What is Calcium D-Glucarate?
(calcium salt of D-glucaric acid) is produced naturally in small amounts by mammals, and can be found in variety of fruits and vegetables (oranges, apples, grapefruit, and cruciferous vegetables) . Calcium D-glucarate is made by combining glucaric acid with calcium to make supplements that people use for medicine .
Calcium D-Glucarate as Estrogen Blocker
Oral supplementation of calcium D-glucarate has been shown to inhibit beta-glucuronidase via its precursor D-glucaro-1,4-lactone  (thus increasing glucuronidation process ). Elevated beta-glucuronidase activity is associated with an increased risk for various cancers (especially hormone-dependent such as breast, prostate, and colon cancer) [1,4,5]. Therefore, calcium D-glucarate is a promising natural solution for the prevention of certain types of cancer. Clinical applications of oral calcium D-glucarate also include regulation of estrogen metabolism [4,6].
Calcium D-glucarate’s inhibition of beta-glucuronidase activity allows the body to eject hormones such as estrogen before they can become reabsorbed. Supplementation of very large doses of calcium D-glucarate have been shown to decrease serum estrogen levels in rats by 23 percent.  However, doses used are so high (approx. 1,000mg/kg) they seem impractical for actual use.
Calcium D-Glucarate Side Effects and Risks
There is not enough information to know if calcium D-glucarate is safe or what the potential side effects might be . Preliminary results of clinical trials in humans show no adverse effects . There are no known drug interactions with calcium D-glucarate, but many drugs and hormones are metabolized in the liver via glucuronidation, thus, supplementing with calcium D-glucarate may increase ejection of these substances and reduce their effectiveness . Testosterone is also a hormone that is glucuronidated, which means calcium D-glucarate may limit the bioavailability of testosterone .
Calcium-d-glucarate: Any correlation with Acne and Anxiety?
Calcium-D-glucarate is the calcium salt of D-glucaric acid and is taken as a supplement with the main purpose of enhancing the hepatic detoxifying capacity, thanks to the fact that it increases the metabolic processes of glucuronidation; consequently, it stimulates the entero-hepatic recirculation of bile salts and the excretion of toxic products and catabolites .
Although there is no scientific evidence of these precise side effects in the medical literature, some reasoning needs to be done to answer these two questions and the starting point is related to the properties of calcium D-glucarate in regulating cholesterol and sex hormone metabolism.
Calcium-d-glucarate and Acne
Acne is an inflammatory dermatosis involving the pilosebaceous glands that is characterized by excessive sebum production and tissue inflammation. Central roles in the pathogenesis of acne are played by some hormones (such as insulin, insulin-like growth factor-1 (IGF-1), androgens, and, to a lesser extent, estrogens and progesterone), the bacterium Propionibacterium acnes, the lipogenesis process, and a pro-inflammatory lipid profile  .
Androgens (including testosterone) increase sebum production, which leads to increased pore clogging and a more habitable micro-environment for Propionibacterium acnes; it has also been demonstrated that an imbalance between estrogen and progesterone levels can promote the development of this dermatologic condition . In fact, the expression of both the androgen receptor (AR) and estrogen receptor (ER) has been demonstrated in the sebaceous gland, and for this reason, the levels of these hormones can influence the glands’ activity .
Calcium D-glucarate acts by decreasing androgens and estrogens and consequently the production of sebum, and by improving the lipid profile, since it decreases the total cholesterol level by lowering LDL lipoproteins, the main responsible for endothelial inflammation and a pro-inflammatory lipidic profile .
On the basis of these considerations, we can assume that calcium D-glucarate may exert a protective or ameliorative role towards acne, due to the overall improvement of hormonal and lipid balance.
Calcium-d-glucarate and Anxiety
Regarding the relationship between Calcium D-glucarate and anxiety levels, it is necessary to differentiate the impact of sex hormones on nervous circuits in males and females because the changes in behavior at the same hormonal concentrations are very different. Both testosterone and estrogens have a protective role against anxiety, but it is in the female that the relationship between levels of sex hormones (and therefore estrogen) and anxiety disorders, is stronger .
There is in fact scientific evidence that shows how estrogens can increase the number of serotonin receptors, as well as its synthesis in the brain.
It is also known that the reduction of serotonin and norepinephrine is one of the main causes of anxiety disorders and depression . For this reason, in the presence of a reduction in estrogen levels, females are more susceptible to hormonal changes than males, with greater development of anxiety disorders. Estrogen deficiency results also in NLRP3 inflammasome activation, thereby leading to neuroinflammation in the hippocampus and conditions like depression and anxiety .
Calcium d-glucarate Conclusions
These reasonings based on scientific studies, notions of dermatology, and neurophysiology allow us to assume that the integration with calcium D-glucarate does not give or predispose to the development of acne as a side effect, while it could determine the development of anxiety in females, especially if the woman is in an estrogen deficiency phase.
In both cases, calcium D-glucarate could have a protective role by indirectly reducing inflammation, thanks also to the improved hepatic clearance. However, specific studies are needed in order to consolidate these assumptions.
(Other common names: Calcium-D Glucarate, Calcium-D-Glucarate, D-Glucarate (GA), D-glucaro-1,4-lactone (1,4 GL))
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