Indole 3 Carbinol Effect on Systemic Lupus Erythematosus



Summary: Systemic lupus erythematosus (SLE), commonly called lupus, is an inflammatory, autoimmune disorder affecting the skin, joints, kidneys, brain and other organs where the body's immune system mistakenly attacks healthy tissue. Lupus predominantly strikes women during the years when they are menstruating and their estrogen levels are highest. The link between lupus and estrogen is an area of intense study as is the role of a natural substance found in all cruciferous vegetables called indole 3 carbinol (I3C).

Indole 3 Carbinol Effect on Systemic Lupus Erythematosus (SLE)

Sex hormones, also known as steroid hormones, play an important role modulating autoimmune disease onset and perpetuation. The class of sex hormones include estrogen, progesterone and testosterone. These hormones help control metabolism, inflammation, immune functions, salt and water balance, development of sexual characteristics, and the ability to withstand illness and injury.

It has been known for many years that certain forms of estrogen are pro-inflammatory. Not the basic forms of estrone, estriol and estradiol, but the hydroxylated form of estrone in particular. Simply put, hydroxylation is a detoxification process. For the purposes of this discussion, we will refer to it as a step in the chemical reactions necessary to convert estrogens into other substances that can be excreted out of the body.

Estrogen metabolism in women with SLE is known to be shifted towards higher production of a hydroxylated estrogen called 16-alpha-hydroxyestrone, a very powerful compound that, research suggests, fuels disease activity. Blood levels of 16-alpha-hydroxyestrone have been found to be higher in both men and women with SLE and rheumatoid arthritis. There is a 70% prevalence in females. This leads to a possible connection that ALL inflammatory, autoimmune conditions have the same higher hydroxylated estrogen levels.

It should be mentioned that estrogen can be created by our body...more by women than men...and both men and women can absorb estrogens or estrogen like substances from the environment.

Cruciferous Vegetable ListCruciferous vegetables, such as broccoli, cauliflower, cabbage and Brussel sprouts, contain a compound called indole-3-carbinol (I3C). I3C increases the activity of a detoxifying enzyme in the liver called Cytochrome P450 1A1. This enzyme shifts estrogen metabolism so that a much weaker estrogenic compound, 2-hydroxyestrone, is produced, thus lessening disease risk.

McAlindon and colleagues from Boston University School of Medicine evaluated whether I3C can help shift estrogen metabolism so that weaker estrogenic compounds would be produced in women with lupus (Lupus 2001;10:779-783). To do so, they conducted a small trial on seventeen premenopausal women, lasting  three months with each woman receiving a 125 mg capsule of I3C, three times a day. To monitor the impact of supplementation on the women's estrogen metabolism, researchers repeatedly measured the ratio of two important estrogen metabolites in urine, 16-alpha-hydroxyestrone (16-alpha-OHE1) and 2-hydroxyestrone (2-OHE1).

2-hydroxyestrone is the competing estrogen in the body to 16-alpha-hydroxyestrone. The ratio between the two is an important measurement that most people never get tested for.  More and more research suggests that when too much of the stronger estrogen metabolite 16-alpha-hydroxyestrone is produced relative to the amount of the weaker metabolite, 2-hydroxyestrone, this increases a woman's risk for diseases influenced by estrogen activity, such as breast cancer and osteoporosis, as well as this study suggests, SLE. This also bodes well for similar effects on other inflammatory conditions.

After just one week of I3C therapy, urinary testing found the 2:16 alpha-hydroxyestrone ratio in the women with lupus had increased over 70%, a change mostly due to increased production of 2-hydroxyestrone. After three months of I3C therapy, researchers noted a "modest" decrease in SLE disease activity as well as a "modest" drop in the use of prednisone, an anti-inflammatory drug. The authors concluded that "I3C does exert metabolic influences on estrogen metabolism in women with SLE which could benefit women with this disorder."

There are many other studies linking I3C to the prevention of or effect on different types of cancers.

So, do these questions make sense to ask:

  1. Does a lifestyle that includes the consumption of cruciferous vegetables lead to healthier outcomes years down the road? A cup of raw broccoli contains approximately 115-165mg of I3C. Approximately the same amount, about 125-150 mg, is contained in 1/4 medium-sized head of raw green cabbage.
  2. Does laboratory testing looking at the ratio of 2:16 hydroxyestrone make sense as a preventative measure for the healthy? Does this test make sense for those diagnosed with autoimmune and/or inflammatory conditions like Addison's Disease, Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease), Hashimoto's thyroiditis, Crohn's Disease, all types of colitis, arthritis, rheumatoid arthritis (RA), psoriatic arthritis, Multiple Sclerosis, Meniere's disease, myasthenis gravis, Raynaud's disease, fibromyalgia, Sjogren's Syndrome, lupus, scleroderma, ankylosing spondylitis, interstitial cystitis, depression, asthma, heart disease, diabetes, Alzheimer’s and osteoporosis? Does this laboratory testing make sense to prevent cancer or to help treat cancer?
  3. Does the inclusion of a dietary supplement of 150 mg. Indole-3-Carbinol (I3C) per tablet make sense if positive lab results are found for the imbalanced 2:16 hydroxyestrone ratio as a preventative measure or as a treatment for those with diagnosed conditions?
My opinion? Yes, to all the above.

The specific laboratory test that will inform us of your ratio of 2:16 hydroxyestrone is from Metametrix Labs and is called Estronex Profile - Urine. The cost of the test is $295. Call Dr. Dahlman's office to order this test kit.



References:

  1. Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo controlled trial of indole-3-carbinol in the treatment of CIN. Gyneeol Oneol. 2000;78:123-129.
  2. Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab Disord 1998;22(3):227-229.
  3. Michnovicz JJ. Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 1991;16:59-66.
  4. McAlindon TE, Gulin J. Chen T, Klug T, Lahita R, Nuite M. lndole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus. 2001;10(11)779-783.
  5. Taioli E, Bradlow HL, Garbers SV, et al. Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev. 1999;23(3):232-237.
  6. Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998;118(6):810.815,
  7. Bradlow HL, Michnovicz JJ. Halper M, Miller DG, Wong GY, Osborne MP. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev. 1994;3(7):591-595.
  8. Michnovicz JJ. Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997;89:718-723.
  9. Zhu BT, Loder DP, Cai MX, et al. Dietary administration of an extract of rosemary leaves enhances the liver microsomal metabolism of endogenous estrogens and decreases their uterotropic action in CD-1 mice, Carcinogenesis. 1998;19 (10) :1821-1827.
  10. Auborn KJ, Qi M, Yan XJ, Teichberg S, Chen D, Madaio MP, Chiorazzi N., Lifespan is prolonged in autoimmune-prone (NZB/NZW) F1 mice fed a diet supplemented with indole-3-carbinol. J Nutr., 2003 Nov;133(11):3610-3.
  11. Sarkar FH, Li Y., Indole-3-carbinol and prostate cancer. J Nutr. 2004 Dec;134(12 Suppl):3493S-3498S.
  12. Karen J. Auborn. Can indole-3-carbinol-induced changes in cervical intraepithelial neoplasia be extrapolated to other food components? J Nutr. 2006;136(10):S2676-S78. PMID: 16988146
  13. Eleanor G. Rogan. The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo. 2006;20(2):221-28. PMID: 16634522






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