Calcium and 1,25-dihydroxyvitamin D3 modulate genes of immune and inflammatory pathways in the human colon: a human crossover trial.

Healthy adults at modestly increased risk of colorectal neoplasia were studied in two randomized crossover trials at Rockefeller University in New York. Participants consumed a controlled Western-style diet and underwent 4-week intervention periods with washout; rectosigmoid mucosal biopsy gene expression was the primary endpoint.

Two 4-week crossover interventions were tested against a Western-style diet: oral calcium carbonate 2 g/day, and oral 1,25-dihydroxyvitamin D3 0.5 mg/day (given as 0.25 mg before the morning and evening meals) with or without calcium carbonate 2 g/day. Each period was separated by a 4-week washout.

The main finding was a biologic interaction in which 1,25-dihydroxyvitamin D3 strongly increased immune response, inflammation, extracellular matrix, and cell-adhesion gene expression in colorectal mucosa, while adding calcium largely reversed these changes toward baseline. Calcium alone produced only modest gene-expression effects. Urine calcium output increased with calcium supplementation in both studies, whereas serum calcium and phosphorus did not change significantly; serum blood urea nitrogen rose marginally with calcium. All subjects completed the interventions without ill effects.

The studies were small, with only 10 participants per crossover trial, and the intervention periods were short at 4 weeks. The primary outcomes were surrogate molecular endpoints rather than clinical colorectal cancer outcomes, and the single-center design in adults already at increased colorectal neoplasia risk limits generalizability.