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Unraveling Metabolism’s Role in Mental Health: Unveiling the Significance of Mitochondria Dysfunction to Explain All the Symptoms of Mental Illnesses

In his ground breaking book Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health–and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More, Dr. Christopher M. Palmer (https://amzn.to/3D2ftc0) brings together decades of research showing that metabolic and mitochondrial dysfunction leads to all symptoms of mental illness.  

When your mitochondria don’t work, your brain doesn’t work. And when your brain doesn’t work, hello, mental issues. Sometimes the disruption is in the brain itself, sometimes in other parts of the body. This post will demonstrate how mitochondria and metabolism are key to keeping us alive and thriving. We will then provide some insights for optimizing your metabolic health.

Researchers only saw mitochondria for their production of ATP, our energy source, for many years. But they do so much more from gene expression, cell health, and maintenance, hormones, and neurotransmitters. Mitochondria are pivotal to our survival, particularly our metabolism.  

What is metabolism?

Metabolism encompasses far more than calorie burning; it profoundly influences every aspect of our body’s functioning. It is the intricate process that enables our bodies to generate energy and regulate vital functions. To fuel our ATP energy production, our bodies require a combination of food, water, essential nutrients (such as vitamins and minerals), and oxygen. Through respiration, we inhale oxygen and exhale carbon dioxide—a byproduct of metabolism.

When we consume food, it undergoes a breakdown into its constituent components: vitamins, minerals, carbohydrates, fats, and amino acids. Alongside these macronutrients, the absorbed vitamins and minerals circulate in our bloodstream, transporting them throughout the body. Upon reaching the cells, these nutrients serve as building blocks for essential cellular components like proteins and membranes. Some may be stored as fat reserves for future use, while the majority undergo conversion into adenosine triphosphate (ATP)—the cell’s primary energy molecule. ATP fuels the cellular machinery, enabling cellular processes to function optimally.

In essence, metabolism can be defined as the intricate network of processes that convert food into energy or provide building blocks for cell growth and maintenance. Additionally, metabolism governs the efficient management of waste products. It determines the functionality and development of our bodies and brains, contributing to cellular health. Moreover, metabolism efficiently allocates resources to different cells, favoring those that are advantageous – promoting their survival while potentially sacrificing weaker or less essential cells. Metabolism acts as the body’s resource management system, constantly adapting to changing environments and circumstances to ensure our survival and well-being. It is a dynamic process that enables us to thrive in optimal conditions and cope with stressors like food scarcity.

Ultimately, metabolism represents the body’s relentless struggle for survival, making it a defining characteristic of life itself, as many authorities recognize.

Metabolism can be understood as energy imbalances within the body, which subsequently affect the proper functioning of cells.

While the brain is a remarkably intricate organ, often attributed to neurotransmitters coordinating cell functions, energy remains the essential foundation for all operations.

Although the brain constitutes only about 2% of body mass, it consumes approximately 20% of its resting energy. Brain cells exhibit remarkable sensitivity to disruptions in energy supply, making the brain acutely aware of any metabolic issues throughout the body.

Absolute and acute energy problems, such as heart attacks, strokes, and death, result in cellular death as an extreme outcome.

However, there are also less dramatic situations where the energy supply to cells becomes compromised. Rather than a complete energy production shutdown, cells may receive insufficient energy, leading to impaired functionality instead of cell death. The duration of these metabolic problems can range from minutes to hours. 

Hypoglycemia, characterized by low blood sugar, serves as a notable example. It commonly occurs when individuals have not eaten for an extended period. Mild cases can cause hunger, irritability, fatigue, or difficulty concentrating, while moderate cases may result in headaches or feelings of depression. Severe cases can lead to hallucinations, seizures, or even coma. In extreme situations, it can cause total metabolic failure and death. Typically, most individuals address the issue by eating, which raises blood sugar levels and restores normal function. 

Additionally, the body has inherent mechanisms to prevent severe hypoglycemia. And although diabetics use insulin or medication to lower blood sugar forcibly, they also face a higher risk of experiencing these harsh consequences. Brain symptoms dominate the effects of hypoglycemia, despite its occurrence throughout the body. Other metabolic problems manifest as chronic disorders with enduring symptoms, like diabetes. Although diabetes is commonly associated with high blood sugar, an intriguing perspective is to view it as an energy shortage or deficit in energy production. 

Glucose is the primary fuel source for cells, but individuals with diabetes struggle to convert glucose into energy. Despite elevated glucose levels in the blood, it encounters difficulties entering cells for utilization. This process requires insulin, a hormone produced by the pancreas, and diabetics either have insufficient insulin or insulin resistance, where the body is less responsive to insulin. Inadequate glucose availability hampers energy production within cells, leading to impaired functionality.

Numerous factors influence metabolism and are in a constant state of flux. It varies among different cells and can involve normal functioning and cellular decay. Some metabolic problems arise from chronic energy deficiency, while others operate at varying levels of control. Some factors impact metabolism broadly, while others are specific to certain body parts, organs, or cells.

When discussing human illnesses and symptoms, we often refer to malfunctions in certain areas of the body or brain. These issues typically stem from problems related to human cell development, function, or maintenance. Proper cell development is crucial to meet the body’s requirements, while function ensures that all components operate correctly at the right times. Maintenance involves preserving overall cellular well-being.

Ultimately, these three fundamental aspects—cell development, function, and maintenance—rely on one key factor: metabolism. Problems with metabolism can result in issues in one or more of these areas, and if significant enough, they manifest as “symptoms.”

Interestingly, metabolism is the common thread connecting mental illnesses. It is the lowest common denominator for all mental disorders, risk factors, and existing treatments. Despite its complexity, addressing metabolic problems often proves feasible through straightforward interventions.

What are mitochondria, and why do they matter to your metabolic health?

When mitochondria aren’t working, neither are we. Mitochondria, the powerhouses of our cells, have a fascinating origin story. It is believed that the first mitochondrion, a single bacterium, emerged around one to four billion years ago. Recent research suggests a close genetic relationship between mitochondria and the modern-day Rickettsia prowazekii, a bacterium responsible for typhus. During ancient times, archaea, another single-cell organism, engulfed this initial mitochondrion, but instead of perishing, they both survived. This symbiotic relationship led to the development of the first eukaryotic cell, which possessed a nucleus. The engulfed bacterium specialized in energy production, while the host organism focused on acquiring nutrients. This groundbreaking union set the stage for the emergence of today’s multicellular life forms.

Over time, other organelles, including the nucleus, evolved alongside mitochondria. While these organelles hold immense importance, mitochondria played a pivotal role in their development and became indispensable. Without mitochondria, these cell components fail to function properly. However, mitochondria themselves have changed. They lost the ability to replicate outside a eukaryotic cell and transferred most of their DNA to the cell’s nucleus, where human DNA resides. Approximately 1,500 mitochondrial genes are now embedded within human DNA, encoding proteins crucial for creating and maintaining mitochondria. These proteins are shared among all mitochondria in a cell.

Nevertheless, mitochondria retained thirty-seven of their genes, allowing them a degree of independence within the cell and from each other. The purpose of this remaining mitochondrial DNA remains a subject of debate. The essential point is that mitochondria and human cells have become mutually dependent, with neither surviving without the other.

Mitochondria’s remarkable journey from an ancient bacterium to an essential organelle within human cells highlights their indispensability for life as we know it.

Despite their small size, mitochondria are significant in the human body. On average, each human cell contains about three to four hundred mitochondria, resulting in a staggering total of approximately ten million billion mitochondria in the body. These tiny powerhouses account for about 10% of our body weight. A single cell may house thousands of mitochondria in metabolically demanding cells, such as brain cells, constituting over 40% of the cell volume.

Mitochondria play a vital role in energy production, particularly in generating adenosine triphosphate (ATP), the cell’s primary energy currency. While a small amount of ATP can be produced without mitochondria through glycolysis, the majority of ATP is synthesized within mitochondria, especially in brain cells. In an average adult human, mitochondria generate around 9 to the power of 1020 ATP molecules every second. Research examining brain cells using specialized imaging techniques revealed that a single neuron in the human brain consumes approximately 4.7 billion ATP molecules per second.

The presence of mitochondria in the right place at the right time is crucial for delivering ATP and recycling adenosine diphosphate (ADP) to maintain cellular processes. Neurons serve as an excellent example. These cells rely on a resting membrane potential, where the inside of the cell has a negative charge compared to the outside. This electrical state is vital for neuronal function and is established through ion pumps that require energy. Cells expend energy to maintain the ion balance, setting the stage for firing signals and performing various functions such as neurotransmitter or hormone release. Mitochondria provide the bulk of the energy required for these processes.

The intricate relationship between mitochondria and cellular function extends beyond energy production. Mitochondria also play a crucial role in maintaining the delicate balance of ions within cells, particularly in neurons. Neurons depend on a resting membrane potential established by ion pumps powered by mitochondrial energy. These pumps transport sodium, potassium, calcium, and other ions across the cell membrane, creating the electrical charge for proper neuronal function.

A cascade of events is set in motion when a neuron is triggered, leading to its specific action, such as releasing neurotransmitters or hormones. This process is akin to a row of dominoes being carefully arranged. It requires energy and coordination to set up the dominoes, but they fall in sequence once triggered. Afterward, the dominoes need to be reset, which demands further energy expenditure. Mitochondria provide the energy needed for these intricate processes to occur smoothly.

Without mitochondria fulfilling their role, the functioning of neurons, and by extension, the entire nervous system, would be compromised. Essential neurological processes, including synaptic transmission, signal propagation, and information processing, heavily rely on the energy supplied by mitochondria. Any disruption in mitochondrial function can lead to a decline in neuronal activity, impaired cognitive function, and various neurological disorders.

Beyond neurons, mitochondria are integral to the function of various organs and tissues throughout the body. They support energy-intensive processes in the heart, skeletal muscles, and other metabolically active tissues. Moreover, mitochondria are vital in maintaining cellular homeostasis by regulating processes such as apoptosis (programmed cell death) and calcium signaling.

The significance of mitochondria extends beyond their individual contributions to cellular function. They are interconnected and form a dynamic network within cells, constantly undergoing fusion and fission processes to adapt to changing cellular demands. This dynamic nature allows for the distribution of energy resources and the optimal functioning of the entire mitochondrial network.

Understanding mitochondria’s origins and essential role sheds light on their significance in human health and disease. Dysfunction in mitochondrial processes can have far-reaching consequences, leading to various disorders known as mitochondrial diseases. These disorders can affect multiple organ systems, manifesting as metabolic, neurological, muscular, or developmental impairments.

Advancements in our understanding of mitochondrial biology and its implications for human health have paved the way for potential therapeutic interventions. Researchers are exploring strategies to enhance mitochondrial function, such as targeting mitochondrial DNA, improving cellular energy production, and developing treatments for mitochondrial diseases. By deciphering the intricacies of mitochondria, we unlock the potential to address a wide range of health challenges and optimize human well-being.

In summary, with their ancient origins and crucial role in energy production and cellular function, mitochondria are essential components of human life. From powering neurons to sustaining vital organ systems, mitochondria’s contributions are fundamental to our existence. By unraveling the complexities of mitochondria, we can further our understanding of human health and strive towards innovative treatments and interventions that harness the power of these remarkable organelles.

What are some of the functions of mitochondria beyond ATP production?

Mitochondria have various functions beyond ATP production that are crucial for human health and metabolism. Let’s explore some of these roles:

Calcium regulation: Mitochondria directly regulate calcium levels within cells, which act as important signals for cellular function. Disrupted mitochondrial function can lead to imbalances in calcium regulation, affecting cell activity and overall health.

Metabolism regulation: Mitochondria produce mitochondrially derived peptides, such as humanin, MOTS-c, and SHLP1-6, broadly affecting metabolism, cell survival, and inflammation. These peptides, encoded by mitochondrial DNA, allow mitochondria to communicate and regulate metabolism throughout the body.

Neurotransmitter production and regulation: Mitochondria are involved in the production, secretion, and regulation of neurotransmitters in nerve cells. They provide the energy and building blocks required for neurotransmitter synthesis and release. Disruptions in mitochondrial function can lead to imbalances in neurotransmitter levels, impacting normal brain function.

Immune system function: Mitochondria play a vital role in immune system function, including fighting off pathogens and regulating inflammation. When cells are stressed, mitochondria release components that act as danger signals, triggering immune responses and low-grade inflammation.

Stress response regulation: Mitochondria help control and coordinate the body’s stress response, both physical and mental. When cells experience stress, mitochondrial dysfunction can lead to changes in metabolism, gene expression, and adaptations. Improper mitochondrial function can impact stress response mechanisms and contribute to various health problems.

Hormone regulation: Mitochondria are involved in synthesizing, packaging, and releasing hormones. They provide the energy required for hormone production, and in some cases, mitochondria in other cells have receptors for specific hormones, allowing for intercellular signaling.

Reactive oxygen species (ROS) management: Mitochondria generate reactive oxygen species (ROS) as byproducts of fuel burning. While excessive ROS can be harmful, small amounts serve as important signaling molecules within cells. Mitochondria help regulate ROS production and participate in their cleanup processes.

Understanding these functions of mitochondria provides insights into their impact on human health and metabolism. Dysfunctional mitochondria can lead to various health disorders and disrupt vital cellular processes. Researchers aim to develop strategies to improve overall health and treat related conditions by studying and addressing mitochondrial function.

How do we know that metabolic issues lead to mental disorders?

Neuroimaging studies have provided strong evidence linking metabolic issues to mental disorders. Techniques such as functional magnetic resonance imaging (fMRI), near-infrared spectroscopic imaging (NIRSI), positron emission tomography (PET), blood-oxygen-level-dependent imaging (BOLD), and single-photon emission computed tomography (SPECT) allow us to observe metabolic differences in the brains of individuals with mental disorders. These imaging methods indirectly measure cerebral blood flow changes associated with neural activity, serving as markers of brain metabolism and activity. These studies effectively capture metabolic changes in the brain by assessing glucose levels oxygen levels, or using radioactive tracers. Increased neuronal activity requires more energy, indicating higher metabolism, while resting neurons consume less energy. Through neuroimaging, we can observe these metabolic patterns and their connection to mental disorders.

What mental disorders have metabolic, i.e., mitochondrial dysfunction, been identified as the major cause?  

Mitochondrial dysfunction has been identified in various psychiatric disorders, including schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder(ADHD), anorexia nervosa, alcohol use disorder (also known as alcoholism), marijuana use disorder, opioid use disorder, and borderline personality disorder. Conditions like dementia and delirium, typically considered neurological illnesses, are also associated with mitochondrial dysfunction.

It’s important to note that this list is not exhaustive, as mitochondrial dysfunction may exist in other psychiatric diagnoses not yet thoroughly researched. However, the range of disorders mentioned is extensive enough to demonstrate the presence of mitochondrial dysfunction across various psychiatric symptoms and conditions.

Understanding the Diagnosis of Mental Illness in Psychiatry and Western Medicine

When diagnosing mental illnesses within the Western medical world, practitioners heavily rely on signs and symptoms exhibited by patients. It’s important to note the distinction between signs and symptoms. Signs are objective indicators of an illness that others can observe or measure, such as seizures, blood pressure measurements, laboratory values, or abnormalities detected through brain scans. On the other hand, symptoms are subjective experiences that patients communicate, including moods, thoughts, pain, or numbness. Psychiatry primarily relies on symptoms for diagnosis, encompassing conditions like irritability, anxiety, fear, depression, abnormal thoughts or perceptions, and impaired memory. Mental disorders can manifest as physical symptoms like sleep disturbances, slowed movements, fatigue, and hyperactivity. While some of these symptoms can be observed, clinicians often depend on patients to report them, categorizing them as symptoms rather than signs. Unfortunately, there are no laboratory tests, brain scans, or objective examinations that can definitively diagnose mental disorders.

Psychiatric diagnoses are based on the concept of syndromes, which involve clusters of signs and symptoms that commonly coexist without a known cause. An example from the medical field is acquired immunodeficiency syndrome (AIDS), initially classified as a syndrome before its viral cause was identified in the 1980s. Similarly, every psychiatric diagnosis is considered a syndrome due to the nature of psychiatric disorders. When mental symptoms are attributable to a medical or neurological condition, they are not classified as psychiatric disorders. Neurological diseases, cancers, infections, and autoimmune disorders can all affect the brain. In such cases, patients are diagnosed and treated by medical specialists outside of psychiatry, even if their mental symptoms are indistinguishable from those seen in individuals with “pure” psychiatric disorders. Psychiatrists and mental health professionals are left with cases where the precise cause remains unknown, which poses a significant challenge in advancing mental healthcare. Without a clear cause, treatments often target symptoms rather than address the underlying disorders.

Medical treatments can be categorized as disease-modifying or symptomatic. Disease-modifying treatments aim to address the root cause of an illness, such as using antibiotics to eliminate bacteria causing an infection. On the other hand, symptomatic treatments focus on reducing symptoms to alleviate suffering and improve daily functioning without directly changing the course of the illness. In mental health, most treatments fall under the symptomatic category. Psychiatric medications, electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS) are primarily symptomatic treatments. While these interventions can significantly reduce symptoms and induce remission in some cases, they do not appear to modify the underlying diseases themselves, as evidenced by the high rates of ongoing symptoms and relapses among individuals with mental disorders.

In the mental health field, circular reasoning is often used to support theories about the causes of mental illness. If a treatment effectively alleviates symptoms, it is sometimes assumed to have been the cause of the illness. However, there are no objective tests available to definitively diagnose mental disorders. Instead, clinicians rely on checklists of symptoms and criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM).

The introductory remarks of DSM-5 acknowledge the lack of understanding regarding the causes of psychiatric diagnoses. It is worth noting that many medical disorders frequently coexist with mental disorders, highlighting a bidirectional relationship between the two. For instance, individuals with diabetes are two to three times more likely to develop major depression. When they do, the depressive episode lasts four times longer than those without diabetes. Additionally, mental disorders are associated with a higher prevalence of overweight or obesity. While psychiatric medications have been linked to weight gain, it is important to recognize that treatments alone do not completely explain this phenomenon.

Metabolic abnormalities have consistently been observed in individuals with mental disorders, even among those who do not exhibit recognized metabolic disorders such as obesity, diabetes, or cardiovascular disease.

Remarkably, the risk factors for both mental and metabolic disorders share striking similarities. These risk factors span biological, psychological, and social domains, encompassing diet, exercise, smoking, substance use, sleep patterns, hormones, inflammation, genetics, epigenetics, and the gut microbiome. Additionally, factors like relationships, love, having a sense of purpose in life, and stress levels are also influential. Each of these risk factors has been associated with an increased risk for metabolic and mental disorders, which can be directly linked to metabolism.

Moreover, all the symptoms commonly associated with mental disorders can be traced back to metabolism, specifically to the role of mitochondria, which act as the master regulators of metabolic processes. This highlights the intricate connection between mental health and metabolic functioning.

In the current mental healthcare landscape, most available treatments can be considered symptomatic rather than disease-modifying. These treatments, encompassing biological, psychological, and social interventions, primarily aim to alleviate symptoms and improve the well-being and functionality of individuals. While they can provide significant relief and even induce complete symptom remission in some cases, they do not directly address the underlying causes of mental disorders.

The diagnosis of mental illnesses within the Western medical world heavily relies on the recognition and evaluation of signs and symptoms. With the absence of objective tests, mental disorders are diagnosed based on the presence of symptom clusters known as syndromes. However, the root causes of these disorders remain elusive, which presents challenges for developing targeted treatments. The complex interplay between metabolic and mental health factors further highlights the need for a comprehensive understanding of the underlying mechanisms. Ongoing research endeavors to unravel these connections and to develop more effective interventions that can actually modify the course of mental disorders.

So, how can you reverse, treat, or mitigate metabolic dysfunction?

Dr. Palmer says you must reverse longstanding metabolic problems to begin long-term healing. He suggests the following areas.

Optimize Mitochondrial Biogenesis – i.e. increasing the number of mitochondria in your cells, increasing your metabolic capacity.

Optimize Mitophagy – give cells the enzymes and materials they need to eliminate old defective mitochondria and replace them with new, healthy ones.  

Optimize Autophagy– give cells the enzymes and materials they need to replace the cells themselves, preventing disease and dysfunction and replacing them with new functioning cells.  

We want to take it a step further and give you actionable steps. Our book Minerals Revolution: Why Western medicine missed the science on why we are getting sick and what we can do outlines a protocol to optimize your mineral levels. Optimized mineral levels are the missing link. Without sufficient mineral levels, your mitochondria and metabolism become dysfunctional.  Correcting this is a straightforward and easy-to-follow protocol.  To learn more, check out the book and protocol on Amazon.   

We cannot recommend enough taking a deeper dive and reading Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health–and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More, by Dr. Christopher M. Palmer (https://amzn.to/3D2ftc0)

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Acetyl-l-carnitine deficiency in patients with major depressive disorder
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