The bodies detoxification system is deivided into 3 phases (Phase I, II, and III). Phase I and II were delineated several decades ago and are fairly well understood when studied alone, but there were always problems in application to the body. Over the last decade, the third phase was described (mostly in the context of resistance to chemotherapeutics) and in this phase lies the keys to understaning systemic detoxification ability…or lack thereof. The synthesis I will present clarifies alot of confusion as to mechanism that has existed for years in alternative and progressive medical circles. The first installment will present a simple overview of the system with focus on the control that Phase III exerts over the whole system and how intestinal health in turn affects Phase III. The intestines are especially important in the context of mercury amalgam since large amounts of mercury are swallowed each day, coating the intestinal epithelia with inorganic mercury.

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(1). Ironically, exposure to certain toxins contributes to intestinal inflammation. For example, the corrosion of amalgam mercury results in mercuric mercury (HgII) release. When swallowed with saliva, HgII can cause intestinal inflammation and initiate this negative feedback(2).

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, preparing the toxin for conjugation to a hydrophilic biomolecule in Phase II. The conjugate is then moved through a series of Phase III 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 III transporters. When transporters down-regulate, Phase II activity, which is coupled to Phase III is also turned down(3). Phase I activity, however, does not get down-regulated. Phase I oxidation continues but is no longer coupled to Phase II conjugation.
Inhibiting glutathione activity in the intestines. Phase III transporters bring glutathione (GSH) into the intestines from the liver(4) GSH is the primary anti-oxidant for quenching free-radical reactions in the intestines(5). A deficiency of GSH is a symptom of inflammatory bowel diseases, including Crohn’s Disease(6). Thus down-regulation of Phase III transporters can be self-propagating as oxidative stress stops the flow of this crucial antioxidant.
Recent research at the Nestle Cancer Center in Switzerland8 examined genetic expression of the body’s detoxification pathways and found that the small intestine and the liver work together tightly to coordinate detoxification and metabolism. They also found that glutathione activity is predominantly modulated from the small intestine. This finding supports our model of Phase III transporters in the intestines controlling Phase II pathways and points to the centrality of the intestines in any detoxification protocol.

Cited Literature
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.; Ottenhoff, 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, O., 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. Borchers, A. T.; Selmi, C.; Meyers, F., J.; Keen, C. L.; Gershwin, M. E., Probiotic and Immunity. Journal of Gastroenterology 2009, 44, 26-46.
10. Summers, A. O.; Wireman, J.; Vimy, M. J.; Lorscheider, F. L.; Marshall, B.; Levy, S. B.; Bennett, S.; Billard, L., Mercury released from dental “silver” fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates. Antimicrobial Agents and Chemotherapy 1993, 37, (4), 825-834.
11. Horvath, K.; Perman, J. A., Autism and gastrointestinal symptoms. Current Gastroenterology Reports 2002, 4, (3), 251-258.
12. Holmes, A. S.; Blaxill, M. F.; Haley, B. E., Reduced levels of merucyr in first baby haircuts of autistic children. International Journal of Toxicology 2003, 22, 277-285.
13. Albert, A.; Pirrone, P.; Elia, M.; Waring, R. H.; Romano, C., Sulphation deficit in “low-funcitoning” autistic children: A pilot study. Biologoical Psychiatry 1999, 46, (3), 420-424.
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 MDCK distal tubular cells. Kidney International 2003, 63, 976-986.

This suite of analyses makes the former practice of “Challenge Testing” (taking a pharmaceutical chelating compound to increase urinary mercury elimination) obsolete. Challenge testing was truly a “black box” approach that did not reveal anything about the form of mercury present in the body, and worse still, the different agents used for challenge testing (EDTA, DMSA, DMPS) had very different efficiacies for different forms, leading to a very muddy interpretation of results. For example DMSA is not efficient for inorganic mercury and thus will only yield high results if there is alot of methylmercury present - thus a tuna-eater with no amalgams will show high while a fish-abstainer with a mouth full of amalgmas will show low, leading to a completely off-base analysis of mercury burden.

Challenge testing was also incorrectly promoted as an indicator of body burden beyond what non-challenged testing could offer; this idea seemed to persist despite clear research showing that the results reflected predominantly blood levels with a bit of kidney burden as well. If only using total mercury testing perhaps this was the best route, but with a full suite of speciation testing far more information is available than from a conventional challenge test, and the patient is not put through a potentially “challenging” procedure (i.e. if the kidneys are already damaged and not filtering well, why force more blood-borne mercury into them?…and if it does not come out the weakened kidneys, then where does it go?).

Keep tuned for more information on human biomonitoring with mercury speciation testing!

Thanks to Colorado Business Magazine for introducing us to our neighbors throughout the state of Colorado!

Stop by our booth and say hello!

Thank you to the Florida Department of Health for their feedback and support!

Dr. Shade and we at Quicksilver Scientific are looking forward to sharing our knowledge toward the betterment of human health!

Many believe the FDA classification will require patients to give “informed consent” before receiving mercury fillings in the future.

In the meantime, the FDA must change their distribution materials from endorsing amalgams to taking a more neutral stance. The ruling was made on Monday, June 2.

Mercury fillings, called dental amalgams, are 50% mercury by weight, and as shown in the popular IAOMT Smoking Teeth video, these fillings continuously release mercury vapor into the mouth.

Based on QS’s superior patented technology, the new biota method can provide researchers with highly accurate methylmercury and inorganic mercury data. This same method was utilized by Dr. Dan Cristol (College of William and Mary) to determine mercury species in spiders, a study that was recently published in “Science” (April 2008).

The biota method, developed by QS President Dr. Christopher Shade is titled “Automated simultaneous analysis of monomethyl and mercuric Hg in biotic samples by Hg-thiourea complex liquid chromatography following acidic thiourea leaching”.

The paper will be published in an upcoming issue of Environmental Sciences and Technology (ES&T) journal.

Read the abstract of the study, published by Dan Cristol (College of William and Mary) in the renowned journal Science.

MSNBC: One solution to pollution is not eating spiders

For more indepth coverage, see the Science Daily article, Mercury In River Moves Into Terrestrial Food Chain Through Spiders Fed To Baby Birds.