Saving a Million Hearts

In 2013 a group of ICIM members gathered to discuss an integrative, preventative approach to the Saving a Million Hearts initiative, including chelation therapy. Here are video clips of their conversations. The event was organized by Terry Chappell MD, and Jeannette Soriano MD is the facilitator.

Jeannette Soriano

Saving a Million Hearts Outline

Saving a Million Hearts Introduction from an Integrative Medicine Perspective

Dr. Terry Chappell, Dr. Lambert Parker, and Dr. James Carter discuss the “Saving a Million Hearts” initiative of the CDC and other medical groups. These three integrative doctors talk about the importance of going beyond pharmaceuticals.

Saving a Million Hearts: Stress and Lifestyle

Dr. John Wilson, Dr. James Carter, Dr. Ellie Campbell discuss diet, stress, and lifestyle as they relate to cardiovascular disease. Includes reference to an Alpha-Stim study by ICIM member William Eidleman MD.

Saving a Million Hearts: Informed Consent

Dr. Terry Chappell and Dr. Russ Jaffe discuss the importance of having informed consents as part of the patient education process for integrative medicine and chelation therapy for cardiovascular disease.

Saving a Million Hearts: Testing for Risk Factors

Dr. Conrad Maulfair, Dr. Ellie Campbell, Dr. Robban Sica, and Dr. Joe Hickey discuss what cardiovascular risk factors should be explored for effective prevention of heart attack and stroke.

Saving a Million Hearts: Metabolic Syndrome

Dr. Joe Hickey, Dr. Robban Sica, Dr. Ellie Campbell, Dr. Conrad Maulfair talk about the testing they do to screen for Metabolic Syndrome in their integrative practices, and discuss what treatments they recommend to their patients.

Saving a Million Hearts: Testing and Treating Cholesterol

Dr Rick Mason, Dr. Joe Hickey and Dr. Garry Gordon discuss cholesterol’s role in heart disease- to test or not to test! What is the dietary impact? What kind of cholesterol should we focus on? HDL, LDL, lipids, proteins, triglycerides… what wisdom will the future of medicine hold? Is there a cholesterol propaganda scheme? What are treatment strategies?

Saving a Million Hearts: Blood Pressure

Dr. Joe Hickey, Dr. Lambert Paker, Dr. Muhammad Ashraf discuss blood pressure tips for check ups, monitoring and treatment.

Saving a Million Hearts: Toxic Metals Q&A

Dr. Robin Bernhoft, Dr. Jim Smith, Dr. John Wilson answer questions from some of the most experienced chelation doctors in the country about diagnosing and treating heavy metal toxicity, with a focus on EDTA chelation.

Saving a Million Hearts: Chelation Protocols I

Dr. Robban Sica, Dr. Terry Chappell, and Dr. Garry Gordon discuss the IV chelation protocols that they have used.

Saving a Million Hearts: Chelation Protocols II

Dr. Robban Sica, Dr. Terry Chappell, and Dr. Garry Gordon discuss the IV chelation protocols that they have used.

Saving a Million Hearts: Micronutrients 

Dr. Chuck Mary and Dr. Rick Mason, CoQ10, Magnesium, Copper and other micronutrients’ role in the body and for prevention of cardiovascular disease.

Saving a Million Hearts: Women’s Health and Allergy Testing in Cardiovascular Disease

Dr. Robban Sica, Dr. Russell Jaffe, Dr. Ellie Campbell, and Dr. John Wilson discuss the role allergies can play in cardiovascular disease, laboratory testing, and special considerations for women’s health.

Dr. Chappell’s article “Saving a Million Hearts can be found here



Magnesium deficiency or composition of the infusate used in the load test?

Robert Waters MD


Mg Man Cal tiss-04-17-08

Serum/plasma measurements do not reflect magnesium deficits in clinical situations and magnesium load tests are used as a more accurate method to identify magnesium deficiency in a variety of disease states as well as in subclinical conditions. The objective of this study was to determine if people are indeed magnesium deficient or if the apparent magnesium deficiency is due to the composition of the infusate used in the load test.

Magnesium load tests were performed on 7 patients using three different Mg solution infusions- a Mg-EDTA (ethylene diamine tetraacetic acid)-nutrient cocktail used in EDTA chelation therapy containing several components including vitamins and minerals and the same cocktail without EDTA and an infusion of an identical amount of magnesium in normal saline solution.  There was no significant difference in the amount of magnesium retained in the 24 hours after infusion among the three infusates.  All infusates resulted in very high magnesium retention compared to previous published magnesium load studies.  Magnesium deficiency may be widespread and the relationship of Mg deficiency to related diseases requires further study.


Mg is the fourth most abundant cation in the body and its intracellular concentration is exceeded only by potassium [1].  Mg activates more than 300 enzymes in the human body [2].  Deficiency of Mg has been linked to a variety of clinical disease states including hypertension, myocardial infarction, cardiac dysrhythmias, coronary spasm and premature artherosclerosis [3].  In addition, patients with diabetes have been found to be at particular risk for Mg deficiency [4].  Conditions related to the deficiency of Mg may be linked to its functions as a cofactor for enzymes related to cell respiration, glycolysis and ion transport (e.g. Na-K-ATPase).  In fact, the central position of Mg in its role in energy storage, transfer and utilization is mediated through its function in the formation of Mg-ATP, the ultimate form of stored energy in biological systems.  In addition, Mg has functions related to protein synthesis through its action on nucleic acid polymerization, binding of ribosomes to RNA and the synthesis and degradation of DNA [5].  Mg is also an integral player in calcium biology via its ability to maintain low resting concentrations of intracellular calcium ions.  It competes with calcium for membrane binding sites and as such has been described as a “calcium channel blocker” [6].

In degenerative diseases, Mg deficiency has been shown to be related to the generation of free radicals [7].  Mg deficiency has also been shown to negatively influence the generation of nitric oxide and therefore the impact of such deficiency may be responsible in part for the pathogenesis of endothelial dysfunction and its relationship to vascular disease, diabetes and other diseases associated with aging [8].

In a previous study, we showed that after the infusion of 686 mg of elemental Mg as Mg sulfate, in an EDTA chelation “cocktail”, 83% of the infused Mg was retained in the initial 24 hours following infusion [9]. This degree of retention of Mg has generally been recognized to represent evidence of severe Mg deficiency.  However, in that study, it was not clear if the apparent Mg retention was due to a true Mg deficiency or if the components of the chelation cocktail affected Mg retention.  Guldager et al. [10] infused 3 g of EDTA in saline, without any Mg, into a group of peripheral vascular disease patients and collected 24 hour urines of the patients and controls.  There was a highly significant decrease in the Mg in the 24 hour urines of the EDTA patients vs the controls indicating that the EDTA increased Mg retention.  The serum Mg in these patients did not increase so it is probable that the EDTA caused Mg to enter intracellular compartments.  This present study was designed to determine the effects of components of the Mg infusates on Mg retention.


The study was approved by the Clinic Human Studies Review Board, Wisconsin Dells, WI.  The study was explained to the subjects and patients signed an informed consent before the study.  Data are available to the participants upon request.  Participants did not incur any medical fees as a result of their participation and were not paid for their participation.

At the onset of the study, patients were instructed in the accurate collection of 24-h urine specimens to avoid metal contamination.  Twenty-four-hour urine samples were collected in 4-L sample containers (Fisher Scientific Co., Pittsburgh, PA) 2d prior to chelation therapy (d 1 and d 2), the day of chelation therapy (d 3), and the following day (d 4).  Control urine samples were collected on Monday and Tuesday and the post-infusion urine samples on Wednesday and Thursday.  In Phase 1 of the study, on Wednesday morning of the study week, an intravenous infusion of 2.25 g of EDTA mixed in sterile water with 5 g of sodium ascorbate, 2500 units of heparin, 3 mL of 2% procaine, 100mg pyridoxine HCl, 4 meq KCl, 1 mL of 8.4% sodium bicarbonate, 1000 µg hydroxycobalamin, 1 mL vitamin B complex, and 7 mL magnesium sulfate equivalent to 686 mg of elemental magnesium was given in an arm vein over a 2.5 hour period. During phase 2, patients received an identical infusion without any EDTA and during phase 3 subjects received 686 mg elemental Mg in saline [9] [11].  Order of the phases was random.  The procedures were two to four weeks apart.  Magnesium contents of the urine samples were measured and the Mg retention calculated using the following formula modified from Jeppesen [12]:

%Mg retention = [infused Mg – (urine Mg on day 3 – average urine Mg on days 1 and 2)/ infused Mg] X 100.

Day 3 was the following day after the infusion; days 1 and 2 were baseline days immediately preceding the infusion. In addition, Mg content was also measured on day 4.

Since the time of our original chelation study, published and anecdotal data have revealed that the clinical efficacy of EDTA chelation therapy could be achieved with a smaller dose of EDTA with fewer potential side effects.  Therefore, we reduced the dose of EDTA to 2.25 g.

Magnesium concentrations in the urine were determined using flame atomic absorption using a Perkin-Elmer 5000 flame atomic absorption spectrometer using standard techniques (Perkin-Elmer, Norwalk, CT) and reference materials as described [13].

Statistics: Statistical analyses of the data were performed using 2-Way Analysis of Variance (SAS Institute, Cary, NC, version 9.1).  The main effects were the variable components of the infusions in the 3 Phases.  Values are mean ±  SEM.


Means for magnesium losses among the three Phases were not statistically different.  Approximately 70% of the infused Mg was retained during the 24-h period after the infusion (day 3) in Phase 1.  Retention of Mg in Phases 2 and 3 were similar.  By day 4, the 24-h Mg excretion was not significantly different from the averages of days 1 and 2 in all three Phases of the study.


In this study, Mg retention was greater than 70% for all infusates.  High Mg retention is probably not due components of the infusate since infusion of Mg added to saline also led to significant Mg retention. The presence of EDTA in the cocktail did not increase the retention of Mg and retention was still approximately 72% when Mg sulfate was added to saline alone and infused.  Suboptimal Mg status appears to be present in essentially all of the subjects.

From analyzing the data on Mg load tests published over the last 30 years, it appears that there is great variation in the percentage of Mg that can be expected to be retained by normal patients vs. patients with various medical conditions.  It is clear that serum/plasma Mg measurements do not necessarily reflect Mg deficits in clinical situations [14].  Thus alternative measurements of Mg status were attempted and ultimately the Mg retention test was suggested as a more accurate method to identify Mg deficiency in a variety of disease states as well as in subclinical conditions.  Other methods including bone Mg, muscle Mg, NMR spectroscopy, single ion channel analysis, leukocyte Mg, intraerythrocyte Mg and Mg balance studies are more expensive and/or invasive but may not be more informative than the Mg load test.  Even the intracellular Mg measurements have shown inconsistent correlation with serum levels and other tissue levels as well as Mg load test data [15].

Table 2 summarizes the data from a number of intravenous load tests.  In most of the studies, the demarcation in Mg retention between patients and controls is roughly 20%.  In our present study, all groups of patients had Mg retention of at least 70%.  The presence of EDTA at a dose of 2.25g in the infused Mg preparation did not explain the high retention since when EDTA was omitted from the infusate, Mg retention remained high.  However, we cannot, with certainty, conclude that EDTA results in no greater Mg retention since we only used 2.25g of EDTA in the infusions vs the prior study of 3.0g which resulted in an even greater retention of 83% [9].   The results of Guldagner, et al also suggest a causal Mg retention by 3g of EDTA without any Mg added to the infusate [10].

Components of the infusate in the present study also appear to have little influence on magnesium retention since the Phase 2 Mg retention cocktail without EDTA, but otherwise the same vitamins and minerals, was not different from the cocktail containing only Mg and saline.  Patients in our earlier study [9] all had evidence of degenerative diseases and retained even greater amounts of Mg than the patients in our present study and the dose of EDTA in that study was 3 g. Earlier studies of the therapeutic effects of EDTA used 5 g of EDTA per treatment, 5 days per week, and showed dramatic positive clinical effects as well as objective evidence of benefits such as improved EKG’s, reduction in the calcification of heart valves and dissolution of metastatic calcification in the kidneys [16] [17]. Only further studies on the dose dependent effects of EDTA  as well as careful choice of “normal” vs. “diseased” patients can help resolve the issue of whether EDTA can influence calcium and magnesium dynamics in vivo in correlation with clinical and biochemical findings.

A number of studies using the Mg retention test have shown that patients with corornary heart disease are Mg deficient compared to controls.  Jeppesen reasoned that Greenlanders have a lower rate of myocardial infarction as a result of their high serum Mg, low serum calcium and prolonged bleeding time (known to be induced by Mg administration) [12].   After administering 30 mmoles of intravenous Mg over 12 hours in patients with acute myocardial infarction, the infarction patients retained 42% of the infused Mg over the next 24 hours compared to only 22% in the control group.  He also obtained quadricep muscle biopsies, which revealed an increased Mg content in the control group vs the acute myocardial infarction groups but differences were not statistically significant.

Sjogren et al. [18] showed patients with Crohn’s disease had lower tissue concentrations of Mg compared with controls and after IV infusions of 60 mmole Mg, the Crohn’s patients had significantly higher Mg retention than the controls.  Gullestad et al. [19] showed that Mg retention in the 24 hour urine was 3-4% in a group of individuals without known predisposition for Mg deficiency after an infusion of 30 mmoles Mg sulfate.  This was significantly lower than that for 661 hospitalized patients with known predisposition to Mg deficiency (cardiovascular disease, alcoholism, etc. whose percent retention varied from 16 – 38%).  Interestingly, the serum Mg was similar in the patient groups and the controls except for the alcoholics, hypertensives and young healthy controls who had significantly reduced levels.

This later finding, particularly in reference to “young healthy” controls, brings up the probability that dietary intake of Mg is suboptimal and Western diets may be contributing to an increasing problem of Mg deficiency which may be a component of the growing epidemic of the metabolic syndrome and related diseases.

This possibility is supported by manuscripts of Resnick and associates spanning from 1984  to 2000 [20] [21].  Using Mg-specific selective ion electrode apparatus and 31P-NMR spectroscopy, there was a significant correlation between intracellular ionized Mg as well as intracellular free Mg and the presence of NIDDM [22].  Other studies reported increased intracellular calcium, decreased intracellular Mg and decreased cytosolic pH with the presence of essential hypertension [23].  A 1992 study revealed that oral glucose loading, even in normal subjects, elevates free calcium and suppresses free Mg [24].  These data suggest, in the author’s words, “an ionic hypothesis of cardiovascular and metabolic disease in which a generalized defect in cell ion handling is present in all tissues.”  This trend leads to, in different tissues, the features of the metabolic syndrome, hypertension, obesity, insulin resistance and left ventricular hypertrophy, the latter related both to hypertension and, independently, vasoconstriction and increased contractility caused by high cytosolic calcium and lowered free Mg [24].  Arterial stiffness, as measured by High Frequency Ultrasound analysis, is known to correlate with hypertension and coronary heart disease [25].  Resnick et al. [26] showed, using direct magnetic resonance determination of aortic distensibility, that in essential hypertension, there are statistically significant correlations between fasting glucose, abdominal visceral fat and in situ intracellular Mg.

In a rat model, Barbagallo et al. [27] showed that glucose, at increasing mM concentrations, caused a significant increase in cytosolic free calcium in vascular smooth muscle.  The authors suggest that these cellular effects of hyperglycemia may underlie the predisposition of patients with diabetes and patients with insulin resistance to hypertension and vascular diseases.  The same group of investigators showed that aging itself is associated with the onset of the elevation of intracellular calcium and reduction of intracellular Mg that is indistinguishable from effects seen in essential hypertension and diabetes mellitus independent of age [28].  These changes may predispose older persons to cardiovascular and metabolic diseases.

Wells et al. [28] identified a previously unknown genetic defect in Mg metabolism in salt-sensitive essential hypertension.  This Mg binding defect results in the inhibition of Mg entry into the cell thereby reducing Mg dependent enzymes from operating efficiently.  The resulting lowering of Mg ATP results in the inability to extrude sodium ions and hypertension develops as a consequence of smooth muscle dysfunction.  The authors also found the Mg binding defect was found in every one of 24 patients with type 2 diabetes suggesting that this defect in Mg transport may be a contributor to NIDDM.  These findings are of possible importance when considered in conjunction with the studies described above [18] [21-24 [26] [27].

Gullestad et al. evaluated 88 healthy Norwegians ages 18 to 66 years using a 30 mmole intravenous Mg load test over 8 hours and measured the 24 hour urinary Mg excretion [29].  They found no correlation between Mg retention and serum Mg or basal urinary Mg.  The Mg retention in these healthy patients was 10.6 to – 4%.  The lowest and highest second standard deviation values were -19.5% and 27.5% respectively.  This result agrees well with the above historical consensus.

Another study by Gullestad et al. [30] on “healthy free-living elderly Norwegians,” mean age 73 ± 6, using the same load test of 30 mmoles of  Mg revealed a retention of 28% compared to 6% in younger controls.  This finding also roughly agrees with the literature and is very interesting when considered in the light of the findings of Barbagallo et al. [27] that elderly people show intracellular calcium and Mg ion concentrations similar to those found in hypertensives and people with diabetes.

A study of Mg deficiency using the “short-term” Mg loading test by Rob et al. [31] revealed that even low dose (0.1 mmole Mg per Kg of body weight) infused over one hour was still able to differentiate Mg adequate patients from renal transplant patients with known Mg deficiency. After treatment with 5 mmoles of Mg per kilogram body weight for four months, a cohort of the latter group reduced their Mg retention from 47% on average to 16%.  The placebo transplant patients continued to retain the infused Mg at 58% of the dose.  The utility of this short-term, low dose Mg retention test can clearly help identify Mg deficiency and help ensure that patients are adequately repleted.

Finally, we could ask which tissue cells are the benefactors of the increased Mg retention in the patients studied.  Bone may be a tissue compartment that may have taken up the infused magnesium since two-thirds of the total body Mg content is contained in skeletal tissue[32].  This is especially likely since it is known that the Mg content of bone falls with age [33] and in the osteoporotic state [34].  If the diet is Mg deficient and the small intestine and kidney can’t effectively increase Mg absorption, bone releases the element into the extra cellular fluid to maintain the serum level [35].


These data demonstrate that Mg deficiency may be widespread.  The composition of the infusate used in magnesium load tests appears to have minimal influence on magnesium retention and does not explain the reported magnesium deficiency.  The importance of dietary factors, especially Mg, in the causation of the present epidemic of metabolic syndrome and its associated complications calls for additional efforts to identify and treat patients at risk of magnesium deficiency.

Table 1:  EDTA and cocktail effects on magnesium losses and retention on the day of the infusions (day 3) minus average of days 1 and 2


1 263 285 345
2 245 156 50
3 203 116 116
4 193 144 198
5 182 210 276
6 133 80 96
7 205 289 268
MEAN ± SEM 203 ± 16 182 ± 31 193 ± 41
% Retention of infused magnesium 70.3 ± 2.3 73.3 ± 4.5 71.9 ± 6.0


Values are mean ± SEM.  All infusates contained 686 mg of Mg.

Values for COCKTAIL, COCKTAIL MINUS EDTA and SALINE are urinary magnesium losses (mg) on day 3 minus the average for days 1 and 2.  There were no significant differences among the three different infusates tested.





Table 2:  Intravenous magnesium load tests in patients and controls

Reference Country Patients, Mg Retention, % Disease/Condition Controls, Mg Retention, %
Thoren [36]
Caddell et al. [37]
Bohmer & Mathiesen [38]
Ryzen et al. [39]
Fort & Lifshitz [40]
Jeppesen [12]Sjogren et al. [18]
Rasmussen et al. [41]
Martin [42]
Gullestad et al.  [19]
Gullestad et al.  [29]
Gullestad et al. [30]
Ozono et al. [43]
Toral Revuelta et al. [44]
Hebert et al. [45]
Papzachariou et al. [46]
Waters et al. [9] 
No patients
G.I. fluid loss
Post partum women
IDDM children
MICrohn’s disease
Various diagnoses
No patients
Malnourished elderly
Intensive care patients
Not given

Citations are in chronological order.

*NC denotes no controls.



The authors would like to thank the late Dr. Mildred Seelig for her advice and encouragement during the initial stages of this study.




Reference List


  1. Burtis CA, Ashwood ER (1999) Tietz Textbook of Clinical Chemistry. WB Saunders Company, Orlando, FL
  2. Sauberlich HE (1999) Laboratory Tests for the Assessment of Nutritional Status. CRC Press, Boca Raton, FL
  3. Selig MS (1980) Magnesium Deficiency in Pathogenesis of Disease. Plenum Medical Book Co, New York, NY
  4. Walti MK, Zimmermann MB, Walczyk T, Spinas GA, Hurrell RF (2003) Measurement of magnesium absorption and retention in type 2 diabetic patients with the use of stable isotopes. Am J Clin Nutr 78:448-453
  5. al-Ghamdi SM, Cameron EC, Sutton RA (1994) Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis 24:737-752
  6. Taranenteo VM (1991) Efficacy of vascular wall protection from atherosclerotic damage using various calcium antagonists. Patol Fiziol Eksp Ter 31:5-7
  7. Weglicki WB, Mak IT, Kramer JH, Dickens BF, Cassidy MM, Stafford RE, Philips TM (1996) Role of free radicals and substance P in magnesium deficiency. Cardiovasc Res 31:677-682
  8. Mak IT, Komarov AM, Wagner TL, Stafford RE, Dickens BF, Weglicki WB (1996) Enhanced NO production during Mg deficiency and its role in mediating red blood cell glutathione loss. Am J Physiol 271:C385-C390
  9. Waters RS, Bryden NA, Patterson KY, Veillon C, Anderson RA (2001) EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 83:207-221
  10. Guldager B, Jorgensen PJ, Grandjean P (1996) Metal excretion and magnesium retention in patients with intermittent claudication treated with intravenous disodium EDTA. Clin Chem 42:1938-1942
  11. Anderson RA, Bryden NA, Waters R (1999) EDTA chelation therapy does not selectively increase chromium losses. Biol Trace Elem Res 70:265-272
  12. Jeppesen BB (1986) Magnesium status in patients with acute myocardial infarction: a pilot study. Magnesium 5:95-100
  13. Anderson RA, Polansky MM, Bryden NA (1984) Strenuous running:  acute effects on chromium, copper, zinc and selected clinical variables in urine and serum of male runners. Biol Trace Elem Res 6:327-336
  14. Gitelman HJ, Welt LG (1969) Magnesium deficiency. Annu Rev Med 20:233-42:233-242
  15. Durlach J (1992) New trends in international magnesium research. Magnes Res 5:1-4
  16. Clarke NE, Clarke CN, Mosher RE (1955) The “in vivo” dissolution of metastatic calcium. American Journal Medical Science 229:142-146
  17.  (1956) Treatment of Angina Pectoris with disodium ethylene diamine tetraacetic acid. Journal Medical Science 232:22-34
  18. Sjogren A, Floren CH, Nilsson A (1988) Evaluation of magnesium status in Crohn’s disease as assessed by intracellular analysis and intravenous magnesium infusion. Scand J Gastroenterol 23:555-561
  19. Gullestad L, Dolva LO, Waage A, Falch D, Fagerthun H, Kjekshus J (1992) Magnesium deficiency diagnosed by an intravenous loading test. Scand J Clin Lab Invest 52:245-253
  20. Resnick LM, Gupta RK, Laragh JH (1984) Intracellular free magnesium in erythrocytes of essential hypertension: relation to blood pressure and serum divalent cations. Proc Natl Acad Sci 81:6511-6515
  21. Barbagallo M, Gupta RK, Dominguez LJ, Resnick LM (2000) Cellular ionic alterations with age: relation to hypertension and diabetes. J Am Geriatr Soc 48:1111-1116
  22. Resnick LM, Altura BT, Gupta RK, Laragh JH, Alderman MH, Altura BM (1993) Intracellular and extracellular magnesium depletion in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36:767-770
  23. Resnick LM (1992) Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme. J Am Soc Nephrol 3:S78-S85
  24. Resnick LM (1992) Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders. Am J Med 93:11S-20S
  25. Yufu K, Takahashi N, Anan F, Hara M, Yoshimatsu H, Saikawa T (2004) Brachial arterial stiffness predicts coronary atherosclerosis in patients at risk for cardiovascular diseases. Jpn Heart J 45:231-242
  26. Resnick LM, Militianu D, Cunnings AJ, Pipe JG, Evelhoch JL, Soulen RL (1997) Direct magnetic resonance determination of aortic distensibility in essential hypertension: relation to age, abdominal visceral fat, and in situ intracellular free magnesium. Hypertension 30:654-659
  27. Barbagallo M, Resnick LM, Dominguez LJ, Licata G (1997) Diabetes mellitus, hypertension and ageing: the ionic hypothesis of ageing and cardiovascular-metabolic diseases. Diabetes Metab 23:281-294
  28. Wells IC, Agrawal DK, Anderson RJ (2004) Abnormal magnesium metabolism in etiology of salt-sensitive hypertension and type 2 diabetes mellitus. Biol.Trace Elem Res 98:97-108
  29. Gullestad L, Midtvedt K, Dolva LO, Norseth J, Kjekshus J (1994) The magnesium loading test: reference values in healthy subjects. Scand J Clin Lab Invest 54:23-31
  30. Gullestad L, Nes M, Ronneberg R, Midtvedt K, Falch D, Kjekshus J (1994) Magnesium status in healthy free-living elderly Norwegians. J Am Coll Nutr 13:45-50
  31. Rob PM, Dick K, Bley N, Seyfert T, Brinckmann C, Hollriegel V, Friedrich HJ, Dibbelt L, Seelig MS (1999) Can one really measure magnesium deficiency using the short-term magnesium loading test? J Intern Med 246:373-378
  32. Martini LA (1999) Magnesium supplementation and bone turnover. Nutr Rev 57:227-229
  33. Tohno S, Tohno Y, Masuda M, Minami T, Moriwake Y, Utsumi M, Yamada M (1999) A possible balance of magnesium accumulations among bone, cartilage, artery, and vein in single human individuals. Biol Trace Elem Res 70:233-241
  34. Matsuzaki H (2006) [Prevention of osteoporosis by foods and dietary supplements. Magnesium and bone metabolism]. Clin Calcium 16:1655-1660
  35. Laires MJ, Monteiro CP, Bicho M (2004) Role of cellular magnesium in health and human disease. Front Biosci 9:262-276
  36. Thoren L (1963) Magnesium deficiency in gastrointestinal fluid loss. Acta Chir Scand 10:Suppl 306-Suppl 365
  37. Caddell JL, Saier FL, Thomason CA (1975) Parenteral magnesium load tests in postpartum American women. Am J Clin Nutr 28:1099-1104
  38. Bohmer T, Mathiesen B (1982) Magnesium deficiency in chronic alcoholic patients uncovered by an intravenous loading test. Scand J Clin Lab Invest 42:633-636
  39. Ryzen E, Elbaum N, Singer FR, Rude RK (1985) Parenteral magnesium tolerance testing in the evaluation of magnesium deficiency. Magnesium 4:137-147
  40. Fort P, Lifshitz F (1986) Magnesium status in children with insulin-dependent diabetes mellitus. J Am Coll Nutr 5:69-78
  41. Rasmussen HS, McNair P, Goransson L, Balslov S, Larsen OG, Aurup P (1988) Magnesium deficiency in patients with ischemic heart disease with and without acute myocardial infarction uncovered by an intravenous loading test. Arch Intern Med 148:329-332
  42. Martin BJ (1990) The magnesium load test: experience in elderly subjects. Aging (Milano) 2:291-296
  43. Ozono R, Oshima T, Matsuura H, Higashi Y, Ishida T, Watanabe M, Yoshimura M, Hiraga H, Ono N, Kajiyama G (1995) Systemic magnesium deficiency disclosed by magnesium loading test in patients with essential hypertension. Hypertens Res 18:39-42
  44. Toral R, Jr., Martinez HD, Martinez RM, Llobell SG, Peralba Vano JI, Ribera Casado JM (1996) Intravenous magnesium load test in elderly patients with protein-energy malnutrition. Magnes Res 9:293-298
  45. Hebert P, Mehta N, Wang J, Hindmarsh T, Jones G, Cardinal P (1997) Functional magnesium deficiency in critically ill patients identified using a magnesium-loading test. Crit Care Med 25:749-755
  46. Papazachariou IM, Martinez-Isla A, Efthimiou E, Williamson RC, Girgis SI (2000) Magnesium deficiency in patients with chronic pancreatitis identified by an intravenous loading test. Clin Chim Acta 302:145-154

Address all correspondence to:

Dr. Robert S. Waters, Waters Preventive Medical Center, PO Box 357,Wisconsin Dells, WI 53965, Phone: 608-254-7178, FAX: 608-253-7139, Email:



Prevention of Lower-Extremity Amputation with EDTA Chelation Therapy

By H. Joseph Holliday, MD, FACAM, RVT; 2000


This patient review was designed to compare the lower-extremity amputation rate of patients treated with traditional surgery interventions with those who received EDTA chelation for treatment of peripheral vascular insufficiency. The patient populations were similar and the follow-up period was compatible between chelation patients and those progressing to amputation after surgery. All amputations occurred within 1 year after surgery. The chelation-treated group was observed for 36 months. 89 patients were treated surgically with 8 failures leading to amputation (9% amputation rate). Rest pain was relieved in 9 of 14 patients after surgery. Therefore, 64% of the patients who presented with rest pain experienced improvement in quality of life with no rest pain after surgery. Five patients with continued rest pain after surgery required amputation. Seventy-six patients (87%) were able to walk without claudication after surgery. Twenty-two chelation patients received a combined total of 750 treatments. Four patients presented with rest pain and all but 1 patient received total relief after an average of 12 treatments; consequently, 75% of patients with rest pain were improved. The patient who experienced no improvement in rest pain stopped chelation after 12 treatments. Twenty-one patients completed 30 or more EDTA treatments; of those patients, 20 experienced an increase in walking distance without pain. The patient who did not experience an increase in walking distance without pain received complete relief from rest pain. None of the patients receiving chelation therapy progressed to amputation. Chelation treated patients were found to have a lower amputation rate than surgically treated patients with comparable lower-extremity arterial disease. Symptom relief with chelation is excellent. Therefore, EDTA chelation can be considered an option to surgical intervention for the initial and complete treatment of patients with lower-extremity arterial occlusive disease.

Click for Full Text PDF

Holliday, MD: Carotid Restenosis: A Case for EDTA Chelation

By H. Joseph Holliday, MD, FACA, RVT


Carotid restenosis has been found in up to 25% of patients after carotid endarterectomy. The most common cause of restenosis is continuation of the atherosclerotic process. Surgery can be beneficial in stroke prevention and should be considered in those patients at high risk for stroke. However, surgery does not arrest the disease of atherosclerosis. This report demonstrates a 10% reduction in the degree of stenosis in a patient treated with EDTA chelation for restenosis of a carotid artery after endarterectoy. EDTA chelation does arrest and reverse atherosclerosis and should be used in conjuction with surgery or as a primary treatment for carotid restenosis as well as for vascular occlusive disease in any artery whether initial or recurrent.

Click for full text PDF

Effect of chelation therapy on progressive diabetic nephropathy in patients with type 2 diabetes and high-normal body lead burdens.

Chen KH1, Lin JL, Lin-Tan DT, Hsu HH, Hsu CW, Hsu KH, Yen TH., 2012


A previous study in type 2 diabetic patients with high-normal body lead burdens showed that EDTA chelation therapy for 3 months slows progressive diabetic nephropathy during a 12-month follow-up. The effect of a longer course of therapy on kidney function decrease over a longer follow-up is not known.


A 12-month run-in phase, then a randomized single-blind study with a 27-month intervention.


University medical center; 50 patients (serum creatinine, 1.5-3.9 mg/dL) with high-normal body lead burden (≥80-<600 μg) were randomly assigned to the treatment and control groups.


The treatment group received weekly chelation therapy for 3 months to reduce their body lead burden to <60 μg and then as needed for 24 months to maintain this level. The control group received placebo for 3 months and then weekly for 5 weeks at 6-month intervals for 24 months.


The primary end point was change in estimated glomerular filtration rate (eGFR) over time. A secondary end point was a 2-fold increase in baseline serum creatinine level or the requirement for renal replacement therapy.


Body lead burdens were assessed by EDTA mobilization tests and eGFR was calculated using the equation for Chinese patients with type 2 diabetes.


Mean baseline eGFRs in the treatment and control groups were similar. After 3 months of chelation therapy, the change in eGFR in the treatment group (+1.0 ± 4.8 mL/min/1.73 m(2)) differed significantly from that in the control group (-1.5 ± 4.8 mL/min/1.73 m(2); P = 0.04). In the subsequent 24-month intervention, the yearly rate of decrease in eGFR (5.6 ± 5.0 mL/min/1.73 m(2) per year) in the treatment group was slower than that (9.2 ± 3.6 mL/min/1.73 m(2) per year; P = 0.04) in the control group. 17 (68%) control-group patients and 9 (36%) treatment-group patients achieved the secondary end point.


Small sample size, not double blind.


A 27-month course of EDTA chelation therapy retards the progression of diabetic nephropathy in type 2 diabetic patients with high-normal body lead burdens.

Inhibition of paraoxonase activity in human liver microsomes by exposure to EDTA, metals and mercurials.

Gonzalvo MC1, Gil F, Hernández AF, Villanueva E, Pla A. 1997


lab-work-1575846-640x960Inhibition of paraoxon hydrolase (paraoxonase) activity by ‘in vitro’ exposure to EDTA, Mg2+, Co2+, Ba2+, La3+, Zn2+, Cu2+, Hg2+, p-hydroxymercuribenzoate (p-OH-MB) and phenyl mercuric acetate (PMA) was investigated in human liver microsomes. Enzyme activity was totally inhibited by 1 mM EDTA in a time-dependent manner, in contrast to previous data obtained in rat liver where an EDTA-resistant fraction was detected. The possible influence of postmortem changes in these results was checked in a parallel experiment using rat livers with different postmortem intervals. From our results the existence in human liver of an EDTA-resistant fraction cannot be discarded. Ba, La and PMA showed immediate inhibition. By contrast the other compounds tested were time-dependent inhibitors. Ba and Zn showed the highest IC50 values. Cu and mercurials (Hg, p-OH-MB, PMA) were the most potent inhibitors of human liver paraoxonase. Kinetic analysis (Lineweaver-Burk and Dixon plots) indicated that different inhibitors exhibit different inhibition patterns: competitive (EDTA, Ba, La, Cu, p-OH-MB and PMA), non competitive (Zn) and mixed (Hg). The pretreatment of sample with dithiothreitol (DTT) protects against the inhibitory effect of mercurials. Furthermore after inhibition by mercurials the activity was restored by DTT. These results confirmed the essential role of the -SH groups to maintain the catalytic activity of paraoxonase and suggest the existence of two types of -SH groups that could differ in their localization.

Full Text PDF:

EDTA Redistribution of Lead and Cadmium Into the Soft Tissues in a Human With a High Lead Burden – Should DMSA Always Be Used to Follow EDTA in Such Cases?

by Crinnion WJ


Intravenous sodium calcium ethylene diamine tetra acetic acid (EDTA) and oral 2,3-dimercaptosuccinic acid (DMSA) have both been used to reduce the burden of lead in humans. Each of these agents enhances the mobilization of lead from different areas of the body – EDTA from the trabecular bone and DMSA from the soft tissue. A study of Korean battery workers revealed that EDTA appeared to increase the soft tissue burden of lead, resulting in increased levels of aminolevulinic acid and greater subsequent lead mobilization with DMSA. This case report discusses a patient with a higher-than-normal lead burden who exhibited increased tissue lead burden after intravenous EDTA. The elevated tissue burden of lead was still present, albeit lower, after five consecutive days of oral DMSA therapy. If this single case is representative of a typical human response to the use of intravenous (IV) EDTA for lead, then it suggests that all persons undergoing such treatment should be administered oral DMSA for a minimum of one week after EDTA treatment.

TACT Trial: EDTA Chelation Therapy for Atherosclerosis

Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction

Lamas-Gervasio-CARDIOLOGYGervasio A. Lamas, MD; Christine Goertz, DC, PhD; Robin Boineau, MD, MA; Daniel B. Mark, MD, MPH; Theodore Rozema, MD; Richard L. Nahin, PhD, MPH; Lauren Lindblad, MS; Eldrin F. Lewis, MD, MPH; Jeanne Drisko, MD; Kerry L. Lee, PhD ;

Importance Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.

Objective To determine if an EDTA-based chelation regimen reduces cardiovascular events.

Design, Setting, and Participants Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.

Interventions Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.

Main Outcome Measures The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036.

Results Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.

Conclusions and Relevance Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.

Trial Registration Identifier: NCT00044213

Treatment of lead toxicity with chelation was first reported with EDTA in the early 1950s.1Apparent success in reducing metastatic calcium deposits2 led Clarke et al3 in 1956 to treat angina patients with EDTA, and others to use chelation for various forms of atherosclerotic disease.4– 6Chelation therapy evolved to constitute infusions of vitamins and disodium EDTA, a drug that binds divalent and some trivalent cations, including calcium, magnesium, lead, cadmium, zinc, iron, aluminum, and copper, facilitating their urinary excretion.7,8

Over the next decades, based on favorable anecdotal and case report experience, chelation practitioners increased their use of EDTA for coronary and peripheral artery disease. The 2007 National Health Statistics Report compared chelation use since 2002 and noted an increase of 68%, from 66 000 to 111 000 adults using chelation therapy,9 although the indications for therapy were not clearly defined, and the prevalence of use of chelation therapy for cardiovascular disease is unknown.

Three small clinical trials have assessed the effects of chelation on surrogate outcomes, such as walking distance in patients with claudication (2 trials with 185 patients total) and time to exercise-induced ischemia in patients with coronary disease (1 trial with 84 patients). These studies did not find any evidence of treatment efficacy but were underpowered for evaluation of clinical events.10– 12 As a consequence, mainstream medical organizations consider the therapeutic value of chelation for atherosclerotic vascular disease unproven13 and the use of this therapy potentially dangerous. Disodium EDTA, particularly when infused too rapidly, may cause hypocalcemia and death.14 The Trial to Assess Chelation Therapy (TACT) was conducted to respond to the public health problem posed by EDTA chelation therapy: large numbers of patients being exposed to undefined risks for unproven benefits.

EDTA chelation therapy in the treatment of vascular disease.

Chappell LT1, Janson M.


A retrospective analysis of treatment results from 2870 patients, with various chronic degenerative and age-associated diseases, who were treated with di-sodium magnesium EDTA chelation therapy, suggests that the case against EDTA Chelation Therapy should be re-opened.

Using qualitative but never-the-less standardized criteria for improvement, our analysis shows that EDTA Chelation Therapy resulted in “marked” improvement in 76.89% and “good” improvement in 16.56% of patients with ischemic heart disease; also, “marked” improvement in 91% and “good” improvement in 7.6% of patients with peripheral vascular disease and intermittent claudication. In a group of patients with cerebro-vascular and other degenerative cerebral diseases, 24% had “marked” improvement, and 30% had “good” improvement. Of four patients with scleroderma, three had “marked” improvement and one had “good” improvement. Seventy-five percent of all of the patients had “marked” improvement in “geriatric symptomatology of vascular origin”.

The authors recommend renewed study of EDTA Chelation Therapy. The possibility of a “tomato effect”, i.e., a drug which works, but the majority of physicians believe that it doesn’t work, needs to be ruled out. A favorable climate needs to be created, in which FDA-approved studies of its usefulness in treating peripheral vascular disease can take place.

Should EDTA chelation therapy be used instead of long-term clopidogrel plus aspirin to treat patients at risk from drug-eluting stents?

by Chappell LT, 2007red-pills-1526972-639x384

Abstract: The recently discovered increased risk of blood clots, leading to myocardial infarction and sudden death beginning six months after medicated stents are implanted in patients following percutaneous transluminal coronary angioplasty (PTCA), has left cardiologists pondering what course of action to take. The purpose of adding implanted medication to a stent is to prevent thrombin accumulation and restenosis. However, these stents may increase, rather than decrease, the risk. Although long-term treatment with clopidogrel bisulfate (Plavix) plus aspirin for at least 12 months has been suggested as a preventive treatment, there is no evidence from randomized, controlled trials that this treatment is effective for more than six months. Clopidogrel also increases the risk of major bleeding episodes. The author served as the primary investigator for a study that showed cardiovascular patients treated with EDTA chelation therapy had a lower rate of subsequent cardiac events, including myocardial infarction and death, than those treated with cardiac medications, PTCA, or coronary artery bypass graft (CABG). The data also indicated chelation therapy might be effective in preventing thrombosis and cardiac events from stent implantation. There is evidence EDTA chelation therapy might prevent hypercoagulability resulting from the placement of stents, although not specifically medicated stents. Based on the limited data currently available, intravenous EDTA may be safe and effective for treating patients who have implanted medicated stents. Prospective clinical trials are needed, and EDTA should be included in those trials.