Reproductive aged women need their estrogen, no doubt about it. There has been interest in the “metabolism” and “detoxification” of estrogen and how that might be related to optimizing hormonal health in women. Hormonal health has implications in not just gynecological conditions, but also mental health, immune health, cardiac health, bone health and more. The research is still evolving in terms of how does supporting estrogen metabolism and detoxification affect other aspects of health, and use of supplements that support these pathways is still unfolding in the area of clinical outcomes. That said, understanding estrogen metabolism, detoxification and excretion can lead to a functional medicine approach to supporting hormone pathways and hopefully, improved clinical management and enhanced patient health.
DIM (Diindolylmethane)
DIM is an indole compound derived from metabolites found in cruciferous vegetables. When broccoli or other cruciferous vegetables are chewed, plant enzymes are released and convert plant glucosinolates into indole-3 carbinol (I3C). Once I3C is exposed to stomach acid, it condenses to form DIM. DIM itself can also be taken as a dietary supplement.
Estrogen produced in the body (endogenous estrogen) needs to be metabolized and packaged up for elimination through the kidneys and GI tract. The liver is involved in two steps of estrogen metabolism, called phase 1 and phase 2 detoxification. During Phase 1, the liver converts endogenous estrogen to 3 metabolites: 2-hydroxyestrone (2-OHE1), 4-hydroxyestrone (4-OHE1) and 16-hydroxyestrone (16-OHE1). In phase 2, the liver conjugates and prepares the estrogen metabolites for excretion through the kidneys and bowels. DIM works during Phase 1 to help the liver make more of the favorable 2-OHE1 and reduce the production of the less favorable 4-OHE1 and 16-OHE1.1
Clinical Takeaways:
- Think of DIM when you have determined that phase 1 and/or phase 2 estrogen detoxification pathways require additional support to influence hormonal balance, breast health or health in general
- Think of DIM if you have evidence of excess 4-OHE1 and/or 16-OHE1 estrogen metabolites
Calcium D-glucarate (CDG)
CDG is a calcium salt made from calcium and D-glucaric acid, a compound that helps support liver detoxification pathways. Glucaric acid is also found in many fruits and vegetables and can inhibit beta-glucuronidase activity, which can influence the increased excretion of xenobiotics and conjugated estrogens.
Calcium D-glucarate plays an important role in elimination of the products the liver has prepared for excretion. Remember there are two steps in the liver to process compounds that need to be excreted by the body: Phase 1 and Phase 2 liver detoxification. Following the first phase of detoxification, intermediate metabolites can be produced (sometimes more reactive than their initial form), which requires phase 2 detoxification to prepare them for easier elimination by the gut and kidneys. Hormones, medications, metabolic byproducts, neurotransmitters, and various toxins are neutralized via phase II liver detoxification through a variety of processes, including glucuronidation. Glucuronidation is the process of binding (conjugating) Phase 1 metabolites to glucuronic acid. These bound metabolites are then either excreted in bile to be eliminated through a bowel movement or eliminated via the kidneys in the urine. Conjugation enables the body to transport endogenous (made in the body) and exogenous (taken into the body) waste without risk of it being reabsorbed.
Beta-glucuronidase is an enzyme produced by colonocytes and certain bacteria found in our gut (primarily E. coli and other anaerobes) that can inhibit the excretion of the products the liver has packaged up, including estrogen metabolites. This enzyme deconjugates metabolites so they are available to be reabsorbed by the gut. Imbalances in gut bacteria may lead to higher levels of beta-glucuronidase and possibly interfere with estrogen elimination. This highlights an important connection between gut health and hormonal balance. By inhibiting beta-glucuronidase activity, calcium D-glucarate can help promote the metabolism and elimination of estrogen by the body. Of the different metabolites of glucaric acid, calcium D-glucarate appears to have the longest inhibitory effect on beta-glucuronidase.2
Clinical Takeaways:
- Estrogen metabolism and excretion support
- Detoxification and promoting the body’s natural detoxification processes.
References:
1. Thomson C, Ho E, Strom M. Nutr Rev, 2016 May 30;74(7):432–443.
2. Walaszek Z, Szemraj J, Narog M, et al. Cancer Detect Prev 1997; 21:178-190.
