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DTPA Chelation Therapy with Ancillary Treatment. Evaluation of Results. May 2021.

There are two elements to treatment for GDD (and actually all of the heavy metal Deposition Diseases) 1. remove the heavy metal, and 2. control the immune response of the host.

Background. Choice of Chelator

This critical point: the chelator used must have a high stability for the metal chelated. The stability constant should be known between chelator and the metals that are being chelated.

To illustrate: EDTA has a stability of 17 (10 to the power of 17) and DTPA has a stability of 22.46 with Gd. This means that DTPA is 300,000 times more stable with Gd than EDTA (yes I have those zeroes correct). This means that it can hold onto Gd much, much better than EDTA, and therefore redistribution is very minimal with DTPA and relatively prominent with EDTA - I estimate perhaps 1% redistribution with DTPA and 30% with EDTA. This does not mean that EDTA cannot pull a lot of Gd out of tissues, as urine Gd results show high urine Gd even with EDTA (and DMSA as well). So stability refers to hanging on to the metal, and does not mean ability to mine the metal out of tissue. The stability of Gd with DMSA and DMPS has not as yet been determined.. I am trying to obtain those numbers.

The best way to think of this is that the stability of the chelator of Gd out of tissues is exactly as important and same concept as stability of the GBCAs themselves. High stability GBCAs (thermodynamic stability): Dotarem, Prohance, Multihance, are preferred over lower stability agents: Omniscan and Optimark. In fact because of the stability issue, the European Medicine Agencies have banned the use of Omniscan and Optimark (and Magnevist) because of lower stability... But these agents are still much more stable than Gd-EDTA.

The importance of stability when considering a chelator to remove Gd (or other heavy metal) is of equal importance as stability is for an administered GBCA, if the stability of a chelator is unknown: it is like administering to a patient a GBCA for MRI study, and telling them this: "I will now inject you with Gd-XYTA. We have no idea how stable it is, but here we go" It would be unethical, perhaps criminal to do this with an MR contrast agent - the same is true with chelators to remove them.

So I hope this illustration makes this point clear.: the stability of a chelator with heavy metals deposited in the body is critical.

So DTPA is the most stable chelator available for Gd (HOPO is more stable still). But also important is that overall it is very stable for most other heavy metals. This is critical, as I have mentioned in atleast one earlier blog, because all chelators move all metals - but if they have low stability there will be a lot of redistribution. Everyone has atleast several metals in them: among them, everyone has lead (Pb).

So EDTA, DMSA, and DMPS will chelate Gd, but it is dirty chelation - meaning a lot of redistribution occurs. That is for example, Gd picked up in skin and dropped off in brain.

All chelators remove Gd; and all chelators, including stable ones, will result in re-equilibration (le Chatelier's principle); but only weak chelators will also redistribute significantly. So if a person has deposition disease to a particular metal (GDD is the example we focus on), all chelators will result in Flare from removal (starts early and lasts generally 1 week), and Flare from re-equilibration (starts 4 weeks and plateaus 2-3 months, then drops). Weak chelators will also result in Flare from redistribution (starts early and lasts generally 1 week). So with DTPA there is always two forms of Flare (removal and re-equilibration) and with EDTA always three (removal, redistribution, and re-equilibration).

Everyone with GDD therefore experiences Flare from DTPA, but just removal (early Flare) and re-equilibration (late Flare 4 weeks +).

Two properties effect Flare: the amount Gd removed and the extent of host reaction to remoblizing Gd. If you don't have a Flare reaction, you don't have Deposition Disease, you have Storage Condition. The amount removed generally can be predicted from the number of GBCAs administered and secondarily when they were administered (more Flare when GBCA injection more recent) and also the type (more with linear). The extent of host reaction, in the majority of individuals is based on how soon chelation is performed after GDD initiated. That is one of the important reasons we do not chelate within 3 months (immunologic memory strong early after start of GDD) and also because patients may recover on their own within 3 months with no chelation. In some people with certain severe Tcell dysregulation or severe Multiple Chemical Sensitivity Syndrome their Flare may be severe even somewhat regardless of how recent the disease started, but it also compounds the recency issue. Unfortunately, at this point in time it is difficult/ impossible to predict this last category, and can only tell by trying standard chelation, also with full immune dampening, and see what happens.

So with experience, the below are the groups that represent general experience:

  1. Individuals with just one GBCA injection, treatment 3 months to 1 year after initiation of GDD, 5 chelations may be sufficient to get to 80% + better.

  2. Individuals with more complex circumstances, it appears that 15 Ca/Zn-DTPA chelations seems to be the point where they achieve durable 80% + better. This may suddenly happen right at 15.

  3. Very complex stories: 20+ GBCAs and/or extremely sick. Unknown number: probably 20+ chelations, more high potency immune modulation. Improvement is expected but in range 60%-70%.

What is very critical to realize on the path of all groups, including group 1, the Flares will cause zig zag response with variable worsening, and /or varying even new symptoms on the path. Stopping early and permanently, because of Flares means that 80% recovery probably will not occur.

If treatment is stopped too early because of the subject's upset at Flaring, then 80% recovery likely will not result, but an eventual lesser recovery actually still is likely (below). Any properly done Gd removal is helpful. After the plateauing phase of re-equilibration Flare, individuals may begin to feel somewhat better- this is an effect of the DTPA chelation having been done (to remove some of the offending Gd), and late Flare of re-equilibration stabilized, and not a beneficial effect of having stopped chelation. Note that I always use the description of 'properly performed chelation'.

The analogy I have used previously and I repeat it here. Stopping chelation too early is like stopping an antibiotic too early, especially for problem infections like osteomyelitis (bone is an appropriate analogy to GDD, as bone deposition is a major issue with GDD and is a major reason why many chelations need to be done) and TB. Infection is an excellent comparator, because bacteria are also exogenous invading entities, like Gd, but the infectious organism can also replicate. Osteomyelitis generally requires 4-6 weeks of iv antibiotics. If you stop at 1 week you cannot expect to get better. In fact in the infection situation often what happens when stopping early, is that one has created a population of bacteria that are resistant to the antibiotic, they will then replicate, and now the infection is antibiotic resistant and may be devastating or lethal. With TB, the situation also a little more complex, duration of treatment is usually 3 months and double or triple antibiotics are used. If one decides one only wants just one of the antibiotics, and then stops that early as well. The same situation has developed: incomplete treatment and likely now more virulent disease.

How this situation arises with Gd and GDD: a certain number of cycles of removal/ re-equilibration/ removal (this cycle always occurs with chelation) must occur for sufficient Gd to be removed to achieve 80% + recovery, and that the host is able to learn to ignore the Gd that is left. That number of cycles is 5 for simple GDD (usually meaning 1 GBCA injection, and that one often being Multihance, Dotarem, or Prohance) and 15 for most sufferers.

When is chelation enough?

When the patient reports they feel 80% back to themselves- stopping or atleast pausing chelation, but continuing all ancillary treatments (probably ancillary treatment is a lifelong commitment) is appropriate. I use also 24 hr urine results, comparing pre to post- chelation (looking for less than 4 times amount of Gd post- compared to pre-), is a reasonable goal, and absolute post results in the mid yellow territory of a 24 hr urine Gd report (about 3 micrograms Gd per 24 hrs). Clinical improvement trumps urine results however.

Spontaneous recovery and Progression?

This depends on the group one is in (using the above 3 groupings). Also the critical thing is that no additional GBCA has been administered.

Group 1. Up to 1 month after GDD develops, 30% of subjects spontaneously recover. At 3 months, if still quite sick, of that population, no chelation (NC) 1/5 spontaneous recover (over 2 years), 2/5 stay stable, 2/5 get worse.