Mercury Challenge Tests: A Scientific Review PDF

CHALLENGE TESTS FOR MERCURY DOES THE “CHALLENGE TEST” REALLY SHOW YOU THE “BODY BURDEN” OF MERCURY?? For over two decades now, many clinical metals toxicologists have been relying on “challenge tests,” also called provocation tests, to diagnose mercury and other metal toxicities. The diagnostic prem...

CHALLENGE TESTS FOR MERCURY DOES THE “CHALLENGE TEST” REALLY SHOW YOU THE “BODY BURDEN” OF MERCURY?? For over two decades now, many clinical metals toxicologists have been relying on “challenge tests,” also called provocation tests, to diagnose mercury and other metal toxicities. The diagnostic premise of the testing is that it shows the “body burden” of the individual – that pool of deeply held metals that represents our lifetime accumulation of unexcreted metals. The literature examining the challenge tests ranges from the years 1991 through 2001 and has thus far failed to find any evidence of the challenge tests revealing any more than recent exposures, and in some instances (Frumkin et al, 2001) failing to see exposures made clear by ambient testing. Recently, challenge tests have come under fire from federal authorities as a diagnostic tool. The problem is not really that the challenge tests have no use (especially in the case of lead, where EDTA challenge testing is documented to have slightly better correlations with bone lead than a do blood lead measurements, or the case of gadolinium where levels in blood and urine are undetectable without EDTA provocation); the problem is instead the way they are generally used and interpreted. There are many practitioners who use the data from challenge tests in scientifically and clinically valid ways, but in general use the challenge test has three main flaws: 1. The propagation of the myth of a special relevance of the pool identified by the challenge (i.e. “body burden”) and the yes/no interpretation (i.e. “I found mercury in the patient”) 2. The use of a non challenged reference range to compare the challenged test to; this is probably the biggest problem from a regulatory standpoint since there is such obvious potential for over-treatment 3. The lack of standardization of the challenge conditions a. DMPS has very different strength and specificity than DMSA b. IV vs. oral administration has vastly different pharmacokinetics c. Use of adjuncts such as EDTA, glutathione, and glycine vastly changes the dynamics of the test and its output. The measurement of mercury in the body and extrapolation to body burden and toxic conditions is a very complicated field, requiring acute clinical discernment, including integration of patient history, current exposures, symptomology, and effect of comorbidities. The simplification and deification of the challenge test is no longer serving the evolution of the field of clinical metals toxicology, and it is now time for the adoption of better tools. At Quicksilver Scientific, we have develop advanced mercury testing that 1) identifies different sources of mercury by measuring the relative amounts of the two main forms of mercury in the body, methylmercury and inorganic mercury, and 2) quantifies excretion capabilities for those two forms. Unfortunately, instead of being welcomed by the community, there has been quite a bit of angry backlash and accusation, born mostly of a stubborn refusal to move forward. So to the question, “Does the challenge test really show you ‘body burden’ of mercury?”; let’s see what the scientific literature says... quicksilverscientific.com Quicksilver Scientific, Inc. 1376 Miners Dr. Ste 103 Lafayette, CO 80026 Article #1 – DMSA Challenge in Post-Industrial Exposure versus General Population Studies of DMPS show that there is a difference in urinary excretion between exposed and unexposed groups. In the Frumkin study, there was a difference between in excretion PRIOR to DMSA treatment (p values); however following treatment, there was none. Ambient levels were actually a BETTER predictor of past exposure than challenged levels. Also, in this study, there was no signal from amalgam surfaces during DMSA treatment. However, such a signal is clearly evident in studies with DMPS treatment. Discussion: Two main points come out of this study. One is the inability of the challenge test to show historical exposure, and this is with a group that was industrially exposed to extreme levels of mercury. The second point is the inequality of DMSA and DMPS. Though many people know that DMPS is stronger than DMSA, we have seen with mercury speciation analysis that DMSA biases toward methylmercury and DMPS biases toward inorganic mercury. quicksilverscientific.com Quicksilver Scientific, Inc. 1376 Miners Dr. Ste 103 Lafayette, CO 80026 Article #2 – DMPS Challenge in Short versus Long Term Occupational Exposure This DMPS study aimed to show long-term body burden in older dentists versus acute exposure in short-term factory workers. The test aimed to show long-term accumulation in dentists versus short-term acute exposure in industrial workers. The challenge test failed to show a different pattern than the pre-challenged testing of plasma and urine showed – i.e. the DMPS challenge just amplified previously-existing signals. Above: Linear correlation between pre-challenged urine and pre-challenged plasma quicksilverscientific.com Quicksilver Scientific, Inc. 1376 Miners Dr. Ste 103 Lafayette, CO 80026 Above: Linear Correlation between 300mg-PO DMPS-challenged urine and pre-challenged urine. Discussion: Clearly DMPS is very effective in mobilizing inorganic mercury, but the mobilization merely amplified a signal that existed in the ambient data. No “body burden” was revealed. quicksilverscientific.com Quicksilver Scientific, Inc. 1376 Miners Dr. Ste 103 Lafayette, CO 80026 Article #3 – DMSA Challenge in Post-Occupational Exposure Both blood and non-provoked urine show the differences in the populations, even three years after removal from the source. Pre- and Post-challenged urines were very well correlated. quicksilverscientific.com Quicksilver Scientific, Inc. 1376 Miners Dr. Ste 103 Lafayette, CO 80026 Article #4 – DMPS Challenge in Patients with Amalgam Fillings Discussion: DMPS challenge certainly shows recent loading, but fails to show difference between people who never had amalgam and people who formerly had amalgam and people who never had amalgam, thus failing to show historical exposure. A closer analysis of rate of excretion during chelation shows the difference between amalgam-free and amalgam removed, but this would not be obvious upon clinical observation. quicksilverscientific.com Quicksilver Scientific, Inc. 1376 Miners Dr. Ste 103 Lafayette, CO 80026