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Chelation Therapy for Heavy Metals. Understanding Biochemical and Physiological Principles.

I have read/ heard recent descriptions of failures with chelators other than DTPA, for metals other than Gd, and it occured to me that perhaps few practitioners actually understand sufficiently the science behind chelation. This is relatively straight-forward. This blog is extremely important.

'Failures' recently described, include: EDTA failed to treat lead poisoning and patient became worse after one chelation; DMSA 'failed' to treat mercury, after 1 chelation levels of mercury were unchanged in the urine. This latter mis-interpreted as failure because DMSA does not enter the cell, but only removes extracellular mercury.

Here are the points about how chelation works related to patient physiology.

Toxicity from heavy metals (separate from radioactivity toxicity in radioactive heavy metals) should be understood on the basis of the individual's immune reactivity to the metal. The amount of heavy metal that causes reactivity generally shows variability between individuals, regarding the amount that can make an individual sick. So heavy metals retained in the body should be thought of in two categories: not making the individual sick (Storage Condition) and making the person sick (Deposition DIsease). There is also the other important variable of the duration of presence of the heavy metal in the body, that can be transient or persistent (and gradations between them). This is generally unknown for the majority of heavy metals, but is fundamentally knowable. As a whole Storage condition for heavy metals is very common (ie: everyone has lead in them) and Deposition Disease is relatively rare (for Gd, and likely lead 1 in 10,000 for mild disease, 1 in 100,000 for severe disease).

These are the rules:

  1. Presence of heavy metal is either in a Deposition Disease (rare) state or a Storage Condition state (common).

  2. An effective chelator for that metal has a high log stability constant for that metal. This is a knowable property, so using a chelator to treat a heavy metal, this value must be known. For example DTPA has mildly superior stability constant for lead than EDTA. So DTPA is a better chelator for lead than EDTA, and should be the treatment of choice.

  3. If a person has a Deposition Disease for a heavy metal, effective removal will result in a Flare phenomenon (transient worsening of symptoms associated with that heavy metal). For example mercury results in a pronounced disorder of thinking (paranoia, energetic psychosis: Mad Hatter's Disease). If there is no Flare of symptoms when using an effective chelator in a therapeutic dose, there is no Disease state, just Storage. When using a strong chelator, the more metal that is removed the greater the impulse for strong flare. This therefore is a very good thing. This is termed Metal Removal Flare, and arises immediately to a few days after the chelation.

  4. Control of Metal Removal Flare is performed with immune dampening concurrent to chelation. We employ iv steroids. Flare will still be present but manageable.

  5. Effective chelation requires multiple chelation sessions, generally 5 chelations would be the minimal for most. This is because the removal of a heavy metal generally occurs by: more effective removal of the metal from loosely bound reservoirs (eg: skin) and much less, or no, primary removal from tightly bound reservoirs (eg: bone). So effective total body removal of a heavy metal must make use of le Chateliere's principle: everything strives to be in equilibrium (re-equilibration process). Removing much of the metal from skin and little from bone) results in an imbalance of quantities in various reservoirs. With time, the metal, shifts some of its content from bone back to skin to re-equilibrate. When re-equilibration occurs, the other feature is that a fair amount of that metal is also experiencing increased elimination through urine, as re-equilibration is occurring generally by movement of the metal through the blood stream, and much of the blood stream metal is removed by the kidneys. This occurs in ernest generally about week 3 and progresses to approximately month 3 after chelation., where many p[ateau. This is termed Metal Re-equilibration Flare. The individual must go through several chelations, with some spacing in between (1 - 4 weeks) in order to make use of re-equilibration, and the resultant removal of the metal from durable reservoirs.

  6. At the present time, my opinion is that Flare primarily reflects a systemic process of increased pro-inflammatory cytokine release, and to a much lesser extent movement of the metal from one organ system to be deposited into another. That is the metal itself being now deposited in brain, when it was previously in the bone for example. This physical re-equilibration does occur in small amounts, but my opinion is that it is the cytokine release of the entire process; Gd leaving bone, Gd in circulation, Gd re-equilibration depositing in brain. But the bulk cytokine release of all 3 effects including generic re-equilibration to skin and other non-brain tissue, causes systemic release of cytokines, which is the major driver for re-equilibration Flare including neurological. In cases of severe Re-equilibration Flare, to prevent substantial movement of the metal by re-equilibration (for example to the brain), the essential treatment is further chelation, starting as soon as possible, and then carrying on chelation at regular shorter intervals (1-2 weeks).

  7. Because of these Flare effects and the nature of the step-wise process of total body metal removal, persistent periods of symptom improvement may not be appreciated till after the third-fifth chelation in most, and after an even greater number of chelations in those with large volume metal content. So perseverance is crucial when getting appropriate chelation.

  8. 24 hour urine measurements for removal of a heavy metal remain relatively unchanged, until the total body reservoir (that is bone content for many heavy metals) is reduced, and up until that time re-equilibration maintains a fairly high level of the metal in urine. This is a good thing if an effective chelator is used, as this maintenance reflects re-equilibration is occurring. It is imperative for treatment success that re-equilibration occurs. Timing intervals between chelation will effect the urine content, as the time interval is longer, the amount of the metal that re-equilibrates increases, and urine content increases. When the urine content of the heavy metal starts dropping (at consistent time intervals between chelations) this indicates that the bone reservoir is now finally being depleted, because it no longer restores Gd content to soft tissues at prior equilibration levels,.

  9. Extracellular vs intracellular removal of a heavy metal. There are many that think that it is ideal if the chelator goes into cells and removes metals that are intracellular. This may be true, but my concern is: if the chelator goes into the cell, might it also then stay in the cell, perhaps especially if it has bound the metal and now is a larger molecule? Extracellular removal may therefore be safer, as it may also make use of le Chateliere's principle: as the extracellular quantity of the metal is removed, the total body content re-equilibrates with the metal moving from the intracellular space to the extracellular space. Research into this is lacking and should be performed.

So summarizing the above: Most people receiving chelation probably do not medically need it because they are in a Storage Condition state. This would also be shown by the simple observation that they feel no Flare. The lack of Flare may be mis-interpreted as correct management is being done and the right chelator is being used, neither of which is likely correct. Metal Removal Flare occurs early after chelation, and Metal Re-equilibration Flare occurs later, in individuals who are in a toxic state from that metal (that is Deposition DIsease). The occurrence of a Flare should not be misinterpreted as treatment failure, but actually most often a reflection of treatment success- the metal is being pulled out early on, and the metal is re-equilibrating with time.. Persistent symptom improvement commonly does not begin to be observed till after the third chelation. This point is only true if an effective chelator has been used. The effectiveness determined in large measure by stability constant, which is readily knowable. Other factors such as route of administration and molecule size also play a role.

Management of Removal Flare is done with concurrent immune dampening. Management of Re-equilibration Flare is achieved by decreasing the interval between chelations (ie: shortening the interval from 4 weeks to 1-2 weeks).

Everyone performing chelation and everyone receiving chelation for any heavy metal should read this blog in order to understand what the physiological processes are (in short). A number of reports describing 'treatment failure' ironically may actually represent 'treatment success'. It is tragic when this misunderstanding occurs because patients will suffer.

Richard Semelka, MD


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