Diet and Systemic Inflammation
Condition: Low-grade Chronic Inflammation; Intestinal Permeability; Type 2 Diabetes Mellitus; Cardiovascular Disease; Obesity
MeSH terms: Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation
Study type: Interventional

Summary: 
      People with chronic low-grade inflammation have a higher risk for certain diseases such as
      cardiovascular disease or type 2 diabetes. While it is known that obese people are more
      likely to show signs of low-grade inflammation than lean individuals, it is unclear what
      causes this inflammation. In the proposed study, the investigators will examine whether the
      sugar fructose, when consumed in a sweetened beverage, triggers low-grade inflammation in
      healthy men and women compared with other caloric sweeteners.
    

Detailed description: 
      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.
    

Intervention name(s): Fructose-sweetened beverages; Glucose-sweetened beverages; High-fructose corn syrup-sweetened beverages
Intervention type(s): Other; Other; Other
Intervention description(s): In addition to consuming a standardized diet, subjects will be asked to consume 4 servings per day of a fructose-sweetened beverage for 8 days. The amount of fructose consumed will be 25% of the subject's estimated daily calorie requirement.; In addition to consuming a standardized diet, subjects will be asked to consume 4 servings per day of a glucose-sweetened beverage for 8 days. The amount of glucose consumed will be 25% of the subject's estimated daily calorie requirement.; In addition to consuming a standardized diet, subjects will be asked to consume 4 servings per day of a high-fructose corn syrup-sweetened beverage for 8 days. The amount of high-fructose corn syrup consumed will be 25% of the subject's estimated daily calorie requirement.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Inflammation; Intestinal permeability; Type 2 diabetes mellitus; Cardiovascular disease; Obesity; Sweetened beverages; Sugar; Fructose; Glucose; High-fructose corn syrup