Research ArticleThe Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease
Introduction
Non-alcoholic fatty liver disease (NAFLD) is an umbrella term encompassing simple steatosis, as well as non-alcoholic steatohepatitis (NASH). NASH can lead to cirrhosis, liver failure, and hepatocellular carcinoma in up to 20% of cases, and NASH-associated liver disease is increasing rapidly as an indication for liver transplantation in the United States [1], [2].
Excess hepatic fat deposition is a hallmark of NAFLD. Thirty percent of adults in developed countries are suggested to have excess fat accumulation in the liver [3], [4], and this figure can be as high as 50% amongst individuals with type 2 diabetes mellitus (DM), and 80% in the centrally obese subjects [5], [6]. A defect in insulin sensitivity is the key pathogenic feature of type 2 and NAFLD. In fact, individuals with NAFLD almost invariably have at least one other clinical feature of insulin resistance: elevated serum concentrations of triglycerides (TG), lowered serum concentrations of high density lipoprotein cholesterol (HDL-C), impaired glucose tolerance, central adiposity, and hypertension. This constellation of features is termed the metabolic syndrome (MetSy) and provides an estimate of cardiovascular disease (CVD) risk, but can also indicate the degree of insulin resistance. Although not formally recognised as part of the MetSy, NAFLD is closely related to with this syndrome [5].
Studies suggest that the severity of insulin resistance is correlated with the likelihood of progression from benign steatosis to NASH and the development of fibrosis [6], [7], [8], [9]. Therefore, therapies that improve insulin sensitivity are also of benefit in NAFLD. Furthermore, as the prevalence of NAFLD, obesity, and type 2 DM are all associated with an increased caloric intake and a sedentary lifestyle [10], lifestyle modification remains the therapy of choice for NAFLD, particularly given the size of the affected population.
There are few studies examining optimal dietary strategies for NAFLD. The ideal diet would lead to a reduction of steatosis and an improvement in insulin sensitivity. A previous dietary comparison suggested that the Mediterranean diet (MD), a diet high in monounsaturated fatty acids (MUFA) was the only one of three diets to reduce serum alanine aminotransferase (ALT) levels [11]. A recent meta-analysis demonstrated that omega-3 fatty acids, found in the MD, were beneficial in reducing hepatic steatosis [12].
The MD has been extensively investigated in terms of benefits in relation to reduction of cardiovascular risk [13] and improvement in insulin sensitivity [14], [15], [16], [17], [18], [19], however, studies specifically examining its effect on NAFLD have not been performed. We hypothesized that in individuals with NAFLD an MD intervention would improve insulin sensitivity and reduce steatosis to a greater extent than the currently recommended diet.
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Subjects
The criteria for inclusion in the study were: evidence of steatosis both on ultrasonography and histology (>grade 1 steatosis [33% steatotic hepatocytes]) [20]; presence of MetSy, as defined by the presence of at least three clinical features using National Cholesterol Education Program Adult treatment Panel III (NCEP ATP III) criteria [21]; as well as consumption of no more than seven/ten standard alcoholic drinks per week for women/men. Subjects with type 1/2 diabetes were excluded due to
Results
Fourteen subjects were recruited. One subject was ineligible for the study due to insufficient histological steatosis, and a second subject was excluded after intravenous access difficulties at the first clamp study. Therefore, a total of 24 diets were completed by 12 subjects. There were no differences in physical activity at the commencement of the two diet periods, as recorded by the pedometer for each subject.
The order of the diets for each subject was randomised. The baseline
Discussion
Although NAFLD is rapidly increasing in prevalence and is now a significant cause of chronic liver disease [3], [34], there is a lack of therapeutic options that address both the progression of liver fibrosis and the associated insulin resistance.
Several medications including vitamin E have recently been shown to be ineffective in preventing fibrosis [35], and while other pharmaceutical therapies, such as thiazoladinediones, have had some success in improving liver histology, they have
Financial support
M Ryan was supported by an NHMRC Neil Hamilton Fairley Fellowship. This project was also supported by an Early Career Researcher Grant from the University of Melbourne.
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
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