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Diet and Systemic Inflammation

18 Years
65 Years
Open (Enrolling)
Low-grade Chronic Inflammation, Intestinal Permeability, Type 2 Diabetes Mellitus, Cardiovascular Disease, Obesity

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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

Inclusion Criteria:

- Age: 18-65 years;

- Normal weight group (n=12): BMI 20-25 kg/m2;

- Obese group (n=12): BMI 30-40 kg/m2;

- Weight stable to within 10 pounds for 6 months prior to entering the study, and at
their lifetime maximum weight (or within 10 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, statins, β-blockers, anabolic steroids,
glucocorticosteroids, non-steroidal anti-inflammatory drugs, warfarin, antibiotics,

- Presence of anemia, recent (2 months) blood donation, or recent (2 months)
participation in another study that involves blood draws;

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

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

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Outcome Measure:

Fasting plasma C-reactive protein

Outcome Description:

The concentration of C-reactive protein in fasting plasma will be measured by high-sensitivity assay at the beginning (day 1) and end (day 9) of each 8-day dietary period.

Outcome Time Frame:

Beginning (day 1) and end (day 9) of each diet period.

Safety Issue:


Principal Investigator

Mario Kratz, MS, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center


United States: Institutional Review Board

Study ID:

NHLBI R21 HL108257



Start Date:

October 2011

Completion Date:

December 2013

Related Keywords:

  • Low-grade Chronic Inflammation
  • Intestinal Permeability
  • Type 2 Diabetes Mellitus
  • Cardiovascular Disease
  • Obesity
  • Inflammation
  • Intestinal permeability
  • Type 2 diabetes mellitus
  • Cardiovascular disease
  • Obesity
  • Sweetened beverages
  • Sugar
  • Fructose
  • Glucose
  • High-fructose corn syrup
  • Cardiovascular Diseases
  • Diabetes Mellitus
  • Diabetes Mellitus, Type 2
  • Inflammation
  • Obesity



Fred Hutchinson Cancer Research CenterSeattle, Washington  98109