Obesity, Iron Regulation and Colorectal Cancer Risk
Condition: Colon Inflammation; Iron Malabsorption; Obesity; Diet Modification
MeSH terms: Malabsorption Syndromes; Obesity; Inflammation
Study type: Interventional

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.
    


Intervention name(s): High heme iron diet; Low iron diet; Plant-based high non-heme iron diet
Intervention type(s): Other; Other; Other
Intervention description(s): 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.; 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.; 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.
Intervention MeSH terms: Iron
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Typical American Diet with "high" heme/non-heme iron (16 mg)
Typical American Diet with "low" iron (8 mg)
Plant-based Diet with "high" non-heme iron (16 mg)
Masking: None (Open Label)
Primary purpose: Other