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Supporting female AND male hormonal health with 3,3′-diindolylmethane
The healing power of Brassica vegetables like broccoli, cauliflower, Brussels sprouts, cabbage, and kale comes in large part from the phytochemical indole-3-carbinol (I3C), which naturally breaks down in the gut to a constituent known as 3,3′-diindolylmethane (DIM) (pronounced “dim”).[1] Consumption of cruciferous vegetables is associated with a reduction of inflammation,[2],[3] decreased risk of cardiovascular disease,[4],[5] and even lower risks of certain types of cancer.[6],[7],[8] DIM also supports healthy hormone metabolism and detoxification, and thus can be helpful in alleviating a number of hormonal-related issues in both men and women.
DIM and women
There are different estrogen metabolites in the body, some of which are more estrogenic and potentially harmful, while others are likely more protective.[9] DIM’s primary virtue with regard to women’s health comes from its role in helping the body to make a better balance of the “good estrogen” (2-hydroxy-estrone) compared to the “bad estrogen” (16-alpha-hydroxy-estrone).[10],[11] DIM also has anti-estrogenic activity, competing with estrogen for binding sites on cells and reducing proliferation.[12] By these actions, DIM may help reduce the risk of certain hormone-sensitive cancers.[13],[14] It is important to note, however, that DIM supplements should not be used by pregnant women.[15]
Balancing estrogen types and levels is beneficial in alleviating the symptoms of benign breast ailments (such as fibrocystic breast disease) and premenstrual syndrome (PMS). DIM in particular supports this aim when synergized with the herb chaste berry (Vitex agnus-castus), or vitex, as it’s also commonly known.
Chaste berry acts on the hypothalamic-pituitary-ovarian axis, increasing the production of luteinizing hormone (LH), a hormone produced by the brain to trigger ovulation.
Chaste berry acts on the hypothalamic-pituitary-ovarian axis, increasing the production of luteinizing hormone (LH), a hormone produced by the brain to trigger ovulation.[16] By supporting LH production, chaste berry helps shift the ratio of estrogen to progesterone in the body in favor of progesterone, thus further supporting fertility as well.[17],[18],[19] By directly binding to dopamine receptors, furthermore, chaste berry also helps lower prolactin levels,[20],[21],[22] which in turn can help mitigate breast pain, irregular menstrual cycles, and infertility.
DIM and men
DIM is also of value in the management of issues related to the prostate gland and their associated lower urinary tract symptoms.
Although the focus is often on testosterone when it comes to men’s health, estrogen levels are also important to monitor. Because the two hormones act in balance with one another, estrogen excess can cause symptoms of testosterone insufficiency. Estrogen also affects the growth and differentiation of prostate cells, both directly and indirectly, and thus increases the risk of benign prostatic hyperplasia (BPH).[23]
Because the two hormones act in balance with one another, estrogen excess can cause symptoms of testosterone insufficiency.
By shifting estrogen metabolism to support the “good” form of estrogen and reducing the “bad,” DIM may protect prostate tissue from BPH, prostatic inflammation,[24] and may even prevent cellular changes that can contribute to cancer.[25],[26],[27]
Yet estrogen isn’t the only hormone to watch in men. Dihydrotestosterone (DHT) is derived from testosterone in the body by way of an enzyme known as 5-alpha-reductase. During fetal development, DHT plays an essential role in the development of the prostate gland and penis. Later in life, DHT supports the biological characteristics of males like body hair, deep voice, and increased muscle mass.[28] An excess of DHT, however, contributes to male-pattern baldness and prostate gland enlargement (such as that seen in BPH).[29]
When it comes to prostate health, therefore, DIM works particularly well when used alongside the plant Serenoa repens (saw palmetto).[30] Saw palmetto inhibits 5-alpha-reductase, the enzyme that converts testosterone to DHT, thereby reducing the risk of BPH and other prostate ailments.[31] Saw palmetto has also been shown to reduce estrogen levels in the prostate gland, further benefitting those with BPH.[32]
Minimizing the activity of estrogen and levels of DHT are therefore therapeutic goals in the prevention and management of prostate ailments[33],[34] – goals supported through supplementation with DIM and saw palmetto.
Eat your (DIM-packed) veggies!
So when mom says eat your Brussels sprouts? You may want to take her up on it.
…Or just crack open a bottle of DIM.
Click here to see References
[1] Bradlow HL, Zeligs MA. Diindolylmethane (DIM) spontaneously forms from indole-3-carbinol (I3C) during cell culture experiments. In Vivo. 2010 Jul-Aug;24(4):387-91.
[2] Navarro SL, et al. Cruciferous vegetables have variable effects on biomarkers of systemic inflammation in a randomized controlled trial in healthy young adults. J Nutr. 2014 Nov;144(11):1850-7.
[3] Jiang Y, et al. Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women. J Acad Nutr Diet. 2014 May;114(5):700-8.e2.
[4] Lockheart MS, et al. Dietary patterns, food groups and myocardial infarction: a case-control study. Br J Nutr. 2007 Aug;98(2):380-7.
[5] Zhang X, et al. Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. Am J Clin Nutr. 2011 Jul;94(1):240-6.
[6] Higdon JV, et al. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007 Mar;55(3):224-36.
[7] Tse G, Eslick GD. Cruciferous vegetables and risk of colorectal neoplasms: a systematic review and meta-analysis. Nutr Cancer. 2014;66(1):128-39.
[8] Lam TK, et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):184-95.
[9] Telang NT, et al. Induction by estrogen metabolite 16 alpha-hydroxyestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. J Natl Cancer Inst. 1992 Apr 15;84(8):634-8.
[10] Reed GA, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev 2005;14:1953-1960.
[11] Niwa T, et al. Alterations in estradiol metabolism in MCF-7 cells induced by treatment with indole-3-carbinol and related compounds. Steroids 1994;59:523-527.
[12] Riby JE, et al. Ligand-independent activation of estrogen receptor function by 3,3′-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167-177.
[13] Hong C, et al. Bcl-2 family- mediated apoptotic effects of 3,3′-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol 2002;63:1085-1097.
[14] Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-129.
[15] Furukawa S, et al. Indole-3-acetic acid induces microencephaly in rat fetuses. Toxicol Pathol. 2004;32(6):659-67.
[16] Murray T, Brown D. Vitex agnus castus (Chaste Tree). Pharmacology of Natural Medicines. 1135-1139.
[17] Boon H, Smith M. The Botanical Pharmacy: The Pharmacology of 47 Common Herbs. Kingston, ON: Quarry Press, Inc.; 1999;76-81.
[18] Vitex agnus-castus. Alt Med Rev. 2009:14(1)67-70.
[19] Weiss RF. Herbal medicine. Gothenburg, Sweden: Ab Arcanum; 1988.
[20] Wuttke W, et al. Chaste tree (Vitex agnus-castus) – pharmacology and clinical indications. Phytomedicine 2003;10:348-357.
[21] Sliutz G, et al. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Horm Metab Res. 1993;25:253-255.
[22] Jarry H, et al. Agnus castus as dopaminergous effective principle in mastodynon N. Zeitschrift Phytother. 1991;12:77-82.
[23] King KJ, et al. Effect of increasing ratio of estrogen: androgen on proliferation of normal human prostate stromal and epithelial cells, and the malignant cell line LNCaP. Prostate. 2006 Jan 1;66(1):105-14.
[24] Kim EJ et al. 3,3′-diindolylmethane suppresses 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin via the downregulation of inflammatory mediators. Mol Carcinog 2010 Jul; 49(7): 672-83
[25] Li Y, Sarkar FH. Role of BioResponse 3,3′-diindolylmethane in the treatment of human prostate cancer: clinical experience. Medical Principles and Practice 2016; 25 Suppl 2:11-17
[26] Le HT, et al. Plant-derived 3,3′-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 2003 Jun 6;278(23):21136-45. Epub 2003 Mar 27.
[27] Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. Plant-derived 3,3′-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem 2003;278:21136-21145.
[28] Olaf Hiort, MD. Normal sexual development. UpToDate. Waltham, Mass.: UpToDate; 2017. www.uptodate.com. Accessed August 2, 2018.
[29] Carilla E, et al. Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate. J Steroid Biochem. 1984;20:521-523.
[30] Morgia G, Mucciardi G, Galì A, et al. Treatment of chronic prostatitis/chronic pelvic pain syndrome category IIIA with Serenoa repens plus selenium and lycopene (Profluss) versus S. repens alone: an Italian randomized multicenter-controlled study. Urol Int. 2010;84(4):400-406.
[31] Yarnell E, Abascal K. Serenoa repens (Saw Palmetto). Pharmacology of Natural Medicines. 1021-1025.
[32] Di Silverio F, et al. Evidence that Serenoa repens extract displays antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy. Eur Urol. 1992;21:309-314.
[33] Kim EH, et al. The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia. Asian J Urol. 2018;5(1):28-32.
[34] Ho CK, Habib FK. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol. 2011 Jan;8(1):29-41.
The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
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Dr. Erica Zelfand
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