DISCUSSION: CELLULAR DETOX™ contains SGS (with sulforaphane), Calcium D-Glucarate and Bifidobacterium Longum which have been documented to induce the Phase-2 detoxification enzyme systems, protect cells from dangerous chemicals and prevent cellular DNA damage.

30 Vegi-Caps
AOR04210
Lactovegetarian

300 mg

AOR™ guarantees that no ingredients not listed on the label have been added to the product. Contains no corn, wheat, gluten, nuts, soy, eggs, fish or shellfish.

Suggested Use:
Take 1 capsule daily with food, or as directed by a qualified health care professional.

Main Applications:
Detoxification
Reduces cancer risk
Antioxidant

Source:
SGS – Broccoli powder
D-glucarate – Pharmaceutical synthesis
B. longum – Bacterial culture, from dairy

Pregnancy/Nursing:
Do not use if pregnant or nursing.

Cautions:
None Known.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

The Truth about Detoxification

Detoxification involves the removal of toxic substances from the body. Detoxification occurs mainly in the liver, but the kidneys, gastrointestinal tract and skin are also important when it comes to clearing toxins from the body. Unfortunately, detoxification has also become synonymous with cleansing - a term loosely used to describe all sorts of treatments aimed at purifying or purging the body. Many such treatments are unproven, make little sense physiologically, and can even be dangerous. True detoxification begins at the cellular levels, and involves enhancing the body’s natural mechanisms for eliminating toxins and harmful substances. Many natural compounds have been shown to support this process.

The Benefits of Sulforaphane

Numerous studies have shown that the consumption of large quantities of fruits and vegetables, particularly leafy green vegetables, as a part of a healthy diet, is associated with a reduced incidence of cancer. High intakes of these vegetables, called cruciferous vegetables, have been associated with lower risk of lung and colorectal cancer in epidemiological studies. Research has indicated that the cancer preventative action of these vegetables is linked to their high content of compounds called isothiocyanates. One such isothiocyanate is Sulforaphane glucosinolate. This natural compound found in broccoli sprouts that has been shown to inhibit tumor formation and support healthy detoxification. Sulforaphane extracts have several benefits for cancer patients. These include:

• Protecting DNA from mutagens
•  Inhibiting the cellular proliferation of pre-cancerous cells
• Inducing apoptosis in cancer cells
• Impeding the progression of benign tumors into malignant tumors
• Preventing metastasis (cancer spread)
• Inhibiting the formation of new blood vessels (angiogenesis) which feed tumors
• Stimulating the immune system
• Inducing Phase II liver detoxification enzymes

Sulforaphane is a potent inducer of phase II detoxification enzymes, which are the enzymes in the liver responsible for the detoxification of toxins and carcinogens. Enhanced Phase II detoxification greatly assists the body in reducing the overall toxic burden as well as affording substantial other health benefits in immune function, heart health, anti-inflammatory and anti-cancer effects.

Perhaps the most widely studied aspect of sulforaphane is its potential as an anti-cancer agent.  This has been examined in a number of different species and tissues, including prostate, skin, colon, breast, uterine, ovarian, bladder, and the pancreas. Sulforaphane’s anti-cancer effect is attributed to a number of mechanisms including the stimulation of phase II detoxification enzymes, normal apoptosis (cell suicide), cell cycle arrest in cancer cells (preventing replication), reduction of the spread of tumours (metastases) and the inhibition of blood supply to cancer cells (angiogenesis).

Sulforaphane also has powerful antioxidant effects, and can help reduce oxidative stress in the body. It has also been shown to reduce inflammation, support cardiovascular health, reduce blood pressure and lessen allergy symptoms.

D-Glucarate

D-glucarate is a naturally occurring compound that plays a very important role in the detoxification of toxins and carcinogens.  One very important detoxification pathway in the body is the glucuronidation pathway.  Through glucuronidation toxic substances, environmental carcinogens and even excess levels of some hormones are neutralized, and then eliminated from the body.  This important detoxification process can be disrupted by the enzyme beta-glucuronidase, which acts to reactivate the neutralized toxins. Impaired glucuronidation has been linked to susceptibility to many cancers and other diseases in humans and in other species. Human research reveals links between toxic environments, glucuronidation, and beta-glucuronidase; and also between glucuronidation, beta-glucuronidase activity, and cancer and other diseases.

The primary action of D-glucarate is to inhibit the enzyme beta-glucuronidase, thereby promoting detoxification and allowing toxins to be effectively neutralized and eliminated from the body before they can do significant damage.  Research has shown that D-glucarate can inhibit breast cancer development in mice by as much as 70% and has been shown to protect animals against other cancers, such as those of the colon, the lung, the skin, and the liver. Preliminary studies in humans show that D-Glucarate supplements are safe, and that they have the same effects on beta-glucuronidase in people that they do in animals.

Bifidobacterium longum (BB-536)

This highly beneficial probiotic strain has been shown to help promote carcinogen detoxification and to help prevent certain types of cancers. Evidence has shown that this bacteria acts to enhance the immune system, suppress the growth of harmful bacteria that secrete toxic substances, bind and eliminate toxic substances and potential carcinogens and secrete anti-tumor compounds. Many probiotics have been shown to reduce beta- glucuronidase activity in the colon, thereby preventing the reactivation of dangerous compounds.

In one study rats were exposed to toxic heterocyclic amines. Heterocyclic amines are compounds formed when meat is broiled or charred. These compounds are readily present in the human diet and have been shown to induce tumor formation in rats. The study found that rats supplemented with BB-536 showed dramatically reduced tumor formation in the colon, small intestine and liver. Further studies suggest that BB-536 actually binds to heterocyclic amines, and also works through other indirect methods to prevent these compounds from causing DNA damage in the colon.

References:

Walaszek Z, Szemraj J, Narog M, Adams AK, Kilgore J, Sherman U, Hanausek M. "Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention." Cancer Detect Prev. 1997; 21(2): 178-90.

Heerdt AS, Young CW, Borgen PI. "Calcium glucarate as a chemopreventive agent in breast cancer." Isr J Med Sci. 1995 Feb-Mar; 31(2-3): 101-5.

Abou-Issa H, Moeschberger M, el-Masry W, Tejwani S, Curley RW Jr, Webb TE. "Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis." Anticancer Res. 1995 May-Jun; 15(3): 805-10.

Reddy BS and Rivenson A. Inhibitory Effect of Bifidobacterium longum on Colon, Mammary, and Liver Carcinogenesis Induced by 2-Amino-3-methylimidazo[4,5-/]quinoline, a Food Mutagen. Cancer Research. 1993; 53: 3914-3918.

Zsivkovits M et al. Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains. Carcinogenesis. 2003; 24(12): 1913-1918.

Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention.

Walaszek Z, Szemraj J, Narog M, Adams AK, Kilgore J, Sherman U, Hanausek M. Cancer Detect Prev. 1997; 21(2): 178-90.

D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of carcinogens and tumor promoters/progressors by inhibiting beta-glucuronidase and preventing hydrolysis of their glucuronides. 1,4-GL and its precursors, such as potassium hydrogen D-glucarate and calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or adjuvant cancer preventive and therapeutic agents. In our study, 1,4-GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives may be prerequisite for their inhibition of chemical carcinogenesis in rodents and prevention of breast, prostate, and colon cancer in humans.

Calcium glucarate as a chemopreventive agent in breast cancer.

Heerdt AS, Young CW, Borgen PI. Isr J Med Sci. 1995 Feb-Mar; 31(2-3): 101-5.

Although it appears that progress is being made in the treatment of breast cancers of all stages, the etiological agents still remain unclear and render the search for preventive agents extremely difficult. What is clearly required in this situation is a nontoxic compound that can potentially affect various pathways that may be responsible for the rising incidence of breast cancer. In this review, we present the rationale for the use of an agent such as calcium glucarate, which may both change the internal hormonal milieu and also directly detoxify any environmental agents responsible for breast cancer. It is hoped that present and future clinical trials will help to better elucidate the role for this agent in the chemoprevention of breast cancer.

Inhibitory Effect of Bifidobacterium longum on Colon, Mammary, and Liver Carcinogenesis Induced by 2-Amino-3-methylimidazo[4,5-/]quinoline, a Food Mutagen.

Reddy BS and Rivenson A. Cancer Research. 1993; 53: 3914-3918.

The inhibitory effect of lyophilized cultures of Bifidobacterium longum on 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced carcinogenesis was investigated in male and female F344 rats. Beginning at 5 weeks of age, male and female rats were divided into various experimental groups and fed one of the high-fat, semipurified diets containing 0 and 0.5% lyophilized cultures of B. longum with or without 125 ppm IQ in the diet. All animals were continued on this regimen until the termination of the study. All animals were necropsied during the 58th week. The results indicated that dietary B. longum significantly inhibited the IQ-induced incidence (percentage of animals with tumors) of colon (100% inhibition) and liver (80% inhibition) tumors and multiplicity (tumors/animal) of colon, liver, and small intestinal tumors in male rats. In female rats, dietary supplementation of Bifidobacterium cultures also suppressed the IQ-induced mammary carcinogenesis to 50% and liver carcinogenesis to 27% of those observed in animals fed the control diet, but the differences did not reach a statistical significance at P < 0.05; however, the mammary tumor multiplicity (tumors/animal) was significantly (P < 0.05) inhibited in female rats fed the diet containing Bifidobacterium cultures. These findings suggest that Bifidobacterium supplements in the diet inhibit IQ-induced colon and liver tumors and to a lesser extent mammary tumors in F344 rats.

Chemoprotection by sulforaphane: Keep one eye beyond Keap.
Myzaka MC and Dashwood RH. Cancer Letters; 2006, 233(2): 208-218
Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, with particularly high levels detected in broccoli and broccoli sprouts. Over a decade ago, this phytochemical was identified as a likely chemopreventive agent based on its ability to induce Phase 2 detoxification enzymes, as well as to inhibit Phase 1 enzymes involved in carcinogen activation. Considerable attention has focused on SFN as a ‘blocking' agent, with the ability to modulate the Nrf2/Keap1 pathway, but recent evidence suggests that SFN acts by numerous other mechanisms. SFN induces cell cycle arrest and apoptosis in cancer cells, inhibits tubulin polymerization, activates checkpoint 2 kinase, and inhibits histone deacetylase activity. The latter findings suggest that SFN may be effective during the postinitiation stages of carcinogenesis, as a ‘suppressing' agent. Moreover, pharmacological administration of SFN may be a promising therapeutic approach to the treatment of cancers, including those characterized by increased inflammation and involving viral or bacterial-related pathologies. The present review discusses the more widely established chemoprotective mechanisms of SFN, but makes the case for additional work on mechanisms that might be of importance during later stages of carcinogenesis, beyond Keap1.

Chemoprotective Glucosinolates and Isothiocyanates of Broccoli Sprouts: Metabolism and Excretion in Humans.
Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Cancer Epidemiology Biomarkers & Prevention; 2001, 10: 501-508
Broccoli sprouts are a rich source of glucosinolates and isothiocyanates that induce phase 2 detoxication enzymes, boost antioxidant status, and protect animals against chemically induced cancer. Glucosinolates are hydrolyzed by myrosinase (an enzyme found in plants and bowel microflora) to form isothiocyanates. In vivo, isothiocyanates are conjugated with glutathione and then sequentially metabolized to mercapturic acids. These metabolites are collectively designated dithiocarbamates. We studied the disposition of broccoli sprout glucosinolates and isothiocyanates in healthy volunteers. Broccoli sprouts were grown, processed, and analyzed for (a) inducer potency; (b) glucosinolate and isothiocyanate concentrations; (c) glucosinolate profiles; and (d) myrosinase activity. Dosing preparations included uncooked fresh sprouts (with active myrosinase) as well as homogenates of boiled sprouts that were devoid of myrosinase activity and contained either glucosinolates only or isothiocyanates only. In a crossover study, urinary dithiocarbamate excretion increased sharply after administration of broccoli sprout glucosinolates or isothiocyanates. Cumulative excretion of dithiocarbamates following 111-µmol doses of isothiocyanates was greater than that after glucosinolates (88.9 ± 5.5 and 13.1 ± 1.9 µmol, respectively; P < 0.0003). In subjects fed four repeated 50-µmol doses of isothiocyanates, the intra- and intersubject variation in dithiocarbamate excretion was very small (coefficient of variation, 9%), and after escalating doses, excretion was linear over a 25- to 200-µmol dose range. Dithiocarbamate excretion was higher when intact sprouts were chewed thoroughly rather than swallowed whole (42.4 ± 7.5 and 28.8 ± 2.6 µmol; P = 0.049). These studies indicate that isothiocyanates are about six times more bioavailable than glucosinolates, which must first be hydrolyzed. Thorough chewing of fresh sprouts exposes the glucosinolates to plant myrosinase and significantly increases dithiocarbamate excretion. These findings will assist in the design of dosing regimens for clinical studies of broccoli sprout efficacy.

Safety, Tolerance, and Metabolism of Broccoli Sprout Glucosinolates and Isothiocyanates: A Clinical Phase I Study.
Shapiro TA, Fahey JW, Dinkova-Kostova AT, Holtzclaw WD, Stephenson KK, Wade KL, Ye L, Talalay P. Nutrition and Cancer; 2006, 55(1): 53-62.

Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day acclimatization period on a crucifer-free diet, the broccoli sprout extracts were administered orally at 8-h intervals for 7 days (21 doses), and the subjects were monitored during this period and for 3 days after the last treatment. Doses were 25 μmol of glucosinolate (cohort A), 100 μmol of glucosinolate (cohort B), or 25 mol of isothiocyanate (cohort C). The mean cumulative excretion of dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8 ± 8.6% and 19.6 ± 11.7% of dose, respectively) and very much higher and more consistent in cohort C (70.6 ± 2.0% of dose). Thirty-two types of hematology or chemistry tests were done before, during, and after the treatment period. Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone, total triiodothyronine (T3), and free thyroxine (T4)] function were examined in detail. No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.