DIM + I3C by Seeking Health

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Benign prostatic hyperplasia (BPH). Although there is interest in using oral diindolylmethane for BPH, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition.
• Breast cancer. It is unclear if oral diindolylmethane is beneficial in patients at high risk for developing breast cancer. Details: Preliminary clinical research in healthy pre- and post-menopausal patients at high risk for breast cancer due to the BRCA mutation shows that taking diindolylmethane (DIM-Evail, Designs for Health Inc) 100 mg daily for 1 year is associated with a 5% decrease in breast density, as measured by the amount of fibroglandular tissue, when compared with baseline (103830). It is unclear whether this reduces the risk of developing breast cancer. Also, the validity of this finding is limited by the lack of a control group.
• Cervical dysplasia. It is unclear if oral diindolylmethane is beneficial in patients with cervical dysplasia. Details: Clinical research in patients with mild cervical abnormalities shows that taking a specific product (BioResponse-DIM, BioResponse) as 150 mg, providing 45 mg diindolylmethane, daily for 6 months does not improve colposcopy or biopsy results when compared with placebo (93836). Additionally, clinical research in patients with grade 2 or 3 cervical neoplasia shows that taking this same product as 2 mg/kg diindolylmethane daily for 12 weeks does not affect Pap smear, colposcopy, or histology results when compared with placebo; however, both groups showed significant improvements when compared with baseline (47709).
• Colorectal cancer. Although there is interest in using oral diindolylmethane for colorectal cancer, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition.
• Mastalgia. Although there is interest in using oral diindolylmethane for mastalgia, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition.
• Obesity. Although there is interest in using oral diindolylmethane for obesity, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition.
• Premenstrual syndrome (PMS). Although there is interest in using oral diindolylmethane for PMS, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition.
• Prostate cancer. Although there is interest in using oral diindolylmethane for prostate cancer, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition.
• Uterine cancer. Although there is interest in using oral diindolylmethane for uterine cancer, there is insufficient reliable information about the clinical effects of diindolylmethane for this condition. More evidence is needed to rate diindolylmethane for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Breast cancer. Although there has been interest in using oral indole-3-carbinol for breast cancer, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
• Cervical dysplasia. It is unclear if oral indole-3-carbinol is beneficial in patients with cervical dysplasia. Details: Preliminary clinical research shows that taking indole-3-carbinol 200-400 mg orally daily for 12 weeks is associated with complete regression of precancerous lesions in 45% to 50% of women with grade II or III, biopsy-proven cervical intraepithelial neoplasia (CIN, cervical dysplasia), the majority of whom are positive for human papilloma virus (HPV) infection (7173).
• Colorectal cancer. Although there has been interest in using oral indole-3-carbinol for colorectal cancer, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
• Fibromyalgia. Although there has been interest in using oral indole-3-carbinol for fibromyalgia, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
• Liver disease. Although there has been interest in using oral indole-3-carbinol for liver disease, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
• Nonmelanoma skin cancer. It is unclear if oral indole-3-carbinol is beneficial in patients with nonmelanoma skin cancer. Details: Preliminary clinical research in patients with vulvar intraepithelial neoplasia (VIN), a precancerous condition that can progress to squamous cell carcinoma, shows that taking indole-3-carbinol 200 mg or 400 mg daily for 6 months improves symptoms and reduces lesion size and severity when compared with baseline. However, tissue biopsies taken from the women with the most severely affected areas did not show any improvement in grade of VIN (93241). The validity of this finding is limited by the small study size and lack of a comparator group. Additionally, it is unclear if treatment with indole-3-carbinol reduces the risk of progression to cancer.
• Ovarian cancer. It is unclear if oral indole-3-carbinol is beneficial in patients with ovarian cancer. Details: Preliminary clinical research in patients with previously untreated stage III-IV ovarian cancer shows that taking indole-3-carbinol 200 mg orally twice daily with or without epigallocatechechin-3-gallate (EGCG) 200 mg twice daily, in conjunction with neoadjuvant chemotherapy and surgery, increases median overall survival and progression-free survival by 16 and 18 months, respectively, when compared with chemotherapy and surgery alone. The addition of indole-3-carbonol with or without EGCG also reduced the tumor recurrence rate by about 16% when compared with chemotherapy and surgery alone (98610).
• Recurrent respiratory papillomatosis. It is unclear if oral indole-3-carbinol is beneficial in patients with recurrent respiratory papillomatosis. Details: Preliminary clinical evidence shows that taking indole-3-carbinol 200 mg twice daily for a mean of 57.6 months (range 31 months to 76 months) after complete surgical removal of respiratory papillomas stops regrowth in about a third of patients and slows regrowth, reducing the need for repeated surgery, in another third (7172,47645,93239).
• Systemic lupus erythematosus (SLE). It is unclear if oral indole-3-carbinol is beneficial in patients with SLE. Details: Preliminary clinical research shows that taking indole-3-carbinol 125 mg orally three times daily for 3 months does not significantly decrease disease activity when compared with baseline in women aged 20-49 years with SLE (93240). More evidence is needed to rate indole-3-carbinol for these uses.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. The typical diet supplies 2-24 mg of diindolylmethane daily (7170,7176,7664).

POSSIBLY SAFE ...when used orally and appropriately in medicinal doses. Diindolylmethane has been used with apparent safety at a dose of 45 mg daily for up to 6 months or at a higher dose of 100-140 mg daily for up to 3 months (47709,47729,93836,103830).

POSSIBLY UNSAFE ...when used orally in doses of 600 mg daily. In one clinical study, two cases of grade 3 asymptomatic hyponatremia were associated with taking diindolylmethane 600 mg daily (47729).

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods. The typical diet supplies 2-24 mg of diindolylmethane daily (7170,7176,7664).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods. The typical diet supplies 2-24 mg of diindolylmethane daily (7170,7176,7664). There is insufficient reliable information available about the safety of diindolylmethane when used in amounts greater than those found in foods during pregnancy and lactation; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Doses up to 400 mg daily have been used safely for 3-76 months (7173,93239,93240,93241). There is also some evidence that 400 mg twice daily can be used safely for 4 weeks (93242).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts. There is limited evidence from 9 children with recurrent respiratory papillomatosis that indole-3-carbinol can be safely used in children ages 1.2-16 years for 12-76 months at doses of 6-17 mg/kg of body weight daily (7172,93239).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of indole-3-carbinol when used during pregnancy and lactation; avoid using.

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CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, diindolylmethane might lower serum levels of CYP1A2 substrates.  Details In vitro evidence suggests that diindolylmethane can induce CYP1A2 (7667,47745). Theoretically, it might increase metabolism of CYP1A2 substrates and lower serum concentrations. This interaction has not been reported in humans.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, diindolylmethane might increase the risk of hyponatremia if used with sodium-depleting diuretics.  Details Large doses of diindolylmethane (600 mg daily) have been associated with two cases of asymptomatic hyponatremia in clinical research (47729).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, diindolylmethane might increase or decrease the effects of estrogens.  Details Diindolylmethane might have mild estrogenic or antiestrogenic effects (7664). Theoretically, large amounts of diindolylmethane might interfere with hormone replacement therapy.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, indole-3-carbinol might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details In vitro research shows that indole-3-carbinol inhibits platelet aggregation (98611).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, indole-3-carbinol might increase the metabolism of CYP1A2 substrates and lower serum concentrations.  Details Animal research shows that indole-3-carbinol induces CYP1A2 enzymes (7187).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Indole-3-carbinol might interfere with the effects of estrogen therapy.  Details Preliminary clinical and in vitro evidence shows that indole-3-carbinol has antiestrogenic activity (7173,47621,93238,93240).

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General ...Orally, diindolylmethane is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, gas, headache, nausea, rash, and vomiting.
Serious Adverse Effects (Rare):
Orally: Drug rash with eosinophilia and systemic symptoms (DRESS).

Dermatologic ...Orally, diindolylmethane can cause rash (47615,93836). In one case report, a patient developed drug rash with eosinophilia and systemic symptoms (DRESS) after consuming a product containing diindolylmethane, vitamin E, and broccoli powder. An allergen patch test was positive for diindolylmethane (93840).

Endocrine ...Orally, diindolylmethane was associated with grade 3 asymptomatic hyponatremia in 2 of 4 patients taking 600 mg daily for 28 days in one clinical study. Hyponatremia was not seen in the 8 patients taking diindolylmethane 150-450 mg daily (47729).

Gastrointestinal ...Orally, diindolylmethane can cause nausea, vomiting, diarrhea, and gas (47652,47676,47709,47729,93836).

Genitourinary ...Orally, diindolylmethane can cause the urine to darken (93836).

Hematologic ...In one case report, a 65-year-old male developed a deep vein thromboembolism (DVT) and bilateral pulmonary emboli (PE) within a few weeks of initiating treatment with diindolylmethane. It is unclear if diindolylmethane contributed to this event; the patient was at increased risk for emboli due to his age, weight, tobacco use, and possible history of pulmonary embolism (93835).

Hepatic ...In one case report, a patient developed drug rash with eosinophilia and systemic symptoms (DRESS), involving elevated liver transaminases, after consuming a product containing diindolylmethane, vitamin E, and broccoli powder. An allergen patch test was positive for diindolylmethane (93840).

Immunologic ...In one case report, a patient developed drug rash with eosinophilia and systemic symptoms (DRESS) after consuming a product containing diindolylmethane, vitamin E, and broccoli powder. The patient developed fever, activated lymphocytes, and swollen lymph nodes. An allergen patch test was positive for diindolylmethane (93840).

Musculoskeletal ...Orally, diindolylmethane has been reported to cause arthralgias (47615).

Neurologic/CNS ...Orally, diindolylmethane can cause headache (47652,47676,93836). One case has reported ischemic stroke in a 38-year-old female with a history of a patent foramen ovale (PFO), traumatic subdural hematoma, right partial hemicraniectomy, and use of several supplements, including 200 mg of diindolylmethane daily, vitamin D3, vitamin K2, elderberry, caffeine, and possibly cannabis (112895). It is unclear if diindolylmethane contributed to this event; the patient was at increased risk for stroke due to PFO and other factors.

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General ...Orally, indole-3-carbinol seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, imbalance, nausea, rash, tremor, unsteadiness.

Dermatologic ...Orally, indole-3-carbinol has been associated with reports of rash (93242). A woman taking indole-3-carbinol 375 mg daily for treatment of systemic lupus erythematosus (SLE) developed a generalized maculopapular rash which resolved when indole-3-carbinol was discontinued and recurred when it was restarted (93240).

Gastrointestinal ...Orally, indole-3-carbinol increases gastrointestinal motility and has been associated with diarrhea (93242,93243).

Neurologic/CNS ...Indole-3-carbinol has been associated with reports of unsteadiness and imbalance, especially at higher doses (7172). An adult male taking 400 mg twice daily for treatment of recurrent respiratory papillomatosis developed imbalance and tremor after 10 days of treatment. This resolved when the dose was halved (93238). Two children who took 3 times the intended weight-based dose of indole-3-carbinol in one day developed unsteadiness and nausea (93238).

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