Effects of a Western-type Diet on Colorectal Inflammation

• Circulating endotoxin levels [ Time Frame: visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention ] [ Designated as safety issue: No ]
• Expression profiles of pro- and anti-inflammatory genes in rectosigmoid biopsies [ Time Frame: visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention ] [ Designated as safety issue: No ]
• Gut permeability [ Time Frame: visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention ] [ Designated as safety issue: No ]
• Inflammatory cytokines in the colorectal mucosa and serum [ Time Frame: visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention ] [ Designated as safety issue: No ]
• Luminal and adherent gut microbiota [ Time Frame: visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention ] [ Designated as safety issue: No ]
• Fecal calprotectin levels in the stool samples [ Time Frame: visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention ] [ Designated as safety issue: No ]

This study will look at the inflammatory (changes usually associated with infection/injury to the body) and bowel permeability (bowel's ability to allow contents to enter the body) effects of a Western-style diet (high fat and low in calcium) and a prudent-style diet (low fat and high in calcium) on the colon (large bowel). This study may provide information to prevent colorectal cancer in a high-risk population

Hypothesis: Compared to a prudent-style diet, does a western-style diet increase colorectal inflammation thereby increasing gut permeability and causing increased endotoxins and markers of systemic inflammation.

This is a single blind crossover study. Subjects will be randomized to begin on either a WD or a PD for 30 + 3 days. Once that dietary intervention is complete, subjects will have a four (4) week wash-out period and then will be placed on the other dietary intervention for 30 + 3 days. The following study measures are performed during both the dietary intervention study periods. All the baseline tests will be repeated at the end of each dietary intervention period.

• Dietary Supplement: Western style diet (high fat and low in calcium)
  Subjects will be randomized to begin on either a WD or a PD for 30 + 3 days. Once that dietary intervention is complete, subjects will have a four (4) week wash-out period and then will be placed on the other dietary intervention for 30 + 3 days
• Dietary Supplement: Prudent-style diet (low fat and high in calcium)
  Subjects will be randomized to begin on either a WD or a PD for 30 + 3 days. Once that dietary intervention is complete, subjects will have a four (4) week wash-out period and then will be placed on the other dietary intervention for 30 + 3 days

• Active Comparator: Western style diet
  high-fat, low-calcium diet
  Intervention: Dietary Supplement: Western style diet (high fat and low in calcium)
• Active Comparator: Prudent diet
  low-fat, calcium-sufficient diet
  Intervention: Dietary Supplement: Prudent-style diet (low fat and high in calcium)

Inclusion Criteria:

• Healthy male or post-menopausal ( 2 years after menopause or stopping HRT)healthy female subjects
• Age between 50 and 72 years
• At increased risk for colorectal cancer (this includes those have had a colorectal adenoma excised, or have a first or second degree relative with colorectal neoplasia).

Exclusion Criteria:

• Personal history of cancer other than non-melanoma skin cancer within the past 10 years
• History of hereditary non-polyposis colon cancer
• Intestinal malabsorption, inflammatory bowel disease
• Prior gastrointestinal surgery other than appendectomy or surgery of the esophagus
• Any excess bleeding or coagulation disorders
• Subjects taking anti-coagulants, sterol-binding resins, NSAIDs other than aspirin, < 600mg per day, other study medications, or other multiple medications that might, in the view of the study physicians, alter colonic function or inflammation
• Total cholesterol greater than 240mg/dl, triglycerides > 600mg, LDL-C > 175
• Subjects with a history of coronary artery disease
• HIV positive subjects
• Subjects taking antibiotics, anti-diabetes, hormone replacement therapy, oral, transplanted or injected contraceptives (thyroid hormone therapy is permitted as long as the subject is euthyroid)
• Currently participating in other clinical studies or completed participation in other clinical studies within the last 30 days