Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie-matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials.

Many commonly known antioxidants, from probucol to vitamin E, are fat-soluble and have been shown to be most effective when administered with meals. Following meal consumption, these compounds are incorporated into intestinal lipoproteins, known as chylomicrons, and secreted into the circulation. These lipid-carrying particles are responsible for the transport of newly absorbed dietary fat for delivery to peripheral tissues. In the bloodstream, chylomicrons interact with heparin-releasable lipases common known as lipoprotein lipase and hepatic triglyceride lipase. Bothe lipases are anchored along the endothelial wall via heparan sulfate proteoglycans and have triglycerides as their preferred substrate. During this process, as dietary triglycerides are hydrolyzed and transported across the endothelium, we hypothesize that antioxidants carried in chylomicrons would be delivered directly to the arterial wall where they would be most effective in quenching reactive oxygen species generated by activated macrophages. Thus, the metabolism of postprandial lipoproteins is a key process in the defense against oxidative stress and may provide the path for effective antioxidant management. In this chapter, we will review the evidence in support of the hypothesis that postprandial lipoproteins may contribute to the delivery of fat-soluble antioxidants that are administered orally.