Why “Provoked” Testing for Heavy Metals Is Improper

Robert S. Baratz, M.D., D.D.S., Ph.D.
June 24, 2016

Under ordinary circumstances, the body takes in a certain amount of heavy metals from the environment (food, air, water) and excretes a similar amount. Essentially, what goes in comes out, and proper testing will reflect the individual’s average daily exposure. Chelationists—and others who profit from their work—see things differently. They claim that many people have trouble excreting heavy metals that supposedly accumulate and make them sick. Some also claim—improperly—that autism is caused by heavy metal intoxication. Provoked testing is also called “challenge testing.”

Because blood and urine levels reflect what is taking place in the body tissues, the simple way to test such claims is to measure blood or urine levels of the ions. In standard urine testing, samples are collected for 24 hours in specially washed containers. When tests of this type are done in people with no signs of toxicity or obvious exposure, the levels of lead, mercury, and other heavy metals are very low. Chelationists, however, claim that standard tests fail to detect “hidden body stores” and that additional effort must be taken to demonstrate them. The method they use—called “provoked” testing—is done by administering a chelating agent that temporarily increases the excretion of heavy metals into the urine. The increase is then interpreted as “proof” of toxic levels, even when the person has no symptoms of toxicity or history of exposure to toxic substances.

Provoked testing has been severely criticized by the scientific community and regulatory agencies:

  • In 2009, the American College of Medical Toxicology (ACMT), which is the leading organization of toxicology experts, issued a position statement which concluded that provoked 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.” [1]
  • In 2010 The Medical Letter on Drugs and Therapeutics, which is the scientific community’s most respected drug advisory, criticized the use of provoked testing as a prelude to inappropriate chelation therapy and that “the results of provoked urine testing are not an acceptable basis for such treatment.” [2]
  • In 2012, the AMCT and U.S. Centers for Disease Control and Prevention held a conference on chelation therapy at which provoked testing was denounced [3].
  • Several state boards have disciplined physicians who used provoked testing and have ordered them to stop [4].

Chelating agents work by strongly binding to the metal ions circulating in the blood (serum) and forcing their excretion through the urine. Chelation temporarily accelerates the removal of ions that the body would normally remove slowly. It should not be used, however, unless a person has a dangerously high level level in addition to symptoms of toxicity. When chelation is administered to someone who does not have a high level, the serum levels of ions temporarily fall and the urine levels temporarily rise [5-7]. The chelating agent is cleared from the blood within a few hours. The blood and urine levels of ions gradually return to their pre-chelation (steady state) levels.

Chelationists claim that (a) “body burden” can be estimated by comparing the patient’s urine levels before and after provocation and that (b) the temporary rise in urine levels represents removal of “hidden body stores” of these ions. However, these claims are incorrect [8-9]. During provoked removal, the same ions that would normally be excreted are excreted—only faster. Most important, the amount removed does not indicate how much was there to begin with or was left behind. Further, most provoking agents are not specifically selective in what they remove.

Imagine a classroom with 60 seats and one student in each seat. If one student goes from the room into the hallway each minute, the room will empty on one hour. If two students leave per minute, the room will empty in half an hour. If you reasoned like a chelationist, you would conclude that at some arbitrary time (say 15 minutes), the number of students who have entered the hallway reflects the number who were originally in the room—and that if more arrive in the hall sooner, there must have been more in the room to begin with. The fallacy of this thinking is obvious, but this is what chelationists do by measuring ions in the urine during short periods of time after the patient takes a chelating agent that accelerates excretion.

Illnesses due to heavy metal toxicity are not common and are unlikely to occur without obvious exposure. Studies of industrial workers have shown that there are dose/response relationships between exposures to metal ions and any adverse consequences. Until a critical level is obtained, no adverse consequences are noted. These dose/response relationships dictate safe exposure levels for workers that allow for exposures up to eight hours a day for fifty weeks a year. These are then codified into concepts such as TLV (threshold limit value) and PEL (permissible exposure limit). Non-industrial exposures are always many orders of magnitude less than these safety limits. As workers begin to exceed the TLV, the point at which symptoms of excess exposure begin, specific changes for a specific metal ion can occur. Stopping exposure at this point will return the worker to a normal, symptom-free state. Extremely large quantities of foreign or excessive divalent metal ions can cause adverse effects by binding to essential enzymes, structural proteins, or other sites. In order for such toxicity to happen, large quantities of the ion must circulate and get to an essential site, where it presumably does its damage. Multiple forces and mechanisms exist to prevent this from happening. Selective absorption mechanisms, binding to plasma proteins, and the blood-brain barrier are three of the many barriers that prevent unwanted ions from causing havoc in the body. Typically the only corrective action required is removal from further exposure. The body will then continue excreting excess ions until it reaches its baseline steady state. There is no evidence that low-level exposures of metal ions commonly found in food, water, and air are harmful or that amalgam fillings and thimerosal-containing vaccines pose any risk to the general public.

Federal Regulation Needed

The laboratories that test provoked specimens for chelationists are certified by CLIA, the federal agency that certifies laboratories. CLIA examines only how tests are performed to ensure that measurements are accurate. It does not consider how the laboratories interpret their findings. Widely used diagnostic tests require FDA clearance or approval, but the agency has not attempted to regulate tests that are used only by the laboratories that develop them. During the past few years, however, the FDA has become concerned about laboratory-developed tests that are used to guide treatment decisions. In 2015, it reported on twenty such tests, noting that some of them can cause patients to undergo unnecessary treatments and potentially delay diagnosis of their true condition [10]. The report classified provoked testing for heavy metals as “a test linked to treatments based on disproven scientific concepts” and noted that (a) in clinical use, patients with positive urine chelation challenge tests may not have heavy metal toxicity and (b) false-positive results may lead to the administration of therapies that are inappropriate, unproven, and/or dangerous [11].

The Bottom Line

In my opinion:

  • There is no logical reason to screen people for toxicity unless there is real reason to believe they have been exposed.
  • Provoked testing that misleads people into thinking that they need chelation is unethical.
  • Like all other drugs, chelation agents can cause adverse effects.
  • The use of chelation therapy for nonexistent poisoning entails risk without benefit and is unethical.
  1. Charlton N, Wallace, KL. Post-chelator challenge urinary metal testing. American Journal of Toxicology 6:74-75, 2010.
  2. Nonstandard uses of chelation therapy. The Medical Letter 52: 75-76, 2010.
  3. Ruha A-M. History and current recommendations for provoked challenge urine testing. AMCT/CDC seminar on the use and abuse of metal chelation therapy, Feb 29, 2012.
  4. Barrett S. How “provoked” urine metal tests are used to mislead patients. Quackwatch, May 26, 2017.
  5. Gonzolez-Ramirez D and others. Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans. II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in Monterrey, Mexico. Journal of Pharmacology and Experimental Therapeutics 272:264-274, 1995.
  6. Maiorina RM and others. Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans. III. Urinary mercury after exposure to mercurous chloride. Journal of Pharmacology and Experimental Therapeutics 277:938–944.
  7. Ruha A-M and others. Urine excretion following meso-dimercaptosuccinic acid challenge in fish eaters. Archives of Pathology and Laboratory Medicine 133:87-92, 2009.
  8. Allain P and others. Effects of an EDTA infusion on the urinary elimination of several elements in healthy subjects. British Journal of Clinical Pharmacology 31:347-349, 1991.
  9. Frumkin H. Diagnostic chelation challenge with DMSA: A biomarker of long-term mercury exposure? Environmental Health Perspectives 109:167–171, 2001.
  10. Laboratory developed tests. FDA Web site, Nov 17, 2015.
  11. FDA Office of Health Strategy and Analysis. The public health evidence for FDA oversight of laboratory developed tests: 20 case studies. Nov 16, 2015.

Dr. Baratz, who practices in Braintree, Massachusetts. has extensive training and practical experience in internal medicine, occupational medicine, emergency medicine, oral medicine, dentistry, material science, and research methodology. He is a faculty member in the department of medicine at Boston University School of Medicine and Tufts University School of Medicine. He also serves as a medical and dental consultant to many state licensing boards, federal agencies, insurance companies, and the legal profession.

This article was revised on June 24, 2016.