Gadolinium Storage Condition (GSC): What Does the Future Hold?
Gadolinium Storage Condition is the term for individuals have have undergone GBCA administration, and are not sick from the Gd. There are at least 10 million individuals with meaningful GSC, but in essence everyone who has received a GBCA and does not have either NSF or GDD has some gadolinium (the great majority miniscule amounts) retained in their body. But by the same token everyone also has some lead, some mercury, some chromium, and some arsenic, etc - a function of living in the modern age.
So meaningful refers to readily detectable by modern techniques in organ systems, especially the bone. This is especially true if the individuals have undergone administration of linear GBCAs.
Studies by Gibby and White in 2004 and 2006 showed gadolinium in bone in subjects with normal kidneys who underwent even 1 GBCA administration , both with linear and macrocyclic agents, linear > macrocyclic. Kanda et al first showed MRI findings of Gd in the brain in subjetcs who received > 5 GBCA administrations with liner nonionic agents in 2015. Ken Maravella et al showed Gd in multiple tissues (bone much greater than brain) in 2017. Current reports in 2018 have shown that everyone who received a GBCA intravenously have Gd, at least transiently, present in cerebral spinal fluid (CSF).
All this sounds very scary since Gd is a toxic heavy metal, right? Well apparently for the vast majority of us the answer is amazingly NO. Despite all the evidence of retention of Gd in essentially everyone, the vast majority of individuals are not sick from the Gd. Why is this?
My opinion is that the answer lies in the host immune system and how it manages potentially toxic heavy metals. A combination of critical factors of the host's management of chemical physiology and immune system render Gd (and lead, and chromium, etc) essentially nontoxic in the great majority of individuals (this is likely also only if the burden of toxic metal is not overwhelming). A major component is that in most of us, the immune system does not react substantially to either intact GBCA or to dissociated GBCA bound through host chemical physiology into Gd-salts (Gd-phosphate, Gd-carbonate, etc) and into Gd -host protein macromolecules. The host response to rapidly detoxify Gd by binding into salts or into proteins. The distribution and type of host detoxification differs if the dissociation occurs in the blood circulation or host tissues, and likely also between different host tissues. Remarkably these processes render toxic Gd ostensibly largely inert in the majority of individuals. This speciation of Gd(refers to the form the Gd is in: intact chelate, Gd-salt, Gd-protein) , are retained by the host in such a fashion that the great majority of individuals are remarkably not sick, and perfectly fine.
Experience with the great majority of 300 million individuals who have received GBCAs support this contention.
But will this retained Gd always be safe? At this point it is not entirely clear. Some of the GDD patients seem to get sick after they had already received one or a few GBCA administrations, and not after the first one. They were apparently fine after the first one or a few GBCA administrations, and only became sick after a later administration after a string of GBCAs. The majority of GDD sufferers though become sick after just one GBCA exposure.
Sickness after the second or subsequent exposures, would be like classic anaphylaxis physiology, where the host first develops a cell/antibody sensitization after the first exposure, and once sensitized subsequent exposures result in reactions (classic IgE antibody allergic response).
Most, maybe 70% clearly react with the initial exposure, termed awkwardly, anaphylactoid reaction, which is commonly described for the acute hypersensitivity reactions with radiology contrast agents. Anaphylactoid reactions involve direct effect on basophils and mast cells to release histamine and other substances, and IgD antibodies may be involved. The complement pathway is always tied in to all of this. There are at least 10 variations of all of these reactions described, which I take to mean that there are at least 100, and considerable interaction between many variants.
Perhaps better terms for anaphylaxis and anaphylactoid reactions could be used- musing: second strike histamine reaction for anaphylaxis and first strike histamine reaction for anaphylactoid.
So we don't know how many GSC patients may go on to develop GDD after multiple GBCA administrations (this is still relatively small number of the total individuals getting GBCA) but the unknown factor is conditions that result in future greater release of Gd from body stores. The most important circumstances for increased release of stores of Gd, are release from bone, and these would arise from: puberty, pregnancy, post-surgery, post major medical illness, and osteopenia of menopause or old age. What happens then when there is a greater release of Gd from body stores? Most of the time: nothing. But probably not all of the time.
It is not however unreasonable that individuals should be concerned about Gd in their body, as physicians we call these individuals the worried well. I myself have maybe undergone atleast 12 GBCA administrations, most in a Louis Pasteur type scenario. I myself am not that concerned about me after 12. However, I think it understandable, if subjects have received 10 GBCA administrations, they may ask questions about the future. Perhaps since I have received 12, I may think that 20 administrations seems like a reasonable number to start being concerned. Then there are those that have received 50 or more GBCAs - personally I had not thought such an overuse of GBCA and MRI was possible - but it has been. The time interval between GBCAs is also likely important. 12 administrations with each GBCA administered with a 1 year interval, has allowed a fair amount of time for Gd to naturally be eliminated from the body. 12 GBCAs in 1 month is a different story.
Hubbs Grimm and Sharon Williams, leaders of one of the major gadolinium toxicity patient advocacy groups, have done incredible work on studying urine Gd content in GDD patients who have received GBCAs, and now Hubbs and Williams are in the process of subcategorizing individual brands of GBCA to develop body elimination analysis curves using 24 hour urine gadolinium. This will allow the derivation of tables for various agents at various time points post-injection. It may be not unreasonable for persons who had received GBCAs and were extremely worried about the future, although not suffering from GDD now, to obtain 24 hr urine Gd from one of the major and affordable labs, Doctors Data or DirectLabs.com, to find out how much Gd they are currently eliminating from their systems. At this point the data is of greatest accuracy if you know the agent used, when you received it, and if you received only one brand of GBCA (that is only Magnevist, or only Gadavist, or only Multihance, or only Omniscan, or only Dotarem, etc). Contact Sharon Williams about performing the urine test and sending her the data for analysis at: Sharon@GadoliniumToxicity.com
Some individuals may be so concerned (perhaps especially if it is their child) that they may want the Gd chelated out of their systems. At present DTPA would be the only chelating agent I would recommend. One good news is that if you have GSC you will not experience a Flare reaction that GDD patients suffer from... you didn't get sick when Gd was initially administered to you (because your immune system did not react) so you won't get sick when Gd is pulled out of you. I do not have specific recommendations on this at the present time, but I probably would not consider it on myself unless I had > 20 GBCA administrations. I would also add, to the present time, I have not seen GDD develop from childhood GBCA administrations > as we learn more this may change though. Ofcourse the ideal type of chelating agent for GSC subjects, especially if they have had > 20 GBCA injections would be an oral agent, because to get most of the Gd out, especially from bone, may take one year of chelations, which would be awful if done iv, but ideal with daily oral chelator. The best candidates right now appear to be oral DTPA and oral HOPO.