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About Life Extension
Established in 1980, the Life Extension Foundation is a 501 (c) (3) non profit organization dedicated to finding new scientific methods for eradicating old age, disease and death. The largest organization of its kind in the world, the Life Extension Foundation has always been at the forefront of discovering new scientific breakthroughs for use in developing novel disease prevention and treatment protocols to improve the quality and length of human life. Read More
At Metagenics, patient health is our greatest concern. Metagenics has built a reputation on nutraceuticals and medical foods that meet the high expectations of health care professionals worldwide. But what we care about most is serving the best interests of the patients who use our products and services with a goal of improving health and reversing chronic illness. Read More
About Pure Encapsulations
Pure Encapsulations was founded to formulate and manufacture the highest quality line of hypo-allergenic supplements available... Pure Encapsulations supplements are hypoallergenic. All two-piece capsules are hypoallergenic and vegetarian. There are absolutely no added coatings, binders, shellacs, artificial flavors, artificial sweeteners or colors, fragrance or excipients in our products that would disrupt or diminish the bioavailability of any of their ingredients. Read More
Zetpil-RX is the health care professional's top choice for highly absorbed suppository forms of DMSA, Glutathione, Amino Acids, Iron, and more. This method offers an effective solution for individuals that suffer from poor and/or inadequate intestinal absorption, or for those that are in a deteriorated state of health. Products support the Prostate, Brain & Memory, Stress Reduction, Detoxification, and a variety of nutritional deficiencies. Zetpil suppositories provide support for Diabeties, Heart Disease, Cancer, and so many other debilating dieases. Read More
IMD - Intestinal Metals Detox Protocol
IMD - Intestinal Metals Detox
A System for Removing Metals from the Intestines
and Catalyzing Whole Body Detoxification
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Quicksilver Scientific has developed an innovative supplement product known as IMD (Intestinal Metals Detox), designed to promote the safe and effective therapeutic detoxification of mercury and other toxic metals from the body. This proprietary compound "reboots" and optimizes key biological detoxification processes for the safe removal of metals through the intestines and reduces the liver and kidney stress common with pharmaceutical chelation therapy. IMD optimizes the natural action of glutathione in the intestines by using insoluble thiol groups to bind and remove heavy metals accumulated in the intestines and to directly quench free-radicals. IMD:
- Binds mercury and other heavy metals in the intestines and escorts these harmful contaminants out of the body.
- Intercepts methylmercury and other heavy metals trapped in enterohepatic circulation.
- Leads to lowering of blood mercury levels, allowing organ and tissue bound mercury to safely drain into the blood at a natural rate (Figure 2, page 5).
- mproves the body's natural detoxification ability by quenching free radicals and stopping metal- catalyzed free-radical reactions which can lead to inflammation and cause down-regulation of detox transporters (Phase 11/ transporters-OATs, cMOAT, MRPs, etc).
- Fortifies the link between the intestines and the immune system.
2.1 Active Chemistry of IMD
The Intestinal Metals Detox (IMD) is a proprietary formula that consists of highly purified silica with covalently attached metal-binding groups. Both the silica base and the binding agent are GRAS (generally recognized as safe) by the FDA for use in human food. The specific chemistry of the compound has several benefits over other detoxification remedies:
- The active binding groups out-compete other compounds for metals in the intestines.
- Because IMD does not enter the bloodstream, it will not lead to spikes in blood mercury levels or kidney/liver overload. In fact, preliminary data suggests increased liver functioning in some patients, as measured by changes in bilirubin levels.
- The chemistry of the attachment between binding groups and silica ensures the compound will not suffer significant breakdown in the intestines.
2.2 Disruptions in Natural Body-Wide Detoxification
Intestinal inflammation inhibits elimination of toxins by causing a strong down-regulation of the body's natural detoxification pathways. Ironically, exposure to certain toxins contributes to intestinal inflammation. For example, the corrosion of "silver" dental amalgam alloy results in mercuric mercury (Hg) release. When swallowed with saliva, Hg can cause intestinal inflammation and initiate this negative feedback.
Healthy Detoxification (Figure 1, left)
Detoxification processes occur throughout the body. A healthy detoxification pathway typically involves three phases. Phase I involves oxidative activation of a toxin. This prepares the toxin for conjugation to a hydrophilic bio-molecule in Phase II. The conjugate is then moved through a series of Phase II transporters, leading to intestinal or kidney excretion.
Impaired Detoxification (Figure 1, right)
Intestinal inflammation disrupts detoxification in two ways.
- Inhibiting the conjugation of toxins throughout the body and inhibiting transport of toxins into the intestines. Intestinal inflammation down-regulates Phase II transporters. When transporters down-regulate, Phase I activity, which is coupled to Phase III, is also turned down. Phase I activity, however, does not get down-regulated. Phase I oxidation continues but is no longer coupled to Phase I conjugation.
- Inhibiting glutathione activity in the intestines. Phase II transporters bring glutathione (GSH) into the intestines from the liver. GSH is the primary anti-oxidant for quenching free-radical reactions in the intestines. A deficiency of GSH is a symptom of inflammatory bowel diseases, including Crohn's Disease. Thus down-regulation of Phase II transporters can be self-propagating as oxidative stress stops the flow of this crucial antioxidant.
Recent research at the Nestle Cancer Center in Switzerland examined genetic expression of the body's detoxification pathways and found that the small intestine and the liver work together to coordinate detoxification and metabolism. The Nestle Center also found that glutathione activity is predominantly modulated from the small intestine. This finding supports our model of Phase II transporters in the intestines controlling Phase I pathways and points to the centrality of the intestines in any detoxification protocol.
3. Data Supporting IMD Safety and Efficacy
3.1 Historical Use of Insoluble Thiolated Compounds
The concept of an IMD-type product is not entirely new. It was successfully tested and used in the 1970's. However, absorbable chelators such as DMSA and DMPS received greater clinical exposure and were adopted by the medical community during the 1980's and 90's. The most researched version of an IMD-type product used in the 1970's took the form of thiolligand attached to a polymer backbone (polystyrene-divinyl-benzene - a polymerized organic solvent similar to toluene). This thiolated polymer resin (termed polythiol resin) was well-researched to prove safety and efficacy in animal and human studies. In fact, it was used during a mercury poisoning outbreak in Iraq. The Quicksilver innovation of a silicon dioxide (same formula as quartz) backbone for IMD provides a much more natural substrate for the human body that will not provoke a reaction from the immune system in the gut. Potential toxicity will be due to the thiol groups more than the backbone, so the toxicity studies on the polythiol resin outlined below apply to IMD.
3.1.1 Animal Safety Study
A safety study was conducted in 1973 by Schwetz et al. to evaluate the effects of the polythiol resin on embryonal, fetal and neonatal development in rats. The study evaluated doses of 150 and 1500 mg/kg/day (administered at various time periods to evaluate different periods of development). Assuming a 75 kg human, this is 11,250 mg per day at the low dose and 112,250 mg per day at the high dose. A normal dose of IMD is 100-200 mg and the density of silica is roughly 2X that of the polymer resin. A polymer resin has roughly 2X the amount of thiols per weight due to its higher volume, so 100mg of IMD has the equivalent volume and equivalent amount of thiol as 50mg polythiol resin. This makes the low dose of the safety study ~220 times the lower normal dosage of IMD and the high dosage in the study ~2200 times the lower normal dose of IMD. Despite the high dosing, the 150mg/kg/day dosage showed "no effect on the developing embryo, fetus, or neonate." The high dosing (2200X our dosing rate) showed some delay in ossification of skull bones but no teratogenic effects. Some effect is not surprising at this high dose.
3.1.2 Animal Efficacy Study
Effectiveness of the polythiol resin at lowering body burden of mercury was evaluated in a feeding trial where mice were injected with methylmercury and then fed a control diet or the same diet with polythiol resin added to it. After 42 days of resin treatment, mercury levels in blood, brain, kidney and liver had been reduced by a factor of 7.2,6.0,7.2 and 10.0 respectively. The comparison between treated and untreated animals is highlighted in the reproduced table below.
The reduction in organ levels points to the rapid redistribution of methylmercury that occurs throughout the body (quotes in panel to left). The mechanism of cleaning the blood through the intestines leads to efficient lowering of organ burdens as well.
The study also found that the resin reduces absorption of mercury in the diet by 50%, which has profound implications for prophylaxis of people with high-fish diets.
3.1.3 Human Use for Iraq Methylmercury Poisoning
The polythiol resin was used to treat human subjects during the methylmercury poisoning outbreak of 1971-72, where homemade bread was made from wheat treated with a methylmercury fungicide. 11 The efficacy was judged against absorbable chelators DMPS (dimercapto propane sulfonate), PEN (D-penicillamine), and NAP (n-acetyl-DL-penicillamine). The results (reproduced at left) showed a -3-fold lowering of methylmercury of the animal study, we can presume that this lowering of life in the blood. Based on the findings methylmercury also occurs in the brain/organs. The polythiol resin outperformed PEN and NAP. It also compared favorably with DMPS (the most powerful, but also the most aggressive and potentially nephrotoxic mercury chelator).
3.2 Recent Results with Silica-based Thiol - IMD
Small-scale clinical trials and case studies with IMD provide results consistent with the Iraq polythiol trial, however at a ~10 to 100 fold lower dosage. Iraq poisoning dosage ranged from 2,250 to 16,500 mg/day for a 75-kg person. Typical IMD use is only 100-200mg/day. This increase in efficacy is made possible by the unique proprietary thiol group linked to the silica particle.
3.2.1 Half-life Lowering with IMD.
Half-life of MeHg was measured after a single dose of high-Hg fish. With a dosage of 200mg/day of IMD, the half life was measured at 17 days and the time back to baseline at 40 days. This compares with an untreated half-life of 60 days and a polythiol resin treatment half-life of 19 days (Iraq study). A study of fish-mercury half-life done by Clarkson 12 shows a half-life of 44-64 days and a time to baseline of 160 days after a single dose of high-Hg fish. IMD is showing a roughly 4 fold increase in depuration rate in comparison to no treatment.
3.2.2 Short-Term Clinical Use
Small-scale clinical trials were conducted with patients undergoing dental amalgam revision. In Clinic 1, after 7-10 days of treatment with IMD, patients experienced an average 23.9% decrease in total blood mercury (Table 1 at left). Very little change is seen in people who did not use IMD. This period of rapid decay in blood level is usually followed by a slower decay as the body re- equilibrates and releases mercury from both intracellular and extracellular spaces into the blood.
3.2.3 Long-term Use - Case Studies
Long-term data from Dr. Christopher Shade shows that IMD use combined with dental revision steadily decreases methyl (MeHg) and inorganic mercury (Hg) blood levels over a period of months. Blood Hg shows a two-phase reduction featuring a rapid initial decrease followed by slower decrease (Figure 2). Fecal excretion data (not shown) reveals release and excretion from bodily stores (from 1/30th to 1/10th of the blood burden of MeHg excreted per day). Blood MeHg levels constantly equilibrate with (and track) the body burden, which is consistent with other reports.
These decreases are especially significant when comparing these results to a large-scale baseline study of patients undergoing dental revision without any detoxification. This study showed that total blood mercury levels did not decrease following revision. Dental revision actually promoted an increase in MeHg over time (Figure 3), whereas patients who did not undergo dental revision had stable levels of blood MeHg and Hg. The increase in blood MeHg after revision is consistent with our model: Following removal of the intestine's irritating mercury source (i.e. amalgam), activity of Phase I enzyme Glutathione S-Transferase increases and moves mercury out of cells into the bloodstream. Unfortunately, enterohepatic circulation prevents it from leaving the body.
Other Long-Term Case Studies:
Several hundred patients have now used IMD during long-term detoxification. Monitoring data from three of the initial patients is shown to the left.
Patient #1 was a long-time fish consumer that had amalgams for most of her life - they were removed several years before the detox. She ceased fish consumption during the detox and her MeHg levels fell -70% over three months.
Patient #2 still had dental amalgams and ate a lot of fish. He neither removed his amalgams nor ceased fish consumption, yet still managed to have a 30% decrease in MeHg over 6 months of use.
Patient #3 had amalgams and ate large amounts of tuna salad. With removal of his amalgams and cessation of fish consumption, he achieved an 80% removal of MeHg and 90% removal of Hgl/ in 6 months.
3.2.4 Evidence for Opening of Phase II Transporters with IMD
Bilirubin is a by-product of hemoglobin breakdown. Accumulation of bilirubin in the blood is the cause of jaundice and is generally considered to be a sign of poor liver function. Extensive experimentation demonstrates that the major problem associated with bilirubin excretion is the failure of Phase II transporters to move the conjugated bilirubin from the liver into the intestines. This is the same transporter that moves glutathione and glutathione conjugates (including mercury glutathione) into the intestines and sulfate conjugates into the urine. There is abundant anecdotal evidence of a connection between mercury toxicity and bilirubin buildup. This anecdotal connection is seen on Gilbert Syndrome Web Forums, where flare-ups of GS are cited after amalgam placements or unprotected amalgam removals.
In the IMD trials conducted on patients with recent dental revision, there has been rapid and dramatic lowering of blood bilirubin in those with elevated levels of this compound. This data supports the model demonstrating that IMD opens Phase II transporters and consequently up-regulates Phase /I conjunctions. According to the model, Phase II transporters up-regulate as a result of the reduced amount of inflammation and toxic metals present in the gut (Figure 1, Page 2). Because of these broad-spectrum effects on the whole detoxification system, many practitioners are using IMD outside the scope of metals-specific detoxification. IMD is now becoming an important component in whole-body/general detoxification protocols.
Quicksilver Scientific does not imply that IMD will cure any disease. This document is designed to aid health practitioners by synthesizing multiple studies on human detoxification pathways. Cited references and further information on our clinical studies, received testimonials and plans for future studies are available upon request.
1. Kalitsky-Szirtes, J.; Shayeganpour, A.; Brocks, D. R; Piquette-Miller, M., Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metabolism and Disposition 2004,32, (1),20-27.
2. Nadarajah, V.; Neiders, M. E.; Aguirre, A; Cohen, R E., Localized cellular inflammatory responses to subcutaneously implanted dental mercury. Journal of Toxicology and Environmental Health 1996, 49, (2), 113-126(14).
3. Cnubben, N. H. P.; Rietjens, I. M. C. M.; Wortelboer, H. M.; van Zanden, J.; van Bladeren, P. J., The interplay of glutathione-related processes in antioxidant defense. Environmental Toxicology and Pharmacology 2001, 10, 141-152.
4. Oude Elferink, R J. P.; OUenhoff, R; Liefting, W.; de Haan, J.; Jansen, P., L.M., Hepatobiliary transport of glutathione and glutathione cojugate in rats with hereditary hyperbilirubinemia. Journal of Clinical Investigation 1989, 84, 476-483.
5. Martensson, J.; Jain, A; Meister, A., Glutathione is required for intestinal function. Proceding of the Natural Academy of Sciences 1990, 87, 1715-1719.
6. Sido, B.; Hack, V.; Hochlehnert, A; Lipps, H.; Herfarth, C.; Droge, W., Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut 1998, 42, 485-492.
7. Ruemmele, F. M.; Bier, D.; Marteau, P.; Rechkemmer, G.; Bourdet-Sicard, R; Walker, W. A; Goulet, 0., Clinical evidence for immunomodulatory effects of probiotic bacteria. Journal of Pediatric Gastroenterology and Nutrition 2009, 48, 126-141.
8. Much, D. M.; Crespy, V.; Clough, J.; Henderson, C. J.; Lariani, S.; Mansourian, R; Moulin, J.; Wolf, R; Williamson, G., Hepatic cytochrome P-450 reductase-null mice show reduced trascriptional response to quercetin and reveal physiological homeostasis between jejunum and liver. American Journal of Physiology - Gastrointestinal and Liver Physiology 2006,291, G63-G72.
9. Schwetz, BA; Spencer HC; Gehring PJ, A study of prenatal and postnatal toxicityof a sulfhydryl resin in rats. Toxicology and Applied Pharmacology 1974,27,621-628.
10. Clarkson, TW; Small, H; Norseth, T, Excretion and absorption of methyl mercury after polythiol resin treatment. Archives of Environmental Health 1973, 26, 173-176.
11. Clarkson, TW; Magos, L.; Cox, C.; Greenwood, MR; AMin-Zaki, L; Majeed, MA; AI-Damluji., K; Test of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak. Journal of Pharmacology and Experimental Therapeutics 1981, 218, (1), 74-83.
12. Kershaw, TG; Dhahir, PH; Clarkson, TW, The relationship between blood levels and dose of methylmerucry in man. Archives of Environmental Health 1980, 35(1),28-36.
13. Berglund, F; Berlin, M, Risk of methylmercury cumulation in man and mammals and the relation between body burden of methyl mercury and toxic effects, in Miller M, Berg GG (eds): Chemical Fallout. Springfield, IL, Charles Thomas Publisher, 1969, p. 258.
14. Halbach, S.; Vogt, S.; Kohler, W.; Felgenhauer, N.; Welzl, G.; Kremers, L.; Zilker, T.; Melchart, D., Blood and urine mercury levels in adult amalgam patients of a randomized controlled trial: Interaction of Hg species in erythrocytes. Environmental Research 2008,107,69-78.
15. Wortelboer, H. M.; Balvers, M. G. J.; Usta, M.; van Bladeren, P. J.; Cnubben, N. H. P., Glutathione-dependent interaction of heavy metal compounds with multidrug resistanc proteins MRP1 and MRP2. Environmental Toxicology and Pharmacology 2008,26, 102-108.
16. Ng, K. H.; Lim, B. G.; Wong, K. P., Sulfate conjugating and transport functions of MOCK distal tubular cells. Kidney International 2003, 63, 976-986.
IMD Pro Strength Intestinal Cleanse binds heavy metals in the gut, both ingested and excreted by the body with bile, to safely eliminate via the bowels. Neutralizes and prevents absorption of the heavy metals and free-radical generation catalyzed by them.
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Quicksilver Scientific Vitamin C and R Lipoic Acid Drops with Etheric Delivery Phospholipid Encapsulation System, 1.7 oz Bottle
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Clear Way Cofactors Proprietary blend of phytoextracted polyphenolics, sodium buffered R-Alpha Lipoic Acid, targeted vitamins, selenium, standardized kelp extract and high-potency Lumbrokinase designed to maximize metal detoxification pathways.
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Quicksilver Scientific EDTA and R-Lipoic Acid with Etheric Delivery Phospholipid Encapsulation System, 4 oz Liquid
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IMD Intestinal Cleanse binds heavy metals in the gut (ingested metals and metals excreted by the body with the bile) to safely eliminate with the bowels. Neutralizes and prevents absorption of the heavy metals and free-radical generation catalyzed by them
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