Cancer Prevention Program
PI: Mario Kratz, PhD
The United States and most western countries face an epidemic of obesity and associated cardiometabolic diseases. Although the etiology of these conditions is likely multi-factorial, there is strong evidence to suggest that diet composition and specifically the intake of different sugars might play a role in this epidemic. On a population level, the consumption of sugars has increased sharply in the United States since the 1970’s, and shows a temporal pattern similar to the increased rates of obesity. The two sugars most frequently ingested are sucrose and high fructose corn syrup (HFCS), both of which consist of ~50% glucose and ~50% fructose. Much of the sugar consumed today comes from sweetened beverages such as soda or fruit juices. This is of concern, as a large number of studies have shown that the consumption of these beverages predisposes individuals to excess calorie intake, weight gain, and an increased risk of obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). This seems to be the case for beverages with added sucrose or HFCS, such as soda, as well as fruit juices and fruit drinks that contain natural fruit sugar.
A recent study suggests that the fructose content of such beverages increases intra-abdominal fat mass and induces insulin resistance and dyslipidemia. Our preliminary data from an ongoing pilot study suggest an additional mechanism, namely that the fructose content of such beverages triggers low-grade chronic inflammation. This is intriguing in that low-grade chronic inflammation has been implicated in the etiology of both T2DM and CVD.
We will recruit 12 obese and 12 non-obese men and women who are free of chronic inflammatory or metabolic disease. In a double-blind, randomized cross-over design, each subject will complete three 8-day standardized dietary periods that will differ only in the type of sweetened beverage administered. Specifically, subjects will be asked to drink four servings of a beverage each day that is sweetened with glucose, fructose, or HFCS (55% fructose, 45% glucose). All solid food will be provided for each of the three 8-day diet periods, and will be consumed ad libitum. Subjects will be admitted to clinic on day one and day nine of each diet phase. During all clinic visits, we will collect fasting blood and a stool sample. At day nine clinic visits, we will perform the lactulose/mannitol-test to assess intestinal permeability. In a subset of subjects, we will also perform a subcutaneous abdominal adipose tissue biopsy on day nine. The proposed study has the potential to identify a dietary trigger of low-grade inflammation, a likely contributor to CVD and T2DM. The public health impact of this project might be considerable given that the consumption of fructose in the population is pervasive, and is modifiable on an individual as well as a population level.