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Heavy Metal Testing, Chelation Provoked Samples & Irrelevant Reference Ranges

November 5, 2012

A number of laboratories offer testing for toxic metals (Pb, Hg, Cd, As, etc.) through blood, urine, hair and stool samples. Because they’ve been around longer than any of the synthetic chemicals, we know more about the health effects of heavy metals than any other group of toxins and a generous list of conditions and symptoms are being attributed to metal toxicities. These toxicities are real, and we all need to avoid new exposures and some people need therapy aimed at pulling these metals out of us. The trick is figuring out who that is.

Enter chelation. There’s little if any doubt that chelating agents (DMSA, EDTA, DMPS, etc.) bind to and increase the urinary and stool excretion of various metals (both toxic and non-). However, with only two recent exceptions (discussed below), the labs performing this testing have conventionally used some underhanded hokus-pokus to make the results look worse than they are. How did they do this? The labs have typically reported chelation-provoked sample results and unprovoked samples on the same reference range. That may not sound bad, but it’s a “big no-no” in medicine. The result of comparing chelation-challenged toxic metal testing to the “normal” unprovoked ranges (which themselves are internally established) is the common appearance of shockingly high levels of the poisonous metals. (See graphic)

DD heavy metal test

Some might argue that an experienced clinical eye may not need separate reference ranges for provoked samples. Perhaps true, but one could just as easily suggest that this kind of misreporting of results is the rails on which many alarmed patients are getting rolled into expensive, long term and potentially risky chelation therapy programs that they may not need.

Let me back up a bit for perspective. As alternative functional practitioners, we strive to use the best science available to diagnose to treat marginalized patients who aren’t getting the care they need from conventional medicine. Our practices serve as the testing grounds for new ideas and ideally as safe harbors for today’s “medical refugees.” Together, our practices subdivide the “syndromes” through investigating hidden causes and probing for responses to alternative treatments. We’re frequently decades ahead of convention, and though always improving, sometimes we end up lost in the sticks. There is always a degree of doubt in what we do, and a wise course to take is one of the open-minded skeptic.

My concern is that the apples-to-oranges comparison of chelation challenged vs. unprovoked samples is being paired with a “generous” list of health problems attributed to metal toxicity. The result is that patients may get shuttled toward months (or years) of chelation treatments on some very questionable diagnostic grounds. It’s not unheard of for chelation educators to suggest that patients’ with provoked results that don’t go up be kept on the protocols because their tissues are “holding onto the metals” for reasons admittedly not understood. Be that as it may, the financial incentives for both for the providers and labs are also apparent—and concerning.

To be clear, I’m not suggesting that chelation treatment has not helped a significant portion of patients undergoing treatment. In fact, I’m reasonably confident that it has. What concerns me most is that the lab testing could and should be more specific regarding which chelating agent was used and at what dose and therefore refine the diagnosis of metal toxicity and application of chelation itself.

Lets look at what’s out there in terms of metal testing:

Doctors Data has a long history in alternative testing for metals. A longstanding limitation of what they offer is that whether the sample was obtained from a provoked or unprovoked patient they still use a single reference range. The bottom of the report offers this explanation: “Reference intervals and corresponding graphs are representative of a healthy population under non-provoked conditions. Chelation (provocation) agents can increase urinary excretion of metals/elements.”

Genova Diagnostics also does urinary metal testing. They too offer a single range based on a healthy population under non-provoked conditions. In the commentary of their report they white: “Provocation with challenge substances is expected to raise the urine level of some elements to varying degrees, often into the cautionary or TMPL range. The degree of elevation is dependent upon the element level present in the individual and the binding affinities of the challenge substance.”

Metametrix (recently purchased by Genova) recently started offering a single “catch-all” chelation-provoked reference range in addition to the unprovoked normal range. This is a big step in the right direction, but its notable that their chelation ranges were created by pooling samples received from patients that were provoked with undisclosed (and presumably widely variable) amounts of “DMSA, EDTA, or other chelating agents.” Also notable is that there is no indication whether the samples came from healthy or sick patients.

Quest Diagnostics offers blood and urine testing of toxic metals. Quest only published reference ranges for the 24 hour urine test. Some may applaud their conservative reference ranges while others might deride them for dismissing as “normal” what may be clinically significant levels. No chelator specific levels reference ranges were offered. Here’s what they listed:
· Arsenic: 24-Hour Urine ≤80 µg/L
· Cadmium: 24-Hour Urine ≤5.0 µg/L
· Lead: 24-Hour Urine <80 µg/L
· Mercury: 24-Hour Urine ≤20 µg/L (Toxic ≥150 µg/L)

LabCorp offered the following reference ranges for urinary toxic metals (random and 24 hour) including separate reference ranges for Lead with specific doses of IV EDTA and PO DMSA chelation challenges:
· Arsenic: 0-50 μg/L, 0-50 μg/24 hours; inorganic arsenic: <20 μg/L
· Cadmium: <2.0 μg/g creatinine, <3.0 μg/24 hours
· Lead: <50 μg/L, <80 μg/24 hours; 150 μg/g creatinine
· Lead with chelation therapy: <600 μg/24 hours (after 1g IV EDTA or 2g DMSA PO)
· Mercury: <5.0 μg/g creatinine, <20.0 μg/L

Of the five labs I looked into, there was not a lot of agreement on reference ranges. Only LabCorp dared offer a chelator-specific reference range for one metal. (Bravo!) The only problem was that LabCorp appears to have brazenly strayed into treatment recommendations by suggesting specific doses of IV EDTA and PO DMSA without regard to the patients weight! (WHOOPS!) Every other chelation challenge protocol I have seen, suggested dosing in mg/kg—close, but yet so far. Metametrix stuck a nonspecific toe into chelation challenged reference-arranging, but I fear that they failed to shed distinguishing light on the murky situation.

So it’s fair to say that metal toxicity testing is a developing science. It will be a lot of work for the labs to standardize reference ranges for various doses of the different chelating agents for each toxic metal. Still, this work needs to be done. Of concern is that without meaningful and chelator-specific reference ranges, practitioners may be making diagnoses based on apples to oranges comparisons and then may perhaps mistakenly urge patients into long, expensive, and potentially dangerous chelation programs that may or may not actually be addressing an underlying problem.

In all honestly, I must admit that while I have studied toxic metal testing and have even taken a course in clinical chelation, but mostly for a the reasons mentioned above, I have not yet used the testing or chelation on patients myself. Stilll, I do strive to be that open-minded skeptic I mentioned earlier in this post.

So I embarked on a chelation challenge on myself. I decided to do a three-day oral DMSA chelation protocol on myself and then collect a sample. This amounted to 500mg DMSA TID x 3 days. (~22mg/kg DD, TID, x3 days). I then did a six hour collection starting immediately after the last dose of DMSA. Yes, I was being a bit of a maverick. I didn’t want to do a single dose challenge, because I was concerned that this might routinely lead to alarmingly high test results with no way to make a fair comparison to mid-protocol benefits. In my mind, one can not fairly compare urinary metals collected after a single “challenge dose” of a chelator to a sample collected after a different protocol. That’s why I made my challenge the same as a common DMSA protocol: ~20mg/kg DD TID x3 days on, followed by seven days off. (Lather, Rinse, Repeat.)

Stay tuned: I’ll post my results next. It might be interesting, because as a medical student I set the class record (out of 100 students) for the hair mercury testing back in 1999. At the time, I had just had the thimerosol preserved Hep-B series, other travel vaccines, and was in the habit of eating 2-4 cans of albacore tuna a week (ala The Zone diet).

trmorrisnd headshotDr. T.R. Morris is a licensed naturopathic medical doctor (ND). He is currently serving as faculty and consultant to the Institute for Functional Medicine (IFM). The IFM mission is to revolutionize medicine by teaching the latest genetic, nutritional, hormonal and other biochemically-based integrative medicine techniques to MDs and other practitioners looking for new tools to prevent and treat chronic disease. In the past, T.R. served as the medical director of a large integrative clinic and taught (genetics, physiology, biochemistry, microbiology, cellular & molecular biology) for 10 years for various medical programs in the Puget Sound. He sees patients in person (or long-distance via Skype consultations) from his home office in Seattle.
Contact Dr. Morris

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3 Comments leave one →
  1. Mark Su permalink
    November 12, 2012 3:05 am

    Question came in forma colleague, Dr. Mark Su.:

    Dr Morris, so what did you end up doing with this project? I would have voted for management in one way or another, presumably the more convenient or lower cost method since you were, to my understanding, asymptomatic.
    I think the key for me in utilizing the reference ranges without differentiation b/w chelated and “au naturale” is that a) it can be used as a trending level over time; and b) if it’s normal, well, no need to worry!
    Unless one were to argue that “it’s ok” to have low lying levels, I presume the intent to test would be based on an intent to treat. So the decision would need to be made pre-testing: depending on whether the person was symptomatic or asymptomatic, what would we do with the result? If I had a patient who was asymptomatic but was “just worried” and needed reassurance for whatever reason, or was just curious, I would make it clear- “if this comes back even mildly positive, are we going to treat?” If they are symptomatic, then I would treat regardless of how positive/high the result was.
    Pragmatically, it would just make sense to test with the provoked challenge in most cases, no? Because if, unprovoked, the test is (-), one would arguably still not be sure whether there was harbored toxin, right? (Still new to this, so asking legitimately, not redundantly.) Seems like there’d be few times that a negative result with unprovoked testing would be of yield, with confidence, except perhaps to provide reassurance to a patient who I would not want to further pursue investigations, or treatment, for toxins (or toxicants, as Dr. Cline put it today at the conference).
    Thoughts?
    Mark

  2. November 12, 2012 1:00 pm

    My DMSA Urine challenge test results are are in:

    What I did was a program of 500mg DMSA-PO, TID x 3 days collecting urine for 6 hours after the last dose of DMSA. At 148#, this amounts to about 22.3mg/kg/day. I was aiming for 10-20mg/kg/day, but the DMSA came in 250mg capsules, and I wanted to “go big” rather than just dabble in the DMSA trial. This protocol was suggested to me by Paul Anderson, ND in Seattle, WA. (Note: I received five free sample bottles of DMSA from Priority One when I signed up for an account and requested them.)

    The reason I did a three-day challenge and collected at the end is that I wanted to avoid an alarming early-runoff and also the under-explained reluctant metal release scenarios. I did not do a pre-chelation test because I did not see the value in it. Here’s why: if chelation works to grab and pull metals through the urine (and I believe it does), we’d see lower numbers for the metals with high affinity for DMSA in a pre-chelation sample. I had no side effects, other than urine that smelled like a sulfur spring. If anything changed, I perhaps felt mentally clearer and sharper.

    Before I share my results, let’s review the Doctors Data caveat:
    “Reference intervals and corresponding graphs are representative of a healthy population under non-provoked conditions. Chelation (provocation) agents can increase urinary excretion of metals/elements.”

    They are essentially admitting that they (like all the other labs I’ve seen) have no valid reference range for chelated samples. For many practitioners, and even more patients, the perception-bending damage would have already been done. Putting chelation-challenged results on a non-chelated scale is not too unlike giving someone IV glucose and then testing for a fasting blood sugar. In both cases, an alarming and out of normal result really ought to be expected. This is why it’s not a fair comparison, and why I am concerned about irrelevant reference ranges being coupled with a broad list of indicating symptoms leading to patients getting shuttled into highly-profitable chelation programs.

    Be that as is may, here are my outside of “reference range” results:
    Lead (Pb): 9.6 (“reference range” <2.0) = ~5x unchelated "normals"
    Mercury (Hg): 4.9 (“reference range” <3.0) = almost double unchelated "normals"
    Thallium (Tl): 0.6 (“reference range” <0.5) = barely elevated compared to unchelated "normals" (though DMSA does not have high affinity to Tl).

    The only other abnormal was a Low Creatinine of 34.4 (RR = 45-225). I'm not sure what to make of this, because my kidney function has always been normal.

  3. November 20, 2012 1:30 pm

    Dr Su. Thank you for waking up this thread. In my own case, I just did the one cycle of oral DMSA (500mg DMSA-PO, TID x 3 days = 22mg/kg/day) for the challenge testing and stopped at that. Because the labs can not provide meaningful reference ranges for challenge testing, I was intrigued, but not especially alarmed, when two toxic metals came back high. That they were Pb & Hg *was* interesting however. I have been considering, but apparently not too urgently, doing more rounds of oral DMSA and/or oral DMPS. I am not considering any IV therapy options.

    You asked: “Pragmatically, it would just make sense to test with the provoked challenge in most cases, no? Because if, unprovoked, the test is (-), one would arguably still not be sure whether there was harbored toxin, right?”

    Challenge testing results frequently come back positive because they are being compared to a reference ranges primarily developed on unchallenged samples. It’s not really a fair test to establish toxicity. I do think there probably is value in comparing test results over time using the same challenge protocol. For instance, if I did my DMSA protocol 3x/month (3 out of every ten days), and repeated the challenged testing at 6 and 12 months, we’d ideally see decreasing levels of the toxic metals in my challenged urine. This is assuming we had addressed the dietary or environmental source of the metals in the first place. How do you know when to stop treatment? That’s a good question, and I’m not sure that the lab tests have a great answer. Waiting until chelator challenged toxic heavy metals in urine fall within unchallenged “low” or “normal” ranges would seem like possible over-treatment. Remember that chelators will grab other divalent cations including nutritional ones (Ca, Mg, Zn, Cu, etc.), and that the therapy is not without risks.

    I don’t doubt that with chelation, more metals (toxic and not) are likely to come out in the urine and stool. My fundamental concern with chelation is that we can not be sure that we are not redistributing metals from one part of the body to another (i.e. from the gut, bones, and blood where they are less harmful and into the kidneys, liver, brain and endocrine organs where they are more harmful). This is why I actually like DMSA, because it reportedly has poor absorption from the GI (~20%).

    Keep the questions and comments coming. I’d be happy to hear from someone in the pro-chelation camp here–especially from someone willing to acknowlegde and examine the attendant assumptions.

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