Introduction
The incidence of non-alcoholic fatty liver disease (NAFLD) has been rising globally, linked to increasing obesity rates [1]. Excessive caloric intake and sedentary lifestyles are major contributors to NAFLD, which, if not properly treated, can evolve into a more severe condition, such as non-alcoholic steatohepatitis (NASH), characterized by necroinflammation and faster fibrosis [2]. The only therapeutic approaches are lifestyle modification and weight loss, which consistently reduce liver steatosis and fibrosis [3,4,5]. However, emerging evidence underscores the importance of dietary composition related to NAFLD. The Mediterranean diet (MD) is considered the diet of choice for treating NAFLD as recommended by EASL–EASD–EASO guidelines [6,7,8]. Moreover, several studies have demonstrated that certain components of the diet can either promote or inhibit the progression of NAFLD. Foods rich in refined carbohydrates, fructose, saturated fatty acids, and trans fatty acids have been associated with liver steatosis and inflammation, exacerbating NAFLD [9,10]. Conversely, monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, and dietary fibers have been found to inhibit liver fat accumulation by reducing the process of de novo hepatic lipogenesis [11,12,13]. The role of monounsaturated fat intake in NAFLD is still controversial, with conflicting results in different studies. Some studies suggest a beneficial effect of foods rich in monounsaturated fats, like olive oil, on reducing liver fat and inflammation [14,15,16]. In contrast, others report a potentially detrimental effect that might be due to an impairment of hepatic mitochondrial fatty acid oxidation that is influenced by energy metabolism and body composition [17,18]. The purpose of this study was to assess whether an increase in extra virgin olive oil consumption is associated with a lower prevalence of NAFLD with a possible differential effect by body weight, independently from other food intake, and multiple sociodemographic and metabolic risk factors in a prospective cohort living in a Mediterranean country.
The MICOL Study
The MICOL Study is a population-based prospective cohort originally recruited to investigate cholelithiasis epidemiology. Subjects were randomly drawn from the electoral list of Castellana Grotte in 1985 and followed up until 2016, with four repeated assessments about every 8 years. In 2005–2006, a young random sample of subjects (PANEL Study) aged 30–50 years was added to balance the cohort aging. Extensive data on sociodemographic factors, anthropometric measurements, health status, and lifestyle were collected through questionnaires, with medical history confirmed through verbal interviews. Additionally, participants completed a Food Frequency Questionnaire, underwent liver ultrasound examinations, and provided biological samples. The baseline was set at the third cohort assessment (2005–2006), encompassing a heterogeneous population with a wide age range. A total of 2436 subjects, with 52% men aged between 30 and 89 years, were included in the analysis, with an NAFLD prevalence of 33%. All participants provided signed informed consent. Full details of the study have been previously published [19,20].
Outcome, Clinical, and Dietary Data
Liver steatosis was assessed using ultrasound imaging (Hitachi H21 Vision, Hitachi Medical Corporation, Tokyo, Japan) with a 3.5 MHz transducer. The presence or absence of hyperechogenic liver parenchyma was used to determine the presence of steatosis [6,21]. NAFLD was defined as the presence of steatosis from unknown causes. Therefore, subjects with secondary causes of steatosis were excluded from the study, including those with fatty liver disease due to excessive ethanol consumption (AFLD definition > 30 g/day for men and >20 g/day for women), the use of steatogenic drugs, viral hepatitis B based on an ELISA serum test for surface antigen (HBsAg), and viral hepatitis C based on an antibody (anti-HCV) search confirmed by the Strip Immunoblot Assay RIBA HCV 2.0. Covariates were selected from known risk factors. Sociodemographic information, medical history, family history of chronic diseases, smoking status, and dietary habits were obtained from questionnaires administered during the baseline assessment and follow-up visits. Anthropometric measurements were taken using standardized procedures. Weight was measured using the SECA® body composition analyzer (Seca Deutschland, Hamburg Germany), to the nearest 0.1 kg, and height was measured using a wall-mounted stadiometer. Waist and hip circumference were measured with the patient’s feet joined, abdominal muscles relaxed, and arms hanging down the body. Body mass index (BMI) was calculated as weight divided by height squared (kg/m2). Blood samples were collected after at least 12 h of fasting, and routine biochemical assays were performed using standard laboratory methods. Measurements included total bilirubin, glucose, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Participants’ dietary intake was assessed using the European Prospective Investigation into Cancer and Nutrition (EPIC) food frequency questionnaire (FFQ). This questionnaire asked participants to estimate the frequency and quantity of specific foods consumed, reported in times per week, month, or year. The FFQ also included information on the average quantity of each food consumed per day. To aid in estimating portion sizes, participants were provided with photos showing examples of different portion sizes (small, medium, and large) for various foods. Total energy intake was calculated by summing the kilocalories from each food item. Food items were grouped into eight MD components, similarly to Trichopoulou et al. [22], without alcohol intake. These components, expressed in grams per day, included extra virgin olive oil, legumes, cereals (including bread and potatoes), fruits, vegetables, fish, meat and meat products, and milk and dairy products. All procedures were conducted in accordance with the ethical standards of the institutional research committee (IRCCS Saverio de Bellis Research) and followed the principles outlined in the 1964 Helsinki Declaration. The MICOL study received ethical committee approval (DDG-CE-347/1984, DDG-CE-453/1991, DDG-CE-589/2004, and DDG-CE-782/2013) for the ethical conduct of the research.
Discussion
The results of this prospective study, involving 2436 middle-aged and older adults, suggest that a higher intake of EVOO is linked to a reduced prevalence of NAFLD and an improved metabolic profile, specifically in individuals who are overweight or obese. However, these benefits were not observed in individuals with a normal weight, where EVOO intake was associated with significant increases in levels of liver transaminases and triglycerides. Our findings also show that the beneficial effect of olive oil is not mediated by other factors such as age, sex, diet, smoking, and various metabolic and sociodemographic variables. Based on these findings, it is recommended that individuals with a BMI higher than 25 include olive oil in their diet as part of the management of NAFLD. A high-calorie diet rich in saturated fats, refined carbohydrates, fructose, and red meat increases the risk of NAFLD [9,24]. Consistently, in our study, we found that a high intake of refined cereals was associated with an increased risk of NAFLD. Conversely, an energy-restricted Mediterranean-like diet consisting of extra virgin olive oil, legumes, vegetables, nuts, fish and whole grains helps prevent NAFLD [6,7,25,26,27,28]. However, not all studies have reported consistent findings [29,30]. Our data suggest that a high intake of EVOO prevents fatty liver, and interestingly, the risk of the disease seems to reach a maximum decrease with an 85 g/day intake of EVOO, equivalent to seven tablespoons/day. This aligns with the findings of the PREDIMED trial, which showed that supplementing the Mediterranean diet with at least four tablespoons of olive oil per day reduced hepatic steatosis from 33% to 8.8% in overweight and obese older adults at high cardiovascular risk [27]. Another randomized trial found that consuming 20 g of olive oil per day led to a lower fatty liver grade in overweight/obese NAFLD patients compared to those consuming the same amount of sunflower oil, independent of cardiometabolic risk factors [31]. Monounsaturated fatty acids, the primary component of EVOO, have been observed to have both protective and detrimental effects on liver steatosis and inflammation in animal studies and cell cultures [18,32]. The impact of these fatty acids on liver health appears to be complex and context-dependent. Our study suggests that this inconsistency may be influenced, in part, by body composition and related metabolic adaptations. Interestingly, in a prospective cohort study involving 3882 elderly Caucasians, increased consumption of animal proteins was initially associated with a higher risk of NAFLD. However, when adjusting for BMI, the statistical significance was lost [33]. Additionally, the rich concentration of polyphenols found in EVOO may play a role in its potential benefits against steatosis. These phytochemicals possess properties that can help reduce oxidative stress, inflammation, and promote liver health, thereby contributing to the potential antisteatotic effects of EVOO [32,34,35,36]. Our study has some limitations. Firstly, the cross-sectional design of the analysis prevents us from drawing definitive conclusions, as in randomized controlled trials with controlled effects. Secondly, there is a possibility of reverse causality, as patients at high risk may have already modified their diet. However, when adjusting for lifestyle characteristics and risk factors, the inverse association between EVOO and NAFLD remained significant. It is important to note that dietary assessment in epidemiological studies can be affected by recall bias and misreporting, which can attenuate the associations. We conducted a sensitivity analysis, which yielded similar results to the initial findings, and in the specific obese category, the association was even stronger.
Conclusions
In conclusion, our study highlights the potential benefits of consuming olive oil in the context of NAFLD and emphasizes the importance of considering individual weight status in dietary interventions. The impact of olive oil on NAFLD appears to be primarily influenced by adiposity, independent of other factors. These findings have important implications for public health, considering the increasing prevalence of NAFLD. Additional randomized trials are required to understand the mechanisms and establish optimal EVOO intake for NAFLD prevention and management, accounting for individual weight status.
Read all at: Tedesco, C.C.; Bonfiglio, C.; Notarnicola, M.; Rendina, M.; Castellaneta, A.; Di Leo, A.; Giannelli, G.; Fontana, L. High Extra Virgin Olive Oil Consumption Is Linked to a Lower Prevalence of NAFLD with a Prominent Effect in Obese Subjects: Results from the MICOL Study. Nutrients 2023, 15, 4673. https://doi.org/10.3390/nu15214673