Fructose is mainly consumed with added
sugars (
sucrose and
high fructose corn syrup), and represents up to 10% of total energy intake in the US and in several European countries. This
hexose is essentially metabolized in splanchnic tissues, where it is converted into
glucose,
glycogen,
lactate, and, to a minor extent,
fatty acids. In animal models, high
fructose diets cause the development of
obesity,
insulin resistance,
diabetes mellitus, and
dyslipidemia. Ectopic
lipid deposition in the liver is an early occurrence upon
fructose exposure, and is tightly linked to hepatic
insulin resistance. In humans, there is strong evidence, based on several intervention trials, that
fructose overfeeding increases fasting and postprandial plasma
triglyceride concentrations, which are related to stimulation of hepatic de novo lipogenesis and VLDL-TG secretion, together with decreased VLDL-TG clearance. However, in contrast to animal models,
fructose intakes as high as 200 g/day in humans only modestly decreases hepatic
insulin sensitivity, and has no effect on no whole body (muscle)
insulin sensitivity. A possible explanation may be that
insulin resistance and dysglycemia develop mostly in presence of sustained
fructose exposures associated with changes in body composition. Such effects are observed with high daily
fructose intakes, and there is no solid evidence that
fructose, when consumed in moderate amounts, has deleterious effects. There is only limited information regarding the effects of
fructose on intrahepatic
lipid concentrations. In animal models, high
fructose diets clearly stimulate hepatic de novo lipogenesis and cause hepatic steatosis. In addition, some observations suggest that
fructose may trigger hepatic
inflammation and stimulate the development of hepatic
fibrosis. This raises the possibility that
fructose may promote the progression of
non-alcoholic fatty liver disease to its more severe forms, i.e. non-
alcoholic steatohepatitis and
cirrhosis. In humans, a short-term
fructose overfeeding stimulates de novo lipogenesis and significantly increases intrahepatic fat concentration, without however reaching the proportion encountered in non-
alcoholic fatty liver diseases. Whether consumption of lower amounts of
fructose over prolonged periods may contribute to the pathogenesis of
NAFLD has not been convincingly documented in epidemiological studies and remains to be further assessed.