Can Restricting Fructose Intake Reduce Fatty Liver Disease in Children?
Reducing dietary fructose for as little as 9 days decreases liver fat, visceral fat, and de novo lipogenesis and increases insulin sensitivity, secretion, and clearance in children with obesity and metabolic syndrome, researchers report in the September issue of Gastroenterology. These findings support efforts to reduce sugar consumption.
Consumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. The prevalence of NAFLD in children has more than doubled in the last 20 years. Hepatic fat contributes to development of visceral adipose tissue and other metabolic derangements that lead to type 2 diabetes, dyslipidemia, and cardiovascular disease.
However, it is not clear which specific dietary components in early life contribute to the buildup of fat in the liver. De novo lipogenesis (conversion of fructose to fat in liver) is increased in patients with NAFLD, and might be modified to reduce liver fat.
Fructose is a ubiquitous monosaccharide and a major substrate for de novo lipogenesis (see figure). Fructose occurs naturally only in fruits and some vegetables, but it is added to processed foods and drinks. It goes by almost 60 different names, including high fructose corn syrup and fruit juice concentrate. It has been estimated that 16% of calories in childrens’ diets come from added sugars—well above the recommended level of 5% to 10%. Fructose induces hepatic steatosis in animals.
Jean-Marc Schwarz et al performed a clinical trial to investigate the effects of reducing fructose intake for 9 days in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/day). They measured the effects of isocaloric fructose restriction on de novo lipogenesis, liver fat, visceral fat, subcutaneous fat, and insulin kinetics.
In their study, 41 children, 9−18 years old, had all meals provided for 9 days. The meals had the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. The authors measured metabolic factors before and after fructose restriction. They measured liver fat, visceral fat, and subcutaneous fat by magnetic resonance spectroscopy and imaging.
Schwarz et al found that on day 10 of the diet, liver fat decreased from a median 7.2% at baseline to 3.8%, and visceral fat decreased from 123 cm3 at baseline to 110 cm3. Liver fat decreased in all but 1 of the 38 participants for whom paired data were available. The decrease in liver fat after adjustment for weight change remained statistically significant.
Among the 9 participants who did not lose weight, liver fat still decreased from 9.7% at baseline to 6.3%, and visceral fat decreased from 124 cm3 to 91 cm3.
De novo lipogenesis decreased significantly after 9 days of fructose restriction; the de novo lipogenesis area under the curve value on day 10 decreased from 68% at baseline to 26% after the diet, in childen with low or high baseline levels of liver fat.
Insulin secretion during fasting and in response to an oral glucose tolerance test decreased significantly in children with low and high baseline levels of liver fat. Insulin clearance rate increased significantly only in the group with high liver fat.
Schwarz et al noted that these outcome measures occurred regardless of baseline liver fat content, sex, or race/ethnicity.
They propose that the effects of fructose are specific to liver fat and mediated by de novo lipogenesis. Schwarz et al previously showed that in healthy adults on isocaloric diets, de novo lipogenesis and liver fat were higher during high-fructose feeding compared with low-fructose feeding.
The authors conclude that their findings support fructose restriction as an approach to combat NAFLD and improve insulin kinetics. They say that their findings provide evidence to support public health efforts to reduce sugar consumption.
In an editorial that accompanies the article, Miriam B. Vos and Michael I. Goran say that it will be important to determine whether the effects of fructose reduction are sustained past 9 days. Also, since this study showed the effects of reducing fructose to 4% of total calories, is there a safe level of fructose for a child with NAFLD? Is it possible to make reduce dietary fructose by this amount in the real world?
Vos and Goran state that it is important for physicians, nutritionists, schools, and parents to find ways to reduce fructose in the diets of children and patients with NAFLD.