{"id":779158290536,"title":"Metagenics Calcium D-Glucarate 204g","handle":"metagenics-calcium-d-glucarate-204-g","description":"\u003ch3\u003e\u003cem\u003eAssist Glucuronidation For Oestrogen and Xeno-Oestrogen Detoxification\u003c\/em\u003e\u003c\/h3\u003e\n\u003ch2\u003e\u003cstrong\u003eMetagenics Calcium D-Glucarate 204g\u003c\/strong\u003e\u003c\/h2\u003e\n\u003cp\u003eMetagenics Calcium D-Glucarate Size: 240g\u003c\/p\u003e\n\u003cp\u003eMetagenics Calcium D-Glucarate:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eGlucuronidation is a key phase II process that assists in the detoxification of oestrogen and xeno-oestrogen compounds from the environment.\u003c\/li\u003e\n\u003cli\u003eMetagenics Calcium D-glucarate is a natural glucose metabolite which is an effective inhibitor of β-glucuronidase – an enzyme which deconjugates bound toxins and other metabolic waste products.\u003c\/li\u003e\n\u003cli\u003eBy preventing deconjugation of products of glucuronidation, calcium D-glucarate promotes a net increase in phase II detoxification and is indicated in toxicity-associated conditions, especially those involving excessive oestrogen activity.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- TABS --\u003e\n\u003ch5\u003eDirections\u003c\/h5\u003e\n\u003ch2\u003eDirections: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eOestrogen\/xeno-oestrogen detoxification: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003eCancer: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003eGallstones: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003eDyslipidaemia: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003e1 metric tsp (1.7g) is equal to 1.5g (1500mg) of Calcium D-Glucarate (\u003cspan\u003eCalcium saccharate\u003c\/span\u003e) Stir well and take immediately.\u003c\/p\u003e\n\u003ch5\u003eBenefits\u003c\/h5\u003e\n\u003ch2\u003eBenefits: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Benefits: Metagenics Calcium D-Glucarate\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eCalcium D-glucarate is a natural glucose metabolite which is an effective inhibitor of β-glucuronidase – an enzyme which deconjugates bound toxins and other metabolic waste products. Glucuronidation is a key phase II process that assists in the detoxification of oestrogen and xeno-oestrogen compounds from the environment.\u003c\/li\u003e\n\u003cli\u003eBy preventing deconjugation of products of glucuronidation, calcium D-glucarate promotes a net increase in phase II detoxification and is indicated in toxicity-associated conditions, especially those involving excessive oestrogen activity.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch5\u003eIngredients\u003c\/h5\u003e\n\u003ch2\u003eIngredients: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eCalcium D-Glucarate\u003c\/p\u003e\n\u003ch5\u003eWarnings\u003c\/h5\u003e\n\u003ch2\u003eWarnings: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eNot all cautions and contraindications are listed. For full details, references or more information contact HealthMasters in Australia by email: reception@healthmasters.com.au\u003c\/p\u003e\n\u003ch5\u003eStorage\u003c\/h5\u003e\n\u003ch2\u003eStorage: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eStore below 30° C\u003c\/p\u003e\n\u003ch5\u003eTechnical Information\u003c\/h5\u003e\n\u003ch2\u003eTechnical Information: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003ch2 style=\"text-align: left;\"\u003e\u003cbig\u003e\u003cbig\u003eCalcium D-Glucarate\u003c\/big\u003e\u003c\/big\u003e\u003c\/h2\u003e\n\u003cp\u003eCalcium D-glucarate is a natural glucose metabolite which is an effective inhibitor of β-glucuronidase – an enzyme which deconjugates bound toxins and other metabolic waste products. Glucuronidation is a key phase II process that assists in the detoxification of oestrogen and xeno-oestrogen compounds from the environment. By preventing deconjugation of products of glucuronidation, calcium D-glucarate promotes a net increase in phase II detoxification and is indicated in toxicity-associated conditions, especially those involving excessive oestrogen activity.\u003c\/p\u003e\n\u003ch2\u003eHERBS AND NUTRIENTS THAT MAY ASSIST\u003c\/h2\u003e\n\u003cp\u003eCalcium D-glucarate\u003c\/p\u003e\n\u003ch2\u003eCLINICAL APPLICATIONS\u003c\/h2\u003e\n\u003ch3\u003eKEY ACTIONS:\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003eInhibits β-glucuronidase and increases net phase II glucuronidation\u003c\/li\u003e\n\u003cli\u003eDecreases oestrogen\u003c\/li\u003e\n\u003cli\u003eAnticarcinogenic\u003c\/li\u003e\n\u003cli\u003eImproves lipid and bile metabolism\u003c\/li\u003e\n\u003cli\u003eAnti-inflammatory\u003c\/li\u003e\n\u003cli\u003eAntioxidant\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch3\u003eKEY APPLICATIONS:\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003eOestrogen\/xeno-oestrogen dependent conditions\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cdiv style=\"padding-left: 60px;\"\u003eo Endometriosis\u003c\/div\u003e\n\u003cdiv style=\"padding-left: 60px;\"\u003eo Fibroids\u003c\/div\u003e\n\u003cdiv style=\"padding-left: 60px;\"\u003eo Breast cancer\u003c\/div\u003e\n\u003cul\u003e\n\u003cli\u003eCancer, especially breast and prostate\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eMay also be considered for:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eGallstones\u003c\/li\u003e\n\u003cli\u003eDyslipidaemia\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch2\u003eDOSES\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eOestrogen\/xeno-oestrogen detoxification: 1500-3000 mg daily (1-2 tsp)\u003c\/li\u003e\n\u003cli\u003eCancer: 1500-3000 mg daily (1-2 tsp)\u003c\/li\u003e\n\u003cli\u003eGallstones: 1500-3000 mg daily (1-2 tsp)\u003c\/li\u003e\n\u003cli\u003eDyslipidaemia: 1500-3000 mg daily\u003cspan\u003e (1-2 tsp)\u003c\/span\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch2\u003eBACKGROUND TECHNICAL INFORMATION\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eGlucuronidation\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eGlucuronidation is an important phase II detoxification process which attaches glucuronic acid to a toxin for excretion. Glucuronic acid serves as conjugation compound for the detoxification of a wide variety of endogenous and exogenous substrates, including sex hormones and toxins.1,2 In glucuronidation, the enzyme uridine 5'-diphospho-(UDP)-glucuronosyltransferase (UDG) attaches the water-soluble glucuronic acid to the more fat-soluble substrate, creating a conjugate compound which is now water-soluble for elimination.\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eβ-glucuronidase\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eThe enzyme β-glucuronidase reverses the process of glucuronidation; deconjugating the glucuronic acid from the toxin and ‘re-activating’ it, as it is no longer bound. The amount of a toxin that is eliminated is believed to be largely determined by the balance of conjugation versus deconjugation (Figure 1).\u003c\/p\u003e\n\u003cp\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_1_Glucuronidation_and_deglucuronidation_of_toxins_-_HealthMasters_600x600.jpg?v=1586479530\" alt=\"Calcium D-Glucarate Figure 1 Glucuronidation and deglucuronidation of toxins - HealthMasters\" width=\"600x600\" height=\"600x600\" style=\"display: block; margin-left: auto; margin-right: auto;\"\u003e\u003c\/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 1. Glucuronidation and deglucuronidation of toxins.\u003c\/span\u003e\u003c\/strong\u003e\u003c\/p\u003e\n\u003cblockquote\u003e\n\u003cdiv style=\"text-align: left;\"\u003e\u003cstrong\u003e\u003cem\u003eThe net amount of toxin detoxified is determined by the balance between conjugation via uridine 5'-diphospho—glucuronosyltransferase (UDG) and deconjugation from β-glucuronidase (BG).\u003c\/em\u003e\u003c\/strong\u003e\u003c\/div\u003e\n\u003c\/blockquote\u003e\n\u003cp\u003eHumans synthesise β-glucuronidase and it has been detected in many tissues including liver, kidney, spleen, testes, lung, gastrointestinal tract, and in cancerous and inflamed tissue. Additionally, a dysbiotic gastrointestinal microbiome produces high levels of β-glucuronidase, which can act identically to human β-glucuronidase, by deconjugating glucuronidated substances.4\u003c\/p\u003e\n\u003cp\u003eEssentially, almost any tissue and body compartment can deconjugate glucuronidated compounds and restore their bioactivity via β-glucuronidase. \u003cbr\u003eβ-glucuronidase is believed to have a constitutive role in degrading glycosaminoglycans for tissue remodelling. However, as is the case with many inflammation-induced mediators, down-regulating excessive levels is a useful short or long term strategy in the control of disease, with little risk of compromising normal physiology. Elevated levels of β-glucuronidase have been found in various pathologies and inflammatory disorders, with elevated levels linked to cancer risk.5,6,7 β-glucuronidase levels are naturally suppressed by compounds found in a healthy diet (described below); indicating that control of β-glucuronidase activity can be considered an normal and safe strategy to restore homeostasis in situations of dysbiosis and inflammation.\u003c\/p\u003e\n\u003ch2\u003eINGREDIENTS\u003c\/h2\u003e\n\u003cp\u003eCalcium D-glucarate is glucose-like compound, which upon ingestion is metabolised in the stomach to form D-glucaric acid. D-glucaric acid can be obtained from the diet from plant foods, most notably in grapefruits, apples, oranges and cruciferous vegetables. A diet high in fruits and vegetables is estimated to provide around 200 mg\/day of D-glucaric acid.8 Additionally, humans can synthesis small amounts of D-glucaric acid in the liver from glucose.9\u003c\/p\u003e\n\u003cp\u003eCalcium D-glucarate, and the resulting D-glucaric acid, are further metabolised to create D-glucaro-1,4-lactone (1,4-GL), which has been shown to be the active form of supplemental calcium D-glucarate (Figure 2).10\u003c\/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_2_The_metabolism_of_calcium_D-glucarate_-_HealthMasters_600x600.jpg?v=1586479725\" alt=\"Calcium D-Glucarate Figure 2 The metabolism of calcium D-glucarate - HealthMasters\" width=\"600x600\" height=\"600x600\" style=\"display: block; margin-left: auto; margin-right: auto;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 2. The metabolism of calcium D-glucarate to the bioactive compound D-glucaro-1,4-lactone.\u003c\/span\u003e \u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003e1,4-GL acts to attenuate the deconjugation of products of glucuronidation by inhibiting β-glucuronidase and thus allow the toxin to be eliminated successfully.11\u003c\/p\u003e\n\u003ch2\u003eACTIONS\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eINHIBITS β-GLUCURONIDASE AND INCREASES NET PHASE II GLUCURONIDATION \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eThe key mechanism of action of calcium D-glucarate is inhibition of β-glucuronidase. Calcium D-glucarate therefore has the potential to mitigate deconjugation of glucuronidated compounds, such as oestrogen, and promote safe excretion of the conjugated substance.12,13,14,15\u003c\/p\u003e\n\u003cp\u003eThe ability of calcium D-glucarate to inhibit β-glucuronidase was first demonstrated over sixty years ago and numerous studies since have confirmed its ability. For example, feeding rodents a single dose of calcium D-glucarate results in significant inhibition in β-glucuronidase in several sites, including serum, liver, lung and intestine (Figure 3).16 The activity of β-glucuronidase has been found to be elevated in many disease states, including numerous types of cancers, diabetes, heart disease, rheumatoid arthritis, liver pathology, cholelithiasis, inflammation, jaundice, tuberculosis, and sarcoidosis.17,18\u003c\/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_3_The_effect_of_calcium_D-glucarate_-_HealthMasters_600x600.jpg?v=1586480013\" alt=\"Calcium D-Glucarate Figure 3 The effect of calcium D-glucarate - HealthMasters\" width=\"600x600\" height=\"600x600\"\u003e\u003cbr\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 3. The effect of calcium D-glucarate (CDC) on β-glucuronidase activity in several tissues.\u003c\/span\u003e\u003c\/strong\u003e19\u003cbr\u003e\u003cstrong\u003e* p\u0026lt;0.05 compared to control\u003c\/strong\u003e\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eDECREASES OESTROGEN \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp style=\"text-align: left;\"\u003eInhibition of β-glucuronidase with calcium D-glucarate can allow more substrate to remain conjugated, with a net change of increasing phase II detoxification.20 For example, rats showed a 23% reduction in serum oestradiol and a 55% reduction in oestrone levels when fed calcium D-glucarate (Figure 4).21\u003c\/p\u003e\n\u003cdiv style=\"text-align: left;\"\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_4_Percentage_reduction_in_serum_oestradiol_-_HealthMasters_480x480.jpg?v=1586480091\" alt=\"Calcium D-Glucarate Figure 4 Percentage reduction in serum oestradiol - HealthMasters\" width=\"480x480\" height=\"480x480\" style=\"margin-right: auto; float: none; display: block; margin-left: auto;\"\u003e\u003c\/div\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 4. Percentage reduction in serum oestradiol and urinary oestrone in rats feed calcium D-glucurate.\u003c\/span\u003e\u003c\/strong\u003e 22\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eANTICARCINOGENIC \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eInhibiting β-glucuronidase is considered to be a key mechanism in calcium D-glucaric acid’s anticarcinogenic effect. It is suggested that calcium D-glucarate’s action is largely due to its ability to detoxify hormones and exogenous toxins that are linked to carcinogenesis. Environmental carcinogens and endogenous oestrogens can cause DNA mutations and promote tumourigenesis; therefore promoting of glucuronidation of these toxins can reduce the carcinogenic load.23 Additionally, tumours contain high levels of β-glucuronidase which is linked to inflammation and subsequent metastasis, with researchers suggesting inhibition of β-glucuronidation may attenuate inflammation and metastasis.24,25\u003c\/p\u003e\n\u003cp\u003eOutside of inhibiting β-glucuronidase, calcium D-glucarate has several other anti-carcinogenic actions. It inhibits protein kinase-C activity and induces transforming growth factor β, which can result in an increase in cellular differentiation and regulate progression through the cell cycle. Calcium D-glucarate has also been found to synergistically interact with retinoids and powerfully inhibit carcinogenesis in animal models.26\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eIMPROVES LIPID AND BILE METABOLISM \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eEvidence shows that calcium D-glucarate administration reduces serum cholesterol levels, with research suggesting that it may be modulating steroidogenesis.27 Additional research suggests that calcium D-glucarate is useful for promoting healthy bile flow. β-glucuronidase in the biliary tract can deconguate bile salts, such as bilirubin, which can allow gallstones to precipitate.28 Mice receiving 1,4 GL showed a decrease in the biliary β- glucuronidase activity, indicating a reduction of bile deconjugation.29\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eANTI-INFLAMMATORY \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eRecent evidence shows that 1,4-GL has an anti-inflammatory effect independent of its β-glucuronidase inhibiting action. 1,4-GL was found to inhibit key intercellular inflammatory mediators such as protein kinase C and nuclear factor kappa B.30\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eANTIOXIDANT \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eSeveral recent studies have demonstrated that calcium D-glucarate has a potent antioxidant activity, also independent of inhibition of β-glucuronidase. Saluk-Juszczak et al found that 1,4-GL had a significant antioxidant activity against oxidative damage to lipids and proteins of platelets, induced by very strong oxidants, such as reactive nitrogen species and reactive oxygen species.31 Similarly, Rashid et al found 1,4- GL reduced oxidative stress and improved glutathione status in mice administered the diabetes-inducing compound alloxan.32\u003c\/p\u003e\n\u003ch2\u003eAPPLICATIONS\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eOESTROGEN \/ XENO-OESTROGEN DEPENDENT CONDITIONS \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eA number of female reproductive conditions are linked to elevated systemic and\/or tissue levels and\/or elevated environmental chemicals (“xeno-oestrogens”) (Table 1). The high levels of oestrogens and xeno-oestrogens are thought to contribute to the pathology, through such mechanisms as increasing inflammation, promoting undifferentiated growth and causing DNA damage. One strategy to treat oestrogen\/xeno-oestrogen dominant conditions is to promote detoxification and subsequently reduce body levels of these compounds.\u003c\/p\u003e\n\u003cp\u003eThe use of calcium D-glucarate can be viewed as one tool for reducing oestrogen\/xeno-oestrogen levels by promoting net glucuronidation.\u003c\/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003eTable 1. Female reproductive conditions associated with oestrogen and\/or xeno-oestrogen excess. \u003c\/strong\u003e\u003c\/span\u003e33,34,35,36,37,38,39\u003c\/p\u003e\n\u003ctable style=\"width: 65.3558%;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 25%;\"\u003e \u003cstrong\u003eElevated tissue or serum concentration of oestrogen found in: \u003c\/strong\u003e\n\u003c\/td\u003e\n\u003ctd style=\"width: 27.0667%;\"\u003e\u003cstrong\u003eElevated xeno-oestrogens linked to:\u003c\/strong\u003e\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 25%;\"\u003e\n\u003cul\u003e\n\u003cli\u003eEndometriosis\u003c\/li\u003e\n\u003cli\u003eFibroids\u003c\/li\u003e\n\u003cli\u003eBreast cancer\u003c\/li\u003e\n\u003cli\u003eDysmenorrhoea\u003c\/li\u003e\n\u003cli\u003ePremenstrual syndrome (PMS)\u003c\/li\u003e\n\u003cli\u003ePolycystic ovarian syndrome (PCOS) \u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/td\u003e\n\u003ctd style=\"width: 27.0667%;\"\u003e\n\u003cul\u003e\n\u003cli\u003eEndometriosis\u003c\/li\u003e\n\u003cli\u003eFibroids\u003c\/li\u003e\n\u003cli\u003ePCO\u003c\/li\u003e\n\u003cli\u003eBreast cancer\u003c\/li\u003e\n\u003cli\u003eReduced IVF success\u003c\/li\u003e\n\u003cli\u003eMiscarriage\u003c\/li\u003e\n\u003cli\u003ePremature delivery\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003cp\u003e\u003cbr\u003eGlucuronidation may be impaired in hypothyroidism40 and supporting glucuronidation may assist in oestrogendominant conditions where hypothyroidism is contributing. Clinically, this may be seen in patients presenting with conditions such as endometriosis, fibroids and fibrocystic breast disease.\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eCANCER\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eNumerous studies have identified increased levels of β-glucuronidase, either in the affected tissue or in the serum (Figure 5), in people with tumours.41,42 Table 2 lists the types of cancers found to be associated with elevated β-glucuronidase. Numerous animal studies have shown that oral administration of calcium Dglucarate decreases initiation, promotion and progression of experimental tumours induced by a variety of carcinogens.43 The results of animal studies have led researchers to suggest that that calcium D-glucarate may reduce the risk of lung, breast, prostate, liver, skin, and colon cancer in humans. 44\u003cbr\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_5_Serum_levels_of_-glucuronidase_in_breast_cancer_-_HealthMasters_600x600.jpg?v=1586482112\" alt=\"Calcium D-Glucarate Figure 5 Serum levels of β-glucuronidase in breast cancer - HealthMasters\" width=\"600x600\" height=\"600x600\" style=\"display: block; margin-left: auto; margin-right: auto;\"\u003e\u003c\/p\u003e\n\u003cblockquote\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 5. Serum levels of β-glucuronidase in breast cancer patients compared to controls. 49\u003c\/span\u003e\u003c\/strong\u003e\u003c\/p\u003e\n\u003c\/blockquote\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003eTable 2. Tumour types associated with elevated β-glucuronidase.\u003c\/strong\u003e \u003c\/span\u003e45,46,47,48\u003c\/p\u003e\n\u003ctable style=\"width: 50.5618%;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 21%;\"\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cdiv style=\"text-align: left;\"\u003ebrain\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003ebreast\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003ecolon\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003eliver\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003elung\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003epancreatic\u003c\/div\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/td\u003e\n\u003ctd style=\"width: 11.604%; text-align: left;\"\u003e\n\u003cdiv\u003e\n\u003cul\u003e\n\u003cli\u003epenile\u003c\/li\u003e\n\u003cli\u003eprostate\u003c\/li\u003e\n\u003cli\u003eskin\u003c\/li\u003e\n\u003cli\u003estomach\u003c\/li\u003e\n\u003cli\u003euterus\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/div\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003ch3\u003e\u003cem\u003eGALLSTONES\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eSeveral lines of evidence support the use of calcium D-glucarate for the management of gallstones (cholelithiasis). β-glucuronidase activity in the liver and bile duct is suspected to play a pathogenic role in the condition by deconjugating glucuronidated bilirubin.50,51 One study found that people with cholesterol gallstones (the more common form) or pigment gallstones had 11- and 33-fold greater level of biliary β-glucuronidase than healthy controls, respectively. An animal study investigating the effect of 1,4 GL on bile function found that it significantly lowered biliary β-glucuronidase activity.52\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eDYSLIPIDAEMIA\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003ePreliminary results investigating the lipid lowering effect of calcium D-glucarate found that it reduced total serum cholesterol up to 12 percent, LDL cholesterol up to 28 percent, and triglycerides up to 43 percent. The researchers suggests calcium D-glucarate lowered cholesterol by increasing excretion of bile acids. 53\u003c\/p\u003e\n\u003ch2\u003eCAUTIONS AND CONTRAINDICATIONS\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eCONTRAINDICATIONS\u003c\/em\u003e\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eDigoxin:\u003c\/strong\u003e This drug is metabolised via glucuronidation and therefore levels may be affected by calcium-Dglucarate supplementation. Only use this combination under medical supervision.54,55,56,57\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch3\u003e\u003cem\u003eCAUTIONS\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003e\u003cstrong\u003eDiazepam\/oxazepam:\u003c\/strong\u003e This drug is metabolised via glucuronidation and therefore levels may be affected by calcium-D-glucarate supplementation. Use with caution in patients taking this medication and monitor symptom changes. 58,59,60,61\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eOral contraceptives:\u003c\/strong\u003e Calcium D-glucarate may reduce the efficacy of oral contraceptives. Calcium Dglucarate may impact on the metabolism and elimination of oestrogen via an action on beta-glucuronidase. Barrier forms of contraception may be required.62,63,64,65\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003ePREGNANCY AND BREASTFEEDING\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003e\u003cstrong\u003ePregnancy:\u003c\/strong\u003e Discontinue use if patient becomes pregnant whilst taking this formula. Oestrogen detoxification should be avoided during pregnancy.66,67\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eBreastfeeding:\u003c\/strong\u003e Likely safe when used at recommended doses.68,69\u003c\/p\u003e\n\u003ch5\u003eRecerences\u003c\/h5\u003e\n\u003ch2\u003eReferences:\u003c\/h2\u003e\n\u003cp\u003e1 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e2 Oleson L, Court MH. Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases. J Pharm Pharmacol. 2008 Sep;60(9):1175-82.\u003cbr\u003e3 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e4 Shapira I. et al. Evolving Concepts: How Diet and the Intestinal Microbiome Act as Modulators of Breast Malignancy. ISRN Oncol. 2013 Sep 25;2013:693920\u003cbr\u003e5 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e6 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e7 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e8 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e9 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e10 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e11 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e12 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e13 Walaszek Z, Hanausek-Walaszek M. D-glucaro-1,4-lactone: its excretion In the bile and urine and effect on biliary excretion of β-glucuronidase after oral administration in rats. Hepatology 1988;9:552e7.\u003cbr\u003e14 Oleson L, Court MH. Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases. J Pharm Pharmacol. 2008 Sep;60(9):1175-82.\u003cbr\u003e15 Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.\u003cbr\u003e16 Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.\u003cbr\u003e17 Basińska A, Floriańczyk B. Β-glucuronidase in physiology and disease. Ann Univ Mariae Curie Sklodowska Med. 2003;58(2):386-9.\u003cbr\u003e18 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e19 Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.\u003cbr\u003e20 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e21 Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthraceneinduced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6.\u003cbr\u003e22 Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthraceneinduced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6.\u003cbr\u003e23 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e24 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e25 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e26 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e27 Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthraceneinduced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6.\u003cbr\u003e28 Whiting JF, Narciso JP, Chapman V, Ransil BJ, Swank RT, Gollan JL. Deconjugation of bilirubin-IX alpha glucuronides: a physiologic role of hepatic microsomal β glucuronidase. J Biol Chem. 1993 Nov 5;268(31):23197-201.\u003cbr\u003e29 Macfadyen A, Ho KJ. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on the biliary secretion of β-glucuronidase after oral administration in rats. Hepatology. 1989 Apr;9(4):552-6.\u003cbr\u003e30 Bhattacharya S, Manna P, Gachhui R, Sil PC. D-saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemiamediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling. Toxicol Appl Pharmacol. 2013 Feb 15;267(1):16-29.\u003cbr\u003e31 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e32 Rashid K, Bhattacharya S, Sil PC. Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway. Free Radic Res. 2012 Mar;46(3):240-52.\u003cbr\u003e33 Cavalieri EL, Rogan EG. Unbalanced metabolism of endogenous estrogens in the etiology and prevention of human cancer. J Steroid Biochem Mol Biol. 2011 Jul;125(3-5):169-80.\u003cbr\u003e34 Sasano H, Nagasaki S, Miki Y, Suzuki T. New developments in intracrinology of human breast cancer: estrogen sulfatase and sulfotransferase. Ann N Y Acad Sci. 2009 Feb;1155:76-9.\u003cbr\u003e35 Ezaki K, Motoyama H, Sasaki H. Immunohistologic localization of estrone sulfatase in uterine endometrium and adenomyosis. Obstet Gynecol. 2001 Nov;98(5 Pt 1):815-9.\u003cbr\u003e36 Wang M, Seippel L, Purdy RH, Bãckström T. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20- one. J Clin Endocrinol Metab. 1996 Mar;81(3):1076-82.\u003cbr\u003e37 Wang M, Seippel L, Purdy RH, Bãckström T. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20- one. J Clin Endocrinol Metab. 1996 Mar;81(3):1076-82.\u003cbr\u003e38 Stener-Victorin E, Holm G, Labrie F, Nilsson L, Janson PO, Ohlsson C. Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome? J Clin Endocrinol Metab. 2010 Feb;95(2):810-9.\u003cbr\u003e39 Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013 Dec;42:132-55.\u003cbr\u003e40 van der Heide SM, Joosten BJ, Everts ME, Klaren PH. Activities of UDP-glucuronyltransferase, β-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats. J Endocrinol. 2004 Jun;181(3):393-400.\u003cbr\u003e41 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e42 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e43 Walaszek Z. Potential use of D-glucaric acid derivatives in cancer prevention. Cancer Lett. 1990;54:1-8.\u003cbr\u003e44 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e45 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e46 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e47 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e48 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e49 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e50 Ho KJ, Hsu SC, Chen JS, Ho LH. Human biliary β-glucuronidase: correlation of its activity with deconjugation of bilirubin in the bile. Eur J Clin Invest. 1986 Oct;16(5):361-7.\u003cbr\u003e51 Duvaldestin P, Mahu JL, Metreau JM, Arondel J, Preaux AM, Berthelot P. Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones. Gut. 1980 Aug;21(8):650-5.\u003cbr\u003e52 Macfadyen A, Ho KJ. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on the biliary secretion of β-glucuronidase after oral administration in rats. Hepatology. 1989 Apr;9(4):552-6.\u003cbr\u003e53 Walaszek Z, Hanausek-Walaszek M, Adams AK, Sherman U.Cholesterol lowering effects of dietary D-glucarate. FASEB 1991;5:A930; cited in Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e54 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e55 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e56 eMIMS. Amizide PI. UBM Medica Australia Pty Ltd. 2014.\u003cbr\u003e57 Pharmacology Weekly. CytP450 Substrates. http:\/\/www.pharmacologyweekly.com\/content\/pages\/cytochrome-cyp-p450-enzymemedication- herbs-substrates (date accessed 11 July 2014).\u003cbr\u003e58 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e59 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e60 eMIMS. Amizide PI. UBM Medica Australia Pty Ltd. 2014.\u003cbr\u003e61 Pharmacology Weekly. CytP450 Substrates. http:\/\/www.pharmacologyweekly.com\/content\/pages\/cytochrome-cyp-p450-enzymemedication- herbs-substrates (date accessed 11 July 2014).\u003cbr\u003e62 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e63 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e64 eMIMS. Amizide PI. UBM Medica Australia Pty Ltd. 2014.\u003cbr\u003e65 Pharmacology Weekly. CytP450 Substrates. http:\/\/www.pharmacologyweekly.com\/content\/pages\/cytochrome-cyp-p450-enzymemedication- herbs-substrates (date accessed 11 July 2014).\u003cbr\u003e66 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e67 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e68 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e69 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003c\/p\u003e\n\u003c!-- \/TABS --\u003e","published_at":"2022-10-11T14:11:14+11:00","created_at":"2018-05-21T09:51:04+10:00","vendor":"Metagenics","type":"Metagenics Naturopathic Medicines","tags":["Compounding","Hormonal","Metagenics","Metagenics Hormonal","Naturopathic","PB"],"price":6615,"price_min":6615,"price_max":6615,"available":true,"price_varies":false,"compare_at_price":7350,"compare_at_price_min":7350,"compare_at_price_max":7350,"compare_at_price_varies":false,"variants":[{"id":8167236436072,"title":"Default Title","option1":"Default Title","option2":null,"option3":null,"sku":"CalciumD-Glucarate204gm","requires_shipping":true,"taxable":true,"featured_image":null,"available":true,"name":"Metagenics Calcium D-Glucarate 204g","public_title":null,"options":["Default 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Logo","id":2666525818939,"position":4,"preview_image":{"aspect_ratio":1.0,"height":500,"width":500,"src":"\/\/shop.healthmasters.com.au\/cdn\/shop\/products\/Metagenics_Calcium_D-Glucarate_204_gm_10_off_RRP_-_HealthMasters.jpg?v=1596757056"},"aspect_ratio":1.0,"height":500,"media_type":"image","src":"\/\/shop.healthmasters.com.au\/cdn\/shop\/products\/Metagenics_Calcium_D-Glucarate_204_gm_10_off_RRP_-_HealthMasters.jpg?v=1596757056","width":500}],"requires_selling_plan":false,"selling_plan_groups":[],"content":"\u003ch3\u003e\u003cem\u003eAssist Glucuronidation For Oestrogen and Xeno-Oestrogen Detoxification\u003c\/em\u003e\u003c\/h3\u003e\n\u003ch2\u003e\u003cstrong\u003eMetagenics Calcium D-Glucarate 204g\u003c\/strong\u003e\u003c\/h2\u003e\n\u003cp\u003eMetagenics Calcium D-Glucarate Size: 240g\u003c\/p\u003e\n\u003cp\u003eMetagenics Calcium D-Glucarate:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eGlucuronidation is a key phase II process that assists in the detoxification of oestrogen and xeno-oestrogen compounds from the environment.\u003c\/li\u003e\n\u003cli\u003eMetagenics Calcium D-glucarate is a natural glucose metabolite which is an effective inhibitor of β-glucuronidase – an enzyme which deconjugates bound toxins and other metabolic waste products.\u003c\/li\u003e\n\u003cli\u003eBy preventing deconjugation of products of glucuronidation, calcium D-glucarate promotes a net increase in phase II detoxification and is indicated in toxicity-associated conditions, especially those involving excessive oestrogen activity.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- TABS --\u003e\n\u003ch5\u003eDirections\u003c\/h5\u003e\n\u003ch2\u003eDirections: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eOestrogen\/xeno-oestrogen detoxification: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003eCancer: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003eGallstones: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003eDyslipidaemia: 1.5-3.0g daily (1-2 tsp)\u003c\/p\u003e\n\u003cp\u003e1 metric tsp (1.7g) is equal to 1.5g (1500mg) of Calcium D-Glucarate (\u003cspan\u003eCalcium saccharate\u003c\/span\u003e) Stir well and take immediately.\u003c\/p\u003e\n\u003ch5\u003eBenefits\u003c\/h5\u003e\n\u003ch2\u003eBenefits: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Benefits: Metagenics Calcium D-Glucarate\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eCalcium D-glucarate is a natural glucose metabolite which is an effective inhibitor of β-glucuronidase – an enzyme which deconjugates bound toxins and other metabolic waste products. Glucuronidation is a key phase II process that assists in the detoxification of oestrogen and xeno-oestrogen compounds from the environment.\u003c\/li\u003e\n\u003cli\u003eBy preventing deconjugation of products of glucuronidation, calcium D-glucarate promotes a net increase in phase II detoxification and is indicated in toxicity-associated conditions, especially those involving excessive oestrogen activity.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch5\u003eIngredients\u003c\/h5\u003e\n\u003ch2\u003eIngredients: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eCalcium D-Glucarate\u003c\/p\u003e\n\u003ch5\u003eWarnings\u003c\/h5\u003e\n\u003ch2\u003eWarnings: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eNot all cautions and contraindications are listed. For full details, references or more information contact HealthMasters in Australia by email: reception@healthmasters.com.au\u003c\/p\u003e\n\u003ch5\u003eStorage\u003c\/h5\u003e\n\u003ch2\u003eStorage: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003cp\u003eStore below 30° C\u003c\/p\u003e\n\u003ch5\u003eTechnical Information\u003c\/h5\u003e\n\u003ch2\u003eTechnical Information: Metagenics Calcium D-Glucarate\u003c\/h2\u003e\n\u003ch2 style=\"text-align: left;\"\u003e\u003cbig\u003e\u003cbig\u003eCalcium D-Glucarate\u003c\/big\u003e\u003c\/big\u003e\u003c\/h2\u003e\n\u003cp\u003eCalcium D-glucarate is a natural glucose metabolite which is an effective inhibitor of β-glucuronidase – an enzyme which deconjugates bound toxins and other metabolic waste products. Glucuronidation is a key phase II process that assists in the detoxification of oestrogen and xeno-oestrogen compounds from the environment. By preventing deconjugation of products of glucuronidation, calcium D-glucarate promotes a net increase in phase II detoxification and is indicated in toxicity-associated conditions, especially those involving excessive oestrogen activity.\u003c\/p\u003e\n\u003ch2\u003eHERBS AND NUTRIENTS THAT MAY ASSIST\u003c\/h2\u003e\n\u003cp\u003eCalcium D-glucarate\u003c\/p\u003e\n\u003ch2\u003eCLINICAL APPLICATIONS\u003c\/h2\u003e\n\u003ch3\u003eKEY ACTIONS:\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003eInhibits β-glucuronidase and increases net phase II glucuronidation\u003c\/li\u003e\n\u003cli\u003eDecreases oestrogen\u003c\/li\u003e\n\u003cli\u003eAnticarcinogenic\u003c\/li\u003e\n\u003cli\u003eImproves lipid and bile metabolism\u003c\/li\u003e\n\u003cli\u003eAnti-inflammatory\u003c\/li\u003e\n\u003cli\u003eAntioxidant\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch3\u003eKEY APPLICATIONS:\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003eOestrogen\/xeno-oestrogen dependent conditions\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cdiv style=\"padding-left: 60px;\"\u003eo Endometriosis\u003c\/div\u003e\n\u003cdiv style=\"padding-left: 60px;\"\u003eo Fibroids\u003c\/div\u003e\n\u003cdiv style=\"padding-left: 60px;\"\u003eo Breast cancer\u003c\/div\u003e\n\u003cul\u003e\n\u003cli\u003eCancer, especially breast and prostate\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eMay also be considered for:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eGallstones\u003c\/li\u003e\n\u003cli\u003eDyslipidaemia\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch2\u003eDOSES\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eOestrogen\/xeno-oestrogen detoxification: 1500-3000 mg daily (1-2 tsp)\u003c\/li\u003e\n\u003cli\u003eCancer: 1500-3000 mg daily (1-2 tsp)\u003c\/li\u003e\n\u003cli\u003eGallstones: 1500-3000 mg daily (1-2 tsp)\u003c\/li\u003e\n\u003cli\u003eDyslipidaemia: 1500-3000 mg daily\u003cspan\u003e (1-2 tsp)\u003c\/span\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch2\u003eBACKGROUND TECHNICAL INFORMATION\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eGlucuronidation\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eGlucuronidation is an important phase II detoxification process which attaches glucuronic acid to a toxin for excretion. Glucuronic acid serves as conjugation compound for the detoxification of a wide variety of endogenous and exogenous substrates, including sex hormones and toxins.1,2 In glucuronidation, the enzyme uridine 5'-diphospho-(UDP)-glucuronosyltransferase (UDG) attaches the water-soluble glucuronic acid to the more fat-soluble substrate, creating a conjugate compound which is now water-soluble for elimination.\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eβ-glucuronidase\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eThe enzyme β-glucuronidase reverses the process of glucuronidation; deconjugating the glucuronic acid from the toxin and ‘re-activating’ it, as it is no longer bound. The amount of a toxin that is eliminated is believed to be largely determined by the balance of conjugation versus deconjugation (Figure 1).\u003c\/p\u003e\n\u003cp\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_1_Glucuronidation_and_deglucuronidation_of_toxins_-_HealthMasters_600x600.jpg?v=1586479530\" alt=\"Calcium D-Glucarate Figure 1 Glucuronidation and deglucuronidation of toxins - HealthMasters\" width=\"600x600\" height=\"600x600\" style=\"display: block; margin-left: auto; margin-right: auto;\"\u003e\u003c\/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 1. Glucuronidation and deglucuronidation of toxins.\u003c\/span\u003e\u003c\/strong\u003e\u003c\/p\u003e\n\u003cblockquote\u003e\n\u003cdiv style=\"text-align: left;\"\u003e\u003cstrong\u003e\u003cem\u003eThe net amount of toxin detoxified is determined by the balance between conjugation via uridine 5'-diphospho—glucuronosyltransferase (UDG) and deconjugation from β-glucuronidase (BG).\u003c\/em\u003e\u003c\/strong\u003e\u003c\/div\u003e\n\u003c\/blockquote\u003e\n\u003cp\u003eHumans synthesise β-glucuronidase and it has been detected in many tissues including liver, kidney, spleen, testes, lung, gastrointestinal tract, and in cancerous and inflamed tissue. Additionally, a dysbiotic gastrointestinal microbiome produces high levels of β-glucuronidase, which can act identically to human β-glucuronidase, by deconjugating glucuronidated substances.4\u003c\/p\u003e\n\u003cp\u003eEssentially, almost any tissue and body compartment can deconjugate glucuronidated compounds and restore their bioactivity via β-glucuronidase. \u003cbr\u003eβ-glucuronidase is believed to have a constitutive role in degrading glycosaminoglycans for tissue remodelling. However, as is the case with many inflammation-induced mediators, down-regulating excessive levels is a useful short or long term strategy in the control of disease, with little risk of compromising normal physiology. Elevated levels of β-glucuronidase have been found in various pathologies and inflammatory disorders, with elevated levels linked to cancer risk.5,6,7 β-glucuronidase levels are naturally suppressed by compounds found in a healthy diet (described below); indicating that control of β-glucuronidase activity can be considered an normal and safe strategy to restore homeostasis in situations of dysbiosis and inflammation.\u003c\/p\u003e\n\u003ch2\u003eINGREDIENTS\u003c\/h2\u003e\n\u003cp\u003eCalcium D-glucarate is glucose-like compound, which upon ingestion is metabolised in the stomach to form D-glucaric acid. D-glucaric acid can be obtained from the diet from plant foods, most notably in grapefruits, apples, oranges and cruciferous vegetables. A diet high in fruits and vegetables is estimated to provide around 200 mg\/day of D-glucaric acid.8 Additionally, humans can synthesis small amounts of D-glucaric acid in the liver from glucose.9\u003c\/p\u003e\n\u003cp\u003eCalcium D-glucarate, and the resulting D-glucaric acid, are further metabolised to create D-glucaro-1,4-lactone (1,4-GL), which has been shown to be the active form of supplemental calcium D-glucarate (Figure 2).10\u003c\/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_2_The_metabolism_of_calcium_D-glucarate_-_HealthMasters_600x600.jpg?v=1586479725\" alt=\"Calcium D-Glucarate Figure 2 The metabolism of calcium D-glucarate - HealthMasters\" width=\"600x600\" height=\"600x600\" style=\"display: block; margin-left: auto; margin-right: auto;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 2. The metabolism of calcium D-glucarate to the bioactive compound D-glucaro-1,4-lactone.\u003c\/span\u003e \u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003e1,4-GL acts to attenuate the deconjugation of products of glucuronidation by inhibiting β-glucuronidase and thus allow the toxin to be eliminated successfully.11\u003c\/p\u003e\n\u003ch2\u003eACTIONS\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eINHIBITS β-GLUCURONIDASE AND INCREASES NET PHASE II GLUCURONIDATION \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eThe key mechanism of action of calcium D-glucarate is inhibition of β-glucuronidase. Calcium D-glucarate therefore has the potential to mitigate deconjugation of glucuronidated compounds, such as oestrogen, and promote safe excretion of the conjugated substance.12,13,14,15\u003c\/p\u003e\n\u003cp\u003eThe ability of calcium D-glucarate to inhibit β-glucuronidase was first demonstrated over sixty years ago and numerous studies since have confirmed its ability. For example, feeding rodents a single dose of calcium D-glucarate results in significant inhibition in β-glucuronidase in several sites, including serum, liver, lung and intestine (Figure 3).16 The activity of β-glucuronidase has been found to be elevated in many disease states, including numerous types of cancers, diabetes, heart disease, rheumatoid arthritis, liver pathology, cholelithiasis, inflammation, jaundice, tuberculosis, and sarcoidosis.17,18\u003c\/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_3_The_effect_of_calcium_D-glucarate_-_HealthMasters_600x600.jpg?v=1586480013\" alt=\"Calcium D-Glucarate Figure 3 The effect of calcium D-glucarate - HealthMasters\" width=\"600x600\" height=\"600x600\"\u003e\u003cbr\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 3. The effect of calcium D-glucarate (CDC) on β-glucuronidase activity in several tissues.\u003c\/span\u003e\u003c\/strong\u003e19\u003cbr\u003e\u003cstrong\u003e* p\u0026lt;0.05 compared to control\u003c\/strong\u003e\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eDECREASES OESTROGEN \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp style=\"text-align: left;\"\u003eInhibition of β-glucuronidase with calcium D-glucarate can allow more substrate to remain conjugated, with a net change of increasing phase II detoxification.20 For example, rats showed a 23% reduction in serum oestradiol and a 55% reduction in oestrone levels when fed calcium D-glucarate (Figure 4).21\u003c\/p\u003e\n\u003cdiv style=\"text-align: left;\"\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_4_Percentage_reduction_in_serum_oestradiol_-_HealthMasters_480x480.jpg?v=1586480091\" alt=\"Calcium D-Glucarate Figure 4 Percentage reduction in serum oestradiol - HealthMasters\" width=\"480x480\" height=\"480x480\" style=\"margin-right: auto; float: none; display: block; margin-left: auto;\"\u003e\u003c\/div\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 4. Percentage reduction in serum oestradiol and urinary oestrone in rats feed calcium D-glucurate.\u003c\/span\u003e\u003c\/strong\u003e 22\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eANTICARCINOGENIC \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eInhibiting β-glucuronidase is considered to be a key mechanism in calcium D-glucaric acid’s anticarcinogenic effect. It is suggested that calcium D-glucarate’s action is largely due to its ability to detoxify hormones and exogenous toxins that are linked to carcinogenesis. Environmental carcinogens and endogenous oestrogens can cause DNA mutations and promote tumourigenesis; therefore promoting of glucuronidation of these toxins can reduce the carcinogenic load.23 Additionally, tumours contain high levels of β-glucuronidase which is linked to inflammation and subsequent metastasis, with researchers suggesting inhibition of β-glucuronidation may attenuate inflammation and metastasis.24,25\u003c\/p\u003e\n\u003cp\u003eOutside of inhibiting β-glucuronidase, calcium D-glucarate has several other anti-carcinogenic actions. It inhibits protein kinase-C activity and induces transforming growth factor β, which can result in an increase in cellular differentiation and regulate progression through the cell cycle. Calcium D-glucarate has also been found to synergistically interact with retinoids and powerfully inhibit carcinogenesis in animal models.26\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eIMPROVES LIPID AND BILE METABOLISM \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eEvidence shows that calcium D-glucarate administration reduces serum cholesterol levels, with research suggesting that it may be modulating steroidogenesis.27 Additional research suggests that calcium D-glucarate is useful for promoting healthy bile flow. β-glucuronidase in the biliary tract can deconguate bile salts, such as bilirubin, which can allow gallstones to precipitate.28 Mice receiving 1,4 GL showed a decrease in the biliary β- glucuronidase activity, indicating a reduction of bile deconjugation.29\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eANTI-INFLAMMATORY \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eRecent evidence shows that 1,4-GL has an anti-inflammatory effect independent of its β-glucuronidase inhibiting action. 1,4-GL was found to inhibit key intercellular inflammatory mediators such as protein kinase C and nuclear factor kappa B.30\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eANTIOXIDANT \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eSeveral recent studies have demonstrated that calcium D-glucarate has a potent antioxidant activity, also independent of inhibition of β-glucuronidase. Saluk-Juszczak et al found that 1,4-GL had a significant antioxidant activity against oxidative damage to lipids and proteins of platelets, induced by very strong oxidants, such as reactive nitrogen species and reactive oxygen species.31 Similarly, Rashid et al found 1,4- GL reduced oxidative stress and improved glutathione status in mice administered the diabetes-inducing compound alloxan.32\u003c\/p\u003e\n\u003ch2\u003eAPPLICATIONS\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eOESTROGEN \/ XENO-OESTROGEN DEPENDENT CONDITIONS \u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eA number of female reproductive conditions are linked to elevated systemic and\/or tissue levels and\/or elevated environmental chemicals (“xeno-oestrogens”) (Table 1). The high levels of oestrogens and xeno-oestrogens are thought to contribute to the pathology, through such mechanisms as increasing inflammation, promoting undifferentiated growth and causing DNA damage. One strategy to treat oestrogen\/xeno-oestrogen dominant conditions is to promote detoxification and subsequently reduce body levels of these compounds.\u003c\/p\u003e\n\u003cp\u003eThe use of calcium D-glucarate can be viewed as one tool for reducing oestrogen\/xeno-oestrogen levels by promoting net glucuronidation.\u003c\/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003eTable 1. Female reproductive conditions associated with oestrogen and\/or xeno-oestrogen excess. \u003c\/strong\u003e\u003c\/span\u003e33,34,35,36,37,38,39\u003c\/p\u003e\n\u003ctable style=\"width: 65.3558%;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 25%;\"\u003e \u003cstrong\u003eElevated tissue or serum concentration of oestrogen found in: \u003c\/strong\u003e\n\u003c\/td\u003e\n\u003ctd style=\"width: 27.0667%;\"\u003e\u003cstrong\u003eElevated xeno-oestrogens linked to:\u003c\/strong\u003e\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 25%;\"\u003e\n\u003cul\u003e\n\u003cli\u003eEndometriosis\u003c\/li\u003e\n\u003cli\u003eFibroids\u003c\/li\u003e\n\u003cli\u003eBreast cancer\u003c\/li\u003e\n\u003cli\u003eDysmenorrhoea\u003c\/li\u003e\n\u003cli\u003ePremenstrual syndrome (PMS)\u003c\/li\u003e\n\u003cli\u003ePolycystic ovarian syndrome (PCOS) \u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/td\u003e\n\u003ctd style=\"width: 27.0667%;\"\u003e\n\u003cul\u003e\n\u003cli\u003eEndometriosis\u003c\/li\u003e\n\u003cli\u003eFibroids\u003c\/li\u003e\n\u003cli\u003ePCO\u003c\/li\u003e\n\u003cli\u003eBreast cancer\u003c\/li\u003e\n\u003cli\u003eReduced IVF success\u003c\/li\u003e\n\u003cli\u003eMiscarriage\u003c\/li\u003e\n\u003cli\u003ePremature delivery\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003cp\u003e\u003cbr\u003eGlucuronidation may be impaired in hypothyroidism40 and supporting glucuronidation may assist in oestrogendominant conditions where hypothyroidism is contributing. Clinically, this may be seen in patients presenting with conditions such as endometriosis, fibroids and fibrocystic breast disease.\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eCANCER\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eNumerous studies have identified increased levels of β-glucuronidase, either in the affected tissue or in the serum (Figure 5), in people with tumours.41,42 Table 2 lists the types of cancers found to be associated with elevated β-glucuronidase. Numerous animal studies have shown that oral administration of calcium Dglucarate decreases initiation, promotion and progression of experimental tumours induced by a variety of carcinogens.43 The results of animal studies have led researchers to suggest that that calcium D-glucarate may reduce the risk of lung, breast, prostate, liver, skin, and colon cancer in humans. 44\u003cbr\u003e\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/2075\/8503\/files\/Calcium_D-Glucarate_Figure_5_Serum_levels_of_-glucuronidase_in_breast_cancer_-_HealthMasters_600x600.jpg?v=1586482112\" alt=\"Calcium D-Glucarate Figure 5 Serum levels of β-glucuronidase in breast cancer - HealthMasters\" width=\"600x600\" height=\"600x600\" style=\"display: block; margin-left: auto; margin-right: auto;\"\u003e\u003c\/p\u003e\n\u003cblockquote\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"text-decoration: underline;\"\u003eFigure 5. Serum levels of β-glucuronidase in breast cancer patients compared to controls. 49\u003c\/span\u003e\u003c\/strong\u003e\u003c\/p\u003e\n\u003c\/blockquote\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003eTable 2. Tumour types associated with elevated β-glucuronidase.\u003c\/strong\u003e \u003c\/span\u003e45,46,47,48\u003c\/p\u003e\n\u003ctable style=\"width: 50.5618%;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 21%;\"\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cdiv style=\"text-align: left;\"\u003ebrain\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003ebreast\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003ecolon\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003eliver\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003elung\u003c\/div\u003e\n\u003c\/li\u003e\n\u003cli style=\"text-align: left;\"\u003e\n\u003cdiv\u003epancreatic\u003c\/div\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/td\u003e\n\u003ctd style=\"width: 11.604%; text-align: left;\"\u003e\n\u003cdiv\u003e\n\u003cul\u003e\n\u003cli\u003epenile\u003c\/li\u003e\n\u003cli\u003eprostate\u003c\/li\u003e\n\u003cli\u003eskin\u003c\/li\u003e\n\u003cli\u003estomach\u003c\/li\u003e\n\u003cli\u003euterus\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/div\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003ch3\u003e\u003cem\u003eGALLSTONES\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003eSeveral lines of evidence support the use of calcium D-glucarate for the management of gallstones (cholelithiasis). β-glucuronidase activity in the liver and bile duct is suspected to play a pathogenic role in the condition by deconjugating glucuronidated bilirubin.50,51 One study found that people with cholesterol gallstones (the more common form) or pigment gallstones had 11- and 33-fold greater level of biliary β-glucuronidase than healthy controls, respectively. An animal study investigating the effect of 1,4 GL on bile function found that it significantly lowered biliary β-glucuronidase activity.52\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003eDYSLIPIDAEMIA\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003ePreliminary results investigating the lipid lowering effect of calcium D-glucarate found that it reduced total serum cholesterol up to 12 percent, LDL cholesterol up to 28 percent, and triglycerides up to 43 percent. The researchers suggests calcium D-glucarate lowered cholesterol by increasing excretion of bile acids. 53\u003c\/p\u003e\n\u003ch2\u003eCAUTIONS AND CONTRAINDICATIONS\u003c\/h2\u003e\n\u003ch3\u003e\u003cem\u003eCONTRAINDICATIONS\u003c\/em\u003e\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eDigoxin:\u003c\/strong\u003e This drug is metabolised via glucuronidation and therefore levels may be affected by calcium-Dglucarate supplementation. Only use this combination under medical supervision.54,55,56,57\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch3\u003e\u003cem\u003eCAUTIONS\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003e\u003cstrong\u003eDiazepam\/oxazepam:\u003c\/strong\u003e This drug is metabolised via glucuronidation and therefore levels may be affected by calcium-D-glucarate supplementation. Use with caution in patients taking this medication and monitor symptom changes. 58,59,60,61\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eOral contraceptives:\u003c\/strong\u003e Calcium D-glucarate may reduce the efficacy of oral contraceptives. Calcium Dglucarate may impact on the metabolism and elimination of oestrogen via an action on beta-glucuronidase. Barrier forms of contraception may be required.62,63,64,65\u003c\/p\u003e\n\u003ch3\u003e\u003cem\u003ePREGNANCY AND BREASTFEEDING\u003c\/em\u003e\u003c\/h3\u003e\n\u003cp\u003e\u003cstrong\u003ePregnancy:\u003c\/strong\u003e Discontinue use if patient becomes pregnant whilst taking this formula. Oestrogen detoxification should be avoided during pregnancy.66,67\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eBreastfeeding:\u003c\/strong\u003e Likely safe when used at recommended doses.68,69\u003c\/p\u003e\n\u003ch5\u003eRecerences\u003c\/h5\u003e\n\u003ch2\u003eReferences:\u003c\/h2\u003e\n\u003cp\u003e1 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e2 Oleson L, Court MH. Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases. J Pharm Pharmacol. 2008 Sep;60(9):1175-82.\u003cbr\u003e3 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e4 Shapira I. et al. Evolving Concepts: How Diet and the Intestinal Microbiome Act as Modulators of Breast Malignancy. ISRN Oncol. 2013 Sep 25;2013:693920\u003cbr\u003e5 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e6 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e7 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e8 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e9 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e10 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e11 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e12 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e13 Walaszek Z, Hanausek-Walaszek M. D-glucaro-1,4-lactone: its excretion In the bile and urine and effect on biliary excretion of β-glucuronidase after oral administration in rats. Hepatology 1988;9:552e7.\u003cbr\u003e14 Oleson L, Court MH. Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases. J Pharm Pharmacol. 2008 Sep;60(9):1175-82.\u003cbr\u003e15 Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.\u003cbr\u003e16 Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.\u003cbr\u003e17 Basińska A, Floriańczyk B. Β-glucuronidase in physiology and disease. Ann Univ Mariae Curie Sklodowska Med. 2003;58(2):386-9.\u003cbr\u003e18 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e19 Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.\u003cbr\u003e20 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e21 Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthraceneinduced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6.\u003cbr\u003e22 Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthraceneinduced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6.\u003cbr\u003e23 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e24 Shimoi K, Nakayama T. Glucuronidase deconjugation in inflammation. Methods Enzymol. 2005;400:263-72.\u003cbr\u003e25 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e26 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e27 Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthraceneinduced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6.\u003cbr\u003e28 Whiting JF, Narciso JP, Chapman V, Ransil BJ, Swank RT, Gollan JL. Deconjugation of bilirubin-IX alpha glucuronides: a physiologic role of hepatic microsomal β glucuronidase. J Biol Chem. 1993 Nov 5;268(31):23197-201.\u003cbr\u003e29 Macfadyen A, Ho KJ. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on the biliary secretion of β-glucuronidase after oral administration in rats. Hepatology. 1989 Apr;9(4):552-6.\u003cbr\u003e30 Bhattacharya S, Manna P, Gachhui R, Sil PC. D-saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemiamediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling. Toxicol Appl Pharmacol. 2013 Feb 15;267(1):16-29.\u003cbr\u003e31 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e32 Rashid K, Bhattacharya S, Sil PC. Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway. Free Radic Res. 2012 Mar;46(3):240-52.\u003cbr\u003e33 Cavalieri EL, Rogan EG. Unbalanced metabolism of endogenous estrogens in the etiology and prevention of human cancer. J Steroid Biochem Mol Biol. 2011 Jul;125(3-5):169-80.\u003cbr\u003e34 Sasano H, Nagasaki S, Miki Y, Suzuki T. New developments in intracrinology of human breast cancer: estrogen sulfatase and sulfotransferase. Ann N Y Acad Sci. 2009 Feb;1155:76-9.\u003cbr\u003e35 Ezaki K, Motoyama H, Sasaki H. Immunohistologic localization of estrone sulfatase in uterine endometrium and adenomyosis. Obstet Gynecol. 2001 Nov;98(5 Pt 1):815-9.\u003cbr\u003e36 Wang M, Seippel L, Purdy RH, Bãckström T. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20- one. J Clin Endocrinol Metab. 1996 Mar;81(3):1076-82.\u003cbr\u003e37 Wang M, Seippel L, Purdy RH, Bãckström T. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20- one. J Clin Endocrinol Metab. 1996 Mar;81(3):1076-82.\u003cbr\u003e38 Stener-Victorin E, Holm G, Labrie F, Nilsson L, Janson PO, Ohlsson C. Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome? J Clin Endocrinol Metab. 2010 Feb;95(2):810-9.\u003cbr\u003e39 Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013 Dec;42:132-55.\u003cbr\u003e40 van der Heide SM, Joosten BJ, Everts ME, Klaren PH. Activities of UDP-glucuronyltransferase, β-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats. J Endocrinol. 2004 Jun;181(3):393-400.\u003cbr\u003e41 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e42 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e43 Walaszek Z. Potential use of D-glucaric acid derivatives in cancer prevention. Cancer Lett. 1990;54:1-8.\u003cbr\u003e44 Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44.\u003cbr\u003e45 Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e46 Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz B. Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):422-8.\u003cbr\u003e47 Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62.\u003cbr\u003e48 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e49 Floriańczyk B, Grzybowska L . Activity of β-glucuronidase in blood serum of patients with breast cancer. J Chin Clin Med. 2010 August;5(8): 480-482.\u003cbr\u003e50 Ho KJ, Hsu SC, Chen JS, Ho LH. Human biliary β-glucuronidase: correlation of its activity with deconjugation of bilirubin in the bile. Eur J Clin Invest. 1986 Oct;16(5):361-7.\u003cbr\u003e51 Duvaldestin P, Mahu JL, Metreau JM, Arondel J, Preaux AM, Berthelot P. Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones. Gut. 1980 Aug;21(8):650-5.\u003cbr\u003e52 Macfadyen A, Ho KJ. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on the biliary secretion of β-glucuronidase after oral administration in rats. Hepatology. 1989 Apr;9(4):552-6.\u003cbr\u003e53 Walaszek Z, Hanausek-Walaszek M, Adams AK, Sherman U.Cholesterol lowering effects of dietary D-glucarate. FASEB 1991;5:A930; cited in Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9.\u003cbr\u003e54 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e55 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e56 eMIMS. Amizide PI. UBM Medica Australia Pty Ltd. 2014.\u003cbr\u003e57 Pharmacology Weekly. CytP450 Substrates. http:\/\/www.pharmacologyweekly.com\/content\/pages\/cytochrome-cyp-p450-enzymemedication- herbs-substrates (date accessed 11 July 2014).\u003cbr\u003e58 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e59 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e60 eMIMS. Amizide PI. UBM Medica Australia Pty Ltd. 2014.\u003cbr\u003e61 Pharmacology Weekly. CytP450 Substrates. http:\/\/www.pharmacologyweekly.com\/content\/pages\/cytochrome-cyp-p450-enzymemedication- herbs-substrates (date accessed 11 July 2014).\u003cbr\u003e62 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e63 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e64 eMIMS. Amizide PI. UBM Medica Australia Pty Ltd. 2014.\u003cbr\u003e65 Pharmacology Weekly. CytP450 Substrates. http:\/\/www.pharmacologyweekly.com\/content\/pages\/cytochrome-cyp-p450-enzymemedication- herbs-substrates (date accessed 11 July 2014).\u003cbr\u003e66 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e67 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003cbr\u003e68 Calcium D-Glucarate Monograph. Alt Med Rev; 7(4)336-9.\u003cbr\u003e69 Jellin JM, Ed. Natural Medicines Comprehensive Database. Calcium D-Glucarate. Therapeutic Research Faculty 2011; [webpage] http:\/\/www.naturaldatabase.com\/ (date accessed: 9 January, 2014).\u003c\/p\u003e\n\u003c!-- \/TABS --\u003e"}