Humble but Powerful: Cruciferous Vegetables Detoxify via a Potent Molecule Called DIM - News and Education Blog
Quicksilver Scientific
1376 Miners Dr. Lafayette, CO 80026
Phone: (303) 531-0861 Hours: Mon-Fri, 10:00 AM - 5:00 PM
Quicksilver Scientific LLC Medical & Health United States Are you looking for a scientifically advanced health supplement wholesaler? We sell mercury detoxification and heavy metal tests as well as liposomal products. Monday to Friday: 08:00AM-5:00PM

Humble but Powerful: Cruciferous Vegetables Detoxify via a Potent Molecule Called DIM

Wherever you are on your health crusade, you will want to know about a potent, health-promoting compound called diindolylmethane, commonly known as DIM. You are undoubtedly familiar with the vegetable family known as the cruciferous, and its many satisfying, crunchy, often green constituents – kale, collard greens, cabbage, broccoli, and brussels sprouts – to name a few. Cruciferous vegetables seem to be on every menu now – whether it is the taqueria down the street or the invitation-only new trending restaurant in your city. And with good reason! In addition to the flavors and textures they bring to a meal, crucifers have many health benefits.

 

Unique Health Benefits of Cruciferous

Dietary consumption of cruciferous vegetables has been observed to benefit health and overall longevity in many ways. Higher intakes of cruciferous have been associated with a reduction of inflammation, particularly in women,1,2 decreased risk of heart attack and cardiovascular disease-related mortality,3,4 as well as a lower risk of certain types of cancer.5,6,7 DIM is derived from the cruciferous and may be one of the primary contributors to these benefits. DIM is readily formed during the digestive process when indole-3-carbinol (I3C), a somewhat unstable compound directly derived from cruciferous, is exposed to stomach acid.8 It is also increased in crucifers by cooking, which activates an enzyme (myrosinase) responsible for its conversion.9

One of the mechanisms by which this vegetable family may have a positive impact on health is by supporting the body in detoxification.10 There are different estrogen metabolites in the body, some of which are more estrogenic and potentially harmful, while others are more protective.11 Increased intake of the cruciferous vegetables has been observed to shift estrogen metabolism, increasing the balance of the forms of estrogen which may be more protective and reduce risk of hormonal cancers such as breast cancer.5

What is Detoxification?

Unfortunately, the concept of detoxification has been oversimplified in many health-related circles, where fasting, juicing and yoga retreats are often emphasized. Although these approaches may have benefits, they don’t fully encompass the complexities of the larger process and the necessary steps by which detoxification occurs in the body. Thus, to enter in to a discussion of detoxification, some basic higher-level concepts of physiology and biochemistry are necessary to introduce.

Perhaps the most important molecule in detoxification is glutathione. Glutathione is the body’s main antioxidant and is necessary for cellular detoxification throughout your body.12 Glutathione is necessary to protect the cell’s delicate machinery and to transport toxins out of the cell. One of the steps of detoxification involves the binding of toxins to glutathione, creating larger, inactive, water soluble molecules. These water-soluble molecules can easily be transported out of the cell, into the bile, and out of the body via stool.13 Because glutathione is utilized in the process of removing mercury and many other toxins from the cell, it also can become depleted in settings of increased toxicity.14

Arguably as important as glutathione for the process of detoxification is a protein known as Nrf2 (short for nuclear factor E2-related factor). Nrf2 is a cellular switch that orchestrates antioxidant, de­toxification, and cellular defenses. When activated, Nrf2 can switch on over 200 genes that help the cell generate its own highly pro­tective molecules.15,16

Along with Nrf2 is its cellular helper and teammate, known as the antioxidant response element (ARE). Nrf2 is present in the cytosol of the cell, and responds to oxidative stress by translocating to the nucleus and binding to ARE, the promoter region of genes that encode the transcription of critical components of detoxification: antioxidant elements, detoxification enzymes, and proteins required for glutathione synthesis and recycling.17 This includes the phase II detoxification enzymes glutathione S-transferase (GST), glutathione reductase (GSR), and glutathione peroxidase (GPX).18,19,20 The Nrf2/ARE pathway serves a protective role in the body, and is activated by elevated levels of reactive oxygen species (ROS) as well as exposures to air pollution and heavy metals.21,22

Studies have also shown that the ability to upregulate Nrf2 and its antioxidant supporting action declines with age, which may be one reason the elderly are more susceptible to damage from environmental pollutants.23 Additionally, some of the toxic substances which we are exposed to such as ochratoxin A, one of the most common mold toxins found in foods and water-damaged houses, and indoxyl sulfate, a uremic toxin that is increased with exposure to some toxic heavy metals, act as Nrf2 inhibitors, further contributing to toxicity and impaired detoxification.24,25,26,27

Fortunately, there are natural substances that appear to induce Nrf2 and effectively switch on our detoxification pathways and antioxidant defenses. This includes DIM and other favorites such as lycopene (found in tomatoes) and epigallocatechin gallate, or EGCG (found in green tea).28,29 Increasing intake of these substances in the diet definitely can be helpful, but for many who struggle with things such as hormonal imbalance, mold exposure, and other environmental toxicities, dietary intake is usually not enough.

DIM and Hormones

Many integrative healthcare providers utilize DIM to support the body in the metabolism of hormones. The improved metabolism and elimination of the more dangerous forms of estrogen is proposed to be one of the reasons that DIM and cruciferous consumption may be protective against hormone-dependent cancers.30 DIM induces the expression of cytochrome P450 enzymes that are responsible for metabolizing estrogen.31 By inducing these enzymes, DIM helps modify estrogen balance, increasing levels of 2-hydroxy-estrone, a metabolite of estrogen which has been suggested to be protective against breast cancer.32

DIM and Nrf2

Because mold toxins (mycotoxins) can inhibit Nrf2 and our body’s detoxification pathways, we need a strong Nrf2 inducing agent to restore the protective glutathione system, and the associated enzymes necessary for it to do its job as well as recycle it. DIM has a strong Nrf2 activating effect which is not seen with DIM’s precursor I3C.33 By “turning on” the Nrf2 switch, DIM increases the body’s expression of many drug metabolizing enzymes, detoxification-dependent transporters (necessary to get toxins out of the cell), and other antioxidant enzymes.34

The benefits of Nrf2 activation go beyond recovering from mycotoxin exposure and hormone balance. For instance, our skin cells produce Nrf2 to protect themselves from many conditions which increase oxidative stress, such as UVB exposure.35 Improving Nrf2 activation in the skin may be a means to combat sun-related damage,36 as well as immune-mediated conditions of the skin such as dermatitis and vitiligo.37,38

With oral intake, the highest amounts of DIM are found in the liver, followed by the lungs and kidneys.39 The liver and kidneys are the organs in the body most burdened by detoxification, however with exposure to air pollutants, the protective effect of Nrf2 induction by DIM is also important in our lungs.40 Because the body is less effective at inducing Nrf2 with age, substances that promote Nrf2 are not only important to support the body in detoxification, but also may be a means by which to combat the effects that aging has on our body.41

A Bioavailability Problem and Solution

Although DIM may offer a variety of health benefits, when taken in traditional oral formulations such as tablets and capsules it has poor absorption and relatively rapid clearance.42 Lipid-based formulations such as liposomes and nanoemulsions have been shown to dramatically improve bioavailability of DIM as well as a variety of substances.43,44 Absorption of nanoemulsified DIM begins immediately in the oral cavity, as the tiny, nano-sized particles enter circulation, evading breakdown by digestive secretions. Studies have also show that nanoemulsified delivery formats also prolong the time a therapeutic agent is in circulation, leading to reduced need for dosing.45

 


1 Navarro SL, Schwarz Y, Song X, 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. View Full Paper

2 Jiang Y, Wu SH, Shu XO, 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. View Full Paper

3 Lockheart MS, Steffen LM, Rebnord HM, et al. Dietary patterns, food groups and myocardial infarction: a case-control study. Br J Nutr. 2007 Aug;98(2):380-7. View Abstract

4 Zhang X, Shu XO, Xiang YB, 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. View Full Paper

5 Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007 Mar;55(3):224-36. View Full Paper

6 Tse G, Eslick GD. Cruciferous vegetables and risk of colorectal neoplasms: a systematic review and meta-analysis. Nutr Cancer. 2014;66(1):128-39. View Abstract

7 Lam TK, Gallicchio L, et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):184-95. View Full Paper

8 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. View Full Paper

9 Ciska E, Verkerk R, Honke J. Effect of boiling on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. J Agric Food Chem. 2009 Mar 25;57(6):2334-8. View Abstract

10 Nho CW, Jeffery E. The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous vegetables. Toxicol Appl Pharmacol. 2001 Jul 15;174(2):146-52. View Abstract

11 Telang NT, Suto A, Wong GY, 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. View Abstract

12 Devasagayam TP, et al. Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India. 2004 Oct;52:794-804. View Abstract

13 Zamek-Gliszczynski MJ, et al. Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and GSH metabolites. Eur J Pharm Sci. 2006 Apr;27(5):447-86. View Abstract

14 Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. View Full Paper

15 Bruni F, Polosa PL, Galadeta MN. Nuclear Respiratory Factor 2 Induces the Expression of Many but Not All Human Proteins Acting in Mitochondrial DNA Transcription and Replication J Biol Chem. 2010 February 5; 285(6): 3939–3948. View Full Paper

16 Petri S, Körner S, Kiaei M. Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS. Neurol Res Int. 2012;2012:878030. View Full Paper

17 Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009 May 15;284(20):13291-5. View Full Paper

18 Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22. View Abstract

19 Harvey CJ, Thimmulappa RK, Singh A, et al. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med. 2009 Feb 15;46(4):443-53. View Full Paper

20 Singh A, Rangasamy T, Thimmulappa RK, et al. Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2. Am J Respir Cell Mol Biol. 2006 Dec;35(6):639-50. View Full Paper

21 Risom L, Møller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res. 2005 Dec 30;592(1-2):119-37. View Abstract

22 Simmons SO, Fan CY, Yeoman K, et al. NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent. Curr Chem Genomics. 2011;5:1-12. View Full Paper

23 Zhang H, et al. Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med. 2012 May 1;52(9):2038-46. View Abstract

24 Limonciel A, Jennings P. A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity. Toxins (Basel). 2014 Jan 20;6(1):371-9. View Full Paper

25 Hung SC, et al. Indoxyl Sulfate: A Novel Cardiovascular Risk Factor in Chronic Kidney Disease. J Am Heart Assoc. 2017 Feb 7;6(2). View Full Paper

26 Lan Z, Bi KS, Chen XH. Ligustrazine attenuates elevated levels of indoxyl sulfate, kidney injury molecule-1 and clusterin in rats exposed to cadmium. Food Chem Toxicol. 2014 Jan;63:62-8. View Abstract

27 Bolati D, et al. Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-κB. BMC Nephrol. 2013 Mar 4;14:56. View Full Paper

28 Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signalling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008 Oct;74(13):1526-39. View Full Paper

29 Saw CL, Cintrón M, Wu TY, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011 Jul;32(5):289-300. View Full Paper

30 Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016 Jul;74(7):432-43. View Full Paper

31 Szaefer H, Licznerska B, Krajka-Kuźniak V, et al. Modulation of CYP1A1, CYP1A2 and CYP1B1 expression by cabbage juices and indoles in human breast cell lines. Nutr Cancer. 2012 Aug;64(6):879-88. View Abstract

32 Dalessandri KM, et al. Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7. View Abstract

33 Ernst IM, Schuemann C, Wagner AE, Rimbach G. 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. Free Radic Res. 2011 Aug;45(8):941-9. View Abstract

34 Saw CL, Cintrón M, Wu TY, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011 Jul;32(5):289-300. View Full Paper

35 Gęgotek A, Skrzydlewska E. The role of transcription factor Nrf2 in skin cells metabolism. Arch Dermatol Res. 2015 Jul;307(5):385-96. View Full Paper

36 Kokot A, Metze D, Mouchet N, et al. Alpha-melanocyte-stimulating hormone counteracts the suppressive effect of UVB on Nrf2 and Nrf-dependent gene expression in human skin. Endocrinology. 2009 Jul;150(7):3197-206. View Full Paper

37 Tsuji G, Takahara M, Uchi H, et al. Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect. J Invest Dermatol. 2012 Jan;132(1):59-68. View Abstract

38 Guan CP, Zhou MN, Xu AE, et al. The susceptibility to vitiligo is associated with NF-E2-related factor2 (Nrf2) gene polymorphisms: a study on Chinese Han population. Exp Dermatol. 2008 Dec;17(12):1059-62. View Abstract

39 Anderton MJ, Manson MM, Verschoyle R, et al. Physiological modeling of formulated and crystalline 3,3'-diindolylmethane pharmacokinetics following oral administration in mice. Drug Metab Dispos. 2004 Jun;32(6):632-8. View Full Paper

40 Risom L, Møller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res. 2005 Dec 30;592(1-2):119-37. View Abstract

41 Zhang H, Davies KJA, Forman HJ. Oxidative stress response and Nrf2 signaling in aging. Free Radic Biol Med. 2015 Nov;88(Pt B):314-336. View Full Paper

42 Wu TY, Huang Y, Zhang C, et al. Pharmacokinetics and pharmacodynamics of 3,3'-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes. J Pharmacokinet Pharmacodyn. 2015 Aug;42(4):401-8. View Abstract

43 Paltsev M, Kiselev V, Muyzhnek E, et al. Comparative preclinical pharmacokinetics study of 3,3'-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon? EPMA J. 2013 Dec 10;4(1):25. View Full Paper

44 Yang Z, Lu A, Wong BC, et al. Effect of liposomes on the absorption of water-soluble active pharmaceutical ingredients via oral administration. Curr Pharm Des. 2013;19(37):6647-54. View Abstract

45 Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015 Apr;5(2):123-127. View Full Paper

What is YOUR Multivitamin Really Delivering?
Stress Support 103: Seawater Minerals Support Para...

Related Posts

 

Comments

No comments made yet. Be the first to submit a comment
Already Registered? Login Here
Guest
Saturday, 18 November 2017
If you'd like to register, please fill in the username, password and name fields.