Product Details: D-Glucarate
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DISCUSSION: D-Glucarate is a phytochemical found in such fruits and vegetables as orange pith and broccoli. D-Glucarate inhibits an enzyme known as beta-glucuronidase, which suppresses the body's ability to detoxify many toxins using the glucuronidation pathway. Research supports a role for glucuronidation in protecting cells (especially those of hormone-sensitive tissues such as the breast and prostate) from dangerous environmental chemicals. | ||||||
| 60 Vegi-Caps AOR04023 100% Vegetarian SUPPLEMENT FACTS: Serving Size: 1 Capsule
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*Dietary Reference Intake not established. Other ingredients: microcrystalline cellulose. Capsule: hypromellose, water. AOR guarantees that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, corn, nuts, dairy, soy, eggs, fish or shellfish. Suggested Use Main Applications Source Pregnancy / Nursing Cautions *These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide medical advice to individuals. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes. Any reproduction in whole or part and in print or electronic form without express permission is strictly forbidden. Permission to reproduce selected material may be granted by contacting AOR Inc. Copyright © 2005, Advanced Orthomolecular Research |
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Every moment of every day, every cell in your body is under attack by chemical and biological weapons with the potential to cause cancer. Carcinogenic compounds include not just artificial chemicals (such as persistent organic pollutants (POPs)) in the form of organochlorine pesticides and other such chemicals), but ancient, and even naturally-occurring, cancer-causing substances, including polycyclic aromatic hydrocarbons (PAH), heterocyclic amines (HCAs), fungal toxins (such as aflatoxin), and even excess levels of the sex hormones estrogen and testosterone. |
| • The body makes use of intricate detoxification pathways to process xenobiotic and naturally occurring toxins. One of the most important such pathways is glucuronidation, in which UGT enzymes neutralize carcinogens by binding them to a molecule of glucuronic acid.
• Glucuronidation renders potential carcinogens less hazardous to the cells of the body. It also makes many such chemicals easier for the body to excrete through the urine or the bile. • The vital neutralization of toxins by glucuronidation can be undone by an enzyme known as beta glucuronidase. This enzyme frees up the original carcinogen from its glucuronic acid "handcuffs." Beta-glucuronidase is present in the body's cells and is also produced by some fecal bacteria. The activity of beta-glucuronidase increases with age. • Impaired glucuronidation has been linked to susceptibility to many cancers and other diseases in humans and in other species. Human research reveals links between toxic environments, glucuronidation, and beta-glucuronidase; and also between glucuronidation, beta-glucuronidase activity, and cancer and other diseases. D-Glucarate is a substance made in small amounts by the body, and also found in some foods - most notably oranges and cruciferous vegetables. • D-Glucarate reduces the activity of the killer beta-glucuronidase enzyme in tissues all over the body, including key organs like the liver, spleen, breast, lung, and prostate resulting in higher net glucuronidation activity. This boost to your body's glucuronidation capacity helps to ensure that those pollutants and toxins that have been neutralized by UGTs will stay neutralized, and be safely passed out through the urine or the bile. As you'd expect from a nutrient that is used up in the detoxification process, people exposed to a toxic environment have abnormal levels of D-Glucarate in their tissues and biological fluids. Cancer patients also have disrupted D-Glucarate levels. • Studies in animals have found that D-Glucarate supplements provide powerful, effective support for the body's natural defenses against many kinds of cancer. In one study, giving animals access to D-Glucarate supplements during exposure to the carcinogen DMBA but then had the supplement taken away, the brief intevention still managed to reduce the number of breast tumors the animals formed by 18% compared to animals who never received the supplement. More strikingly, if the scientists waited until the cancerous cells had already formed in the animals, and only then allowed them access to D-Glucarate, breast tumor formation was cut by 42%. And best of all, supplementation began from the first day of chemical exposure, and continued on throughout the study, D-Glucarate cut tumor formation neatly in half. The results of another study were even more impressive: after the animals were exposed to DMBA, those consuming D-Glucarate supplements developed 70% fewer breast tumors than those that did not. The failure of the glucuronidation machinery is also closely associated with prostate cancer. UGT activity is reduced in prostate cancer cells when they are exposed to high levels of dihydrotestosterone (DHT), the form of testosterone most responsible for promoting prostate cancer. Men with prostate cancer are three times as likely as healthy men to have the gene for a weakened version of the UGT enzyme that glucuronidates DHT. • D-Glucarate suppresses the killer beta-glucuronidase enzyme in the prostate just as it does in other tissues. • Scientists at the AMC Cancer Research center now report that D-Glucarate supplements causes a 30% inhibition of the growth of prostate cancer in animals with existing prostatic tumors. In addition to these gender-specific cancer threats, scientists have also piled on evidence that D-Glucarate supplementation protects animals against "equal-opportunity" cancers, such as those of the colon, the lung, the skin, and the liver, and have found elevated beta-glucuronidase activity in the tumors of human victims of lung cancer. Beyond supporting the body's detoxification systems, D-Glucarate supplements also appear to make the cells of the body themselves less prone to carcinogenic stimulation. Preliminary studies in humans show that D-Glucarate supplements are safe, and have the same effects on beta-glucuronidase in people that they do in animals. Studies on D-Glucarate supplements in women at risk for breast cancer have begun. References i. Tukey RH, Strassburg CP. "Human UDP-glucuronosyltransferases: metabolism, expression, and disease." Annu Rev Pharmacol Toxicol. 2000; 40: 581-616. ii. Walaszek Z, Szemraj J, Narog M, Adams AK, Kilgore J, Sherman U, Hanausek M. "Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention." Cancer Detect Prev. 1997; 21(2): 178-90. iii. Heerdt AS, Young CW, Borgen PI. "Calcium glucarate as a chemopreventive agent in breast cancer." Isr J Med Sci. 1995 Feb-Mar; 31(2-3): 101-5. iv. Abou-Issa H, Moeschberger M, el-Masry W, Tejwani S, Curley RW Jr, Webb TE. "Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis." Anticancer Res. 1995 May-Jun; 15(3): 805-10. v. Maroni M, Columbi A, Antonini C. "D-glucaric acid urinary excetion as a tool for biological monitoring in occupational medicine." In Brown SS, Davies DS (eds). Organ-directed toxicity: chemical indices and mechanisms. Oxford; Pergamon Press,1981:161-8. vi. Walaszek Z., Hanausek M., Szemraj J, Adams A. "D-Glucaric acid as a potential tumor marker." In Hanausek M, Walaszek Z (eds). Methods in Molecular Medicine, Vol 14: Tumor Marker Protocols. 1998; Humana press, Totowa, NJ: 487-95. The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide medical advice to individuals. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes. Any reproduction in whole or part and in print or electronic form without express permission is strictly forbidden. Permission to reproduce selected material may be granted by contacting AOR Inc. Copyright © 2005, Advanced Orthomolecular Research |
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| Induction of apoptosis by calcium D-glucarate in 7,12-dimethyl benz [a] anthracene-exposed mouse skin. J Environ Pathol Toxicol Oncol. 2007;26(1):63-73 Singh J, Gupta KP. Environmental Carcinogenesis Division, Industrial Toxicology Research Center, Mahatma Gandhi Marg, Lucknow, India. Calcium glucarate (Cag), a naturally occurring nontoxic compound, suppresses the DMBA-induced tumor development in mouse skin. In the process of understanding the mechanisms of tumor suppression by Cag, we investigated the effect of topical application of Cag on selective and critical events of apoptotic pathway in DMBA-exposed mouse epidermis. Varied doses of DMBA or Cag were used for the study. DMBA had an inhibitory effect on proteases in general and on caspases in particular. Cag tried to reverse the inhibitory effect of DMBA on 3, 8, or 9 caspase in a dose-dependent manner. Cag inhibited activity of Poly ADP-ribose polymerase enzyme, a substrate of caspses, after DMBA exposure. As indicated by western blotting, Cag treatment also inhibited PARP expression induced by DMBA at the level of protein. Cag induced the DMBA-inhibited Ca++/Mg++-dependent endonuclease, an enzyme responsible for the DNA fragmentation during apoptosis. DMBA induced the expression of mutant-p53 and Bcl-2. This induced expression of proteins was reversed when Cag was given along with DMBA. Cag showed a dose-dependent inhibition of DMBA-induced mutant-p53 expression. Similarly Bcl-2 overexpression by DMBA was also inhibited by topical treatment of Cag when given along with DMBA. Inhibition of mutant-p53 and Bcl-2 expression by Cag in DMBA-exposed mouse skin might contribute to the apoptogenic effect possibly exerted by Cag while suppressing the tumor development. The study indicates that Cag induces apoptosis in mouse epidermis, a possible mechanism for tumor suppression, and thus could be considered a promising anticancer agent. Modulation of Biomarkers During Chemoprevention of Mouse Lung Tumorigenesis by D-glucarate. Chest. 2004;125:149S. Margaret Hanausek, PhD; Zbigniew Walaszek, PhD; Janusz Szemraj, PhD; Robert Zoltaszek, MS and Thomas J. Slaga, PhD Several new potential serologic biomarkers for carcinogenesis are under development. The recently discovered oncofetal protein p65 has the potential to be used not only as a tumor marker, but also as a marker in chemoprevention trials for early detection of breast, prostate, and lung cancers. With a view toward early detection of cancer risk, we have studied strain-dependent differences in the expression of p65 in different organs of mice highly susceptible (C3H/HeJ, A/HeJ) and relatively resistant (C57BL/6N) to chemical carcinogenesis. Using reverse transcription polymerase chain reaction, we detected the p65-specific messenger RNA in mammary glands or lungs of young, 7- to 8-week-old female mice of the C3H/HeJ and A/HeJ strains known to spontaneously develop mammary gland or lung tumors, respectively. No p65-specific messenger RNA was detected in a control group of C57BL/6N mice resistant to chemical carcinogenesis. The occurrence of p65-specific messenger RNA in the susceptible organs or mononuclear cell populations of young C3H/HeJ and A/HeJ mice correlated well with the mammary gland and lung tumor incidence, respectively, reported for adult mice of these strains. Thus, expression of p65 examined by reverse transcription polymerase chain reaction may be used for lung cancer risk assessment. The p65 gene expression in A/J mice susceptible to lung cancer development was down-regulated by ß-glucuronidase inhibitors from a group of D-glucaric acid derivatives. Postinitiation treatment with calcium D-glucarate markedly reduced the number of benzo[a]pyrene-induced lung lesions in A/J mice, with mutated K-ras and p53 genes, ie, by 60% and 50%, respectively. Calcium D-glucarate may inhibit promotion and progression of lung tumorigenesis in A/J mice by facilitating DNA adduct removal, as well as by suppressing chronic inflammation and mutagenesis in benzo[a]pyrene-induced lesions. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44. Hanausek M, Walaszek Z, Slaga TJ. Different vitamins and other micronutrients in vegetables, fruits, and other natural plant products may prevent cancer development (carcinogenesis) by interfering with detrimental actions of mutagens, carcinogens, and tumor promoters. The goal of current studies in cancer prevention is to determine the mechanisms of synergistic action of the natural source compounds known to inhibit one or more stages of carcinogenesis, that is, initiation and promotion/progression. Many natural cancer preventive agents are effective inhibitors of tumor initiation, promotion, and/or progression. The mechanism of action is related to their abilities to prevent critical carcinogen metabolism and to increase detoxification of carcinogens and tumor promoters. The authors review here the potential role of the detoxification system and, in particular, the roles of D-glucaric acid and the enzyme beta-glucuronidase in early detection and prevention of cancer. There is now 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-glucarates). 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. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 2000; 40: 581-616. Tukey RH, Strassburg CP. In vertebrates, the glucuronidation of small lipophilic agents is catalyzed by the endoplasmic reticulum UDP-glucuronosyltransferases (UGTs). This metabolic pathway leads to the formation of water-soluble metabolites originating from normal dietary processes, cellular catabolism, or exposure to drugs and xenobiotics. This classic detoxification process, which led to the discovery nearly 50 years ago of the cosubstrate UDP-glucuronic acid (19), is now known to be carried out by 15 human UGTs. Characterization of the individual gene products using cDNA expression experiments has led to the identification of over 350 individual compounds that serve as substrates for this superfamily of proteins. This data, coupled with the introduction of sophisticated RNA detection techniques designed to elucidate patterns of gene expression of the UGT superfamily in human liver and extrahepatic tissues of the gastrointestinal tract, has aided in understanding the contribution of glucuronidation toward epithelial first-pass metabolism. In addition, characterization of the UGT1A locus and genetic studies directed at understanding the role of bilirubin glucuronidation and the biochemical basis of the clinical symptoms found in unconjugated hyperbilirubinemia have uncovered the structural gene polymorphisms associated with Crigler-Najjar's and Gilbert's syndrome. The role of the UGTs in metabolism and different disease states in humans is the topic of this review. Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. Cancer Detect Prev 1997; 21(2): 178-90. Walaszek Z, Szemraj J, Narog M, Adams AK, Kilgore J, Sherman U, Hanausek M. 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 femalerats. 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. Calcium glucarate as a chemopreventive agent in breast cancer. Isr J Med Sci 1995 Feb-Mar; 31(2-3): 101-5. Heerdt AS, Young CW, Borgen PI. Although it appears that progress is being made in the treatment of breast cancers of all stages, the etiological agents still remain unclear and render the search for preventive agents extremely difficult. What is clearly required in this situation is a nontoxic compound that can potentially affect various pathways that may be responsible for the rising incidence of breast cancer. In this review, we present the rationale for the use of an agent such as calcium glucarate, which may both change the internal hormonal milieu and also directly detoxify any environmental agents responsible for breast cancer. It is hoped that present and future clinical trials will help to better elucidate the role for this agent in the chemoprevention of breast cancer. Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis. Anticancer Res 1995 May-Jun; 15(3): 805-10. Abou-Issa H, Moeschberger M, el-Masry W, Tejwani S, Curley RW Jr, Webb TE. The independent effects of the potential cancer chemopreventive agent calcium glucarate (CGT) when fed (128 mmol/kg diet) during the initiation (I), promotion (P) or (I+P) phases of 7,12-dimethylbenzanthracene-induced rat mammary carcinogenesis, was compared to that of the known chemopreventive agent N-(4-hydroxyphenyl) retinamide (4-HPR) fed (2.0 mmol/kg diet) during these same phases. CGT and especially 4-HPR both significantly increased tumor latency when fed during the P-phase. When fed during I, P or I+P phases mammary tumor incidence was reduced compared to the controls 33%, 42% and 67% by 4-HPR and 18%, 42% and 50% by CGT. Similarly, tumor multiplicity was significantly reduced by either agent. For example, as compared to the corresponding control, when fed during the I, P or I+P phases 4 HPR reduced tumor multiplicity 63, 34 and 63%, while CGT reduced tumor multiplicity 28, 42 and 63% respectively. CGT, like 4-HPR, acts on both the I and P phases with the effect being maximal when fed during P and I+P phases. The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide medical advice to individuals. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes. Any reproduction in whole or part and in print or electronic form without express permission is strictly forbidden. Permission to reproduce selected material may be granted by contacting AOR Inc. Copyright © 2005, Advanced Orthomolecular Research |
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