Total body heavy metal burden. A concept that many practitioners of heavy metal treatment do not understand, but this is crucial
Total body heavy metal burden (TBHMB) is a concept that most practitioners of chelation and other heavy metal issues do not fully appreciate.
I have observed this lack of awareness through my work with Gd, and the misinterpretation of results with this metal, and analyzing the misunderstanding of observations made in papers written on other metals, essentially by incorrect interpretation of persistently high presence of metal in removal samples, mainly of urine but also of feces. Using Gd as the standard, persistently high 24 hr urine post chelation has made many GDD sufferers dejected, thinking that the high numbers reflect that the treatment may not be working, because numbers are still high. This does not reflect some failure of chelation, because the amount of Gd removed in urine still seems the same, despite a number of chelations. Quite the opposite, this observation reflects that the heavy metal continues to be removed in a large amount. The vast majority of times this reflects that TBHMB is being reduced by the occurrence of re-equilibration: Gd moving from one durable reservoir (bone) back to less durable reservoirs (skin, soft organs), where chelation then continues to reduce TBHMB. This is a very good thing.. To go over again how this process works, the chelator has directly removed disproportionately more Gd from the more loosely bound reservoir (soft tissues) compared to bone. With time, commencing in earnest at week 3 post chelation, metal moves from tightly bound (bone) to less tightly bound (soft tissues) reservoir regions to re-equilibrate. This is le Chatelier's principle, everything strives to be in equilibrium. As this movement occurs, some of that Gd in transit is also being eliminated in urine.
When the 24 hr urine post chelation starts dropping into the low yellow range (3 mcg - 5 mcg/ 24 hour, this reflects when the TBHMB) is now beginning to drop substantially. It is critical to know that when poor chelators are used for any metal, low numbers may actually reflect the artifact that the chelkator is unable to remove metal, rather than the metal is now very low in TBHMB. I have written in prior blogs on the effect of timing interval between chelation sessions as it effect 24 hr urine measurements (the shorter the interval between chelation, the lower the amount removed on 24 hr urine samples. Probably the most true surrogate for the TBHMB is obtained beginning at 3 months post last chelation. Acceptable surrogates are what we typically measure at 3 weeks - 1 month since prior chelation session.
So factors that influence the amount of metal (we use Gd for this example). that is removed in 24 hr urine post chelation.
what we are most interested in, the effectiveness of the chelator to remove metal. We always then use pre- and post-chelation 24 hr urine measurement.
time when post-chelation urine collection starts (and stops). We use 24 hr urine. We start within 1 hr after chelation. The first urine- hopefully right after or in the middle of chelation - discarded, because most of that urine did not experience chelator. Collection continues for 24 hours. This gives us a 24 hour elimination. Ofcourse if we collected urine for only one hour after we finished (a spot urine test), we would observe a much greater amount of Gd in urine. But as with essentially everything, standardization is always wise, and I like the standard of 24 hr as it also takes into account the uncertainty of diurnal variation of how Gd is eliminated. If we collected urine for just 1 hour using the above start time and then multiplied x 24, likely we would get a number that would be vastly higher (but incorrect) than the 24 hour measurement that we actually perform, because urine removal with chelation follows a decreasing amount decay curve. Greatest removal would then be beginning immediately post-chelation for 1 hour, and decay from there.
time between chelations. The more time between chelations, the greater amount of re-equilibration with have occured. So measuring 24 hr urine with weekly chelations would show a lower amount of Gd post-chelation than chelations spaced every 4 weeks. There would be the tendency then with weekly chelations to think that less Gd is still present in the body, but instead what is shown is less time has been allowed for re-equilibration. The recent prior chelation had already removed a fair amount of Gd from the soft tissue reservoir, and there is less Gd in that location at that time to remove, with weekly chelation. A number of individuals have been alarmed seeing 24 hr urine is low, and then suddenly it is high again after chelations, and then worry that nothing has happened as far as Gd removal. This scenario has often been the result that the early post chelation urines were obtained with weekly chelations, and a later one at monthly, or even longer interval. The most accurate means to see what the total body reservoir of Gd is left is to repeat pre- and post-chelation 24 hour urines at 1 year after the last chelation, because at that time near complete re-equilibration has occurred. I have also heard misinterpretations of urine amounts comparing OSR and DMSA, that higher levels of mercury detected on DMSA later on reflected that DMSA only removes extracellular mercury and OSR intracellular.=, and the intracellular removal is key. The amount of metal removed by a chelator as shown on urine studies is always important, The more removed, the better the chelator. A lot of metal movement between intracellular and extracellular locations also are subject to le Chatelier's principle. The more metal removed is almost always a great thing.
GBCA agents that remain fully intact, Dotarem/ Clariscan and Prohance, the 24 hour urine measurements are routinely low, and this does not reflect (necessarily) that the amount left behind is low, but also represent that DTPA is only modestly effective at removing a fully intact GBCA agent. In this case we must rely heavily on symptomatic improvement, since DTPA can still remove enough of these agents to result in symptom improvement.
With the use of poor chelators there may be both the misinterpretation that there is not that much metal present in the native setting, because what is actually shown is that the chelator is poor at removing the metal, and there may or may not be little metal present.
Chelators that also remove metals by hepatobiliary elimination, in order to observe the full effect, pre- and post-chelation stool measurements should also be obtained.
Stability constant of the chelator with metal in question is critical. It is always critical to decrease the amount of redistribution- the amount of heavy metal picked up and immediately dropped back off in the body.
In the setting of Gd, almost uniquely of the heavy metals, it is possible (and should always be done with GDD sufferers) to control / stop continued intake of heavy metal. So true pure removal can be achieved with chelation. With most other metals, lead being an excellent example, urine measurements will also be affected by the continued uptake of lead into the body. So steady state re-equilibration does not occur.
comparison of Gd removal should only be done with the same chelator, and the most effective chelator is the best approach. You cannot compare how much Gd is left and accessible for removal comparing a strong chelator DTPA, with weaker chelators, EDTA and DMSA. Use only the strongest available chelator.
To perform chelation thoughtfully and effectively it is critical to understand the concept of TBHMB, and all the above described points.
Richard Semelka, MD
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