Happy Friday Everyone! Welcome back to another Friday blog. Today I want to focus on the primary lipid (fat) in the mitochondrial inner membrane (IMM), Cardiolipin, and its function. Why? This is precisely where our energy (ATP) is produced, where biological water is created, and quality control takes place to prevent nearly ALL the chronic disease processes known. What is cardiolipin? What does it do? How can we optimize and protect it? Let's delve in.

Cardiolipin (CL) is the signature phospholipid of mitochondria and is the primary phospholipid in the IMM. CL is composed of mostly linoleic acid (omega 6 PUFA), followed by oleic acid (MUFA), then smaller amounts of stearate (SFA), and palmitic (SFA) and is highly susceptible to oxidation/peroxidation. Cardiac mitochondria have a high PUFA content with several linoleic acid species (unusual) - tetra-linoleic acid being its most prevalent molecule. Why? It has a high affinity for the ADP/ATP carrier and higher affinity for cytochrome C. This is the reason it is optimal for mitochondria and why it hasn't been replaced over evolutionary time. It is unique in having a dimeric conical shape and is involved in mitochondrial cristae structure and function. [Cristae are the curved internal folds of the IMM - functioning to increase surface area as well as create junctions as regulatory gates. Heart and muscle mitochondria, for example, have high density of cristae].

"Phospholipids vary extensively in their acyl composition containing a mixture of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids, yet most phospholipids (>99%) in mammalian membranes avoid multiple PUFAs on the same phospholipid molecule." 

Cardiolipin is required for proper folding and optimal functioning, organizing and serving as an anchor for mitochondrial cytochrome protein complexes. The accumulation of the precursors to cardiolipin "is thought to dysregulate mitophagy, contributing to dysfunctional mitochondrial dynamics and quality control by disrupting cristae curvature and membrane integrity." This makes sense when you are trying to optimize your cristae alignment. Mature cardiolipin requires mostly linoleic acid with specific acyl chains - to function. 

Linoleic acid is an omega 6 fat, which is prevalent in our diets. It is in highly processed foods and seed oils and is in a highly oxidized form. We get a natural form of unoxidized linoleic acid in EVOO, raw nuts and seeds for example. What happens if the linoleic acid you give your mitochondria is oxidized, as in fried food at a restaurant? Can cardiolipin function? The answer is no. What if other oxidized fatty acids get incorporated into cardiolipin? Big problems - for example, incorporation of DHA into cardiolipin due to abnormal remodeling is an important factor in causing Alzheimer's, Parkinson's, Type 2 diabetes and left ventricular dysfunction in myocardial infarction - and likely is a factor with all metabolic disease processes because it affects mitochondrial function as it is typically oxidized. "Pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species."

All membranes in our body contain DHA (omega 3 PUFA) except the inner mitochondrial membrane (IMM) which has reserved its bacterial origin. Mitochondria use cardiolipin, synthesized within the mitochondria, that constitutes up to 20% of total mitochondrial phospholipids in the IMM. Research shows that DHA can incorporate into CL from dietary supplementation, which changes CL's shape - which changes FUNCTION! - reducing cytochrome activity, ATP production, quality and function of cardiolipin. The "remodeling of the phospholipidome with DHA, in particular, leads to a reduction in complex I, IV, V, and I + III activities, potentially through mechanisms involving the formation of lipid domains and phospholipid–protein binding." It appears the incorporation of supplemented DHA is preventing mature cardiolipin formation, causing mitochondrial dysfunction, lower oxidative phosphorylation and ATP as well as apoptosis.

"Due to the variety and tissue specificity of the four acyl chains and their sensitivity to oxidation, CL has also been used as a biomarker in several diseases and disorders. In the early pathology of Type II diabetes, oxidized CL has been observed in circulating plasma. Altered CL profiles have been observed in Alzheimer’s and Parkinson’s Disease. Neuronal specific CL has been found in circulating blood and used to predict injury severity in rodent models of pediatric traumatic brain injury and adult cardiac arrest." 

Cardiolipin coordinates mitochondrial "respirasomes" (respiratory proteins) into super-complexes to optimize electron transfer for the electron transport chain (ETC) to produce ATP. One of its crucial jobs is to provide structural support and stability for CCO (cytochrome C oxidase-complex IV). CCO has 2 copper atoms that transfer electrons to oxygen to create water. They are the "proton wire" moving protons efficiently during ATP production. CCO is also responsible for apoptosis (cell death)- quality control. Without cardiolipin, CCO falls apart. All of this runs efficiently when cardiolipin is functioning. It is also crucial for mitochondrial membrane morphology, protein import, stability, dynamics, biogenesis, mitophagy and apoptosis (death).

Cardiolipin protects the mitochondrial motor, the ATPase, allowing it to run at 100% efficiency. How? It has a relatively unique quality (bis-allylic-carbons) that allows it to exchange its H+ (protium) for ²H (deuterium). Deuterium is an isotope of hydrogen that also has a neutron, so is double the size and weight. Deuterium can't fit into the ATPase and jams it up. Removing deuterium enhances mitochondrial proton tunneling and optimizes ATPase spin at 9,000 rev/sec. In the heart, a single cardiolipin molecule can sequester 8 deuterons before trapping sites are full. "The enzymes involved in metabolizing organic molecules in the mitochondria result in the delivery of deuterium depleted (deupleted) protons to the mitochondrial intermembrane space." Cardiolipin's proximity to the cytochrome complexes allows for quality control by sequestering deuterium away from the ATPase and assists in preventing an inflammatory cascade. Limiting the level of deuterium coming in as well as protecting cardiolipin from peroxidation is key.

Under oxidative stress cardiolipin is peroxidized and migrates to the outer mitochondrial membrane (OMM). The accumulation of oxidized/peroxidized cardiolipin opens the mitochondrial transition pore and releases cytochrome C to the cytosol as a marker for cell destruction. Interestingly, "cancer cells sequester deuterium in order to reduce the deuterium burden in the extracellular space, helping the resident immune cells restore health to their mitochondria, ultimately empowering them to attack and clear the cancer."

Several other molecules help to "scrub" and sequester deuterium while providing light hydrogens to the ATPase pump. "A small number of classes of uniquely structured carbon‐nitrogen rings and bis‐allylic carbon atoms in certain biologically active small molecules may play a crucial role in sequestering deuterium for export into feces or urine." Polyphenols in EVOO exchange light hydrogen with deuterium (H/D). There are hundreds of antioxidants in real food that trap deuterium through H/D exchange - flavanols, polyphenols, flavonoids and other phytonutrients such as quercetin, anthocyanins, apigenin, luteolin, and isoflavones to name a few. Exchange happens at the aromatic rings, which can give insight into potential nutrients that have the most power to exchange their hydrogens for deuterium. The higher the deuterium load on the body, the slower the ATPase spins and less energy is made, more ROS/RNS (reactive species) are generated, increased mitochondrial heteroplasmy (mix of mutated and normal mitochondria) increases, and the more inflamed and sicker we become. We utilize many mechanisms to protect the mitochondria from deuterium.

So, how does our body get rid of deuterium? We utilize multiple organ systems and hydraulic vortices to move fluids and deplete deuterium - then excrete it through detoxification pathways such as urine, feces, saliva and sweat. This should be a light bulb moment if you suffer from constipation. Humans move fluids using hydraulic vortices, including the mitochondrial ATPase, CSF (cerebrospinal fluid), and the cardiac vortices moving massive amounts of blood throughout the body. We normally have around 130-150 ppm of deuterium in the blood; sea water is 155ppm. A high level of deuterium in the blood increases its viscosity by ~ 23%! The increased mass increases the centrifugal pressure gradient. This is NOT good. It is destructive to our vortices - as a vortex's lifespan is limited by its kinematic viscosity - deuterium causes it to dissipate into heat rapidly. 

Without assistance from multiple organ systems to deplete deuterium, mitochondria would not be able to perform high energy oxidative phosphorylation efficiently. A high deuterium load on the body (>130-150ppm) results in accelerated aging, chronic fatigue, metabolic dysfunction, Alzheimer's, cardiovascular disease, and cancer. Our brain takes 20% of total body energy and suffers from inadequate ATP production with a shift to Warburg metabolism (fermentation). When we eat (real) food, we chew breaking down food excreting deuterium in saliva - swallowing, it enters the upper esophageal sphincter - a circular muscle - that works to keep food in the digestive tract and prevent it from entering the respiratory tract. Food is literally mechanically squeezed (peristalsis) through the esophagus and past the lower esophageal sphincter where it enters the stomach. Mechanical gastric churning + stomach acid ~ 1.5pH - where other molecules sequester deuterium in acidic environments - food is broken down into chyme, which is released into the small intestine through yet another sphincter. Pancreatic ductal cells secrete ~2L bicarbonate per day. This binds and traps deuterium. Further, products made by our microbiome trap deuterium for excretion. If you have a Bristol 4 (almost no need for toilet paper) you are ridding deuterium efficiently from this pathway. If not, you could have a higher deuterium load.

Optimizing cardiolipin as well as reducing the deuterium load on the body improves mitochondrial function - preventing and potentially reversing disease processes. Let's look at some strategies that we can implement.

• Eat real locally grown food - Chewing significantly increases blood flow in the common carotid artery - physically pumps CSF (cerebrospinal fluid) nearly doubling outflow, assisting in clearance of glymphatic waste through the cervical lymphatics. This is one way to enhance clearance of deuterium from the CSF. It also stimulates and increases blood flow to the salivary glands and elimination through the digestive tract. "Increasing CSF clearance can reduce the severity of ischaemic or traumatic stroke and other neurological conditions, including migraines."
• Chew masticating gum - for the above reasons (I personally like natural re-mineralizing gum)
• Get a Massage - gentle mechanical draining of neck/cervical lymphatics clear glymphatic waste and restore normal CSF flow.
• Consume good sources of linoleic acid - nuts and seeds and HP-EVOO. (even though it is found in seed oils and processed foods, remember you are getting it in an already oxidized form).
• Eat Fish and Seafood: DHA is in the sn-2 position that is incorporated into the central retinal pathway, brain and nervous system - most fish oil supplements are in the wrong position (sn-1,3) and they are oxidized. 
• Get sunlight - IR light activates mitochondrial cytochrome complexes used for energy production. This is crucial for CCO to be able to make biological water and perform quality control. Sunrise light is "cool" at ~1,800-2,000k. Midday light increases in temperature to 5,750k (same as your technology screens). Late in the day reaches 16,000k. This is why sunrise light is crucial. We make our hormones in "cool" light - by around 10am. We are supposed to expose ourselves to bright light as well to get the level of lux exposure. Take "sunshine" breaks during the day to allow the sun to communicate the right "time" so we optimize circadian rhythm.
• Exercise - many benefits including enhanced blood flow to all organ systems, enhanced excretion of waste including deuterium. However, if you have a high deuterium load, you may need to do some other strategies before placing this type of demand on high-energy tissue like muscle that could potentially be damaging. 
• Sweat - sweating rids the body of deuterium as well as environmental toxins. Sauna and exercise are good ways to increase sweating. Sauna also induces heat shock proteins that are protective. 
• Drink Deuterium-Depleted Water - if you are sick, this is one of the best strategies you can implement as it significantly lowers the deuterium load on the body and enhances mitochondrial function. You can get it on Amazon.
• Eat quality saturated fat - grassfed butter, tallow, coconut oil, lard. Stearate is the third most abundant fat in cardiolipin. Animal fats in particular are low in deuterium as it has been deupleted by the animal.
• Cold Thermogenesis - "cold exposure significantly increased the levels of multiple cardiolipin species in both BAT and WAT." Cardiolipin synthesis in BAT (brown adipose tissue) and WAT (white adipose tissue) is essential for energy homeostasis. The authors noted that mitochondria may prefer these species for optimal function, possibly because of the properties of water around the IMM. Mitochondria respond to cold by producing heat, which due to the physical properties of water shrink the space between the respiratory proteins, enhancing spin on the ATPase to optimize at 9,000 rev/sec.  Cardiolipin is known to bind to UPC-1 (uncoupling protein).
• Consume HP-EVOO (high polyphenol extra virgin olive oil) - 2-4 Tbs raw daily with dose-dependent benefits
  
  • EVOO contains linoleic acid, the primary fat in cardiolipin
  • Oleic acid is the 2nd most abundant fat in cardiolipin
    
  • The combination of oleocanthal, hydroxytyrosol, and oleuropein are cardioprotective in the presence of metabolic syndrome - reduced plaque and "ameliorated cardiac, vascular and endothelial function."
  • Oleuropein exhibits multiple effects: anti-arrhythmic, hypotensive, hypoglycemic, spasmolytic, and antioxidant, anti-infarct, anti-platelet, immunomodulator, antimicrobial
  • EVOO polyphenols upregulate antioxidant pathways to scavenge ROS to prevent oxidation of cardiolipin and other key molecules.
  • There are ~ 36 polyphenols currently known in EVOO. They trap deuterium and assist in efficiency of the ATPase
  • EVOO contains carotenoids (vitamin A), vitamin E and vitamin K. 

So, until next time my friends…Drink, Drizzle, Digest HP-EVOO at least 4 TBS raw daily, - use more for cooking and drizzling onto your food - eat the rainbow of LOCAL organic or wild-sourced veggies and fruits - eat according to what is growing at your latitude and location in season - eat wild-caught, pasture-raised, grass-fed - get early morning sunrise light, plenty of sunshine during the day, sleep in the dark, check your vitamin D3 level and supplement if needed: D3, K2, magnesium, zinc, and boron (- get your trace minerals and electrolytes with good sea salt - Celtic is hand-harvested and Himalayan was formed before plastics - eat foods high in lutein - drink plenty of filtered water. consume digestible and indigestible fiber for your gut microbes - adaptogens (such as mushrooms) and methylation donors (kale, beets, spinach, cruciferous, lion’s mane…), marjoram, rosemary, oregano, parsley and other herbs to detox, enhance overall health and reverse aging and disease - exercise your body and mind - ground barefoot to gain as many electrons as possible, add a few minutes of mindful meditation and breathing exercises to your day to combat stress - take a hot Epsom salt bath and follow with a cold shower/ice plunge - remove EMF (electromagnetic frequency) devices and blue light - use IR (infrared) from incandescent lighting, non-toxic candle or light a fire to enhance sleep and...turn off the light!!   #HP-EVOO 

This blog is intended for informational purposes only. Discuss strategies with your Healthcare Practitioner.