D Glucarate and cancer, effect on estrogen levels by Ray Sahelian, M.D.
June 8 2016

D-glucono-1,4-lactone, sodium D-gluconate and calcium D-glucarate are non-toxic glucose derivatives occurring naturally in fruits and vegetables. Calcium D-glucarate is promoted as an orally bioavailability dietary supplement with potential health benefits without adverse effects. Despite many commercial applications in pharmaceutical and food industries the potential activity mechanisms of glucarate and gluconate are still not very clear.

There is growing evidence for the possible control of different stages of the cancer induction by inhibiting beta-glucuronidase with D-glucaric acid derivatives, especially with its salts (D-glucarate). D-Glucaric acid has been found in many vegetables and fruits. Therefore, the consumption of fruits and vegetables naturally rich in D-glucaric acid or self-medication with D-glucaric acid derivatives such as calcium d glucarate offers a promising cancer prevention approach.

Side effects, safety, toxicity
No major adverse effects have been reported in the medical literature as of 2014.

D Glucarate research study
Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention.
Cancer Detection Prev. 1997.
D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of carcinogens and tumor promoters/progressors by inhibiting beta-glucuronidase and preventing hydrolysis of their glucuronides. 1,4-GL and its precursors, such as potassium hydrogen D-glucarate and calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or adjuvant cancer preventive and therapeutic agents. In our study, 1,4-GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives may be prerequisite for their inhibition of chemical carcinogenesis in rodents and prevention of breast, prostate, and colon cancer in humans.

Postepy Hig Med Dosw (Online). 2008. The biological role of D-glucaric acid and its derivatives: potential use in medicine. D-glucaric acid is a natural non-toxic compound produced in small amounts by mammals, including humans. In mammals, D-glucaric acid and D-glucaro-l,4-lactone are end-products of the D-glucuronic acid pathway. The enzyme D-glucuronolactone dehydrogenase has been found to be responsible for the oxidation of the lactone of D-glucuronic acid to D-glucaro-l,4;6,3-dilactone. This dilactone hydrolyzes spontaneously in aqueous solution to D-glucaro-l,4-lactone, a potent beta-glucuronidase inhibitor. D-glucaric acid is also found in many fruits and vegetables, with the highest concentrations found in grapefruits, apples, oranges, and cruciferous vegetables. b-glucuronidase is present in the circulation and probably all vertebrate tissues and is capable of hydrolyzing glucuronide conjugates. This enzyme is also produced by colonic microflora. Elevated b-glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast and prostate cancer. D-glucaro-l,4-lactone increases detoxification of carcinogens and tumor promoters by inhibiting b-glucuronidase and preventing the hydrolysis of their glucuronides. D-glucaro-l,4-lactone was found to be formed from supplemented D-glucarate salt in the stomach and it is absorbed from the intestinal track, transported with the blood to different internal organs, and excreted in urine and, to a lesser extent, in bile. D-glucaro-l,4-lactone and its precursors exert their anticancer action in part through alterations in steroidogenesis accompanied by changes in the hormonal environment and proliferative status of the target organs. D-glucarates not only suppress cell proliferation and inflammation, but also induce apoptosis. By supplementing D-glucarates, one can favor the body's natural defense mechanism for eliminating carcinogens and tumor promoters and their effects.