The Effect of Fructose vs. Glucose Beverages on Low-Grade Systemic Inflammation

Thesis (Ph.D.)--University of Washington, 2016-04

The epidemics of obesity and related metabolic diseases are a serious health concern worldwide. These conditions are multifactorial in origin and develop over time; however one factor that continues to be implicated in the development of obesity is the intake of sugar-sweetened beverages (SSBs). Consumption of SSBs is also associated with type 2 diabetes (T2DM) and cardiovascular disease (CVD), both independently and through the increased risk conferred by excess body fat. It is not entirely clear though which mechanism(s) SSB consumption might contribute to excess body weight and an increased risk of T2DM and CVD. However, low-grade chronic inflammation underlies both of these diseases and might be a potential link between the SSB-metabolic disease association. It is also unclear whether it is the fructose, rather than the glucose, component of the sweetener that might be responsible for the ill effects associated with SSB consumption. To address these questions, we conducted a randomized, controlled, double-blind crossover design dietary intervention trial to test the effects of beverages sweetened with fructose, high fructose corn syrup (55% fructose, 45% glucose), or glucose on total energy intake and low-grade chronic inflammation. We recruited 12 overweight or obese and 12 normal weight men and women who were free of chronic inflammatory or metabolic disease. Each subject completed each of three 8-day dietary periods during which they consumed four servings per day of beverages sweetened with either fructose, HFCS, or glucose in addition to standardized solid foods that were consumed ad libitum. Total energy intake during the fructose, HFCS, and glucose phases was 116% ± 14%, 116% ± 16%, and 116% ± 16% of the subject’s estimated total energy requirements (p=0.880). In terms of inflammation, fasting plasma concentrations of C-Reactive Protein (CRP) (p=0.457) and interleukin-6 (p=0.933) did not differ significantly at the end of the 3 diet periods. Nor did we detect a consistent differential effect of the diets on measures of adipose tissue inflammation. However, adiponectin gene expression in adipose tissue (p=0.005) was significantly lower following the glucose and HFCS phases compared to the fructose phase. We also did not detect consistent evidence of a differential impact of fructose vs. glucose on measures of intestinal permeability (lactulose-mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Our results indicate that in normal weight to obese adults, consumption of SSBs promotes an increase in overall energy intake over 8 days, which would be expected to result in weight gain over the longer term. Because total energy intake was elevated to the same degree above subjects’ estimated energy requirements, we conclude that fructose, HFCS, and glucose do not differ in terms of their ability to regulate energy intake when consumed in the form of an SSB. Instead, it appears that these sugars consumed in liquid form fail to adequately reduce energy intake from solid foods thereby leading to weight gain. Furthermore, despite this increase in total energy intake, we observed no evidence that consumption of these SSBs differentially affected markers of systemic inflammation, adipose tissue inflammation, or intestinal permeability. Taken together, the increased risk for cardiometabolic disease associated with SSB intake is most likely mediated by adiposity which is the result of excess energy intake over time promoted by incomplete compensation for calories from sugars consumed in liquid form.