The following is a current review of information concerning D-Glucarate.
Much of the stimulus for this work came from the observation that populations who had diets very rich in fruits and vegetables had a lower incidence of cancer. The outcome of this work was the isolation of D-Glucarate from fruits and vegetables. This “purification” and use of D-Glucarate is patented.
In 1986 Walaszek and co-workers demonstrated that taking D-Glucarate orally, in animals and humans, leads to a slow release of a substance that inhibits glucuronidase. D-glucarate functions by inhibiting the dangerous beta-glucuronidase enzyme, thus protecting the critical ?glucuronidation? detoxification mechanism. Glucuronidase is an enzyme that thwarts the body’s efforts to rid itself of cancer causing substances known as carcinogens. Walaszek demonstrated that if you feed animals Glucarate, there is an increase in the level of a substance known as D-Glucaro-lactone, which inhibits glucuronidase. He looked at a model for breast cancer induction in rats, the animal used most frequently for breast cancer research. Rats given anthracene develop breast cancer, but if they were pre-treated with dietary Glucarate, tumor development was blocked in over 70% of the animals. It was shown that when D-Glucarate was fed to the animals, the levels of estradiol (the form of estrogen that causes breast cancer) were decreased in the blood. In summery, D-Glucarate lowers the level of glucuronidase, and in so doing allows the body eliminate harmful carcinogens (cancer causing chemicals).
In 1986 these same researchers found that by giving the “active” agent, D-Glucaro-lactone by mouth favored the reduction of glucuronidase activity for one hour, using the Calcium D-Glucarate salt led to a 5-hour effect. These experiments were performed in animals fed various carcinogens and the level of free carcinogen or carcinogen bound to DNA was measured in the blood. With calcium D-Glucarate, these levels were drastically reduced over a sustained period of time. There was a direct correlation between the decrease in DNA binding of carcinogen and the ability to induce tumor formation. In essence, D-Glucarate administration favors the elimination of carcinogens in the stool, and the effect lasts for hours after a single low dose.
In 1990 Walaszek moved to the MD Anderson Carcinogenesis center at Houston. He published an article showing that Calcium D-Glucarate leads to a decrease in the “proliferation” of tumors themselves, in other words, once present this agent can decrease their growth.
In 1991, 1992, and 1993 there were a number of articles that tested D-Glucarate in human tumor cell cultures. In these studies Glucarate was added to derivatives of retinoic acid (a compound from vitamin A). Results demonstrated that the addition of D-Glucarate led to an increase in the anti-tumor activity of rentinoids.
In 1994 Walaszek and co-workers demonstrated that in certain human tumor cell culture lines, D-Glucarate was a potent anti-proliferative agent when used alone, without retinoic acid. There was an inability to stimulate tumor cell growth by the usual means when the tissue cultures were treated with D-Glucarate.
In 1995 Walaszek and co-workers demonstrated that feeding D-Glucarate to animals was always followed by conversion to the D-Glucaro-lactone product, and that this conversion led to an increase in the blood levels of this compound. In these studies a number of different carcinogens were used to try and induce breast cancer in rats. Although these carcinogens led to breast cancer in rats fed a placebo, those fed Glucarate did not develop breast cancer. The main carcinogen used in these studies was N-methyl-N-nitrosurea.
Work by other investigators, including Walaszek, in 1995 and 1996 showed that Calcium D-Glucarate and the Potassium hydrogen D-Glucarate were both excellent inhibitors of colon cancer in experimental animal models.
The most recent work on specific tumors has shown that the absorption, metabolism, and effectiveness of D-Glucarate was similar in both male and female animals. There is tumor inhibition shown for breast, prostate, lung, and colon cancer, and the mechanism of action is identical in each…there is a decrease in glucuronidase activity, a decrease in carcinogen level (because the body eliminates the carcinogen) and a decrease in tumorogenesis.
In summary, D-Glucarate is a naturally occurring substance that is not present in sufficient amounts to counteract natural and external carcinogens. By supplementing D-Glucarate as the calcium salt, we can get a long lasting effect of Glucarate, and this effect is to favor the body’s natural defense mechanism for eliminating carcinogens. Without Glucarate, the body cannot efficiently eliminate these cancer-causing agents because of the interference from glucuronidase. By supplementing the diet with Glucarate, we can block glucuronidase activity and the body can rid itself of the carcinogens, thus preventing many forms of cancer, including lung, breast, prostate, and colon.
Stewart A. Lonky, MD, FACP
References:
1. Walaszek, Z., Hanausek, M., Szemraj, J., and Adams, A.K. 1998, D-Glucarate acid as a prospective tumor marker. Meth. Mol. Med., 14, 487-495.
2. Walaszek, Z., Szemraj, J., Adams, A.K., and Hanausek, M. 1992, Reduced levels of D-Glucaric acid in mammary tumor-bearing hosts and the effect of its supplementation during estrogen replacement and tamoxifin therapy. Proc. Am. Assoc. Cancer Res. 37: 183.
3. Heerdt, A.S., Young, C.W.., and Borgen, P.I., 1995, Calcium Glucarate as a chemopreventative agent in breast cancer., Isr. J. Med. Sci. 31:101-105.
4. Walaszek, Z. Chemopreventative properties of D-Glucaric acid derivatives. Cancer Bull 1993; 45: 453-457.
5. Walaszek, Z., Szemraj, J., Adams, A.K., Kordari, P., and Hanausek, M.
1992, Reduced levels of D-Glucaric acid in mammary tumor-bearing Host. Breast Cancer Res. Treat., 375: 108.
6. Walaszek, Z., Hanausek, M., Adams, A.K. and Sherman, U. 1991, Cholesterol lowering effects of dietary D-Glucarate. Faseb J., 5: A930.
7. Walaszek, Z., Hanausek, M., Sherman, U. and Adams, A.K. 1990, Antiproliferative effect of dietary glucarate on the Sprague Dawley in rat mammary gland. Cancer Lett. 49: 51-57.
8. Walaszek, Z., Adams, A.K., Sherman, U., Viaje, A., Rotstein, J.B., Hanausek, M. and Slaga, T.J. 1990, Antiproliferate effects of Calcium D-Glucarate (CG) and D-glucaro-1,4-lactone (GL) on the rat mammary gland, colon and mouse skin. Proc. Am. Assoc. Cancer Res., 31: 124. p>
9. Walaszek, Z. 1990, Potential use of D-Glucarate acid derivatives in cancer prevention. Cancer Lett. 54: 1-8.
10. DiGiovanni, J., 1990, Inhibition of chemical carcinogenesis. In: Chemical Carcinogenesis and Mutagenesis II, Cooper, C.S. and Grover, P.L. (eds.), Springer Verlag, Berlin, pp. 159-224.
11. Walaszek, Z., Adams, A.K., and Flores, F., 1989, Inhibition of 7,12-dimethylbenz(a)-anthracene(DMBA)-induced rat mammary carcinogenesis by glucarate. Proc. Am. Assoc. Cancer Res., 30: 170.
12. Abbou-Issa, H., Koolemans-Beynen, A., Minton, J.P. and Webb, T.E., 1989, Synergistic interaction between 13-cis-retinoic acid and glucarate: activity against rat mammary tumor induction and MCF-7 cells. Biochem.
Biophys. Res. Commun.,163: 1364-1369.
13. Dwivedi, C., Oredipe, O.A., Barth, R.F., Downie, A.A. and Webb, T.E., 1989, Effects of the experimental chemopreventative agent, glucarate on intestinal carcinogenesis in rats. Carcinogenesis, 10: 1539-1541.
14. Oredipe, O.A., Barth, R.F., Dwivedi, C. and Webb, T.E., 1989, Chemopreventative activity of dietary glucarate on azoxymethane-induced altered hepatic loci in rats. Res. Commun. Chem. Pathol. Pharmacol., 65:
345-359.
15. Dwivedi. C., Downie, A.A. and Webb, T.E., 1989, Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate. J. Environ. Path. Toxicol. Oncol., 9: 253-259.
16. Walaszek, Z., Hanausek, M., Sherman, U., Del Rio, M. and Adams, A.K., 1989, Effects of (+) glucaric acid derivatives and tamoxifen on human breast cancer cells (MCF-7). Breast Cancer Res. Treat., 14: 175.
17. Walaszek, Z., Flores, F. and Adams, A.K., 1988, Effect of dietary glucarate on estrogen receptors and growth of 7,12-dimethylbenz[a] anthracene-induced rat mammary carcinomas. Breast Cancer Res. Treat., 12: 128.
18. Walaszek, Z., Hanausek-Walaszek, M. and Webb, T.E., 1988, Repression by sustained release or glucuronidase inhibitors of chemical carcinogen-mediated induction of a marker oncofetal protein in rodents. J. Toxicol. Environ. Health, 23: 15-27.
19. Abbou-Issa, H.M., Duruibe, V.A., Minton, J.P., Larroya, S., Dwivedi, C., and Webb, T.E., 1988, Putative metabolites derived from dietary combinations of calcium glucarate and N-(4hydroxypheny)retinamide act
synergistically to inhibit the induction of rat mammary rumors by 7,12-dimethylbenz[a]-anthracene. Proc. Natl. Acad. Sci. USA. 85:4181-4184.
20. Oredipe, O.A., Barth, R.F., Hanausek-Walaszek, M., Sautins, I., Walaszek, Z. and Webb, T.E. 1987, Effects of an inhibitor of B-glucuronidase on hepatocarcinogenesis. Proc. Am. Assoc. Cancer Res.,
28: 156.
21. Oredipe, O.A., Barth, R.F., Hanausek-Walaszek, M., Sautins, I. Walaszek, Z. and Webb, T.E. 1987, Effects of calcium glucarate on the promotion of diethylnitrosamine-initiated altered hepatic loci in rats.
Cancer. Lett., 38, 95-99.
22. Walaszek, Z., Hanausek-Walaszek, M., Minton, J.P. and Webb, T.E. 1986, Dietary glucarate as antipromoter of 7,12-dimethylbenz[a]-anthra-cene-induced mammary tumorigenesis. Carcinogenesis, 7:1463-1466.
23. Minton, J.P., Walaszek, Z., Hanausek-Walaszek, M., and Webb, T.E. 1986, B-Glucuronidase levels in patients with fibrocystic breast disease. Breast Cancer Res. Treat., 8: 217-222.
24. Walaszek, Z., Hanausek-Walaszek, M., Webb, T.E., 1986, Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical to chemical carcinogenesis. Cancer Lett., 33: 25-32.
The results of various animal studies on D-glucarate indicate that this plant extract may be effective in inhibiting cancer during the initiation, promotion and progression phases. The studies have demonstrated that D-glucarate suppressed beta-glucuronidase activity in the blood, liver, intestines, lungs, skin, and bladder. In studies on breast cancer in rats treated with D-glucarate, tumor growth and development were significantly reduced or inhibited. D-glucarate has also been shown to inhibit the growth of transplanted rat prostate tumor and reduce the levels of a tumor marker for prostate cancer. Calcium D Glucarate also lowers serum estrogen levels thus reducing the risk of estrogen related cancers.
Human studies are just now beginning to determine if the results seen in animals will also be found in people. Since D-glucarate has no known side effects when ingested in moderate doses, and is a component of fruits and vegetables that have demonstrated powerful cancer preventative benefits, it would appear appropriate to add this plant constituent as part of an overall program designed to lower the risk of the following cancers:
– General Cancers
– Breast cancer
– Bladder cancer
– Lung cancer
– Skin cancer
– Colon cancer
– Prostate cancer
– Liver cancer
– Basal Cell Cancer
– Squamous Cell Cancer
Uses
Glucaric acid is a chemical made by the body and also consumed in foods. For dietary supplementation, it is combined with calcium to form calcium d-glucarate.
Because it is thought to hasten the elimination of potentially harmful substances from the body, glucaric acid has been promoted for preventing cancer. Calcium d-glucarate is known to decrease the amounts of an enzyme that is believed to be associated with certain cancers – particularly cancers of the breast, colon, and prostate. Additionally, glucaric acid interferes with the reabsorption of estrogen from the gastrointestinal tract. As a result, more estrogen is eliminated and less stays in the blood. High estrogen levels have also been associated with the development and growth of breast, colon, and prostate cancers. While studies conducted in laboratory animals seem to confirm these theories, few studies have been conducted in humans. Furthermore, the doses of glucaric acid given to laboratory animals were quite large; equivalent human doses may be impractical. More research is needed before glucaric acid can be recommended for the prevention or treatment of cancer.
Preliminary results from a few laboratory studies may associate taking glucaric acid with decreased cholesterol levels. In separate studies, kidney damage caused by certain antibiotics was prevented or limited in laboratory animals that had been given glucaric acid. The exact ways in which glucaric acid may produce these effects are not understood and both of these potential uses of glucaric acid require more study.
Precautions
Not enough is known about how glucaric acid or calcium d-glucarate might affect a developing baby or an infant, so it’s use is not recommended while pregnant or breast-feeding.
What side effects should I watch for?
No side effects have been associated with using glucaric acid. Since few reliable studies of its use have been conducted in humans, however, it may have side effects that are not yet known. If you experience unexplained side effects while taking glucaric acid, you should stop taking it and tell your doctor or pharmacist about the side effects.
What interactions should I watch for?
Because it is broken down by certain enzymes in the liver, glucaric acid may possibly interfere with the use of prescription drugs that are processed by the same enzymes. Some of these drugs are:
* diflunisal (Cataflam, Voltaren)
* ketoprofen (Orudis, Oruvail)
* lorazepam (Ativan)
* Lamictal
* morphine
In a research study, drinking alcohol seemed to increase the elimination of calcium d-glucarate from the body. Therefore, the effects of supplemental glucaric acid may be decreased or erased if alcohol is used at the same time.
Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals.
Dosage and Administration
As its calcium salt, calcium d-glucarate, glucaric acid is available in capsules and tablets. Although no recommendations for dosing are available in scientific literature, a commonly suggested dose for cancer prevention is 200 mg once to twice a day. To treat existing cancers, daily doses of 1,200 mg or higher doses, in divided daily doses. Even at these higher doses no side effects have been reported.
Summary
Glucaric acid and its salt, calcium d-glucarate may have some ability to protect against certain cancers by promoting the elimination of estrogen and potentially harmful substances produced in the body. It may also have some effectiveness in lowering cholesterol and reducing kidney damage caused by some antibiotic drugs.
Risks
Although no apparent risks are associated with taking glucaric acid, pregnant and breast-feeding women are advised to avoid it because so little is known about its possible effects.
Side Effects
No side effects have been attributed to taking glucaric acid.
Interactions
Glucaric acid may interact with drugs such as diflunisal, ketoprofen, lorazepam, and morphine that are processed by the same set of enzymes in the liver. Alcohol may decrease the effectiveness of glucaric acid.