Omega-3 Fatty Acids Role In Non-Alcoholic Fatty Liver Disease
- Non-Alcoholic Fatty Liver Disease (NAFLD) affects a large proportion of the global adult population, but there's no agreement on how to treat it.
- Omega-3 fatty acids are beneficial in the treatment of hyperlipidemia and cardiovascular disease and have recently been proposed as a treatment for NAFLD.
- Omega-3 fatty acids are important transcriptional regulators of hepatic genes.
- Clinical studies show that they reduce hepatic steatosis, improve insulin sensitivity, and lower inflammation markers.
- Human clinical trials generally confirm these findings but have significant design flaws.
When we hear or read the word "fat", we think of the fat that's visible on our thighs, arms, and abdomen. But fat supports our internal organs and is even present within them.
The liver, one of our most hard-working organs, normally has a small amount of fat in it, and that's harmless. But a fat-loaded diet or heavy drinking can drastically increase the fat deposits in the liver, hamper its regular functions, and cause fatty liver disease.
This is a condition that can be reversed by taking up regular exercise and changing the mix of foods in your diet — strange though it may sound, a fatty liver can be helped by dietary fat, as long as it falls in the category of unsaturated fats and replaces saturated fats in the diet. As good (unsaturated) fats go, Omega-3 fatty acids are one of the best.
As per research, Omega-3 for fatty liver brings down the level of liver lipids and inflammation, thereby contributing to a reversal of the fatty liver disease. In general, Omega-3 fatty acids have a very beneficial effect on many organ functions; consistent with that, Omega-3 and liver functions are also closely connected.
Omega-3 fatty acids are not made naturally in the human body, so they must be supplied to your body through food. They're found abundantly in foods such as fatty fish (salmon, mackerel, herring, sardines, tuna), nuts and seeds (walnuts, chia seeds, flaxseeds), fruits, and vegetables (avocado, spinach, broccoli).
What is fatty liver?
A fatty liver is characterized by the presence of unwanted or extra fat in the liver. According to research conducted by the National Institutes of Health, United States, the condition is becoming more common all over the world, affecting nearly 25% of the global population. The condition is also linked to several other medical problems, including Type 2 diabetes, obesity, and insulin resistance disorder.
Normal liver cells contain some fat; however, if the amount of fat increases, it can lead to health problems. It can also cause severe liver diseases if left untreated. That's why it is critical to understand the causes, symptoms, and treatment of fatty liver, and where Omega-3 fatty acids figure in it.
Understanding fatty liver disease
Hepatic steatosis is the medical term for fatty liver. The liver is the second largest organ in the human body and is in charge of processing nutrients from the consumed food and drinks as well as filtering out harmful substances.
Fatty liver is defined as having more than 5-10% fat in the liver. Fatty liver disease is classified into two types based on the underlying cause: Alcoholic Fatty Liver Disease (AFLD) and Non-Alcoholic Fatty Liver Disease (NAFLD).
The fatty liver disease initially presents little or no symptoms — the person who has it may not even know it — but over time, it causes severe liver damage, rendering the liver incapable of removing toxins and producing bile as it should.
If your liver contains too much fat, that can cause scarring, inflammation, cirrhosis, and eventually, liver failure.
Non-Alcoholic Fatty Liver Disease
The liver is known as the body's chemical factory, responsible for over 500 vital functions, including infection resistance, fat breakdown, toxin removal from the blood, vitamin and iron storage, protein and hormone production, and blood clotting.
This busy organ, like any other in the body, can develop problems, including Non-Alcoholic Fatty Liver Disease. NAFLD occurs when the following two conditions are met: (1) there is evidence of hepatic steatosis (via imaging or histology); and (2) there are no causes for secondary hepatic fat accumulation (e.g., inborn metabolic errors, Wilson's disease, excessive alcohol intake, hepatitis, iron toxicity, or hepatotoxic drugs or toxins).
NAFLD is a group of fat accumulation disorders in the liver that are not caused by alcohol. NAFLD severity can range from non-alcoholic fatty liver (NAFLD) to non-alcoholic steatohepatitis (NASH) with or without fibrosis to cirrhosis (scarring of the liver). This can lead to hepatocellular carcinoma (liver cancer) in up to 27% of people with NASH and cirrhosis.
Risk factors for NAFLD
- A person's risk of developing NAFLD increases if they have metabolic syndrome (high blood pressure, blood sugar, excess body fat around the waist, abnormal cholesterol, and triglyceride levels).
- Obesity is the most common risk factor, followed by Type 2 diabetes and dyslipidemia (abnormal amount of lipids). Men are twice as likely as women to have the condition.
- Cardiovascular disease is the leading cause of death in NAFLD patients, regardless of other metabolic co-morbidities. Although liver disease or condition is the 12th leading cause of death in the general population, it's the second or third leading cause of death in NAFLD patients. NAFLD is now the third leading cause of hepatocellular carcinoma (cancer).
- Fat infiltration affects more than 5% of liver cells in NAFLD. An abdominal ultrasound is the most commonly used imaging method for diagnosis, and a liver biopsy is a gold standard for determining the degree of fat infiltration.
Symptoms and diagnosis of NAFLD
The majority of NAFLD patients are asymptomatic, but they may experience vague abdominal pain in the upper-right quadrant, fatigue, and malaise. Splenomegaly, ascites (enlarged spleen with fluid accumulation), and other symptoms of chronic liver disease are more common in patients with cirrhosis.
Lab tests typically reveal a 2- to 4-fold increase in serum ALT and AST levels, with serum ALT being greater than serum AST. High levels of bad cholesterol such as triglycerides, LDL cholesterol, and VLDL cholesterol can indicate dyslipidemia, which can result in fatty liver.
Blood tests (serology) are commonly used to detect viral Hepatitis A, B, C, and herpes viruses such as EBV or CMV, as well as rubella and autoimmune diseases.
Other LFT (liver function test) parameters, such as bilirubin, albumin, or prothrombin time, are normal. NAFLD is diagnosed when there's evidence of hepatic steatosis via imaging or histology, no significant alcohol consumption, and no co-existing chronic liver disease. Other additional tests include CT scan, which is a non-invasive scan that uses X-rays to accurately and precisely measure internal organs.
Liver biopsy in NAFLD patients
The gold standard for diagnosing NAFLD is a liver biopsy, but it's usually avoided due to its invasiveness. Newer imaging techniques have proven to be effective in detecting hepatic fibrosis, eliminating the need for a liver biopsy. Transient elastography, a non-invasive technique that uses ultrasound and low-frequency elastic waves to quantify liver fibrosis, is the most commonly used non-imaging technique. MR elastography is another non-invasive imaging technique.
Different stages of NAFLD
- The first reversible stage is fatty liver disease, also known as NAFLD. It is the accumulation of excess fat in the liver without the presence of inflammation. Moving on to the next stage takes about 10-15 years.
- NASH is the second stage, in which excess fat in the liver causes inflammation, resulting in slow liver damage. The average time for progression to liver cirrhosis is 7-15 years, depending on the associated conditions.
- Cirrhosis is an irreversible condition in which the liver has lost its ability to regenerate liver tissue, resulting in permanent damage. This stage increases the risk of liver cancer as well as other cirrhosis-related complications.
- NAFLD is commonly thought to be an adult-only condition, but rates in children are increasing. The average prevalence is around 8%, but in obese children, it has been reported to be as high as 38%.
Adults in developed countries have NAFLD at a rate of 20% to 30%,
NASH at a rate of 2% to 5%, and liver cirrhosis at a rate of 1% to 2%.
- Despite this high prevalence, no drugs are currently approved to treat NAFLD, and diet and exercise remain first-line treatments.
Omega-3 fatty acids and NAFLD
Omega-3 fats are a type of polyunsaturated fat. There are three kinds of Omega-3s:
- Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are primarily found in fish and are also known as marine Omega-3s.
- Alpha-linolenic acid (ALA), the most common Omega-3 fatty acid in most Western diets, is found in vegetable oils and nuts (especially walnuts), flax seeds, flaxseed oil, leafy vegetables, and some animal fat, particularly from grass-fed animals. The human body primarily uses ALA for energy, with very limited conversion to EPA and DHA.
Your body must convert ALA into EPA and DHA, which is an inefficient process because only about 8-20% of ALA is converted to EPA and 0.5-9% to DHA.
Several observational studies have shown that patients with NAFLD have lower relative hepatic levels of EPA and DHA than people who don't have NAFLD. The reason for this is unknown.
What makes Omega-3 fats unique?
They are a component of cell membranes throughout the body and influence the function of cell receptors. They serve as a starting point for the production of hormones that regulate blood clotting, artery wall contraction and relaxation, and inflammation. They also bind to cell receptors that regulate genetic function.
Omega-3 fats have been shown to help prevent heart disease and stroke may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
The Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), specifically EPA and DHA, have been shown to help adults and children with NAFLD. A recent meta-analysis of 18 clinical studies found that Omega-3 supplementation resulted in significant improvements in cardio-metabolic risk factors (total cholesterol, LDL-C, HDL-C, triglycerides, and insulin resistance), liver enzyme levels (ALT and GGT), liver fat content, and steatosis score.
Because EPA and DHA modulate gene expression in the liver, they promote fatty acid oxidation while inhibiting fatty acid synthesis and storage. More specifically, Omega-3 fatty acids inhibit the sterol regulatory element-binding protein 1 (SREBP-1) involved in fatty acid synthesis and storage, while stimulating peroxisome proliferator-activated receptors (PPAR) to increase fatty acid oxidation and PPAR-y to increase insulin sensitivity. The overall fat accumulation is reduced as a result of this gene modulation.
Given the findings of significant improvements in liver fat content, steatosis score, and several cardio-metabolic risk factors in patients with NAFLD after supplementation with n-3 LC-PUFAs, adult and pediatric patients with NAFLD should be encouraged to increase their intakes of n-3 LC-PUFAs.
This intake should be encouraged in conjunction with increased physical activity and caloric restriction, which effectively slows the progression of NAFLD.
Intake quantity of Omega-3 fatty acids
Based on the dosages used in the clinical studies, effective daily intakes for children appear to be 250mg of DHA and approximately 3gm of EPA + DHA for adults.
The minimum effective intake of n-3 LC-PUFAs is unknown, nor is it clear whether EPA is even required for therapeutic effectiveness, given that efficacy in children has been reported with supplements containing only DHA. Additional research is needed to answer these critical questions.
Although beneficial, Omega-3 consumption should be encouraged as one component of a comprehensive treatment plan that also includes a healthy diet and regular exercise (150-200 minutes of moderate to vigorous activity per week).
The Mediterranean diet is especially beneficial for NAFLD.
- This diet not only improves heart health but also reduces insulin resistance and disease severity in people with NAFLD.
- A Mediterranean diet emphasizes fish, fruits, vegetables, beans, whole grains, nuts, seeds, and olive oil while limiting red meat and sweets and eating dairy, eggs, and poultry in small to moderate amounts.
- Although wine consumption is part of the Mediterranean diet, it should be avoided by those with any kind of fatty liver disease, since alcohol puts a load on the already suffering liver.
- People with cirrhosis have to stop drinking permanently because alcohol increases the risk of developing hepatocellular carcinoma.
Other dietary measures for NAFLD include drinking coffee every day, which can slow the progression of liver fibrosis.
All evidence points to the fact that Omega-3 fatty acids are good for fatty liver. Its beneficial impact on liver health would be aided by at least 30 minutes of physical activity 4-5 days per week, as well as the management of sleep and stress issues. Consult a qualified clinical dietician to help you fine-tune your diet to avoid aggravating the fatty liver.
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