RE: Cacium D-Glucarate Cancer Preventer & Detoxifier
----------------- Bulletin Message -----------------
From: § Lori §
Date: Jan 12, 2008 4:00 PM
From: Vaccine Truth
Date: Jan 12, 2008 2:43 PM
Disclaimer: For educational purposes only This information has not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease
Calcium D-Glucarate —A Cancer Preventer?
If you follow the news, you are no doubt aware of the tremendous harm chemicals are doing to the environment and, more importantly, the negative impact of those chemicals on your health. One major concern is the effect of environmental chemicals on hormone sensitive tissue. Mounting evidence is linking excessive levels of hormones and carcinogenic chemicals to breast, prostate, uterine, and probably ovarian cancers.
Your risk of cancer and other serious illnesses increase in relationship to the accumulation of toxic chemicals and toxic levels of steroid hormones.
Under ideal circumstances the body has a biochemical plan in place to help it to inactivate and eliminate hormones, drugs and other undesirable chemicals. One such plan or pathway is glu¬curonidation. Glucuronidation is basically a chemi¬ cal reaction performed by your liver during which a water-soluble substance is combined with a toxin, allowing the toxin to be more easily excret¬ed from the body.
Normally the glucuronidation pathway of elimination works pretty well, unless the body is grossly overloaded with toxins, or unless some other chemical or even parasite or bacteria gets in the way. When this occurs, the body's intricate system of detoxification and elimination is threat¬ened. Consumption of caffeine and processed meats, smoking tobacco, marijuana, even exposure to car-exhaust or pesticides all cause a loss of glucarate which impedes glucuronidation.
However, the good news is that glucuronidation, can be enhanced. Turns out that providing an ample supply of a dietary supplement similar to glucuronic acid called calcium D-glucarate binds the enzyme so that it's unable to free the hormones/toxins being eliminated by the liver.
Calcium D-glucarate is a safe supplement that has no known negative interactions or toxicity, it inhibits the undesirable bacterial enzyme, beta glucuronidase and thus aids our elimination of toxins. Calcium D-glucarate naturally occurs in fruits and vegetables. This may explain the protective effects of vegetables that reduce the risk of cancer. Many of them are abundant sources of D glucarate. They include the cruciferous vegetables cabbage, broccoli, and brussels sprouts.
Other foods that contain it are grapefruit, apples, bean sprouts, and lettuce.
Calcium D-glucarate is relatively inexpensive and is recommended by nutritionists for persons at risk of such cancers. The suggested dose ranges from 200-400 mg per day. If you have had a relatively low exposure to toxins in your life, a low dose may be fine. If you smoke or have lived in a very polluted area you might choose a higher dose, say 500 mg three times a day. I enthusiastically recommend it to my patients, especially female patients who I feel are at elevated risk of breast cancer, men at risk of prostate cancer, or both sexes at risk of colon cancer. The mucosal cells that line the colon may be a hotbed for cancer simply because they are at the end of the line for expo¬sure to a wide variety of poisons being eliminated through the gut. Preventing the uncoupling of a toxin from the eliminating compound also helps protect colon cells from the increased exposure.
Calcium D-glucarate supplements do not take the place of changing your lifestyle to a healthy one But they do offer good support of important detoxification pathways, especially if you've ever been a smoker, a lover of lunchmeats or hot dogs, or of coffee and sodas.
If you are still a smoker, Calcium D-glucarate is a very appropriate supplement for you. It is not a cure for a body loaded with toxins, but it could give your body the support it needs to remain healthier longer.
Calcium D-Glucarate is available at health food stores or online. Here’s to your health and screw the FDA and Drug companies. ~Namaste~
http://www.iherb.com/Search.aspx?c=1&kw=calcium+d+glucarate
The Toxic Avenger: Calcium D-glucarate — a new detoxifying supplement — can help enhance your metabolism, recovery and growth - The Wright Stuff
Jim Wright
Q: I really enjoy you column and have made excellent progress. Although I'm satisfied with my training program and my overall diet, I'm still not getting that final polish on my physique. Is there anything else --perhaps a supplement -- I can use to harden my physique?
A: Maximizing your potential for leanness, hardness and fullness might not be rocket science, but it does take more than popping a few thermogenics, going on a low-carb diet and doing cardio three or four hours a week. It also requires a whole lot more information than I have room to impart here (look for a superfeature on fat loss in our April 2002 issue).
There definitely is, however, one supplement I'd highly recommend to every bodybuilder who wants to support his or her overall health. In addition to lowering cancer risks, this supplement helps to eliminate excess estrogen, among other metabolites, waste products and toxins, that could contribute to fluid retention, gynecomastia (in males) and other undesirable physique effects.
Calcium D-glucarate (C-D-G) is a nontoxic patented form of glucaric acid that is easily absorbed, active in small (and inexpensive) doses and bioavailable in the body for relatively extended periods. Glucaric acid is present in different fruits and vegetables and is made in very small amounts by our own bodies. However, as science has discovered with regard to most beneficial phytochemicals, even if you ate as much of the appropriate foods you could, it would still be difficult if not impossible to consistently get the amount of C-D-G more conveniently available in the supplement. (See the sidebar, "A Quick Guide to C-D-G," for further information.)
Researchers at M.D. Anderson Cancer Center in Houston, Texas, developed the supplemental form of C-D-G. The scientists there were studying why and how a diet high in fruits and veggies reduced the incidence of certain cancers and other degenerative diseases. After many animal and human studies showed that C-D-G could significantly decrease lung, skin, liver, breast, colon and prostate cancers, most by half or more, the agent was developed into a dietary supplement. Even if you're not worried about cancer, C-D-G definitely has something to offer with regard to your physique.
DETOX AND IMMUNITY You don't have to be a genius to realize that optimizing metabolism and growth requires a "clean" internal/chemical environment. That can't be stressed enough. The liver is the key organ for detoxification, as well as for literally hundreds of other reactions that directly impact anabolism and catabolism in muscle and connective tissue. The immune system drives the train of tissue repair.
Detoxifying the body, and thus reducing the associated load on the liver and immune system, allows more of those systems' capacities and more of the body's energy to be directed toward repair of exercise-induced tissue damage, more effective nutrient processing and muscle growth. It should be obvious that a clean internal environment would make a difference in how your body responds to training, especially over the long term.
How do you detox the body and get clean? As we've said repeatedly in past issues, you do that by:
* eating "clean";
* drinking plenty of water;
* ensuring a high fiber intake;
* taking antioxidants (e.g., a complete multivitamin-multimineral supplement);
* and limiting intake of or exposure to toxic substances, such as tobacco, alcohol, environmental pollutants and pharmaceutical drugs (except those prescribed by a physician).
But how many bodybuilders adhere to those rules most of the time? And how many manage to eat the eight to 10 servings of fruits and vegetables daily that are needed to support physique and performance goals? Forget the government-recommended five servings a day; just as with the old recommended daily allowances, they don't cut it for bodybuilders and other serious athletes. That's especially true now that we know that, among their other benefits, fruits and vegetables are so important for overall health and for bodybuilding because of their glucaric acid content.
HOW TO GET DRIER AND HARDER
Supplementing with C-D-G is important to bodybuilders -- male or female -- because it significantly boosts the body's capacity to eliminate toxins and waste products and improves androgen/estrogen balance.
As demonstrated in many studies, supplemental C-D-G has amazing effects on estrogen levels in women, dramatically lowering estrogen-related health problems and diseases. In my own informal studies, I've seen C-D-G improve the physiques of a number of women bodybuilders and fitness athletes, and I'm confident that it can help anyone make progress over time.
Given the chemical similarity between testosterone and estrogen, you might wonder if C-D-G could also reduce testosterone levels or adversely affect muscle building. To answer that, since it's not apparent from the published literature, I queried Thomas Slaga, PHD, director of AMC Cancer Research Center in Denver, Colorado, and an expert on C-D-G. He responded unequivocally that it "would have no effects on free testosterone or on testosterone binding to its receptors in muscle."
As Slaga further explained, "C-D-G is about eliminating excess levels of steroids and sterols and balancing the androgen:estrogen ratio. It's about keeping the 'system' between the lines, so to speak, hormonally, metabolically, etc., thus optimizing the body's potential for moving forward on the path of recuperation and muscle growth."
Dr. Wright welcomes questions about supplements, food and nutrition
What is it? Calcium D-glucarate (C-D-G) is a dietary supplement that helps eliminate toxins and wastes from the body.
Is it found in food? Yes, it's in fruits and vegetables - the highest amounts are in apples, cherries, apricots and grapefruits, as well as other citrus fruits. Significant amounts are also found in broccoli, Brussels sprouts and alfalfa sprouts. However, supplementation is the best way to make sure you get enough.
What supplement forms are available and where can it be purchased? Look for C-D-G in tables and capsules. It is alos now added to some protein/meal-replacement powders. The supplement should be available in quality health-food outlets and in major supermarket and drugstore chains.
What's the best dose? Most of the beneficial results found in studies of C-D-G were achieved at doses of 200-400 milligrams per day. I'd suggest you opt for the higher amount, and don't hesitate to try more if you want, because C-D-G is a natural substance and essentially nontoxic. Take it anytime during the day, with or without food.
Calcium-D-glucarate - Monograph
Introduction
Calcium-D-glucarate is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans. Glucaric acid is also found in many fruits and vegetables with the highest concentrations to be found in oranges, apples, grapefruit, and cruciferous vegetables. (1) Oral supplementation of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microflora and involved in Phase II liver detoxification. Elevated beta-glucuronidase activity is associated wire an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers. (2) Other potential clinical applications of oral calcium-D-glucarate include regulation of estrogen metabolism and as a lipid-lowering agent.
Pharmacokinetics
Upon ingestion and exposure to the acidic environment of the stomach, calcium-D-glucarate is metabolized to form D-glucaric acid. D-glucaric acid is further metabolized in the gastrointestinal tract into three compounds existing in equilibrium and comprised of approximately 40-percent D-glucaric acid, 30-percent D-glucaro-1,4-lactone, and 30-percent D-glucaro-6,3-lactone. These compounds are then transported to the blood and various internal organs, and are subsequently excreted in the urine and bile. Although D-glucaro-1,4-lactone seems to be the most pharmacologically active of the three, it is not commercially available. Also, calcium-D-glucarate administration results in longer inhibition of beta-glucuronidase (five hours versus one hour) than does D-glucaro-1,4-lactone, so it is the compound used. (3)
Mechanism of Action
Calcium-D-glucarate's detoxifying and anticarcinogenic properties are attributed to its ability to increase glucuronidation and excretion of potentially toxic compounds. During Phase II detoxification, chemical carcinogens, steroid hormones, and other lipid-soluble toxins are conjugated with glucuronic acid in the liver (glucuronidation), and excreted through the biliary tract. Beta-glucuronidase is capable of deconjugating these potential toxins, making it possible for them to be reabsorbed rather than excreted. D-glucaro-1,4-lactone is the metabolite that has been shown to inhibit beta-glucuronidase activity, increasing excretion of conjugated xenobiotic compounds and decreasing activity of harmful substances that are most active in their deconjugated state. (4,5) Inhibition of beta-glucuronidase ultimately results in potentially decreasing the risk of carcinogenesis. (6) In addition, by reducing the beta-glucuronidase viability and activity of intestinal bacteria, salts of D-glucaric acid have been shown to enhance enterohepatic circulation and reduce steady state levels of cholesterol synthesis, resulting in decreased serum lipid levels. (7)
Deficiency States
Calcium-D-glucarate is not an essential nutrient so, technically, no deficiency state exists. However, since it is only produced in small amounts by humans, it is important that dietary intake be adequate. Diets low in fruits (particularly oranges, apples, and grapefruit) and cruciferous vegetables (broccoli, cabbage, and brussel sprouts) may result in a relative deficiency of calcium-D-glucarate and its metabolites. Research has shown a low level of D-glucaric acid correlates with a higher level of beta-glucuronidase, which in turn is associated with an increased risk for various cancers. (2)
Clinical Indications
Cancer
The anticarcinogenic properties of D-glucaric acid and its salts have been studied in various animal tumor models, including colon, (8,9) prostate, (2) lung, (10) liver, (11,12) skin, (13) and breast (14-18) cancer, with the mechanism of action for tumor inhibition being very similar in each. These studies demonstrated decreases in beta-glucuronidase activity, carcinogen levels, and tumorigenesis. The preponderance of research, however, has been conducted on mammary tumors in the rat, the animal model most frequently used for breast cancer research.
Breast Cancer
A number of studies have shown calcium-D-glucarate alone, and in combination with retinoids, inhibits mammary carcinogenesis in rats by as much as 70 percent. (3) Natural retinoids have been shown to be effective chemopreventive agents at high doses, but unfortunately the cumulative toxic effects of high doses have restricted their prolonged use. Several studies have demonstrated low-dose retinoids in combination with calcium glucarate interact synergistically to inhibit mammary tumor growth in both animal models and human cell lines. (14-18) The mechanisms responsible for the chemopreventive effects of these two agents may be similar. Both retinoids and calcium-D-glucarate inhibit carcinogenesis during the promotion and initiation phases. Calcium-D-glucarate inhibits protein tyrosine kinase-C activity and induces transformation growth factor beta, possibly resulting in an increase in cellular differentiation and slower progression through the cell cycle. (15) Retinoids induce many of these same biochemical effects. (19) Additionally, calcium-D-glucarate enhances glucuronidation and subsequent excretion of carcinogens and other cancer-promoting agents.
Published human studies on calcium-D-glucarate and breast cancer are few but, due to the encouraging results of the animal studies, the National Cancer Institute has initiated a Phase I trial in patients at high risk for breast cancer at Memorial Sloan Kettering Cancer Center. This trial is examining the use of calcium-D-glucarate as an alternative to tamoxifen's blocking of estrogen receptors. Preliminary results are quite encouraging and due to calcium-D-glucarate's excellent safety profile, it may be a more effective option than tamoxifen, which has numerous side effects. (3) Other human trials are being conducted at M.D. Anderson Cancer Center in Houston, Texas and AMC Cancer Research Center in Denver, Colorado.
Colon Cancer
Studies in rats have shown D-glucarate salts to inhibit colon carcinogenesis alone and in combination with 5-fluorouracil (5-FU). In one study, D-glucarate markedly inhibited azoxymethane-induced colon carcinogenesis as evidenced by a 60-percent reduction in both tumor incidence and multiplicity. It was hypothesized that malignant cell proliferation was suppressed by inhibition of beta-glucuronidase. Another possible mechanism may involve alterations in cholesterol synthesis or its conversion to bile acids. (8) The second study demonstrated that salts of D-glucarate, in combination with 5-FU in rat colon tumor explants, resulted in a potentiation of 5-FU's antitumor activity. D-glucarate alone also showed antitumor activity. (9)
Liver Cancer
Hepatocarcinogenesis is thought to be preceded by premalignant hepatic foci that are subsequently transformed to malignant cells. Two separate rat studies by a group of researchers at Ohio State University have demonstrated calcium-D-glucarate delays the appearance of altered hepatic foci and significantly inhibits hepatocarcinogenesis, if given during both the initiation and promotion phases. Maximal inhibition was obtained when calcium-D-glucarate was administered by gavage prior to the carcinogenic agent, diethylnitrosamine. (11,12)
Lung Cancer
A study conducted on mice demonstrated calcium-D-glucarate inhibits benzo[a]pyrene's ability to bind DNA and induce pulmonary adenomas. (10) Another unpublished phase I clinical trial of 62 patients found D-glucaric acid levels were approximately 29-percent lower in smokers than non-smokers. Regardless of gender, K-ras (an oncogene linked to lung cancer) mutations were found to be present in 38 percent of subjects who smoked, while no K-ras mutations were found in the non-smoking control subjects. It was hypothesized that D-glucaric acid deficiency correlates with K-ras mutations and might be indicative of a higher risk for developing lung cancer. (20)
Skin Cancer
The efficacy of dietary calcium-D-glucarate as a chemopreventative agent has also been studied in the mouse skin tumorigenesis system. Mice were given 7,12-dimethylbenz[a]anthracene (DMBA) to induce skin tumorigenesis and were fed either a regular chow diet or a chow diet fortified with calcium-D-glucarate. When fed the calcium-D-glucarate chow through both the initiation and promotion phases, papilloma formation was inhibited by over 30 percent. The data indicate that supplementation of calcium-D-glucarate results in a marked alteration in the retention, activity, and metabolism of carcinogenic substances. (13)
Estrogen Metabolism
Calcium-D-glucarate's inhibition of beta-glucuronidase activity allows the body to excrete hormones such as estrogen before they can become reabsorbed. Oral administration of large doses of calcium-D-glucarate have been shown to lower serum estrogen levels in rats by 23 percent. (21) Because many breast cancers are estrogen-dependent, calcium-D-glucarate's ability to affect estrogen and other hormone levels has led to Phase I clinical trials at several major cancer centers in the United States. Results of these studies are pending.
Lipid Lowering
Side effects of currently available hypolipidemic agents present a need for safe and effective lipid-lowering agents. D-glucarates have been shown to significantly reduce total serum cholesterol in rats by as much as 12-15 percent and LDL-cholesterol by 30-35 percent. Preliminary results in humans show D-glucarate reduced total serum cholesterol up to 12 percent, LDL-cholesterol up to 28 percent, and triglycerides up to 43 percent. The lipid-lowering effect of calcium-D-glucarate may be attributed to improved enterohepatic circulation, resulting in increased excretion of bile acids and a reduction in steady state levels of cholesterol biosynthesis. (7)
Drug/Nutrient Interactions
There are no known drug interactions with calcium-D-glucarate, but many drugs and hormones are metabolized in the liver via glucuronidation. Therefore, taking calcium-D-glucarate may increase elimination of these substances, possibly reducing their effectiveness.
Side Effects and Toxicity
No adverse effects have been observed after prolonged feeding to rats or mice at concentrations of 70, 140, or even 350 mmol/kg. (6) Preliminary results of clinical trials in humans have shown calcium-D-glucarate is without adverse effects.
Dosage
The recommended oral dosage of calcium-D-glucarate is generally in the range of 1500-3000 mg daily. Until human trials have been completed the optimal dosage remains elusive.
References
(1.) Dwivedi C, Heck WJ, Downie AA, et al. Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol 1990;43:83-92.
(2.) Walaszek Z, Szemraj J, Narog M, et al. Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. Cancer Detect Prev 1997;21:178-190.
(3.) Heerdt, AS, Young CW, Borgen PI. Calcium glucarate as a chemopreventive agent in breast cancer, Isr J Med Sci 1995;31:101-105.
(4.) Horton D, Walaszek Z. Conformations of the D-glucarolactones and D-glucaric acid in solution. Carbohydr Res 1982;105:95-109.
(5.) Walaszek Z, Hanausek-Walaszek M. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on biliary excretion of beta-glucuronidase after oral administration in rats. Hepatology 1988;9:552-556.
(6.) Selkirk JK, Cohen GM, MacLeod MC. Glucuronic acid conjugation in the metabolism of chemical carcinogens by rodent cells. Arch Toxicol 1980;139:S171-S178.
(7.) Walaszek Z, Hanausek-Walaszek M, Adams AK, Sherman U. Cholesterol lowering effects of dietary D-glucarate. FASEB 1991;5:A930.
(8.) Yoshimi N, Walaszek Z, Moil H, et al. Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate. Int J Oncol 2000;16:43-48.
(9.) Schmittgen TD, Koolemans-Beynen A, Webb TE, et al. Effects of 5-fluorouracil, leucovorin, and glucarate in rat colon-tumor explants. Cancer Chemother Pharmacol 1992;30:25-30.
(10.) Walaszek Z, Hanausek-Walaszek M, Webb TE. Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis. Cancer Lett 1986;33:25-32.
(11.) Oredipe OA, Barth RF, Hanausek-Walaszek M, et al. Effects of an inhibitor of beta-glucuronidase on hepatocarcinogenesis. Proc Am Assoc Cancer Res 1987;28:156.
(12.) Oredipe OA, Barth RF, Hanausek-Walaszek M, et al Effects of calcium glucarate on the promotion of diethylnitrosamine-initiated altered hepatic loci in rats. Cancer Lett 1987;38:95-99.
(13.) Dwivedi C, Downie AA, Webb TE. Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate. J Environ Path Toxicol Oncol 1989;9:253-259.
(14.) Abou-Issa H, Koolemans-Beynen A, Meredith TA, Webb TE. Antitumour synergism between non-toxic dietary combinations of isotretinoin and glucarate. Eur J Cancer 1992;28:784-788.
(15.) Webb TE, Abou-Issa H, Stromberg PC, et al. Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate:retinoid combination. Anticancer Res 1993; 13:2095-2100.
(16.) Bhatnagar R, Abou-Issa H, Curley RW, et al. Growth suppression of human breast carcinoma cells in culture by N-(4-hydroxyphenyl) retinamide and its glucuronide and through synergism with glucarate. Biochem Pharmacol 1991 ;41:1471-1477.
(17.) Curley RW, Humpries KA, Koolemans -Beynan A, et al. Activity of d-glucarate analogues: synergistic antiproliferative effect in cultured human mammary tumor cells appear to specifically require the d-glucarate structure. Life Sci 1994;54:1299-1303.
(18.) Abou-Issa H, Moeschberger M, Masry EI, et al. Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis. Cancer Res 1995;15:805-810.
(19.) DeLuca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 1991;5:2924-2933.
(20.) Walaszek Z, Raich PC, Hanausek M, et al. Role of D-glucaric acid in lung cancer prevention. Unpublished research. AMC Cancer Research Center, Denver, CO.
(21.) Walaszek Z, Hanausek-Walaszek M, Minto JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis 1986;7:1463-1466.
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From: § Lori §
Date: Jan 12, 2008 4:00 PM
From: Vaccine Truth
Date: Jan 12, 2008 2:43 PM
Disclaimer: For educational purposes only This information has not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease
Calcium D-Glucarate —A Cancer Preventer?
If you follow the news, you are no doubt aware of the tremendous harm chemicals are doing to the environment and, more importantly, the negative impact of those chemicals on your health. One major concern is the effect of environmental chemicals on hormone sensitive tissue. Mounting evidence is linking excessive levels of hormones and carcinogenic chemicals to breast, prostate, uterine, and probably ovarian cancers.
Your risk of cancer and other serious illnesses increase in relationship to the accumulation of toxic chemicals and toxic levels of steroid hormones.
Under ideal circumstances the body has a biochemical plan in place to help it to inactivate and eliminate hormones, drugs and other undesirable chemicals. One such plan or pathway is glu¬curonidation. Glucuronidation is basically a chemi¬ cal reaction performed by your liver during which a water-soluble substance is combined with a toxin, allowing the toxin to be more easily excret¬ed from the body.
Normally the glucuronidation pathway of elimination works pretty well, unless the body is grossly overloaded with toxins, or unless some other chemical or even parasite or bacteria gets in the way. When this occurs, the body's intricate system of detoxification and elimination is threat¬ened. Consumption of caffeine and processed meats, smoking tobacco, marijuana, even exposure to car-exhaust or pesticides all cause a loss of glucarate which impedes glucuronidation.
However, the good news is that glucuronidation, can be enhanced. Turns out that providing an ample supply of a dietary supplement similar to glucuronic acid called calcium D-glucarate binds the enzyme so that it's unable to free the hormones/toxins being eliminated by the liver.
Calcium D-glucarate is a safe supplement that has no known negative interactions or toxicity, it inhibits the undesirable bacterial enzyme, beta glucuronidase and thus aids our elimination of toxins. Calcium D-glucarate naturally occurs in fruits and vegetables. This may explain the protective effects of vegetables that reduce the risk of cancer. Many of them are abundant sources of D glucarate. They include the cruciferous vegetables cabbage, broccoli, and brussels sprouts.
Other foods that contain it are grapefruit, apples, bean sprouts, and lettuce.
Calcium D-glucarate is relatively inexpensive and is recommended by nutritionists for persons at risk of such cancers. The suggested dose ranges from 200-400 mg per day. If you have had a relatively low exposure to toxins in your life, a low dose may be fine. If you smoke or have lived in a very polluted area you might choose a higher dose, say 500 mg three times a day. I enthusiastically recommend it to my patients, especially female patients who I feel are at elevated risk of breast cancer, men at risk of prostate cancer, or both sexes at risk of colon cancer. The mucosal cells that line the colon may be a hotbed for cancer simply because they are at the end of the line for expo¬sure to a wide variety of poisons being eliminated through the gut. Preventing the uncoupling of a toxin from the eliminating compound also helps protect colon cells from the increased exposure.
Calcium D-glucarate supplements do not take the place of changing your lifestyle to a healthy one But they do offer good support of important detoxification pathways, especially if you've ever been a smoker, a lover of lunchmeats or hot dogs, or of coffee and sodas.
If you are still a smoker, Calcium D-glucarate is a very appropriate supplement for you. It is not a cure for a body loaded with toxins, but it could give your body the support it needs to remain healthier longer.
Calcium D-Glucarate is available at health food stores or online. Here’s to your health and screw the FDA and Drug companies. ~Namaste~
http://www.iherb.com/Search.aspx?c=1&kw=calcium+d+glucarate
The Toxic Avenger: Calcium D-glucarate — a new detoxifying supplement — can help enhance your metabolism, recovery and growth - The Wright Stuff
Jim Wright
Q: I really enjoy you column and have made excellent progress. Although I'm satisfied with my training program and my overall diet, I'm still not getting that final polish on my physique. Is there anything else --perhaps a supplement -- I can use to harden my physique?
A: Maximizing your potential for leanness, hardness and fullness might not be rocket science, but it does take more than popping a few thermogenics, going on a low-carb diet and doing cardio three or four hours a week. It also requires a whole lot more information than I have room to impart here (look for a superfeature on fat loss in our April 2002 issue).
There definitely is, however, one supplement I'd highly recommend to every bodybuilder who wants to support his or her overall health. In addition to lowering cancer risks, this supplement helps to eliminate excess estrogen, among other metabolites, waste products and toxins, that could contribute to fluid retention, gynecomastia (in males) and other undesirable physique effects.
Calcium D-glucarate (C-D-G) is a nontoxic patented form of glucaric acid that is easily absorbed, active in small (and inexpensive) doses and bioavailable in the body for relatively extended periods. Glucaric acid is present in different fruits and vegetables and is made in very small amounts by our own bodies. However, as science has discovered with regard to most beneficial phytochemicals, even if you ate as much of the appropriate foods you could, it would still be difficult if not impossible to consistently get the amount of C-D-G more conveniently available in the supplement. (See the sidebar, "A Quick Guide to C-D-G," for further information.)
Researchers at M.D. Anderson Cancer Center in Houston, Texas, developed the supplemental form of C-D-G. The scientists there were studying why and how a diet high in fruits and veggies reduced the incidence of certain cancers and other degenerative diseases. After many animal and human studies showed that C-D-G could significantly decrease lung, skin, liver, breast, colon and prostate cancers, most by half or more, the agent was developed into a dietary supplement. Even if you're not worried about cancer, C-D-G definitely has something to offer with regard to your physique.
DETOX AND IMMUNITY You don't have to be a genius to realize that optimizing metabolism and growth requires a "clean" internal/chemical environment. That can't be stressed enough. The liver is the key organ for detoxification, as well as for literally hundreds of other reactions that directly impact anabolism and catabolism in muscle and connective tissue. The immune system drives the train of tissue repair.
Detoxifying the body, and thus reducing the associated load on the liver and immune system, allows more of those systems' capacities and more of the body's energy to be directed toward repair of exercise-induced tissue damage, more effective nutrient processing and muscle growth. It should be obvious that a clean internal environment would make a difference in how your body responds to training, especially over the long term.
How do you detox the body and get clean? As we've said repeatedly in past issues, you do that by:
* eating "clean";
* drinking plenty of water;
* ensuring a high fiber intake;
* taking antioxidants (e.g., a complete multivitamin-multimineral supplement);
* and limiting intake of or exposure to toxic substances, such as tobacco, alcohol, environmental pollutants and pharmaceutical drugs (except those prescribed by a physician).
But how many bodybuilders adhere to those rules most of the time? And how many manage to eat the eight to 10 servings of fruits and vegetables daily that are needed to support physique and performance goals? Forget the government-recommended five servings a day; just as with the old recommended daily allowances, they don't cut it for bodybuilders and other serious athletes. That's especially true now that we know that, among their other benefits, fruits and vegetables are so important for overall health and for bodybuilding because of their glucaric acid content.
HOW TO GET DRIER AND HARDER
Supplementing with C-D-G is important to bodybuilders -- male or female -- because it significantly boosts the body's capacity to eliminate toxins and waste products and improves androgen/estrogen balance.
As demonstrated in many studies, supplemental C-D-G has amazing effects on estrogen levels in women, dramatically lowering estrogen-related health problems and diseases. In my own informal studies, I've seen C-D-G improve the physiques of a number of women bodybuilders and fitness athletes, and I'm confident that it can help anyone make progress over time.
Given the chemical similarity between testosterone and estrogen, you might wonder if C-D-G could also reduce testosterone levels or adversely affect muscle building. To answer that, since it's not apparent from the published literature, I queried Thomas Slaga, PHD, director of AMC Cancer Research Center in Denver, Colorado, and an expert on C-D-G. He responded unequivocally that it "would have no effects on free testosterone or on testosterone binding to its receptors in muscle."
As Slaga further explained, "C-D-G is about eliminating excess levels of steroids and sterols and balancing the androgen:estrogen ratio. It's about keeping the 'system' between the lines, so to speak, hormonally, metabolically, etc., thus optimizing the body's potential for moving forward on the path of recuperation and muscle growth."
Dr. Wright welcomes questions about supplements, food and nutrition
What is it? Calcium D-glucarate (C-D-G) is a dietary supplement that helps eliminate toxins and wastes from the body.
Is it found in food? Yes, it's in fruits and vegetables - the highest amounts are in apples, cherries, apricots and grapefruits, as well as other citrus fruits. Significant amounts are also found in broccoli, Brussels sprouts and alfalfa sprouts. However, supplementation is the best way to make sure you get enough.
What supplement forms are available and where can it be purchased? Look for C-D-G in tables and capsules. It is alos now added to some protein/meal-replacement powders. The supplement should be available in quality health-food outlets and in major supermarket and drugstore chains.
What's the best dose? Most of the beneficial results found in studies of C-D-G were achieved at doses of 200-400 milligrams per day. I'd suggest you opt for the higher amount, and don't hesitate to try more if you want, because C-D-G is a natural substance and essentially nontoxic. Take it anytime during the day, with or without food.
Calcium-D-glucarate - Monograph
Introduction
Calcium-D-glucarate is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans. Glucaric acid is also found in many fruits and vegetables with the highest concentrations to be found in oranges, apples, grapefruit, and cruciferous vegetables. (1) Oral supplementation of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microflora and involved in Phase II liver detoxification. Elevated beta-glucuronidase activity is associated wire an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers. (2) Other potential clinical applications of oral calcium-D-glucarate include regulation of estrogen metabolism and as a lipid-lowering agent.
Pharmacokinetics
Upon ingestion and exposure to the acidic environment of the stomach, calcium-D-glucarate is metabolized to form D-glucaric acid. D-glucaric acid is further metabolized in the gastrointestinal tract into three compounds existing in equilibrium and comprised of approximately 40-percent D-glucaric acid, 30-percent D-glucaro-1,4-lactone, and 30-percent D-glucaro-6,3-lactone. These compounds are then transported to the blood and various internal organs, and are subsequently excreted in the urine and bile. Although D-glucaro-1,4-lactone seems to be the most pharmacologically active of the three, it is not commercially available. Also, calcium-D-glucarate administration results in longer inhibition of beta-glucuronidase (five hours versus one hour) than does D-glucaro-1,4-lactone, so it is the compound used. (3)
Mechanism of Action
Calcium-D-glucarate's detoxifying and anticarcinogenic properties are attributed to its ability to increase glucuronidation and excretion of potentially toxic compounds. During Phase II detoxification, chemical carcinogens, steroid hormones, and other lipid-soluble toxins are conjugated with glucuronic acid in the liver (glucuronidation), and excreted through the biliary tract. Beta-glucuronidase is capable of deconjugating these potential toxins, making it possible for them to be reabsorbed rather than excreted. D-glucaro-1,4-lactone is the metabolite that has been shown to inhibit beta-glucuronidase activity, increasing excretion of conjugated xenobiotic compounds and decreasing activity of harmful substances that are most active in their deconjugated state. (4,5) Inhibition of beta-glucuronidase ultimately results in potentially decreasing the risk of carcinogenesis. (6) In addition, by reducing the beta-glucuronidase viability and activity of intestinal bacteria, salts of D-glucaric acid have been shown to enhance enterohepatic circulation and reduce steady state levels of cholesterol synthesis, resulting in decreased serum lipid levels. (7)
Deficiency States
Calcium-D-glucarate is not an essential nutrient so, technically, no deficiency state exists. However, since it is only produced in small amounts by humans, it is important that dietary intake be adequate. Diets low in fruits (particularly oranges, apples, and grapefruit) and cruciferous vegetables (broccoli, cabbage, and brussel sprouts) may result in a relative deficiency of calcium-D-glucarate and its metabolites. Research has shown a low level of D-glucaric acid correlates with a higher level of beta-glucuronidase, which in turn is associated with an increased risk for various cancers. (2)
Clinical Indications
Cancer
The anticarcinogenic properties of D-glucaric acid and its salts have been studied in various animal tumor models, including colon, (8,9) prostate, (2) lung, (10) liver, (11,12) skin, (13) and breast (14-18) cancer, with the mechanism of action for tumor inhibition being very similar in each. These studies demonstrated decreases in beta-glucuronidase activity, carcinogen levels, and tumorigenesis. The preponderance of research, however, has been conducted on mammary tumors in the rat, the animal model most frequently used for breast cancer research.
Breast Cancer
A number of studies have shown calcium-D-glucarate alone, and in combination with retinoids, inhibits mammary carcinogenesis in rats by as much as 70 percent. (3) Natural retinoids have been shown to be effective chemopreventive agents at high doses, but unfortunately the cumulative toxic effects of high doses have restricted their prolonged use. Several studies have demonstrated low-dose retinoids in combination with calcium glucarate interact synergistically to inhibit mammary tumor growth in both animal models and human cell lines. (14-18) The mechanisms responsible for the chemopreventive effects of these two agents may be similar. Both retinoids and calcium-D-glucarate inhibit carcinogenesis during the promotion and initiation phases. Calcium-D-glucarate inhibits protein tyrosine kinase-C activity and induces transformation growth factor beta, possibly resulting in an increase in cellular differentiation and slower progression through the cell cycle. (15) Retinoids induce many of these same biochemical effects. (19) Additionally, calcium-D-glucarate enhances glucuronidation and subsequent excretion of carcinogens and other cancer-promoting agents.
Published human studies on calcium-D-glucarate and breast cancer are few but, due to the encouraging results of the animal studies, the National Cancer Institute has initiated a Phase I trial in patients at high risk for breast cancer at Memorial Sloan Kettering Cancer Center. This trial is examining the use of calcium-D-glucarate as an alternative to tamoxifen's blocking of estrogen receptors. Preliminary results are quite encouraging and due to calcium-D-glucarate's excellent safety profile, it may be a more effective option than tamoxifen, which has numerous side effects. (3) Other human trials are being conducted at M.D. Anderson Cancer Center in Houston, Texas and AMC Cancer Research Center in Denver, Colorado.
Colon Cancer
Studies in rats have shown D-glucarate salts to inhibit colon carcinogenesis alone and in combination with 5-fluorouracil (5-FU). In one study, D-glucarate markedly inhibited azoxymethane-induced colon carcinogenesis as evidenced by a 60-percent reduction in both tumor incidence and multiplicity. It was hypothesized that malignant cell proliferation was suppressed by inhibition of beta-glucuronidase. Another possible mechanism may involve alterations in cholesterol synthesis or its conversion to bile acids. (8) The second study demonstrated that salts of D-glucarate, in combination with 5-FU in rat colon tumor explants, resulted in a potentiation of 5-FU's antitumor activity. D-glucarate alone also showed antitumor activity. (9)
Liver Cancer
Hepatocarcinogenesis is thought to be preceded by premalignant hepatic foci that are subsequently transformed to malignant cells. Two separate rat studies by a group of researchers at Ohio State University have demonstrated calcium-D-glucarate delays the appearance of altered hepatic foci and significantly inhibits hepatocarcinogenesis, if given during both the initiation and promotion phases. Maximal inhibition was obtained when calcium-D-glucarate was administered by gavage prior to the carcinogenic agent, diethylnitrosamine. (11,12)
Lung Cancer
A study conducted on mice demonstrated calcium-D-glucarate inhibits benzo[a]pyrene's ability to bind DNA and induce pulmonary adenomas. (10) Another unpublished phase I clinical trial of 62 patients found D-glucaric acid levels were approximately 29-percent lower in smokers than non-smokers. Regardless of gender, K-ras (an oncogene linked to lung cancer) mutations were found to be present in 38 percent of subjects who smoked, while no K-ras mutations were found in the non-smoking control subjects. It was hypothesized that D-glucaric acid deficiency correlates with K-ras mutations and might be indicative of a higher risk for developing lung cancer. (20)
Skin Cancer
The efficacy of dietary calcium-D-glucarate as a chemopreventative agent has also been studied in the mouse skin tumorigenesis system. Mice were given 7,12-dimethylbenz[a]anthracene (DMBA) to induce skin tumorigenesis and were fed either a regular chow diet or a chow diet fortified with calcium-D-glucarate. When fed the calcium-D-glucarate chow through both the initiation and promotion phases, papilloma formation was inhibited by over 30 percent. The data indicate that supplementation of calcium-D-glucarate results in a marked alteration in the retention, activity, and metabolism of carcinogenic substances. (13)
Estrogen Metabolism
Calcium-D-glucarate's inhibition of beta-glucuronidase activity allows the body to excrete hormones such as estrogen before they can become reabsorbed. Oral administration of large doses of calcium-D-glucarate have been shown to lower serum estrogen levels in rats by 23 percent. (21) Because many breast cancers are estrogen-dependent, calcium-D-glucarate's ability to affect estrogen and other hormone levels has led to Phase I clinical trials at several major cancer centers in the United States. Results of these studies are pending.
Lipid Lowering
Side effects of currently available hypolipidemic agents present a need for safe and effective lipid-lowering agents. D-glucarates have been shown to significantly reduce total serum cholesterol in rats by as much as 12-15 percent and LDL-cholesterol by 30-35 percent. Preliminary results in humans show D-glucarate reduced total serum cholesterol up to 12 percent, LDL-cholesterol up to 28 percent, and triglycerides up to 43 percent. The lipid-lowering effect of calcium-D-glucarate may be attributed to improved enterohepatic circulation, resulting in increased excretion of bile acids and a reduction in steady state levels of cholesterol biosynthesis. (7)
Drug/Nutrient Interactions
There are no known drug interactions with calcium-D-glucarate, but many drugs and hormones are metabolized in the liver via glucuronidation. Therefore, taking calcium-D-glucarate may increase elimination of these substances, possibly reducing their effectiveness.
Side Effects and Toxicity
No adverse effects have been observed after prolonged feeding to rats or mice at concentrations of 70, 140, or even 350 mmol/kg. (6) Preliminary results of clinical trials in humans have shown calcium-D-glucarate is without adverse effects.
Dosage
The recommended oral dosage of calcium-D-glucarate is generally in the range of 1500-3000 mg daily. Until human trials have been completed the optimal dosage remains elusive.
References
(1.) Dwivedi C, Heck WJ, Downie AA, et al. Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol 1990;43:83-92.
(2.) Walaszek Z, Szemraj J, Narog M, et al. Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. Cancer Detect Prev 1997;21:178-190.
(3.) Heerdt, AS, Young CW, Borgen PI. Calcium glucarate as a chemopreventive agent in breast cancer, Isr J Med Sci 1995;31:101-105.
(4.) Horton D, Walaszek Z. Conformations of the D-glucarolactones and D-glucaric acid in solution. Carbohydr Res 1982;105:95-109.
(5.) Walaszek Z, Hanausek-Walaszek M. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on biliary excretion of beta-glucuronidase after oral administration in rats. Hepatology 1988;9:552-556.
(6.) Selkirk JK, Cohen GM, MacLeod MC. Glucuronic acid conjugation in the metabolism of chemical carcinogens by rodent cells. Arch Toxicol 1980;139:S171-S178.
(7.) Walaszek Z, Hanausek-Walaszek M, Adams AK, Sherman U. Cholesterol lowering effects of dietary D-glucarate. FASEB 1991;5:A930.
(8.) Yoshimi N, Walaszek Z, Moil H, et al. Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate. Int J Oncol 2000;16:43-48.
(9.) Schmittgen TD, Koolemans-Beynen A, Webb TE, et al. Effects of 5-fluorouracil, leucovorin, and glucarate in rat colon-tumor explants. Cancer Chemother Pharmacol 1992;30:25-30.
(10.) Walaszek Z, Hanausek-Walaszek M, Webb TE. Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis. Cancer Lett 1986;33:25-32.
(11.) Oredipe OA, Barth RF, Hanausek-Walaszek M, et al. Effects of an inhibitor of beta-glucuronidase on hepatocarcinogenesis. Proc Am Assoc Cancer Res 1987;28:156.
(12.) Oredipe OA, Barth RF, Hanausek-Walaszek M, et al Effects of calcium glucarate on the promotion of diethylnitrosamine-initiated altered hepatic loci in rats. Cancer Lett 1987;38:95-99.
(13.) Dwivedi C, Downie AA, Webb TE. Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate. J Environ Path Toxicol Oncol 1989;9:253-259.
(14.) Abou-Issa H, Koolemans-Beynen A, Meredith TA, Webb TE. Antitumour synergism between non-toxic dietary combinations of isotretinoin and glucarate. Eur J Cancer 1992;28:784-788.
(15.) Webb TE, Abou-Issa H, Stromberg PC, et al. Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate:retinoid combination. Anticancer Res 1993; 13:2095-2100.
(16.) Bhatnagar R, Abou-Issa H, Curley RW, et al. Growth suppression of human breast carcinoma cells in culture by N-(4-hydroxyphenyl) retinamide and its glucuronide and through synergism with glucarate. Biochem Pharmacol 1991 ;41:1471-1477.
(17.) Curley RW, Humpries KA, Koolemans -Beynan A, et al. Activity of d-glucarate analogues: synergistic antiproliferative effect in cultured human mammary tumor cells appear to specifically require the d-glucarate structure. Life Sci 1994;54:1299-1303.
(18.) Abou-Issa H, Moeschberger M, Masry EI, et al. Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis. Cancer Res 1995;15:805-810.
(19.) DeLuca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 1991;5:2924-2933.
(20.) Walaszek Z, Raich PC, Hanausek M, et al. Role of D-glucaric acid in lung cancer prevention. Unpublished research. AMC Cancer Research Center, Denver, CO.
(21.) Walaszek Z, Hanausek-Walaszek M, Minto JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis 1986;7:1463-1466.
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Labels: Cacium D-Glucarate Cancer Preventer and Detoxifier, cancer cure
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