Log stability constants, the binding force between chelators and heavy metals.The critical data point to know when using a chelator.

As I have now written in several blogs, when planning to use a chelator for a particular metal it is important to know the log stability constant between the chelator and the heavy metal. It is also critical to understand just because a chelator binds 1 heavy metal well (the target number I usefor binding effectively is 20) does not mean that it binds other heavy metals well. It is an individual property. This entire scientific field is called coordination chemistry and subcategory chelation. The rockstars in this field have been Arthur E Martell and Robert J Smith. They have been writing the definitive texts on this subject for atleast 1974- 1882 essentially entitled Stability Constants of Metal-Ion complexes.

You may be thinking, even if you are a physician or a scientist: ? Hey, I have never heard of Martell and Smith". And I would respond "Exactly". This is one of the issues in science and medicine that now are so enormous and broad fields.. It is no longer just remembering the names William Osler, Watson and Crick (DNA) and Alexander Fleming (Penicillin). These areas cover such a broad range of disciplines and subject matters, and the knowledge is so deep, the knowing any subject well one tends to be siloed in that individual field and poorly aware of other disciplines., it is nearly impossible for anyone in one isolated field to know the names and significance of individuals in other separate fields. I liken it to when you watch the Olympic games on TV, and waiting for the 100 M sprint, you have to watch other things, like shot - putting. Some huge fat guy steps in the circle to throw the heavy metal ball, you have never seen or heard of him before, and yet it turns out he won the gold medal in 3 consecutive Olympic games. He is the Taylor Swift of shot-putting, and the few fans gathered around, recognize him for who he is, to them he is Taylor.

So getting back, Martell and Smith are the gold medal winners in coordination chemistry and chelation.

So here are some values from their book (with some additions from other source, creating a ranges)

Arthur E Martell and Robert J Smith. authors.

Title: Critical stability constants, Vol 6: Second Supplement.

Plenum Press, NY, NY. 1992.

So here are metals of interest with stability constants of chelators:

Gd 21 (DTPA), 17 (EDTA), 12-14 (DMSA)

Pb (lead) 18.6 (DTPA), 18 (EDTA), 12 (DMSA).

Cadmium 19 (DTPA), 16.5 - 17 (EDTA),, 11-12 (DMSA)

Mercury (inorganic)27 (DTPA), 21 (EDTA),, 19-20 (DMSA)

Mercury (organic, methylmercury) 14-16 (DTPA), 14-16 (EDTA), 14-16 (DMSA)

If you look at these numbers, and consider that essentially everyone has lead, and also additional heavy metals (the additional vary) the stand-out chelator for all of them is DTPA. I would add though that DMSA is equally effective for methylmercury, which is the most common toxic form of organic mercury, so if mercury is the only element you are treating for, then because DMSA is given orally, this may be still the agent of choice.

It should be noted that this text, and even more recent reporting on coordination chemistry do not describe adequately newer developed chelators, such as HOPO and others.

As I look at these numbers the optimal treatment for many critically important heavy metals, should be the approach we have developed for Gd.

I reference this paper, which describes but does not elaborate our technique: they call it chelator with steroids. Also, I would describe the disease as Metal-Induced Immune Mediated Inflammatory Disease........ Autoimmune is used when we don't know the cause, in this case we do, it is heavy metals

Richard Semelka, MD

Autoimmunity Reviews

Volume 23, Issue 3, March 2024, 103509

Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions

Geir Bjørklund a,* , Aleksandra Buha Đorđevi´c b , Halla Hamdan c , David R. Wallace c , Massimiliano Peana d,** a Council for Nutritional and Environmental Medicine, Mo i Rana, Norway b Department of Toxicology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia c Department of Pharmacology, Oklahoma State University Center for Health Sciences, Tulsa, OK, United States d Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Italy

ARTICLE INFO Keywords: Autoimmunity Metal-induced autoimmunity Neurological disorders Prevention Risk reduction Prognosis ABSTRACT Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease. 1. Introduction Autoimmune disorders manifest when the immune system, in an aberrant response, targets the body’s tissues, potentially affecting a spectrum of organs and systems, including the nervous system. Despite ongoing research, the precise etiology of autoimmune disorders remains elusive. However, there is a growing understanding that environmental factors play a significant role in triggering their development. Particularly, exposure to specific metals has been implicated as a contributing factor in the onset of neurological disorders, with autoimmune diseases being one of the notable conditions within this spectrum [1]. In recent years, there has been a heightened focus on the connection between exposure to metals and autoimmunity, supported by a mounting body of evidence that establishes a correlation between metals and the underlying mechanisms of neurological disorders. [2]. This association suggests a complex interplay between metal exposure and the intricate mechanisms involved in the development of autoimmune-related neurological disorders. Several metals, including mercury, gold, nickel, and aluminum, have been linked to the development of neurological autoimmune diseases such as multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). The actions of the metals are diverse and contingent upon the specific metal. The mechanisms related to toxic metal action include producing of free radicals, increasing oxidative stress, alterations in normal mitochondrial function and metal-induced changes in enzyme activity due to metal-protein reactions at sites such as thiol-rich groups [3,4]. Mercury, silver and gold exposure can increase the production of IgG and IgE in Correspondence to: G. Bjørklund, Council for Nutritional and Environmental Medicine, Toften 24, 8610 Mo i Rana, Norway. * Correspondence to: M. Peana, Department of Chemical, Physical, Mathematical and Natural Sciences, Via Vienna 2, University of Sassari, Sassari, Italy. E-mail addresses: bjorklund@conem.org (G. Bjørklund), peana@uniss.it (M. Peana). Contents lists available at ScienceDirect A