A Lifestyle Medicine Approach to Fatty Liver Disease 

The liver is truly an amazing organ. Quietly sitting under our ribs, it filters six cups of blood a minute, keeping what’s important for us and screening out harmful substances. The liver is a factory, producing bile, antibodies and hormones that help with digestion, protect us from infections and regulate many of our body’s functions. It also helps to regulate our blood sugar, protecting us from harmful low blood sugar levels when we need it. And far from being a fine, delicate piece of machinery, it takes a licking and keeps on ticking, actually regenerating better than just about any organ in our body. And yet, one toxic environment is taking a major toll on this fascinating organ – the modern Western lifestyle.  Without most Americans realizing it, our current diet and sedentary lifestyle have led to an epidemic of liver damage. We have all heard of diabetes, heart disease, and colon cancer. But ask people on the street what the most common cause of liver damage is in America, and not many will answer “metabolic dysfunction associated steatotic liver disease (MASLD), or fatty liver disease, to use the common phrase. This common yet serious condition has mostly flown under the radar of the public eye. Most of us don’t know about Global Fatty Liver Day (June), and I’ve never seen a t-shirt reminding us to Walk To Beat Liver Steatosis. Fatty liver is particularly dangerous because it usually doesn’t cause symptoms until the liver is on its last leg, and at that point, it may be too late to do anything about it. But amidst all of this bleak news, there is a bright ray of sunshine. Like so many chronic lifestyle-associated illnesses, MASLD is both preventable and treatable by maximizing our healthy daily habits. 

Definition

The first step to understand fatty liver better is to get some terms straight. Unfortunately, the terminology has changed multiple times, which can be a bit confusing. Fatty liver (aka steatotic liver) is a spectrum of disease, from excessive fatty deposits in the liver, to an inflamed liver, to eventually a scarred and minimally functioning liver, and can have various causes, including heavy alcohol use. When fatty liver is caused by metabolic dysfunction (and not by heavy alcohol use), it is termed metabolic dysfunction associated steatotic liver disease, or MASLD (this was formerly known as non-alcoholic fatty liver disease, or NAFLD).  MASLD is defined as a liver that has more than 5% of its tissue filled with fatty deposits but without significant inflammation, damage or scarring. On the other hand, the more dangerous metabolic dysfunction associated steatohepatitis (MASH) signifies that in addition to the fatty deposits, there is inflammatory damage to the liver cells, which can lead to scarring known as fibrosis, or even advanced scarring, known as cirrhosis of the liver. Those folks that just have MASLD typically rarely get symptoms and don’t die from the disease, though it’s still a sign of significant health problems as detailed later in this article. About 20-30% of people with MASLD go on to develop MASH, and they are at increased risk for cardiovascular disease (CVD), liver cancer, end-stage liver disease, and death.

Epidemiology

MASLD is the most common liver disease in the developed world, affecting about one third of adults in the United States, even up to 46% in one study done in the US military.  MASLD has been called the next global epidemic. Rates of MASH, for example, have tripled since I was a family medicine intern in 2004. Back then, we considered it, “not too big a deal”, compared to liver damage from heavy alcohol consumption or infections like hepatitis C, for example. Now, projected to be diagnosed in 100 million people by 2030, and costing over a 100 billion dollars every year, we are realizing that it truly is a big deal. Most patients are diagnosed in midlife, but there are increasing rates in kids and young adults, too. Unfortunately, MASLD is now the most common form of liver disease in children as well. Without a significant change in trajectory, MASLD is predicted to be the leading condition causing the need for a liver transplant by 2030. 

Cause

While the exact cause of fatty liver isn’t completely worked out yet, we know a lot about what plays a role in its development. MASLD is largely a story of excess unhealthy dietary fat and processed carbohydrate consumption. As one senior editor of Nature Reviews Gastroenterology and Hepatology bluntly put it, fatty liver “could almost be considered the human equivalent of foie gras”. 

At the root of its existence is insulin resistance, which is a state of metabolic dysfunction due to excess consumption of dietary fat and simple carbohydrates. Insulin resistance is thought to lead to an increased uptake of fatty acids by the liver, an increased production of lipids within the liver, and the increased oxidation of these fatty acids, which leads to liver cell damage. Additional factors likely playing a role in the development of MASLD are a lack of protective dietary antioxidants, excessive iron deposition in the liver, dietary and oxidized cholesterol, and the condition known as dysbiosis, an imbalance of our intestinal microbiome with an increased proportion of unhealthy intestinal bacteria that produce substances that harm the liver. 

Risk Factors And Associated Conditions 

Eating an unhealthy diet is a major risk factor for the development of MASLD. A typical Western dietary pattern is high in foods that promote fatty liver, and low in foods that protect against it. In the standard American diet, saturated fat and refined carbohydrates (such as high fructose corn syrup) make up the bulk of the day’s calories. Soft drinks are commonly consumed, and they increase MASLD risk in a linear fashion – the more you drink the higher the risk. The Western dietary pattern also tends to be high in pro-inflammatory foods like red and processed meat, and eating more meat and fewer plants has been associated with an increased risk as well.  The typical American diet is low in antioxidant rich foods such as fruits and vegetables that would be protective. In fact, only about 10-15% of calories in the standard American diet come from minimally to unprocessed plant foods. 

As they share similar risk factors, MASLD comes hand in hand with many of the chronic conditions that affect modern humanity – type 2 diabetes (T2DM), overweight, and elevated cholesterol. Around two thirds of people living with T2DM have fatty liver, and that combination unfortunately increases one’s risk of liver cirrhosis and death. MASLD is found in approximately 75% of people that are overweight, and in more than 90% of those with a BMI >40 . In fact, having any of the components of the metabolic syndrome increase one’s risk of having fatty liver (the metabolic syndrome is a constellation of conditions including elevated blood pressure, fasting glucose, waist circumference, and triglycerides, as well as low HDL, or “good” cholesterol). Emerging evidence also shows an association of fatty liver with hypothyroidism, polycystic ovarian syndrome (PCOS), obstructive sleep apnea (OSA), infection with the human immunodeficiency virus (HIV), and certain genes. 

As one notable example of the relationship between the standard American diet, chronic illnesses and liver disease, Dr. Michael Greger’s video, “How To Prevent Non-Alcoholic Liver Disease”, examines the story of Morgan Spurlock. Featured in the movie, “Supersize Me”, we see that even within just one month of eating nothing but McDonald’s fast food, Spurlock  experiences an increase in his weight, blood pressure, cholesterol, and develops liver injury. A Swedish study replicating this experiment showed how over a month, healthy volunteers developed liver damage by eating two fast food meals a day and becoming more sedentary. Most participants showed abnormal liver tests after just one week.

Symptoms

The majority of patients with MASLD don’t have any symptoms. Sometimes, people may feel fatigue, abdominal fullness, or itching. Only after the disease has progressed to the point of severe liver scarring are symptoms commonly detected, such as yellowing skin and sclera (the “white part” of the eyes) due to excess bilirubin leaking into the blood, and gaining fluid weight, often in the legs and belly. Confusion, sluggishness, and even coma are possible very late in the course of cirrhosis.  

Diagnosis 

Surprisingly, there is no official recommendation to routinely screen adults for MASLD, even for those who are at high risk for it (though children with obesity, or those with overweight and additional risk factors are recommended to be screened). The argument against screening everyone is that most people with MASLD have normal liver enzymes, and early liver disease isn’t well detected on imaging studies. There is actually no blood test or imaging study that completely accurately makes the diagnosis. The “gold-standard” for diagnosis is a liver biopsy. But as this is an expensive and invasive procedure, the diagnosis is often made as a “best-guess” based on a combination of the right clinical picture (overweight, sedentary individual) with elevated liver enzymes (called AST and ALT) and an ultrasound of the liver that shows fatty infiltration. What usually happens is that lab tests or imaging of the liver ordered for other reasons just happen to detect abnormalities suggestive of fatty liver. After seeing abnormal lab results, a health care provider will check for other causes of liver damage, such as alcohol abuse, acetaminophen (Tylenol) overdose, viral hepatitis (like hepatitis B or hepatitis C), or a genetic condition called hemochromatosis which is caused by excessive iron deposits in the liver. Health practitioners at this point will also typically screen for abnormal cholesterol and diabetes. Once the diagnosis is found to be likely based on labs and ultrasound, additional risk scores and imaging will help detect those who have advanced fibrosis of the liver. For those at high risk for fibrosis and cirrhosis, or when other causes of liver disease can’t be ruled-out, a liver biopsy may indeed be necessary. 

Treatment: A lifestyle medicine approach 

4 components: weight loss, a healthy plant-based diet, intermittent fasting, and exercise 

The cornerstone of therapy, which can lead to reversal of the condition if caught early enough in the majority of cases, is weight loss. Losing even 3-5% of body weight can start to improve fatty liver. But losing more, in the range of 7-10% of body weight, can bring about reversal of liver changes seen on liver biopsy, including liver fat deposits, inflammation, and fibrosis.

Several studies involving thousands of participants support the benefits of adopting a healthy, plant-based diet to prevent and address MASLD. A whole-food, plant-based diet is naturally low in calories, processed foods, and saturated fat. These qualities promote weight loss and help reverse the root cause of MASLD – insulin resistance. This dietary pattern is also high in antioxidants, which the liver needs to balance the processes of oxidation. Additionally, people eating this way typically have lower body stores of iron. Excess iron stores are found in 1/3 of patients with MASLD, and this may worsen progression of disease. A WFPB diet is rich in vegetables, fruits, whole grains, legumes (like beans, lentils, split peas and chickpeas), mushrooms, herbs, and spices. These foods are also critical to improving the gut microbiome. Eating a wide variety of plant foods will get lots of prebiotic fiber to feed the healthy gut microbiota. Perhaps in part because of their antioxidant effects, or their role with the microbiome, certain spices such as ginger, nigella sativa, and turmeric may also be helpful. 

As we can see, a WFPB diet helps the liver in a multitude of ways, not just due to the associated weight loss. The Mediterranean diet has also been shown to improve liver fat independent of weight loss. This is likely due in part to the relatively higher amount of antioxidants and unsaturated fats (e.g., found in olives, nuts, and olive oil), compared to saturated fats found in a typical Western eating pattern. While a ketogenic diet can sometimes improve fatty liver, it can also sometimes cause fatty liver (potentially due to the increased dietary iron, oxidative stress, and saturated fat content) and in general has too many additional health and environmental consequences to be recommended. 

In addition to being helpful for blood pressure, cholesterol, and brain health, omega-3 fatty acids seem to improve fatty liver disease. Whole food sources of omega-3’s are ground flax seed, chia seed, and hemp seed. Some people prefer also taking omega-3’s in the form of a DHA/EPA algae supplement (about 250 mg per day).

In addition to weight loss and what we eat, when we eat can help with the prevention and treatment of fatty liver. A number of studies looking at periodic fasting, alternate day fasting, and time-restricted eating have shown either improvements in liver enzymes or a decrease in liver fat content. Often, fasting studies also report a concomitant improvement in weight and insulin sensitivity. So, many Lifestyle Medicine practitioners recommend those with fatty liver to try different types of fasting regimens to see what works for them, and then incorporate this practice into their routine healthy habits. 

Exercise is the fourth component in a lifestyle medicine approach to the management of MASLD. Exercise reduces liver fat even when there is no associated weight loss. A review of 30 studies showed that diet and exercise together reduced weight, insulin resistance, and MASLD better than either alone. Additionally, exercise brings a whole host of well-known benefits such as an improved mood and a decreased risk for heart disease and cancer. In general we recommend shooting for at least 150 minutes of moderate aerobic exercise a week, with two additional days of strength training for added general health benefits. 

Additional treatment considerations 

In addition to a WFPB diet that promotes a healthy microbiome, there may be benefits to supplementing with probiotics. A meta-analysis of four randomized trials involving 134 patients showed an improvement in liver enzymes and insulin resistance. Generally speaking, though, most Lifestyle Medicine practitioners recommend that their patients get their prebiotics and probiotics from whole food sources.  

Some people with fatty liver disease may benefit from daily high-dose vitamin E supplementation. Taking 800 IU/day of vitamin E in a study of non-diabetic individuals showed improvement in MASH. A serious caveat, though, is that taking high-dose vitamin E may lead to an increased risk of prostate cancer, hemorrhagic stroke, and death. Some patients with MASLD and diabetes have shown improvement in their liver condition with certain diabetic medications like the oral medication pioglitazone (trade name Actos) and the injectable GLP-1 antagonists like liraglutide (trade name Victoza), though currently the evidence isn’t strong enough to recommend them as initial treatment for fatty liver disease. Additionally, these medications can have side effects, such as weight gain and heart failure (pioglitazone), and diarrhea, vomiting and headache (liraglutide). Clearly, getting to the root cause of this condition is preferred to simply trying to address it with medications. 

It is also important to do what we can to protect the liver from other conditions that can harm it. Avoiding excessive alcohol intake, liver-toxic medications, and getting vaccinated for hepatitis A and B are all recommended to protect the liver from further damage.

Bariatric surgery may be recommended for those with a BMI over 35, or with a BMI of 30 and living with T2DM. Bariatric surgery has been shown to reverse MASH in up to 85% of the patients within a year after surgery.  Lastly, for those with advanced scarring of the liver that has led to end stage liver disease, liver transplant is the final treatment option. As stated above, unless we make significant improvements in our typical diet and exercise habits, more and more Americans will require liver transplants for this preventable condition.

Summary

MASLD is a very common condition that is caused by a combination of calorie excess, inflammatory foods, and a sedentary lifestyle. The good news is that we can take control of this disease with weight loss, eating a WFPB diet, incorporating intermittent fasting, and exercising. If you or someone you know has MASLD, I suggest working with a Lifestyle Medicine practitioner to help get you on the right path to reverse your disease. Remember, with the right tools and motivation, our health is largely in our control.

 

Originally published by the National Health Association. 

 

About the Author

Jeffrey Pierce, MD specializes in weight management, diabetes, cardiovascular disease, hypertension, cholesterol management, fatty liver disease, cancer prevention, hormonal health and healthy pregnancies, plant-based nutrition, autoimmune disorders, depression and anxiety, digestive health, and dementia prevention. He practices telemedicine at Love.Life Telehealth and speaks Spanish.

Dr. Pierce believes that with the right information and motivation, people can get to the root cause of their illnesses and heal themselves.

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