Short-term weight loss and hepatic triglyceride reduction: Evidence of a metabolic advantage with dietary carbohydrate restriction

Departments of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 03/2011; 93(5):1048-52. DOI: 10.3945/ajcn.110.007674
Source: PubMed


Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipogenesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction.
The aim of this study was to determine the effectiveness of 2 wk of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in subjects with NAFLD.
Eighteen NAFLD subjects (n = 5 men and 13 women) with a mean (±SD) age of 45 ± 12 y and a body mass index (in kg/m(2)) of 35 ± 7 consumed a carbohydrate-restricted (<20 g/d) or calorie-restricted (1200-1500 kcal/d) diet for 2 wk. Hepatic triglycerides were measured before and after intervention by magnetic resonance spectroscopy.
Mean (±SD) weight loss was similar between the groups (-4.0 ± 1.5 kg in the calorie-restricted group and -4.6 ± 1.5 kg in the carbohydrate-restricted group; P = 0.363). Liver triglycerides decreased significantly with weight loss (P < 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects (-55 ± 14%) than in calorie-restricted subjects (-28 ± 23%). Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = -0.606, P = 0.008), posttreatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = -0.797, P < 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P < 0.001).
Two weeks of dietary intervention (≈4.3% weight loss) reduced hepatic triglycerides by ≈42% in subjects with NAFLD; however, reductions were significantly greater with dietary carbohydrate restriction than with calorie restriction. This may have been due, in part, to enhanced hepatic and whole-body oxidation. This trial was registered at as NCT01262326.

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Available from: Santhosh Satapati, Oct 04, 2015
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    • "The macronutrient composition of the diet does not matter for the weight loss outcome, as long as weight loss is achieved, and this usually means that long-term compliance is key [52] [53]. Some data point towards an early beneficial effect of a carbohydrate-deficient diet on hepatic fat and insulin sensitivity [54] [55]. This might not make a difference however in the long-term when overall weight loss is achieved and insulin resistant sites other than the liver are studied [54]. "
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    ABSTRACT: Of all the aspects of non-alcoholic fatty liver disease (NAFLD), the slowest advances have occurred in the therapeutic field. Thirty-five years after its formal description and after 15 years of intense scrutiny from researchers worldwide, there is still no approved drug for the treatment of non-alcoholic steatohepatits (NASH). In the meantime, progress in the understanding of pathophysiology, diagnosis - both invasive and non-invasive, epidemiology and even natural history have been substantial or, at times, spectacular. In contrast, hepatitis C virus (HCV) therapy underwent constant improvement and even before the great acceleration of the past few years, patients were already being offered approved therapies that were increasingly more efficient. What then explains such a slow pace of therapeutic advances in NASH, and will this change in the near future? Here we will review commonly-held myths that have diverted attention from therapy of NASH, obstacles that have slowed down industrial development of drugs for this indication, and recent achievements that will create better conditions for drug development programs. We will also briefly review current knowledge of non-pharmacological and pharmacological management in this early era of NASH therapies. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 04/2015; 62(1S):S65-S75. DOI:10.1016/j.jhep.2015.02.041 · 11.34 Impact Factor
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    • "Additionally, mice fed this ketogenic diet exhibit a distinctive nonalcoholic fatty liver disease (NAFLD) profile including micro- and macrovesicular steatosis with hepatocellular injury and repair. The macronutrient composition that induces this histological signature is atypical for human NAFLD, which is commonly associated with increased carbohydrate intake and activated de novo lipogenesis [16,26,27]. In fact, low carbohydrate diets in humans may improve NAFLD [26–28]. "
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    PLoS ONE 08/2013; 8(8):e74806. DOI:10.1371/journal.pone.0074806 · 3.23 Impact Factor
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    ABSTRACT: Multiple dietary factors have been shown to increase high-density lipoprotein cholesterol (HDL-C) concentrations, and HDL-C has been inversely associated with coronary heart disease (CHD) risk. Replacement of dietary carbohydrate with polyunsaturated, monounsaturated and saturated fat has been associated with progressively greater increases in HDL-C (7-12%) in addition to other lipid changes. Added sugars, but not high glycemic carbohydrates, have been associated with decreased HDL-C. Alcohol consumption has been associated with increased HDL-C (9.2%) independent of changes in other measured lipids. Modest effects on HDL-C (~4-5%) among other lipid and non-lipid CHD risk factors have also been observed with weight loss by dieting, omega-3 fatty acids, and a Mediterranean diet pattern. The CHD benefit of increasing HDL-C is unclear given the inconsistent evidence from HDL-raising pharmacologic trials. Furthermore, pleiotropic effects of diet preclude attribution of CHD benefit specifically to HDL-C. Investigation into functional or other properties of HDL may lend further insight.
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