Colon Inflammation, Diet Modification, Iron Malabsorption, Obesity
Conditions
Brief summary
Obesity is an independent risk factor for colorectal cancer (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In conditions when dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift in the gut microbiota to more pro-inflammatory strains. However, treatments designed to reduce luminal, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity is associated with inflammation-induced, hepcidin-mediated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity. The investigator's objective is to conduct a crossover controlled feeding trial of: 1) a Typical American diet with high heme/non-heme iron, 2) a Typical American diet with low iron, and 3) a Mediterranean diet with high non heme iron and examine effects on colonic and systemic inflammation and the gut microbiome.
Interventions
OTHERHigh heme iron diet
A Typical American diet with high heme/non-heme iron (18 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.
OTHERLow iron diet
A Typical American diet with low heme/non-heme iron (8 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.
OTHERPlant-based high non-heme iron diet
A plant-based diet with high non-heme iron (18 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.
Sponsors
American Cancer Society, Inc.
University of Illinois at Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
1. Typical American Diet with high heme/non-heme iron (16 mg) 2. Typical American Diet with low iron (8 mg) 3. Plant-based Diet with high non-heme iron (16 mg)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Self-identify as Hispanic, African American, or Caucasian. * Meet body mass index (BMI \> = 30.0 kg/m2) and C-reactive protein (CRP) criteria (\> 2.0 mg/dl) * Post-menopausal (no menstruation in the past 12 months) * Weight stable (\< 3% weight change in the past 3 months) * Non-smoker * No major medical problems * Have a working phone * No known allergies, intolerance, medical, secular or religious dietary restrictions
Exclusion criteria
* Chronic constipation (less than three stools per week for several months) * History or intestinal cancer, inflammatory bowel disease, celiac disease, or malabsorptive bariatric surgery * Previous intestinal surgery * H pylori infection or taking H2 blockers (e.g., Zantac, Pepcid) /antacids (e.g., Rolaids) more than 3 times per week * Significant blood loss or blood donation in past 3 months * Active gastrointestinal bleed * Any surgery in the past 3 months * Hemochromatosis * Sickle cell disease * Hereditary polyposis * Rheumatoid arthritis * Type I or Type II diabetes * Smoker * Antibiotic use in the past 2 months * Excessive alcohol consumption \[\> 2 standard alcoholic drinks (12 ounces of beer, 5 ounces of wine, 1 shot of hard liquor) per day\] * Aspirin use \>81 mg/day OR \>325 mg/every other day * Regularly taking probiotics, fiber supplements, Orlistat (over the counter brand name: Alli), or steroids (inhaled or oral)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in colonic inflammation | Baseline and post-diet (day 22) for each of the three 3-week diets | Fecal calprotectin, a proxy for colon tissue inflammation, will be measured from stool an calprotectin immunoassay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in systemic inflammation | Baseline and post-diet (day 22) for each of the three 3-week diets | Circulating C-reactive protein, Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-a) will be measured from serum using immunoassays. |
| Change in stool microbial community profile at the phylum and genus level | Baseline and post-diet (day 22) for each of the three 3-week diets | Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for polymerase chain reactions targeting the V4 variable regions of the 16S ribosomal ribonucleic acid gene. Amplicons generated from polymerase chain reaction will be run on the Illumina MiSeq sequencing platform to profile microbial communities at the phylum and genus level. |
| Change in serum hepcidin | Baseline and post-diet (day 22) for each of the three 3-week diets | Serum hepcidin will be measured using an immunoassay |
Countries
United States
Outcome results
None listed