3,3'-Diindoylylmethane(DIM): DIM is the main active metabolite of indole-3-carbinol, which is found in many cruciferous vegetables including brussel sprouts, turnips, kale and cabbage. The main mechanism of action for DIM is two-fold: it can, in low doses act as an aromatase inhibitor preventing the conversion of testosterone to estrogen (however in high doses can have the opposite effect), and it can modify potent estrogens into healthier estrogens via selectively hydroxylating certain parts of the estrogen molecule.1 For example, 4-hydroxyestradiol is a very potent estrogen that can cause gynecomastia in men. DIM metabolized estradiol into the less potent 2-hydroxy estrone, which is then eliminated. DIM also binds to the aryl hydrocarbon receptor (AhR) which causes a downregualtion of estrogen receptor production. Some studies show that a metabolite of 2-hydroxyestrone, 2-methoxyestradiol can even help displace testosterone that is bound to sex hormone binding globulin (SHBG) to increase free testosterone levels. This is due to 2-methoxyestradiol's high affinity to SHBG.2 Interestingly, 2-hydroxyestradiol is not suppressive to the HTPA where 4-hydroxyestradiol is. This may also indirectly increase testosterone levels.3 Typical doses of DIM are between 100-300mg daily.
- Chang, Yu-Chen, et al. "Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3, 3′-diindolylmethane, a major in vivo product of dietary indole-3-carbinol." Biochemical pharmacology5 (1999): 825-834.
- Avvakumov GV, Grishkovskaya I, Muller YA, Hammond GL. Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol. J Biol Chem. 2002 Nov 22;277(47):45219-25
- Franks S, MacLusky NJ, Naish SJ, Naftolin F. Actions of catechol oestrogens on concentrations of serum luteinizing hormone in the adult castrated rat: various effects of 4-hydroxyoestradiol and 2-hydroxyoestradiol. J Endocrinol. 1981 May;89(2):289-95.