Chelation to test for toxic metals? Read this first.

Whatever their persuasion, doctors have to be alert to the hazards of cognitive dissonance and confirmation bias (automatic opposition to views that differ from one's dogma, ignoring data contrary to prejudice ). For some practitioners the evidence against using  chelation to test for toxic metals such as mercury may require a hard swallow. What does the science show?One study published in the journal Annals of Clinical Biochemistry first notes...

"Oral chelation tests have been used to try to define mercury toxicity in individuals with dental amalgams, who are suffering from a variety of non-specific symptoms."

In their study healthy individuals submitted to an oral chelation challenge with DMSA (dimercaptosuccinic acid). The result was an elevated excretion of mercury giving the false impression of toxicity inconsistent with their healthy condition. Moreover, one study volunteer suffered a serious reaction (more on this at the end of the post). The authors concluded:

"The oral chelation test using DMSA may lead to misleading diagnostic advice regarding potential mercury toxicity and can be associated with serious side effects."

The authors of another paper published in the journal Environmental Health Perspectives set out to answer the question 'is a diagnostic chelation challenge with DMSA a reliable indicator of long-term mercury toxicity?'

"This study assessed diagnostic chelation challenge with dimercaptosuccinic acid (DMSA) as a measure of mercury body burden among mercury-exposed workers."

Their data painted a very clear picture:

"There was no association between past occupational mercury exposure and the urinary excretion of mercury either before or after DMSA administration. There was also no association between urinary mercury excretion and the number of dental amalgam surfaces..."

This doesn't mean that dental amalgams are good for you, but it shows that a chelation challenge is not the tool to find out how you're handling them. In their conclusion they pinpoint the reason why the results of a chelation challenge can be completely misleading as to the actual body burden of the metals in question:

"We believe the most likely reason that DMSA chelation challenge failed to reflect past mercury exposure was the elapsed time (several years) since the exposure had ended. These results provide normative values for urinary mercury excretion both before and after DMSA challenge, and suggest that DMSA chelation challenge is not useful as a biomarker of past mercury exposure."

The authors of a study published in the Archives of Pathology & Laboratory Medicine weigh in with their findings that compare DMSA challenge in fish eaters and non-fish eaters, all of whom were doctors in good health. The baseline (pre-DMSA) levels of mercury excretion, and the post-DMSA levels corresponded to the immediate amount of mercury in the blood (recent fish dinners), leading to their conclusion:

"In this study of healthy physicians, oral DMSA produced a rise in urine mercury excretion both in non–fish eaters and fish eaters. The increase in chelated mercury excretion was higher in fish eaters. A simple rise in chelated mercury excretion over baseline excretion is not a reliable diagnostic indicator of mercury poisoning."

Annals of Internal Medicine published this letter that explains the chemistry behind the misleading elevation in provoked chelation specimens:"Both EDTA and DMPS attach to divalent cations, such as lead and mercury, trace amounts of which circulate harmlessly in the blood. This causes them to be excreted. Provocation has been shown to artificially increase the 24-hour average urine mercury...Because most extra excretion occurs toward the beginning of the test, one can extrapolate that provoked levels would be 2 to 3 times higher than baseline levels if only a 6-hour collection period had been used. Reference ranges for provoked specimens do not exist. Instead, the laboratory performing the tests compares the reported levels to unprovoked reference ranges for 24-hour specimens. Provocation, shortened collection time, and inappropriate reference range comparisons result in laboratory reports commonly showing 1 or more metal concentrations to be elevated."Conclusion:

"Patients who ask about provoked urine test results should be advised that they are not trustworthy."

What does the American College of Medical Toxicology say about the matter? In a recently published position statement, they begin by observing...

"Heavy metals, such as lead and mercury, are ubiquitous in the environment. Exposure in human populations is constantly occurring, and detectable levels of lead and mercury are commonly found in blood and urine of individuals who have no clinical signs or symptoms of toxicity and may be considered background or reference values. Although urine testing for various metals in an appropriate clinical context, using proper and validated methods, is common and accepted medical practice, the use of post-challenge (a.k.a., post-provocation) urine metal testing, wherein specimens are typically collected within 48 hours of chelation agent administration, is fraught with many misunderstandings, pitfalls and risks."

They go on to note...

"Chelating agents have been found to mobilize metals in healthy individuals who have a body burden considered normal...urine specimens collected in relatively close temporal proximity to administration of chelating agents, i.e., post-challenge specimens, are expected to have increased concentrations of metallic elements. This includes elements, such as zinc, that are essential to normal physiologic functions and maintenance of good health."

They further state:

"Currently available scientific data do not provide adequate support for the use of post-challenge urine metal testing as an accurate or reliable means of identifying individuals who would derive therapeutic benefit from chelation...Unfortunately, the practice of post-challenge urine metal testing and its application to assessment of metal poisoning often leads to unwarranted and prolonged oral and/or intravenous administration of chelating agents...Chelation therapy based on such laboratory values, in addition to being of no benefit to patient outcome, may actually prove harmful..."

These scientists apply their entire professional lives to understanding how best to evaluate toxicity in patients. Here is how they sum up their view:

"It is, therefore, the position of the American College of Medical Toxicology that post-challenge urinary metal testing has not been scientifically validated, has no demonstrated benefit, and may be harmful when applied in the assessment and treatment of patients in whom there is concern for metal poisoning."

But what do you do if you have a legitimate concern about heavy metal toxicity? Are there valid, scientific, evidence-based ways to test? Indeed there are, but I'm surprised you've read this far; it's a topic for future posts about the lab tests I use to evaluate the two ways that toxic metals can harm: disruption of biochemical pathways (poisoning) and instigating autoimmune phenomena due to allergic sensitivity (which accounts for many of the catastrophic outcomes due to ill-advised chelation testing).But to end this post on a positive note, I'll conclude with one more paper also published in the journal Environmental Health Perspectives. They begin with the concern that we all share...

"Many people, by means of consumption of seafood or other anthropogenic sources, are exposed to levels of methylmercury (MeHg) that are generally considered to be quite low, but that may nevertheless produce irreversible brain damage, particularly in unborn babies. The only way to prevent or ameliorate MeHg toxicity is to enhance its elimination from the body."

This doesn't address the immune hypersensitivity component, but is valid nonetheless. They devised a test to see whether N-acetylcysteine (NAC), a normal constituent of the body, could reduce mercury levels in a developing embryo (!, rodent). It worked surprisingly well:

"In pregnant rats, NAC markedly reduced the body burden of MeHg, particularly in target tissues such as brain, placenta, and fetus."

And here is the really interesting point:

"Because NAC causes a transient increase in urinary excretion of MeHg that is proportional to the body burden [because it is NOT a chelating agent, but supports the body's own pathways of elimination], it is promising as a biomonitoring agent for MeHg in adult animals. In view of this and because NAC is effective at enhancing MeHg excretion when given either orally or intravenously, can decrease brain and fetal levels of MeHg, has minimal side effects, and is widely available in clinical settings, NAC should be evaluated as a potential antidote and biomonitoring agent in humans."

OK, but what can we legitimately do for humans right now? More to come in future posts...