Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by the accumulation of fat in the liver of individuals who consume minimal or no alcohol. It is strongly associated with metabolic disorders such as obesity, type 2 diabetes, dyslipidemia, and arterial hypertension. With its global prevalence steadily rising, now affecting over 30% of the adult population worldwide and growing annually at a rate of 0.7%, NAFLD has evolved into a complex, diverse, and dynamic ailment. Notably, around 10-15% of NAFLD patients progress to liver fibrosis, and NAFLD stands as a significant risk factor for liver cancer, ranking third in the list of cancer-related deaths according to the latest Globocan report.
Obesity emerges as a significant contributor to NAFLD, with individuals classified as obese being 3.5 times more likely to develop the condition. The shared pathophysiological pathways between these two conditions underpin this association. Moreover, dietary choices play a crucial role in the onset and progression of liver damage and other health-related issues associated with NAFLD. Diets rich in saturated fatty acids, found in ultra-processed foods, full-fat dairy products, red meat, and those utilizing coconut and palm oils, flood the liver with fatty acids, exacerbating liver damage while also promoting adipose tissue hypertrophy, systemic inflammation, and dysbiosis.
Research spanning from 1997 to 2016 in a US cohort highlighted the elevated risks associated with obesity and NAFLD. These risks include cirrhosis and its complications, cardiovascular events, as well as neoplasms beyond the liver, notably gynecological and gastrointestinal tumors. Conversely, lifestyle modifications such as a low-fat hypocaloric diet coupled with exercise, leading to a 10% reduction in body weight, facilitate the resolution of steatosis, inflammation, and regression of fibrosis in NAFLD patients.
Despite its growing prevalence and adverse effects, NAFLD remains an overlooked issue, largely due to a lack of awareness and education among both the public and healthcare professionals. A European primary care record study in 2018 underscored the under-diagnosis and under-reporting of NAFLD, indicating inadequate awareness among primary care physicians and limited resource allocation. A cross-sectional study of 108 primary care clinicians in Australia revealed a similar underappreciation of NAFLD and underestimation of its prevalence. This deficiency is further perpetuated by the absence of globally accepted, evidence-based dietary guidelines for NAFLD prevention. Remarkably, NAFLD remains absent from international and national guidelines concerning obesity and type 2 diabetes, as well as the World Health Organization’s obesity complications webpage. This oversight results in suboptimal management of liver-related complications in individuals with obesity and diabetes. Promoting NAFLD prevention, with a particular emphasis on nutrition and adopting a healthy lifestyle, is crucial to transforming this landscape and enhancing health outcomes, especially for those at risk of NAFLD due to obesity, type 2 diabetes, dyslipidemia, or arterial hypertension.
Dietary Modifications and Lifestyle Changes Hold the Key
Preventing NAFLD hinges on the adoption of a healthy lifestyle that incorporates dietary changes and moderate physical activity. This applies not only to those at risk or already afflicted with NAFLD but extends to the broader population as well. National and international clinical practice guidelines from hepatology, diabetes, and obesity societies worldwide recommend the implementation of lifestyle modifications for managing NAFLD.
Dietary recommendations to prevent NAFLD emphasize calorie reduction and the avoidance of processed and ultra-processed foods, saturated fats, high-fructose foods, and sugar-sweetened beverages. Ultra-processed foods, including items like crisps, mass-produced bread, breakfast cereals, biscuits, and soft drinks, are characterized by lower nutritional quality, higher energy density, and elevated levels of saturated fats, sugars, salt, and additives compared to fresh, healthier foods such as vegetables, fruits, legumes, nuts, vegetable oils (especially olive oil), fish, lean meats, and low-fat dairy products. Prospective cohort studies demonstrate a dose-response relationship between soft drink consumption and NAFLD, reinforcing the benefits of restricting sugar or fructose intake on liver fat, as evidenced in short-term clinical trials involving adolescent boys aged 11 to 16 years.
The global surge in ultra-processed food consumption poses a significant challenge to NAFLD prevention. Numerous studies link a higher share of ultra-processed foods in one’s diet to an increased risk of metabolic disorders and NAFLD. Furthermore, the consumption of ultra-processed foods correlates with calorie overconsumption and weight gain. Given that these items are often more affordable than fresh foods, their consumption is more prevalent among lower socioeconomic groups and, worryingly, is on the rise among children. An analysis of the 2017-18 National Health and Nutrition Examination Surveys in the US uncovered a lower risk of NAFLD among individuals with a college education, a demographic associated with either better diet quality or increased physical activity. Thus, educational and socioeconomic disparities are risk factors for NAFLD.
Diet plays a pivotal role not only in NAFLD development but also in its prevention and management. The Mediterranean diet, characterized by its rich composition of vegetables, fruits, legumes, nuts, whole grains, and fish, has been shown to reduce the risk of NAFLD while improving cardiometabolic health. This diet’s protective effects are attributed, in part, to the anti-inflammatory and antioxidant properties of its components, including polyphenols, flavonoids, carotenoids, and vitamins. Additionally, the Mediterranean diet features a high content of monounsaturated fatty acids, primarily found in olive oil, and a balanced intake of polyunsaturated fatty acids, prioritizing omega-3 sources (fatty fish, nuts, and flaxseed) over omega-6 polyunsaturated fatty acids (safflower, sunflower, soybean, and corn oils). These fatty acids modulate antioxidant signaling pathways and influence inflammatory processes. Moreover, the Mediterranean diet positively impacts the composition and diversity of gut microbiota, with animal studies underscoring the gut microbiota’s role in NAFLD pathogenesis.
Several evidence-based dietary approaches exist for weight loss and NAFLD prevention or management. In addition to the extensively studied Mediterranean diet, hypocaloric low-carbohydrate diets and low-fat diets have demonstrated efficacy in reducing liver fat and related biomarkers. Nevertheless, clinical trials assessing these diets are often limited by short-term follow-up and the use of surrogate biomarkers for NAFLD instead of liver biopsies. A definitive diagnosis remains essential, and long-term lifestyle intervention trials must account for various confounding factors.
Dietary patterns akin to the Mediterranean diet can be found worldwide. The Japanese diet, primarily centered around fish, vegetables, fruits, grains, legumes, coffee, and tea, has been associated with a reduced NAFLD risk. Similarly, the traditional Chinese diet, featuring a predominantly vegetarian menu of vegetables, rice, noodles, and a moderate intake of fish, poultry, and tofu, has shown a lower risk of NAFLD.