Pilot Study: Effect of 3,3′-Diindolylmethane Supplements on Urinary Hormone Metabolites in Postmenopausal Women With a History of Early-Stage Breast Cancer

Dalessandri, Kathie M.; Firestone, Gary L.; Fitch, Mark; Bradlow, H. Leon; Bjeldanes, Leonard F.

doi:10.1207/s15327914nc5002_5

Cited by 91 publications

(61 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In controlled clinical trials, oral supplementation with 300-400 mg/d of I3C has consistently increased urinary 2OHE 1 levels or urinary 2OHE 1 :16αOHE 1 ratios in women [93][94][95][96][97]. Supplementation with 108 mg/day of DIM also increased urinary 2OHE 1 levels in postmenopausal women [98]. However, the relationship between urinary 2OHE 1 :16OHE 1 ratios and breast cancer risk is not clear.…”

Section: Effects Of Indole-3-carbinol On Estrogen Metabolismmentioning

confidence: 99%

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Higdon

Delage

Williams

et al. 2007

Pharmacological Research

916

697

View full text Add to dashboard Cite

Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of 5-9 servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3′-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized controlled trials are needed.

show abstract

Section: Effects Of Indole-3-carbinol On Estrogen Metabolismmentioning

confidence: 99%

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Higdon

Delage

Williams

et al. 2007

Pharmacological Research

916

697

View full text Add to dashboard Cite

show abstract

“…When compared with placebo, BR-DIM resulted in a significant increase in 2OHE 1 (P ¼ 0.02) and a modestly protective shift in the 2OHE 1 :16aOHE 1 ratio (P ¼ 0.059). 84 The ability of DIM to induce CYP enzymes responsible for catalyzing hydroxylation could be responsible for the enhanced production of 2OHE 1 and the limited production of 16aOHE 1 . Additionally, administration of BR-DIM to premenopausal women improves symptoms of cyclical mastalgia, 85 a potential indicator of increased breast cancer risk.…”

Section: Mechanisms Of Action and Surrogate Endpoints In Humansmentioning

confidence: 99%

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

Thomson

Ström

2016

Nutr Rev

View full text Add to dashboard Cite

Diet is a modifiable factor associated with the risk of several cancers, with convincing evidence showing a link between diet and breast cancer. The role of bioactive compounds of food origin, including those found in cruciferous vegetables, is an active area of research in cancer chemoprevention. This review focuses on 3,3 0 -diindolylmethane (DIM), the major bioactive indole in crucifers. Research of the cancerpreventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake.

show abstract

“…These dose levels produced significant changes in the activities of at least two xenobiotic and steroid-metabolizing enzymes and markedly altered the ratio of hydroxylated estrone metabolites in a manner consistent with chemoprevention. The use of 400 mg of I3C daily seems to be safe and effective supplement for women [106,107,109,110]. Other study indicated that DIM supplementation at a dose of 108 mg/day for 30 days increased urinary 2-hydroxyestrone excretions in postmenopausal women with a history of breast cancer [110].…”

Section: Human Clinical Studiesmentioning

confidence: 94%

The Anti-Carcinogenic Effect of Indole-3-Carbinol and 3, 3'-Diindolylmethane and their Mechanism of Action

Fares¹

2014

Med chem

View full text Add to dashboard Cite

Indoles are aromatic heterocyclic organic compound and became the precursor to many pharmaceuticals. Indoles are found naturally in cruciferous plants and indole derivatives, indole-3-carbinole (I3C) and 3, 3'-diindolylmethane (DIM) can also be synthesized by a variety of methods. In vitro studies indicated that I3C and DIM inhibit cell proliferation, caused cell cycle arrest at G1 phase and induced apoptosis. The precise molecular mechanisms by which indole derivatives exert their tumor suppressive effects in human cancer cells are still unclear. It was reported that indoles alter estrogen metabolism. Microarray gene expression profiling and other studies indicated that indoles regulate many genes that are important for the control of cell cycle, cell proliferation, apoptosis, signal transduction, angiogenesis and cell invasion. In addition, it was found that indoles prevent tumor formation of breast and prostate cancer in animal models. Furthermore, these derivatives were evaluated in human clinical trials phase I and phase II as a potential chemopreventive agents against human breast, ovary, and vulvar intraepithelial neoplasia and colon cancers. Preliminary findings of these studies showed a significant clinical improvement. Interestingly, the use of indole derivatives was found to be safe without any indicated side effects. In conclusion, the results provide an evidence of the benefit of indole-derivatives in the prevention and treatment of hormone-dependent and hormone-independent human cancer. Further clinical trials are needed in order to approve the efficacy of indole derivatives in treatment of human cancer and to evaluate the indole use by the Food and Drug Administration (FDA).

show abstract

Pilot Study: Effect of 3,3′-Diindolylmethane Supplements on Urinary Hormone Metabolites in Postmenopausal Women With a History of Early-Stage Breast Cancer

Cited by 91 publications

References 47 publications

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

The Anti-Carcinogenic Effect of Indole-3-Carbinol and 3, 3'-Diindolylmethane and their Mechanism of Action

Contact Info

Product

Resources

About