Diindolylmethane: Uses, Side Effects, Interactions, Dosage

Prostate cancer is the second most prevalent cancer amongst men – in 2007 alone, about 780,000 incident cases were recorded worldwide.

Globally, the incidence of prostate cancer has been rising and currently stands at about 7.2% [3]. Prostate cancer typically develops in men after the age of 50.

As one of the “silent” cancers, prostate cancer rarely manifests with symptoms early in the course of the disease. Cancers affect both men and women alike.

Cancer can have debilitating effects on one’s quality of life as it is a relentless and invasive disease.

Today, patients have limited treatment options for cancer. Broadly, cancer can be treated with chemotherapy, radiotherapy, and surgery.

In men who have prostate cancer, surgery can be associated with retrograde ejaculation, an altered sexual experience, and the loss of fertility [4].

Given the significant public health challenge that cancer represents, it is interesting to evaluate preventative options. Of these, naturally occurring compounds garner interest from the scientific community at large.

In this article, we take a look at a unique compound called diindolylmethane. We critically explore its applications in medicine and health and advocate for its ability to prevent harmful diseases in both men and women.

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What Is Diindolylmethane?

3,3 diindolylmethane (DIM) is a major digestive product that is found naturally in the Brassica (mustard) family of vegetables such as cabbage, brussels sprouts, and broccoli.

DIM has been extensively studied for decades by various research groups. It boasts several rejuvenating properties, such as DNA repair, anti-tumor effects, and anti-viral effects [5-9]. Crucially, DIM is also capable of regulating the sex hormones in the body [10, 11].

Animal studies with mice and rats using DIM have demonstrated a decrease in breast tumors as well as a reduction in the incidence of colon cancers [12].

In addition to these impressive anti-tumor effects, DIM has also been shown to have potent immunomodulating activity. This is because DIM stimulates the production of natural cytokines and free radicals, which are harmful to invading bacteria and viruses [13].

DIM is formed in vegetables during acidic conditions and is a product of another compound known as glucobrassicin.

Once vegetables belonging to the Brassica family are consumed, the bioactive compounds within them are rapidly metabolized.

In the United States, dietary intake estimates for these cruciferous vegetables are low [14]. Indeed, the average consumption of glucobrassicin from vegetable sources is nonspecific and estimated to be lower than in European or Asian countries. The figure below shows the metabolic pathway of DIM, all the way from the vegetable itself to the organs in the body.

The mechanisms of Prostate Cancer

To understand how DIM works, it is beneficial to grasp the mechanisms of cancer. Normal prostate cells are stimulated to grow by growth factors, which enable them to divide.

Normal cellular division is characterized by 6 phases, resulting in two identical ‘daughter’ cells. Each of these phases is normally tightly regulated by checkpoints. These checkpoints function like traffic-lights. The cell is only allowed to pass to the next stage of growth when it receives a “green light.”

A disruption of this cell cycle can lead to unwanted and excessive cellular division. In other words, faulty traffic lights (checkpoints) leads to cancer.

After all, cancer is fundamentally a disease of unregulated and excessive cellular growth. These faulty checkpoints are caused by genetic mutations that can be hereditary (inherited) or acquired.

Diindolylmethane and Prostate Health

Several clinical trials and placebo-controlled studies have validated the anti-cancer properties of DIM. DIM has been shown to inhibit the proliferation of prostate cancer cells by up to 70% [15].

In mice, DIM was shown to significantly reduce the development of tumors by up to 50% when compared with controls. Tumors in mice treated with DIM were significantly smaller as compared to controls [16].

DIM has been shown to inhibit prostate cells from progressing from one growth phase to another. This effect has been extensively studied in oesophageal cancer, colorectal cancer, breast cancer, endometrial cancer, oral cancer, and prostate cancer [17-20].

It also inhibits prostate cancer cell proliferation and causes cancerous cells to die by activating and deactivating specific proteins [21, 22]. This cellular death is known as apoptosis. Prostate cancer requires a blood supply to survive, as blood carries vital oxygen for the metabolism of cells.

Cancers typically exhibit a property known as angiogenesis. Angiogenesis refers to the cancerous cells’ ability to grow their blood supply. DIM disrupts this, effectively stripping prostate cancer of its own blood supply [23-25].

Finally, DIM also boosts the immune system by stimulating an antioxidant response. This improves one’s immune surveillance and stresses cancer cells via oxidation [26, 27].

The above mechanisms of action apply not just to prostate health, but cancers affecting other organs as well.

In summary, DIM stops cancer cells in their tracks at certain growth phases, induces cancer cell death, disrupt cancer cells’ blood supply and stimulates, and antioxidant response. However, DIM also boasts properties that are specific to prostate and mammary cancer.

DIM has been shown to regulate the metabolism of sex hormones, such as oestrogen and testosterone. The male sex hormones, such as testosterone and dihydrotestosterone (DHT), bind to androgen receptors.

This binding has been implicated in the development and growth of prostate cancer. After all, prostate cancer is an androgen driven disease. This is because the growth and replication of prostate cancer cells are dependent upon the androgen receptors[28].

DIM has been shown to have an anti-androgenic effect that regulates this androgen receptor. These androgen antagonist effects underpin the potential for DIM to prevent the development of prostate cancer [29].

Diindolylmethane and Women’s’ Health

In women, DIM has been shown to promote favorable changes in estrogen metabolism and can potentially prevent the development of breast cancer as well [30]. This is because DIM also regulates the growth of estrogen-dependent breast and uterine cells.

Consequently, DIM has beneficial effects as regards the prevention of breast, endometrial, and uterine cancer. In fact, DIM curtails the development of breast cancer at multiple stages. These stages include the initiation, promotion, progression, and spread of breast cancer [31].

DIM has been shown to halt the progression of cervical cancer cells because of its inhibitory effects on estrogen receptors [32].

Lower down in the female genitourinary tract; DIM has also been shown to inhibit the cancerous transformation of cervical cells [33]. This process is known as dysplasia, and it is what gynecologists look out for during a screening Pap smear.

Possible side effects of Diindolylmethane

Although DIM is a naturally occurring compound, it is not without its side effects. The known side effects are as follows:

  • Nausea

  • Diarrhea

  • Bloating

  • Flatulence

However, these side effects are extremely mild, uncommon, and reversible. Some patients report a harmless darkening of urine. This is nothing to be alarmed about, as the excretion of colored DIM metabolites in the urine is responsible for this.

DIM has been established as a safe supplement. However, comprehensive safety studies have not been completed.

Dosage of Diindolylmethane

A review of the up-to-date research on DIM reveals that the standard starting dose is 75mg twice daily. However, a recent phase 1 dose-escalation study at the Karmanos Cancer Institute, Wayne State University, found that a dose of 225 mg twice-daily was preferred [37]. Studies have shown that even at doses of 1000mg, no serious adverse events are reported [38].

Foods containing Diindolylmethane

DIM is metabolized from glucobrassicin, which is abundant in cruciferous vegetables. During chewing, enzymes in the saliva break down glucobrassicin to yield various indoles.

One of these indoles is indole-3-carbinol, which is acid-catalyzed into DIM. Because acid is necessary for this conversion, exposure of the ingested vegetable to stomach acid is essential.

DIM can be found in the following vegetables:

  • Broccoli

  • Bok choy

  • Cabbage

  • Cauliflower

  • Collards

  • Kale

  • Turnips

  • Collard greens

  • Brussels sprouts

  • Kohlrabi

During cooking, the DIM concentrations within the vegetables rise [39]. This is because heat activates myrosinase. Myrosinase is an enzyme that breaks down glucobrassicin. DIM increases by 6 times in boiled cabbage, as compared with uncooked cabbage [39].

After consumption, the concentration of DIM varies depending on the tissue. The highest concentration of DIM is seen in the liver. The concentrations of DIM are modest in the kidneys, lungs, heart, and brain. DIM is excreted from the body in the urine within 24 hours.


Diindolylmethane (DIM) is a naturally occurring compound that can be found in a plethora of vegetables, including broccoli, kale, and cauliflower. It has potent effects on estrogen metabolism and had been shown to help maintain hormone balance.

As a result of its effectiveness, DIM is a key ingredient in Ben’s Estro Clear. By lowering estrogen levels back to a healthy norm, Estroclear helps you regain normal hormone levels and prevents your body from overproducing dangerous DHT to compensate for the high estrogen level.

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