Journal of Advancement in Medicine

Volume 3, Number 2, Summer 1990

$i Mineral Excretion Associated with

. EDTA Chelation Therapy

Hugh D. Riordan, M.D., Emanuel Cheraskin, M.D.,

D.M.D., and Marvin Dirks, B.D., M.A.*
ABSTRACT: This study measured excretion of 11 minerals induced by
EDTA chelation therapy in 25 adults (aluminum, cadmium, calcium, chro-
mium, copper, iron, lead, magnesium, manganese, mercury, zinc). We admin-
istered 20 EDTA infusions (3 g, with magnesium and ascorbate) 1to 2 weeks
apart and measured 24-hr urinary excretions of minerals before treatment
and after treatments 1, 10, and 20. A modest supplement provided replace-
ment nutrient minerals. Long-term excretion was enhanced about 35% for
lead and 60% for cadmium, but not for mercury. Enhanced excretion of essen-
tial minerals was small compared to dietary and supplementary intakes.
These results support the nutritional safety of EDTA chelation therapy by
the protocol used.

Introduction

Intravenous (IV) infusion of ethylenediaminetetraacetic acid (EDTA)

is a generally accepted treatment for acute and high-level lead intox-
ication (1,2). Its possible utility to treat low-level, chronic burden of
lead or cadmium is questioned by some due to possible adverse reac-
tions including kidney damage and depletion of essential minerals
, (3,4). However, these adverse reactions are strongly dependent on the
frequency and infusion rate of chelation therapy, which in the past
were often higher than those now widely used. We explored the possi-
bility that less intense therapy (5) may prove safe enough to use for

Hugh D. Riordan is Director of The Center for the Improvement of Human Function-
ing International, Inc., 3100 North Hillside Ave., Wichita, Kansas 67219 (formerly
The Olive W. Garvey Center for the Improvement of Human Functioning). Emanuel
Cheraskin and Marvin Dirks are respectively Research Consultant and Research As-
sociate at The Center.
Reprint requests should be addressed to Hugh D. Riordan.

111 O 1990 Human Sciences Press

112 JOURNAL OF ADVANCEMENT IN MEDICINE

levels of lead or cadmium intoxication lower than are now generally

considered appropriate for IV EDTA treatment. In addition, we
sought to document nutrient mineral losses during chelation therapy
so that informed decisions can be made about adequate nutritional
supplementation.
Because chronic, low-level intoxication with lead and cadmium has
been implicated as contributing to the current epidemic of hyperten-
sion (6-lo), we studied adults with previously diagnosed hypertension
and selected those with the largest increase in excretion of lead or
cadmium following a challenge infusion of EDTA. We then gave them
a total of 20 EDTA infusions spaced a t least 1 week apart and modest
amounts of replacement minerals in the form of a broad-spectrum,
multivitamin and mineral supplement.
We report here measurements of EDTA-induced excretion of 11
minerals during the first 24 h r following entry into the study and
following infusions 1, 10, and 20. These measurements appear to be
mostly new to the literature and suggest that appropriate EDTA
treatment and mineral supplementation can significantly enhance
excretion of body lead and cadmium without undue loss of essential
minerals. In previous publications from this study we have reported
lack of harm (and possible benefit) to kidney function ( l l ) , undis-
turbed blood chemical profile (12), and improved general clinical
symptomatology (13).

Methods

Local newspaper and television advertisements solicited volunteers

with hypertension for a study of chelation therapy. They were re-
quired to be ambulatory, over age 40, have a 1-year history of diag-
nosed hypertension, and have a blood pressure of a t least 140 mm
systolic and 90 mm diastolic (average of 3 measurements a t least 10
minutes apart). The 127 volunteers were asked to complete screening
laboratory work (24-test multichemical profile, complete blood count,
urine analysis, blood lead and cadmium, and hair minerals), the Cor-
nell Medical Index (id), history questionnaires, and a challenge
chelation with 3 g EDTA and 15 g ascorbate. We selected 25 subjects
with normal kidney function (fasting serum creatinine < 1.7 mg1dL)
who showed a t least a 5-fold increase in 24-hr urinary excretion of
lead or cadmium as a result of the EDTA challenge. Nearly all were
taking antihypertensive medications, which they were advised to con-
 RIORDAN ETAL. 113

TABLE 1
1
Urinary 24-hr Excretion and Supplementary Intake of Minerals
(25 subjects)

Mean
Mean Induced
Post EDTA EDTA- Excretion
Pretreatment Excretion Induced Incl. Non-
Excretion (Treatments Excretion treatment
Mineral Unit Mean (SD) 1, 10, 20) (#2-#1) Days** Supplement*

Aluminum
Cadmium
Calcium
Chromium
Copper
Iron
Lead
Magnesium
Manganese
Mercury
Zinc

*Bronson Insurance Formula; other ingredients include: Phosphorus 250 mg, iodine
150 mcg, molybdenum 100 mcg, selenium 20 mcg, vit. A 7500 IU, vit. D 400 IU, vit.
E 40 IU, ascorbic acid 250 mg, thiamin 2 mg, riboflavin 2 mg, pyridoxine, 3 mg,
cobalamine 9 mcg, niacinamide 20 mg, pantothenic acid 15 mg, biotin 300 mcg, folic
acid 400 mcg, choline 250 mg, inositol 250 mg, PABA 30 mg, rutin 200 mg.
**EDTA-induced excretion (#3), times 20 treatments, divided by 215 d mean dura-
tion of treatments.
***Includes 19 mg mean daily intake from 208 mg in each EDTA infusion (19 mg =
208 mg times 20 treatments, divided by 215 dl.

tinue. Nine subjects who met our criteria for hypertension during the
initial screening tested as normotensive when the treatment phase
began. Subjects signed an informed consent form prior to entering the
study, which was conducted in keeping with the Helsinki Declaration
of 1975.
A series of 20 EDTA infusions (including the initial screening infu-
sion) was administered a t intervals of 1 to 2 weeks. The series was
completed in 27 to 37 weeks (mean 30.8), as convenient for the sub-
114 JOURNAL OF ADVANCEMENT IN MEDICINE

jects. Each infusion contained 3 g disodium EDTA (Keylate: Edetate

Disodium: The Key Co., St. Louis, Missouri), 15 g injectable ascorbic
acid buffered with sodium bicarbonate (Steris, Inc., Glendale, Ari-
zona), 800 mg injectable magnesium chloride, 40 mg procaine, and
1000 units heparin delivered in 590 mL sterile, deionized water. It
was intravenously infused during a period of 3 to 5 hours. Because
the goal was to eliminate toxic minerals, but not essential minerals,
each subject was given a supply of multivitamin and mineral supple-
ments (Table 1) and instructed to take 3 tabletslday (Vitamin and
Mineral Insurance Formula, Bronson Pharmaceuticals, La Canada,
California). Eighteen of the 25 subjects reported already taking a
multinutrient supplement or individual mineral supplements (pri-
marily calcium, zinc, and magnesium).
A 24-hr urine sample was collected from each subject immediately
before and immediately after infusion 1(the screening challenge) and
after infusions 10 and 20; subjects voided prior to infusion and col-
lected for 24 hr. Aluminum, lead, cadmium, and manganese were
measured by use of a Perkin-Elmer HGA-500 graphite furnace and
model 306 atomic absorption spectrophotometer with deuterium back-
ground correction lamp. Calcium, magnesium, iron, copper, and zinc
were analyzed on a Perkin-Elmer 560 spectrophotometer. Mercury
analysis was performed on a Perkin-Elmer MAS-50A mercury an-
alyzer system by the method of Hatch and Ott (15). Except for mer-
cury, measured values were virtually all a t least several times the
detection limits and are believed to be accurate. For mercury, 20% of
individual measurements were less than the detection limit of 0.05
mcgl24 hr. Means were calculated by setting these values equal to
half of the detection limit; because these means are 40 times the de-
tection limits, they, too, are judged to be accurate.

Results

The 24-hr urine samples collected after the first treatment showed
markedly higher amounts of nearly all minerals tested than did the
pre-infusion samples (Figures 1-5). Only mercury showed no statis-
tically significant initial increase (p > 0.05 by paired t-test). There
was a 7-fold increase in mean 24-hr excretion for lead and cadmium,
and a nearly 2-fold increase for aluminum following the first chela-
tion. Among the essential minerals the largest 24-hr increases oc-
curred for manganese (50-fold), zinc (30-fold), iron (8-fold), and cal-
 RIORDAN ETAL. 115

FIGURE 1

Urinary excretion of lead and aluminum (mean + SD), 24-hr

samples before treatment and after infusions 1,10, and 20. Only
small amounts of chelation-induced mineral excretion occur
after the first 24 hr. To avoid overcrowding, some SDs (a
measure of group variability) are shown on only one side of the
means. The increased excretion of aluminum approximately
equals amounts found in the infused solution. Because the
distributions of excretions are often asymmetrical (skewed
toward high excretion), most subjects had excretions less than
the means shown, and the ranges + 1SD do not necessarily
have the same significance that they do with Gaussian
distributions.

Pre
116 JOURNAL OF ADVANCEMENT IN MEDICINE

FIGURE 2

Urinary excretion of calcium and magnesium.

Chelation Nunber

cium (2-fold). These increased excretions during the 1st 24 hr were

maintained throughout the study for all minerals including cadmium
but not for lead (Fig. I), which dropped by nearly one half between
the 1st and 10th infusions (P < 0.0001 by paired t-test, 2-tailed).
Magnesium ex{retion may have declined during the same interval
(P = 0.03), but the decline was small and was not maintained at the
20th infusion (Fig. 2). Unlike lead, aluminum showed a substantial
rise in mean 24-hr excretion between the 1st and 20th infusions (Fig.
1, P = 0.02; see discussion). Mercury excretion appeared to increase
at the 20th infusion (Fig. 3, P = 0.03).
 RIORDAN ET AL. 117

FIGURE 3

Urinary excretion of mercury and cadmium.

1 I I I
15

Chelatian k r nber

The nutrient minerals manganese and chromium also showed sta-

tistically significant increases after many infusions, especially man-
ganese (Fig. 4). These delayed increases and the suggestive rise for
calcium may represent a previously unreported consequence of re-
peated EDTA treatments, or they may be due entirely or in part to
our supplementation with these minerals. This question could be
studied by repeating our experiment without mineral supplements.
Table 1 summarizes the excretion measurements and shows ap-
proximate lower limits for the extra mineral excretion induced by the
20 EDTA infusions. The amounts are lower limits because of the
small, unmeasured amounts of EDTA-induced excretion that may oc-
cur following the first 24hr after each infusion, according to available
information for lead (5,16,17), calcium (16,18), zinc (16,19) and other
minerals (16). Table 1, column #1 shows 24-hr mean excretions be-
fore treatment. Columns #2 and #3 reflect mean excretions during
118 JOURNAL OF ADVANCEMENT IN MEDICINE

FIGURE 4

Urinary excretion of manganese and copper. The increased

excretion of manganese at the 10th and 20th chelations might
be due, all or in part, to the supplement given.

0 I I

Pre 1 10 20

Chelation Number

the first 24 h r following treatments 1, 10, and 20. Column #4 shows

the net EDTA-induced excretion, time-averaged to include the non-
treatment days.
For the toxic minerals shown in Table 1, column #4 shows the fol-
lowing approximate time-averaged increases over pretreatment excre-
tions: lead 35%, cadmium 6Q%, aluminum 10% and mercury 0%
(smaller than the 1st 24-hr increases due to inclusion of non-treat-
ment days). The corresponding time-averaged increases for nutrient
 RIORDAN ETAL. 119

FIGURE 5

Urinary excretion of zinc, iron, and chromium.

I I I
-r
-
-
d

I
-
-
-
-
--
-
-
- -
-
- -
-
-- Iron (1 00 mcg) -
- -
-
- - - -

0 I 1 I I

Pre 1 10 20

minerals were in a comparable range except for manganese and zinc,

for which EDTA-induced excretions were respectively about 7- and
3-fold greater than baseline excretion. However, in absolute amounts
the EDTA-induced excretions of manganese, zinc and all other essen-
tial minerals shown in column #4 were much smaller than usual di-
etary intakes and absorptions (20).
Similarly, the supplements given (Table 1, column #5) were much
larger than the induced excretions: 9-fold larger for zinc, 15-fold for
calcium, and 65- to 3000-fold for the other nutrients studied. These
margins appear ample to compensate for the incomplete absorption of
 120 JOURNAL OF ADVANCEMENT IN MEDICINE

essential minerals. For example, about 15% to 40% of food zinc is

absorbable, depending in part on zinc status (20). Hence, supplemen-
tation with these modest amounts of essential minerals afforded our
subjects good protection against depletion during EDTA treatments
at 1-to 2-week intervals.
Mean 24-hr excretion of lead after the first EDTA infusion was 93
mcg (range, 23 to 166 mcg), much less than the 1200 mcg/3 g EDTA
currently considered to indicate increased lead burden and risk of
chronic lead nephropathy (8). Initial mean blood lead level was 6.8
mcg/dL (range, 2 to 12 mcg/dL); 50 mcg/dL is the current U.S. Depart-
ment of Labor maximum permitted level (occupational safety and
health standard 1910.1025). After 20 EDTA treatments, mean blood
level declined 45% to 3.7 mcgldl, P = 0.000 by paired t-test).
Mean initial 24-hr cadmium excretion was 7 mcg (range, 1.6 to 18
mcg), and mean initial blood cadmium was 0.09 mcg/dL (range, 0.02
to 0.21 mcg/dL). After 20 EDTA treatments, mean blood level was
0.11 mcg/dL, a n insignificant increase.
Group average blood pressures did not change in a consistent direc-
tion or more than 2 mm during the study. Because nearly all subjects
were taking antihypertensive medications, further studies of hyper-
tension may be warranted with subjects not taking such medications
and with those having higher levels of toxic metals.

Discussion

This report is intended to provide new information about the urinary

loss of essential minerals during EDTA infusion therapy, one of the
major concerns about the safety of this therapy. Although generaliza-
tion from our findings may be limited by being derived from selected,
hypertensive subjects, our data seem unlikely to differ broadly from
excretions in other populations receiving medical treatment with
EDTA infusions. The previously published excretion data of which we
are aware are all based on analytical capabilities of 30 years ago, and
are limited primarily to calcium (18) and zinc (19). Another early
study (16) focused on several other minerals (including non-nutrient
ones) but was hampered in some cases by inadequate analytical sensi-
tivity. None of these studies dealt with repeated EDTA infusions
spaced 1 to 2 weeks apart.
In agreement with prior studies, we found that EDTA infusions in-
crease urinary excretion of all toxic and essential minerals studied
 RZORDAN ET AL. 121

except mercury. However, under the conditions of our experiment, the

increased excretions of essential nutrients were all small compared to
-, usual dietary intakes and absorptions. The most significant EDTA-
induced loss in our experiment is presumably the average 1.8 mglday
of zinc. This may be compared to typical daily intakes of 10 to 15 mgl
day (20), and to the amount in the supplement we used.
For all other essential minerals studied, EDTA-induced excretions
were smaller than for zinc, relative to dietary intakes and supplemen-
tary amounts. We conclude that there is negligible risk of depleting
the studied nutrients during EDTA chelation therapy with 3 g EDTA
at intervals of 1 week or more, when used with modest levels of min-
eral supplementation. Further studies are needed to assess other min-
erals such as selenium and molybdenum, and other subjects who
might differ significantly from our selected population.
More frequent EDTA infusions than we used would increase urin-
ary loss of essential minerals but probably not in full proportion to
EDTA dosage. With daily infusion of 3 g EDTA, induced losses of zinc
might approach 15 mg/d in addition to usual non-induced losses. If so,
prolonged treatment would risk zinc depletion even with a 15 mgld
supplement because absorption is never complete. Calcium depletion
might occur as well, if it were not adequately supplemented. Further
studies would be required to assess mineral balance with higher in-
tensity EDTA treatments than we used.
Besides nutrient mineral depletion, two major concerns have been
expressed regarding IV EDTA therapy. One is the fear that this tech-
nique may impair renal function. In earlier reports we, as well as
others, have presented measures of renal function which indicated no
renal impairment, and perhaps even a benefit if treatments are ap-
propriate in composition and administration (11,21-23). The other
concern has been that EDTA chelation invites a metabolic upheaval
either directly or indirectly through the loss of essential minerals. We
have demonstrated the lack of general metabolic upheaval in pre-
vious reports which show overall stability in the usual 24-test multi-
chemical profile (12) and complete blood count.
The observed doubling of aluminum excretion after EDTA treat-
ment puzzled us (Figure 1). Because of uncertainty as to whether
EDTA is an effective aluminum chelator under physiologic condi-
tions, we speculated that the infused solution might contain sufficient
aluminum to account for the observed increases which averaged
about 40 to 60 mcg/24 hr. Analysis of later stocks of various compo-
nents of the infused solutions showed negligible aluminum except in
122 JOURNAL OF ADVANCEMENT IN MEDICINE

the buffered ascorbic acid solution. It contained about 52 mcg per

treatment (26 mcg per 30-mL bottle; duplicate analyses of two sam-
ples of one lot by our lab and by Monroe Laboratories, Southfield,
New York). Because this amount is similar to the observed average
increase in aluminum excretion, the increase might not represent re-
moval of body stores of aluminum.
The manufacturer of our buffered ascorbic acid suggests that this
amount of aluminum is of minimal concern and may originate from
the glass container or rubber seal. The amount is much less than
typical oral intakes from widely used food additives and foods-about
30 mgld according to Bjorksten (24). However, it might not be large
compared to typical daily aluminum absorption, as suggested by our
observation of increased aluminum excretion after many treatments.
Further consideration seems desirable for injectable solutions that
are to be used repeatedly in the same individual. Recent communica-
tions from the manufacturer suggest cause for optimism regarding
the possibility of virtually aluminum-free injectable ascorbate by
early 1990.
Previously there has been little information available about excre-
tion of essential minerals during IV EDTA chelation therapy. This
lack made it difficult to evaluate the nutritional safety of such ther-
apy and prevented well informed decisions about adequate supple-
mentation. We have attempted to supply some of the needed informa-
tion for treatment programs similar to the one used here.

Acknowledgments

The following Center staff were involved in data collection and anal-
ysis and deserve our thanks: Penny Brizendine, ARNP; Georgianna
Cloud; Alfanette McDonald; Milt Poling, R.M.T.; Mavis Schultz, ARNP;
Maurice Van Strickland, M.D.; and Farhad Tadayon, M.S.M.E.
The EDTA used in this study was generously donated by The Key
Co., St. Louis, Missouri.

References .
1. Braunwald E, Isselbacher KJ, Petersdorf RG, Wildon JD, Martin JB, Rauci AS,
eds. Harrison's principles of internal medicine. 11th ed. New York: McGraw-Hill,
1987:852-853.
 RZORDAN ETAL. 123

2. Emmerson BT: Toxic nephropathy. In: Wyngaarden JB, Smith LH, eds. Cecil text-
book of medicine. 17th ed. Philadelphia: WB Saunders Company, 1988598-599.
3. Bridbord K, Blejer HP: Prophylactic chelation therapy in occupational lead poison-
ing: a review. Am Ind Hyg J 1987;38:536-542.
4. Frackelton JP: Monitoring renal function during EDTA chelation therapy. J Holist
Med 1986;8:33-35.
5. Reiders F: Current concepts in the therapy of lead poisoning. In: Seven MJ, ed.
Metal-binding in medicine. Philadelphia: Lippincott 1960:143-145.
6. Batuman V, Landy E, Maesakay JK, Wedeen RP: Contribution of lead to hyperten-
sion with renal impairment. N Engl J Med 1983;309:17-21.
7. Harlan WR, Landis JR, Schmouder RL, Goldstein NG, Harlan LC: Blood lead and
blood pressure: relationship in the adolescent and adult US population. JAMA
1985;253:530-534.
8. Bernard BP, Becker CE: Environmental lead exposure and the kidney. Clin Tox-
icol 1988;26:1-34.
9. Sharp DS, Becker CE, Smith AH: Chronic low-level lead exposure: its role in the
pathogenesis of hypertension. Med Toxic01 1987;2:210-232.
10. Fontana SA, Boulos BM: Blood cadmium level as affected by hypertension, smok-
ing, occupation, and body mass. Am J Hypertens 1988 Ju1;1(3 Pt 3):158S-160s.
11. Riordan HD, Cheraskin E, Dirks M, Schultz M, Brizendine P: Another look a t
renal function and the EDTA treatment process. J Orthomol Med 1987;2:185-187.
12. Riordan HD, Jackson JA, Cheraskin E, Dirks M: The effects of intravenous EDTA
infusion on the multichemical profile. Am Clin Lab 1988; October:42-43.
13. Riordan HD, Cheraskin E, Dirks M, Tadayon F, Schultz M, Brizendine P: EDTA
chelation/hypertension study: clinical patterns as judged by the Cornell medical
index questionnaire. J Orthmol Med 1989;4:91-95.
14. Brodman K, Erdmann AJ J r , Wolff HG: Manual: Cornell medical index health
questionnaire. New York: Cornell University Medical Center, 1949.
15. Hatch WR, Ott WL: Determination of sub-microgram quantities of mercury by
atomic absorption spectrophotometry. Anal Chem 1968;40:2085-2087.
16. Perry HM, Perry EF: Normal concentrations of some trace metals in human urine:
changes produced by ethylenediaminetetraacetate. J Clin Invest 1959;38:1452-
1463.
17. Araki S: On the behavior of "active deposit of lead (Teisinger)" in the Japanese free
from occupational exposure to lead. Ind Health 1973;11:203-224.
18. Spencer H: The use of chelating agents in the study of mineral metabolism in man.
In: Seven MJ, ed. Metal-binding in medicine. Philadelphia: Lippincott
1960;104-114.
19. Perry HM J r , Camel GH: Some effects of CaNa2EDTA on plasma cholesterol and
urinary zinc in man. In: Seven MJ, ed. Metal-binding in medicine. Philadelphia:
Lippincott 1960;43-47.
20. Committee on dietary allowances. Recommended dietary allowances. 9th ed. Wash-
ington DC: Nat Acad Sci, 1980.
21. McDonagh EW, Rudolph CJ, Cheraskin E: The effect of EDTA chelation therapy
plus supportive multivitamin-trace mineral supplementation upon renal function:
a study in blood urea nitrogen (BUN). J Holist Med 1983;5:163-171.
22. McDonagh EW, Rudolph CJ, Cheraskin E: The effect of EDTA chelation therapy
plus supportive multivitamin-trace mineral supplementation upon renal function:
a study in serum creatinine. J Holist Med 1982;4:146-151.
23. Schnert KW, Clague AF, Cheraskin E: The improvement in renal function follow-
ing EDTA chelation and multivitamin-trace mineral therapy: a study in creatinine
clearance. Med Hypoth 1984;15:301-304.
24. Bjorksten J: Longevity, 2. Charleston, South Carolina: JAB Publishing, 1987: 63.