Nutrition & Nonalcoholic Fatty Liver Disease
By Carrie Dennett, MPH, RDN
Vol. 25 No. 1 P. 30
Dietitians have a central role in prevention and treatment.
Fatty liver used to be a condition that people associated with heavy alcohol use, but it’s substantially less common than nonalcoholic fatty liver disease (NAFLD). Both conditions involve excess fat buildup in the liver—known as steatosis—but NAFLD is the most common liver disease and the leading cause of liver-related mortality globally. It’s estimated to affect 25% to 30% of people, but a 2021 systematic review and meta-analysis found that the global prevalence was more than 32% and continuing to grow at an alarming rate.1-3 Currently, nutrition and lifestyle interventions are the frontline treatments.
There are two types of NAFLD: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Patients with NAFL have steatosis but little to no inflammation, and typically don’t develop liver damage or complications—unless they progress to NASH. NASH involves steatosis as well as inflammation and liver damage, which can cause fibrosis or liver scarring.4 Fibrosis stage 1 (F1) is minimal scarring, but if scarring progresses to F4, it’s known as cirrhosis, in which the liver is permanently damaged and functionally impaired. F2 is considered a crucial point for therapeutic intervention to prevent liver cancer or end-stage liver disease.5
While NAFLD generally is characterized by progression from NAFL to NASH, it’s unclear which patients will progress and at what rate. Disease progression also may not be linear but rather have periods of disease progression and regression.6 Genetic variations can increase NAFLD severity and raise the risk of progression to cirrhosis.7
Who’s Developing NAFLD?
In the United States, experts estimate that about 24% of US adults have NAFLD, but only 1.5% to 6.5% of US adults have NASH.1 Prevalence rates in North America and Europe aren’t increasing as fast as they are in Asia, which is experiencing increased urbanization with an upwardly mobile economic drift that’s accompanied by a more sedentary lifestyle and increased consumption of calorie-dense foods.8
NAFLD can affect people of any age, race, or ethnicity. However, people are more likely to develop NAFLD as they get older, and it’s most common among Hispanics, followed by non-Hispanic whites and Asian Americans—including those of East Asian and South Asian descent—and is less common among non-Hispanic Blacks.4,9 As with many diseases, the causes of NAFLD are multifactorial. Diet, lifestyle, and certain health conditions can play a causal role, but so can genetics—which may explain why prevalence is higher in certain racial and ethnic groups.10
Men are more likely to develop NAFLD than women, although data from the National Health and Nutrition Examination Survey (NHANES) suggest that women who were younger in age when they first gave birth have an increased risk of developing NAFLD later in life.3,11 Compared with women who were aged 30 to 32 when they first gave birth (the reference group), women who were younger than 18 had a 54% higher risk, women aged 18 to 20 had a 60% higher risk, those aged 21 to 23 had a 40% greater risk, and those aged 24 to 26 had a 33% greater risk.11
Symptoms and Causes
Experts believe the cause of NAFLD may center around the “adipose tissue expandability” hypothesis. The hypothesis proposes that when individuals consume more calories than they use, their subcutaneous adipose tissue (SAT) expands. But once their SAT cells’ capacity to store energy is exceeded and individuals reach their “personal fat threshold”—which can vary widely from person to person—the body starts depositing fat in visceral adipose tissue, skeletal muscle, and organs such as the liver, pancreas, and heart.12 When the liver’s capacity for secreting or oxidizing fatty acids is surpassed, fat starts to accumulate, filling liver cells with large fat droplets, which can damage or scar the cells.13
Several health conditions may increase the risk of accumulating fat in the liver and developing NAFLD, including the following:
• insulin resistance or type 2 diabetes;
• metabolic syndrome, or one or more of its traits (high blood pressure, high triglycerides, low HDL cholesterol, high blood sugar, large waist circumference);
• high total or LDL cholesterol; and
• a BMI in the “overweight” or “obese” range, especially among people who gain weight around their abdomen rather than around their hips or shoulders.
Research suggests there’s a bidirectional aspect to these associations, as patients with NAFLD have elevated risk of developing CVD, type 2 diabetes, and the conditions associated with metabolic syndrome.14
A 2022 study used data from the UK Biobank to explore whether BMI and waist circumference were causally associated with NAFLD. The authors found that higher waist circumference was causally linked to liver fat accumulation and NAFLD, regardless of BMI, but that BMI itself isn’t linked once waist circumference is factored in. The authors also concluded that the effect of abdominal adiposity on type 2 diabetes risk was substantially larger than the effect of liver fat on type 2 diabetes risk.15
NAFLD is typically considered a silent disease. Even someone with NASH who has developed cirrhosis may not exhibit symptoms. When symptoms are present, they’re usually limited to fatigue—which could be attributed to many other factors—or discomfort in the upper right side of the abdomen.
Diagnosis and Treatment
To diagnose NAFLD, health care providers use a patient’s medical history—specifically, a history of health conditions that increase NAFLD risk—a physical exam and blood tests. Increased levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase are suggestive of NAFLD. Blood samples also may be used to calculate Fibrosis-4 or aspartate aminotransferase to platelet ratio index to identify whether advanced liver fibrosis is present.4
Imaging tests such as ultrasound, CT, and MRI can’t diagnose NAFLD by themselves but may be used as part of the diagnostic process. Fibrosis, if present, may show up as nodules in the liver. A liver biopsy can confirm a NASH diagnosis and determine severity, but generally, this isn’t recommended unless there’s suspicion of NASH with advanced fibrosis, cirrhosis, or other forms of advanced liver disease.4
Currently, there are no drug therapies for NAFLD, although potential medications are undergoing clinical trials. While complications of cirrhosis may be treated pharmaceutically or surgically, dietary and lifestyle interventions remain the first-line strategy in managing NAFLD and slowing or preventing its progression.
Gradual weight loss of 3% to 5% of total body weight by creating a calorie deficit often is recommended to improve steatosis and prevent NAFL from progressing to NASH, but a weight loss of 7% to 10% may be needed to improve fibrosis and prevent NASH from becoming more severe.4,16 However, interventions of this type may not be appropriate for many patients, including those with a history of eating disorders. And, as with intentional weight loss for any reason, there’s a high likelihood of weight regain.17
Physical activity has been shown to regulate liver fat—including counterbalancing the adverse effects of overfeeding—independent of weight loss or overall adiposity, if the activity is habitual. Physical activity intervention studies have found that observed reductions in liver fat levels during the intervention aren’t sustained if participants return to inactivity post intervention, and other research has observed that habitual inactivity is associated with higher liver fat content.12 So, what activity dose is needed? Data suggest that patients who maintain more than 150 minutes per week of physical activity or who increase their activity level by more than 60 minutes per week have a pronounced decrease in liver enzymes, independent of weight loss.4
Role of Nutrition in NAFLD
To prevent or manage NAFLD, physical activity paired with a healthful diet are the primary options, pending successful clinical drug trials. Research has evaluated overall dietary patterns as well as macro- and micronutrients, although most micronutrient research has been conducted in animals.
An analysis of data from the 2017–2018 cycle of the NHANES for 3,900 US adults aged 18 or older found that a healthful, plant-based diet was associated with lower odds of having NAFLD, an association that was stronger in non-Hispanic whites.18 Healthful plant-based diets generally are defined as having a higher intake of fruits, vegetables, whole grains, nuts, legumes, tea, and coffee and a lower intake of refined grains, high-sugar foods, and animal-based foods.
One benefit of a healthful plant-based diet is that it contains components that support healthy gut microbiota. Researchers have observed differences in the gut microbiota between patients with NAFLD and those without, but it’s unclear whether this is cause or consequence because most research on this relationship has been conducted on animals.19
Results published in 2022 from a one-year follow up of 5,867 participants aged 55 to 75 from the PREDIMED-Plus trial in Spain, all with BMIs between 27 and 40 kg/m2, and all with metabolic syndrome, found that higher consumption of ultraprocessed foods and beverages—as defined by the NOVA classification system—was “directly and robustly” associated with higher levels of NAFLD-related biomarkers.20 Examples of NOVA-defined ultraprocessed foods include soft drinks, sweets and pastries, packaged snack foods, processed meats, preprepared frozen meals, dairy-based desserts, and “instant” products. Low adherence to a Mediterranean diet explained about one-half of the observed association, saturated and trans fats were responsible for 17% to 21% of the association, fiber explained 15% of the association, and glycemic load (GL) explained 11%. Liver health markers improved as consumption of unprocessed or minimally processed foods increased during follow up. PREDIMED-Plus is a six-year randomized clinical trial assessing the efficacy of a calorie-restricted Mediterranean diet, physical activity promotion, and behavioral support on weight loss and primary prevention of CVD in this population.
Multiple studies have found benefits from Mediterranean-type diets in managing NAFLD. One 2018 review of cross-sectional and longitudinal studies found that these diets were associated with lower incidence or severity of NAFLD and, when used as dietary intervention, may improve liver enzyme levels or liver fat independently of BMI.19 However, the authors emphasized that available studies at that time were small and few in number, and more research was needed. They also noted that the Mediterranean diet is rich in polyunsaturated fats as well as nutrients and phytochemicals with antioxidant properties, which may explain the potential promise for NAFLD prevention or management.
Isocaloric feeding studies have observed that diets rich in saturated fatty acids tend to cause fat accumulation in the liver, while diets rich in mono- or polyunsaturated fatty acids decrease fat accumulation. 13 Multiple studies also have found that, in general, NAFLD patients consume fewer omega-3 fatty acids from fish, seeds, walnuts, or other sources.7 And a recent systematic review and meta-analysis found that omega-3 supplementation of more than 3 g per day can help reduce liver fat and liver enzymes.21
Another systematic review of 15 randomized controlled trials evaluating the effects of low-fat diets vs low-carb diets on NAFLD found a lack of consensus, in part due to differing definitions of “low-fat” and “low-carb” among the various trials—definitions ranged anywhere from 8% to 45% carbs for low-carb diets and 15% to 30% for low-fat diets. Both types of diets decreased liver enzymes when calories also were reduced, with a more marked improvement observed with low-fat diets.22
It appears that the type of carbohydrate matters more than a precise percentage of carbohydrates in the diet—for general health and for NAFLD alike—and there has been particular focus on intake of added fructose and the glycemic index (GI) and GL of the diet as it relates to NAFLD risk. A 2020 systematic review and meta-analysis published in the British Journal of Nutrition analyzed the influence of all foods on NAFLD development and found that added fructose intake in the form of sucrose or high-fructose corn syrup was positively associated with the likelihood of having NAFLD.23 A 2021 review in Nutrients concluded that fructose metabolism is implicated in the development and progression of NAFLD through multiple pathways.24 Notably, one cross-sectional study from Finland found that higher fructose intake was associated with lower risk of NAFLD—but most of the fructose consumed in this population came from fruit, not sugar-sweetened beverages.25
Evidence supporting a low-glycemic diet for prevention or management of NAFLD isn’t as robust as that in support of reducing added sugars.12 However, a crossover trial in which eight healthy men, average age 20, consumed either a high- or low-GI diet for seven days found an increase in liver fat with the high-GI diet, followed by a decrease with the low-GI diet.26 A small intervention study involving children and adolescents with NAFLD found that modest reductions in fructose, GI, and GL resulted in improvements in plasma markers of liver dysfunction.27 Overall, research has failed to reach consistent conclusions on associations between the likelihood of NAFLD and intake of vegetables, fruit, legumes, whole grains, or refined grains.23 Authors of a 2019 review say that large-scale, randomized controlled studies using long-term low-GI and GL diets with equivalent calorie intake to that of control groups are needed to draw conclusions about effects on NAFLD.28
Another analysis of NHANES data from 2001–2016 found that having adequate blood levels of vitamin D was significantly associated with decreased mortality from CVD and all other causes in patients with NAFLD.29 However, the relationship between vitamin D and NAFLD is complex and unclear, and it may be that variations in genes related to vitamin D metabolism are what affect NAFLD risk.30
In the Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With NASH Study, researchers found that a daily 800 IU dose of natural vitamin E from food sources—not synthetic vitamin E—improved NASH. The drug pioglitazone performed no better than placebo.31 The Treatment of Nonalcoholic Fatty Liver Disease in Children trial, which randomized 173 patients aged 8 to 17 to receive 400 IU of the natural form of vitamin E, metformin, or placebo, found that vitamin E improved the most severe form of fatty liver disease in some children, although neither vitamin E nor metformin performed better than placebo in reaching the primary study outcome of sustainably reducing alanine aminotransferase levels.32 However, the American Association for the Study of Liver Diseases currently recommends using only vitamin E in patients without diabetes who have biopsy-proven NASH.4
For dietitians working with clients and patients with NAFLD, or who have high risk of developing it, the most evidence-based nutrition and lifestyle interventions at this time include helping patients do the following7,16:
• Reduce dietary fat to 30% of daily calories, replacing saturated fats and trans fats in the diet with unsaturated fats from nuts, seeds, avocados, olives, and olive oil, and especially with omega-3 fatty acids from fish, walnuts, flax, and chia seeds. Multiple studies have found that nut intake is inversely associated with the likelihood of having NAFLD.23
• Limit carbohydrates to 50% of daily calories, and emphasize low-glycemic, high-fiber carbohydrates such as vegetables, whole grains, legumes, and most fruits.
• Avoid foods and beverages that contain large amounts of added sugars, especially fructose.
• Increase protein to 20% of daily calories from plant sources, fish, and lean, unprocessed animal sources.
• Reduce red and processed meats.
• Minimize intake of alcohol, which can further damage the liver.
• Develop a sustainable physical activity routine of at least 150 minutes per week.
While Mediterranean-style dietary patterns, as well as vegetarian/vegan dietary patterns, and the DASH diet are consistent with these individual recommendations, other cultural dietary patterns could be adjusted to meet client preferences.
— Carrie Dennett, MPH, RDN, is the nutrition columnist for The Seattle Times, owner of Nutrition By Carrie, and author of Healthy for Your Life: A Holistic Guide to Optimal Wellness.
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