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 overweight/obese (BMI between 25.0 and 40 kg/m2) and 12
normal weight (BMI between 20 and 24.9 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.

Inclusion Criteria:

- Age: 18-65 years;

- BMI 20-40 kg/m2;

- Weight stable to within 10 pounds for 6 months prior to entering the study, and at
their lifetime maximum weight (or within 30 pounds of it; excluding pregnancy);

- Ability to be admitted for ~30 minutes on three occasions, and ~6 hours on three
occasions to the FHCRC Prevention Center;

- Ability to provide informed written consent;

- Willingness to consume only food and beverages provided by the Human Nutrition
Laboratory of the FHCRC Prevention Center for three periods of 8 days each.

Exclusion Criteria:

- Presence or history of chronic inflammatory, autoimmune or metabolic diseases;

- Presence of phenylketonuria, hereditary fructose intolerance, fructose malabsorption,
or malabsorption syndromes;

- Abuse of alcohol (>2 drinks per day), smoking, or use of recreational drugs;

- Current or recent (within three months) intake of medications likely to interfere
with study endpoints (insulin, antidiabetics, β-blockers, anabolic steroids,
glucocorticosteroids, daily high-dose non-steroidal anti-inflammatory drugs,
warfarin, antibiotics, probiotics);

- Presence of anemia, recent (within 2 months) history of anemia;

- Anyone not willing or able to eat the provided food;

- Current or recent (within 12 months) pregnancy or breastfeeding.