Mercury Autism Tests Are Flawed
Please everyone go read the Quackwatch article on urine metal testing. The article makes it crystal clear what the problems with this technique are. If you are a parent of a child diagnosed with autism who is considering or has done heavy metals testing you will especially find this article interesting.
posted by Interverbal at 7:18 PM
19 Comments:
I have seen this sort of commentary on provoked tests before. However, what is normally missing, as is in this case, a suggestion of an alternative method of testing.
@MJ
More info here:
http://www.quackwatch.com/01QuackeryRelatedTopics/Tests/mercurytests.html
Oops. Here's the link:
Mercury Testing
Hi MJ,
You are right, an alternative is missing. That is okay, because I didn't wrote the article for such a purpose. It deserves its own topic I think. If you would like to see it worked on, you could request it.
Best wishes,
Interverbal,
I read this with great interest, but I have some comments on the article.
Paragraphs 1 and 2 are accurate from what I can tell. No issues there.
My issues start in Paragraph 3 when he describes how mercury/lead are measured in urine. He states micrograms per gram of creatin when the reference material he provides gives the measurement in nmol/mol. This is a significant issue because the conversion between microgram to nmol is non-trivial and involves the atomic weight at reference temperatures of the element being calculated.
I also have an issue with this statement:
"Because most of the extra excretion occurs toward the begining of the test, it is safe to assume that the provoked levels would have been 2-3 times as high if a 6-hour collection period had been used."
There is no scientific evidence provided to support this "assumption". It clearly assumes some sort of linear scale but does not provide any data to support this. For now, I have to assume this is pure speculation on the part of the author especially since the reference study provided states: "The blood concentration of DMSA peaks in 3 hr, and the half-life is 3.2 hr (15). DMSA-induced excretion of both lead (16) and mercury (17) peaks within 2 hr. In the clinical setting, chelation challenge would therefore require urinary collection only over several hours." It looks like it is intended to be used exactly the way described by Quackwatch contrary to their objection. Even worse, his broad based assumption can't be correct, because it clearly depends on the half life of the specific chelating agent being used.
Next we read:
"Practitioners who use the urine toxic metals test typically tell patients that provocation is needed to discover "hidden body stores" of mercury or lead. However, the above experiment proved that provocation raises urine levels as much in exposed workers as in unexposed control subjects and that rise is temporary, should be expected, and is not evidence of "hidden stores.'"
This is not at all the case. As described in the reference study, provocation is indeed used to determine hidden body stores of metals because blood/metal concentrations don't give a good indicator of metals bound in other organs. Even though the study results concluded that for mercury industrial workers, DMSA chelation challenge did not represent historical exposure (note they never stated body burden) they concluded the most likely reason was lack of granularity, not efficacy of the methodology or agent. "We believe that the most likely cause of the inability of DMSA chelation challenge to quantify past mercury exposures was the elapsed time between the exposures and the testing. As discussed above, most mercury is cleared within 1–2 months, apparently to levels too low to be assayed by DMSA challenge." (p 170)
In paragraph 5:
"Standard laboratories that process non-provoked samples use much higher reference ranges [3],"
Given that the reference data provided stated nmol/m I wonder what the mg/g numbers are. Do you have the actual numbers?
Quackwatch appears to be associating some sort of conspiracy regarding to the reference ranges. Reference ranges are standard for lab results and they are usually age and sex based (could be weight based as well). The numbers provided in the reference material are averages across all adults. I would not expect this to correlate to the specific results of any individual. This would be especially relevant if the patient was a child.
According to Quackwatch, the conspiracy continues: "But that's not all. A disclaimer at the bottom of the above lab report states—in boldfaced type!—that "reference ranges are representative of a healthy population under non-challenge or nonprovoked conditions."
Yes, that's exactly what the reference range means. That is how labs report data. Where is the conspiracy?
We go on: "In other words, they should not be applied to specimens that were obtained after provocation. Also note that the specimen was obtained over a 6-hour period, which raised the reported level even higher."
Yes, reference ranges should be applied to methods of collection similar to the reference. The laboratory has nothing to do with the collection. That is the job of the physician. This is all normal. That is why Doctor's don't like to give lab results to patients directly, because interpretation is required. The collection time of the specemin is completely irrelevant here. Why it is raised as an issue wrt to the reference range of unchallenged urine tests is confusing.
"The management at Doctor's Data knows that provoked testing artificially raises the urine levels."
No doubt. That is not their concern.
"Yet their report classifies values in the range of 5-10 µg/g as "elevated."
Yes, according to the reference ranges they provided under the conditions they described. No issues here.
"The report also states that "no safe reference levels for toxic metals have been established.""
Is this untrue? To my knowledge this is accurate.
"Practitioners typically receive two copies of the report, one for the practitioner and one to give to the patient. Very few patients understand what the numbers mean. They simply see "elevated" lead or mercury, and interpret the "no safe levels" disclaimer to mean that any number above zero is a problem."
This is a problem between the patient and the practitioner, not the lab. The reference material in this article (the CMA) actaully describes exactly this scenario of patient confusion from OTHER LABS.
"The patient is then advised to undergo "detoxification" with chelation therapy, other intravenous treatments, dietary supplements, or whatever else the practitioner happens to sell."
I don't see how this broad based generalization applies to everyone, especially since it doesn't apply to the lab which is main topic of discussion here. This is a potential issue with specific practitioners. But Mr. Barrett, doesn't give any details about any practitioners, so this is also a red herring without actual evidence.
"This advice is very, very, very wrong."
Which advice is he referring to? The information from the lab is accurate and well articulated. Mr. Barrett is talking about a hypothetical situation here.
"No diagnosis of lead or mercury toxicity should be made unless the patient has symptoms of heavy metal poisoning as well as a much higher nonprovoked blood level. And even if the level is in the 30s—as might occur in an unsafe workplace or by eating lead-containing paint—all that is usually needed is to remove further exposure. Chelation therapy is rarely necessary."
Now Mr. Barrett is issuing advice without providing any evidence. If he wanted to discuss the merits of testing for body metal burden, why all the theatrics about the lab report? The reference study he provided outlines that challenge testing is indeed a valid methodology. They also state using DMSA is quite safe. The evidence provided by Mr. Barrett contradicts his own broad based generalization. Clearly a knowledgeable practitioner should be using reference data (from a study hopefully, or from their own clinical experience) for challenge testing for DMSA (or whatever agent is used) and making judgements based on that.
Mr. Barrett goes on to discuss Chelation therapy without any references. Interesting that he notes chelating agents are applied intraveneously when the single study he provided used an oral chelating agent. In conclusion he writes: "The urine toxic metals test described above—whether provoked or not—is used to persuade patients they are toxic when they are not."
Again hypothetical. He is implying that standard laboratory results are always used to defraud people. That's like saying the card reader at gas stations are always used to fraudulantly capture your PIN number.
The only reference he provides for his opinions are his own references. His reference to the Omnibus case is interesting but doesn't apply to any specific cases or arguments he makes.
This article starts out as a campaign against DoctorsData yet the issues he raises are red herrings as they don't apply to the laboratory. They apply to individual practioners and their use of the resulting data. From what I can tell, the laboratory is reporting exactly what they should be.
His writing and references appear to fall far below your usual scientific standard especially given his lack of peer-reviewed reference material for any of his key points, especially the point that Provoked testing is a scam. His own reference study lists it as a legitimate and SAFE diagnostic tool.
One last observation:
I have read numerous people constantly warning about the dangers of Chelation and in fact, I've heard that there is hesitancy study it's efficacy in Autistic children for ethical reasons. However the reference study provided here, clearly labels chelation challenges as a standard for challenge testing for lead and mercury -- although the study concludes the results don't appear to reflect historical industrial mercury exposure for these particular workers. This study was performed against healthy controls and a healthy exposed population without any ethical issues. In fact, the study itself states that the use of DMSA is quite safe. (p 167)
I can only conclude that the ethical objections are merely a Red Herring without more specifics.
Another observation, this is typical of the quackwatch writing I have read: Lots of fact mixed with unsubstantiated assumption and innuendo.
IV if you could wade through mr Schwartz voluminous post I'd appreciate it. Apparently he's been living under a rock these past years and doesn't realise that kids are routinely given elevated metal toxicity levels solely through the artificial device of provocation. He then demonstrates he does not know what a reference range means or how this might be applied to these provoked kids results. The significance of the Omnibus discussion didn't seem to register either. Of course when he started out with some cockamamie story about the non trivial conversion of ugram to nmol with atomic weights (no kidding) and temperature (what is he talking about)i realised that this sort of routine chemical calculation is obviously beyond him. No reason why it shouldn't be of course but another finding that this guy does not know what he is talking about. You're the fairest person I know. Is there anything salvageable in his post?
Hi Schwartz,
“My issues start in Paragraph 3 when he describes how mercury/lead are measured in urine. He states micrograms per gram of creatin when the reference material he provides gives the measurement in nmol/mol. This is a significant issue because the conversion between microgram to nmol is non-trivial and involves the atomic weight at reference temperatures of the element being calculated.”
Quackwatch lists [2] as the reference here. This is Frumkin et al. (2001) and they use micrograms, not nmol. The one that uses nmol/mol is [3] is Brodkin et al. (2007).
“There is no scientific evidence provided to support this "assumption". It clearly assumes some sort of linear scale but does not provide any data to support this. For now, I have to assume this is pure speculation on the part of the author especially since the reference study provided states: "The blood concentration of DMSA peaks in 3 hr, and the half-life is 3.2 hr (15). DMSA-induced excretion of both lead (16) and mercury (17) peaks within 2 hr. In the clinical setting, chelation challenge would therefore require urinary collection only over several hours." It looks like it is intended to be used exactly the way described by Quackwatch contrary to their objection. Even worse, his broad based assumption can't be correct, because it clearly depends on the half life of the specific chelating agent being used.”
I agree only that stating “2-3 times as high” is on shaky ground. A better statement would be to simply say that a 6 hour collection period will very likely appear elevated compare to a 24 hour collection such as Frumkin et al used.
“This is not at all the case. As described in the reference study, provocation is indeed used to determine hidden body stores of metals because blood/metal concentrations don't give a good indicator of metals bound in other organs. Even though the study results concluded that for mercury industrial workers, DMSA chelation challenge did not represent historical exposure (note they never stated body burden) they concluded the most likely reason was lack of granularity, not efficacy of the methodology or agent. "We believe that the most likely cause of the inability of DMSA chelation challenge to quantify past mercury exposures was the elapsed time between the exposures and the testing. As discussed above, most mercury is cleared within 1–2 months, apparently to levels too low to be assayed by DMSA challenge." (p 170)”
Yes, it is the case. Look at what the Quackwatch author(s) said specifically. They are exactly correct. The Quackwatch authors say:
“However, the above experiment proved that provocation raises urine levels as much in exposed workers as in unexposed control subjects and that rise is temporary, should be expected, and is not evidence of “hidden stores.””
That is entirely correct based on Frumkin et al.
“Given that the reference data provided stated nmol/m I wonder what the mg/g numbers are. Do you have the actual numbers?”
No,
“Quackwatch appears to be associating some sort of conspiracy regarding to the reference ranges. Reference ranges are standard for lab results and they are usually age and sex based (could be weight based as well). The numbers provided in the reference material are averages across all adults. I would not expect this to correlate to the specific results of any individual. This would be especially relevant if the patient was a child.”
I don’t think so. What Quackwatch is talking about is the comparison of persons who have been given a challenge agent to a scale normalized with people who were not given a challenge agent. This is not a conspiracy; it is just exceptionally poor statistical practice. This is a Stats 101, type of error. DD caters to this.
“According to Quackwatch, the conspiracy continues: "But that's not all. A disclaimer at the bottom of the above lab report states—in boldfaced type!—that "reference ranges are representative of a healthy population under non-challenge or nonprovoked conditions."”
It is not a conspiracy; it is just irony so thick you would have to cut it with a knife.
“No doubt. That is not their concern.”
But it is my concern…. A big concern. I don’t absolve the DD either. They are still the ones who run the tests, even though it was administered with a challenge agent.
“The collection time of the specemin is completely irrelevant here. Why it is raised as an issue wrt to the reference range of unchallenged urine tests is confusing.”
Quackwatch is saying that the scale the company was not normalized with a collection period over 6 hours. I don’t know how they came to that conclusion, but if it accurate then yes it is a problem.
“Is this untrue? To my knowledge this is accurate.”
This is true. I don’t think Quackwatch was raising an issue here as much as pointing out an interesting fact.
“I don't see how this broad based generalization applies to everyone, especially since it doesn't apply to the lab which is main topic of discussion here.”
I would argue that it applies to many…. many practitioners in the realm of autism. Quackwatch was taking aim at a broader issue than just DD here.
“Which advice is he referring to? The information from the lab is accurate and well articulated. Mr. Barrett is talking about a hypothetical situation here.”
The advice to undergo chelation. As to the lab, the information might be well articulated, but it is not accurate. It is unlikely that lab reports would violate basic stats principles and still maintain accuracy.
“If he wanted to discuss the merits of testing for body metal burden, why all the theatrics about the lab report?”
I presume because the lab reports are based on terrible statistical practice.
“The reference study he provided outlines that challenge testing is indeed a valid methodology.”
I would recommend re-reading the article for comprehension purposes.
“Interesting that he notes chelating agents are applied intraveneously when the single study he provided used an oral chelating agent.”
They are sometimes applied intravenously, but you are right it should have been broader.
“Again hypothetical. He is implying that standard laboratory results are always used to defraud people.”
These are not standard laboratory results. That is the core of the Quackwatch argument, but not their only point. And while I agree that they may or may not be used to defraud people, I would argue that often enough in the realm of autism…. They are used just so.
“This article starts out as a campaign against DoctorsData yet the issues he raises are red herrings as they don't apply to the laboratory. They apply to individual practioners and their use of the resulting data. From what I can tell, the laboratory is reporting exactly what they should be.”
A red herring is an irrelevant distraction, used to prove another’s argument in wrong. I don’t think I saw any of those. I think the Quackwatch article deals with multiple issues related to the problems on this issue…. Not just problems with DD. That is permissible. Further, breaking statistical practice was done by DD. I am not willing to excuse them because others then misinterpret their already bad data.
Schwartz, I will grant that the 2-3 times as high bit is shaky (as to just saying that it should be higher). But that is all relative to the points you raised.
Hi Alyric,
Schwartz takes issue with Quackwatch's claim that the 6 hour collection of urine increases what is found by 2-3 times compared to a 24 hour collection. He is right to do so. This could be correct, but it is not shown to be. A safer statement would have been just to say the 6 hour collection very likely increases what is found.
I think Schwartz's numerous other contributions in this discussion should be questioned rather rigorously.
Alyric,
Please point out something specific that was incorrect.
"and doesn't realise that kids are routinely given elevated metal toxicity levels solely through the artificial device of provocation."
I outlined this quite clearly. It is an issue with individual practitioners, and has nothing to do with the lab. If you could point out any evidence provided in the article of such an organized Scam that might actually be helpful.
"He then demonstrates he does not know what a reference range means or how this might be applied to these provoked kids results."
I certainly understand what the reference range means. The reference range provided by the lab is for measurements taken under the conditions described on the lab report, nothing more. Clearly if different types of measurements are taken, these ranges are not relevant. Again, as I stated, that is an issue for lab result interpretation. If you have any evidence of organized fraud, please present it.
"The significance of the Omnibus discussion didn't seem to register either."
It is used as an anecdote to try and persuade you that this case applies to all cases.
"Of course when he started out with some cockamamie story about the non trivial conversion of ugram to nmol with atomic weights (no kidding) and temperature (what is he talking about)i realised that this sort of routine chemical calculation is obviously beyond him."
Personal attacks are unnecessary. Since the conversion is required to validate the claims, it is a pretty glaring ommission for the author of the article to not include it. Personally, I don't feel like tracking down the atomic weight of the various elements. Last time I recall looking this up, temperature was mentioned, but I might be mistaken on that count. Either way, I notice you didn't provide the conversion factor, so again, your comment has no practical value.
As per usual, you didn't address any specific point, so I can only conclude that the objective of your post was to hurl personal insult.
Schwartz, IV has very nicely answered for me. You however are culpable for so disingenuously attempting to trivialise the use of DD results for the purpose of chelating small children based on the spuriously elevated results from provoked tests. Do you think this is some kind of game? There are real consequences to these kinds of quackery as the Omnibus points out very clearly. The treatment of Colton Snyder is abominable.
Interverbal,
"...Quackwatch lists [2] as the reference here..."
In paragraph 3 he is talking about reference ranges here: "When testing is performed, the levels are expressed as micrograms of lead or mercury per grams of creatinine (µg/g) and compared to the laboratory's "reference range."" His only reference to lab reference ranges is the CMA document [3] which lists the ranges in mol based units.
"I agree only that stating “2-3 times as high” is on shaky ground. A better statement would be to simply say that a 6 hour collection period will very likely appear elevated compare to a 24 hour collection such as Frumkin et al used."
His sentence implies that using a 24 hour range is the "appropriate" technique, when if you read Frunkin et al, they imply that the longer collection period is not the norm: "It is also possible that our urinary collection procedure—specifically, collecting urine for 24 hr rather than a shorter interval— accounted for the negative findings. Other studies have collected urine for shorter intervals, in the range of 8 hr, based on the rapid action of DMSA in effecting mercury excretion [e.g., Aposhian et al. (49)]. A longer collection may have diluted our results by diluting the mercury in our specimens, causing the results for the highly exposed and the unexposed to converge."
"Yes, it is the case. Look at what the Quackwatch author(s) said specifically. They are exactly correct. The Quackwatch authors say:
“However, the above experiment proved that provocation raises urine levels as much in exposed workers as in unexposed control subjects and that rise is temporary, should be expected, and is not evidence of “hidden stores.””"
First, they were only testing a single chelating agent, so applying the results of this study as a "proof" of all chelation challenges is incorrect. Second, it is obvious that the increased release of metals comes from somewhere in the body -- as well described in the introduction when they introduce chelating agents. Quackwatch can only conclude that there was no difference in release between controls and the occupational workers. There is not a single reference to "hidden stores" nor any discussion of where the increased release of metals come from in Frumkin et al. The quackwatch statement is not anywhere near correct in it's broad based assumptions. In fact, Frumkin et al state:
"However, a long terminal elimination phase has been described (36), with mercury retention in nervous system, kidneys, and other soft tissues. Consequently, there could also be a role for DMSA chelation challenge some time after mercury exposure, especially if exposure had been prolonged and intense. Support for this notion comes from animal evidence (37) that DMSA draws mercury with special avidity from the kidneys— an important mercury storage site known to have a relatively slow turnover (38). Indeed, DMSA chelation challenge has been used
clinically on a limited basis following mercury exposure (15,26,39). A related agent used in Europe, 2,3-dimercaptopropane-1-sulfonic acid (DMPS), has been used in a similar manner (40,41)."
Here are the actual conclusions from the study:
"We conclude that DMSA chelation challenge, according the protocol described here, is not useful in retrospective exposure assessment among mercury workers."
"The results do not support this hypothesis, and suggest that DMSA chelation challenge is not useful in quantifying past mercury exposure."
The authors draw no conclusions on the ability of the agent to detect any hidden stores let alone disprove it across all chelating agents. As described in the introduction, different chelating agents work differently on different metals and even possibly in different parts of the body. In fact they limit the conclusions on DMSA
This is from the abstract: "Chelation challenge testing has been used to assess the body burden of various metals. The bestknown example is EDTA challenge in lead-exposed individuals. This study assessed diagnostic chelation challenge with dimercaptosuccinic acid (DMSA) as a measure of mercury body burden among mercury-exposed workers."
Quackwatch would be wise to refrain from making broad based conclusions on such a narrow study hypothesis.
"What Quackwatch is talking about is the comparison of persons who have been given a challenge agent to a scale normalized with people who were not given a challenge agent. This is not a conspiracy; it is just exceptionally poor statistical practice. This is a Stats 101, type of error. DD caters to this."
That appears to be the allegation. Evidence please.
"Do you have the actual numbers?... No, "
So you can't validate the assertion that the DoctorsData reference numbers are wrong. Do you not agree that reference ranges are usually age and sex specific? If so, how does providing a general adult average as a reference (in significantly different units) make any sense?
"But it is my concern…. A big concern. I don’t absolve the DD either. They are still the ones who run the tests, even though it was administered with a challenge agent."
Laboratories take samples, and provide test results. They also provide reference ranges for testing done under normal conditions as is clearly outlined on the test results. They have no input into the analysis of the data or how it is used -- as they shouldn't. How exactly do you hold them responsible. Do you have evidence that other labs provide more detailed reference ranges based on some arbitrary criteria provided with the lab sample? Evidence please.
"Quackwatch is saying that the scale the company was not normalized with a collection period over 6 hours. I don’t know how they came to that conclusion, but if it accurate then yes it is a problem."
IF it is accurate? This is surprising given that the Frumkin et al states that shorter collection periods are more often used. It also appears dependent on the half life of the chelating agent. Such a generalized assumption doesn't seem to match the assertions put forth. Evidence to the contrary would be required at this point.
"This is true. I don’t think Quackwatch was raising an issue here as much as pointing out an interesting fact."
An interesting fact that is undoubtedly required for legal protection. An interesting fact that is also found on EPA, FDA, and CDC sites. I don't see why it is so interesting. This was included for emotive appeal despite the standard nature of it's inclusion.
"I would argue that it applies to many…. many practitioners in the realm of autism. Quackwatch was taking aim at a broader issue than just DD here."
If they want to allege systematic fraud, then evidence is required. The only evidence they provide shows that DoctorsData is providing lab results with well documented standardized reference ranges. Evidence please. In this case, I'll even accept personal anecdote.
"The advice to undergo chelation. As to the lab, the information might be well articulated, but it is not accurate. It is unlikely that lab reports would violate basic stats principles and still maintain accuracy."
Please point out the inaccurate information in the lab report. The lab is reporting a measurement and a reference range under which collection procedures it applies. Where is the statistical issue?
"I presume because the lab reports are based on terrible statistical practice."
Please be more specific here. What statistical practise is being violated in the lab report?
"I would recommend re-reading the article for comprehension purposes."
From the study introduction: "Because chelating agents bind metals and promote their urinary excretion, theoretically they can be used in challenge tests to assess metal levels. The rationale for diagnostic chelation challenge is straightforward: If a person has an elevated body burden of a metal, then administration of a chelating agent should cause a short-term increase in the urinary excretion of that metal. The most commonly used chelation challenge test has been EDTA administration following lead exposure (6,7), although British Anti-Lewisite and penicillamine have also been used (8)."
http://www.drugs.com/mmx/sodium-calcium-edetate.html
It is an accepted to use EDTA as a diagnostic tool for chelation challenge.
"These are not standard laboratory results. That is the core of the Quackwatch argument, but not their only point. And while I agree that they may or may not be used to defraud people, I would argue that often enough in the realm of autism…. They are used just so.
As I stated earlier, there is no evidence that these laboratory results are non-standard. Simple proof would be to reference a "standard" lab result. Why is none provided? Why is NO evidence provided. As I stated earlier, any evidence would be helpful as these are pretty nasty allegations against the lab. An accusation of fraud should be accompanied by some sort of evidence!
"Further, breaking statistical practice was done by DD. I am not willing to excuse them because others then misinterpret their already bad data."
Again, what statistical practise is being broken? In order to provide relevant reference ranges for every possible scenario (if they even have such ranges) they would have to include a lengthy questionnaire with the sample which collected all sorts of chelation protocol information. I require evidence before I'll believe this is standard practise among labs.
Alyric,
"IV has very nicely answered for me."
Glad someone else did the heavy lifting for you.
"You however are culpable for so disingenuously attempting to trivialise the use of DD results for the purpose of chelating small children based on the spuriously elevated results from provoked tests."
Since you haven't outlined any specific issues, I reject your argument.
"Do you think this is some kind of game?"
Not at all. Allegations of systematic fraud at the expense of patients' health is quite serious. That's why I demand evidence. Why you don't is puzzling.
"There are real consequences to these kinds of quackery as the Omnibus points out very clearly. The treatment of Colton Snyder is abominable."
There are real consequences to any medical error or incompetance. Given that medical error is one of the leading causes of death in the US, this is a widespread problem and hardly the domain of Autism practitioners. Invoking a single case does not imply systemic fraud. It still has nothing to do with the lab and everything to do with the practitioners.
Interverbal,
Let me illustrate an example:
When I go to a doctor and he requests a blood test for cholesterol, he fills out a lab requisition form with my basic demographic information and checks off the tests he wants done.
My blood is then taken, and the sample sent to the lab. The lab returns the cholesterol levels and compares them to a reference range based on my age and sex.
Now, if I was on any variety of medication (which is not specified on the lab requisition form) the reference ranges provided by the lab would be completely inapplicable to me. A similar problem would exist if I had an illness affecting those results. The lab would not change the reference ranges, nor would they be expected to. The job of ignoring the reference range is the responsibility of the practitioner who knows the details of the case.
This is standard government run lab procedure.
Hi Schwartz,
“In paragraph 3 he is talking about reference ranges here: "When testing is performed, the levels are expressed as micrograms of lead or mercury per grams of creatinine (µg/g) and compared to the laboratory's "reference range."" His only reference to lab reference ranges is the CMA document [3] which lists the ranges in mol based units.”
The reference ranges are the DD reference ranges. The DD lab report uses (µg/g).
“His sentence implies that using a 24 hour range is the "appropriate" technique, when if you read Frunkin et al, they imply that the longer collection period is not the norm”
Well the quote you pull from Frumkin et al states:
"It is also possible that our urinary collection procedure—specifically, collecting urine for 24 hr rather than a shorter interval— accounted for the negative findings. Other studies have collected urine for shorter intervals, in the range of 8 hr, based on the rapid action of DMSA in effecting mercury excretion [e.g., Aposhian et al. (49)].”
This says nothing about 24 hours not being the norm. The author is just discussing what other studies have done.
“First, they were only testing a single chelating agent, so applying the results of this study as a "proof" of all chelation challenges is incorrect.”
That is just fine, but if you want to take that interpretation then the EoHarm and AoA crew should stop advocating the benefit of DMSA provocation tests and stick to advocating for EDTA, ALA, cilantro, and/or other chemicals/herbs right? And if this is what the research says….. then why haven’t they been saying this all along?
“Second, it is obvious that the increased release of metals comes from somewhere in the body -- as well described in the introduction when they introduce chelating agents. Quackwatch can only conclude that there was no difference in release between controls and the occupational workers.”
The issue isn’t whether mercury and or other heavy metals are stored in internal organs. We already know they are. That is not being challenged. The issue is “hidden stores”. This would be large amounts of mercury et al. squirreled away building toxicity slowly or suddenly too (it can be either) which causes children to develop autism and persons of venerable age to develop heart problem.
“The authors draw no conclusions on the ability of the agent to detect any hidden stores let alone disprove it across all chelating agents.”
Using DMSA, you are not going to produce a difference between people who had mercury exposure in their past and people who did not. In both groups the challenge agent temporarily increased the amount both groups excreted and then it, both groups quickly went down. That is what the article says.
If you use DMSA to as a challenging agent it is going to artificially raise the mercury excreted for a short time. I can anecdotally report that parents are sometimes (maybe often) told that by using a challenge agent they are uncovering hidden stores because autistics are poor excretors. In reality it seems that DMSA temporarily raises the amount of mercury excreted even by people without exposure. This is the point the Quackwatch article makes. It is consistent with Frumkin et al.
“That appears to be the allegation. Evidence please.”
Friis, R. H., Seller, T. A. (2004). Epidemiology for public health practice, 3rd ed. Sundbury, MA: Jones and Bartlett Publishers.
Logic should also tell you without any help from me. You have not shown me that you understand the difference between norm referenced and criterion based assessment. Now, when you survey a broad range of individuals for the purpose of creating a normalized reference you simultaneously create the conditions of who will be included in your group. You create limits. After you have collected data you distribute the data ranging from the mean. You distribute scores from the average based on the standard deviation for that data set (called “SD” on the lab report form). Generally through correlative research scientists try to attach a clinical significance to a given SD in a given direction. This is the step that is missing in mercury research, but folks tend to guess what fits where.
So, because the statistical basis for your mean and standard deviation is derived under specific conditions, guess what happens when you change those conditions and then try to apply your score. Hint: The mean and standard deviation no longer apply along with any correlated clinical significance and therefore the entire exercise is epically pointless. I can think of some ways to get around this if certain research avenues were pursued, but they haven’t been.
“So you can't validate the assertion that the DoctorsData reference numbers are wrong. Do you not agree that reference ranges are usually age and sex specific? If so, how does providing a general adult average as a reference (in significantly different units) make any sense?”
No I can’t. And age and sex specific references are needed only if different genders or ages were not used to create the normed distribution of interest. If they were, then there is no issue.
“Laboratories take samples, and provide test results. They also provide reference ranges for testing done under normal conditions as is clearly outlined on the test results. They have no input into the analysis of the data or how it is used -- as they shouldn't.”
They are ones taking data on a sample administered under a challenge condition and comparing it to a normalized distribution. Even without bad interpretation, this practice is poor all by itself.
“How exactly do you hold them responsible.”
I don’t want to hold them responsible; I want to hold them accountable. The way to do that is to regulate the practice via law or professional licensing regulations.
“Do you have evidence that other labs provide more detailed reference ranges based on some arbitrary criteria provided with the lab sample? Evidence please.”
There is no scale for mercury normalized for challenge testing. It doesn’t exist on this planet. Any lab that compares samples taken under a challenge condition to a normalized distribution for mercury is engaging in a problematic practice. That is all.
IF it is accurate? This is surprising given that the Frumkin et al states that shorter collection periods are more often used.
“IF it is accurate? This is surprising given that the Frumkin et al states that shorter collection periods are more often used.”
But…. the authors don’t say that.
“I don't see why it is so interesting. This was included for emotive appeal despite the standard nature of it's inclusion.”
It is interesting because, it calls into question the practice of assigning a clinical value to a given score. I don’t agree at all that it was included for emotive appeal.
“If they want to allege systematic fraud, then evidence is required. The only evidence they provide shows that DoctorsData is providing lab results with well documented standardized reference ranges. Evidence please. In this case, I'll even accept personal anecdote.”
You know what Schwartz, no. I am not going to do it. This type of recommendation is so easy to find on any major autism = mercury advocacy site that I actually refuse to do it. I am just not interested in wasting my time.
“Please point out the inaccurate information in the lab report. The lab is reporting a measurement and a reference range under which collection procedures it applies. Where is the statistical issue?”
It is the practice of comparing incorrectly as I have already explained multiple times. This is what I mean when I say a problem with the statistical practice at DD and elsewhere. I am willing to answer specific questions about this issue, but I am not willing to answer this general point again in this discussion.
“It is an accepted to use EDTA as a diagnostic tool for chelation challenge.”
Yes, and guess what, lead does have a standardized scale for challenge agents! A doctor discussed it with me a few years back.
“As I stated earlier, there is no evidence that these laboratory results are non-standard.”
Except of course that they violate basic statistical practice.
“Simple proof would be to reference a "standard" lab result. Why is none provided? Why is NO evidence provided.”
Because there is no reason to. The way DD does the test violates statistical practice. This is what I mean when I say a problem with the statistical practice at DD and elsewhere. I am willing to answer specific questions about this issue, but I am not willing to answer this general point again in this discussion.
Interverbal,
"The reference ranges are the DD reference ranges. The DD lab report uses (µg/g)."
If his sentence refers to DD data, then this is correct. If he is lecturing about generalized testing (which it sure sounds like) then he should note that a variety of measurements can be used, like the ones he provides as "standardized" reference levels.
"This says nothing about 24 hours not being the norm. The author is just discussing what other studies have done."
From paragraph #2 Mr Barrette states:
"The standard way to measure urinary mercury and lead levels is by collecting a non-provoked urine sample over a 24-hour period."
He provides no evidence to support this, the reference study he produces does not state this, and in fact states with DMSA shorter periods are more likely in a clinical setting. The study references to other studies using shorter periods tends to support my notion that 24-hour period is not standard.
Unless there is evidence to the contrary, I reject his assertion that 24 measurement is a standard since it is completely unsubstantiated by any evidence provided.
"That is just fine, but if you want to take that interpretation then the EoHarm and AoA crew should stop advocating the benefit of DMSA provocation tests and stick to advocating for EDTA, ALA, cilantro, and/or other chemicals/herbs right? And if this is what the research says….. then why haven’t they been saying this all along?"
You should take that up with them. I am discussing the article you posted and my contention that almost none of the serious systemic allegations are supported by any evidence and that the broad based scientific statements of fact are also unsubstantiated by the evidence provided.
"The issue isn’t whether mercury and or other heavy metals are stored in internal organs. We already know they are. That is not being challenged. The issue is “hidden stores”. This would be large amounts of mercury et al. squirreled away building toxicity slowly or suddenly too (it can be either) which causes children to develop autism and persons of venerable age to develop heart problem."
That sounds like Mr. Barrette's definition of "hidden stores". Since safe levels of stored mercury are not articulated anywhere that I know of, no one can say whether the resulting values are representative of a healthy result or whether they are "large". I suggest that if Dr. Barrette wants to use his own terms, he should define those terms ahead of time. As it reads right now, it is completely ambiguous and arbitrary. Certainly not scientific.
"Using DMSA, you are not going to produce a difference between people who had mercury exposure in their past and people who did not. In both groups the challenge agent temporarily increased the amount both groups excreted and then it, both groups quickly went down. That is what the article says."
It's more specific than that. Using DMSA you are not going to be able to detect long term exposure from occupational exposure from that study, or from Amalgam fillings. This is an important distinction since we know different types of mercury break down and store in different organs. We also know the method of exposure can also change the location of mercury storage. We also know that different chelating agents extract metals from different body organs at different rates. Given this large number of known variables, the more general conclusion you stated is not correct, let alone Mr Barrette's even broader conclusion.
Furthermore, unless you can show that these occupational workers were exposed to injected ethyl mercury than you can't apply any conclusions to those trying to test for body burden accumulation of injected ethyl mercury. However, given the study results, I would personally be skeptical on DMSA's ability to determine the body burden of injected mercury. I remember reading that several of the chelating agents are quite poor in extracting mercury stores, but I don't remember which ones, or where I read it.
"If you use DMSA to as a challenging agent it is going to artificially raise the mercury excreted for a short time."
I think the following would be a better description: Using a DMSA challenge will extract some stored mercury in the body for a short period of time. I suspect someone has probably studied which organs are specifically targeted and the statement can probably be made more accurate.
"I can anecdotally report that parents are sometimes (maybe often) told that by using a challenge agent they are uncovering hidden stores because autistics are poor excretors. In reality it seems that DMSA temporarily raises the amount of mercury excreted even by people without exposure. This is the point the Quackwatch article makes. It is consistent with Frumkin et al."
They are most definately uncovering hidden stores of mercury in the body -- hidden because they don't show up on a blood/mercury test. The Quackwatch article is trying to make far more points. They are alleging that DoctorsData is reporting non standard results -- which he provides no evidence to support. They are also alleging that all challenge test results are fraudulant -- which they are not. They are alleging systematic fraud in the use of these reports -- without providing any evidence.
The issue he is trying to raise is that a simple increase in mercury excretion is not necessarily indicative of a health problem and a comparison to the reference ranges should not be done because the reference ranges are useless for chelation challenge results. What should happen is the increased amount should be compared to a reference range for a target they are trying to achieve. Again, this has everything to do with the practitioners. I am certain you will find incompetent practitioners or even fraudsters incorrectly analysing this data, but the article infers that this is the standard behaviour in the practitioner industry. The reference material [3] provided in the quackbuster article illustrates how "standard" lab results still caused quite a bit of confusion in patients. Clearly this is not the exclusive domain of DD.
"Logic should also tell you without any help from me. You have not shown me that you understand the difference between norm..."
My argument has nothing to do with the incorrect application of the reference ranges. My position is that actions taken based on lab results are the domain of the practitioner. The lab provides results, and reference data that they have. Perhaps the practise of providing reference range for unchallenged normal people is non-standard for a sample taken under chelation challenge. I need to see other lab results to substantiate that allegation.
If you read the instruction text provided by Doctor's data they state quite clearly:
"
For essential elements, the mean and the reference range (plus or minus 1 SD) apply to human urine under non-challenge, non-provocation conditions. Detoxification therapies can cause significant deviations in essential element content of urine. For potentially toxic elements, the expected range also applied to conditions of non-challenge or nonprovocation. Diagnostic or therapeutic administration of detoxifying agents may significantly raise urine content of potentially toxic elements. Descriptive texts appear in this report on the basis of measured results and correspond to non-challenge, nonprovocation conditions."
http://www.doctorsdata.com/repository.asp?id=31
A far more comprehensive section in the result outlines sources of mercury, symptoms of mercury poisoning, and is full of references. Mr. Barrette is being misleading by omitting this from his article.
"No I can’t. And age and sex specific references are needed only if different genders or ages were not used to create the normed distribution of interest. If they were, then there is no issue."
I think you're misunderstanding my point. I am asserting that it is standard laboratory practise to provide reference ranges for healthy people under normal
conditions only. Most times, a reference range is actually specified as a reference limit, and is indeed specified based on age and sex. The reason is simple: the upper bound for an acceptable range averaged over many age groups might very well prove to be quite toxic for a child. I don't know if this is the practise for lead and mercury levels but it is certainly the practise with items such as cholesterol.
"No I can’t. And age and sex specific references are needed only if different genders or ages were not used to create the normed distribution of interest. If they were, then there is no issue."
My point is that Mr Barrette's allegation that the reference ranges used by DoctorsData are low is still unsubstantiated.
"They are ones taking data on a sample administered under a challenge condition and comparing it to a normalized distribution. Even without bad interpretation, this practice is poor all by itself."
I fully agree that the practise is poor. Having worked for a standard lab in result collection and distribution for a short while, I find the whole industry full of poor practices -- no different from many medical processes but that is a different topic. However, if Mr Barrette wants to single DD out as being non-standard, then he needs to provide evidence that other labs would provide different reference ranges under varying conditions. I remain unconvinced since no evidence has been provided. Providing such evidence if it existed would be a simple matter.
"I don’t want to hold them responsible; I want to hold them accountable. The way to do that is to regulate the practice via law or professional licensing regulations."
OK, but if this is standard lab practise, then your issue should be raised with all laboratory establishments and the lack of regulation, not DD.
"There is no scale for mercury normalized for challenge testing. It doesn’t exist on this planet. Any lab that compares samples taken under a challenge condition to a normalized distribution for mercury is engaging in a problematic practice. That is all."
Again, the allegation is that DoctorsData is behaving contrary to industry standards. My position there is clear.
"You know what Schwartz, no. I am not going to do it. This type of recommendation is so easy to find on any major autism = mercury advocacy site that I actually refuse to do it. I am just not interested in wasting my time."
If these websites are saying that applying reference ranges based on standard measurement conditions to chelation challenged results and drawing incorrect conclusions, then the article should reference those sites and point out the incorrect instructions. Allegations of systemic fraud are very serious. I do not accept a handful of websites as sufficient evidence of systemic fraud, nor does the article in question even refer to a single one.
"It is the practice of comparing incorrectly as I have already explained multiple times."
OK, your position is clear.
"Yes, and guess what, lead does have a standardized scale for challenge agents! A doctor discussed it with me a few years back."
You missed the point. I originally made the statement that the reference study states that chelation challenge is a valid methodology. You rudely recommendeded I re-read the study for "comprehension purposes". I provided the text from the study which outlines how chelation challenges are a valid methodology for determining body burden of metals. I also provided other references to support it. I think I've supported my original statement.
"Except of course that they violate basic statistical practice."
We disagree since I feel the lab is just providing data. That aside, your argument does not provide any evidence that the practise is non-standard. That would require a result from a lab you consider to be "standard".
"Because there is no reason to. The way DD does the test violates statistical practice. This is what I mean when I say a problem with the statistical practice at DD and elsewhere. I am willing to answer specific questions about this issue, but I am not willing to answer this general point again in this discussion."
There you go again saying that DD does the test. They don't perform the challenge test and they don't make any clinical recommendations for individuals. To prove that they engage in a non-standard reporting practise, Mr Barrette requires an example of the standard practise. If the practise of always providing reference ranges under non challenge conditions is industry wide, then there is no deviation from standard practise. The article has not provided any evidence.
This article:
* alleges non-standard practise without providing any evidence of how the practise deviates from the standard. (he infers other labs provide chelation challenge reference ranges, or no reference ranges without providing evidence)
* makes broad based scientific statements of fact that are unsubstantiated by the evidence provided (standard ways to measure urine metal levels are 24 hours)
* makes broad based scientific statements of fact that are unsupported by the references he provides. (the above experiment proved...)
* alleges the lab uses artificially low reference ranges without providing the range other labs use ("Standard laboratories that process non-provoked sampels use much higher...")
His points on the reference ranges may actually be valid, but there is no data referenced to support it. The practise of including non applicable reference ranges based on the collection method may be non-standard, but there is no referenced standard lab results to substanatiate the allegation.
If Mr Barrette wants to warn people about the improper use of lab results by fraudsters or incompetents that is perfectly valid, and I encourage him and others to do so. But he should not allege serious systemic fraud without any evidence, he should not allege non-standard practise without comparing them to evidence of standard practise, and he should not claim to be science based and then broadly apply overstated and unsupported definitive statements of fact, otherwise anyone with a keen eye will note the inconsistency.
Hi Schwartz,
“He provides no evidence to support this, the reference study he produces does not state this, and in fact states with DMSA shorter periods are more likely in a clinical setting.”
No, it says only that a shorter period is necessary.
“In the clinical setting, chelation challenge would therefore require urinary collection only over several hours.”
“Unless there is evidence to the contrary, I reject his assertion that 24 measurement is a standard since it is completely unsubstantiated by any evidence provided.”
As you like
“You should take that up with them. I am discussing the article you posted and my contention that almost none of the serious systemic allegations are supported by any evidence and that the broad based scientific statements of fact are also unsubstantiated by the evidence provided.”
But I did take it up with them. I wrote this post. The Quackwatch post and my supporting post, take on a specific view. You have come to the table with a different view i.e. (DMSA might be different from EDTA) from the one we argued against. That is fine, but it doesn’t have bearing relative to why the points were made.
“I suggest that if Dr. Barrette wants to use his own terms, he should define those terms ahead of time. As it reads right now, it is completely ambiguous and arbitrary. Certainly not scientific.”
Don’t miss the point. The fact that what constitutes mercury poisoning is ambiguous is not in question. The problem is the claim that provoking agents allow us to uncover hidden hordes of mercury (apologies to Mark Blaxill).
“It's more specific than that. Using DMSA you are not going to be able to detect long term exposure from occupational exposure from that study, or from Amalgam fillings. This is an important distinction since we know different types of mercury break down and store in different organs. We also know the method of exposure can also change the location of mercury storage. We also know that different chelating agents extract metals from different body organs at different rates. Given this large number of known variables, the more general conclusion you stated is not correct, let alone Mr Barrette's even broader conclusion.”
Give me a peer reviewed reason to agree that the mercury the workers were exposed to and thimerosal mercury should respond differently to DMSA and I will entertain that argument.
“Furthermore, unless you can show that these occupational workers were exposed to injected ethyl mercury than you can't apply any conclusions to those trying to test for body burden accumulation of injected ethyl mercury.”
If you would like to argue against it using peer reviewed research then I will read patiently.
“I think the following would be a better description: Using a DMSA challenge will extract some stored mercury in the body for a short period of time.”
Both of our statements are correct. The difference is mine deals with reference to an existing scale.
“Again, this has everything to do with the practitioners. I am certain you will find incompetent practitioners or even fraudsters incorrectly analysing this data, but the article infers that this is the standard behaviour in the practitioner industry.”
The difference between you and I here, is that I don’t care this is a standard practice. The problem isn’t that the practice is substandard the problem is the practice is wrong. This is a broader problem that just DD, but that doesn’t get DD off the hook.
“If you read the instruction text provided by Doctor's data they state quite clearly”
Yes, they explain relevant facts important to interpretation, but they still run the tests anyway.
“I think you're misunderstanding my point. I am asserting that it is standard laboratory practise to provide reference ranges for healthy people under normal conditions only. Most times, a reference range is actually specified as a reference limit, and is indeed specified based on age and sex. The reason is simple: the upper bound for an acceptable range averaged over many age groups might very well prove to be quite toxic for a child.”
I understand what you have written, but I have no clue what your point could be relative to our discussion.
“I fully agree that the practise is poor. Having worked for a standard lab in result collection and distribution for a short while, I find the whole industry full of poor practices -- no different from many medical processes but that is a different topic.”
Agreed then.
“Again, the allegation is that DoctorsData is behaving contrary to industry standards. My position there is clear.”
Relative to our conversation this is not a point in dispute.
“If these websites are saying that applying reference ranges based on standard measurement conditions to chelation challenged results and drawing incorrect conclusions, then the article should reference those sites and point out the incorrect instructions. Allegations of systemic fraud are very serious. I do not accept a handful of websites as sufficient evidence of systemic fraud, nor does the article in question even refer to a single one.”
It is individuals on those sites who make the claims. These tend to be “discussion” groups. I wouldn’t call it systematic fraud. I would call it a bunch of caring, concerned people who do not grasp basic science or statistics.
“You missed the point. I originally made the statement that the reference study states that chelation challenge is a valid methodology. You rudely recommendeded I re-read the study for "comprehension purposes". I provided the text from the study which outlines how chelation challenges are a valid methodology for determining body burden of metals. I also provided other references to support it. I think I've supported my original statement.”
I took my own advice and re-read what you wrote. I must still be missing the point, because it looks to me that you are a still misrepresenting the paper. The valid test is for lead, not mercury. Your original statement doesn’t draw this distinction and since the topic here is mercury not lead, then is a continuing concern I have. I cite your original comment as wrong and will continue to do so. Also, the comment wasn’t made to be rude, but to give you a chance to double check your comprehension and fix your mistake. Everyone makes occasional comprehension mistakes. I would suggest that if you don’t want your comprehension to be called into question, then I would think this blog will be very frustrating for you.
“We disagree since I feel the lab is just providing data.”
As you like
“There you go again saying that DD does the test. They don't perform the challenge test and they don't make any clinical recommendations for individuals.”
Pure semantics…. They run the statistical testing.
Schwartz you are always welcome here and may continue on this topic as long as you see fit, but our discussion seems to have trickled down now to a number of points I just don’t care about.
Interverbal,
"Schwartz you are always welcome here and may continue on this topic as long as you see fit, but our discussion seems to have trickled down now to a number of points I just don’t care about."
I agree. I'll skip most of the individual arguments since we're down to a couple of key points besides our general disagreements.
WRT to comprehension... I am no longer offended.
The quackwatch article actually describes both lead and mercury tests in the first sentences. The quackwatch article also effectively states that challenge testing (broad based term) is not necessary for lead or mercury, only blood levels or symptoms of poisoning are required for diagnosis. "No diagnosis of lead or mercury toxicity should be made unless the patient has symptoms of heavy metal poisoning as well as a much higher nonprovoked blood level."
The references in the Frumkin et al study (numbers 6, 7 and 8) refer to challenge testing being used to detect body burdens of lead and mercury.
From reference #8 "The urinary mercury level after DMPS administration is a better indicator of exposure and renal mercury burden than is the mercury level measured in the urine before DMPS is given."
Thus, the Frumkin et al study clearly references the fact that chelation challenge using DMPS is a good method for determining hidden mercury stores in the body even without overt signs of poisoning contrary to Mr. Barrette's assertions.
"It is individuals on those sites who make the claims. These tend to be “discussion” groups. I wouldn’t call it systematic fraud. I would call it a bunch of caring, concerned people who do not grasp basic science or statistics."
That is unfortunate. I fully support a less polarized warning/tutorial that doesn't make broad based generalizations or accusations of systemic fraud.
I would avoid using that quackwatch site as a reliable source of information. Stephen Barrett has made numerous claims which are false including the claim that he is a Medical Board Certified psychiatrist. Check out the court case where this is documented:
Court Case: Stephen Barrett, M.D. vs. Tedd Koren, D.C. and Koren Publications, Inc.
Court of Common Pleas of Lehigh County for the State of Pennsylvania
Court Case No.: 2002-C-1837
http://www.canlyme.com/quackwatch.html
Hi Mike,
"including the claim that he is a Medical Board Certified psychiatrist"
I disapprove of the way you framed the problem, because Barrett never actually made that claim. Barrett was a licensed and practicing psychiatrist. This was at the time when you didn't have to pass the board certification test to be licensed. He retired in good standing with his licensing body.
I am afraid I don’t care whether Barrett was a practicing psychiatrist, or a newspaper editor, or a stay-at-home mom. I only care about the quality of his arguments. And the substance in his autism work is solid. Relative to Barrett’s autism work, if you have evidence that he made an error I encourage you to present it; you are welcome to do so here.
Also, I cannot help but to wonder what a news bulletin about this is doing on a Canadian Lyme Disease site. However, I can say that I thought rather poorly of it. It brings us such overt silliness as this:
“During the course of his examination, Barrett also had to concede his ties to the AMA, Federal Trade Commission (FTC) and Food & Drug Administration (FDA).”
I am afraid my view of the Canadian Lyme Disease Foundation is rather damaged because of it.
Thank you for your time.
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