Estro-D-Tox by MDLogic

POSSIBLY EFFECTIVE

• Colorectal cancer. Consumption of cruciferous vegetables, including broccoli, seems to reduce the risk of developing colorectal cancer. Details: Epidemiological research has found that the highest intakes of cruciferous vegetables, including broccoli, are associated with an 18% to 20% reduced risk of developing colorectal neoplasms when compared with the lowest intakes (14148,96187,96189).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bladder cancer. It is unclear if consumption of broccoli reduces the risk of developing bladder cancer. Details: Epidemiologic research has found that eating about 1.75 cups daily of cruciferous vegetables, such as broccoli or cabbage, is associated with a 30% reduced risk of developing bladder cancer (14864).
• Breast cancer. It is unclear if consumption of broccoli reduces the risk of developing breast cancer. Details: Epidemiological research has found that consumption of broccoli is associated with a modestly reduced risk of developing breast cancer in premenopausal adults. However, broccoli consumption does not seem to be associated with breast cancer risk in postmenopausal adults (14146).
• Fibromyalgia. Broccoli has only been evaluated in combination with ascorbigen; its effect when used alone is unclear. Details: A small clinical study in females with fibromyalgia shows that taking one capsule containing ascorbigen 100 mg and broccoli powder 400 mg once daily for one month improves pain by 18% and reduces physical impairment by 20% when compared with baseline (19605). It is unclear if this effect is due to broccoli, ascorbigen, or the combination. The validity of these findings is limited by the lack of a comparator group.
• Gastric cancer. It is unclear if consumption of broccoli reduces the risk of developing gastric cancer. Details: A small epidemiological study has found that higher consumption of broccoli is associated with a reduced risk of developing gastric cancer when compared with lower consumption (14148).
• Hypercholesterolemia. Broccoli has only been evaluated in combination with cabbage; its effect when used alone is unclear. Details: A small clinical study in patients with mild to moderate hypercholesterolemia shows that consuming 160 grams of a beverage containing broccoli, cabbage, and fruit twice daily for 12 weeks reduces levels of low-density lipoprotein (LDL) cholesterol by 8.5% when compared with baseline. It is unclear if the improvement from baseline differed when compared with those consuming a similar beverage without broccoli and cabbage (19607). It is unclear if this effect is due to broccoli, cabbage, or the combination.
• Prostate cancer. It is unclear if consumption of broccoli reduces the risk of developing prostate cancer; the available research is conflicting. In patients with prostate cancer, broccoli has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some epidemiological research has found that consumption of Brassica vegetables, such as broccoli, Brussels sprouts, cauliflower, and cabbage, is associated with a reduced risk of developing prostate cancer (14145). However, other epidemiological research has found no association (14147,15172). Clinical research in adults with prostate cancer shows that taking a whole food formulation containing broccoli powder 100 mg, turmeric powder 100 mg, pomegranate whole fruit powder 100 mg, and green tea extract 20 mg three times daily for 6 months prevents an increase in prostate specific antigen (PSA) levels. Mean PSA levels increased by 15% in the whole food formulation group, compared with 79% in the placebo group. Also, 46% of those taking the whole food formulation showed final PSA levels that were the same or lower than initial PSA levels, compared with 14% of those in the placebo group (89730). However, it is not yet known whether the whole food formulation reduces the risk of prostate cancer progression or recurrence. It is unclear if these effects are due to broccoli, other ingredients, or the combination. More evidence is needed to rate broccoli for these uses.

(Read more about BROCCOLI)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Breast cancer. Although there has been interest in using oral calcium D-glucarate for preventing breast cancer, there is insufficient reliable information about the clinical effects of calcium D-glucarate for this purpose.
• Colorectal cancer. Although there has been interest in using oral calcium D-glucarate for preventing colorectal cancer, there is insufficient reliable information about the clinical effects of calcium D-glucarate for this purpose.
• Prostate cancer. Although there has been interest in using oral calcium D-glucarate for preventing prostate cancer, there is insufficient reliable information about the clinical effects of calcium D-glucarate for this purpose. More evidence is needed to rate calcium D-glucarate for these uses.

(Read more about CALCIUM D-GLUCARATE)

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.

(Read more about DIINDOLYLMETHANE)

POSSIBLY EFFECTIVE

• Prostate cancer. Oral sulforaphane seems to delay increases in levels of prostate specific antigen (PSA) in patients with prostate cancer. Details: One clinical study in adults who have undergone radical prostatectomy shows that taking a specific sulforaphane product (Prostaphane, Nutrinov) 20 mg three times daily for 6 months attenuates a rise in PSA levels after 3 months, with an 86% increase in the time needed for PSA levels to double when compared with placebo (95251). A small clinical study in adults with recurrent prostate cancer shows that taking a sulforaphane-rich broccoli sprout extract 35.2 mg daily for up to 20 weeks increases the time needed for PSA levels to double by 57% when compared to pre-treatment changes in PSA levels (95260).

POSSIBLY INEFFECTIVE

• Helicobacter pylori. Oral sulforaphane does not seem to improve the H. pylori eradication rate when used in combination with triple therapy treatment. Details: Clinical research shows that taking one capsule of broccoli sprout extract 250 mg, providing sulforaphane 1 mg, three times daily for 4 weeks in combination with clarithromycin-based triple-therapy treatment does not increase H. pylori eradication rate when compared with triple therapy alone or in combination with Saccharomyces boulardii (108138).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral sulforaphane is beneficial for improving cognitive function in older adults. Details: Clinical research in older adults shows that taking the sulforaphane precursor glucoraphanin (Kagome Co., Ltd.) 30 mg daily for 12 weeks modestly improves some measures of cognitive function, specifically working memory and processing speed, when compared with placebo. Half of all patients also underwent brain-training by playing a specific game (Brain Age) 15 minutes daily and the other half played an active control game (Tetris). However, the combination of brain-training and glucoraphanin does not seem to be more beneficial than either intervention alone (108133).
• Allergic rhinitis (hay fever). It is unclear if oral sulforaphane is beneficial for allergic rhinitis. Details: Clinical research in patients with grass-induced allergic rhinitis shows that using a daily steroid nasal spray in conjunction with an oral broccoli seed and sprout extract (Avmacol, Nutramax) 1500 mg daily, providing sulforaphane 60-70 micromoles, for 3 weeks improves nasal flow and symptom severity for up to about 30 minutes when compared with using a saline spray and oral placebo. However, use of either intervention alone did not improve nasal flow or symptoms when compared with placebo (108132). This study was small and may not have been adequately powered to detect beneficial effects of sulforaphane alone.
• Asthma. It is unclear if oral sulforaphane is beneficial for asthma. Details: Preliminary clinical research in adults with asthma shows that taking broccoli sprout extract containing sulforaphane 17.6 mg daily for 14 days attenuates the bronchoconstriction effects of methacholine by approximately 21% when compared to baseline. However, after taking sulforaphane, 20% of patients experienced a worsening of bronchoconstriction and 20% experienced no change. Taking sulforaphane did not improve most measures of pulmonary function, including forced expiratory volume, forced vital capacity, lung capacity, and residual capacity (95262).
• Autism spectrum disorder. It is unclear if oral sulforaphane is beneficial in children or adults with autism spectrum disorder; any benefits seen in clinical studies may not be considered clinically significant. Details: One small clinical study in children 4-12 years old with moderate to severe autism symptoms shows that taking sulforaphane 10-20 mg daily in combination with risperidone for 10 weeks improves irritability scores by 14% and hyperactivity scores by 12% when compared with placebo and risperidone. However, it is unclear if these improvements are clinically meaningful. Taking sulforaphane did not improve stereotypic, social/lethargy, or speech scores when compared with placebo. Children weighing up to 45 kg took approximately 10 mg daily and children weighing at least 45 kg took approximately 20 mg daily (104537). Another small clinical study in children 3-12 years old with moderate to severe autism symptoms shows that taking sulforaphane as a specific broccoli seed and sprout extract blend (Avmacol, Nutramax) daily for 15 weeks does not improve clinical impressions or most symptoms of autism when compared with placebo. The extract blend was dosed to provide approximately 1 mcmol sulforaphane per pound or 2.2 mcmol per kg body weight (108131). This study was small and may not have been adequately powered to detect differences between groups. Sulforaphane has also been evaluated in older children or young adults. A small study in males 13-27 years of age with autism shows that taking sulforaphane daily for 18 weeks improves behavior scores by 33% and social scores by 17% when compared with placebo. After treatment discontinuation, behavior and social scores returned to baseline levels. Dosing was weight-based as follows: sulforaphane 26.6 mg daily in those weighing at least 91 kg, 17.6 mg daily in those weighing 45-91 kg, and 8.8 mg daily in those weighing up to 45 kg (95267). A small study in males and females 7-21 years of age with autism shows that taking sulforaphane as a specific broccoli seed and sprout blend (Avmacol, Nutramax Laboratories Consumer Care, Inc.) daily for 12 weeks improves social scores by 6%, but does not affect behavior scores, when compared with baseline. It is unclear if this improvement is clinically meaningful. The product used in this study contains glucoraphanin and myrosinase and was dosed to provide approximately 2.5 mcmol of glucoraphanin per pound of body weight (98501). The validity of these findings is limited by the lack of a comparator group.
• Cancer. Although there is interest in using oral sulforaphane for cancer, there is insufficient reliable information about the clinical effects of sulforaphane for this condition.
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral sulforaphane is beneficial for COPD. Details: Preliminary clinical research shows that taking sulforaphane 4.4 mg or 26.6 mg daily for 4 weeks does not improve symptoms of COPD when compared with placebo (95268).
• Depression. It is unclear if oral sulforaphane is beneficial for depression. Details: A small clinical trial in patients with mild to moderate depression related to cardiac interventions shows that taking sulforaphane (Acer) 30 mg daily for 6 weeks reduces depression score by at least 50% in 30% of patients, compared with only 7% of those taking placebo. However, there was no significant difference in remission rate between groups (108136).
• Exercise-induced muscle damage. It is unclear if oral sulforaphane is beneficial for exercise-induced muscle damage. Details: A small clinical trial in adult males shows that taking sulforaphane 30 mg daily for 4 weeks attenuates an increase in creatine kinase levels at 24 hours following heavy resistance exercise when compared with placebo. This suggests that sulforaphane may reduce muscle damage associated with exercise (108135). However, another small preliminary clinical trial in young adult males shows that taking the sulforaphane precursor glucoraphanin (Kagome Co., Ltd.) 30 mg daily, starting 2 weeks before exercise and continuing until 4 days after, does not reduce markers of muscle damage, including aldolase, aspartate aminotransferase, lactate dehydrogenase, or creatine kinase, when compared with not taking sulforaphane (108134).
• Exercise-induced muscle soreness. It is unclear if oral sulforaphane is beneficial for exercise-induced muscle soreness. Details: A small preliminary clinical trial in young adult males shows that taking the sulforaphane precursor glucoraphanin (Kagome Co., Ltd.) 30 mg daily, starting 2 weeks before exercise and continuing until 4 days after, reduces palpation-related muscle soreness and improves range of motion two days after exercise when compared with not taking sulforaphane. However, there was no difference between groups on days 1, 3, or 4 and there was no difference in pain related to extension (108134).
• Liver disease. Although there is interest in using oral sulforaphane to improve liver health, there is insufficient reliable information about the clinical effects of sulforaphane for this use.
• Pregnancy-induced hypertension. It is unclear if oral sulforaphane is beneficial for hypertension during pregnancy. Details: A small nonrandomized clinical trial in patients with pregnancy-induced hypertension or pre-eclampsia shows that taking broccoli extract modestly decreases diastolic, but not systolic, blood pressure, when compared with baseline. Patients took a single dose of either four or eight tablets of a myrosinase-activated broccoli seed extract (BroccoMax, Jarrow Formulas) providing an unknown dose sulforaphane (108130). This study was small and may not have been adequately powered to detect differences in blood pressure.
• Schizophrenia. It is unclear if oral sulforaphane is beneficial for schizophrenia. Details: Preliminary clinical research in patients with schizophrenia shows that taking sulforaphane as a specific broccoli seed and sprout blend (Avmacol, Nutramax) daily for 16 weeks does not improve positive or negative symptoms when compared with taking placebo (108137).
• Sickle cell disease. Although there is interest in using oral sulforaphane for sickle cell disease, there is insufficient reliable information about the clinical effects of sulforaphane for this condition.
• Sunburn. Although there is interest in using topical sulforaphane for sunburn prevention, there is insufficient reliable information about the clinical effects of sulforaphane for this use. More evidence is needed to rate sulforaphane for these uses.

(Read more about SULFORAPHANE)

LIKELY SAFE ...when used orally in food amounts (14145). There is insufficient reliable information available about the safety of broccoli when used in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (14145). There is insufficient reliable information available about the safety of broccoli when used in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about BROCCOLI)

There is insufficient reliable information available about the safety of calcium D-glucarate.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of calcium D-glucarate during pregnancy and lactation; avoid using.

(Read more about CALCIUM D-GLUCARATE)

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.

(Read more about DIINDOLYLMETHANE)

LIKELY SAFE ...when used orally in amounts found in foods (10264).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Sulforaphane-rich broccoli sprout extract has been used with apparent safety in clinical studies at a sulforaphane dose of up to 35.2 mg daily for up to 20 weeks (95260,95262,95265,95267,95268,104537,108136,108137,108138). A specific brand of sulforaphane (Prostaphane, Nutrinov) has been used with apparent safety in clinical research at a dose of up to 60 mg daily for up to 6 months (95251). A specific broccoli seed extract (BroccoMax, Jarrow Formulas) containing glucoraphanin 180 mg daily has been used with apparent safety in clinical research for up to 8 weeks (95269).

CHILDREN: LIKELY SAFE
when used orally in amounts found in foods (10264). There is insufficient reliable information available about the safety of sulforaphane in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods (10264). There is insufficient reliable information available about the safety of sulforaphane in medicinal amounts.

(Read more about SULFORAPHANE)

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP1A2.  Details Pharmacokinetic research in humans shows that eating 500 grams of fresh broccoli daily for 6-12 days can increase CYP1A2 activity by 10% to 200% (19608,95722). Induction of CYP1A2 activity by broccoli is attributed to its glucosinolate constituents (19608).

CYTOCHROME P450 2A6 (CYP2A6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP2A6.  Details Pharmacokinetic research in humans shows that eating 500 grams of broccoli daily for 6 days increases CYP2A6 activity by 135% to 550%. Induction of CYP2A6 activity is attributed to its glucosinolate constituents (19608).

(Read more about BROCCOLI)

ALCOHOL (Ethanol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use with alcohol might decrease calcium D-glucarate activity.  Details There is some evidence that urinary excretion of calcium D-glucarate metabolites increases in people consuming alcohol (779).

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, calcium D-glucarate might increase the clearance of drugs that undergo glucuronidation.  Details The calcium D-glucarate metabolite, D-glucaro-1,4-lactone, inhibits the enzyme beta-glucuronidase, reducing deconjugation of glucuronides in the intestine and thereby reducing reabsorption of the drugs (772,3952,107377).

KANAMYCIN Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, calcium D-glucarate may reduce plasma levels of kanamycin.  Details Calcium D-glucarate may increase the rate of kanamycin elimination, which may decrease its clinical and adverse effects (777).

(Read more about CALCIUM D-GLUCARATE)

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.

(Read more about DIINDOLYLMETHANE)

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sulforaphane might alter the levels and clinical effects of CYP1A2 substrates.  Details Animal and in vitro research shows that sulforaphane inhibits CYP1A2 enzyme activity. However, its precursor glucoraphanin also appears to increase the expression of the CYP1A2 enzyme, which could lead to increased metabolism of CYP1A2 substrates (12701,105083,105085). These effects have not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sulforaphane might increase the levels and effects of CYP2E1 substrates.  Details In vitro evidence shows that sulforaphane inhibits CYP2E1 enzymes (105083). This interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sulforaphane might increase the levels and effects of CYP3A4 substrates.  Details Animal and in vitro research shows that sulforaphane inhibits CYP3A4 enzyme activity and downregulates its expression (105083,105434,105435). This interaction has not been reported in humans.

(Read more about SULFORAPHANE)

General ...Broccoli is well tolerated when consumed as food. A thorough evaluation of safety outcomes when broccoli is taken as medicine has not been conducted.

Dermatologic ...Topically, allergic reactions to broccoli have caused contact dermatitis (14158).

Hepatic ...In one case report, a 56-year-old adult developed elevated transaminases, with alanine aminotransferase (ALT) 5. 8 times above normal, aspartate aminotransferase (AST) 2.4 times above normal, and gamma-glutamyl transpeptidase (GGT) 5.1 times above normal. This was thought to be related to the consumption of 800 mL of broccoli juice daily over a 4-week period. Values returned to normal 15 days after cessation of juice consumption (96191).

Immunologic ...Topically, allergic reactions to broccoli have caused contact dermatitis (14158).

(Read more about BROCCOLI)

General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.

(Read more about CALCIUM D-GLUCARATE)

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.

(Read more about DIINDOLYLMETHANE)

General ...Orally, sulforaphane seems to be well tolerated.
Most Common Adverse Effects:
Orally: Bowel discomfort, heartburn, stomach upset, and vomiting.

Gastrointestinal ...Orally, sulforaphane and sulforaphane-rich extracts can cause bowel discomfort, stomach upset, heartburn, and vomiting (95251,95252,95260,95265,95267,95268,98501,104537,108132). A specific stabilized form of sulforaphane (Cavamax W6) caused mild stomach upset in 60% of subjects in a small study (95252). However, in some clinical studies, the gastrointestinal side effects reported with sulforaphane did not occur more frequently than with placebo (95268).

Hepatic ...Orally, sulforaphane has been associated with one case of elevated liver enzyme levels. However, the patient ran a marathon the day before testing, and levels returned to normal within one week (95262).

Neurologic/CNS ...Orally, sulforaphane has been reported to cause headache in one clinical study (104537). In another clinical trial, insomnia and irritability were reported (108131). Sulforaphane has also been associated with two cases of seizure in males with autism. In one case, a patient with a recent history of seizure experienced a seizure after taking sulforaphane for 3 weeks. In another case, a patient with seizures which had been well-controlled with antiepileptic drugs for more than 1 year experienced a seizure 3 weeks after discontinuing sulforaphane. It is unclear if sulforaphane precipitated seizures in these patients (95267).

Other ...Orally, sulforaphane has been reported to cause increased weight gain. In one clinical study in males 13-27 years of age with autism, patients taking sulforaphane gained an additional 4 pounds on average over 18 weeks when compared with those taking placebo (95267).

(Read more about SULFORAPHANE)