Abstract
Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting.Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements.Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05.Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was −9.59 ± 2.87% in the VLCKD group and −1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were −32.0 cm2 for VLCKD group and −12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005).Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.
Highlights
More important than overall body weight, in overweight individuals and patients with obesity, the distribution of fat is strongly associated with the metabolic disturbances that lead to comorbidities [1, 2]
In a proportion of these patients, the presence of chronic hepatic inflammation leads to more advanced forms of disease, i.e., non-alcoholic steatohepatitis and fibrosis, with the potential of liver failure and increased risk of hepatocellular carcinoma [8]
The first-line treatment of non-alcoholic fatty liver disease (NAFLD) consists of weight loss and lifestyle modifications such as physical exercise and dietary regimens based on calorie restriction [9, 10]
Summary
More important than overall body weight, in overweight individuals and patients with obesity, the distribution of fat is strongly associated with the metabolic disturbances that lead to comorbidities [1, 2]. Visceral adipose tissue (VAT) accumulation is associated with increased peripheral insulin resistance and often a systemic low-grade chronic inflammatory state, known as lipoinflammation [3,4,5]. Liver fat accumulation, in this context called non-alcoholic fatty liver disease (NAFLD), is associated with peripheral insulin resistance and a local inflammatory response, resulting in prolonged hepatocellular injury [6]. Very LC ketogenic diet (VLCKD) has been proposed as an effective weight loss intervention potentially suitable for the treatment of NAFLD and for the reduction of VAT, which may be beneficial to reduce the state of insulin resistance and end-organ damage [16,17,18]. The treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting
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