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The following is a current review of
information concerning D-Glucarate by Stewart
A. Lonky, MD, FACP
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
to 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.
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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