Non-alcoholic fatty liver disease (NAFLD) is a condition of hepatic steatosis in the absence of excessive alcohol consumption [1]. The spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which can lead to fibrosis and finally hepatocellular carcinoma [2]. As a consequence of the obesity epidemic, this liver pathology (NAFLD) is emerging as an important public health issue and is the most common cause of chronic liver disease in Western countries, with a prevalence of about 20–30% the general adult population [1]. The pathogenesis of NAFLD is multifactorial and triggered by environmental factors such as unbalanced diets or/and overnutrition as well as by sedentary lifestyles [1]. Concerning the diagnosis of NAFLD, liver biopsy is considered the “gold standard” of steatosis, fibrosis, and cirrhosis. However, it is rarely performed because it is an invasive procedure with a significant degree of sampling error [2]. Thus, investigators are focusing on the design and application of non-invasive liver damage scores for the diagnosis and management of liver disease [3].

Nowadays, the treatment of NAFLD is based on lifestyle modifications, such as changes in dietary patterns [4]. Thus, weight loss, exercise, and healthy eating habits are the main strategies to reduce the incidence and prevalence of NAFLD, although the metabolic mechanisms are still poorly understood [5]. Previous studies have evidenced a role of weight loss on NAFLD management [6]. However, further investigations to elucidate the interplay between specific dietary components and fatty liver combined with weight loss are necessary [7], as the number of randomized controlled studies conducted in this area remain scarce [8]. In this context, the aim of this study was to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in obese individuals with features of metabolic syndrome after six months of follow-up and to assess the role of fiber content (quality and quantity) in metabolic outcomes.

The average age of participants was 49 ± 9 years, of which 50.5% were women. At the beginning of the study, no significant differences were observed between dietary groups. After 6 months, the mean of body weight loss was 7.9 ± 4.8 kg and 9.7 ± 5.4 kg in the AHA and RESMENA dietary groups, respectively (Table 1). Both nutritional treatments significantly reduced BMI, CI, WC, total and android fat mass, as well as IDF (International Diabetes Federation) of metabolic syndrome after 6 months of nutritional intervention. Likewise, the cardiometabolic risk factors (Triglycerides/glucose ratio (TyG index), waist-to-height ratio, % diabetes, % hypertension) showed significant reductions with both diets. However, the changes (baseline vs. 6 months) in the reported variables did not differ between the RESMENA and AHA dietary strategies, with the exception of high-density lipoprotein cholesterol (HDL-c) levels, which were significantly increased in AHA compared to the RESMENA group at the end of study (Table 1). Regarding dietary intake, the analysis of weighed dietary records showed that total fiber intake was higher during the intervention period than the intake before starting the nutritional program (baseline) in both dietary groups, while participants from the RESMENA dietary group showed a significantly higher intake of insoluble fiber after six months (Table 1).

In relation to liver health, a significant decrease was observed in ALT, GGT, and M30 levels as well as NAFLD_LF score, FLI, HSI, VAI and BAAT scores with both dietary strategies (AHA and RESMENA) after 6 months of follow-up (Table 2). Given that transaminases showed significant difference at baseline between dietary groups, the analyses concerning transaminases were adjusted by ALT and AST values at baseline. AST values only showed a significant reduction in the RESMENA group. In contrast, fragments of M65 only obtained significant improvements in the AHA group. In addition, the BARD score did not show relevant improvements either dietary group. It is important to note that the changes (baseline vs. 6 months) in the reported variables were not different between dietary strategies (Table 2). Thus, both dietary strategies were equally effective regarding liver status. Consequently and based on previous investigations [20,21], both dietary groups were merged for the analysis of fiber consumption because they produced similar outcomes for all relevant variables and markers.

We analyzed the potential role of dietary macronutrients (carbohydrates, fat, and proteins) on liver status (FLI), and no significant associations were observed: carbohydrates (β = 0.011; p = 0.751; R = 0.0017), lipids (β = 0.126; p = 0.084; R = 0.049), saturated fatty acids (β = −0.017; p = 0.431, R = 0.009), monounsaturated fatty acids (β = −0.031, p =0.390, R = 0.001), polyunsaturated fatty acids (β = −0.198; p = 0.209; R = 0.208), omega-3 fatty acids (β = −0.930; p = 0.288; R = 0.051), and proteins β = −0.66; p = 0.480; R = 0.008). In order to analyze the specific role of fiber on liver health, the predictors of liver damage according to high and low (<50th percentile vs. ≥50th percentile) consumption of different types of fiber were assessed at the end of the study (Table 3). Insoluble fiber and fiber from fruits showed interesting results, since participants with higher consumption of these types of fiber reduced markers of liver status associated with fatty liver. It is important to highlight that a high consumption of insoluble fiber resulted in improvements in FLI, HSI, NAFLD_LFS, while significant improvements in GGT and transaminases (AST and ALT) were observed as a result of fruit fiber consumption.

Reinforcing this idea, a linear regression analysis was carried out to assess the influence of changes in the consumption of different types of fiber in changes in the FLI. Fiber from fruits demonstrated a positive relationship (R-adjusted: 0.049; p = 0.048; Figure 2). The effect of each fiber group was also analyzed: vegetables (β = 0.287; p = 0.138, R = 0.037), cereals (β = −0.295; p = 0.608, R = 0.004), insoluble (β = 0.491; p = 0.159, R = 0.033), soluble (β = −0.472; p = 0.545, R = 0.002). The linear regression model was adjusted by age, total energy (kcal), and physical activity (metabolic equivalent of the task, MET) changes (Table 4). When these variables were jointly considered, the predictors of the model explained up to 11.6% of the variation of changes in the FLI (adjusted R² = 0.116; P_model < 0.026).

The design of new dietary strategies for NAFLD prevention and for the reduction of causal factors is needed [22]. Increasing rates of obesity and MS are having an important impact on the rising incidence and prevalence of liver diseases such as NAFLD; thus, well-designed dietary interventions are necessary [22]. In this context, the present study compared the effects of two energy-restricted dietary strategies on anthropometric, biochemical, and non-invasive markers of liver status in obese individuals with MS features after 6 months of follow-up. Regarding weight loss, body composition, IDF criteria, and cardiometabolic risk, both dietary regimens had equal effect on most metabolic markers. HDL-c concentrations were increased in both dietary groups, but only reached significance in the AHA group. This outcome might be expected, since the AHA diet is specifically based on the AHA guidelines [23], which focus on cardiovascular care and therefore on lipid profile management. Interestingly, the RESMENA diet had a positive effect on body weight by reducing android fat mass—a body region which has been commonly associated with hepatic steatosis [24]. On the other hand, current research has focused on identifying biomarkers to predict NASH or NAFLD [25,26]. In this context, Bedogni et al. (2006) designed a simple scoring system named FLI which includes TG, GGT, BMI, and WC, and it is easily calculated [12]. FLI was developed for the prediction of fatty liver disease and shows a good area under the curve of 0.84 [26]. The accuracy of FLI in comparison with the ultrasonography method for detection and quantification of hepatic steatosis has been validated in several countries [12,27]. Furthermore, previous studies [17,28,29,30] have demonstrated and validated other non-invasive markers of liver status that were used in this study (CK18-fragments, HSI, VAI, BARD and BAAT score, NAFLD_LFS) in addition to GGT and transaminases. By employing these non-invasive biomarkers and scores to assess liver status, we showed that energy-restriction within both dietary patterns produced similar and significant beneficial effects on liver status, as shown in other dietary studies [31]. The BARD score did not indicate improvements after either of the nutritional interventions, which might be due to the fact that the BARD score is used to exclude advanced fibrosis in NAFLD, and other authors have noted that its sensitivity is low [30,32]. Considering the global results presented in this study, particularly improvements in android fat and liver status, we propose RESMENA as a novel dietary strategy to be explored in subjects with obesity and fatty liver.

Energy restriction is a key factor for the management of NAFLD [33]. Indeed, the American Association for the Study of Liver Diseases (AASLD) recommends a loss of at least 3–5% of body weight to improve steatosis and a greater weight loss (up to 10%) to improve necroinflammation [34]. Other investigations have also demonstrated that weight loss interventions are effective in reducing NAFLD severity [6]. However, not only is the amount of energy a key component to be considered, but also the quality of the diet. In relation to fatty acids, diets rich in saturated fat and cholesterol and low in polyunsaturated fat have been associated with NASH [6], while omega-3 fatty acids have been proposed for the treatment of NAFLD or NASH [34,35]. In fact, the Mediterranean diet can reduce liver fat even in the absence of weight loss, and is the most recommended dietary pattern for NAFLD [36,37]. The Mediterranean diet is characterized by reduced carbohydrate intake (especially sugars and refined carbohydrates), and an increased intake of monounsaturated and omega-3 fatty acids. In the present study, both dietary patterns (AHA and RESMENA) included the same energy restriction (−30% E) and were designed taking into account the effect of a different distribution of macronutrients as well as the beneficial role of specific dietary components. In the present work, energy restriction was a key factor involved in the improvement of liver health; however, other dietary components—particularly fiber—may also be involved in the management of steatosis. Several studies have reported that fiber may play an important role in obesity and related diseases such as insulin resistance and liver diseases [38]. To our knowledge, this is the first study evaluating the association between types of fiber and liver status in subjects with obesity and metabolic syndrome following an energy-restricted diet. Although adherence to the dietary strategies was similar, resulting in no differences in macronutrient distribution, a variety of hepatic damage markers were lower in those individuals who had a higher fiber intake. In particular, fiber derived from fruit had a beneficial impact, suggesting that not only energy restriction but also other dietary components positively influence liver health.

In this context, Zelber-Sagi et al., 2011 suggested that the consumption of diets higher in fiber could have a preventive role in hepatic disease [39]. Fiber contains components which are not classified as essential nutrients, but could be important mediators in human health. In fact, a pilot study of seven patients with NASH reported a significant decrease in aspartate aminotransferase levels compared to a placebo after 8 weeks of supplementation with oligofructose at 16 g/day [40]. Another study providing 10 g/day of psyllium fiber to 12 patients over the course of three months found a normalization of transaminases and GGT levels [41]. Dietary fiber can be divided in two groups—soluble and insoluble—based on physical, chemical, and functional characteristics [42]. Insoluble fibers are insoluble in water and gastric fluids. Soluble fiber dissolves in water and can resist gastrointestinal enzymatic digestion; therefore, soluble fiber can pass the small intestine to reach the colon where it can be fermented by intestinal microbiota [43]. This suggests that both soluble and insoluble fibers could have different roles in gastrointestinal health [44]. For this reason, different fiber types were investigated in the present study. Interestingly, we found two important fiber groups that could have a major effect on the reduction of predictors of liver heath: insoluble fiber and fiber from fruits. Although increasing dietary fiber has a favorable effect on body weight [45], and several studies suggest that fermentation activities of the gut microbiota may be a possible contributor to NAFLD [46], data regarding the effect of different types of fiber remain unclear [47]. Therefore, current research is warranted to determine the optimal dietary fibers for prevention and reduction of fatty liver disease accompanying obesity.

A limitation of this study is that NAFLD was evaluated using non-invasive markers instead of imaging techniques and/or liver biopsies. However, the design of the current trial is based on validated non-invasive and affordable markers, which makes them an optimal form of diagnosis in clinical practice. In relation to improvements in liver status, other components occurring in the dietary pattern such us antioxidants, vitamins, fatty acids, energy restriction etc., may also explain the observed benefits on liver health, as they could work synergistically with fiber. In addition, comparisons involving means or regression analyses showed the same trend, although the statistical outcomes were more confirmatory when adjusted by age, total energy, and MET, which is in agreement with the expectations. The discordance between the results obtained with different analysis merits attention before concluding that all observed results are due to fruit fiber. On the other hand, one of the main strengths of the present research is that it is a randomized controlled trial, considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a nutritional intervention. Moreover, the fact that every dietary pattern has been personally designed for each patient, taking into account sex, height, initial body weight, and physical activity, should also be highlighted. Finally, it is important to point out that a well-recognized healthy dietary pattern (AHA) was used as reference, which demonstrates that the positive results obtained with the RESMENA diet are of significance.

These data support that the RESMENA diet may be a valid strategy to counteract MS features and liver damage accompanying obesity. In addition, this study reveals that the type of dietary fiber differentially impacts liver health status in obese subjects under energy restriction. However, these results should be interpreted with caution, since other components contained in fruits, in addition to fruit fiber, could be involved in the observed benefits.