Article

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

ABSTRACT

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 clinicaltrials.gov as NCT01262326.

  • Source
    • "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]. "
    [Show abstract] [Hide abstract] 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.
    Preview · Article · Apr 2015 · Journal of Hepatology
  • Source
    • "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]. "
    [Show abstract] [Hide abstract] ABSTRACT: Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.
    Full-text · Article · Aug 2013 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Concomitant with the obesity epidemic, a fatty liver due to nonalcoholic causes has become the most common liver disorder. Nonalcoholic fatty liver disease (NAFLD) covers a range from benign steatosis to nonalcoholic steatohepatitis (NASH), which in turn may progress to cirrhosis. NAFLD predicts, independent of obesity, the metabolic syndrome and type 2 diabetes and can progress to cirrhosis. This review focuses on studies in humans addressing effects of dietary changes in NAFLD. Cross-sectionally, increased intake of fructose and simple sugars characterizes patients with NAFLD compared with weight-matched controls. Increased fructose intake is also associated with hepatic insulin resistance and fibrosis severity in NASH. Intake of saturated fat may also be increased in NAFLD. Dietary intervention studies have shown that liver volume and fat content changes significantly within a few days in response to caloric restriction or excess despite no or small changes in body weight. Weight loss by bariatric surgery decreases liver fat and inflammation but effects on fibrosis are uncertain. Hepatic insulin sensitivity generally changes in parallel with changes in liver fat content in NAFLD. Human data are limited regarding effects of isocaloric changes in diet composition on liver fat content. Maintenance of normal body weight and avoidance of intake of excess lipogenic simple sugars would seem beneficial for prevention of NAFLD and its metabolic consequences.
    Preview · Article · Nov 2010
Show more