THE LIVER TO HEART CONNECTION: NON-ALCOHOLIC FATTY LIVER DISEASE AND HEART PROBLEMS

Cardiovascular disease is usually the result of a culmination of factors that impact overall metabolism. The liver is one of the prime metabolic organs responsible for both fat and glucose handling, and hence any abnormal enlargement of the liver contributes substantially towards heart problems.

The below article describes what non-alcoholic fatty liver disease is and how it can increase the risk for cardiovascular disease, as well as what one can do about it.

A Brief Look at Non-Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease is defined as a chronic state of hepatic (liver) steatosis, with abnormal enlargement of the liver and eventual liver damage. Steatosis refers to the excess accumulation of fat in tissues. The liver is designed to store many basic nutrients to assist in regulating metabolism, including fats. Non-alcoholic fatty liver disease is usually diagnosed when stored liver fat exceeds 5-10% of the liver’s weight.

Non-Alcoholic Fatty Liver Disease as a Component of Metabolic Syndrome. Metabolic syndrome shares many similarities with diabetes, NAFLD, cardiovascular disease, and obesity. Some definitions suggest that all of these conditions are merely groups of symptoms that can be derived from metabolic syndrome, with NAFLD being the liver manifestation.

Prevalence. NAFLD is the most common liver disease. It is estimated that NAFLD affects up to 30% of those living in developed countries and up to 10% of people in developing countries.^[1]

Types and Disease Stages. Non-Alcoholic Fatty Liver Disease can be further divided into Non-Alcoholic Fatty Liver (NAFL) and non-alcoholic fatty steatohepatitis (NASH). NASH can be seen as the progression of NAFL, where the liver has excess fat and becomes inflamed, resulting in swollen liver cells and the formation of lobules that perpetuate liver cell damage. This eventually goes on to cause cirrhosis, which refers to liver injury and is usually indicative of liver fibrosis (overly thick or scarred tissue). Some individuals with cirrhosis go on to contract liver carcinoma.

Symptoms. Most people do not experience any symptoms of non-alcoholic fatty liver or NASH. Nevertheless, a few individuals might report fatigue, right upper quadrant abdominal discomfort, abnormal enlargement of the liver, acanthosis nigricans, and lumps of fatty tissue growing just under the skin. NAFLD can progress to cirrhosis as the condition worsens.

Symptoms of liver cirrhosis include^[2]:

• Jaundice (yellowing of the skin or eyes)
• Swollen abdomen and legs
• Nausea and appetite loss
• Abdominal pain, especially near the liver (upper right side of the belly)
• Fatigue and weakness
• Reduced cognition

Despite being relatively asymptomatic, non-alcoholic liver disease often predisposes people to acquiring other lifestyle disorders, such as diabetes or cardiovascular disease. Symptoms of such comorbidities may be apparent and perhaps worse in the presence of a fatty liver. Difficulties with breathing may also occur as a result of fatty liver disease.

Risk factors. Being the liver manifestation of metabolic syndrome, the risk factors for developing fatty liver disease are very similar and often apply to heart disease. These include:

• Obesity
• Insulin resistance
• Respiratory problems^[3]
• High blood pressure
• High cholesterol
• Menopause and reproductive diseases^[4]
• Medications that interfere with liver function, such as amiodarone, tamoxifen, or corticosteroids
• Environmental pollutants and excessive chemical exposure^{[5] [6]}
• Chronic stress^[7]
• Sedentary lifestyle
• High carbohydrate and high-fat diet, low in nutrients and fiber
• High alcohol consumption
• Genetic disorders that interfere with fat or liver metabolism, such as Wilson disease

Non-Alcoholic vs. Alcoholic Fatty Liver Disease

Fatty liver disease may also result from high alcohol intake, being referred to as alcoholic liver disease. There is very little difference between alcoholic and non-alcoholic fatty liver disease, with both comprising the same stages from steatosis to cirrhosis, contributing towards metabolic syndrome and increasing the risk for cardiovascular disease. Despite this, they are regarded as clinically separate syndromes that require different treatments. Men are nine times more likely to contract alcoholic liver disease than women, which may be attributed to the higher average intake of alcohol amongst men.^[8]

Disease Differences. In-depth studies have shown that those with alcoholic fatty liver disease are more likely to suffer from inflammation and fibrosis of liver veins, as well as immune infiltration of the liver that serves to perpetuate underlying inflammatory disease processes. On the contrary, those with non-alcoholic fatty liver disease are more prone to undergoing pathological changes to liver cells that result in their degeneration and liver disease progression.

How CVD and NAFLD are Linked: The Cardiovascular Dangers of an Enlarged Liver

Available evidence suggests that liver disease can cause heart problems. The following are the most significant complications besides cancer in those with early-stage non-alcoholic fatty liver disease.

Liver Function and Cardiovascular Health. The liver is the blood’s filtration system and gatekeeper. It serves as a barrier between the gut and the rest of the body, managing the transport of nutrients and waste between the two. This includes the management of energy substrates, such as fats and glucose, for overall bodily energy production throughout all tissues. When liver function becomes unbalanced, it often predisposes the internal systemic circulation to inflammation as a result of less efficient filtration and energy substrate management. The health of the cardiovascular system is also important for optimal liver function due to regulating circulation and tissue oxygenation.

Fatty Liver Increases Cardiovascular Risks. Non-alcoholic fatty liver disease patients are at a significantly greater risk for developing hypertension, cardiomyopathy (any disease that promotes a stiff heart), arrhythmias, coronary heart disease, atherosclerosis, and cardiovascular events, both fatal and non-fatal. These include heart attacks, stroke, and angina pectoris. Additionally, those with fatty liver are more than twice as likely to contract diabetes than those without, which may also contribute to the higher degree of cardiovascular mortality seen in this population.

Shared Mechanisms Between Cardiovascular and Liver Disease. In line with these shared risks, fatty liver and heart disease are both often associated with the same underlying causes, such as dyslipidemia (fat dysmetabolism) and insulin resistance, which are characteristic of metabolic syndrome. Common pathways shared between cardiovascular diseases and fatty liver disease are briefly explained below^[9]:

• Liver Fat Over Production and Dysmetabolism. In non-alcoholic fatty liver disease, the liver absorbs too much fat and/or produces excessive amounts of glucose or fructose as a result of a high carbohydrate diet. This increases inflammation as well as the production of triglycerides and cholesterol, especially very low-density lipoprotein (LDL) cholesterol. Excess fat either accumulates in the liver or enters systemic circulation, where it can clog the bloodstream, get deposited into adipose tissue, or accumulate in other organs and tissues. The liver becomes swollen with a reduced capacity for processing metabolites properly and fulfilling its many metabolic functions. This results in the poor uptake of fats from the bloodstream, reduced fat burning in the liver, and improper regulation of body fat. Excess systemic fat interferes with blood flow, places pressure on the heart, promotes vascular damage and can increase systemic inflammation. All these factors can elicit the development of atherosclerosis, coronary heart disease and other cardiovascular conditions.
• Insulin Resistance, Hyperglycemia, and Dyslipidemia. A high carbohydrate intake (especially of isolated fructose and other similar sugars) is linked with increased liver fat production.^[10] The liver seems to preferentially use dietary carbohydrates instead of dietary fats for this purpose. This is similarly associated with promoting hyperglycemia and insulin resistance, which may be further exacerbated by pancreatic fat accumulation and dysfunction. Insulin resistance perpetuates higher fat and glucose levels in the bloodstream, as well as low-grade systemic inflammation, capable of contributing to fatty liver disease, cardiovascular disease, or diabetes. This is one prime reason that all these conditions are typically lumped under metabolic syndrome.
• Reduced Blood Flow. Circulatory issues constitute other dangers of an enlarged liver. Besides vascular inflammation described above, lower levels of nitric oxide and higher levels of pro-thrombotic factors may also arise as a result of non-alcoholic fatty liver disease. The more dysfunctional the liver becomes, the less it is able to process, including amino acids and waste products. Asymmetric dimethyl arginine (AMDA) is one such product that the fatty liver battles to break down and which inhibits the formation of nitric oxide, an essential vasodilator. Liver damage can increase the release of pro-thrombotic factors as well, which can promote platelet coagulation^[11] and further reduce optimal blood flow. This ultimately contributes towards fibrosis of the liver (end-stage liver disease) and/or atherosclerosis or coronary heart disease.
• Gut Dysbiosis. Metabolic syndrome is often linked to gut dysbiosis, wherein the diversity of bacteria in the gut is diminished and unbalanced. This has been shown to correlate with the severity of symptoms in diabetes, cardiovascular disease, and fatty liver diseases. The gut microbiome helps to regulate overall metabolism, as well as liver function. When it gets imbalanced, it can give rise to low-grade inflammation and increased intestinal permeability, which allows for bacterial metabolites to enter the bloodstream. The liver is the first organ to be affected by these metabolites, which trigger inflammatory immune responses that can contribute to metabolic and other diseases. If the gut is balanced, the intestine is not abnormally permeable and collectively, the gut bacteria can produce essential nutrients that are required for optimal metabolism and liver function.

Can Liver Disease Cause Heart Failure? Non-alcoholic fatty liver disease is known to increase the risk of heart failure by 3.5 times on average^[12]. It is possible for advanced severe liver disease (cirrhosis) to cause heart failure. However, individuals with a fatty liver that are predisposed to heart failure are likely to have a comorbid cardiovascular condition as well.

Can Fatty Liver Cause Chest Pain? While a patient with a fatty liver may have chest pain from time to time, chest pain due to fatty liver is not likely. End-stage liver disease may promote cardiovascular disease and is likely to occur with heart problems. This may give rise to heart palpitations, arrhythmias, angina, and chest pain. Early fatty liver disease is associated with gastroesophageal reflux and heartburn^[13]. Heartburn can occur if one’s diet is overly acidic or too high in fat without enough fiber or alkalizing nutrients to balance the net effect.

Non-Alcoholic Fatty Liver Disease: Treatment and Prevention

There are currently no prescribed medications for fatty liver disease. As it is an often asymptomatic condition until it reaches a late stage, practitioners will often see the patient for a comorbidity, such as heart disease, and proceed to treat that instead. The patient may be prescribed medications to control excess fat and cholesterol, insulin, blood glucose, blood pressure, or thrombosis.

If fatty liver disease is diagnosed, the patient is often advised to make healthy dietary and lifestyle changes that promote weight loss and help maintain a stable metabolism. If liver disease is not too far advanced, these changes often yield great results. If advanced enough, the patient may require a liver transplant.^[14]

The below suggestions may help to prevent non-alcoholic fatty liver disease or lessen its progression.

Physical Activity. Exercise is the first protocol a doctor is likely to prescribe to a patient with fatty liver disease. All forms of exercise have been shown to help improve abnormal enlargement of the liver in varying degrees^[15]. Aerobic exercise has consistently helped reduce excessive liver fat, cholesterol, and insulin resistance. Resistance training can lower body fat levels yet has been shown to have less success with correcting biomarkers of liver damage than aerobic exercise^[16]. It may be best to begin with resistance training and slowly increase aerobic exercise until one becomes fitter, especially if breathing is difficult during physical activity. It is recommended to exercise for a minimum of 150 mins per week, split over the course of the week.

Nutritious Diet Enriched with Prebiotics and Probiotics. Like all conditions that fall under metabolic syndrome, a nutritious diet is recommended to help correct any potential energy deficits. In the case of a fatty liver, a low-carb and low to moderate-fat diet is recommended, such as the DASH diet or the Mediterranean Diet^[17]. These diets are typically plant-based and high in fiber-rich foods, which form the right substrate for healthy gut bacteria (also referred to as prebiotics) to thrive. Various strains of probiotic bacteria are indicated for regulating fat metabolism in those with cardiometabolic conditions such as non-alcoholic fatty liver disease. Benefits include reducing excess triglycerides, stored liver fat, and inflammation.^[18] These include lactobacillus and bifidobacterium strains, which can be found in abundance in kefir, yogurt, and most lacto-fermented vegetables.

Honing In on Specific Phytochemical-Rich Foods. Specific nutrients are known to help ameliorate excess liver fat and improve its overall function.^[19] The foods these nutrients are found in can help to tailor a nutritionally balanced diet plan. Carotenoids^[20] such as beta-carotene, astaxanthin and lycopene, anthocyanins, resveratrol, flavonoids in spices, and tea tannins, are all examples. These can be consumed in the form of carrots, beets, tomatoes and other brightly colored fruits and vegetables, leafy greens, dark berries, turmeric, garlic, ginger, cardamom, and other spices, as well as (good quality) coffee and teas including green tea and milk thistle.

Swap Added Sweetener and Sugar for Low-Fructose Fruit. Most refined simple sugars and sweeteners can contribute towards increasing fat production in the liver, with refined foods often containing an excessive amount. Fructose is known to be a particular concern, as it enhances the uptake of glucose into cells, especially liver cells. High-fructose corn syrup, dextrose, and maltose are examples of hidden forms of fructose commonly added to processed goods. Fruit juice also contains an extremely high proportion of fructose relative to other nutrients. While whole fruits contain some fructose, they are usually balanced by prebiotic fibers and other antioxidant nutrients, some of which have blood glucose and lipid-lowering effects. Fruits with a low glycemic index tend to be best in this regard and ought to be consumed instead of sweetened processed goods.

Vitamin E in the diet is linked to a lower risk of acquiring a fatty liver. Studies reveal that it may help to reduce liver fat absorption as well as protect against liver fibrosis and lessen biomarkers linked to liver damage^[21]. These effects are more prominent when vitamin E-rich foods are coupled with a plant-based wholefood diet and exercise.

Folate. High homocysteine levels are associated with the development of both non-alcoholic fatty liver disease and cardiovascular disease^[22]. Homocysteine levels can be kept in check by maintaining adequate levels of folate (vitamin B9).

Other Nutrients. In addition to the above recommendations, the contributions of trace minerals zinc, copper, and selenium^[23], other B vitamins, and omega-3 fats^[24] have also been shown to help protect against fatty liver disease in several studies. Balancing one’s diet with a healthy variety of foods is important for boosting liver health.

Minimizing Toxin Exposure. Placing less pressure on the liver can help to improve its functioning. This demands avoiding potential pollutants and chemicals in the environment that may contribute to faulty metabolism and liver damage. Taking precautions with detergents or heavy chemical agents, such as with gloves or masks, can help. Air filtration, if living in an area with poor air quality, can also be beneficial. Additionally, one ought to maintain good hygiene practices.

Conclusion

The origins of non-alcoholic fatty liver disease, cardiovascular disease, diabetes, and obesity appear to share common root causes that are collectively referred to as metabolic syndrome. The liver is responsible for regulating a large portion of overall metabolism as the interface between the gut and systemic circulation. Excessive uptake and production of liver fat can cause the bloodstream to become clogged and for the liver to become enlarged and less functional. These processes greatly increase the risk for all cardiovascular conditions and events, as well as for liver damage. Sedentary living and consuming a non-nutritious diet high in refined carbohydrates and fats are known to be some of the most common causes of both non-alcoholic fatty liver disease and heart problems. Correcting these factors with regular physical exercise and the implementation of a nutrient-dense plant-based diet can help to prevent fatty liver and reduce the risk of developing cardiometabolic conditions.

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