Diindolylmethane (DIM)

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 20 years or so it has been discovered that supplemental use of DIM, and its precursor indol-3-carbinol (I3C), can reduce excessive estrogens by stimulating their metabolism in the liver in addition to a possible beneficial shift in estrogen metabolism pathways.

Research on estrogen metabolism, specifically the metabolites 2-hydroxyestrone and 16-alpha-hydroxyestrone, suggests that 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. Studies have 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.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. 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. The research on the safety of various estrogen metabolites is fairly limited and only suggests these links so at this stage we recommend to test them if you are at a high risk and aim to obtain a healthy balance but do not obsess over the numbers too much.

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.

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 a Transdermal DIM Gel has been developed which is easily absorbed and shown to positively influence estrogen metabolite imbalances as well as reducing overall estrogen levels.