At the start of a new year, functional medicine practitioners and their patients often turn their attention to detoxification. After the indulgences of the holidays, many people choose the new year to make a fresh start with their diet and exercise routines, and they like to start things off with a “clean slate,” so to speak. Detox protocols with a defined duration can be helpful as a reset strategy, but detoxification is an activity the liver, kidneys, skin, and other organs perform daily all year round. Several specific compounds can aid the body in performing this critical task. Today, let’s focus on calcium-D-glucarate.

Calcium D-glucarate is calcium bound to d-glucaric acid, a natural compound produced in small amounts by the human body and found abundantly in various plant foods, such as broccoli, cabbage, kale, apples, oranges, and grapefruit. (Apples and broccoli have as much as 3.5 g/kg of calcium-d-glucarate, compared to 0.1 g/kg in grapes and lettuce.) Research shows that d-glucaric acid derivatives help support the body’s defense against toxins and excess steroid hormones, making calcium d-glucarate a potentially beneficial compound to support healthy detoxification.

In the GI tract, calcium d-glucarate is metabolized into three compounds, the most active of which is D-glucaro-1,4-lactone. This metabolite increases the detoxification of carcinogens by inhibiting β-glucuronidase, an enzyme present in circulation and also produced by colonic bacteria. The presence of this enzyme in the colon is of particular importance with regard to detoxification, because it is capable of deconjugating (breaking apart) potential toxins that are being eliminated via the phase II detoxification glucuronidation pathway, allowing them to be reabsorbed back into the body rather than being excreted. D-glucaro-1,4-lactone is not available as a supplement, but as a precursor, calcium-D-glucarate may be helpful for ultimately reducing activity of β-glucuronidase. Plus, calcium-D-glucarate has been shown to have longer inhibitory effects against β-glucuronidase than D-glucaro-1,4-lactone itself, so it might be the preferred form anyway.

During liver detoxification, some compounds—including various hormones, such as estrogen—are modified via glucuronidation, a process whereby glucuronic acid is attached to a toxin or normal metabolic product (for example, excess steroid hormones) in order to create a less toxic conjugate that can be more easily eliminated from the body. In the case of liver detoxification, such substrates include xenobiotic substances—compounds that are foreign to the body—such as environmental pollutants and pharmaceutical drugs, as well as endogenously produced compounds like excess estrogens and androgens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. Once bound to glucuronic acid, these toxins, excess hormones, and metabolic waste products are more easily eliminated—that is, unless something like β-glucuronidase unbinds them.  

Elevated estrogen is associated with breast and ovarian cancers, gynecomastia, prostate cancer, and possibly obesity. Estrogen, of course, is an essential hormone in both women and men, but various dietary and environmental factors may be elevating estrogen and estrogen-mimicking compounds in the body to levels above that which are biologically normal, potentially resulting in an altered hormone balance that’s playing a role in various pathologies. With this in mind, some individuals—both females and males—may benefit from nutritional and supplementation interventions to reduce excess estrogen.

Via inhibition of β-glucuronidase, calcium d-glucarate may be helpful in facilitating detoxification by reducing the reabsorption of potentially harmful and proliferative estrogens and environmental toxins. Calcium-D-glucarate appears to be safe at relatively high doses, and there are no known drug interactions with the compound. However, many drugs and hormones are metabolized in the liver via glucuronidation, and it’s possible that taking supplemental calcium-D-glucarate may enhance elimination of these substances, thereby reducing their half-life and possibly reducing their efficacy.