Comparing chelators for chelation of heavy metals. Critical issues to understand.

This is an expansion on an email sent to a particular person. The information is however of such importance that I have created it into a blog.

The importance of short term pre- (within 3 days of chelation) and then post-chelation (starting after first urination post-chelation) 24 hr urine results is that is clearly shows two things: 1) pre-chelation shows the native elimination of various metals, and 2) post-chelation, the extent to which a chelator is able to remove a metal. Comparison between chelators at least 1 month apart reveals a comparison between them regarding their relative effectiveness. Probably no other measure and treatment in all medicine is more accurate in assessing effectiveness.

In selecting chelators, it is appropriate to assess their removal capability based on: 1) intrinsic stability constant of chelator with the metal of interest, and 2) the real world data of the pre- and post 24 hour urine determination. In general I do not recommend random use of a chelator if no useful stability constant is known (such as stability with Gd or with lead).

There is an enormous amount of confusion of what the amount of metal removed post-chelation in 24 hour urine samples represents. It is straightforward, it reflects: 1) intrinsic ability of the chelator to remove the metal, and 2) in individuals undergoing serial chelation, the interval between the prior chelation and the current chelation. The longer the interval, the larger the amount of metal removed, which reflects the effects of re-equilibration (le Chateliere's principle). A short interval between prior chelation and current would show relatively lower removal (based on relatively little re-equilibration having been allowed to occur), and a greater interval would show more..

Looking at the comparison between DMSA and DTPA, these results have shown that DTPA is much superior to DMSA to remove Gd (already expected based on stability constants) but also superior to remove lead (our prior findings have shown this), but interestingly also show improved removal of Cesium and Thallium, which would not necessarily be predicted in advance, because these stability constants with DTPA and DMSA with these metals have not been determined. The finding suggests adequate removal of Cesium and Thallium with DTPA, but also that the amounts are so high (even pre-chelation) you may need to eliminate all cruciferous vegetables from your diet, not just kale (kale I have focused on in the past).. Also to stay away from significant auto and industrial pollution. Had DTPA not shown very high elimination of Cesium and Thallium I would have recommended you try Prussian Blue (produced by Heyl, Germany) to compare these metals removals to what DTPA accomplished. The comparison though may still be of interest.

The above observations should also include correction of this common misunderstanding: many individuals have undergone DMSA or EDTA chelation for lead and/or mercury and the assumption has been when these metals were no longer detected that it reflected these metals were now fully removed. 1) it is impossible to remove all amounts of metals even with the perfect chelator, and more importantly 2) what is actually shown is that DMSA or EDTA are no longer able to remove more of the metal, either because of the low concentration left, in part reflecting the amount left is minimal, and/or critically that the agents are limited in their ability to show removal of metal when it remains solely in the most durable repository (generally bone). Waiting some months, to allow for more re-equilibration out of bone may reveal more metal post-chelation. Important to understand that it does not (necessarily) mean more metal has been introduced in the body, but that more time elapsed has allowed the metal retained to move from bone to reservoirs easier to remove metal from (eg: skin).

I have described this essential point before, but worth repeating here: A number of individuals have been disappointed seeing the post-chelation amounts of Gd still being high, making the incorrect impression that chelation is not working. What is critical to understand though is that it is showing continued effective elimination of total Gd content from the body. This continued high urine amount of Gd reflects the effects of re-equilibration, of Gd moving from bone back to reservoirs easier to remove by chelation. When the post-chelation amount of Gd eventually starts dropping, this shows that total body reservoir of Gd is now being reduced. So this is extremely powerful information. Remember the effect of time interval between chelations on this measure.

Additional important tidbit: 1. I use 24 hour urine testing because I assume based on knowledge of everything else (most notably serum Creatinine (sCr)) that there is diurnal variation in the elimination of... everything.... That said, since I have not studied diurnal variation of Gd removal post-chelation, knowing it must be present, I take that out of the equation, by simply sampling the full 24 hr, and all measures are not 100% accurate and written in stone, there are multiple variables present that can effect elimination, probably at least 5 important and another 95 with some contribution. 3. removal of Gd from bone original I thought was like the melting of an ice cube, relatively constant melting, now I consider it more likely reflects the melting of ice in a large land mass (tragically like Greenland and Antarctica) a fair amount is the constant dripping of melting ice, but this is interspersed with the breaking off of ice bergs of varying size.

A final important observation is that all chelators show some removal of all metals, and chelators with low stability constants for critical metals should essentially never be used, unless they are followed in short interval by a stronger chelator. So DMSA or DMPS should never be used in subjects with GDD, unless within a few days they are followed by DTPA to remove the redistributed Gd by the wealer Gd chelator.

So what I know now, of FDA- approved available chelators:

1. chelation with DTPA with concurrent steroids/antihistamines is the most effective method to remove Gd in GDD subjects.

2. chelation with DTPA with concurrent steroids/ antihistamines is the most effective method to remove lead in Lead Deposition Disease patients.

3. For most other metals, a comparison trial as described above is useful to determine the more effective chelator. But there must be pre-existent empiric evidence that the tested chelators in principle should be effective, otherwise the results of Redistribution Flare may be disastrous.

This is one of the more important blogs, re-read it again to understand the 15 or so critical points described above.

Richard Semelka, MD