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.
Section snippets
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.
References (46)
- et al.
Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma
Gastroenterology
(2002) Nonalcoholic steatohepatitis and the metabolic syndrome
Am J Med Sci
(2005)- et al.
Association of nonalcoholic fatty liver disease with insulin resistance
Am J Med
(1999) - et al.
Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis
J Hepatol
(2012) - et al.
Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments
J Am Coll Cardiol
(1996) - et al.
Prevention and control of type 2 diabetes by Mediterranean diet: a systematic review
Diabetes Res Clin Pract
(2010) - et al.
Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis
Am J Clin Nutr
(2010) - et al.
Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease
Am J Clin Nutr
(2007) - et al.
Food consumption patterns in the 1960s in seven countries
Am J Clin Nutr
(1989) - et al.
Can the Mediterranean diet lower HbA1c in type 2 diabetes? Results from a randomized cross-over study
Nutr Metab Cardiovasc Dis
(2011)
Does a Mediterranean diet reduce the mortality risk associated with diabetes: evidence from the Melbourne Collaborative Cohort Study
Nutr Metab Cardiovasc Dis
Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up
J Am Diet Assoc
Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values
Hepatology
Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States
Liver Transpl
Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures
Liver Int
Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population
Am J Physiol Endocrinol Metab
Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease
Hepatology
The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD
Hepatology
Associations between liver histology and severity of the metabolic syndrome in subjects with nonalcoholic fatty liver disease
Diabetes Care
Soft drink consumption linked with fatty liver in the absence of traditional risk factors
Can J Gastroenterol
A modified Mediterranean diet is associated with the greatest reduction in alanine aminotransferase levels in obese type 2 diabetes patients: results of a quasi-randomised controlled trial
Diabetologia
A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study
Diabetes Obes Metab
Adherence to Mediterranean diet and health status: meta-analysis
BMJ
Cited by (541)
Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial
2024, American Journal of Clinical NutritionAnthocyanins: Potential phytochemical candidates for the amelioration of non-alcoholic fatty liver disease
2024, Annales Pharmaceutiques FrancaisesNutrition and dietary restrictions in cancer prevention
2024, Biochimica et Biophysica Acta - Reviews on CancerAssociation between physical activity and diet quality of obese and non-obese MAFLD
2024, Nutrition, Metabolism and Cardiovascular Diseases