Hello Everyone! Welcome back to another Friday blog. Today I want to highlight fatty liver disease, which has literally doubled since 1994 (21..4% from 1988-1994). "Non-alcoholic liver disease (NAFLD) is now termed metabolic dysfunction-associated steatotic liver disease (MASLD), emphasizing the key metabolic factors of obesity, insulin resistance, vascular dysfunction and dyslipidaemia." When I wrote the blog "Do You Have A Fatty Liver?" - blog # 62 two years ago - the prevalence in the US was 34% of adults. Today it is estimated that >40% of adults (some experts say 45%) and 25% of children here in the US have a fatty liver. That's roughly a 20+% increase in 2 years. These numbers are likely grossly under-represented. Why? doctors don't test for it, don't understand how to interpret blood work and are not up to date on the literature. This is coupled by the fact that >93% of us are metabolically unwell and are unaware - which is terrifying. Let's delve in.

Fatty liver underlies many chronic disease processes such as obesity, IR (insulin resistance), T2D (type 2 diabetes), Alzheimer's and dementias, CVD (cardiovascular disease), HTN (high blood pressure), CKD (chronic kidney disease), PCOS (polycystic ovarian syndrome), Autoimmune diseases and even cancer. Testosterone has dropped by 50% in the last 50 years and we are living shorter lives. So, how is this happening to so many of us - including our children - what exactly is causing it - and how do you know if you have it? You can ask your MD to test for it (MRI, CT scan, DEXA, sonogram) or just do a simple measurement of your waist and hips. If you are a man, you want the waist to measure <40", and for women <35." The ratio of waist/hips should be .90 for men, .80 for women. You can also calculate your liver enzymes from bloodwork AST/ALT ratio. If the range is <1.0 you have "normal" liver,1.0-1.9, you have a "fatty" liver. If the ratio is 2.0+, you have cirrhosis or scarring. 

Sadly, our SAD (standard American diet) full of highly-processed food (doesn't meet the definition of food), high in fructose, sugar, synthetic dyes, preservatives, gums, trans-fats and inflammatory oils and absence of fiber is the primary driver for this metabolic dysfunction that leads us down the road of chronic diseases. These metabolic diseases are really symptoms - our body's cry for help. Much like little babies who cry and are unable to tell us what is wrong, our 30 trillion cells cry out by giving us symptoms. Our body is saying "ouch" and we need to be paying close attention! We need to literally go through a checklist of our cell's needs. Our body is trying to tell us stop putting substances into our body that are causing harm, give it nutrients it requires to be able to repair and function, get more sunshine, water, exercise or sleep. When we ignore these symptoms and continue to cause injury to our body - we get in trouble. 

These metabolic disease processes all have a common underlying problem - mitochondrial dysfunction, which IS metabolic dysfunction.

"According to the Third National Health and Nutrition Examination Survey, the mean consumption of fructose was estimated to be 54.7 g/day (range from 38.4 to 72.8) and accounted for 10.2% of total caloric intake. Consumption was highest among adolescents (12-18 years) at 72.8 g/day (12.1% of total calories). One-fourth of adolescents consumed at least 15% of calories from fructose. The largest source of fructose was sugar-sweetened beverages (30%) followed by grains (22%) and fruit or fruit juice (19%). In commercial processing food and sugar-sweetened beverages, the common sweeteners are sucrose (containing 50% saccharose and 50% fructose) and high fructose corn syrup (containing up to 55% fructose)."

Let's take a look at the top 4 things we are consuming that harm our mitochondria and leads to metabolic dysfunction:

1. Fructose is toxic to our mitochondria. When we consume HFCS (high fructose corn syrup), sugar (half sucrose and half fructose), fruit juice (high fructose and no fiber) and highly-processed foods - loaded with HFCS and sugar - we injure our mitochondria and inhibit 3 mitochondrial enzymes crucial for the production of energy (ATP). Metabolism of fructose results in increased UA (uric acid) production and elevated triglycerides. It also inhibits bone (long or cortical) growth and highjacks the growth mechanism to generate cancer! 

• AMPKinase (activated protein kinase) - "guardian of metabolism and mitochondrial homeostasis" - this enzyme is an energy sensor/switch. It controls cell growth and is involved in glucose uptake and lipid (fat) oxidation to produce ATP while turning off energy-consuming processes like glucose and lipid production as well as autophagy and mitogenesis - making new mitochondria.
• ACAD-1 (- acyl-CoA dehydrogenase -1) - this enzyme is responsible for cutting or breaking long-chain fatty acids into 2C (2 carbon) fragments for ketone production.
• CPT1α - (carnitine palmitoyltransferase - 1) - this enzyme transports fatty acids into the mitochondrial matrix for oxidation and production of ATP - "fructose suppresses transcriptional activity of PPARα and its target CPT1α, the rate limiting enzyme of acylcarnitine production." 

2. Trans-Fats - poison to our body - processed oils high in omega 6 create trans-fats when heated repeatedly (as in restaurants and fried foods) or when they are hydrogenated - The problem is food companies are able to say "no trans-fats" if they started with an oil that wasn't trans-fat or hydrogenated (like Crisco) to begin with. Examples of foods that are hiding trans-fats: commercial baked goods (cakes, cookies, pies), shortening, microwave popcorn, stick margarine, frozen pizza, refrigerated dough (biscuits, rolls) nondairy coffee creamer and fried foods. If their processing creates trans-fats, they are not required to report it. 

• Gut Microbes are unable to break the double bond in trans-fats. This is why processed food companies used them to keep foods "fresh" for literally years - think of a Hostess cupcake, twinkie or Little Debbie honey bun - these can survive for years in an unopened package. 
• Mitochondria - ancient microbes - also cannot process or break down trans-fats - therefore, your body is unable to process these! These poisons get stored in the liver as liver fat, as well as the arteries causing massive dysfunction.
• Trans-fats create a stiffer more hardened structure that completely disrupts the cell membrane function making the cell less pliable, decreasing function.

3. Dysregulated Branched-Chain Amino Acids (BCAAs) - Valine, leucine, isoleucine are essential amino acids and must be consumed in the diet. Let me preface this section by saying most of us don't get enough dietary protein. The recommendations from the latest literature range from .7-1.0g protein per pound of ideal body weight. Protein is not only satiating but curbs cravings and provides a thermogenic effect. If we are exercising, our muscles can utilize these amino acids. Specifically, BCAAs in excess - as happens with muscle breakdown - can be converted to fat droplets deposited in the liver and triglycerides leading to arterial damage and inflammation in multiple organ tissues. It is imperative to exercise to hang onto our muscle and prevent muscle loss. "Increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxidation, the tricarboxylic acid cycle (TCA) cycle, and oxidative phosphorylation. High serum BCAAs is found in fatty liver disease, T2D, IR (insulin resistance), cirrhosis and several cancers.

• High levels in the blood are found with IR and metabolic dysfunction. "Elevated plasma BCAA levels correlate with the severity of insulin resistance...impaired insulin action leads to dysregulated BCAA degradation."
• Muscle tissue is altered when serum levels are elevated. "Decreased glycolysis and increased fatty acid oxidation in muscle cause excess NADH and acyl-CoAs production, and impair BCAA transamination." Exercise is very important here as roughly 20% of our skeletal muscle is made up of BCAAs. Sarcopenia (muscle loss) from not exercising can lead to elevated serum BCAAs levels.
• Strikingly, the literature points to our microbiome as key in regulating BCAAs. Certain microbial species also make BCAAs and can drive up serum levels. Lacking key regulatory species is associated with elevated serum BCAAs levels and metabolic dysfunction. Implementing prebiotics (food for our gut microbiome) and probiotics (actual species of gut microbes) can help balance our gut microbiome and correct metabolic dysfunction. "Specific gut microbial species and/or prebiotics have unique potential to restore BCAA metabolism and treat obesity/T2DM." For example, F. prausnitzi is a keystone species that is inversely correlated with serum BCAA levels and severity of IR. This species is severely depleted and disrupted with the Covid spike protein - whether injected or acquired naturally.

4. Alcohol - like fructose, alcohol is a mitochondrial poison. Alcohol significantly alters the metabolism, utilization and storage of fat. It also makes the liver more susceptible to secondary insults - including increased vulnerability to ROS (reactive oxygen species), oxidative stress, gut-derived endotoxins, and inflammatory adipocytokines (TNF-a and others). Prolonged, chronic use can cause a lot of damage. Alcohol is primarily metabolized and detoxified by liver enzymes. Alcohol dehydrogenase (ADH) pathway leads to a decreased ratio of NAD+/NADH creating a depletion in energy, while P450 enzymes work to detoxify it for excretion - remember these are the enzymes that are totally disrupted from glyphosate exposure. When you shut down your detox enzymes, everything else becomes even more toxic.

• Alcohol inhibits FAO (fatty acid oxidation) - that is it inhibits the ability to burn fat for fuel - instead it does the opposite, so avoid it if your goal is weight or fat loss.
• It induces lipogenesis - that is the generation of fat!!! It activates multiple enzymes involved in the generation/synthesis of fat.
• It inhibits AMPkinase - the guardian of metabolism. Alcohol affects the liver very much like fructose.  
• reduces adiponectin - secreted by fat cells - "the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease."
• increases TNF-a (tumor necrosis factor- alpha) - this is an inflammatory cytokine that damages the liver
• alters the lipid (fat) droplet or storage form of triglycerides, metabolism and decreases vLDL (very low density lipoprotein) secretion from the liver. 
• Alters iron metabolism - increasing deposition of iron in the liver
• Depletes B vitamins and minerals.
• Depletes ATP - energy in the cell by altering the NAD+/NADH ratio - "An alteration in the NAD⁺/NADH ratio or the NAD⁺ pool size can lead to derailment of the biological system and contribute to various neurodegenerative disorders, aging, and tumorigenesis."
• Heavy use can result in ALD (alcoholic liver disease) - death of liver cells via apoptosis (active and well-coordinated) or necrosis ("passive and highly inflammatory form of cell death").
• Creates hypoxia (low oxygen levels)
• Bacterial endotoxins damage liver cells
• Scarring begins to form replacing liver tissue - this is cirrhosis and leads to severe functional impairment and liver cancer.
• Scarring leads to secondary failure of other organs, including the kidney.

What can we do to prevent or reverse fatty liver disease? As you can see from the list below there is A LOT that we can do. 

• Remove what's harming our cells - highly-processed foods, high amounts of sugar and fructose, glyphosate, trans fats and inflammatory oils high in omega 6 that destroy the function of our cell membranes and grains that spike blood sugar and insulin.
• Replace vitamins, minerals and nutrients our cells need to thrive - eat real whole foods grown without pesticides and herbicides, take a good multivitamin like grassfed beef organ complex, minerals, good sea salt or electrolyte powder.
• Go organic - remove glyphosate and other pesticides and herbicides as much as possible. Glyphosate disrupts the liver's ability to detoxify - shop local farmer's markets or grow your own.
• Lower UA (uric acid) by removing high levels of fructose, sugar and alcohol (particularly beer).
• Lower insulin - (fasting insulin should ideally be 1-3). Eat low glycemic - foods that are high in fiber that don't produce a big spike in blood sugar and insulin - focus on fat, protein and fiber - let your carbohydrates come from vegetables and low-glycemic fruits.
• Resistive exercise - to build and maintain muscle mass. Preventing muscle loss is key in keeping levels of branched-chain amino acids regulated.  Exercise increases oxygenation throughout the body, enhances endogenous production of antioxidants, utilizes branched-chain amino acids to build muscle tissue and protects the liver.
• Activity - move your body - don't sit for long periods. We are built to move - house clean, stretch, walk - getting 10,000 - 12,000 steps daily is crucial for our wellbeing. Activity thermogenesis can burn up to 2,000 calories per day.
• Fix the gut - restore a healthy microbiome with plenty of prebiotic fiber, probiotic rich cultured or fermented foods, polyphenols and healthy fat. Take a probiotic. Remove fluoride sources from water, toothpaste and mouthwash as it kills the oral microbiome and is a neurotoxin. Remove glyphosate as it is an antibiotic and alters the microbiome.
• Get plenty of sunshine - helps to enhance circadian rhythm, synthesize vitamin D, NO (nitric oxide), aids in detoxification and creates a "battery" in the cell through the production of exclusion zone water.
• Hydrate - Mild dehydration triggers an enzyme (aldose reductase) to convert glucose to fructose driving up triglycerides and uric acid - triggers the conversion of stored glycogen in the liver to fat - all further driving fatty liver. Your body does this on purpose because if you are very dehydrated, the body will burn stored fat as a source of water. Filter your water, avoid plastic, drink a minimum of 1/2 your body weight in ounces - ideally closer to your ideal body weight in ounces and replenish electrolytes.
• IF - intermittent fasting - try 14-72 hours and give your body a break from digesting food - allow it to access its clean-up system of autophagy (starts at 17-18 hrs). This drops insulin and allows you to start tapping into the fat-burning system. 
• Sleep - this is when repair happens - lack of sleep is stressful to the body and inhibits fat loss due to the spike in cortisol. Guard your sleep and aim for 7-9 hrs.
• Manage stress - chronic stress drives up cortisol temporarily - blood sugar increases, insulin increases, blood pressure elevates and the adrenal glands fatigue causing cortisol levels to drop and increased inflammation.
• Milk Thistle - Powerful antioxidant properties on the liver - "the hepatoprotective effect of milk thistle (and silymarin) is not exclusively due to their antioxidant action and other mechanisms seem to be involved. Anti-inflammatory and antifibrotic activities and an increase in irisin, a newly discovered polypeptide, are the proposed mechanisms. Drink daily as a tea or take as a supplement. 
• Enhance detoxification - consume cruciferous vegetables high in sulfur such as broccoli, arugula, Brussel's sprouts, bitter lettuces, dandelion root, herbs like oregano, marjoram, rosemary, parsley, thyme, cilantro...
• Omega 3 fats - Focus on DHA and EPA from fatty fish - salmon, cod, anchovy, sardines, kippers, etc. - take a cold processed clean fish oil such as Alaskan Cod Liver Oil. Include plant sources of ALA like chia seeds, hemp hearts, flax seeds.
• HP-EVOO (high polyphenol extra virgin olive oil) - rich in polyphenols that feed our mitochondria, microbiome, enhance our antioxidant systems, decrease inflammation, protect our DNA, work epigenetically to turn off cancer genes and promote health and longevity. Oleic Acid in EVOO enhances cell membrane function and pliability. Further, taking a shot of EVOO first thing in the morning on an empty stomach enhances autophagy (clean up system) and tells the brain that no glucose is needed in the bloodstream - burn stored fat. This enhances fat burning and reverses fatty deposits on your organs and in your belly. 

So, until next time my friends…Drink, Drizzle, Digest HP-EVOO at least 4T raw daily, - use more for cooking and drizzling onto your food - eat the rainbow of organic or wild-sourced or organic veggies (7-9 C) and low-glycemic fruits (to get the rainbow of gut microbes!) - eat wild-caught, pasture-raised, grass-fed - get plenty of sunshine - supplement magnesium, zinc, vitamin D3 + K2 - 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 your body weight in oz of water - get a good pre/probiotic - 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 - add a few minutes of mindful meditation to your day to combat stress - take a hot Epsom salt bath and follow with a cold shower/ice plunge - practice “earthing” as an anti-inflammatory - 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