Radical Biology 101
“Do you have a testosterone protocol?” “Do you have a fertility protocol?” “Do you have a gut health protocol?” Endless questions like these indicate that Huberman and his ilk have accomplished their goal: obfuscating the origin of the disease process. We are programmed, both by mainstream and “alternative” health, into thinking that the causes of disease are numerous and that the treatments are varied. “Do these 10 things to fix this.” “Take these 10 things to fix that”. Mix in the cacophony of Christ-pilled carnivores evangelizing low carb, elimination diets, and the army of #chronicillness Truther moms promoting mold toxicity and parasite paranoia, and the mind of the over-educated health newcomer becomes thoroughly fragmented. To be clear, all disease is initiated by oxidative stress, specifically within the mitochondrial electron transport chain.
What is the electron transport chain?
The mitochondrial electron transport chain (ETC) is the process in which electrons are transferred across the mitochondrial membrane through protein complexes I-IV. As they do so, they facilitate a series of redox reactions that power the formation of a hydrogen ion gradient across the inner membrane space. This gradient is then used to drive hydrogen ions through the complex V, ATPsynthase pump to produce adenosine triphosphate (ATP), the body’s primary energy currency. Those who have researched deuterium depletion are very familiar with complex V– it functions exactly like a water wheel does to produce power. This method of energy production is called oxidative phosphorylation, and is the reason why mitochondria are known as the “powerhouse of the cell”; they are the body’s high-performance engines, fueled by electrons. Loss of electrons within the ETC leads to the formation of reactive oxygen species (ROS) and oxidative stress.
How do electrons leak from the electron transport chain?
Heavy metals like mercury, cadmium, arsenic, lead etc. have a high affinity to bind with the sulfur thiol groups of the ETC protein complexes, altering their form and interfering with their function. These sulfur groups are critical in facilitating the transfer of electrons through the ETC as they can both donate and accept electrons in what are known as reduction-oxidation reactions or redox reactions. Additionally, they serve as binding sites for iron-sulfur (Fe-S) clusters which are also capable of transferring electrons through the mitochondrial protein complexes. As thiol function is impaired by heavy metals, electrons can escape the ETC (primarily at complexes I and III) and interact with oxygen to form the powerful ROS, superoxide (O2-).
What are reactive oxygen species?
ROS are oxygen-containing molecules that have one or more unpaired electrons in their outer shell making them highly unstable, yet extremely important to cellular redox signaling. Under normal conditions, antioxidants moderate ROS activity by “donating” electrons through a reduction reaction, thus pairing the unpaired electrons in the outer shells of ROS and stabilizing them. However, if not reduced, ROS will “steal” electrons from other molecules via an oxidation reaction. O2- produced as a result of electron leakage in the ETC is typically broken down, or dismutated, by the endogenously produced antioxidant superoxide dismutase (SOD) into hydrogen peroxide (H2O2). The less reactive H2O2 plays a central role in turning on and off pathways like AMPK and mTOR, before it is eventually reduced into hydrogen and water by antioxidants like catalase and glutathione. If the production of either O2- or H2O2 exceeds the antioxidant system’s capacity to reduce them, oxidative stress results.
How do ROS contribute to oxidative stress?
As excess ROS like O2- and H2O2 steal electrons from other molecules, they create an oxidative cascade in which every oxidized molecule in turn steals electrons from those next to it. This “free radical” damage results in lipid peroxidation within the mitochondrial membrane, making it permeable and allowing hydrogen ions from the inter membrane space to leak out, thus depolarizing the electrochemical gradient necessary for ATP production. As hydrogen transport slows but electrons continue to be shuttled into the ETC, more electrons leak out and form O2-. Since sulfur atoms are highly susceptible to oxidation, the thiol groups and Fe-S clusters in the ETC transport proteins (already damaged by the presence of heavy metals) become additionally impaired.
To make matters worse, when the Fe-S clusters are oxidized, they can release free iron. If unbound iron or copper is present alongside O2-, it undergoes the Fenton reaction and produces the powerful hydroxyl radical (OH-). Iron can literally rust in the body just like an old car– this one of the most important concepts to understand as all diseases are linked to this phenomena. Likewise, if there is aluminum present, O2- can form aluminum oxide (AlO2-), an even more stable form of superoxide. As the antioxidant system becomes overwhelmed under these conditions, elevated ROS production incites a vicious feedback loop in which electron transport and ATP synthesis further slow.
How does oxidative stress alter genetic expression?
The overproduction of ROS leads to a cellular energy deficiency, or “low redox” state, which causes (among other things) mitochondrial DNA (mtDNA) mutations. As mtDNA is responsible for encoding the ETC transport proteins in the first place, transcriptional errors lead to defective proteins which are unable to efficiently transfer electrons, adding fuel to the oxidative fire. Mitochondrial mutagenic activity can also negatively impact nuclear DNA (nDNA) methylation, shifting nDNA expression towards a disease state. Eventually, prolonged mitochondrial dysfunction triggers apoptosis, or programmed cell death, via activation of the P53 protein pathway (except in a cancerous state).
Conclusion
This is a general overview of the origins of the disease process from a molecular level. The repercussions from this sequence of events are observed in every single disorder ranging from depression, to reproductive issues, cancer, to liver dysfunction, neurodegenerative diseases like Alzheimer’s/dementia, insomnia, hair loss, skin disorders… you name it. The mitochondrial redox state dictates genetic expression and determines the health of the individual; this is epigenetics at play.
The war against oxidation begins at the mitochondrial level. Rogue electron leakage needs to be contained, while simultaneously antioxidant defenses must be bolstered. After completing these two missions, oxidative stress decreases, ATP production is maximized and healthy mitochondrial DNA transcription is able to transpire. As a result, eugenic epigenetic expression. In the next post, we’ll discuss how the CLRLY Liver Detox protocol tactically combats oxidation, and for those who are prepared, I'll share the best practices for heavy metal chelation: the final frontier in optimizing biological function.
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