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Diindolylmethane

 

 

Study nature, love nature, stay close to nature.

It will never fail you.

 

-Frank Lloyd Wright

 

 

The primary role of Diindolylmethane (DIM) is to change the way estrogen is metabolized in the body. DIM helps break estrogen down into metabolites that have antioxidant properties. In doing so it helps protect the body from damage by free radicals. DIM is often used to manage hormone levels, especially for testosterone and estrogen. It also provides support for the prostate, antioxidant activity, and weight management. DIM can also help manage menstrual symptoms including moodiness and breast tenderness.

 

 

 

 

DIM is a component of Indole-3-carbinol found in cruciferous vegetables, cabbages, and mustard plants. It is in broccoli, Brussels sprouts, cauliflower and kale. Lab studies suggest it has anti cancer benefits. It may be beneficial for fighting and preventing cancers of the bladder, breast, ovaries, lymphatic system, nasal passages, and prostate. Studies suggest DIM may also offer some protection from ionizing radiation.

Estrogen

 

 

Estrogens are hormones that are important for sexual and reproductive development, mainly in women. Though referred to as female sex hormones, estrogen is also required by men. Estrogen refers to chemically similar hormones and consist of estrone, estradiol and estriol.

In women, estrogen is produced mostly in the ovaries. Some is produced by fat cells and the adrenal gland. Estrogen plays a role in the development of female sex characteristics including pubic hair, armpit hair, wider hips and breasts. It also helps regulate the menstrual cycle, control lactation and other changes in the breasts at adolescence, the menstrual cycle and during pregnancy. Estrogen also plays a role in blood clotting, vaginal lubrication and many other bodily functions.

Men produce lower levels of estrogen from the adrenal glands and the testes.

Testosterone

 

Testosterone is an important component of the hormone equation in both men and women. It is known for regulating the development and maintenance of male characteristics in vertebrates. These include male distribution of body hair, a deeper voice, and male genital development. Testosterone is also identified as an anabolic (growth) hormone due to its ability to promote protein synthesis. Active protein synthesis produce stronger bones and bigger muscles, especially after exercise. It also increases metabolic rates and consumes fat which results in making the body leaner. Testosterone also supports mood and libido. It has a clear anti-depressant response and promotes interest in sex for both men and women.

Free testosterone crosses easily into the brain, muscles and fat cells. Most of the desirable effects of testosterone comes from free testosterone. Free testosterone represents about 2% of total testosterone in men and less in women.

Causes of Hormonal Imbalance

 

 

 

Causes of Hormonal Imbalance

 

 

 

A number of factors contribute to the disruption of our hormonal balance. Some are natural however most has to do with modern living and lifestyle choices.

 

Modern Environment

 

Our modern environment is flooded with synthetic estrogens known as xenoestrogens. These synthetic estrogens are absorbed primarily through our skin and digestive tract. Xenoestrogens mimic the estrogen in your body in ways which result in lower testosterone levels and increased estrogen levels. They can be found in feedlot beef and dairy that is pumped up with synthetic growth hormones. Other sources include plastics, paper receipts, household cleaning products, soap, hand sanitizers, hair, nails and body care products, cosmetics, non-organic fruit, pesticides, fungicides, herbicides and more.

 

Xenoestrogens disrupt the internal balancing mechanisms of the body, raising the estrogen burden and potentially the risks of breast cancer. Xenoestrogens accumulate in body fat such as breast tissue. They can displace natural estrogens from the receptor sites of the cell. Xenoestrogens are toxic to our DNA and are widely seen as a contributor to the rising rate of breast cancer in western countries.

 

Lifestyle

 

Alcohol, smoking, obesity, lack of exercise, stress, adrenal fatigue, and exhaustion all contribute to estrogen imbalance. Moreover, the chronic inflammation associated with these conditions increases the conversion of testosterone into estrogen.

 

Aging

 

Menopause is a natural biological process in women that can happen in their 40s or 50s. In the US the average age for menopausal women is 51. Menopause can occur earlier for smokers. It happens when the ovaries reduce production of the hormones estrogen and progesterone. During this transition, the amount of progesterone may be reduced more quickly than the estrogen, resulting in a kind of estrogen dominance.

 

Andropause, the male equivalent of menopause, is associated with reduced levels of testosterone. Unlike menopause, the decrease in hormones and the development of symptoms is more gradual (see graph below). About one third of men in their 50s will experience the symptoms of andropause. Men approaching their senior years while experiencing andropause may have a number of symptoms related to the condition and could be at risk of other serious health conditions such as osteoporosis. A specific issue with male aging has to do with the aromatase enzyme that converts testosterone into estrogen. Aromatase activity increases with age and has been associated with abdominal obesity, inflammation, and diabetes. This change, together with a fall in testosterone levels, is referred to as andropause.

 

Diet

 

The awareness of GMO foods and the risks associated with their consumption has been on the rise in recent years. However North Americans have been consuming GMO-based foods for 20 years now. Genetically modified microbial enzymes were the first application of genetically modified organisms in food production and were approved in 1988 by the US FDA. By 1995, GMO based potatoes, tomatoes, soybeans, and squash had received marketing approval. In 2015, 92% of corn and 94% of soybeans produced in the US were genetically modified strains.1 Corn is a common input for many other food products. These products include cereals, snack foods, salad dressings, soft drink sweeteners, whiskey, chewing gum, peanut butter, hominy grits, taco shells and other flour products, specialty corn including white and blue corn, and popcorn. Soybeans also has widespread use in food production and can be found in meat substitutes, tofu, soy sauce, bread crumbs, crackers, meal replacements, simulated bacon bits, and cooking sprays.

 

Insulin Resistance

 

Insulin resistance occurs when the body has more sugar than it can handle. The syndrome is associated with rising rates of obesity and diabetes. Insulin resistance indirectly raises estrogen levels by increasing body fat because the fats store estrogen.

 

Hormone Replacement Therapy and Birth Control

 

Hormone Replacement Therapy (HRT) products and many oral contraceptives contain estrogen without the necessary progesterone to maintain a proper balance. Moreover, the hormones used in both HRT and birth control tend to be synthetic hormones that are toxic and easily metabolized by the liver.

 

High Sex Hormone-Binding Globulin Production and Its Feedback Effect

 

High estrogen levels causes the liver to produce more of the carrier protein for testosterone, which is known as sex hormone-binding globulin (SHBG), leading to less free testosterone. High levels of SHBG lock up free testosterone making it unavailable to support mood or metabolism. This feedback effect results in even greater imbalance between estrogen and testosterone.

 

People should consider themselves fortunate if they have not been affected. However, if you are not ill or showing signs of estrogen dominance does not mean your hormones are in balance. You may be at an earlier stage, or just a little out of balance. Sometimes we become so adept at coping that we do not notice the symptoms anymore. We recommend that you try DIM for a few weeks and see if it improves the quality of your life.

 

 

 

DIM at Work

 

 

 

Estrogen comes in different forms and all are needed in the body in balanced amounts. When the different estrogens become unbalanced it can lead to various health issues. One common estrogen imbalance occurs when 16-hydroxy levels are too high relative to 2-hydroxy levels. DIM naturally balances the estrogen hormones by increasing or decreasing an estrogen hormone by directing it through different metabolic pathways. It directs the estrogen factory to make more of the protective estrogens and less of the other kinds. The 2-hydroxy metabolites of estrogen promoted by DIM are the only hormone metabolites known to increase levels of the free form of testosterone. Higher 2-hydroxy levels provide the best balanced response to low testosterone, in men and women.

 

 

Benefits of Diindolylmethane (DIM)

 

 

Benefits of DIM

 

 

 

DIM improves metabolism naturally by working with your hormones and adjusting their action to avoid hormonal imbalance. It helps produce more of the protective estrogens and these estrogens compete with testosterone for protein binding. This results in higher free testosterone levels which is the more active form of testosterone. The protective estrogens, along with increased free testosterone, increase fat mobilization and a fat-burning metabolism.

 

Many of the benefits that are attributed to estrogen, including its ability to protect the heart and brain with its antioxidant activity, are known to come from this protective estrogen known as 2-hydroxy estrogens. When DIM increases the 2-hydroxy estrogens, there is a simultaneous reduction of other estrogen metabolites, such as 16-hydroxy and 4-hydroxy. Increased production of 16-hydroxy and 4-hydroxy estrogens is promoted by obesity, social drinking, and exposure to a number of man-made environmental chemicals. If we want to achieve a healthy estrogen balance, boosting 2-hydroxy estrogen production while lowering 16-hydroxy and 4-hydroxy estrogens is generally considered a step in the right direction.

 

More Free Testosterone

 

DIM supports free testosterone without changing overall testosterone levels. It does not raise testosterone levels but supports its activity through its effects on estrogen metabolism. This helps to maintain higher levels of free testosterone. 2-hydroxy estrogen metabolites support more efficient fat metabolism and boost free testosterone. Higher free testosterone levels lead to more efficient muscle growth, weight loss and improved mood.

 

Muscle Growth

 

Increased free testosterone levels lead to the development of stronger and more metabolically active muscles. 2-hydroxy estrogen metabolites and free testosterone provide a hormonal signal for muscles to grow by adding more of the structural protein needed for size, strength, and movement. DIM assists in the conversion of estrogen to protective estrogen. It protects stressed muscle cells and allows more efficient repair and growth. Less pain with more gain.

 

 

Weight Loss

 

2-hydroxy estrogen metabolites support more efficient fat metabolism. There is also a weight loss feedback mechanism at play that works in your favor. Individuals with stronger muscles have a greater capacity to burn fat and maintain a lean body. Studies suggest a connection between high testosterone-to-estrogen ratios and lean body mass, increased fat-burning metabolism, and less abdominal fat.

 

 

 

Mood

 

Slow estrogen metabolism can reduce the activity of the small amount of testosterone present in women. Free testosterone in women is closely linked to positive mood, interest in sex, and an active aerobic metabolism. In men, low levels of free testosterone along with high estrogen levels are associated with excess body fat, reduced sex drive, depression, irritability and erectile dysfunction.

 

 

 

 

Prostate Health

 

DIM can help improve prostate health and help guard against prostate enlargement. As men age, unmetabolized estrogen accumulates in the prostate tissue. Exposure of human prostate tissue to un-metabolized estrogen in the laboratory resulted in activation and increased production of prostate-specific antigen protein (PSA). Elevated levels of PSA are associated with prostate cancer and other prostate disorders. DIM directly slows the production of PSA from prostate cells, independent of its effects on estrogen metabolism.

 

Improved Circulation and Memory

 

2-hydroxy estrogen metabolites provide antioxidant protection for the heart and brain.
Estrogen’s healthy metabolism supports better functioning heart and circulation, and improved memory. The risk of early heart attack associated with higher estrogen levels has been documented in several large studies, including the Framingham Heart Study in the United States. The results indicate that men with the highest estrogen levels have the greatest risk of heart attack at a younger age.

 

Immune System Support

 

DIM has also been shown to help control viral infections, support immune function and reduce certain forms of inflammation.

 

Scientists discovered that DIM is a potent modulator of the innate immune response system and this lead to the discovery of DIM’s anti-viral properties (including anti-viral properties against the Human Papilloma Virus). It is being investigated for use in a variety of viral and bacterial infections including HPV, HIV, Hepatitis, Influenza, the Pandemic Flu and antibiotic resistant bacteria. It has also shown potential for immune deficiency conditions, dermatological conditions such as acne caused by infections, and multiple forms of cancer. Given the many favorable biological activities, including immune modulation, apoptosis promotion and suppression of inflammation, the National Cancer Institute has begun clinical studies of DIM for treating many forms of cancer.

 

A study was done to test the hypothesis that DIM modulates the immune function in mice and rodents.2 The effects were evaluated in panel tests that included splenocyte (spleen blood cells) proliferation , reactive oxygen species generation (free radicals), cytokine production (immune signalling) and resistance to viral infection. The findings suggest that DIM may be a potent stimulator for the immune system.

 

DIM has been shown to have promising cancer protective activities, especially against mammary neoplasia in animal models.3 In this study, it was observed that DIM activated a signaling pathway in human breast cancer cells. DIM activated the expression of the IFNgamma receptor (IFNGR1) and IFNgamma-responsive genes which involves immune signalling. These results reveal unique immune activating and potentiating activities of DIM in human tumor cells that may contribute to its established effectiveness against various tumor types.

 

Detox Support

 

DIM promotes healthy cell cycle functions and hormone metabolism that support the liver. Low doses of DIM along with Folate and B12 can help alter estrogen detoxification pathways in the gut and liver and improve the 2:16 -hydroxy ratios while reducing excessive estrogen activity.

 

Lower Risk of Cancer

 

Numerous studies suggest that DIM has the potential to fight a variety of cancers. This includes cancers of the bladder, breast, ovaries, prostate, lymphatic system, nasal cavity, and more. The research on these cancers will be briefly discussed later. The range of cancers affecting us is not surprising given the widespread and sustained exposure to synthetic estrogens that we have had in North America.

Benefits Summary

 

 

Benefits Summary

 

 

 

DIM helps to eliminate active estrogen by promoting its conversion to the protective estrogen metabolites. These protective estrogen metabolites, which have a great attraction to the SHBGs that bind to testosterone, help move testosterone off those proteins, creating more free testosterone. By using DIM we can raise protective estrogens and free testosterone levels in the same stroke. Higher free testosterone levels can improve muscular development, mood, fight depression, support memory and support the immune system. Other benefits of free testosterone and a higher testosterone-to-estrogen ratio include more interest in sex, longer-lasting erections, and improved cardiovascular health.

 

In addition to numerous benefits throughout the body DIM appears to have anti-cancer and some radiation protection benefits.

Potential Cancer Fighting Benefits

 

 

Potential Cancer Fighting Benefits

 

 

 

Protective estrogens act as powerful antioxidants. These estrogen metabolites help reduce the risk of a range of cancers that are associated with increased free-radical damage. This includes cancer of the breast, ovaries, prostate, bladder, nasal cavity and leukemia.

We will now briefly touch upon some of the research done in these areas.

 

Breast and Ovarian Cancer

 

Lab studies has shown that DIM reduces the production of two proteins needed for breast and ovarian cancer to spread.4 The UCLA team behind this study plans to test the theory using mice. Cancer cell membranes have high levels of a surface receptor known as CXCR4, while the organs to which the cancers spread secrete high levels of CXCL12, a ligand (binder or molecular link) that binds to the cancer cell surface receptor. This stimulates cancer cells and acts like a homing device, drawing the cancer cells to other organs like the liver and brain. DIM-treated cancer cells had significantly reduced movement toward CXCL12.

 

A pilot study to examine the effect of DIM on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer showed an increase in the 2-hydroxy metabolites.5 The subjects were postmenopausal women aged 50-70 years from Marin County, California, with a history of early-stage breast cancer. The treatment group received 100 mg of DIM per day for 30 days. DIM-treated subjects showed a significant increase in levels of 2-hydroxy, diindolylmethane, and cortisol.

 

Human breast cancer cell lines were studied to better understand its mechanisms.6 DIM was found to inhibit the growth of all four breast cancer cell lines.

 

Prostate Cancer

 

Unmetabolized estrogen accumulates overtime in prostate gland tissue in men as they age and also in the prostate gland around age 50. Estrogen is associated with the degree of prostate enlargement. DIM appears to help prevent the spread of cancer cells and also encourages their programmed cell death.7 DIM is able to stop the cell cycle progression of human prostate cancer cells. DIM induces apoptosis and inhibited growth, angiogenesis, and invasion of prostate cancer cells.8 Results suggest that DIM could be a potent agent for the prevention and/or treatment of both hormone sensitive as well as hormone-resistant prostate cancer. DIM also supports the growth inhibition effect on human prostate cancer cells.9

 

Bladder Cancer

 

Bladder cancer has been shown to resist programmed cell death with altered expression of both pro-apoptotic and anti-apoptotic proteins. A 2016 study showed the administration of DIM along with lupeol inhibited the progression of bladder cancer in rats.10 Lupeol is a pharmacologically active compound found in a variety of plants, including mango. It is also found in dandelion coffee. The DIM and lupeol treatment induces apoptosis and cellular proliferation by its anti-carcinogenic properties.

 

Leukemia

 

Eukaryotes are organisms whose cells have a nucleus enclosed within membranes (e.g. humans). G1 is the first of four phases of the cell cycle that takes place in eukaryotic cell division. DIM has been shown to induce G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells.11

 

Nasal Cancer

 

A study demonstrated that DIM induced apoptosis and inhibited proliferation in nasopharyngeal carcinoma cells by down-regulating the activity of telomerase.12 A carcinoma is a cancer that begins in a tissue which lines the inner or outer surfaces of the body. Telomerase, like telomeres, is a key component to cell aging. In addition to prolonging healthy cell life, we can also benefit from reduced cancer cell life. The study confirmed that DIM had pro‑apoptotic and anti‑proliferative effects in nasopharyngeal carcinoma cells by regulating telomerase.

 

Protection from Radiation

 

Protection from Radiation

 

 

 

DIM offers some protection against ionizing radiation by a unique mechanism. One study reported that DIM in a multi-dose schedule protected rodents against lethal doses of total body irradiation for up to 13 grays.13 A dose of about 3-5 grays could kill a person within a few weeks if not treated. The finding suggests that DIM is a potent radio-protector that functions by stimulating survival signaling.

When To Use DIM

 

 

When To Use DIM

 

 

 

Any healthy issues relating to testosterone and estrogen levels is an indication that a DIM supplement may helpful. Premenstrual Syndrome (PMS) symptoms are the most common indications that women may need DIM. These symptoms include fatigue, bloating, weight gain, breast tenderness, acne, sleep disturbances, and appetite changes such as overeating or food cravings. Men benefit from DIM as well, especially those with low testosterone levels, which can cause low moods and a poor libido. It is common for men who train for muscle mass to take DIM for less inflammation and better recovery.

 

Doses and Safety

 

 

Doses and Safety

 

 

 

Doses for pre-menopausal women with symptoms of estrogen dominance, which include breast pain, painful periods, excessive periods, and PMS, are about 130 – 300 mg per day.

 

For men, the usual dose is 130 – 400 mg per day taken with food. The higher end of the range are for men working through a physical conditioning plan.

 

A study using single-doses of DIM in drug-free, non-smoking, healthy men and women showed no adverse effects were for doses up to 200 mg. At 300 mg dose, one of six subjects reported mild nausea and headache and one also reported vomiting.14

 

Initially, taking DIM may cause headaches and darkened urine. Supporting kidney function is recommended when starting to take DIM. The Zen Haus DIM-Select™ formula, which includes selected herbal and plant extracts, targets effectiveness and potency. This may result in a regular dose being too strong for some people. If the effects of taking DIM are overwhelming try taking a half-dose each day and increasing the dose later. Zen Haus DIM-Select™ tablets are scored for this purpose. Consistency is important but it is also fine to skip a day once in a while. There is no need to make up for any missed doses.

 

DIM is not recommended for pregnant and lactating women who may be pregnant or who are trying to become pregnant.

Summary

 

 

Summary

 

 

The protective estrogen metabolites are natural regulators of energy metabolism. They promote the active release of stored fat for more energy during exercise. DIM contributes to improved estrogen metabolism naturally by working with your hormones and adjusting their action to avoid hormonal imbalance.

Hormonal imbalance may have natural causes as well as those stemming from modern living and lifestyle choices.

  • Aging brings about menopause in women and andropause in men.
  • The modern environment in North America is flooded with xenoestrogens
  • Lifestyles involving alcohol, smoking, obesity, lack of exercise, stress and adrenal fatigue
  • Consumption of GMO-based foods
  • Insulin resistance increases body fat where more estrogen is stored
  • Hormone Replacement Therapy and Birth Control
  • Sex Hormone-Binding Globulin Production Feedback Effect

 

DIM increases 2-hydroxy estrogen production and there is a simultaneous reduction of other estrogen metabolites, such as 16-hydroxy and 4-hydroxy. The 2-hydroxy metabolites of estrogen promoted by DIM are the only hormone metabolites known to increase levels of free testosterone.

 

2-hydroxy estrogen has protective qualities and have a great attraction to the SHBGs that bind to testosterone. This displaces testosterone from SHBGs and effectively creates free testosterone. DIM helps raise both protective estrogens and free testosterone. Higher free testosterone levels can improve muscular development, mood, fight depression, support memory and support the immune system. Other benefits include more interest in sex, and improved cardiovascular health.

 

Estrogen imbalance or dominance is typically often seen as a women’s health issue but men are also affected. Excess estrogen in men can lead to significant health problems, such as prostate enlargement, weak or short-lived erections and breast development.

 

Protective estrogens act as powerful antioxidants. These estrogen metabolites help reduce the risk of a range of cancers that are associated with increased free-radical damage. There is ongoing research for the relationship between DIM and cancers of the breast, ovaries, prostate, bladder, nasal cavity and leukemia.

 

These days hormone regulation and related issues like weight gain and fatigue are a primary concern. Also, the incidence of breast cancer and prostate cancer are too common to ignore. As we begin to understand the causes and appreciate the negative effects of our environment and lifestyle we expect that there will be some course correction. However, this will take time. For now, DIM can help correct and protect against hormone imbalance, particularly in the case of estrogen dominance.

 

References

 

1) Adoption of Genetically Engineered Crops in the U.S.: Recent Trends in GE Adoption. Retrieved from https://www.ers.usda.gov/data-products/adoption-of-genetically-engineered-crops-in-the-us/recent-trends-in-ge-adoption.aspx

 

2) Xue, L., Pestka, J. J., Li, M., Firestone, G. L., Bjeldanes, L. F. (2007). 3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo. The Journal of nutritional biochemistry, 19(5), 336-344. https://doi.org/10.1016/j.jnutbio.2007.05.004

 

3) Riby, J.E., Xue, L., Chatterji, U., Bjeldanes, E.L., Firestone, G.L., Bjeldanes, L.F. (2006). Activation and Potentiation of Interferon-γ Signaling by 3,3′-Diindolylmethane in MCF-7 Breast Cancer Cells. Molecular Pharmacology, 69(2), 430-439. https://doi.org/10.1124/mol.105.017053

 

4) Hsu, E. L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R. T., & Hankinson, O. (2009). Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals. Journal of Oncology, 491985. https://doi.org/10.1155/2009/491985

 

5) Dalessandri, K.M., Firestone, G.L., Fitch, M.D., Bradlow, H.L., Bjeldanes, L.F. (2004) Pilot Study: Effect of 3,3′-Diindolylmethane Supplements on Urinary Hormone Metabolites in Postmenopausal Women With a History of Early-Stage Breast Cancer. Nutrition and Cancer, 50:2, 161-167. https://doi.org/10.1207/s15327914nc5002_5

 

6) Wang, Z., Yu, B.W., Rahman, K.,W., Ahmad, F., Sarkar, F.H. (2008) Induction of growth arrest and apoptosis in human breast cancer cells by 3,3-diindolylmethane is associated with induction and nuclear localization of p27kip. Molecular Cancer Therapeutics, 7(2), 341–349. https://doi.org/10.1158/1535-7163.MCT-07-0476

 

7) Vivar O.I., Lin, C.L., Firestone, G.L., Bjeldanes, L.F. (2009) 3,3′-Diindolylmethane induces a G(1) arrest in human prostate cancer cells irrespective of androgen receptor and p53 status. Biochemical Pharmacology, 78(5), 469-476. https://doi.org/10.1016/j.bcp.2009.05.008.

 

8) Chinnakannu, K., Chen, D., Li, Y., Wang, Z., Dou, Q.P., Reddy, G.P., Sarkar, F.H. (2009). Cell Cycle‐Dependent Effects of 3,3′‐Diindolylmethane on Proliferation and Apoptosis of Prostate Cancer Cells. Journal of Cellular Physiology, 219, 94-99. https://doi.org/10.1002/jcp.21650

 

9) Tsai, J., Chou, C. Liu, S., Liang, W., Kuo, C., Liao, W., … Jan, C. (2012). Effect of diindolylmethane on Ca2+ homeostasis and viability in PC3 human prostate cancer cells. Journal of Receptors and Signal Transduction, 32(5), 271-278. https://doi.org/10.3109/10799893.2012.707212

 

10) Prabhu, B., Sivakumar, A., Sundaresan, S. (2016). Diindolylmethane and Lupeol Modulates Apoptosis and Cell Proliferation in N-Butyl-N-(4-Hydroxybutyl) Nitrosamine Initiated and Dimethylarsinic Acid Promoted rat Bladder Carcinogenesis. Pathology & Oncology Research, 22(4), 747-754. https://doi.org/10.1007/s12253-016-0054-9

 

11) Shorey, L.E., Hagman, A.M., Williams, D.E., Ho, E., Dashwood, R.H., Benninghoff, A.D. (2012). 3,3′-Diindolylmethane Induces G1 Arrest and Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia Cells. PLoS ONE, 7(4), e34975. https://doi.org/10.1371/journal.pone.0034975

 

12) Li, F., Xu, Y., Chen, C., Chen, S., Xiao, B., Tao, Z. (2015). Pro-apoptotic and anti-proliferative effects of 3,3′-diindolylmethane in nasopharyngeal carcinoma cells via downregulation of telomerase activity. Molecular Medicine Reports, 12, 3815-3820. https://doi.org/10.3892/mmr.2015.3836

 

13) Fan, S., Meng, Q., Xu, J., Jiao, Y., Zhao, L., Zhang, X., … Rosen, E.M. (2013). DIM (3,3′-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. Proceedings of the National Academy of Sciences of the United States of America, 110(46), 18650-5. https://doi.org/10.1073/pnas.1308206110

 

14) Reed, G.A., Sunega, J.M., Sullivan, D.K., Gray, J.C., Mayo, M.S., Crowell, J.A., Hurwitz, A. (2008). Single-Dose Pharmacokinetics and Tolerability of Absorption-Enhanced 3,3′-Diindolylmethane in Healthy Subjects. Cancer Epidemiology Biomarkers and Prevention, 17(10), 2619-24. https://doi.org/10.1158/1055-9965.EPI-08-0520

 

 

 

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