Spotlight on Kylie Kavanagh, DVM
Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates
Kavanagh K, Wylie AT, Tucker KL, Hamp TJ, Gharaibeh RZ, Fodor AA, Cullen JM. Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates. Am J Clin Nutr. 2013 Aug;98(2):349-57. doi: 10.3945/ajcn.112.057331
Significant controversy rages on regarding the causative role of dietary fructose in obesity and fatty liver diseases. Fructose is predominantly consumed as high fructose corn syrup, which differs from sugar in its sweetness, rate of absorption, and the insulin response stimulated from its consumption. Clinical trials indicate negative health consequences may only occur when fructose is consumed within a diet that has excess calories. Some animal studies suggest fructose impairs intestinal integrity, which then allows bacterial products to circulate. Clinical studies support fructose being uniquely bad for fatty liver diseases.
We assessed the effects of fructose in different monkey studies. We hypothesized that the fructose in the diet disrupted the intestinal barrier, and that bacterial products would circulate directly to the liver inciting inflammation prior to the accumulation of any excess fat. We first assessed non-human primates after chronic ad libitum access to high fructose diets (24% of calories [population average is ≈ 11% ;HFr) or a low fat, low fructose diet (CTL). Monkeys allowed ad libitum HFr developed fatty liver in contrast to CTL diets, and the extent of ectopic fat was related to duration of feeding. Diabetes incidence was also increased.
We then wanted to eliminate the possibility that excess calories were to blame for the liver disease. Ten middle-aged, weight-stable, fructose-naïve monkeys were stratified into HFr and CTL groups fed for only 6 weeks at caloric levels required to maintain weight stability. Monkeys consuming calorically controlled HFr showed dramatic increases in biomarkers of liver damage (serum biochemistry) and inflammation. The monkeys had higher endotoxemia measured as lipopolysaccheride levels in the portal circulation (LPS) and greater amounts of the binding protein for LPS in circulation (LBP-1).There was trend for greater hepatitis that was related to the amount of bacterial translocation, however overt HS did not develop. We examined the intestinal bacterial profile which did not change in this short period of time and thus is not likely to be the cause of the degraded mucosal barrier.
We conclude that even in the absence of weight gain, fructose rapidly causes liver damage that we suggest is secondary to endotoxemia and intestinal barrier dysfunction. Fatty liver relates to the duration of fructose consumption and total calories consumed, but develops in concert with low-grade hepatitis that is present even in those consuming a high fructose diet but are not overweight and consuming appropriate amount of calories. This has important implications for diseases that have inflammation as an underlying cause (diabetes, cardiovascular disease, immunological disorders) and re-emphasizes the importance of what we eat, and that all calories are not equal.