Flame Retardants: Dangerous chemical now in breast milk
06 December 2007
Flame retardant chemicals, which are in household furniture, textiles and electronic equipment, have found their way into human breast milk. Scientists aren’t sure how this may affect the developing child, but it’s feared it may cause neurological problems and disrupt thyroid function.
One study has found that the level of the retardant PBDE (polybrominated diphenyl ethers) has increased 200 times in breast milk in women in North America, while another study in Sweden has discovered the level has increased 60 times in a span of 25 years.
PBDEs have regularly been included in a range of household and office items since the 1970s, but scientists have only recently discovered just how dangerous the chemical can be. Regulators across Europe and the US have banned some elements of the chemical, and the brominated mix will be removed under new legislation that comes into force in 2008.
But items of furniture and furnishings that contain the original compound are still in millions of homes. Unlike other pollutants such as PCBs and DDT, the PBDEs particularly affect infants. Scientists have found a direct link between breast milk and household dust, and they estimate that toddlers’ exposure to PBDEs from household dust is 100 times greater than that for adults because of breast milk and more hand-to-mouth contact.
(Source: The Lancet, 2007; 370: 1813-4)
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Detoxification – for Your Health
Stimulating your detoxification systems can be done through a number of nutrients.
phase 1 Stimulation
· Thngeretin (from tangerines)
· Riboflavin and carotenoids (such as beta-carotene, alpha-carotene, lycopene, lutein, and astaxanthin)
Phase 1 stimulation can render some chemicals toxic – the following nutrients protect against this toxicity.
phase 1 Inhibition
· Hesperidin (oranges)
· Naringenin (grapefruit)
· Resveratrol (grape skins)
· Quercetin (onions, teas, apples, and most vegetables)
· Apigenin (celery, parsley, and ginkgo biloba)
· Ferulic acid (fruits)
· Chlorogenic acid (Mackintosh apples, blueberries, eggplant)
phase 2 Stimulation
· Indole-3-carbinol (broccoli, Brussels sprouts and other cruciferous vegetables)
· Isothiocyanates and sulforaphane (broccoli and Brussels sprouts)
· Thurine (an amino acid – available as a supplement)
· Glutathione (supplied by N-acetyl L-cysteine, ellagic acid and alpha-lipoic acid – all
available as supplements)
· Glycine (an amino acid supplement – high intakes can cause excitotoxicity)
· MSM (methylsulfonylmethane – a supplement)
· Quercetin (teas, onions, cranberries, and most vegetables)
Stinlulation for Both Phase 1 and phase 2
· Curcumin (from the spice turmeric, also a supplement)
· Astaxanthin and canthaxanthin (from all vegetables and fruits and also available as a supplement called mixed carotenoids
Six Additional Supplements That Improve Liver Health
Your liver plays a crucial role in your overall health. Here are nutrients that focus on protecting the liver.
· Lecithin (phosphatidylcholine)
· Curcumin also protects the liver from free radical damage and improves bile flow
· Alpha-lipoic acid has been shown to protect the liver from some extremely powerful toxins and from hepatitis C and A damage.
· Silymarin (extracted from the milk thistle plant) protects the liver and brain and stimulates liver regeneration.
· Vitamin C (as magnesium ascorbate) protects the liver from free radical damage
· Magnesium protects the liver from free radicals and inflammation and increases glutathione levels
THE LIVER AND DETOXIFICATION
The liver keeps us clean on the inside and prevents dangerous chemicals from penetrating their way deeper into our bodies. The liver is the gateway to the body and in this day and age has an enormous workload that frequently overloads its detoxification systems. The liver must cope with every toxic chemical in our food chain as well as excessive amounts of unhealthy fats and animal protein that are ubiquitous in fast foods. Let us examine in more detail the mechanisms by which the liver keeps our internal body clean.
THE LIVER FILTER
If we examine the liver under a microscope we see rows of liver cells separated by spaces called sinusoids. Sinusoids are structured like a filter or sieve through which the blood stream is filtered. During this process the filter removes unwanted particulate matter, microorganisms and metabolic waste products. These noxious thing are ingested by specialized cells in the sinusoids called “Kupffer cells” which break down and destroy these things, rendering them harmless. The sinusoids and Kuffer cells are like a “garbage disposal unit” inside the liver. Thus you can see that the liver is the filter and cleanses the blood stream which is of vital importance.
Inside the liver cells (hepatocytes) we find sophisticated enzyme pathways or chemical pathways that have evolved over millions of years, to breakdown toxic substances. Every drug, artificial chemical, pesticide and hormone is broken down or metabolized by these pathways inside the liver cells. Basically there are two major detoxification pathways inside the liver cells which are called the Phase One and Phase Two pathways.
This is called the cytochrome P450 enzyme system where a liver cell takes a toxic chemical and through a process of oxidation, reduction, hydrolysis or hydroxylation turns it into a less harmful substance. During this process oxygen free radicals are generated, so there is a need for antioxidants, especially Vitamin C, to prevent cellular damage. For efficient phase one detoxification to occur the liver requires adequate amounts of the nutrients selenium, folic acid, vitamins B2, B3, B6, phophatidyl choline and bioflavonoids. If these nutrients are lacking, toxic chemicals will become far more dangerous. Fast foods and processed foods are deficient in these vital liver nutrients. Thus although many people are over-eating they are still suffering with malnutrition which exacerbates toxic overload. Dr. Sandra Cabot’s Liver Cleansing Diet reduces the toxic load on the liver and also provides the vital nutrients required by the liver for detoxification.
This is called the conjugation pathway whereby the liver cells add either a glycine or sulphate molecule to a chemical to make it water soluble. It can then be excreted from the body via fluids such as urine or bile. Through conjugation the liver is able to turn drugs (xenobiotics and hormones), neurotransmitters and phenolic compounds into excretable substances. For efficient phase two detoxification the liver requires Vitamin E, carotene, sulphur containing amino acids (taurine, methionine, cysteine), glycine, glutamine, choline and inositol. Cruciferous vegetables (cabbage, cauliflower, broccoli, brussel sprouts) are a good source of natural sulphur compounds for the liver. These things can spike up and support the phase two detoxification system. The liver cleansing diet has been designed to support and enhance the phase one and two liver detoxification systems. If the phase one and two detoxification pathways become overloaded, there will be a build up of toxins in the body. Many of these toxins are fat soluble and incorporate their way into the fatty cell membranes where they may stay for years, if not a lifetime. Some of these toxins, such as pesticides, petrochemicals and aspartame are highly toxic to the nervous system and endocrine glands producing chronic neurological and hormonal dysfunction. They are also carcinogenic and have been implicated in the rising incidence of breast, prostrate and brain cancer. If the filtering and/or detoxification system in the liver are inefficient this will cause harmful substances and micro-organisms to build up in the blood stream. This will increase the workload of the immune system, which may then become overloaded and hyperstimulated. This often is so in symptoms of immune dysfunction such as allergies, inflammatory states, recurrent infections, swollen glands, chronic fatigue or auto-immune disease. These disorders are very common today and usually get treated on a symptomatic basis with drugs. Unfortunately thousands of people visit doctors everyday complaining of these symptoms and rarely does anyone think of the liver. The simplest and most effective way to take the load off the immune system, is to improve liver function. Dr. Sandra Cabot has been able to help many people with chronic immune and liver dysfunction through her LIVER CLEANSING DIET BOOK. In this book she fully explains that you cannot have a healthy immune system if your liver is dysfunctional. This is a revelation for millions of people struggling with poor health. Should the reader be interested, Dr. Cabots book may be ordered by calling 1-888-782-7014.
The Liver Doctor
Calcium-D-glucarate is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans. Glucaric acid is also found in many fruits and vegetables with the highest concentrations to be found in oranges, apples, grapefruit, and cruciferous vegetables. (1) Oral supplementation of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microflora and involved in Phase II liver detoxification. Elevated beta-glucuronidase activity is associated wire an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers. (2) Other potential clinical applications of oral calcium-D-glucarate include regulation of estrogen metabolism and as a lipid-lowering agent.
Upon ingestion and exposure to the acidic environment of the stomach, calcium-D-glucarate is metabolized to form D-glucaric acid. D-glucaric acid is further metabolized in the gastrointestinal tract into three compounds existing in equilibrium and comprised of approximately 40-percent D-glucaric acid, 30-percent D-glucaro-1,4-lactone, and 30-percent D-glucaro-6,3-lactone. These compounds are then transported to the blood and various internal organs, and are subsequently excreted in the urine and bile. Although D-glucaro-1,4-lactone seems to be the most pharmacologically active of the three, it is not commercially available. Also, calcium-D-glucarate administration results in longer inhibition of beta-glucuronidase (five hours versus one hour) than does D-glucaro-1,4-lactone, so it is the compound used. (3)
Mechanism of Action
Calcium-D-glucarate’s detoxifying and anticarcinogenic properties are attributed to its ability to increase glucuronidation and excretion of potentially toxic compounds. During Phase II detoxification, chemical carcinogens, steroid hormones, and other lipid-soluble toxins are conjugated with glucuronic acid in the liver (glucuronidation), and excreted through the biliary tract. Beta-glucuronidase is capable of deconjugating these potential toxins, making it possible for them to be reabsorbed rather than excreted. D-glucaro-1,4-lactone is the metabolite that has been shown to inhibit beta-glucuronidase activity, increasing excretion of conjugated xenobiotic compounds and decreasing activity of harmful substances that are most active in their deconjugated state. (4,5) Inhibition of beta-glucuronidase ultimately results in potentially decreasing the risk of carcinogenesis. (6) In addition, by reducing the beta-glucuronidase viability and activity of intestinal bacteria, salts of D-glucaric acid have been shown to enhance enterohepatic circulation and reduce steady state levels of cholesterol synthesis, resulting in decreased serum lipid levels. (7)
Calcium-D-glucarate is not an essential nutrient so, technically, no deficiency state exists. However, since it is only produced in small amounts by humans, it is important that dietary intake be adequate. Diets low in fruits (particularly oranges, apples, and grapefruit) and cruciferous vegetables (broccoli, cabbage, and brussel sprouts) may result in a relative deficiency of calcium-D-glucarate and its metabolites. Research has shown a low level of D-glucaric acid correlates with a higher level of beta-glucuronidase, which in turn is associated with an increased risk for various cancers. (2)
The anticarcinogenic properties of D-glucaric acid and its salts have been studied in various animal tumor models, including colon, (8,9) prostate, (2) lung, (10) liver, (11,12) skin, (13) and breast (14-18) cancer, with the mechanism of action for tumor inhibition being very similar in each. These studies demonstrated decreases in beta-glucuronidase activity, carcinogen levels, and tumorigenesis. The preponderance of research, however, has been conducted on mammary tumors in the rat, the animal model most frequently used for breast cancer research.
A number of studies have shown calcium-D-glucarate alone, and in combination with retinoids, inhibits mammary carcinogenesis in rats by as much as 70 percent. (3) Natural retinoids have been shown to be effective chemopreventive agents at high doses, but unfortunately the cumulative toxic effects of high doses have restricted their prolonged use. Several studies have demonstrated low-dose retinoids in combination with calcium glucarate interact synergistically to inhibit mammary tumor growth in both animal models and human cell lines. (14-18) The mechanisms responsible for the chemopreventive effects of these two agents may be similar. Both retinoids and calcium-D-glucarate inhibit carcinogenesis during the promotion and initiation phases. Calcium-D-glucarate inhibits protein tyrosine kinase-C activity and induces transformation growth factor beta, possibly resulting in an increase in cellular differentiation and slower progression through the cell cycle. (15) Retinoids induce many of these same biochemical effects. (19) Additionally, calcium-D-glucarate enhances glucuronidation and subsequent excretion of carcinogens and other cancer-promoting agents.
Published human studies on calcium-D-glucarate and breast cancer are few but, due to the encouraging results of the animal studies, the National Cancer Institute has initiated a Phase I trial in patients at high risk for breast cancer at Memorial Sloan Kettering Cancer Center. This trial is examining the use of calcium-D-glucarate as an alternative to tamoxifen’s blocking of estrogen receptors. Preliminary results are quite encouraging and due to calcium-D-glucarate’s excellent safety profile, it may be a more effective option than tamoxifen, which has numerous side effects. (3) Other human trials are being conducted at M.D. Anderson Cancer Center in Houston, Texas and AMC Cancer Research Center in Denver, Colorado.
Studies in rats have shown D-glucarate salts to inhibit colon carcinogenesis alone and in combination with 5-fluorouracil (5-FU). In one study, D-glucarate markedly inhibited azoxymethane-induced colon carcinogenesis as evidenced by a 60-percent reduction in both tumor incidence and multiplicity. It was hypothesized that malignant cell proliferation was suppressed by inhibition of beta-glucuronidase. Another possible mechanism may involve alterations in cholesterol synthesis or its conversion to bile acids. (8) The second study demonstrated that salts of D-glucarate, in combination with 5-FU in rat colon tumor explants, resulted in a potentiation of 5-FU’s antitumor activity. D-glucarate alone also showed antitumor activity. (9)
Hepatocarcinogenesis is thought to be preceded by premalignant hepatic foci that are subsequently transformed to malignant cells. Two separate rat studies by a group of researchers at Ohio State University have demonstrated calcium-D-glucarate delays the appearance of altered hepatic foci and significantly inhibits hepatocarcinogenesis, if given during both the initiation and promotion phases. Maximal inhibition was obtained when calcium-D-glucarate was administered by gavage prior to the carcinogenic agent, diethylnitrosamine. (11,12)
A study conducted on mice demonstrated calcium-D-glucarate inhibits benzo[a]pyrene’s ability to bind DNA and induce pulmonary adenomas. (10) Another unpublished phase I clinical trial of 62 patients found D-glucaric acid levels were approximately 29-percent lower in smokers than non-smokers. Regardless of gender, K-ras (an oncogene linked to lung cancer) mutations were found to be present in 38 percent of subjects who smoked, while no K-ras mutations were found in the non-smoking control subjects. It was hypothesized that D-glucaric acid deficiency correlates with K-ras mutations and might be indicative of a higher risk for developing lung cancer. (20)
The efficacy of dietary calcium-D-glucarate as a chemopreventative agent has also been studied in the mouse skin tumorigenesis system. Mice were given 7,12-dimethylbenz[a]anthracene (DMBA) to induce skin tumorigenesis and were fed either a regular chow diet or a chow diet fortified with calcium-D-glucarate. When fed the calcium-D-glucarate chow through both the initiation and promotion phases, papilloma formation was inhibited by over 30 percent. The data indicate that supplementation of calcium-D-glucarate results in a marked alteration in the retention, activity, and metabolism of carcinogenic substances. (13)
Calcium-D-glucarate’s inhibition of beta-glucuronidase activity allows the body to excrete hormones such as estrogen before they can become reabsorbed. Oral administration of large doses of calcium-D-glucarate have been shown to lower serum estrogen levels in rats by 23 percent. (21) Because many breast cancers are estrogen-dependent, calcium-D-glucarate’s ability to affect estrogen and other hormone levels has led to Phase I clinical trials at several major cancer centers in the United States. Results of these studies are pending.
Side effects of currently available hypolipidemic agents present a need for safe and effective lipid-lowering agents. D-glucarates have been shown to significantly reduce total serum cholesterol in rats by as much as 12-15 percent and LDL-cholesterol by 30-35 percent. Preliminary results in humans show D-glucarate reduced total serum cholesterol up to 12 percent, LDL-cholesterol up to 28 percent, and triglycerides up to 43 percent. The lipid-lowering effect of calcium-D-glucarate may be attributed to improved enterohepatic circulation, resulting in increased excretion of bile acids and a reduction in steady state levels of cholesterol biosynthesis. (7)
There are no known drug interactions with calcium-D-glucarate, but many drugs and hormones are metabolized in the liver via glucuronidation. Therefore, taking calcium-D-glucarate may increase elimination of these substances, possibly reducing their effectiveness.
Side Effects and Toxicity
No adverse effects have been observed after prolonged feeding to rats or mice at concentrations of 70, 140, or even 350 mmol/kg. (6) Preliminary results of clinical trials in humans have shown calcium-D-glucarate is without adverse effects.
The recommended oral dosage of calcium-D-glucarate is generally in the range of 1500-3000 mg daily. Until human trials have been completed the optimal dosage remains elusive.
(1.) Dwivedi C, Heck WJ, Downie AA, et al. Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol 1990;43:83-92.
(2.) Walaszek Z, Szemraj J, Narog M, et al. Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. Cancer Detect Prev 1997;21:178-190.
(3.) Heerdt, AS, Young CW, Borgen PI. Calcium glucarate as a chemopreventive agent in breast cancer, Isr J Med Sci 1995;31:101-105.
(4.) Horton D, Walaszek Z. Conformations of the D-glucarolactones and D-glucaric acid in solution. Carbohydr Res 1982;105:95-109.
(5.) Walaszek Z, Hanausek-Walaszek M. D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on biliary excretion of beta-glucuronidase after oral administration in rats. Hepatology 1988;9:552-556.
(6.) Selkirk JK, Cohen GM, MacLeod MC. Glucuronic acid conjugation in the metabolism of chemical carcinogens by rodent cells. Arch Toxicol 1980;139:S171-S178.
(7.) Walaszek Z, Hanausek-Walaszek M, Adams AK, Sherman U. Cholesterol lowering effects of dietary D-glucarate. FASEB 1991;5:A930.
(8.) Yoshimi N, Walaszek Z, Moil H, et al. Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate. Int J Oncol 2000;16:43-48.
(9.) Schmittgen TD, Koolemans-Beynen A, Webb TE, et al. Effects of 5-fluorouracil, leucovorin, and glucarate in rat colon-tumor explants. Cancer Chemother Pharmacol 1992;30:25-30.
(10.) Walaszek Z, Hanausek-Walaszek M, Webb TE. Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis. Cancer Lett 1986;33:25-32.
(11.) Oredipe OA, Barth RF, Hanausek-Walaszek M, et al. Effects of an inhibitor of beta-glucuronidase on hepatocarcinogenesis. Proc Am Assoc Cancer Res 1987;28:156.
(12.) Oredipe OA, Barth RF, Hanausek-Walaszek M, et al Effects of calcium glucarate on the promotion of diethylnitrosamine-initiated altered hepatic loci in rats. Cancer Lett 1987;38:95-99.
(13.) Dwivedi C, Downie AA, Webb TE. Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate. J Environ Path Toxicol Oncol 1989;9:253-259.
(14.) Abou-Issa H, Koolemans-Beynen A, Meredith TA, Webb TE. Antitumour synergism between non-toxic dietary combinations of isotretinoin and glucarate. Eur J Cancer 1992;28:784-788.
(15.) Webb TE, Abou-Issa H, Stromberg PC, et al. Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate:retinoid combination. Anticancer Res 1993; 13:2095-2100.
(16.) Bhatnagar R, Abou-Issa H, Curley RW, et al. Growth suppression of human breast carcinoma cells in culture by N-(4-hydroxyphenyl) retinamide and its glucuronide and through synergism with glucarate. Biochem Pharmacol 1991 ;41:1471-1477.
(17.) Curley RW, Humpries KA, Koolemans -Beynan A, et al. Activity of d-glucarate analogues: synergistic antiproliferative effect in cultured human mammary tumor cells appear to specifically require the d-glucarate structure. Life Sci 1994;54:1299-1303.
(18.) Abou-Issa H, Moeschberger M, Masry EI, et al. Relative efficacy of glucarate on the initiation and promotion phases of rat mammary carcinogenesis. Cancer Res 1995;15:805-810.
(19.) DeLuca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 1991;5:2924-2933.
(20.) Walaszek Z, Raich PC, Hanausek M, et al. Role of D-glucaric acid in lung cancer prevention. Unpublished research. AMC Cancer Research Center, Denver, CO.
(21.) Walaszek Z, Hanausek-Walaszek M, Minto JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis 1986;7:1463-1466.
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