Heavy metal chelation

Garry Gordon EDTA 2002 second draft

Andy Cutler potocol Both Dimercaptosuccinic Acid and DimercaptoPropane Sulfonic Acid are mentioned as chelation agents. The SW College of Naturopahic Medicine conducted a DMSA clinical trial of autistic kids in 2008

Definitely not the Cutler method as dosing used was very high 10mg/kg/dose 3x/day x 3 days.

Cutler uses much lower dose (at least initially) and every 4h would be 6x/day.

Interesting thing is that 1 round was nearly as good as 7 (3 days every 2 weeks) due to the initial round having such beneficial effect.

The cool thing about 1 round helping suggests that the cycle of oral microbiome to detox can be done quickly back and forth maybe alternating weekly so oral microbiome every 2 weeks and detox every 2 weeks.

I find it odd that Adams does not appear come back to beneficial things such as this as well as the FMT. Probably as both things are not accepted. Maybe he could not get approval for future studies. There is still something odd about it.

The EDTA clinical Trial

The one clinical trial we have to assess the safety of EDTA for the purpose of chelation of calcium from atherosclerotic plagues used injected EDTA. Unfortunately we do not know how EDTA is absorbed. We can point to some possibilities such as the monocarboxylic and The MCTs transport compounds such as lactate and pyruvate. SLC13A5 is the Na+ coupled citrate transporter that transports a variety of tricarboxylic acids but has a prefrence for citrate. Pept1, aka the peptide tanasporter and SLC15A1, is responsible for absorption of di- and tri-amino acid peptides.

Quicksilver Scientific sells the disodium salt of EDTA. The frustrating thing is that we do not know how and if EDTA is absorbed by the gastrointestinal tract. It does make sense, hypothetically, that NA2-EDTA could be taken up by pept1. The structures of two glutamate di-peptides are shown to make the case. Would this mean that EDTA for the purpose of oral chelation would be best taken without food or at least on a low protein meal? Back to the tiral, the participants were expected to receive 40 of these doses within a year. [2] The actual dose is being calculated based on the glomerular filtration rate.

Some screen capture highlights documenting the basic dosing and the safety monitoring.

Back to Gary Gordon

Second Draft, May 15, 2002

Note: Garry Gordon does not seem that removed form the TACT, trial to assess chelation therapy [2]mentality. The following are some highlights of his second draft.

By Garry F. Gordon MD DO MD (H.) – Chairman, Peer Review Committee on Chelation for the
Arizona Board of Homeopathic Medical Examiners. Direct IV push of CALCIUM EDTA* 50 mg per Kg body weight (not to exceed 3 gms) given with no dilution through a 23-gauge butterfly infusion needle
10-15 Capsules Oral Essential Daily Defense**
(First dose can be 5 caps on arising or 2 to 4 hours before the IV Second dose 5 capsules again immediately when the IV push is given
Third dose of 5 capsules may be taken that evening, or 4 + hours after the IV push)
**Available at Longevity Plus, Payson, AZ (800-580-7587) http://www.longevityplus.com
One-Minute Push of Calcium EDTA

Cites some Eurppean experiences with IV.
We have physician colleagues that have taken over 2000 IV’s of 3 gram dosages, at the slow 1.5

  • Some discussion on slow versus fast IV influsion/”pushes”
  • The provocative urine and fecal mineral tests appropriately done will routinely find such elevated levels in virtually every patient, that they will want the treatment
  • Goes off on the bad polluters of lead and mercury and how your patients deserve his treatment.
  • More propagantda and cites some European MDs that have worked with hin on higher doses of oral EDTA, such as the over 6 GM daily by mouth I have been on now for 6 + months, and over 2 Gm daily for years
  • However almost any patient by sending a fecal and a 6-hour urine mineral test off after the old method of chelation and then repeating these two tests a few days later using my well proven oral EDTA product (EDD), combined with 1-minute IV EDTA technique. The resulting dramatic increase in toxic metals seen in urine and feces using this protocol will astound and convince you.
  • Some discussion was given for the rectal route when the patient has a sensitive stomach and/or is unable to swallow.
  • Need for informed consent, explain to patients better nitric oxide levels and more energy, bu caution that the next arteriogram or heart scan, and some, particularly those
  • We recognize that any renal testing related to chelation therapy, unless it is forDOCUMENTABLE metal poisoning cases, is not considered reimbursable by some insurance companies such as Medicare, since they feel the test is being done to monitor an uncovered experimental therapy.
  • Goes on about convincing patients that paying out of pocket for urine heavy metal testing. Says nothing about stopping the therapy once the urine tests show a decrease in excreted heavy metals.
  • Claims that oral EDTA is only 5-18% absorbed so the remainder can remain in the intestine where it is able to chelate any toxic metals presented through the bile through the bowel/capillary interface by the IV EDTA.
  • makes a good case for oral EDTA also wants the stool samples sent to Doctors Data for ICP-MS analysis. .
  • Thus, our patients deserve to be shown accurately just how relatively toxic they are and I know of no way better than following this protocol and collecting URINE and FECAL material for testing to establish this information.”
  • Seems somewhat flippant about renal testing then says he will leave it to the physician in charge.
  • Plug for oral EDTA and Daily Defense and how much your patients deserve to pay for fecal heavy metal testing..
  • Please recommend 10 to 15 of the oral broad-spectrum chelator EDD, containing EDTA andother chelators such as Garlic, malic acid, dl methionine, etc. the day you give the IV push. The IV and another 5 capsules again immediately when the IV push is given to help prevent anyenterohepatic re-absorption of toxic metals. The third dose may be taken that evening, or even
  • Plugging for Daily Defense and his garlic thing.
  • An ORAL provocative challenge.1000 mg of EDTA dose for every 35 pound of body weight so that a 175-pound patient may now receive a full 5 gm of ORAL EDTA as a provocative test when they arnot able to take the IV push. we might also provide 3 gm of the dose as 1 level tsp of ORAL EDTA (pure powder in water or juice, pleasant tasting and easy to take) and the other 2 gm as 15 capsules of the EDD. This is because without the additionof EDD to the provocative test, we are not getting any of the necessary thiol groups (SH-as we
  • For the patients receiving parenteral EDTA of any kind, the toxic heavy metals presented to theGI tract by the portion of the IV EDTA that does go through the liver and into the bile, is trapped and held in the intestine by the generally poorly absorbed oral EDTA, which in this case is an
  • Discusses several alternative medicine anti-inflammatory approaches.

Finding good studies on oral route EDTA is difficult because the much maligned TACT studies included oral multivitamins. More of Garry Gordan’s work will not be reviewed on this site.


Dr Adrian does not like EDTA chelation therapy but prefers DMSA. This site didn’t really reference real studies.

PubChem has a nice review on the drug warnings

BOXED WARNING/ The use of this drug in any particular patient is recommended only when the severity of the clinical condition justifies the aggressive measures associated with this type of therapy.

US Natl Inst Health; DailyMed. Current Medication Information for Endrate (edetate disodium, anhydrous) injection, solution (May 2006). Available from, as of February 16, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=290c3e9c-c0c6-440a-1a9c-46e3e2b07a77

Clinical studies of edetate disodium did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

US Natl Inst Health; DailyMed. Current Medication Information for Endrate (edetate disodium, anhydrous) injection, solution (May 2006). Available from, as of February 16, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=290c3e9c-c0c6-440a-1a9c-46e3e2b07a77

Fatal medication errors have occurred that involve confusion between edetate calcium disodium (calcium EDTA) and edetate disodium (no longer commercially available in the US). Children and adults have mistakenly received edetate disodium instead of edetate calcium disodium; at least 5 deaths have occurred as a result of inadvertent administration of edetate disodium. Although both edetate calcium disodium and edetate disodium are heavy metal antagonists, the 2 drugs were originally approved by the US Food and Drug Administration (FDA) for different uses and have different effects; edetate disodium was formerly FDA approved for use in selected patients for the emergency treatment of hypercalcemia or for the control of ventricular arrhythmias associated with cardiac glycoside toxicity. Use of edetate disodium may result in a substantial, and sometimes fatal, decrease in serum calcium concentrations. In June 2008, FDA withdrew its prior approval for edetate disodium because of safety concerns following a review of the risk-benefit profile of the drug. FDA stated that it was not considering additional action regarding edetate calcium disodium at that time; most of the fatalities following administration of an EDTA drug have involved medication errors in which edetate disodium was administered instead of edetate calcium disodium. FDA has not received reports of any fatalities resulting from the administration of edetate calcium disodium that involve a medication error.

American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011

Edetate Disodium Injection is contraindicated in anuric patients. It is not indicated for the treatment of generalized arteriosclerosis associated with advancing age.

US Natl Inst Health; DailyMed. Current Medication Information for Endrate (edetate disodium, anhydrous) injection, solution (May 2006). Available from, as of February 16, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=290c3e9c-c0c6-440a-1a9c-46e3e2b07a77


went to FDA.gov and failed to find any dire..EDTA is in all sorts of processed food and hopefully on the GRAS list.

The EPA summarized a toxicology study that is not free.

This is but a small sampling:

In all available toxicology studies (rodent and nonrodent species), the lowest dose reported to the FDA that caused toxicological effects was 750 mg/kg/day of either Tetrasodium EDTA, Calcium Disodium EDTA, or Disodium EDTA. … I’ve editied out the opthalmic, IB, and cutaneous toxicology remarks.

  • The acute oral LD5o of Disodium EDTA was ca 3.7 mg/kg in male and female rats. …
  • Some studies have demonstrated toxic effects, such as increased permeability and severe congestion and hemorrhage, occurring in the intestine.
  • A short-term toxicity study fed Trisodium EDTA Trihydrate to rats and found that male rats fed and gt; = 10,000 ppm and female rats fed and gt; = 14,700 ppm had soft stools, a sign of compound-related toxicity. No signs of organ toxicity or gross pathologic changes were observed. Rats treated for 21 days with Calcium Disodium EDTA died of nephrosis. Administration of EDTA in drinking water to mice at a concentration of 3.4 mM caused changes in the mineral content of certain tissues.
  • Eighty rats fed 5.0% and 10.0% Disodium EDTA for 13 weeks had significantly decreased feed consumption and body weight gain compared to controls. Rats of the high-dose group also had slightly pale livers at necropsy. No other signs of toxicity were observed. …
  • In several studies rabbits, rats, and dogs were fed Calcium EDTA (high dose 250 mg/kg), Disodium EDTA (high dose 5.0%), and Calcium Disodium EDTA (high doses 250 mg/kg/day and 1.0%). No gross or microscopic abnormalities were observed..
  • Pregnant rats fed 3% Disodium EDTA at various stages of gestation demonstrated gross malformations when supplemented with 100 ppm zinc as opposed to 1000 ppm zinc. Maternal and fetal toxicity were not observed with ZnEDTA (dosed at 8 and 20 mmol/m2/day) or ZnCaEDTA (8 mmol/m2/day). EDTA administered by gavage and in feed to rats on GDs 7 to 14 at 1000 mg/kg/day and 1250 mg/kg/day, respectively, caused maternal toxicity and malformations in the offspring. In mice, however, offspring of dams treated with 1000 mg/kg/day EDTA orally on GDs 8 to 12 demonstrated no malformations. It has been suggested that the zinc deficiency produced by EDTA resulted in teratogenic effects.

The DMSA clinical trial

flow chart of the DMSA trial design [2] The brand and the amount of GSH in the cream are not given. It was also not mention if GSH can diffuse past the stratum corneum. The introduction gave a good argument for plasma GSH being low in ASD. The dosage was 10 mg/kg-dose, 3×/
day, for 3 days. The DMSA was compounded individually for each child from pharmaceutical grade DMSA (over 99% pure) supplied by Spectrum Chemical. Parents collected all urine ~8 hours after the first
dose and for approximately 8 hours after the 9th dose. High excretors entered the 2nd phase.

Dosage of Glutathione
The daily topical dosage of glutathione was approximately 180 mg of reduced l-glutathione in a lotion of isopropyl myristate, mineral oil, caprylic/capric trigliceride, and vitamin E acetate. The placebo was identical in packaging and formulation except it did not contain glutathione. To be honest, I think this is an unnecessary expense for the parents and I also think keeping the GSH reduced is also problematic.

Dosage of DMSA
The dosage of oral DMSA was 10 mg/kg per dose, in 3 doses per day. This is the dosage recommended in the
Physician’s Desk Reference (PDR), and the dosage they used in our previous 9-dose study [3]. All we know about the inert materials was that one was methyl cellulose. We also know that DMSA has a very strong odor. We were not told how the odor was masked in order for the kids to take it.

GSH creamN-acetyl cysteine cream
DMSASpectrum Chemicalnot applicable
urine heavy metalDoctor’s
Data Laboratories
well water test strips: Pb, Hg, Cu, Fe JNW and Hofun

The Adams group used the Doctor’s Laboratories range to select children excreting above the 95% of the reference range of those not on chelation therapy to enter the second phase. The lab used the gold standard ICP-MS to quantitate the heavy metals. We may get away with semi-quantitative strips that are used for water testing. Many are available from Amazon.com. This may be an inexpensive to determine if the chealtion therapy is working. We will need to call the vendors

Phase Two
1) The blood chemistry, CBC, and RBC glutathione were re-measured at the beginning of phase 2. If liver and renal function were normal, if CBC’s were not low, and if there was significant excretion of metals in Phase I, then the children were selected to continue into phase two

2) Autism Diagnostic Observation Schedule (ADOS) examinations were administered (approximately 1 hour
assessment) by an ADOS-certified evaluator to further characterize the participants. Each child was always examined by the same evaluator at the beginning and end. Of the 41 participants that were evaluated and finished the study, 81% met the criteria for Autism, 12% more met the criteria for ASD, and 7% did not meet the criteria for ASD, according to the sum of the Communication + Social Scores. All children continued on in the study, since they all had a previous clinical diagnosis of ASD.

3) Parents filled out two questionnaires on severity of autism, the Pervasive Developmental Disorders – Behavior Inventory (PDD-BI) and Severity of Autism Scale (SAS).

4) Children received the DMSA or placebo, and took them for up to 3 rounds. Each round consisted of 3 days of DMSA/placebo (as in Phase 1), followed by 11 days of no DMSA/placebo. The children who had originally received glutathione lotion were given DMSA, and those who had received the placebo “glutathione” lotion received the placebo “DMSA”. The families continued to be blinded in the
second phase of the study. This design resulted in one group of children who had topical glutathione and oral
DMSA challenge followed by continued administration of DMSA and a second group of participants who underwent a single round of DMSA challenge without topical glutathione and who subsequently did not receive any further
5) Urine was collected after the 9th dose of DMSA (or placebo) at the end of the 2nd round in Phase 2. This was shipped to Doctor’s Data for testing.
6) After the 3rd round of DMSA (or placebo) in Phase 2, blood chemistry and CBC were measured again. If children had normal kidney/liver function and normal CBC, and if they continued to have elevated excretion of toxic metals in their urine based on their 2nd round of testing, they were given another 3 rounds of DMSA/placebo.
7) After the 6th round of DMSA in Phase 2, a final blood chemistry and CBC were measured.
8) When the participants finished Phase 2 (after either 3 or 6 rounds), an ADOS evaluation was conducted by the same evaluator who conducted the first evaluation. The parents again filled out the ATEC, SAS, and PDD-BI, as well as the Parental Global Impressions questionnaire. The professional working with the child was asked again to fill out the ATEC form for the child.

Monitoring excretion over time

Some of the Adams strategy was to stop the DMSA as soon as the excretion of heavy metals stopped.

Figure 2 above and below excretion of toxic metals Percentage change in urinary excretion of toxic metals. a: Percentage Change in Urinary Excretion of Toxic Metals after 1st and 9th Dose of DMSA in Phase 1. (n = 63). b: Percentage Change in Urinary Excretion of Toxic Metals after 1st and 9th dose of Round 1, and then 9th dose of Rounds 3, 5, and 7, for the group who received 7 rounds of DMSA. (n = 20).

It looks like the big changers are Pb and Sn followed by Hg. The environmental sources of Pb and Hg are obvious.

This study must have cost a small fortune. We need to figure out if the water testing Pb strips can detect normal amount of Pb in urine.

Pb from paint and Hg from fish are the ones most responsive to the chelation therapy. Note that arsenic is increasing in going from round 2 and round 4. Is this increase the same for all the trial participants. Note that As is increasing? One thing that is missing in a lot of these data are standard deviations. The “”” tells us that the change is significant.


(only correlations >0.31 in magnitude are listed, corresponding to p =0.01 on an individual comparison basis)

What tables 4 and 5 tell us is that Pb test strips can predict excretion of Tl, As, and Al. I’m not sure we really care about Table 6.


Note: The Adams group remarked that that they had to perform the liver enzyme test in their trial because a previous lead detox study with DMSA to treat lead poisoning for 21 days showed an increase in liver enzymes. The Adams group saw no such increase because they only treated for three consecutive days with an 11 day gap for phase 2.

Phase 2 Participation

49 children began Phase 2, and 41 finished (including 5
in treatment group who finished early due to low excretion of urinary toxic metals after 2nd round of DMSA in Phase 2.

  • 1 was discontinued due to elevated liver enzymes due to
    their psychiatric medication.
  • 1 dropped due to a death in the family
  • 2 dropped due to perceived lack of benefit – 1 was on
    placebo, and 1 was on DMSA.
  • 4 dropped due to adverse effects: sleep problems (on DMSA) behavior and some skills worsened (on DMSA)
  • 5 participants completed Phase 2, Round 2, but their urinary excretion of toxic metals had decreased below our cut-off and did not qualify them to continue into the rest of Phase 2; so, they completed the study after receiving 1 round of DMSA in Phase 1 and 2-3 rounds in Phase 2.

Loss of essential metals

The authors seem to think that potassium and chromium are potential issues. These could be easy to supplement. The Hofun test strips, available on Amazon, test for Cr in addition to Cu, Hg, Pb, and Fe.

Correlating heavy metals with improvements

The actual test results correlated with heavy metals in the urine were a separate publication.[4] The Adams group stopped the potentially liver damaging detox protocol as soon as the appearance of heavy metals in the urine abated. Assuming that we cannot use ICP-MS for daily urine collections, we need to think about the heavy metals detoxed that correlate with improvements.

There are more tests and tables like this one. The real power in monitoring the detox process comes, in my opinion, in figuring out which heavy metal is important.

Dr Haley and OSR

OSR is eneramide, a compound developed to treat Hg poisoning. This compound is made from two dietary agents containing sulfur, Cysteimine is a breakdown product of cyst 24 hour half life in blood of rats. Gets into the plasma and penetrates every tissue of the body and gets into the blood. binds Hg, Cd, Pb… also binds unbound Fe. Binds to Hg and does not let go. Also called NMBI.


  1. Lamas GA, Anstrom KJ, Navas-Acien A, Boineau R, Kim H, Rosenberg Y, Stylianou M, Jones TLZ, Joubert BR, Santella RM, Escolar E, Aude YW, Fonseca V, Elliott T, Lewis EF, Farkouh ME, Nathan DM, Mon AC, Gosnell L, Newman JD, Mark DB; TACT2 Investigators. The trial to assess chelation therapy 2 (TACT2): Rationale and design. Am Heart J. 2022 Oct;252:1-11. PMC free article
  2. Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr J. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A–medical results. BMC Clin Pharmacol. 2009 Oct 23;9:16 PMC free articlehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774660/
  3. Amadi CN, Orish CN, Frazzoli C, Orisakwe OE. Association of autism with toxic metals: A systematic review of case-control studies. Pharmacol Biochem Behav. 2022 Jan;212:173313.
  4. Amadi CN, Orish CN, Frazzoli C, Orisakwe OE. Association of autism with toxic metals: A systematic review of case-control studies. Pharmacol Biochem Behav. 2022 Jan;212:173313.Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr J. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B – behavioral results. BMC Clin Pharmacol. 2009 Oct 23;9:17. PMC free article
  5. OSR by Dr Haley
  6. Schutzmeier P, Focil Baquerizo A, Castillo-Tandazo W, Focil N, Bose-O’Reilly S. Efficacy of N,N’bis-(2-mercaptoethyl) isophthalamide on mercury intoxication: a randomized controlled trial. Environ Health. 2018 Feb 14;17(1):15. PMC free article
  7. Skalny AV, Skalnaya MG, Bjørklund G, Nikonorov AA, Tinkov AA. Mercury as a possible link between maternal obesity and autism spectrum disorder. Med Hypotheses. 2016 Jun;91:90-94.
  8. Ke T, Antunes Soares FA, Santamaría A, Bowman AB, Skalny AV, Aschner M. N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization. Toxicol Rep. 2020 Jul 31;7:930-937. PMC free article

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