shrinkage, an indicator of starvation. Increasingly it has become apparent that feeding and nourishing mitochondria with wholesome ketones—which do not require insulin—can help restore mitochondrial health and relieve brain starvation. Substantiating the potential for some level of recovery, patients with mild cognitive impairment who were fed ketones in the form of medium-chain triglycerides (MCTs)—such as those present in coconut oil—have experienced improvement in brain symptoms. 11

Overuse and misuse of antibiotics in childhood also damages mitochondria, which can arrest children’s physical and mental development. Antibiotics are a likely contributor to the neurodevelopmental disorders such as autism and ADHD that are plaguing today’s children. 12

FEEDING THE MITOCHONDRIA
For mitochondrial and overall health, individuals must select and eat the highest-quality foods possible—allowing food to be the “medicine” it was meant to be—instead of consuming a diet of denatured processed foods and synthetic vitamins, which insufficiently supports health. The best dietary choices are organic, non-GMO, pasture-raised, grass-fed, traditional foods that are not overprepared, packaged, processed or preserved with additives, colors or chemicals that degrade overall food quality.

Unfortunately, health-conscious individuals often virtuously cite the “grocery list” of high-quality foods that they buy without realizing that they may be failing to prepare these foods properly. Most modern people lack their ancestors’ traditional knowledge and dietary literacy about health-promoting methods of food preparation.

The best place to start and continue on a path to high-quality, properly prepared food is by following the research and accumulated wisdom of the dentist Weston A. Price, a former director of the American Dental Association’s Research Institute. On his scientific travels worldwide, Dr. Price studied the diets of traditional people on five continents. He then assembled the accumulated wisdom of humanity on traditional diets in his seminal treatise, Nutrition and Physical Degeneration, which represents essential reading for anyone concerned with food and health. The Weston A. Price Foundation is a leading advocate for the return to nutrient-dense diets and covers Dr. Price’s findings in its materials and on its website. Nourishing Traditions by Sally Fallon Morell provides comprehensive instruction on proper food preparation techniques.

Mitochondria burn two main fuels: glucose (sugar) and ketones (a normal, carbon-based metabolic product). Because the standard American diet (SAD) supplied by modern food producers has given rise to a widespread sugar addiction, most people tend to burn glucose. Glucose can be considered a “dirty fuel” because its metabolism produces ROS. It is also highly addictive its removal from the diet can lead to common withdrawal symptoms such as headaches, nausea, malaise and lightheadedness. After becoming more informed about diet and nutrition, replacing a sugar-based diet with a diet based on healthy fats is, therefore, essential. Ketones—made from fat—are the preferred mitochondrial fuel because they are clean-burning, healthy and produce less ROS.

THE ROLE OF AMPK
AMPK (adenosine monophosphate-activated protein kinase) is an enzyme responsible for multiple metabolic functions. High levels of AMPK are found in the liver and brain as well as skeletal muscle. In a complex process, AMPK helps control metabolism by detecting and comparing the quantities of both ADP and ATP. If it senses that low-energy ADP is more abundant than high-energy ATP, AMPK becomes activated. Once activated, AMPK performs a variety of essential metabolic functions:

• It increases the levels of energy-charged ATP
• Changes fat metabolism by lowering triglycerides and raising HDL cholesterol levels, which decreases hard-to-lose visceral fat
• Decreases chronic inflammation
• Initiates autophagy (the purging of cellular trash) and mitophagy (the removal of dysfunctional mitochondria), both of which clean up cellular debris to increase lifespan
• Maintains cellular polarity needed to confirm tissue identity
• Promotes the formation of new mitochondria (mitochondrial biogenesis).

AMPK is not available in foods nor as a supplement but is activated by several herbal plants, some nutrients, lifestyle influences and some prescription medications. Researchers at Spain’s University of Seville also have described how excessive quantities of food can deactivate AMPK and increase oxidative stress, exposing mitochondria to DNA damage. 13 These imbalances in AMPK and mitochondrial function can initiate a cascade of inflammatory changes related to metabolic disorders such as obesity and diabetes that are at pandemic levels. As key elements for cellular energy production, AMPK and mitochondria require nutrient and lifestyle changes when imbalanced to activate AMPK as well as treat and remedy metabolic disorders. 13

One researcher summarizes how AMPK’s activation of mitochondrial function helps offset diseases and improves overall health as follows:

Indeed, current evidence indicates that AMPK activators may reduce risk for atherosclerosis, heart attack, and stroke help to prevent ventricular hypertrophy and manage congestive failure ameliorate metabolic syndrome reduce risk for type 2 diabetes and aid glycemic control in diabetics reduce risk for weight gain decrease risk for a number of common cancers while improving prognosis in cancer therapy decrease risk for dementia and possibly other neurodegenerative disorders help to preserve the proper structure of bone and cartilage and possibly aid in the prevention and control of autoimmunity. 14

FURTHER MITOCHONDRIAL CARE
The proper feeding of mitochondria is the most important change to facilitate better health. Lifestyle changes such as intermittent fasting and exercise are also fundamental to wellness. Fasting, or more appropriately, intermittent fasting—a salutary habit of eating only during a six- to ten-hour period each day—increases and resets the mitochondria, changing them from sugar consumers to ketone consumers. During a fast, the body metabolizes body fat until food is available. Some fat is converted to ketones, a preferred fuel, thereby boosting and activating the mitochondria for fat digestion.

Exercise is the second mitochondrial builder. Because exercise requires energy, the mitochondria multiply to supply the extra energy. One researcher explains, “Endurance exercise training increases mitochondria size, number, and oxidative activity.” 10 Exercise can explain weight loss through this ability to increase the number of healthy mitochondria. Additional healthy mitochondria not only increase metabolism but also burn more fuel.

HEALTHY AGING
Current scientific research verifies the premise that both declining numbers and dysfunction of mitochondria translate into aging. As a physician-researcher, Dr. Graveline confirms with evidence and personal experience in The Dark Side of Statins that a debilitating aging process results from mitochondrial damage: “The mitochondrial theory of aging proposes that aging, and the development of age-related degenerative diseases, are primarily the result of accumulated oxidative damage to mitochondrial membranes and DNA, over time.” 15

Thus supporting mitochondrial health can help control the aging process as well as improve overall health. 16 Summarizing the current scientific and medical research, which individuals must consider as fundamental health care knowledge, researchers at the National Institutes of Health have acknowledged that “mitochondria appear to play a central role in regulating cellular life span.” 17 Stated another way, cellular longevity enhances human longevity.

Understanding how mitochondrial health relates to overall health equips people to make choices that support wellness, help control body weight and manage the effects of aging—major aspects of happiness and a long life. From these observations about the mitochondria, one can also derive a general principle of cancer prevention: if something is known to cause cancer, it also damages mitochondria, and measures that prevent cancer will likely protect, heal and multiply the number of mitochondria. This knowledge puts the keys to health in each individual’s hands.

LIKELY CONTRIBUTORS OF MITOCHONDRIAL DYSFUNCTION
Many factors—chemicals, foods, modern lifestyle habits and electromagnetic fields—have been implicated as causes of mitochondrial dysfunction. Included in this list are antibiotics, fructose, glyphosate, cell phones and statin drugs, as well as other drugs, chemicals, foods and additives.
ANTIBIOTICS: Many types of radicals are formed in biological systems, but the most worrisome, derived from oxygen, are referred to as reactive oxygen species (ROS) or oxygen free radicals. Dousing mitochondria with antibiotics causes the formation of ROS—a relationship confirmed by scientists writing in 2013 in Science Translational Medicine, who observed that “clinically relevant doses of bactericidal antibiotics. . . cause mitochondrial dysfunction and ROS overproduction in mammalian cells.” 3 This is because mitochondrial DNA is similar to the DNA of bacteria, so antibiotics that kill bacteria also harm mitochondria.
FRUCTOSE: An abundance of fructose in the diet, and especially high-fructose corn syrup, overloads mitochondria and halts metabolism. Fructose is then changed to triglycerides, which are the precursor to body fat and eventual obesity. A paper in the Journal of Nutrition and Metabolism explains that uric acid, a “byproduct of uncontrolled fructose metabolism,” increases rapidly following fructose ingestion. In turn, “[u]ncontrolled fructose metabolism leads to postprandial [after eating] hypertriglyceridemia [increased fats in blood], which increases visceral adipose deposition [obesity].” 4 In addition, UCLA researchers have described how pancreatic cancer cells readily use fructose to divide and multiply. 5
GLYPHOSATE: In 2015, the World Health Organization (WHO) ranked glyphosate as a Class 2A probable carcinogen. Glyphosate originally was patented as an antibiotic and is known to eradicate beneficial, probiotic gut bacteria. 6 Again, because the DNA of mitochondria and bacteria are similar, substances like glyphosate that eliminate bacteria may also harm mitochondria.
CELL PHONES: In 2011, the WHO ranked cell phones as a Class 2B possible carcinogen. Studies confirm that changes occur in mitochondrial DNA with exposure to electromagnetic energy transmitted by cell phones. Because Wi-Fi uses the same digital, pulsed signals, it is also implicated in mitochondrial damage. According to researchers at the Centre of Excellence in Biotechnology and Development in New South Wales, Australia, radiofrequency electromagnetic radiation (RF-EMR) “in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation.” 7
STATIN DRUGS: Duane Graveline, MD, is a retired family physician and former U.S. Air Force flight surgeon. Graveline discusses the effects of cholesterol-lowering statin medications on mitochondria on a webpage titled “PQQ and statin damage.” He says, “Those. . . following my research over the years will know that I consider mitochondrial DNA damage as the ultimate result for many people. . . taking statins.” 8

BENEFICIAL FOODS AND SUPPLEMENTS
It is life-enhancing to choose foods and supplements wisely—the more natural the nutrients, the more that the mitochondria respond in beneficial ways. Although mitochondrial supplements are still “a work in progress,” they represent a growth market for “customers looking for an energy boost and an anti-aging solution.” 18 The list below summarizes foods and supplements beneficial to mitochondrial health.
HEALTHY FATS: Replacing the lowfat/vegetable oil directive that has held sway for forty years, scientific studies as well as current nutritional understanding confirm the dietary wisdom that the healthiest fats are butter saturated animal fats (such as lard, tallow, chicken schmaltz and duck fat) tropical oils (such as coconut, palm kernel and palm oils) and tree nut fats (such as macadamia). These healthy fats are the foremost recommendation for dietary sources of ketones. Dr. Thomas Seyfried, Yale University and Boston College researcher, argues in Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer in favor of treating cancer nutritionally with saturated fats because they convert to ketones more readily than polyunsaturated oils. 19
MCT OIL: “With a couple of exceptions,” state researchers in the Annals of the New York Academy of Sciences, “there is normally no opportunity to consume medium-chain fatty acids from the diet.”. 20 Coconut oil and palm kernel oil are the two exceptions. Coconut oil contains C6, C8, C10 and C12 triglycerides. Medium-chain triglyceride (MCT) oil is made from coconut oil but contains only the C8 and C10 triglycerides, which are directly converted in the liver to ketones. For those who do not like the taste or smell of coconut oil, MCT oil has virtually no taste or smell.
PQQ: PQQ (pyrroloquinoline quinone) is the only supplement that increases the number of mitochondria and improves mitochondrial function. It is found naturally in egg yolks (from free-range chickens), vegetables like parsley and celery, and fruits like kiwi and papaya. Integrative physician Isaac Eliaz explains that PQQ is similar to CoQ10 and “is another nutrient that can increase mitochondrial ATP production, while also increasing the number of mitochondria.” 21
CO-ENZYME Q10: CoQ10, also known as ubiquinone, is involved in energy production and is abundant in organs like the heart that require high amounts of energy. In fact, CoQ10 is a chemical supplement necessary for mitochondrial survival. With advancing age, when bodily production of CoQ10 declines, an exogenous or dietary supply is required. Organ meats are packed with CoQ10, but most people don’t eat them as a result, supplementation must provide this valuable nutrient. In The Dark Side of Statins, Dr. Duane Graveline cautions: “Few seniors have the CoQ10 adequacy of their youth. Supplementation is not only important for this group, but critical for most.” 15 Others also attest to CoQ10’s importance: “Even as the range of benefits expands beyond mitochondria, CoQ10 remains at the top of mitochondria nutrients.” 18
COLOSTRUM: Colostrum—the first milk mothers produce—is not only safe for all babies but is essential for newborns to ingest immediately. Although raw milk is considered nature’s perfect food, colostrum is fifteen times more potent in health-giving properties. Colostrum contains fats, vitamins, minerals, proteins, polypeptides (antibodies), growth factors and antioxidants. In the definitive work on the use of mammalian colostrum, Peptide Immunotherapy: Colostrum, a Physician’s Reference Guide, Dr. Andrew Keech provides biochemical evidence for colostrum as a source of antioxidants. Dr. Keech states, “One such antioxidant, glutathione, has been described as the ultimate antioxidant. It is well-documented that glutathione and its precursors are present in colostrum in relatively high levels.” 22 High glutathione levels correlate with long life. In the Journal of Alzheimer’s Disease, researchers contend that colostrum “decelerates the aging process” through “improvement in senescence-associated mitochondrial dysfunction and a decrease in ROS generation.” 23
KOMBUCHA: Kombucha is a tart, bubbly drink from the Ural Mountains of Russia. Kombucha is a refreshing source of a potent, detoxifying substance called glucuronic acid. A proven cancer preventive, glucuronic acid works in the liver to convert toxins into harmless forms that the liver can then excrete. A 2011 study published in Pathophysiology found that kombucha tea “modulate[d] the oxidative stress induced apoptosis [i.e., natural programmed cell death] in…hepatocytes probably due to its antioxidant activity and functioning via mitochondria dependent pathways and could be beneficial against liver diseases, where oxidative stress is known to play a crucial role.” 24
MAGNESIUM: One of the major mineral deficits of the American diet is magnesium, which functions as a co-factor to vitamin B6, both of which are necessary for the metabolism of proteins. To be biologically active, ATP “must be bound to a magnesium ion,” and “[w]hat is called ATP is often actually Mg-ATP [magnesium-ATP].” 25
SELENIUM: Selenium is a nonmetal mineral, which when combined with a protein has antioxidant properties that protect the mitochondrial membrane. Selenium is found in Brazil nuts, fish, red meat, chicken, egg whites and milk. Dietary selenium is required to form biologically active selenoproteins, which are enzymes that function as antioxidants. 26 In The Dark Side of Statins, Dr. Graveline confirms that “well over 30 selenoprotein enzymes have been discovered for the element selenium, expressing an unusually wide range of physiological applications with multisystem involvement. These enzymes are highly beneficial in preventing mitochondrial damage, premature aging, and many chronic diseases—similar to the antioxidant role of CoQ1O.” 15 However, according to the National Institutes of Health Office of Dietary Supplements website, very high doses of selenium can be toxic.
B VITAMINS: The B vitamins are spark plugs for metabolism—especially B12, B6, thiamin (B1), riboflavin (B2) and niacin (B3). In symbiotic support, B12 is largely responsible for proper formation of every cell in the body, and B6 is necessary for the complete digestion of all proteins. When B2 and B3 are utilized in the body, they convert to FADH2 and NADH, key molecular elements of the ATP-producing Krebs cycle.
D-RIBOSE: D-ribose, which occurs widely in nature, is essential to make the energy-carrying ATP molecule and plays a role in energy recovery and fatigue prevention. D-ribose “comprises the backbone of RNA, the basis of genetic transcription and, through the removal of one hydroxyl group, becomes DNA. Because of this, D-ribose is a promising element of any attempt to repair DNA damage. Additionally, once phosphorylated, ribose can become a subunit of ATP.” 27
L-CARNITINE: Found in animal tissue, L-carnitine acts as a carrier, moving fatty acids to the mitochondria. L-carnitine “is our only carrier for fat metabolism and without L-carnitine, all energy potentially derived from fat would be lost.” 28
COD LIVER OIL: By providing omega-3 fatty acids, cod liver oil enhances the mitochondrial membrane, which allows the release of ROS, thereby reducing their danger. Research in The Journal of Physiology shows how “the current data strongly emphasize a role of omega-3 in reorganizing the composition of mitochondrial membranes.” 29 However, the Weston A. Price Foundation points out that while cod liver oil provides vitamins A, D, and omega-3 fatty acids, it’s important to balance these with omega-6 arachidonic acid from animal fats.
ALPHA-LIPOIC ACID: Alpha-lipoic acid (ALA) is present in meat as well as vegetables and fruits in smaller quantities. ALA provides mitochondrial antioxidant effects and delays body aging. In an article in Metabolism, researchers affirm the disease-preventive qualities of lipoic acid, which “possesses antioxidative and antidiabetic properties.” 30

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This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Fall 2019

About Wayne Feister

Dr. Wayne Feister has had a 33-year general practice as an osteopathic physician in Rawson, Ohio, and specializes in musculoskeletal pathology. He received his degree in osteopathic medicine from Ohio University College, completed his internship at Osteopathic Hospital in Michigan and is certified in prolotherapy and sclerotherapy. He is vice president of both the American Osteopathic Association of Prolotherapy Regenerative Medicine and the Ohio Academy of Osteopathy, served as past chair of the Osteopathic Principles/Practices Committee (Centers for Osteopathic Research/Education) and is also a member of the International College of Integrative Medicine. He enjoys sharing his knowledge and experience with future medical professionals through positions at the Ohio University Heritage College of Osteopathic Medicine and Bowling Green State University Department of Public and Allied Health. He has collaborated on numerous published journal articles to increase public awareness of osteopathic medicine and prolotherapy. Dr. Feister also uses vitamin and mineral nutrition to remedy disease, as well as encouraging a traditional diet. A committed WAPF member, he has helped establish eight chapters and is a regular speaker at chapter meetings. A veritable country doctor, he and his wife follow a traditional diet, raise chickens and dairy cows and grow produce on their Ohio family farm. Dr. Feister acknowledges Carole Elchert’s editing assistance for this article.


The past decade has revealed a new role for the mitochondria in cell metabolism – regulation of cell death pathways. Considering that most tumor cells are resistant to apoptosis, one might question whether such resistance is related to the particular properties of mitochondria in cancer cells that are distinct from those of mitochondria in non-malignant cells. This scenario was originally suggested by Otto Warburg, who put forward the hypothesis that a decrease in mitochondrial energy metabolism might lead to development of cancer. This review is devoted to the analysis of mitochondrial function in cancer cells, including the mechanisms underlying the upregulation of glycolysis, and how intervention with cellular bioenergetic pathways might make tumor cells more susceptible to anticancer treatment and induction of apoptosis.

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Mitochondrial ROS regulate signaling

In the mid-1990s, NADPH oxidase activity had been demonstrated to promote signaling pathways involved in cell proliferation through oxidation of particular cysteine residues in proteins, modulating their activity [14–16]. By contrast, mitochondrial ROS (mROS) were proposed to be produced only under pathological conditions to invoke damage [17]. However, in the late 1990s, mROS emerged as signaling molecules that communicate between mitochondria and the rest of the cell under physiological conditions. An early example of this retrograde signaling under physiological conditions is the observation that hypoxic conditions stimulate mitochondria to release ROS, resulting in the stabilization of hypoxia inducible factors (HIFs) and the induction of genes responsible for metabolic adaptation to low oxygen [2, 18]. Subsequently, mROS were shown to regulate cellular metabolism and tumor necrosis factor receptor signaling [19–21]. Eight sites in the mitochondrial inner membrane and matrix have been implicated in the production of ROS [22]. The factors that control mROS production include the concentration of oxygen available to mitochondria, the redox state of the different electron transport chain complexes and mitochondrial membrane potential [23]. In the past decade, mROS have been shown to regulate a wide range of biological processes, including oxygen sensing, epigenetics, autophagy, innate and adaptive immune responses, stem cell proliferation and differentiation, and hormone signaling [24–28].

A scientific colleague and friend once quipped, ‘If you don’t have a mechanism just say it is ROS’. There is some justification for this remark, since ROS have been linked to a wide variety of biological outcomes, including proliferation, differentiation, metabolic adaptation and senescence, though with no insight into the specific mROS targets required to invoke such diverse biological outcomes, or the mechanism involved. It is important to note that mROS targets that relay signaling could be localized in any or all of the mitochondrial matrix, the intermembrane space, or the cytosol. Furthermore, given the reactivity and toxicity of ROS at high levels, it seems likely that lower levels of mROS may be generated that invoke distinct biological outcomes. Control of different stem cell fates by ROS is an example of different levels of ROS invoking different biological outcomes. The two salient features of stem cells are their ability to self-renew, and their ability to differentiate into specialized tissues [29, 30]. An emerging model is that quiescent stem cells reside at low levels of ROS and slight increases in ROS are necessary signals for self-renewal and cellular differentiation [31–33]. ROS levels above those required for self-renewal or differentiation impair these critical two stem cell properties and result in stem cell hyper-proliferation, resulting in stem cell exhaustion [34]. Going forward, it will be important to systematically quantify the ROS levels generated by mitochondria and their targets that are necessary for stem cell proliferation, differentiation and exhaustion in a given stem cell model system.

One interesting development over the past two decades has been the change in perspective on the role of mROS signaling in aging. Originally the free radical theory of aging proposed that, during the aging process, damaged mitochondria produced increasing amounts of ROS leading to tissue damage [35]. However, in most studies antioxidants have not extended lifespan of model organisms and clinical trials using antioxidants in humans have not shown any beneficial effects on age-related diseases [36]. On the contrary, recent evidence in yeast, Caenorhabditis elegans, and mice suggests that increasing mitochondrial generation of ROS can activate cellular stress pathways to dampen tissue degeneration, promote healthy aging and increase lifespan [37–40]. Based on the studies from the past two decades, an emerging model of mROS and signaling suggests that low levels (picomolar to nanomolar range) of mROS are necessary to maintain homeostatic biological processes, while slightly elevated levels of mROS initiate pathways for adaptation to stress. Much higher levels of mROS trigger cell death or senescence.


Mitochondria Inherited from Mother Can Influence Offspring’s Risk of Common Diseases

The results of a study by researchers at the University of Cambridge suggest that mitochondria—the “batteries” that power our cells—may play an unexpected role in common diseases such as type 2 diabetes (T2D) and multiple sclerosis. The study, involving data from more than 350,000 participants in the UK Biobank (UKBB), found that genetic variants in mitochondrial DNA passed to offspring could increase the risk of developing different conditions, as well as influence characteristics such as height and lifespan. There was also evidence that some changes in mitochondrial DNA were more common in people with Scottish, Welsh or Northumbrian genetic ancestry, implying that mitochondrial DNA and nuclear DNA (which accounts for 99.9% of our genetic make-up) interact with each other.

Research co-lead Joanna Howson, PhD, who carried out the work while at the Department of Public Health and Primary Care at the University of Cambridge, said, “Aside from mitochondrial diseases, we don’t generally associate mitochondrial DNA variants with common diseases. But what we’ve shown is that mitochondrial DNA— which we inherit from our mother—influences the risk of some diseases such as type 2 diabetes and MS as well as a number of common characteristics.” Research co-lead Patrick Chinnery, PhD, from the MRC Mitochondrial Biology Unit at Cambridge, added, “If you want a complete picture of common diseases, then clearly you’re going to need to factor in the influence of mitochondrial DNA. The ultimate aim of studies of our DNA is to understand the mechanisms that underlie these diseases and find new ways to treat them. Our work could help identify potential new drug targets.”

The scientists say the findings could ultimately help to identify new drug targets, but they could also have implications for the success of a new technique known as mitochondrial transfer therapy that is being developed to prevent offspring developing mitochondrial diseases. Howson and colleagues report their findings in a paper titled in Nature Genetics, which is titled “An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank.”

Almost all the DNA that makes up the human genome is contained within the nuclei of our cells. Nuclear DNA codes for the characteristics that make us individual as well as for the proteins that do most of the work in our bodies.

Our cells’ mitochondria provide the energy to power cellular processes. They do this by converting the food we consume into ATP, a molecule that can release energy very quickly. Mitochondria also contain a tiny amount of DNA—mitochondrial DNA, mtDNA —which makes up only 0.1% of the overall human genome, but is passed down exclusively from mother to offspring. The authors explained, “The 16,569-bp human mitochondrial genome has a compact genomic organization, with

95% of the sequence encoding 13 proteins, 22 transfer RNAs and 2 ribosomal RNAs that are essential for oxidative phosphorylation (OXPHOS) and production of cellular energy in the form of ATP.”

While errors in mitochondrial DNA can lead to mitochondrial diseases, which can be severely disabling, until now there had been little evidence that variants in mitochondrial DNA can influence more common diseases. Several small-scale studies have hinted at this possibility, but scientists have been unable to replicate their findings. “Mitochondrial DNA (mtDNA) variation in common diseases has been underexplored,” the University of Cambridge team noted. “Initial mtDNA association studies in complex traits were underpowered and yielded conflicting findings that were rarely replicated.”

For their newly reported research, the team developed a technique to study mitochondrial DNA and its relation to human diseases and characteristics in samples taken from 358,000 volunteers as part of U.K. Biobank, a large-scale biomedical database and research resource.

The results suggested that in fact mitochondrial DNA might influence diseases such as type 2 diabetes, multiple sclerosis, and factors such as liver and kidney function, blood count parameters, lifespan and height. “When applied to the UKBB, the workflow has provided a comprehensive reference dataset of mtDNA variant–trait associations to date, highlighting 260 new mtDNA–phenotype associations,” the authors wrote. Interestingly, they pointed out, “Mitochondrial dysfunction has been observed in several of the diseases that were associated with mtSNVs [mitochondrial single nucleotide variants] in our analyses, such as multiple sclerosis, T2D and abdominal aortic aneurysms.”

Some of the effects were seen more extremely in patients with rare inherited mitochondrial diseases—for example, patients with severe disease are often shorter than average—whereas the effects in healthy individuals tended to be much subtler, likely accounting for just a few millimeters’ height difference, for example.

There are several possible explanations for how mitochondrial DNA exerts its influence, the team suggested. One is that changes to mitochondrial DNA lead to subtle differences in our ability to produce energy. However, it is likely to be more complicated, affecting complex biological pathways inside our bodies—the signals that allow our cells to operate in a coordinated fashion.

Unlike nuclear DNA, which is passed down from both the mother and the father, mitochondrial DNA is inherited exclusively from the mother. This would indicate that the two systems are inherited independently, so that there should be no association between an individual’s nuclear DNA and mitochondrial DNA. However, this was not what the team’s results indicated. The study found that certain nuclear genetic backgrounds are associated preferentially with certain mitochondrial genetic backgrounds, particularly in Scotland, Wales and Northumbria. This suggested that our nuclear and mitochondrial genomes have evolved—and continue to evolve—side-by-side and interact with each other.

One reason that may explain this is the need for compatibility. ATP is produced by a group of proteins inside the mitochondria called the respiratory chain. There are over 100 components of the respiratory chain, 13 of which are coded for by mitochondrial DNA, the remainder being encoded by nuclear DNA. Even though proteins in the respiratory chain are being produced by two different genomes, the proteins need to physically interlock like pieces of a jigsaw.

If the mitochondrial DNA inherited by a child was not compatible with the nuclear DNA inherited from the father, the jigsaw would not fit together properly, thereby affecting the respiratory chain and, consequently, energy production. This might subtly influence an individual’s health or physiology, which over time could be disadvantageous from an evolutionary perspective. Conversely, matches would be encouraged by evolution and therefore become more common.

This could have implications for the success of mitochondrial transfer therapy, a new technique that enables scientists to replace a mother’s defective mitochondria with those from a donor, to prevent her child from having a potentially life-threatening mitochondrial disease.

“It looks like our mitochondrial DNA is matched to our nuclear DNA to some extent – in other words, you can’t just swap the mitochondria with any donor, just as you can’t take a blood transfusion from anyone,” Chinnery said. “Fortunately, this possibility has already been factored into the approach taken by the team at Newcastle who have pioneered this therapy.”

The authors concluded, “Our current findings establish the key role played by mtDNA variants in many quantitative human traits, and confirm their contribution to common disease risk … understanding mitochondrial genetic architecture and the interaction between the nuclear and mitochondrial genomes will be important for reducing the burden of cardiometabolic and neurodegenerative diseases, among others … The atlas of UKBB mtSNV–trait associations provided here lays a firm foundation for future studies at the whole-mitochondrial genome level.”


Nutrient cofacto rs needed for healthy mitochondrial function:

  • Krebs cycle – B1, B2, B3, B5, Fe, Mg, Mn and lipoic acid (all of the B vitamins are necessary for mitochondrial function) (Ubiquinol)- Coenzyme Q10 supports mitochondrial energy production in the electron transport chain by carrying electrons from cytochrome to cytochrome in order for ATP to be produced in the mitochondria. Without CoQ10, there is no electron transfer
  • Alpha-Lipoic acid– Alpha-Lipoic Acid (ALA) is a mitochondrial fatty acid that is highly involved in energy metabolism. It is a potent anti-oxidant compound and works with mitochondria and the body’s natural anti-oxidant defenses. – Ozone is a powerful mitochondrial stimulant. The fundamental underlying cause behind all degenerative disease from diabetes to heart disease to cancer is decreased mitochondrial energy production. Ozone can often correct this problem. Ozone also increases antioxidant protection by activating Nrf2 more than any other therapy. Under conditions of stress or growth factor stimulation, activation of Nrf2 counteracts the increased reactive oxygen species production in mitochondria. Any Nrf2 activator, was found to promote mitophagy, thereby contributing to the overall mitochondrial homeostasis.
  • Acetyl-L-Carnitine– Acetyl-L-Carnitine is well-known for its ability to protect the mitochondria. Acetyl-L-carnitine (ALC) is derived from the acetylation of carnitine in the mitochondria. Carnitine acetylation helps eliminate oxidative products from the body. – Melatonin is a potent antioxidant protecting mitochondria, which are exposed to abundant free radicals. It also increases reduced glutathione, SOD and GPx. – Resveratrol is a naturally occurring polyphenol found in more than 70 species of plants, including grapes, cranberries and peanuts, which was shown to confer diverse physiological effects such as cancer protection, microvascular protection, neuroprotection, cardioprotection, antidiabetic protection and mitochondrial function support. – N-Acetyl Cysteine (NAC) is the precursor for the powerful antioxidant glutathione, has also been effective in treating mitochondrial dysfunction.

References:

Fonslow, B. R., Stein, B. D., Webb, K. J., Xu, T., Choi, J., Kyu, S., & Iii, J. R. Y. (2013). NIH Public Access. Curr Treat Options Neurol ., 10(1), 54–56. http://doi.org/10.1038/nmeth.2250.Digestion

Fonslow, B. R., Stein, B. D., Webb, K. J., Xu, T., Choi, J., Kyu, S., & Iii, J. R. Y. (2013). NIH Public Access. Curr Treat Options Neurol ., 10(1), 54–56. http://doi.org/10.1038/nmeth.2250.Digestion

Neustadt, J., & Pieczenik, S. R. (2008). Review Medication-induced mitochondrial damage and disease, 780–788. https://doi.org/10.1002/mnfr.200700075

Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., … Auwerx, J. (2006). Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1?? Cell, 127(6), 1109–1122. http://doi.org/10.1016/j.cell.2006.11.013

Alcaín2, J. M. V. and F. J. (2013). Sirtuin activators and inhibitors, 38(5), 349–359. https://doi.org/10.1002/biof.1032.Sirtuin

Fonslow, B. R., Stein, B. D., Webb, K. J., Xu, T., Choi, J., Kyu, S., & Iii, J. R. Y. (2013). NIH Public Access. Curr Treat Options Neurol ., 10(1), 54–56. http://doi.org/10.1038/nmeth.2250.Digestion

Liu, J. (2008). The effects and mechanisms of mitochondrial nutrient ??-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: An overview. Neurochemical Research, 33(1), 194–203. http://doi.org/10.1007/s11064-007-9403-0

Lee, C. P. (1999). Following Traumatic Brain Injury in Rats, 16(11).


Mitochondrial metabolism in immunosurveillance

Mitochondria influence immunosurveillance via both cancer cell-intrinsic and cancer cell-extrinsic mechanisms. On the one hand, mitochondria are the source of many danger signals released by cancer cells as they die, and these signals are crucial for the activation of dendritic cells (DCs) to optimally prime tumor-targeting immune responses 187 . On the other hand, mitochondrial metabolism is involved in many functions linked to anticancer immunity, including (but not limited to) inflammasome activation, the establishment of protective immunological memory as well as the differentiation and tumoricidal activity of specific macrophage subsets 188,189 .

The best characterized mitochondrial product that participates in the elicitation of immune responses to dying cancer cells is ATP 190 . Extracellular ATP — which dying cancer cells can release in considerable amounts only if they can mount autophagic responses before death 191,192 — mediates indeed prominent immunostimulatory and chemotactic functions upon binding to purinergic receptor P2X 7 (P2RX7) and purinergic receptor P2Y2 (P2RY2), respectively, on the surface of DCs or their precursors 193,194,195 . In line with this notion, autophagy-deficient malignant cells lose the ability of driving anticancer immunity as they succumb to chemotherapy or radiation therapy in vivo, a detrimental effect that can be partially corrected by inhibiting extracellular ATP degradation by ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1 best known as CD39) 191,196,197 . Moreover, autophagy activation with caloric restriction or molecules that mimic the biochemical effects of starvation boosts the therapeutic efficacy of immunogenic treatment modalities (including anthracycline-based chemotherapy) in rodent tumor models, an effect that is abolished by the depletion of ATG5 or ATG7 as well as by the overexpression of CD39 196,198,199 . Mitochondria contain many other molecules that can operate as extracellular danger signals, including (but not limited to) N-formylated peptides and mtDNA 187 . However, while the relevance of some of these molecules in other disease settings (e.g., systemic inflammatory response syndrome) is well-established 200 , their role in anticancer immunity remains to be fully elucidated. Indeed, the receptor for N-formylated peptides (which is expressed by DCs) appears to be required for dying cancer cells to elicit a tumor-targeting immune response, but it does so by binding to another danger signal, i.e., annexin A1 (ANXA1) 201 . That said, the release of mtDNA upon MOMP promotes the secretion of type I interferon by malignant cells, and this is required for the activation of optimal anticancer immune responses upon chemotherapy and radiation therapy 202,203,204,205 . Thus, mtDNA also operates as an intracellular danger signal to connect intracellular stress responses to the preservation of extracellular homeostasis 206 .

CTLs and helper T cells responding to antigenic stimulation engage in a proliferative response that — similar to cancer cell proliferation — extensively relies on glycolysis and is supported by mitochondrial fragmentation 207,208,209 . In addition, mitochondrial ROS are required not only for proximal TCR signaling, but also for the activation of multiple transcription factors necessary for optimal T-cell functions, such as NF-κB and nuclear factor of activated T-cells 1 (NFATC1 best known as NFAT) 210,211 . At odds with their effector counterparts, memory T cells predominantly rely on fatty acid oxidation and OXPHOS to support their metabolic needs, a result of a metabolic reprogramming that involves not only mitochondrial elongation but also mechanistic target of rapamycin complex 1 (MTORC1) inhibition coupled to autophagy activation 208,212,213 . Intriguingly, a similar metabolic profile is also displayed by immunosuppressive cell types including CD4 + CD25 + FOXP3 + regulatory T cells and myeloid-derived suppressor cells 214,215 , which presumably renders them less sensitive to metabolic competition for glucose within the tumor microenvironment.

Macrophage polarization and activity are also influenced by mitochondrial metabolism. On the one hand, inhibition of the ETC appears to promote the differentiation of macrophages toward a pro-inflammatory and tumoricidal state (generally referred to as M1), which display a predominantly glycolytic metabolism secondary to the autophagic removal of mitochondria 216,217,218 . Conversely, M2-polarized macrophages, which generally exert tumor-supporting functions, preferentially employ OXPHOS as a source of ATP, especially in hypoxic conditions 219,220 . However, the oxidative burst that underlies the phagocytic activity of M1 macrophages depends on ROS of direct or indirect (via NADPH) mitochondrial derivation 221 . A similar consideration applies to the pro-inflammatory activity of M1 macrophages, which relies on ROS-dependent NF-κB transcriptional responses as well as on the activation of the so-called inflammasome, a supramolecular platform that produces IL1β and IL18 in a ROS- and mtDNA-dependent manner 222,223 .

Taken together, these observations exemplify the intricate involvement of mitochondrial metabolism in anticancer immunosurveillance (Figure 4).

Mitochondrial metabolism in immunosurveillance. Mitochondria are fundamental for the recognition of cancer cells by the immune system, as well as for the consequent activation of a tumor-targeting immune response. On the one hand, mitochondrial products including ATP, reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) operate as danger signals, either extracellularly (like ATP) or intracellularly (like ROS and mtDNA). On the other hand, mitochondrial ROS are required for T-cell activation in response to TCR engagement, and oxidative phosphorylation (OXPHOS) is required for the establishment of immunological memory as well as for the tumoricidal and pro-inflammatory activity of M1 macrophages (MΦ). However, OXPHOS also supports the differentiation of immunosuppressive cells including M2 macrophages, CD4 + CD25 + FOXP3 + regulatory T (TREG) cells and myeloid-derived suppressor cells (MDSCs). CTL, cytotoxic T lymphocyte.


Clinical Significance

Mitochondria is a vital cell organelle and in case of any disruption in its functions, besides instant death, the following health complications occur.

  • Alzheimer’s disease – Alzheimer disease means memory loss and disorientation that can last for days or months.
  • Diabetes – is another dangerous condition where a body cannot process the glucose properly.
  • Cancer – is a very dangerous disease where the human body gets amid abnormal cells. The cancerous, abnormal cells have the potential to eat away the healthy cells and this can lead to a person to die.
  • Muscular dystrophy – if the mitochondria is not functioning properly then this can also lead to muscular dystrophy. This is another dangerous condition where your bones become weaker without any visible cause.
  • Lou Gehrig’s disease – affects the Nerve cells in the brain and spinal cord.

These diseases are to name a few. A simple blip could wipe out the whole virility of the living organism while a prolonged fault could prove fatal for the unfortunate soul.


Mitochondrial Disease

Mitochondria are central to how our cells work and contribute in all sorts of ways to our well-being. In addition to their main role in making the energy stored in food available to power our bodies, mitochondria are also central to how cells are put together and die, how they respond to infections and injury, and in the changes that lead to cancer and ageing. Consequently, damage or disruption to mitochondria underlies many human pathologies and diseases. These range from genetic disorders that affect how mitochondria are made, to acute injuries such as heart attack and stroke, and on to chronic disorders such as obesity and diabetes and degenerative conditions such as Parkison’s and Alzheimer’s diseases. Therefore a better understanding of how mitochondria work and why they stop working well in disease is vital so we can develop new treatments for many diseases.

The work of the Mitochondrial Biology Unit is focussed on improving this understanding and on using the knowledge to develop new types of therapy for diseases involving mitochondrial damage.

How mitochondrial damage contributes to human diseases

The mitochondrial damage that causes disease can be divided into two broad categories, primary or secondary damage. The primary category is due to genetic defects in the DNA within mitochondria (mitochondrial DNA) or to a defect in a gene in the cell nucleus that is important for mitochondrial function. These genetic defects mean that mitochondria are incorrectly assembled or do not work properly. Often these “mitochondrial diseases" show up in babies or young children, and affect the brain, heart or other essential organs that use a lot of energy. However, there are many other forms of mitochondrial disease that show up in adults, for example leading to blindness or diabetes.

The other type of mitochondrial disorders, secondary mitochondrial dysfunction, is caused by damaging events during the patient’s lifetime. For example in a heart attack the damage is started by a blockage in a blood vessel in the heart, but this kills cells of the heart by disrupting their mitochondria. Similarly, there is a wide range of other disorders in which mitochondrial damage plays a significant role, including sepsis, neurodegenerative diseases, obesity, organ transplantation, cancer, autoimmune diseases, ageing and diabetes. Therefore mitochondrial damage is central to many of the most serious disorders facing our ageing population.

Therapies for mitochondria

As mitochondria are central to so many important diseases they are an important target for new therapies and drugs. Surprisingly, mitochondria have long been neglected by the pharmaceutical industry and overcoming this oversight is a key goal of the MBU.

Some of the ways we are investigating are to address the genetic defects causing primary mitochondrial diseases by developing gene therapies that replace the defective gene in the nucleus. A related approach is to treat the disease by replacing, repairing or "switching off" the damaged gene inside the mitochondria. Complementary approaches are to try and develop drugs that prevent the damage associated with mitochondrial diseases. For example, the MBU is developing drugs that are designed to go to mitochondria in patients in order to block damage in heart attack or stroke.

Finally, the MBU is also investigating new methods to measure how well mitochondria are working so that we can diagnose damage more easily and also detect whether a new treatment has worked or not.

Finding out more

There are a number of places you can find out more about mitochondria and mitochondrial disease. We can recommend:


Quantum Biology 4: Metabolic Syndrome

Readers Summary:

  1. How are all scientific disciplines tied together?
  2. What balances scientific observation vs. evidence-based medicine?
  3. How does entrance into the electron chain transport help/hurt us?
  4. How can Niacin help metabolic syndrome?
  5. What are the downstream effects?

We have shared a lot of information in the EMF and Quantum Biology series. Today, we are going to tie some of these concepts together to give you a picture of what the causes of metabolic syndrome might really be. This disease is now a runaway neolithic disease over the last 20 years. The fact that close to 26 of the population is obese and T2D is now no longer just a disease of obese people should begin to get scientist asking a better question of the real etiology of this condition. It really has not. They remain prisoners to old beliefs about the disease. What is clear today, when a person has the up to date current perspective of published biology, chemistry, and biology, is that all disciplines are connected deeply. Biology is the science of life, but it becomes one with physics, and the science of matter and its motion. We only seem to become aware of this situation while living our lives and becoming very observant of this synergy. Our living as sentient beings makes us the real experts on the laws of real nature. Science is based on observation of nature at its core. Evidence-based medicine is far off this target today. This may help you understand why Metabolic Syndrome is a runaway disease today. In 2012, the US government spent 270 billion dollars on treatment for this one condition. 20 years ago it was around a billion dollars. Something has radically changed environmentally and it is not the 9 billion inhabitants genes on this planet that have adapted this quickly. Their epigenetic pressures however have, and this is the source of the medical bill we get. You need to begin to question much of what you believe about neolithic disease today. Today’s blog delves into deep connections of those disciplines to help you understand what confuses your doctors today. Metabolic Syndrome is being treated via a cookbook called evidence-based medicine. Much of what we believe about this disease is based upon a house of cards.

Today’s conventional wisdom advice is that people are told to eat a high carb and low-fat diet to combat metabolic syndrome by the system. They are treated with drugs to lower glucose levels and drugs to raise endogenous insulin levels, or insulin itself while living mostly inside under blue light. The numbers of diabetics just grow exponentially when we do this. This should be a sign to change course to a new approach. We might consider a ketogenic diet to tackle this disease while cutting artificial light, EMF, pesticides, and the use of omega six industrial oils. So far this has fallen on deaf ears. All mitochondrial diseases and inefficiencies are tied to alterations in calcium metabolism in mitochondria. This is precisely how EMF acts in a biologic construct. So now that we live in an altered field 100 of the time because of the modern tech boom you might see why I think the smoking gun is obvious. Biology and physics just need to get their researchers together to see the picture I am painting.

When you eat a ketogenic diet most clinicians seem to have forgotten what really happens in a human’s biochemistry in their liver. We begin to force electrons to bypass complex one at the inner mitochondrial membrane during electron transport and enter complex two more consistently. FADH2 is an integral component of complex two. You originally heard about this in the quantum electron post, but what did not I tell you? Why does a ketogenic diet work in T1D, T2D, and to lose weight? When you lose water conduction (protonicity) to make energy, you begin to use ATP as a primary fuel source. The real problem arises when you no longer can make adequate ATP because of a protein conformational change which happens at cytochrome 1 called NADH. What allows this change? Might it have something to do with the hydrogen in NADH?

When this happens at the inner mitochondrial membrane you lose the ability of proper nanoscopic protein folding of cytochrome 1 and the result is constant chronic inflammation leak and a change of the “H” in NADH that depletes us of energy/information that leads to a loss of Vitamin D3 and causes a steady decline in the ability to make endogenous hormones from the PPP. The reason is the PPP needs NADPH to operate. The “H” in NADPH is critical to the operation of the process.

Geeks: the ketogenic diet with glucose depletion– When this is the dietary template over a period of a few weeks it induces nuclear gene transcription via mitochondrial signaling. When mitochondrial signaling is altered we get something called mitochondrial heteroplasmy. Mitochondrial heteroplasmy refers to the cellular phenotype where there exists a population of normal mitochondria called wild-type in many papers and books, and mutated mitochondria called mtDNA mutations. This scenario occurs in several inherited genetic disorders but also occurs with accelerated aging due to poor epigenetics. Accelerating aging is seen in T2D, Metabolic Syndrome, Obesity, and PCOS. This is why these diseases all share some degree of mitochondrial damage. In in vitro studies of artificially created cybrid cells with mitochondrial heteroplasmy, a glucose-depleted (not glucose free), bathed in a ketogenic cell media, promoted an increase in wild-type mitochondria and decreased the proportion of mutant mitochondria. This means a ketogenic diet can potentially reverse a disease process at the mitochondrial level if mitochondrial signaling is altered in the pathophysiology of the disease. That signaling need the sun to operate. The sun restores autophagy and apoptosis in the colony of mitochondria. In Metabolic Syndrome it is the key factor.

A ketogenic diet is one that features ketone bodies as energy sources rather than glucose and involves metabolism in the cytoplasm instead of in mitochondria. Why is this important? The cytoplasm is where coherent water is bound to the positive semiconductors in carbon nanotubes. This is precisely where the quantum effects of energy transduction would occur. Any decrease in cytosolic energy levels is then directly transmitted to the mitochondria as a signal. This signal is used to drive molecular pathways in mitochondria that tell the mitochondria what is the best choice to make for the cell, and then it stimulates that pathway to completion. This is how mitochondria sculpt intracellular evolution. Some of these processes are called mitophagy and mitochondrial biogenesis. Mitophagy is autophagy of the mitochondria itself. It has its own biologic pathway distinct from cellular autophagy with its own signaling. Mitophagy or mitochondrial biogenesis are closely coupled to avoid mitochondrial depletion (apoptosis) in tissues and cause cell death. This coupling is maintained by melatonin levels. If it did not operate this way organs would fail early because mitochondria would undergo chronic apoptosis. When this does fail in pancreatic beta cells, we see the development of T2D. Metabolic syndrome is also associated with high blood pressure. The reason this occurs is that metabolic syndrome patients rarely get any UVA sunlight to make nitric oxide in their skin to release it to lower their blood pressure. This is why diabetic have thick skin and so many dermatologic changes. Excessive autophagy without mitochondrial biogenesis overstresses the remaining “good” mitochondria, triggering cell suicide or apoptosis because of a lack of melatonin. Clearing our bad mitochondrial engines is a healthy thing for the cell and the organ involved. When this process slows or fails we get chronic organ failure. This is how heart failure and kidney failure develop in Metabolic Syndrome. Glucose inhibitors such as 2-deoxyglucose which prevent glycolysis and are essential “calorie restriction mimetics” have also been shown to select for healthy mitochondria and to get rid of damaged mitochondria. What else is a calorie restriction signal? The cold environment is very helpful for diabetics. Since most diabetics do not go out enough and spend most of their time inside close to the power grid this rarely happens. This is how the diet and the environment were effectively used to transduce the outside signals of the world to the internal signals in the cell in the mitochondria to drive intracellular decision making. The ketogenic diet is a dietary induction of selective mutant mitophagy. Ketogenic diets are designed to naturally occur in cold climates for a deep evolutionary purpose. They help reverse the damage the mitochondria face in the spring and summer months when carbohydrates are supposed to fueling electron chain transport via the diet. These foods are designed to cause more leakiness at cytochrome one over 4-6 months. In winter, life is looking to repair the damage with ketosis. When you never face a true winter in life, well you get Metabolic Syndrome.

The paleosphere calls people with this defect metabolic deranged. I do not. I call it a mitochondrial inefficiency because of uncoupled autophagy/apoptosis cycles. Circadian biology controls this process. It means diabetics have to rely on ATP from food electrons/protons to maintain ECT flow because they have lost their main ability to generate piezoelectric currents in collagen and water in their bodies. Normally humans can maintain ATP production without food using UVA and IRA light from the sun via the skin and eyes to lower food intake to keep motions on the ECT moving. This throws off the nanoscopic precision required for quantum tunneling that occurs in the inner mitochondrial membrane and this causes increased ROS and metabolic syndrome. Vitamin B3 can really help for those with minor protein folding issues at cytochrome 1 early on in this disease process.

Niacin: This is also why niacin works in these diseases because it is a ketone mimic drug. Why? Niacin also is known as vitamin B3, nicotinic acid and vitamin PP is an organic compound with the formula C6H5NO2 and one of the 40 to 80 essential human nutrients. In fact, when niacin deficiency is present it is one of 5 vitamins that causes a pandemic disease condition called pellagra. But it can be used to bypass a “broken” cytochrome 1 when misfolding (due to a chronic ATP deficiency, think EMF 7). Why is understanding this hardcore biochemistry important? It underpins why understanding precision that QED requires is paramount in semiconduction. Without the proper protein folding, you lose quantum tunneling of electrons and you lose the ability slowly to remain an omnivore. This is where QED takes us. Vitamin B3 can help activate PPP when they are broken for some reason when we are ketotic from a dietary standpoint using vast amounts of coherent water as I laid out in the quantum electron blog post. This occurs because it helps restore anions to the TCA and urea cycle. The PPP is responsible for making the chemical rings found in all human hormones using NADPH. The hydrogen in NADPH must come from the anions in the TCA cycle. They become unstable as well when intracellular water is lost because cholesterol is a polar molecule as well and does well in a lipid and water environment to act. Its action at receptor sites is critically important in how the hormones work in the nucleus to turn on and off our epigenome.

People continually forget sun exposure makes water in the matrix and cytosol of cells because of the order and information processing in mitochondria

Yes, people, niacin is a precursor to NAD + /NADH (cytochrome 1) and NADP + /NADPH (the magic of the PPP), which play essential metabolic roles in all living cells as I showed in EMF 4. The key is where the hydrogen comes from and what isoform it is in the matrix. Niacin cannot be directly converted to nicotinamide, but both compounds could be converted to NAD and NADP in vivo using matrix derived hydrogen and this information is very valuable when you have liver leptin resistance, metabolic syndrome, or epilepsy. It also is important for those with liver viral diseases like hepatitis B, C, D, and E. These patients also tend to well on niacin and a higher-saturated fat diet for these reasons. This type of fat helps make matrix water.

When cytochrome 1 has misfolded electron transport proteins (quinolone issue of CoEnQ10) you need to bypass it 100 of the time by eating fats, predominately, because if you don’t, your mitochondria begin to make massive amounts of ROS that overwhelm the cell, thereby lowering your vitamin D levels as well as most other hormones. This is due to the pregnenolone steal syndrome we spoke about in the Hormone 101 blog post, and as time elapses, eventually shortens its telomeres to cause cellular signaling problems that lead to either senescence or cancer. The reason why this occurs is more interesting.

NAD + builds up in relation to NADH levels on a per unit basis biochemically. Increasing the NAD+ in comparison to NADH changes a most of the mechanistic reductive biochemistry that occurs downstream. This occurs by signaling in the protein kinase B pathways of cells. Why is that a big deal you ask? The AKT pathway is also known as protein kinase B pathway (PKB). It is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. It is a major player in all things tied to metabolic syndrome via melatonin controls

Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes. Akt1 is also able to induce protein synthesis pathways and is, therefore, a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy, and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer. Akt (now also called Akt1) was originally identified as the oncogene in the transforming retrovirus, AKT8. In a mouse which is null for Akt1 but normal for Akt2, glucose homeostasis is unperturbed, but the animals are smaller, consistent with a role for Akt1 in growth. In contrast, mice which do not have Akt2, but have normal Akt1, have mild growth deficiency and display a diabetic phenotype (insulin resistance/ T2D), again consistent with the idea that Akt2 is more specific for the insulin receptor signaling pathway. The role of Akt3 is less clear, though it appears to be predominantly expressed in the brain. It has been reported that mice lacking Akt3 have small brains. This is what many belief causes brain shrinkage in all the neurodegenerative disorders that are linked to cytochrome 1 issues. This also happens to be why every neurodegenerative disease describes to date has an element of protein folding mishaps tied to its pathophysiology. PCOS is tied to this early on in its evolution before the more chronic diseases like metabolic syndrome develop fully. It is a gateway disease for what is coming in future years.

Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport in cells. Here is where metabolic syndrome eventually leads to severe T2D.

The follow through for the biochemistry geeks? AKT1 is involved in the PI3K/AKT/mTOR pathway and other signaling pathways. These all cause massive changes in cell cycle signaling and in cellular communication. mTOR is a huge factor in longevity and in cancer progression via the dysregulation of the p 53 gene. Inflammation or ROS must be present simultaneously for this to happen. If inflammation is not present mTOR activation increases protein synthesis and promotes survival. Why? Collagen is the P semiconductor of life. It is made from protein. High dietary protein won’t harm or kill you unless excessive inflammation, RNS, or ROS from cytochrome 1 misfolding is also present. This changes electron flow in mitochondria. That ruins autophagy programming. This ruins information processing in the mitochondria. Context and details matter in quantum biology and too many scientists, researchers, and doctors remain unaware of these pitfalls. I spoke about this very issue in Cold Thermogenesis 6 blog post 18 months ago.

Let’s talk about chronic fatigue patients. Do they suffer from the same condition but on a more subacute level? Yes, they do. Patients with ME/CFS patients usually have dramatic increases than normal levels of ventricular lactate in the CSF, and 36 less GSH in the cortical regions of the brain. The cortex is bathed in surface CSF that usually is not able to “proton superconduct” for many reasons. Fluoride is a dielectric blocker in CSF. The industrial omega 6 PUFA fats in the surface of their cell membranes in their cortical neurons are the most common reasons for avalanche collapse of proton superconduction in “CSF water” by displacing iodine and causing an upregulation of lactate production to use as a fuel when ketone is not present for energy production to make maximum ATP. When we have an energy inefficiency in the brain we get neurodegenerative disorders soon following. This is why Alzheimer’s disease and metabolic syndrome are bedfellows. Today we call diabetes type 3 diabetes. It is also why so many fibromyalgias and chronic fatigue patients also have similar phenotypes.

Neurons in the CNS and PNS love lactate, especially when they are suboptimal in ATP production or suffering from a neurodegenerative disease. Neurons become inefficient because of poor mitochondrial function due to lowered ATP production. This poor ATP recycling is the signal to the neurons and the brain mitochondria that they are trying to increase proton superconduction in CSF (density of CSF water) to improve CMRO2 and the current in the brain’s other semiconductor, water. The higher CMRO2 is the less the brain relies on ATP and the more it uses water superconduction. It is like a high octane fuel for neurons. Patients with ME/CFS are very energy inefficient and subsequently, they have high lactate levels in their CSF because they ARE energy inefficient and poor ATP recyclers. The lactate supply in the brain is made by up-regulation of MCT1 which is called monocarboxylic acid transporter 1. People with ME/CFS generally generate a lot of superoxide in the brain as the cause of their disease and not being able to make a lot of ATP and this is why they eat way too many carbs too fast recycle ATP. This never allows them to open their proteins fully to open the maximum amounts of water binding sites to foster water/proton superconduction.

Neurons in the brain try to avoid superoxide generation at all costs and neurons usually attempt to increase lactate production as a consequence to offset superoxide generation to use lactate as a secondary fuel source to ketones. Most people with ME/CFS do not use ketones for electrons along their inner mitochondrial membrane for ECT instead, they use glucose for fuels because they are no longer metabolically flexible due to the defects of protein folding at cytochrome 1 (NADH), because of what I wrote about in EMF 4. I believe this effect is due to anion depletion of the TCA by protons isoforms. They use too much complex one because of glucose, glutamate fuels are needed to quickly make ATP and they try to run their mitochondria on NADH complex one. It can lead to misfolding if they can not make enough ATP to complete the task. Oxygen and ROS are kept low in this clinical scenario. If oxygen was raised oncogenesis would be more likely. When this fails you activate apoptosis pathway and some of the things I spoke about in the recent webinar I did.

When you have metabolic syndrome you really want to access ECT at FADH2, or complex two in electron chain transport on the inner mitochondrial membrane instead using FFA or the ketogenic diet to bypass this issue in these diseases. When one fuels their diet with glucose/carbs you are increasing ROS and superoxide as a consequence. The more you use these fuels the more you increase ROS and superoxide and limit your ability to make ATP. I covered this in big detail in EMF 4.

Electron-dense foodstuffs supply the best possible neuronal FADH2: NADH (F/N) ratio of 0.2 to minimize ROS, ELF-UV light release, and superoxide generation. Moreover, this is why this pathway of electrons gives one FADH2 for 5 NADHs when you do this to minimize superoxide maximally. I talked about this very issue in the quantum electron blog post over two years ago. The more NADH you make the higher lactate will be made to offset the glucose in the brain. Lactate actually allows the mitochondria to make more matrix water to recycle hydrogen atoms to NADH and NADPH. This is why we need to use lactated Ringer’s solution for people with mitochondrial diseases. This shows you why the brain really does not like nor need a lot of glucose as a first line fuel contrary to what most believe or regurgitate. Ketones and lactate support fat metabolism optimally in neuronal use from foods/fuels to protect the brain.

QUANTUM GEEKS: When you think back to Quantum biology one I told you a sphere within a sphere creates an electrical tension or a difference…………. a mitochondrion within a cell is also a sphere within a sphere. The Earth and the ionosphere are also a sphere within a sphere. On Earth, this relationship creates the Schumann resonance frequency. This frequency of the Earth matches alpha wave frequency in the brain. This is no coincidence. In cells, the proper yoking of the alpha waves to circadian rhythms allows for the proper oscillation frequency that quantum tunneling requires on the inner mitochondrial membrane. This implies the ELF of the environment sets the tone for how biochemistry operates. The field the cell finds itself in is how the genome will be expressed. Darwin said in 1859, that the conditions of existence are far more important than natural selection. Today, conditions of existence have been renamed epigenetics. The environment’s ELF controls epigenetics. This insight maybe your surprise corollary how the macrocosm of the environment meets the microcosm of the cellular milieu. Our mitochondria are designed to resonate with the Schumann frequency and the brains alpha’s rhythms. In fact, every spherical organelle suspended in the cell cytosol’s water and collagen cyto-architecture filled with water. The ELF field a cell finds itself in can structure the water in the cytosol by changing bonding strength and bonding angles in water’s hydrogen bonding network. This improves or ruins energy and information transfers inside the cytosol. If it is ruined the cell has to rely more on ATP and less on semiconduction. This creates more ROS. These factors are all determined by your photoperiod and circadian rhythms. These frequencies are in the ELF band of the electromagnetic spectrum of energy to control the frequency and energy oscillations along the ECT that allow for proper tunneling in your ECT on your inner mitochondrial membrane. They yoke quantum time with neurologic or biologic time in the brain or cells in order for proper cellular metabolism and order and limit entropy or stress. This is precisely what a zero entropy systems is.

HOW IMPORTANT IS CURRENT OF FLOW TO CELLULAR ENERGY/INFO PRODUCTION?

The more energy inefficient we are the more reverse flow we get in ECT on the inner mitochondrial membrane and we get electron flow that results in backward flow and leakiness on cytochrome one. Quantum tunneling on the inner mitochondrial membrane requires the nanoscopic precision of the cytochromes and precision of the aromatic amino acids in the proteins that make them up………why? Increasing the distance between two coupled carriers by 1.7 Å slows the rate of electron transfer 10-fold. The flow (current) causes a sharp change in the NAD + and NADH ratio and results in superoxide formation. How do you ask? When we eat food it is broken down to electrons from its substrate foodstuffs. The electron density of these foods is determined by the power density of light in the seasons they normally grow in around the globe. For example, foods low in electron density, grow in the summertime because the power of the sun in our environment is offset by the lower density of electrons in food. This means in summer our matrix makes less water than it does in winter. It works like this because we do not need as much water because more light is present to be buried in the exclusion zone of water in summer months to power life.

It is also why fruits have a high water content to offset the lower electron density and higher fructose and glucose levels. The higher the sugar level the more superoxide is made to cause ROS. This is called energy/information balance and why evolution selected for the formation of leptin. Leptin is a “photoelectric effect accountant” for the brain. It also allows the brain to know the information in the sunlight that programs food electrons and moves food protons. When foods with lots of fructose or glucose are eaten a lot of NADH is made which fuels generation of superoxide. NADH is an electron transfer protein that requires excellent movement of substrates in the TCA cycle to give the H to NAD + . When there is a lot of NADH is around and not enough solar stimulus in the eye or skin, we tend to eat more foods to make up the deficit, the electrons begin to access other points to the electron transport chain’s CoEnQ10 coupling mechanism. These cytochromes are called electron transporting proteins that work via quantum tunneling mechanisms. Their names are flavoprotein dehydrogenase, mtG3Pdehydrogease, NADPH dehydrogenase for example.

By transferring electrons from the food to the cytochrome proteins it chemically reduces the proteins that CoEnQ10 couple too. Electrons delivered to the ECT from other cytochromes than cytochrome 1 promotes excessive reverse electron flow through complex I. This is what excessive fat or ketones can do. As a result superoxide generation begins and signals the cell to become insulin resistant because so many electrons are present. A person who employs a ketogenic diet does not get metabolic syndrome if they get decent sun exposure because they quickly become able to uncouple ECT and direct the excess electrons due to temperature changes. A person who eats a lot of fat but also eats a lot of foods that use cytochrome one, like glucose and fructose becomes leptin resistant. People who are Leptin resistant can not uncouple well. If a person can not uncouple, ECT metabolic syndrome is the result. To uncouple ECT requires UCP3, a high T3 level, a decent Vitamin A level, and leptin sensitivity all to be present in neurologic and quantum time. Vitamin A biology is linked to all opsin photoreception in humans. So if one is in any blue light it is physically impossible for this to happen. Blue light also destroys melatonin levels and this uncouples autophagy from apoptosis as well. When you are leptin resistant, as I mentioned in the Oprah blog post if you can’t uncouple and you develop metabolic syndrome and its associated conditions related to mitochondrial dysfunction.

In ME/CFS patients, they also constantly and chronically activate the PI3K/AKT/mTOR pathways like a diabetic does, but they do it for different metabolic reasons. This is why the disease phenotype presents differently. Under the hood, however, the quantum biochemistry is the same but the biophysical levers that control them are absent. It is caused by poor energy utilization at the mitochondrial level in neurons in the CNS and PNS to cause the symptoms of fibromyalgia. Now you can see why when this pathway is activated many bad things can happen that are common to T1D, T2D, most cases of leptin resistance with elevations in HS CRP.

These steps are just bus stops on the way to either final pathway and we call them neolithic diseases or diseases of aging. This gives you an insight into the etiology of the “quantum causes” and effects seen in metabolic syndrome early at the mitochondrial level. All low energy state diseases alter quantum tunneling of electrons in some fashion to cause the disease they do. Life and death is a dance of energy utilization along our inner mitochondrial membrane and on our water molecules to transfer energy for life well.