Rationale in the Use of EDTA Chelation Therapy for my Patients with Multiple Chronic Diseases
July 15, 2020
According to the Centers for Disease Control and Prevention; the National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) tell us that 6 in 10 adults in the U.S. have chronic disease (29). They site heart disease, cancer, chronic lung disease, stroke, Alzheimer’s disease, diabetes, and chronic kidney disease.
Wikipedia defines degenerative disease as “the result of a continuous process based on degenerative cell changes, affecting tissues or organs which will increasingly deteriorate over time.”
Fortunately, we now have another tool as physicians to help slow this continuous process. The tool is chelation therapy, a man-made amino acid, calcium ethylenediaminetetraacetic acid (EDTA). Its electro chemical structure and charge attracts toxic heavy metals, transition metals that have the opposite charge. The complex is then primarily excreted in the urine. Lead, mercury, arsenic and cadmium are typical examples.
EDTA chelation therapy was first approved by the United States Food and Drug Administration in 1953 to treat lead poisoning in both pediatric and adult patients.
EDTA chelation therapy is normally administered intravenously each week for 20-40 sessions.
Shortly after the U.S. F.D.A. approved EDTA for metal poisoning removal, physicians began to observe a medical serendipity during treatment of their patients with improved perfusion of their cardiovascular diseases. Clark and Mosher published on this observation reporting 19 of 20 patients receiving EDTA for their lead poisoning were having less angina (17) in 1955.
Since then, physicians have published and shared these perfusion benefits with their colleagues worldwide to present. Innumerable articles have been published with exponential frequency and strength.
The 2008 National Health Statistics Report stated that 111,000 people used chelation in 2007 (13)(24). Annually that would be over 1.5 million in the last ten years. The American College for the Advancement in Medicine founded in 1972 trains hundreds of physicians in the use of EDTA chelation therapy each year.
Cardiovascular diseases are the number one cause of death globally. An estimated 17.9 million people died from CVD’s in 2016, representing 31% of all global deaths. Of these deaths 85% are due to heart attack and stroke, according to W.H.O. 17 May 2017.
The Centers for Disease Control and Prevention report that 647,000 Americans die from heart disease each year (National Vital Statistics Reports vol. 68, number 6 June 24 2019).
Low levels of environmental lead exposure is an important but largely overlooked risk factor for CVD mortality in the USA. Bruce P Lanphear, 2018, reported the population attributable fraction of concentration of lead in blood for all cause mortality was 18%, which is 412,000 deaths annually (4).
Andy Menke, MPH reported (28) “environmental lead exposures remain a significant determinant of cardiovascular mortality in the general population, constituting a major public health problem.”
Chronic lead exposure from the environment is 95% deposited in the bone with an estimated half life of over 30 years. By middle age our bones begin to demineralize, and we can become auto intoxicated from our stored cortical bone lead. Marc G Weisskopf’s Bone Lead Concentration and death from all causes reported “that bone lead, but not blood lead was associated with an increased mortality rate that was more apparent for CVD and specifically between patella lead and ischemic heart disease.” (28)
The Agency for Toxic Substances and Disease Registry (ATSDR) reports on “The ATSDR for 2019 that Arsenic is #1, lead is #2, mercury is #3 and cadmium is #7 out of 275 toxins.”
The Comprehensive Environmental Response Compensation and Liability Act (CERCLA) sec 104 (i) requires ATSDR and the EPA “to prepare a list in order of priority of substances… which are determined to pose the most significant potential threat to human health due to their known or suspected toxicities.”
On November 4, 2012, the (TACT) Trial to Assess Chelation Therapy, investigators reported publicly the first large-scale, 1,708 patients, randomized, placebo-controlled trial evidence “that EDTA Chelation Therapy significantly reduced cardiac events in stable post-myocardial infarction patients.”(6)(1)
The science to date supports seeing toxic heavy metals as an emerging cardiovascular risk factor we can safely moderate. Solenkova et al reported “There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor.” (13) In this article they show “urine lead may be used to assess lead exposure and for monitoring of therapy for lead toxicity.”
The new TACT-2 (6) seeks to replicate the 2012 findings (1) and is currently ongoing. In this study they are also focusing on mechanisms where heavy metal toxins injure vascular systems. Here also they are using urine lead pre and post chelation infusion testing as a valid instrument to assess lead exposure (2).
The urine collection study typically screens for 20 heavy metal toxins. These studies showed following EDTA chelation infusion the excretion of lead increased 3,830% and cadmium was 514% over baseline. This was also demonstrated by Arenas et al (21), Zenith H Alam (3) and Byung-kook Lee (22).
Furthermore, we are exposed to multiple environmental toxins regularly (7). One only needs to recall Flint Michigan’s lead pipes contaminating thousands of peoples drinking water in 2015 and the IQ damage done to their children (31).
There are interactions to consider as multiple toxins are affecting our health and mortality. Dong-soon Bae (23) reports “these metals often occur together, such as arsenic, cadmium, lead and mercury” and “as the mixture concentration increased, a trend of additivity changed to synergistic cytotoxicity… they also mediate development of additional pathologic conditions in individuals exposed chronically to low levels.”
Rajiv Chowdhury et al (5) showed “there was a linear dose response relationship for arsenic, lead, cadmium with cardiovascular outcomes… these findings reinforce the importance of environmental toxic metal ions in cardiovascular risk, beyond the roles of conventional behavioral risk factors.”
Mechanistically, EDTA chelation functions as an antioxidant reducing reactive oxygen species (ROS) thus reducing lipid peroxidation, nitric oxide formation enhanced, glutathione function enhanced, and many enzyme functions critical to mitochondrial function for energy production of ATP are enhanced. It is also known to have a mild anticoagulation effect.
See the report by N D Vaziri et al on the Effect of Lead on Nitric Oxide Synthase Expression in Coronary Endothelial Cells (25) and S.J. Stohs on the Oxidative Mechanisms in the Toxicity of Metal Ions (26).
Most now agree that hypertension and lead chronic toxicity is a modifiable and treatable risk factor (14). Here the author N D Vaziri found “chronic lead exposure can trigger a cascade of events that may culminate in the development of hypertension and CVD, by promoting oxidative stress and inflammation, by disturbing NO signaling pathways.” He also tells us “in recent years, increasing evidence has emerged pointing to the role of oxidative stress as a major mediator of lead-induced hypertension.”
“Lead and other metal ions deplete glutathione producing reactive oxygen species producing lipid peroxidation, DNA damage, and altered calcium and sulfhydryl homeostasis.” S J Stohs (26).
“In diabetics it has been found that antioxidants, or transition metal chelators (like EDTA) can ameliorate retinopathy and neuropathy suggesting that oxidative stress contributes to these conditions… as the glycation theory of diabetic complications unfolded, metal catalyzed glucose auto-oxidation and oxidation of glycated residues emerged.” (27) reported Vincent M. Monnier.
Many of the glucose-associated oxidative modifications have been attributed to the Fenton Chemistry carried out by transition metals.
There is a risk for chronic renal disease in patients without diabetes from environmental lead exposure. Ja-Liang Lin, M.D. reported “Repeated chelation therapy may improve renal function and slow the progression of renal insufficiency.” (32)
Chiara Foglieni stated “EDTA administration resulted in the preservation of both function and histological parameters of rat kidneys.”(33) This was after imposing ischemic injury to the kidneys compared to controls. She continued to state “This data provides evidence that EDTA treatment is able to protect rat kidneys from ischemic damage possibly through the stimulation of NO production.”
Note must be made of the heavy metal toxin gadolinium used in imaging studies. There is brain deposition and other tissues. Kidney deposition and chronic inflammatory fibrosis has been reported as nephrotic systemic fibrosis (NSF). Tomonori Kanda stated “a history of exposure to gadolinium-based contrast agents, and this condition was named nephrogenic systemic fibrosis.” (10)
Gadolinium’s neurotoxicity is well reviewed by Alessandro Fulgenzi where he states “Oxidative injury is linked to Pb-induced neurotoxicity and chronic exposure to Pb can induce cognitive dysfunction.” (8) He does an exhaustive review of all known causes and related mechanisms involved in direct neurotoxicity, including the other metals arsenic, cadmium and mercury. He also uses the EDTA urine collection pre and post treatment as validated tools in monitoring toxicity burden and reduction correlating to clinical improvement.
Th Vorvolakos wrote an article entitled “There Is No Safe Threshold for Lead Exposure: A Literature Review” where he stated “lead affects the cholinergic, dopaminergic and gloutamergic systems, thus intervening in the normal function of neurotransmission.” (34) Lead as an environmental toxin increases neurologic and psychiatric morbidity. Should all military, police and firefighters be encouraged to learn, track, and reduce their likely burden from their work exposure? This needs to be addressed.
It would appear EDTA for lead reduction in chronic exposure has been well studied over 50 years.
With worldwide reporting and use in clearly millions of people over 50 years, it appears when given by trained physicians, it is very safe.
It also appears to have many clinical applications covering the six chronic degenerative diseases. This appears to be largely related to the antioxidant sparing effect of EDTA chelation. It is enhancing microcirculation throughout the body possibly improving oxygenation with better perfusion, literally from head to toe.
It makes sense to reduce any toxic. substance from our total body burden.
When you go to the internet as any patient might do and type in “What is Chelation Therapy” it offered “WebMD” entitled “What is chelation therapy?”. There it states “when metals like lead, mercury, iron and arsenic build up in your body, they can be toxic. Chelation therapy is a treatment that uses medicine to remove these metals so they don’t make you sick.”
Susan Ipaktchian wrote an article for Stanford University School of Medicine as director of print and web communications. Office of Communications & Public Affairs News Center November 24, 2008 “14 drugs identified as most urgently needing study for off-lavel use, a Stanford Professor says.” In it she stated “a 1985 study found that of the 100 most common uses of marketed drugs, 31 of those uses did not have approval from the FDA. And a study that Stanford led in 2006 showed that of the estimated 21 percent of off-label drug uses in 2001, 73 percent did not have strong scientific support… Once a drug is approved and on the market, though, physicians may choose to prescribe it for any condition.”
EDTA chelation is being used to remove lead. This is what it was FDA approved for. This is not a mechanism question. The science of today, not 1953, supports a broader definition of lead toxicity or burden.
This tool EDTA has promise to impact favorably chronic degenerative disease today. We need FDA approval today to help patients with the “right to try” it covered by insurance as far too many cannot afford it.
As Dr. Gervasio A Lamas principal investigator for the TACT Trial stated May 26, 2015 in his article “Chelation Therapy – a new look at an old treatment for heart disease, Particularly in Diabetics… We learned the results of our work. Did chelation work to reduce heart events in a vulnerable population with a prior heart attack? It turns out that it did. And it was safe.” (13)
Bibliography
1. “The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trail to Assess Chelation Therapy (TACT)”
a. Esteban Excolar, MD
b. Cir Cardiovasc Qual Outcomes. 2014;7:15-24
2. “Enhanced Vasculotoxic Metal Excretion in Post-Myocardial Infarction Patients Following a Single Edetate Disodium-Based Infusion”
a. Ivan A Arenas, Ana Navas-Acien, Ian Ergui, Gervasio A Lamas
b. Environmental Research Volume 158, October 2017, pages 443-449
3. “Urinary Metal Levels after Repeated Edetate Disodium Infusions: Preliminary Findings”
a. Zenith H. Alam
b. Int. J. Environ. Res. Public Health 2020, 17(13), 4684; https://doi.org/10.3390/ijerph17134684
4. “Low-level lead exposure and mortality in US adults: a population-based cohort study”
a. Prof Bruce P Lanphear MD
b. https://doi.org/10.1016/S2468-2667(18)30025-2 Vol 3 April 2018
5. “Environmental Toxic Metal Contaminants and Risk of Cardiovascular Disease: Systematic Review and Meta-Analysis”
a. Rajiv Chowdhury
b. BMJ. 2018 Aug 29;362:k3310
6. “Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Edetate Disodium Chelation Therapy”
a. Gervasio A. Lamas, MD
b. Journal of the American College of Cardiology Vol.67.No.20,2016
7. Agency for Toxic Substances and Disease Registry, Substance Priority List (for 2019)
a. https://www.atsdr.cdc.gov/spl/index.html#2019spl
8. “EDTA Chelation Therapy for the Treatment of Neurotoxicity”
a. Alessandro Fulgenzi
b. Int J Mol Sci. 2019 Feb 26;20(5):1019. doi: 10.3390/ijms20051019
9. “Gadolinium Deposition in the Brain”
a. Tomonori Kanda
b. Magnetic Resonance Imaging. 2016 Dec;34(10):1346-1350. doi: 10.1016/j.mri.2016.08.024.
10. “Brain Gadolinium Deposition After Administration of Gadolinium-Based Contrast Agents”
a. Tomonori Kanda
b. Jpn J Radiol. 2016 Jan;34(1):3-9. doi: 10.1007/s11604-015-0503-5. Epub 2015 Nov 25.
11. “Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals”
a. Maria Elena Ferrer
b. Hindawi Publishing Corporation. Biomed Research International. 2016;2016:8274504. doi: 10.1155/2016/8274504. Epub 2016 Nov 8.
12. “Is Lead Chelation Therapy Effective for Chronic Kidney Disease? A Meta-Analysis”
a. Shi-Kun Yang
b. Nephrology (Carlton). 2014 Jan;19(1):56-9. doi: 10.1111/nep.12162.
13. “Chelation Therapy: A New Look at an Old Treatment for Heart Disease, Particularly in Diabetics”
a. Gervasio A Lamas MD
Page 6 of 7
b. Circulation 131(21):e505-6 · May 2015
14. “Interplay of Reactive Oxygen Species and Nitric Oxide in the Pathogenesis of Experimental Lead-Induced Hypertension”
a. N D Vaziri
b. Clinical and Experimental Pharmacology and Physiology. 2007 Sep;34(9):920-5. doi: 10.1111/j.1440-1681.2007.04644.x.
15. “Chelation Therapy: Overlooked in the Treatment and Prevention of Diabetes Complications?”
a. Norma Frizzell, John W Baynes
b. Future Med Chem. 2013 Jun;5(10):1075-8. doi: 10.4155/fmc.13.73.
16. “Lead, Cadmium, Smoking, and Increased Risk of Peripheral Arterial Disease”
a. Ana Navas-Acien
b. Circulation. 2004 Jun 29;109(25):3196-201
17. “The in Vivo Dissolution of Metastatic Calcium; An Approach to Atherosclerosis”
a. N E Clarke, C N Clarke, R E Mosher
b. Am J Med Sci. 1955 Feb;229(2):142-9. doi: 10.1097/00000441-195502000-00004.
18. Cardiovascular diseases (CVDs): Key Facts
a. World Health Organization. 17 May 2017
b. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
19. Centers for Disease Control and Prevention – National Vital Statistics Reports – Volume 68, Number 6
20. “Low-level toxicity of chemicals: No acceptable levels?”
a. Bruce P. Lanphear
b. PLoS Biol. 2017 Dec; 15(12): e2003066.
21. “Enhanced Vasculotoxic Metal Excretion in Post-Myocardial Infarction Patients Following a Single Edetate Disodium-Based Infusion”
a. Ivan A Arenas, Ana Navas-Acien, Ian Ergui, Gervasio A Lamas
b. Environmental Research Volume 158, October 2017, pages 443-449
22. “Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites.”
a. B K Lee, B S Schwartz, W Stewart, and K D Ahn
b. Occupational and Environmental Medicine. 1995 Jan; 52(1): 13–19.doi: 10.1136/oem.52.1.13
23. “Toxicological Interactions Among Arsenic, Cadmium, Chromium, and Lead in Human Keratinocytes”
a. D S Bae, C Gennings, W H Carter Jr, R S Yang, J A Campaign
b. Toxicological Sciences. 2001 Sep;63(1):132-42. doi: 10.1093/toxsci/63.1.132.
24. “Current Use of Chelation in American Health Care”
a. Paul M. Wax
b. J Med Toxicol. 2013 Dec; 9(4): 303–307.
25. “Effect of lead on nitric oxide synthase expression in coronary endothelial cells. Role of superoxide”
a. Nosratola D Vaziri
b. Hypertension 37(2):223-6 · March 2001. DOI: 10.1161/01.HYP.37.2.223
26. “Oxidative Mechanisms in the Toxicity of Metal Ions”
a. S J Stohs, D Bagchi
b. Free Radical Biology and Medicine. 1995 Feb;18(2):321-36. doi: 10.1016/0891-5849(94)00159-h.
27. “Transition metals redox: reviving an old plot for diabetic vascular disease”
a. Vincent M. Monnier
b. J Clin Invest. 2001 Apr 1; 107(7): 799–801.
Page 7 of 7
28. “Blood Lead Below 0.48 μmol/L (10 μg/dL) and Mortality Among US Adults”
a. Andy Menke, Paul Muntner, Vecihi Batuman, Ellen K. Silbergeld, and Eliseo Guallar
b. Circulation. 2006;114:1388–1394. https://doi.org/10.1161/CIRCULATIONAHA.106.628321
29. Centers for Disease Control and Prevention, The National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)
30. “A Prospective Study of Bone Lead Concentration and Death From All Causes, Cardiovascular Diseases, and Cancer in the Department of Veterans Affairs Normative Aging Study”
a. Marc G Weisskopf
b. Circulation. 2009 Sep 22;120(12):1056-64. doi: 10.1161/CIRCULATIONAHA.108.827121.
31. “Intellectual Impairment in Children With Blood Lead Concentrations Below 10 Microg Per Deciliter”
a. Richard L Canfield
b. N Engl J Med. 2003 Apr 17;348(16):1517-26. doi: 10.1056/NEJMoa022848.
32. “Environmental Lead Exposure and Progression of Chronic Renal Diseases in Patients without Diabetes”
a. Ja-Liang Lin, M.D., Dan-Tzu Lin-Tan, R.N., Kuang-Hung Hsu, Ph.D., and Chun-Chen Yu, M.D.
b. New England Journal of Medicine 348(4):277-86 · January 2003
33. “Protective Effect of EDTA Preadministration on Renal Ischemia”
a. Chiara Foglieni
b. BMC Nephrol. 2006 Mar 15;7:5. doi: 10.1186/1471-2369-7-5.
34. “There Is No Safe Threshold for Lead Exposure: Α Literature Review”
a. Th Vorvolakos, S Arseniou, M Samakouri
b. Psychiatriki. Jul-Sep 2016;27(3):204-214. doi: 10.22365/jpsych.2016.273.204.
35. “Excess Lung Cancer Among Workers Exposed to Lead”
a. A Anttila, P Heikkilä, E Pukkala, E Nykyri, T Kauppinen, S Hernberg, K Hemminki
b. Scand J Work Environ Health. 1995 Dec;21(6):460-9. doi: 10.5271/sjweh.62.
36. “14 Drugs Identified as Most Urgently Needing Study for Off-Label Use, Stanford University Professor Says”
a. Susan Ipaktchian
b. Stanford Med School News Center. Nov 24 2008