Diindolylmethane, or DIM for short, is a very important phytonutrient found in cruciferous vegetables such as broccoli, cabbage, cauliflower, brussels sprouts and bok choy. In the last 10 years or so it has been discovered that supplemental use of DIM, and its precursor indol-3-carbinol (I3C), is associated with a beneficial shift in estrogen metabolism.
Research on the minor metabolites of estrogens, specifically the metabolites 2-hydroxyestrone and 16-alpha-hydroxyestrone has revealed the 2-hydroxyestrone metabolite is a “good” estrogen, while the 16-alpha-hydroxyestrone metabolite is a “bad” estrogen because it tends to damage DNA and cause abnormal cellular proliferation. Research findings indicate that if the ratio of the “good” estrogen metabolite (2-hydroxyestrone) to the “bad” estrogen metabolite (16-alpha-hydroxyestrone) is low then an increased risk of breast cancer results. The use of DIM and I3C in humans has been found to be effective in adjusting the pathways of estrogen metabolism to favor the production of the good estrogen metabolite, 2-hydroxyestrone. The shift in estrogen metabolites was found to be significant which showed an approximate 75% increase in production of 2-hydroxyestrone (“good” metabolites) and a 50% decrease in 16-hydroxyestrone (“bad” metabolites). This relationship has been documented in several case-control studies.
Other studies have also documented that low levels of 2-hydroxy metabolites are associated with breast cancer in women, breast cancer in men, uterine cancer, cervical cancer, and systemic lupus erythematosis. Therefore women with breast cancer, high risk of developing breast cancer and women taking estrogen supplementation could potentially in theory benefit from the use of either DIM or I-3-C.
In addition DIM has been shown to exhibit anti-proliferative and anti-androgenic properties in androgen-dependent human prostate cancer cells. It suppressed cell proliferation of LNCaP cells and inhibits DHT stimulation of DNA synthesis. Moreover it also inhibited endogenous PSA transcription and reduced intracellular PSA proteins induced by DHT. These results taken together with its effects on reducing estrogens and improving their metabolite balance DIM appears to be a unique bifunctional hormone disrupter. For these reasons men with high estrogens may also potentially benefit from the use of DIM.
DIM has been shown to result in a significant increase in the 2/16 ratio at one tenth the dose of I3C. In addition animal studies have clearly shown that it is DIM and not I3C that is the active promoter of greater 2-hydroxylation of estrogen which is associated with a cancer-resistant estrogen metabolism. DIM is also less reactive and less of a liver enzyme inducer than I3C. This difference accounts for a number of the side effects seen with I3C. Doubling the typical dose of I3C from 400 to 800 mg/day causes dizziness and unsteady gait, signs of nervous system toxicity in humans. No side effects of any sort are seen when pure DIM is used even in huge doses in animals, or when the usual dose of 40 mg/day of DIM is tripled in human subjects. Since supplemental DIM does not result in the wide array of enzyme induction that I3C provokes, there is less chance of interaction with other nutrients, hormones, or medications. In addition I3C has been shown to increase testosterone metabolism which can result in decreased levels which may be detrimental especially for males. For all these reasons we recommend the use of DIM instead of I3C.
As a consequence of DIM’s ability to safely and efficiently increase 2-hydroxy estrogen metabolite levels these unique estrogen metabolites are known to stimulate progesterone production, and compete with testosterone for protein binding. Thus it helps maintain an optimal estrogen/progesterone balance and also helps testosterone remain in its unbound, free and active form which can also be of great benefit to both men and women.
The usual dose for DIM is 25 to 100mg daily for women and 50 to 100mg a day for men. Due to its crystalline structure and poor water solubility the absorption of DIM when given orally is very poor. To overcome this various DIM complexes have been made by several companies in order to increase its oral absorption however 100mg of the DIM-complex only provides 25mg of DIM with the other 75mg being the complexing agent. Therefore two to four capsules are required each day for a therapeutic dose which can become expensive. Other companies have tried to emulsify DIM with lecithin and other fats in a gel capsule in attempt to improve its absorption. In order to overcome these absorption issues our laboratory has developed a transdermal liposomal DIM gel which is easily absorbed and shown to positively influence estrogen metabolite imbalances as well as reducing estrogen levels themselves.
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