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CALCIUM D-GLUCARATE



Table of Contents
image Trends in fruit and vegetable consumption among adults in 16 US states: Behavioral Risk Factor Surveillance System, 1990-1996.
image D-glucaric acid content of various fruits and vegetables and cholesterol- lowering effects of dietary D-glucarate in the rat
image Effect of calcium glucarate on beta-glucoronidase activity and glucarate content of certain vegetable and fruits
image Dietary glucarate-mediated inhibition of initiation of diethylnitrosamine-induced hepatocarcinogenesis.
image Wheat bran and psyllium diets: effects on N-methylnitrosourea-induced mammary tumorigenesis in F344 rats.
image Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis.
image Antiproliferative effect of dietary glucarate on the Sprague-Dawley rat mammary gland.
image Calcium glucarate as a chemopreventive agent in breast cancer
image Growth suppression of human breast carcinoma cells in culture by N-(4-hydroxyphenyl)retinamide and its glucuronide and through synergism with glucarate
image Activity of D-glucarate analogues: Synergistic antiproliferative effects with retinoid in cultured human mammary tumor cells appear to specifically require the D-glucarate structure
image D-Glucarate a Nutrient Against Cancer
image Antitumour synergism between non-toxic dietary combinations of isotretinoin and glucarate
image Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis.
image Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis.
image Chemopreventative activity of dietary glucarate on azoxymethane-induced altered hepatic foci in rats
image Potential use of D-glucaric acid derivatives in cancer prevention.
image Effects of the experimental chemopreventative agent, glucarate, on intestinal carcinogenesis in rats.
image Glucuronidation of Drugs and other Compounds
image Potential use of D-glucaric acid derivatives in cancer prevention

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Trends in fruit and vegetable consumption among adults in 16 US states: Behavioral Risk Factor Surveillance System, 1990-1996.

Li R, Serdula M, Bland S, Mokdad A, Bowman B, Nelson D
Division of Nutrition and Physical Activity, Centers for Disease Control and Prevention (MS K25), Atlanta, GA 30341-3717, USA. ril6@cdc.gov
Am J Public Health 2000 May;90(5):777-81

OBJECTIVES: This study examined trends in fruit and vegetable consumption among adults in 16 US states. METHODS: Data from telephone surveys were used to stratify respondents by sociodemographic and health-related characteristics. RESULTS: The proportion of adults who consumed fruits and vegetables at least 5 times daily was 19%, 22%, and 23% in 1990, 1994, and 1996, respectively. While the proportion increased among those with active leisure-time physical activities and normal weight, it remained almost the same among inactive people and dropped among the obese. CONCLUSIONS: Progress in fruit and vegetable intake from 1990 to 1994 was encouraging, but it changed little between 1994 and 1996.



D-glucaric acid content of various fruits and vegetables and cholesterol- lowering effects of dietary D-glucarate in the rat

Walaszek Z.; Szemraj J.; Hanausek M.; Adams A.K.; Sherman U.
Bio-Organic/Nat. Product Chem. Lab., Biomedical Horizons Institute, P.O. Box 695,Smithville, TX 78957 United States
Nutrition Research ( NUTR. RES. ) (United States) 1996, 16/4 (673-681)

The beneficial properties of different vitamins, minerals, and other micronutrients have been studied for quite some time. But only recently has the potential usefulness of D-glucaric acid and its derivatives in disease prevention been demonstrated. D-Glucaric acid is an end product of the D- glucaronic acid pathway in mammals. Its dietary sources include different fruits and vegetables. In the present study, D-glucaric acid content in various fruits and vegetables was found to range from about 0.1 g/kg in grapes and lettuce to about 3.5 g/kg in apples and broccoli. It was also shown that purified diets containing calcium D-glucarate or potassium hydrogen D-glucarate markedly lowered serum levels of cholesterol in female Sprague-Dawley rats. The D-glucarates reduced total serum cholesterol in rats by up to 14% (P<0.05) and lowered LDL-cholesterol by up to 35% (P<0.05), but had no effect on HDL cholesterol. These results provide a starting point for further studies of the mechanism by which D-glucaric acid salts lower serum cholesterol.



Effect of calcium glucarate on beta-glucoronidase activity and glucarate content of certain vegetable and fruits

Dwivedi C.; Heck W.J.; Downie A.A.; Larroya S.; Webb T.E.
College of Pharmacy, South Dakota State University, Brookings, SD 57007
United States
Biochemical Medicine and Metabolic Biology ( BIOCHEM. MED. METAB. BIOL. ) (United States) 1990, 43/2 (83-92)

Glucarate is normally present in tissues and body fluids and in equilibrium with D-glucaro-1,4-lactone, a natural inhibitor of beta-glucuronidase activity. Dietary calcium glucarate, a sustained-release from of glucarate, elevates the blood level of D-glucaro-1,4-lactone which suppresses blood and tissue beta-glucuronidase activity. A single dose of CaG (4.5 mmole/kg body weight) inhibited beta-glucuronidase activity in serum and liver, lung, and intestinal microsomes by 57, 44, 37, and 39%, respectively. A chronic administration of calcium glucarate (4% in diet) also decreased beta-glucuronidase activity in intestinal and liver microsomes. Maximal inhibition of beta-glucuronidase activity in serum was observed from 12 noon to 2:00 PM. In contrast, maximum inhibition of beta-glucuronidase activity in intestinal and liver microsomes occurred during mornings, although a secondary depression in intestinal microsomes also occurred around 4 PM. A 4% calcium glucarate supplemented diet also inhibited beta-glucuronidase activity by 70% and 54%, of the bacterial flora obtained from proximal (small intestine) and distal (colon) segments of intestine, respectively. Due to the potential effect of dietary glucarate on net glucuronidation and on other metabolic pathways, glucaric acid levels in various foods were determined. The glucaric acid content varied from a low of 1.12 - 1.73 mg/100 g for broccoli and potatoes to a high of 4.53 mg/100 g for oranges

Dietary glucarate-mediated inhibition of initiation of diethylnitrosamine-induced hepatocarcinogenesis.

Oredipe OA; Barth RF; Dwivedi C; Webb TE
Ohio State Univ., Dep. Pathol., 165 Hamilton Hall, 1645 Neil Ave.,
Columbus, Ohio 43210.
Source: TOXICOLOGY; 74 (2-3). 1992. 209-222

Previously, it has been reported that calcium glucarate is a potent inhibitor of chemical carcinogenesis, including phenobarbital-promoted diethylnitrosamine-initiated hepatic toxicity expressed as altered hepatic foci in rats. The purpose of the present study was to determine whether calcium glucarate could inhibit the immediate and delayed appearance of altered hepatic foci when fed to rats during the initiation phase of diethylnitrosamine-induced hepatocarcinogenesis. The effects of dietary mode of administration of carbon glucarate on the initiation phase of hepatocarcinogenesis were also examined. Since diethylnitrosamine is not known to undergo glucuronidation and calcium glucarate has been shown to enhance clearance of circulating estrogens, an indirect mechanism of action of calcium glucarate was also evaluated by pretreating rats an anti-estrogen, tamoxifen, prior to partial hepatectomy and administration of diethylnitrosamine. Calcium glucarate significantly inhibited both the early and delayed appearance of altered hepatic foci and exerted maximal inhibition when administered by gavage prior to diethylnitrosamine. Maximal inhibition was obtained when calcium glucarate was provided continuously in the diet of animals up to 5 and 7 months. Pretreatment of animals with tamoxifen before partial hepatectomy and diethylnitrosamine resulted in maximal inhibition of the initiation phase of hepatocarcinogenesis. This suggests but does not prove that the anti-carcinogenic activity of calcium glucarate was due to decreased liver proliferation. In the present study, the proliferation of ductal epithelial and oval cells appeared to be associated with the administration of diethylnitrosamine. Collectively, our data suggest that calcium glucarate inhibited the initiation phase of diethylnitrosamine-induced hepatocarcinogenesis.


Wheat bran and psyllium diets: effects on N-methylnitrosourea-induced mammary tumorigenesis in F344 rats.

Cohen LA, Zhao Z, Zang EA, Wynn TT, Simi B, Rivenson A
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla,
NY 10595, USA.
J Natl Cancer Inst 1996 Jul 3;88(13):899-907

BACKGROUND. Experimental and epidemiologic evidence suggests that increased dietary fiber is associated with decreased breast cancer risk. Little is known about the role played by different types of fiber and, particularly, mixtures of soluble and insoluble fibers similar to those consumed by human populations in reducing breast cancer risk. High intake of fiber may suppress bacterial hydrolysis of biliary estrogen conjugates to free (absorbable) estrogens in the colon and thus may decrease the availability of circulating estrogens necessary for the development and growth of breast cancers. PURPOSE. The purpose of this study was to evaluate the effect of wheat bran (an insoluble fiber) and psyllium (a soluble fiber) alone and in combination on overall + status, on fecal bacterial beta-D-glucuronidase (a key diet-responsive estrogen-deconjugating enzyme) activity, and on the induction of mammary tumors in rats treated with N-methylnitrosourea (MNU). METHODS. One hundred fifty virgin female F344 rats were fed the NIH-07 diet from 28 days of age until 50 days of age; they were then given a single dose (40 mg/kg of body weight) of MNU by tail vein injection. Three days later, they were randomly assigned to one of five experimental dietary groups (30 animals per group). Soft, white wheat bran (45% dietary fiber content) and psyllium (80% dietary fiber content) were added to a modified (high-fat) American Institute of Nutrition (AIN)-76A diet at the following percents, respectively: 12% + 0% (group 1), 8% + 2% (group 2), 6% + 3% (group 3), 4% + 4% (group 4), and 0% + 6% (group 5). Blood, urine, and feces were collected and analyzed by radioimmunoassay techniques for estrogens. Cecal contents were analyzed for bacterial beta-D-glucuronidase activity. After 19 weeks on the experimental diets, the rats were killed, and mammary tumors were counted and classified by histologic type. Cumulative tumor incidence was evaluated by the Kaplan-Meier life-table method and the logrank test. Tumor number was evaluated by the chi-squared test of association, and tumor multiplicity was evaluated by the Mantel-Haenszel chi-squared test. All statistical tests were two-tailed. RESULTS. As the level of psyllium relative to that of wheat bran increased, the total tumor number and multiplicity of mammary adenocarcinomas in rats decreased as a statistically significant linear trend across groups 1-5 (P < .05). Compared with the group given wheat bran alone, the group given the 1:1 (wheat bran:psyllium) combination had maximum protection against mammary tumorigenesis, while the groups given the 4:1 or 2:1 (wheat bran:psyllium) combination or psyllium alone had intermediate protection. No statistically significant differences in circulating estrogens or urinary estrogen excretion patterns were observed among the five experimental groups. Fecal estrogen excretion, however, decreased with increasing levels of psyllium (P < .01), and cecal beta-D-glucuronidase activity exhibited a decreasing trend with respect to the increasing psyllium content of the diet across groups 1-5 (P < .01). CONCLUSIONS. The addition of a 4%:4% mixture of an insoluble (wheat bran) fiber and a soluble (psyllium) fiber to a high-fat diet provided the maximum tumor-inhibiting effects in this mammary tumor model. Although increasing levels of dietary psyllium were associated with decreased cecal bacterial beta-D-glucuronidase activity, these changes were not reflected in decreased circulating levels of tumor-promoting estrogens. Therefore, the mechanism(s) by which mixtures of soluble and insoluble dietary fibers protect against mammary tumorigenesis remains to be clarified.


Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis.

Walaszek Z, Hanausek-Walaszek M, Webb TE
Cancer Lett 1986 Oct;33(1):25-32

Serum beta-glucuronidase activity is shown to differ quantitatively in the following strains of mice, listed in order of increasing activity: C3H, C57BL/6 less than BALB/c, DBA/2, ICR less than SENCAR, A/He. The level of the enzyme in the murine strains is shown to correlate with the urinary excretion of 17-ketosteroids, which in turn reflects the endogenous level of androgens. Dietary calcium D-glucarate, an in vivo beta-glucuronidase inhibitor, reduced the steady state level of both beta-glucuronidase and 17-ketosteroid excretion in the highly susceptible A/He and SENCAR strains to that of strains known to be resistant to chemical carcinogenesis. Sensitivity of the A/He strain is significantly reduced by dietary calcium glucarate, which is shown to inhibit DNA binding and the induction of pulmonary adenomas by benzo[a]pyrene.


Antiproliferative effect of dietary glucarate on the Sprague-Dawley rat mammary gland.

Walaszek Z, Hanausek M, Sherman U, Adams AK
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957.
Cancer Lett 1990 Jan;49(1):51-7

Dietary glucarate has previously been shown to inhibit chemical carcinogen-induced rat mammary tumorigenesis. It is demonstrated in this paper that in the mammary gland of the female Sprague-Dawley rat, feeding glucarate at a dose of 70 mmol/kg AIN76A diet for 2 weeks beginning at 35 days of age, markedly reduces [3H]thymidine labeling. Specific histochemical staining for beta-glucuronidase is used to show that the glucarate diet fed to rats for 2-4 weeks inhibits beta-glucuronidase activity in the mammary gland and has a marked antiproliferative effect on mammary epithelium. Glucarate may inhibit rat mammary carcinogenesis, in part, by changing the proliferative status of the target organ.


Calcium glucarate as a chemopreventive agent in breast cancer

Heerdt A.S.; Young C.W.; Borgen P.I.
Breast Service, Memorial Sloan-Kettering Cancer Ctr., 1275 York
Avenue,New York, NY 10021 United States
Israel Journal of Medical Sciences ( ISR. J. MED. SCI. ) (Israel) 1995, 31/2-3 (101-105)

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.


Growth suppression of human breast carcinoma cells in culture by N-(4-hydroxyphenyl)retinamide and its glucuronide and through synergism with glucarate

Bhatnagar R.; Abou-Issa H.; Curley Jr. R.W.; Koolemans-Beynen A.;
Moeschberger M.L.; Webb T.E.
Department of Surgery, College of Medicine, Ohio State University,Columbus, OH 43210 United States
Biochemical Pharmacology ( BIOCHEM. PHARMACOL. ) (United Kingdom) 1991, 41/10 (1471-1477)

The inhibitory effects of N-(4-hydroxyphenyl)retinamide (HPR) and its glucuronide derivative on the growth of MCF-7 human breast cancer cells in vitro were compared. The results indicate that the glucuronide had slightly greater potency and much less cytotoxicity than the free retinoid. At a concentration of 10sup -sup 6 M, HPR inhibited MCF-7 cell growth by approximately 25%, whereas an equimolar concentration of the glucuronide caused a 40% growth inhibition. Higher concentrations of HPR were highly cytotoxic. At a 10sup -sup 5 M concentration of the glucuronide, cell viability was 77%, and 65% of the cells were able to resume growth. On the other hand, at 10sup -sup 5 M HPR, cell viability dropped to 49%, and only 15% of the cells were capable of resuming growth. The lower cytotoxicity and higher potency of the retinoid glucuronide compared to the parent retinamide suggest that the conjugate may have a chemotherapeutic advantage over the parent compound. The apparent higher efficacy of HPR in combination with glucarate (GT) compared to the single agents could be due to increased net formation of HPR glucuronide conjugate following conversion of GT to the beta-glucuronidase inhibitor, D-glucaro-1,4-lactone. However, HPLC analysis of the cell metabolites did not show any detectable levels of the retinoid glucuronide upon treatment of MCF-7 cells with HPR and GT.


Activity of D-glucarate analogues: Synergistic antiproliferative effects with retinoid in cultured human mammary tumor cells appear to specifically require the D-glucarate structure

Curley Jr. R.W.; Humphries K.A.; Koolemans-Beynan A.; Abou-Issa H.; Webb
T.E.
Medicinal Chem./Pharmacognosy Div., College of Pharmacy, Ohio State
University, 500 W. 12th Ave.,Columbus, OH 43210 United States
Life Sciences ( LIFE SCI. ) (United States) 1994, 54/18 (1299-1303)

D-Glucarate has shown modest chemopreventive and synergistic chemopreventive effects with retinoids in a number of tumor models as well as a similar antiproliferative effect in MCF-7 human tumor cells in culture. It has been postulated that D-glucarate exerts some of its effects by equilibrium conversion to D-glucarolactone, a potent beta-glucuronidase inhibitor. In the present study, D-glucarate and a number of its analogues, including D-glucarolactone, were evaluated as antiproliferatives in the MCF- 7 model with and without added retinoid. Results suggest that the effects of glucarate are reasonably specific for its structure and may not require conversion to glucarolactone.


Slaga,T. J. 1999. D-Glucarate a Nutrient Against Cancer. Keats Publishing - Lincolnwood, Chicago Illiinois. page 33


Antitumour synergism between non-toxic dietary combinations of isotretinoin and glucarate

Abou-Issa H.; Koolemans-Beynen A.; Meredith T.A.; Webb T.E.
Ohio State Univ. College of Medicine, 320 W. 10th Ave.,Columbus, OH 43210
United States
European Journal of Cancer Part A: General Topics ( EUR. J. CANCER PART A GEN. TOP. ) (United Kingdom) 1992, 28/4-5 (784-788)

Dietary calcium glucarate (CGT) increased the activity of non-toxic levels of dietary isotretinoin against preestablished tumors in the chemically-induced rat mammary tumour model. In the range of 1.0-1.5 mmol/kg diet, isotretinoin enhanced tumour growth by 20% over a 4 week course of treatment. Tumour growth inhibition not exceeding 15% was observed only at dosages as high as 2.0 mmol/kg, i.e. in the cumulative toxicity range. Growth inhibition by 64 mmol/kg diet of CGT alone was marginal, varying from zero to 8%. In contrast, the combination of 1.0 mmol/kg of isotretinoin and 64 mmol/kg of CGT caused a reversible inhibition of tumour growth, culminating in a net decrease in tumour volume of 20%. This study documents the marginal enhancement of tumour growth by high sub-optimal concentrations of isotretinoin alone, and describes conditions for inhibition of tumour growth by sub-optimal concentrations of the natural retinoid. Related in vitro studies on retinoid sensitive and insensitive cell lines suggest that the anticancer activity of the combination is dependent on sensitivity of the cells to retinoids.


Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis.

Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE
Carcinogenesis 1986 Sep;7(9):1463-6

Using as a criterion the inhibition of serum beta-glucuronidase activity, dietary calcium D-glucarate is shown to serve as an efficient slow-release source in vivo of D-glucaro-1,4-lactone, the potent endogenous inhibitor of this enzyme. Using the 7,12-dimethylbenz[a]anthracene model of mammary tumor induction in rats it is shown for the first time that feeding the rats calcium D-glucarate-supplemented diet after treatment with the carcinogen, inhibits tumor development by over 70%. Supportive evidence is presented for the theory that calcium D-glucarate inhibits or delays the promotion phase of mammary carcinogenesis by lowering endogenous levels of estradiol and precursors of 17-ketosteroids. Therefore, dietary glucarate can be used to lower blood and tissue levels of beta-glucuronidase, and in turn of those carcinogens and promoting agents which are excreted, at least in part, as glucuronide conjugates.


Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis.

Abou-Issa H, Moeschberger M, el-Masry W, Tejwani S, Curley RW Jr, Webb TE
Department of Surgery, College of Medicine, Ohio State University, Columbus 43210, USA.
Anticancer Res 1995 May-Jun;15(3):805-10

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.


Chemopreventative activity of dietary glucarate on azoxymethane-induced altered hepatic foci in rats

Oredipe O.A.; Barth R.F.; Dwivedi C.; Webb T.E.
Department of Pathology, The Ohio State University, Columbus, OH 43210
United States
Research Communications in Chemical Pathology and Pharmacology ( RES. COMMUN. CHEM. PATHOL. PHARMACOL. ) (United States) 1989, 65/3 (345-359)

Previous studies have shown that dietary calcium glucarate, an inhibitor of beta-glucuronidase, is a potent inhibitor of promotion of diethylnitrosamine-induced altered hepatic foci, 7,12-dimethylbenzanthracene-induced mammary tumorigenesis and benzo(a)pyrene-induced lung carcinogenesis. The present study was undertaken to test the chemopreventive activity of calcium glucarate on azoxymethane-induced hepatocarcinogenesis in female Fischer 344 rats. A series of experiments were carried out over 36 weeks to evaluate the effects of calcium glucarate on the initiation and promotion phases separately and also in combination with each other. A calcium gluconate group was included and used as a negative calcium control. Histopathologic evaluation of H and E stained liver sections of all animals in this study showed that a statistically significant inhibition of hepatocarcinogenesis only occurred when dietary calcium glucarate supplementation was provided throughout the combined initiation and promotion phases. This inhibitory effect approximately equaled the summation of that obtained when calcium glucarate was fed only during initiation phase and only during promotion phase.


Potential use of D-glucaric acid derivatives in cancer prevention.

Walaszek Z
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957.
Cancer Lett 1990 Oct 8;54(1-2):1-8

There is now growing evidence from animal models for the possible control of different stages of the carcinogenic process by the beta-glucuronidase inhibitor D-glucaro-1,4-lactone and its precursors such as D-glucaric acid salts, D-glucarates. D-Glucaric acid is a natural, non-toxic compound produced in small amounts by mammals, including humans. It was recently found in some vegetables and fruits. D-Glucaro-1,4-lactone and D-glucarate exhibit potent antiproliferative properties in vivo. Some human subpopulations could have reduced risk of cancer development by ingesting food rich in D-glucaric acid or self-medication with D-glucarates alone or in combination with other chemopreventive agents.


Effects of the experimental chemopreventative agent, glucarate, on intestinal carcinogenesis in rats.

Dwivedi C, Oredipe OA, Barth RF, Downie AA, Webb TE
Department of Physiological Chemistry, College of Medicine, Ohio State University, Columbus 43210.
Carcinogenesis 1989 Aug;10(8):1539-41

Dietary calcium glucarate was previously shown to protect effectively against chemically-induced mammary, lung, liver and skin carcinogenesis in rodents, whereas the negative dietary calcium control, calcium gluconate, had no effect. In the present study the chemopreventative activity of dietary calcium glucarate was evaluated in the azoxymethane intestinal carcinogenesis model using the Fischer strain rat. The protocol limited the duration of azoxymethane treatment to 3 weeks to permit the evaluation of the separate effects of glucarate on the initiation and promotion phases. Control rats, treated with azoxymethane and maintained on a low fat chow diet throughout the 32-week experiment had an intestinal adenocarcinoma incidence of 55%, with an equal incidence of 27.7% in the small and large intestines. There was no significant difference between this control group and a negative calcium control group fed 128 mmol/kg chow of calcium as calcium gluconate. In contrast to these two control groups, supplementation of the diet of azoxymethane-treated rats with 128 mmol/kg diet of calcium glucarate during both the initiation and promotion phases significantly inhibited the overall induction of adenocarcinomas in the intestine, the incidence in the entire intestine and in the small and large intestines being 11.8, 5.8 and 5.8%, respectively. When fed only during the initiation phase, the inhibition again was statistically significant, the corresponding values being 11.8%, 5.8 and 5.8%. When calcium glucarate was fed during the promotion phase, a statistically significant inhibition of adenocarcinoma induction was observed only in the colon where the incidence was 5.5%. Weight gain was similar in all groups. These and related data indicate that dietary glucarate exerts a significant inhibitory effect on azoxymethane-induced intestinal and in particular colon carcinogenesis in the rat, decreasing their incidence and size and reducing their metastic potential.


Dutton, G.J. 1980. Glucuronidation of Drugs and other Compounds. Boca Raton, FL.: CRC Press


Potential use of D-glucaric acid derivatives in cancer prevention

Walaszek Z.
Department of Carcinogenesis, Science Park-Research Division, The
University of Texas M.D. Anderson Cancer Center, P.O. Box 389,
Smithville, TX 78957 United States
Cancer Letters ( CANCER LETT. ) (Ireland) 1990, 54/1-2 (1-8)

There is now growing evidence from animal models for the possible control of different stages of the carcinogenic process by the beta-glucuronidase inhibitor D-glucaro-1,4-lactone and its precursors such as D-glucaric acid salts, D-glucarates. D-Glucaric acid is a natural, non-toxic compound produced in small amounts by mammals, including humans. It was recently found in some vegetables and fruits. D-glucaro-1,4-lactone and D-glucarate exhibit potent antiproliferative properties in vivo. Some human subpopulations could have reduced risk of cancer development by ingesting food rich in D-glucaric acid or self-medication with D-glucarates alone or in combination with other chemopreventive agents.