Trial Information

Diet and Systemic Inflammation

The objective of this proposal is to investigate whether fructose-sweetened beverages
trigger low-grade systemic inflammation in healthy men and women. Low-grade systemic
inflammation, specifically elevated plasma concentrations of C-reactive protein (CRP), is a
risk factor for cardiovascular disease (CVD). While it is known that obesity is associated
with inflammation, the causes of low-grade inflammation in humans are not well understood.
In a pilot study, the consumption of large amounts of fructose-, but not glucose- or
aspartame-sweetened beverages potently induced low-grade inflammation in healthy, lean,
young men and women in as little as 8 days. The investigators propose to extend these
findings by (a) enrolling a greater number of subjects, (b) enrolling obese as well as
non-obese subjects, and (c) including a beverage that is sweetened with high fructose corn
syrup (HFCS). HFCS is one of the primary sugars consumed in the United States, and a major
source of dietary fructose. Our primary specific aim is to assess whether the consumption of
fructose- or HFCS-sweetened beverages promotes systemic low-grade inflammation, as measured
by plasma concentrations of CRP and IL-6. The investigators hypothesize that plasma CRP and
IL-6 concentrations will be elevated after consumption of fructose-containing beverages
(fructose and HFCS) when compared to a glucose-sweetened beverage. Our secondary specific
aim is to assess whether the consumption of fructose- or HFCS-sweetened beverages lowers
plasma adiponectin concentrations. Specifically, the investigators hypothesize that total
and high molecular weight (HMW)-adiponectin concentrations in fasting plasma will be lower
after subjects have consumed the fructose- or HFCS-sweetened beverages, compared to a
glucose-sweetened beverage.

The investigators will recruit 12 obese (BMI between 30 and 40 kg/m2) and 12 non-obese (BMI
between 20 and 25 kg/m2) 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. Following each dietary period, the investigators will collect fasting blood to
measure markers of systemic inflammation and plasma concentrations of total and
HMW-adiponectin. We will also assess changes in adipose tissue inflammation and intestinal
permeability as potential mechanisms by which fructose-sweetened beverages may trigger
systemic inflammation. This study has the potential to identify a dietary trigger of
low-grade inflammation, a likely contributor to CVD and metabolic diseases. 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.