DIM or diindolylmethane, a commonly used supplement, is a metabolite of I3C (indole-3-carbinol), found abundantly in healthy vegetables such as broccoli, cabbage, cauliflower and kale. Cancer patients often try to include random dietary supplements along with their ongoing cancer treatments to improve their quality of life or treatment efficacy, with the assumption that taking any natural or plant based supplements along with their ongoing treatments are always safe and can cause no harm. This is not always true. Based on the cancer type and treatment, the impact of these supplements can vary and can even interfere with specific cancer treatments. In this blog, we discuss on one such clinical study which found that DIM (diindolylmethane) can interfere with Tamoxifen, a standard of care treatment for breast cancer, and reduce the levels of the active metabolite of Tamoxifen. The DIM-tamoxifen interactions could potentially affect the therapeutic efficacy of Tamoxifen and is hence better not to include DIM supplements as part of the breast cancer patients’ diet while undergoing Tamoxifen treatment. This highlights the need for a personalized nutrition plan with the right foods and supplements to support the specific cancer treatment and gain benefits and stay safe.
Use of DIM (diindolylmethane) in Breast Cancer
There is a large number of breast cancer survivors that self-prescribe bio-active dietary plant derived supplements with the intention to prevent cancer recurrence and obtain survival benefits. The choice of supplements they take is random based on referrals from friends and family, or based on their web searches and information on the internet.
A commonly used supplement is DIM (diindolylmethane), a metabolite of I3C (indole-3-carbinol), found in cruciferous vegetables like broccoli, cauliflower, kale, cabbage, Brussels sprouts. This widespread use of DIM amongst breast cancer patients could be based on the findings from observational clinical studies including the Women’s Healthy Eating and Living (WHEL) study of over 3000 breast cancer patients that found an association of decreased risk of breast cancer recurrence in women taking Tamoxifen therapy, who also consumed cruciferous vegetables as part of their diet. This association as per the researchers could be linked to the activity of phytochemicals like DIM in these cruciferous vegetables that have anti-cancer and anti-inflammatory properties (Thomson CA, Breast Cancer Res Treat., 2011). Another recent meta-analysis of 13 case-control and prospective cohort studies also suggested that an overall high consumption of cruciferous vegetables (rich in indole-3-carbinol) such as broccoli, kale, cabbage, cauliflower and spinach in the diet was significantly associated with a 15% lower risk of breast cancer (Liu X et al, Breast, 2013).
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DIM (diindolylmethane) and Tamoxifen Interactions in Breast Cancer
Breast cancer patients with hormone positive (Estrogen Receptor ER+) breast cancer are treated with adjuvant Tamoxifen endocrine therapy for an extended time of 5-10 years after their surgery and chemo-radiation treatments. Tamoxifen is a selective estrogen receptor modulator (SERM) that acts by competing with the estrogen hormone for binding to the ER in breast tissue, thus inhibiting pro-cancer effects of estrogen. Tamoxifen, an oral drug, is metabolized by the cytochrome P450 enzymes in the liver into its bioactive metabolites that are the key mediators of tamoxifen efficacy. There are some common plant derived supplements that can interfere with the metabolism of Tamoxifen and thereby reduce the concentration of the drug below its therapeutic threshold. One randomized, double-blind, placebo controlled clinical trial of the use of DIM supplement, the metabolite of the indole-3-carbinol compound from cruciferous vegetables, along with Tamoxifen, in breast cancer patients, has shown this alarming trend of tamoxifen metabolite reduction, that breast cancer patients on DIM supplement need to be aware of.
Details of the Study
Details of the randomized, placebo-controlled clinical trial to evaluate the proposed breast cancer chemopreventive activity of DIM in breast cancer patients taking Tamoxifen therapy are summarized below (NCT01391689) (Ref: Thomson CA, Breast Cancer Res. Treat., 2017).
- There were 130 women prescribed Tamoxifen, who were randomly divided into two groups: a group that received for 12 months either DIM supplement at 150 mg, twice a day, or a placebo. 98 women completed the study (51 placebo group, 47 DIM group).
- The primary endpoint of the study was to assess the change in urinary levels of the metabolites of estrogen hormone 2/16-hydroxyestrone, that is the anti-tumorigenic metabolite. Other secondary endpoints were also assessed including serum estrogens, breast density using mammography or MRI, and levels of tamoxifen metabolites.
- DIM increased the level of the anti-tumorigenic estrogen metabolite compared to placebo, which is a positive chemopreventive result.
- There was no change found in the breast density between the two groups.
- The surprising finding was that there was a reduction in the plasma levels of the pharmacologically active metabolites of tamoxifen (endoxifen, 4-hydroxy tamoxifen, and N-desmethyl tamoxifen). In the DIM group, there was a statistically significant reduction in the plasma levels of the active metabolites of tamoxifen, with the effects of this reduction evident at 6 weeks and stabilized over time. The levels of active tamoxifen metabolites for women in the DIM group was observed to be below the therapeutic threshold for tamoxifen efficacy.
Although the decrease in tamoxifen levels indicates an interference or interaction between DIM and Tamoxifen metabolism, the researchers of this study suggest further research to determine if the decreased levels of active tamoxifen metabolites would significantly reduce the clinical benefits of tamoxifen. However, since the clinical data is showing a trend of interaction between DIM (metabolite of indole-3-carbinol) and tamoxifen, it would be preferable for breast cancer patients on tamoxifen therapy to veer on the side of caution and avoid taking DIM while on Tamoxifen therapy. A plant-based diet including cruciferous vegetables containing indole-3-carbinol may provide the required benefit over taking a dietary supplement of DIM while on hormonal therapy for breast cancer.
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