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. 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. |
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