DIM (Diindolylmethane)

Thomson et al. (Breast Cancer Research and Treatment, 2017; PMID 28560655): 12-month randomized placebo-controlled trial; 130 women taking tamoxifen for breast cancer were randomized to a microencapsulated DIM formulation, 150 mg twice daily, or placebo, and 98 (47 DIM, 51 placebo) completed, so the biomarker results rest on 98. The primary endpoint was originally breast density; on the data and safety monitoring board's advice, after bilateral mastectomies hampered recruitment, it was changed to the urinary 2/16-hydroxyestrone ratio, and the original primary, breast density on mammography and MRI, did not change. The urinary 2/16 ratio rose and SHBG rose against placebo; plasma tamoxifen metabolites, including endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen, were LOWER in the DIM group (P<0.001). The authors state that whether this lowering reduces the clinical benefit of tamoxifen is not known. Funded by the National Cancer Institute; the active and placebo capsules were supplied by the maker of the studied product. No trial has shown that raising the 2/16 ratio changes a cancer outcome. Other randomized trials, different populations: Castañon et al. (Br J Cancer, 2012; PMID 22075942): the largest DIM trial, 551 women with low-grade cervical cytological abnormalities, 150 mg/day for 6 months, funded by Cancer Research UK using the same maker's formulation; no effect on cytology or HPV clearance. Dalessandri et al. (Nutr Cancer, 2004; PMID 15623462): pilot trial, 19 postmenopausal breast cancer survivors, 108 mg/day for 30 days; 2-hydroxyestrone rose, the 2/16 ratio change was not significant (P=0.059). Godínez-Martínez et al. (Nutr Cancer, 2023; PMID 36111381): 60 premenopausal women, 75 mg/day for 30 days; the urinary ratio did not rise. Grade C: one randomized trial on surrogate hormonal endpoints, in a population taking a cancer drug whose active metabolites DIM reduced.