Excessive and heavy consumption of alcohol over a long period of time

1. How Many Drinks Does is Take To Get “Fatty”? Fatty Liver Disease Can lead to Metabolizes as Excessive and heavy consumption of alcohol over a long period of time One drink of alcohol (ethanol) Alcoholic Fatty Liver Disease (AFLD) Overview of the pathway of ethanol metabolism The consumption of 2 to 8 cans of beer or 3 to 6 glasses of wine/ hard liquor each day for more than ten years can increase the risk of fatty liver disease. This is approximately 40 - 80 g of alcohol per day6. The Metabolic Pathway of Ethanol and Alcoholic Fatty Liver Disease Risk Factors Liver and its Functions The liver is one of the largest organs in the body and has many functions including metabolic, regulatory, and digestive functions. Examples include detoxifying the blood, converting fats and cholesterol, storing iron, and metabolizing alcohol. It is able to process what you eat and drink into energy and nutrients that can later be used by the body. One of its most important jobs is removing toxins and harmful substances from the blood. Because alcohol is a toxin, chronic and excessive alcohol consumption can overwhelm the liver, leading to increased fat in and damage to crucial liver cells 5,8,9. Since ethanol cannot be excreted, it must be metabolized. The liver is primarily responsible for alcohol metabolism, but alcohol can also be metabolized in the brain, pancreas, and stomach. Ethanol is broken down in the cytosol of hepatocytes.  The enzyme alcohol dehydrogenase then catabolizes ethanol  into acetaldehyde. During this process, NAD+ is reduced to NADH, which means that NAD+ gains electrons.  Acetaldehyde is toxic and damages the liver even though it reacts shortly after it is produced. It is then catabolized in the mitochondria of hepatocytes  by aldehydedehydrogenase  to create acetate. Acetate is further broken down into water and carbon dioxide in tissues, which allows it to be excreted from the body 1,8.‪  ‬Overtime, excessive alcohol consumption can lead to the accumulation of fat in liver cells, called fatty liver disease. The accumulation of NADH in the mitochondria from ethanol metabolism signals to the liver that  beta fatty acid oxidation is not needed for oxidative phosphorylation. This decreases beta fatty acid oxidation and lipolysis in hepatocytes. NADH also inhibits gluconeogenesis by preventing lactate from being oxidized to pyruvate. Another effect of excess NADH is that the citric acid cycle stops as the substrates isocitrate and alpha-ketoglutarate are blocked, which causes a build-up of acetyl-coA. The build-up of acetyl-coA signals to the liver that fatty acid synthesis and triglyceride formation are favorable3. Excessive ethanol consumption also allows more fat  to enter the liver as  free fatty acids from adipose tissue and as chylomicrons from the small intestine.The formation of lipoproteins and the export of fatty acids from the liver are decreased as well7. Excessive alcohol consumption also affects enzyme activity. The activity of the sterol regulatory element-binding Signs & Symptoms Nutritional Implications The signs and symptoms of AFLD are mostly asymptomatic with no signs of tenderness. However if signs do occur, they may include weakness, fatigue, and weight loss2. Alcoholic liver disease has many nutritional implications. Specifically, a decrease in bile production will disrupt the breakdown of fats, which prevents fat-soluble vitamins such as A, D, E, and K from being absorbed. This also increases fat absorption in the liver. Thiamine, folate, and vitamin B12 may also become deficient because their absorption is decreased with increased alcohol consumption. Poor absorption of nutrients may be attributed to increased swelling in the intestine and gut and decreased enzymatic activity for carbohydrate breakdown. The normal metabolism of sugars, fats, and proteins are altered in the liver during alcohol metabolism because the body prioritizes alcohol metabolism. This can prevent the normal breakdown of fat, which results in the formation of triglycerides that are deposited in the liver. The increased accumulation of triglycerides contributes to alcoholic fatty liver disease. Increased alcohol consumption also alters carbohydrate metabolism. Glycogen is the storage form of carbohydrates in the liver. However, when there is an inadequate amount of glycogen due to increased fat build-up in the liver, the body uses other metabolic pathways for energy. This can lead to the breakdown of muscle, which is why patients with alcoholic liver disease experience muscle wasting, increased nitrogen excretion, and a negative nitrogen balance8. • Complications of AFLD usually occur after years of heavy drinking and they can be very serious. They may include: • Build up of fluid in the abdomen • Bleeding from the veins in the esophagus or the stomach • Enlarged spleen • High blood pressure in the liver • Brain disorders and coma • Kidney failure • Liver cancer2 Complications protein 1c is increased and the enzyme proliferator-activated receptor is decreased. These changes in enzyme activity promote lipogenesis and intracellular fat accumulation in liver cells.  It also decreases the activity of AMPK, which is a negative effector for acetyl-coA carboxylase. Acetyl-coA carboxylase is an enzyme that influences CTP1 and malonyl-coA to decrease fatty acid breakdown and increase fatty acid synthesis. Therefore, fatty acid synthesis is promoted. The accumulation of fat in hepatocytes is the result of continuous, excessive alcohol consumption over a long period of time. This is because the detrimental effects of ethanol metabolism that lead to an imbalance of fat production and breakdown are amplified. The result is that liver cells become filled with fat and the individual is diagnosed with fatty liver disease. If the individual does not adopt abstinence from alcohol, the disease can become more serious as the detrimental effects of ethanol metabolism continue to compound. Hepatitis and cirrhosis may result as serious consequences. Alcoholic Fatty Liver Disease Alcoholic fatty liver disease, otherwise known as steatosis, is the build-up of excessive fat in liver cells. It is classified as the earliest stage of alcohol-related liver disease and occurs in individuals who consume large amounts of alcohol for a long period of time. If an individual drinks more alcohol than the body can process, an imbalance will disrupt the livers’ breakdown of fats and other nutrients. The build-up of fat in the liver will then lead to fatty liver disease. Normally, if an individual stops drinking alcohol once diagnosed with fatty liver disease, it can go away. Over 15 million people in the United States abuse alcohol consumption and 90% of those people will develop fatty liver disease2. Treatments Treatments for the stages of alcoholic liver disease may include abstinence from alcohol completely, corticosteroids and enteral nutrition for severe alcoholic hepatitis, and/ or a liver transplantation for severe liver failure. A nutritional diet with vitamin supplements are both important and necessary for the first few days while abstaining from alcohol 5,2. Overview of Alcoholic Liver Disease Stage 1: Alcoholic Fatty Liver Disease Accumulation of fat in the liver and is potentially reversible. Stage 2: Alcoholic Hepatitis Inflammation of the liver, scarring, and cell death. It may be reversible if diagnosed early. Stage 3: Alcoholic Cirrhosis Severe scarring and irreversible damage to the liver that prevents normal function3,5. Created By: Dani Gould, Jackie Ferretti, TearaHairaston, and Carisa Ingersoll