Onsite testing supervised by:
Theodore Rozema M.D. (1998)
Summary: The test results clearly demonstrate
the high level of effectiveness of removing lead from the human body
with Calcium disodium EDTA rectal suppositories.
The effect of lead poisoning is one of the most common and
preventable pediatric health problems today.
Currently the primary form of medical intervention consists of
expensive and painful CaEDTA intramuscular injection.
The availability if an easily administered effective medical
treatment is an important component in controlling the worldwide
lead poisoning epidemic.
Introduction: Childhood lead poisoning is one
of the most common pediatric health problems in the world today, and
it is entirely preventable and reversible.
Enough is now known about the sources and pathways of lead exposure,
about ways of preventing this exposure, and about ways of reducing
the lead content of the body to begin efforts to eradicate
permanently this disease. The persistence of
lead poisoning, in light of all that is known, presents a singular
and direct challenge to public health authorities, clinicians,
regulatory agencies, and society.
Lead is ubiquitous in the human environment as a result of
industrialization. It has no known physiologic
value. Children are particularly susceptible to
lead’s toxic effects. Lead poisoning, for the
most part, is silent: most poisoned children
have no symptoms. The vast majority of cases,
therefore, go undiagnosed and untreated. Lead
poisoning is widespread. It is not solely a
problem of inner city or minority children. No
socioeconomic group, geographic area, or racial or ethnic population
is spared.
Previous lead statements issued by the Center for Disease Control
(CDC) have acknowledged the adverse effects of lead at lower and
lower levels. In the most recent previous CDC
lead statement, published in 1985, the threshold for action was set
at a blood lead level of 25 mcg/dL, although it was acknowledged
that adverse effects occur below that level. In
the past several years, however, the scientific evidence showing
that some adverse effects occur below that levels at least as low as
19 mcg/dL in children has become so overwhelming and compelling that
it must be a major force in determining how we approach childhood
lead exposure.
It is not possible to select a single number to define lead
poisoning. Epidemiologic studies have identified
harmful effects of lead in children at blood levels at least as low
as 10 mcg/dL. Some studies have suggested
harmful effects at even lower levels, but the body of information
accumulated so far is not adequate for effects at even lower levels,
but the body of information accumulated so faris not adequate for
effects below 10 mcg/dL to be evaluated definitely.
As yet, no threshold has been identified for the harmful
effects of lead.
Because 10 mcg/dL is the lower level of range at which effects
are now identified, primary prevention activities are typically
directed at reducing children’s blood levels to 10 or 14 mcg/dL.
While the overall goal should be to reduce children’s blood
levels below 10 mcg/dL, there are entrenched reasons for not
attempting to do interventions directed at individual children to
lower blood lead levels of 10 – 14 mcg/dL.
First, practical medical interventions for children with blood lead
levels in this range would have been previously unavailable.
Second, the sheer numbers of children in this range would
preclude effective case management in establishing intravenous
therapy. Clearly a simple and effective therapy
such as suppository is needed.
Background:
Lead is a poison that affects virtually every system in the body.
The risks of lead exposure are not based on theoretical
calculations. They are well known from studies
of children themselves and are not extrapolated from data on
laboratory animals or high-dose occupational exposure.
Since 1970, our understanding of childhood lead poisoning has
changed substantially. As investigators have
used more sensitive measures and better study designs, the generally
recognized level for lead toxicity has progressively shifted
downward. Before the mid-1960s a level above 60
mcg/dL was considered toxic. (Chilsolm and Harrison, 1956).
By 1978, the defined level of toxicity had declined 50% to 30
mcg/dL.
Lower blood lead levels cause adverse effects as low as 10
mcg/dL, which do not cause distinctive symptoms, are associated with
decreased intelligence and impaired neurobehavioral development.
(Davis and Svendsgaard, 1987; Mushak et al., 1989).
The concern about adverse effects on central nervous system
functioning at blood lead levels as low as 10
mcg/dL is based on a large number of rigorous epidemiologic and
experimental studies. Several well-designed and
carefully conducted cross-sectional and retrospective cohort studies
in many different countries have been conducted.
(Lansdown et al., 1986; Fulton et al., 1987;
Ferguesson et al., 1988; Silva et al., 1988; Bergomi et al., 1989;
Hansen et al., 1989; Hatzakis et al., 1989; Winneke et al., 1990;
Lyngbye et al., 1990; Needleman et al., 1990; Yule et al., 1981;
Hawk et al., 1986; Schroder et al., 1985). Some
inconsistencies can be found in the results of these studies, but
the weight of the evidence clearly supports the hypothesis that
decrements in children’s cognition are evident at blood lead levels
well below 25 mcg/dL. No threshold for the
lead-IQ relationship is discernable from these data. Recent
evaluation of 24 major cross-sectional studies provide strong
support for the hypothesis that children’s IQ scores are inversely
related to the lead burden (Needleman and Gatsonis, 1990).
According to the Natural Resources Defence Council, blood lead
levels as low as 10 mcg/dL, which do not cause distinctive symptoms,
are associated with reading and learning disabilities, reduced
attention span and behavioral problems.
The ramifications of the proliferation of lead pollution from
industrialization combined with the devastating effects on health
are sobering. A simple and effective therapy,
such as EDTA chelation via suppository, is urgently needed.
Methods:
A cluster of previously untreatable children with high blood lead
levels was desired for the purpose of testing the efficacy of
Calcium disodium EDTA rectal suppositories to remove toxic metals
from the human body.
1.)
Determination of the study area:
Friends of lead free children, a non-profit organization
connected to Columbia University and Fordham University, assisted in
the search. A residential neighborhood in Haina,
Dominican Republic was selected. The residential
neighborhood was located adjacent to a battery recycling plant.
All preliminary testing indicated 100% of residents as
markedly toxic with lead.
2.)
The selection of subjects into the study:
Children who had been identified with blood lead levels over 10
mcg/dL were determined in a twenty-our (24) hour urine collection by
Ion Coupled Plasma Emission Spectroscopy. Hg.
Analysis was determined by cold-water mercury vapor analysis.
3.)
Individual treatment of lead overload:
Cautious removal of lead from body depots was achieved through
the use of Calcium disodium EDTA rectal suppositories.
The use of suppositories provided for the prevention of local
corrosive action of toxic metals on mucus membranes.
4.)
Compensation:
Compensation was not paid to subjects, however, no charges were
incurred by participants for the drug and laboratory testing.
5.)
Safety:
By determining the concentration of heavy metals in urine
following provocative stimulation, the therapy with EDTA was
scientifically determined, providing a safe treatment program.
The study simultaneously provided diagnostic information
regarding heavy metal burden as well as a defined treatment protocol
for lead toxicity in a pediatric population.
EDTA is a substance with low systemic and local toxicity and is
generally well tolerated. The drug per se has
been classified as GRAS by the FDA. No cases of
anaphylaxis have been reported through the oral administration of
EDTA or through its use as a food additive.
6.)
Alternative therapies:
Alternative therapies were available for the treatment of metal
intoxications, including (R,S) –2,3-dimercapto propane-1-sulfonic
acid (DMPS) as well as its close standing analog DMSA.
A significant advantage of using EDTA suppositories in
pediatric population include:
a.)
Cooperative binding constant for lead.
b.)
The suppository route of administration at bedtime was (is)
an easy and acceptable delivery system.
c.)
The antioxidant/free radical quenching role of EDTA made it
superior over other agents due to the fact that neurological
dysfunction was (is) recognized as a result of free radical mediated
damage.
e.)
EDTA is an ANTIDOTE to counteract the TOXIC action of lead
from the environment.
7.)
Medical Care:
Medical care was provided by Universidad de Autonomia de Santa
Domingo. In the event of medical emergency
connected with the study, subjects were to contact the appropriate
center, but this was never necessary. In
addition, all participants could receive product and clinical
information by calling: Ted Rozema M.D. ,
principal investigator.
8.)Data coordination:
Data was coordinated and maintained by the principal
investigator, all data was statistically analyzed.
Information was made available to all appropriate authorities
including IRB of the GLCCM and the FDA.
9.)Clinical laboratory:
Clinical laboratory facilities and medical support were provided
by AmScot Medical Laboratories, Inc. To ensure
the safety and integrity of the study, the following analyses were
to be assessed:
a.)
Base line:
Smac 18 with CBC – manual differentiation
Blood lead determination
Urine (24 hour collection) heavy metals to include: Pb, Cd, Hg,
As, Ni, Al
B2 – microglobulin (serum)
Anti-TPO
Total Ca/Ca2+ Mg/Mg2+
Pt/APTT
PTH
b.)
Provocative EDTA challenge”
Blood lead determination
Urine 9 hour- heavy metals -: Pb, Cd, Hg, As, Ni, Al
B2 – microglobulin (serum)
Total Ca/Ca2+ Mg/Mg2+
Pt/APTT
PTH
c.)
Mid study evaluation
Blood lead determination
CBC – Manual differential
Urine 9 hour- heavy metals -: Pb, Cd, Hg, As, Ni, Al
B2 – microglobulin (serum)
Total Ca/Ca2+ Mg/Mg2+
PTH
d.)
Post study (6 weeks)
Blood lead determination
Smac 18 with CBC- manual differentiation
Urine 9 hour- heavy metals -: Pb, Cd, Hg, As, Ni, Al
B2 – microglobulin (serum)
Total Ca/Ca2+ Mg/Mg2+
PTH
Research protocol:
A study to determine the efficacy of Calcium disodium EDTA used
as a rectal suppository n removing toxic metals form the human body.
Subjects: children with proven lead toxicity (blood levels > 10
mcg/dL)
Study Design:
1.)Enrollment
2.)Blood lead levels drawn to enter into study with simultaneous
determination of urine lead excretion (total urine minerals- if
possible with parental assistance).
3.)Treatment phase
4.)Placement of a rectal suppository containing 2 grams of
Calcium Disodium EDTA nightly for 10 days- then 10 days without EDTA
– the placement of the EDTA suppository for 10 days- continue this
program for two courses of treatment. EDTA
5.)Laboratory determinations:
Pre
After 10 days After 10
days After 10 days
Blood XX Supp
XX no supp
XX Supp
XX
Urine XX Supp
XX no supp
XX Supp
XX
Purpose is to demonstrate gradual reduction of both blood and
urine lead levels over time with a simple and cost-effective method.
It was anticipated that methods to reduce lead intake would be in
place during and after this study.
Unfortunately, no environmental mitigation was ever enacted.
Specimen Collection Regimen:
Pre study:
1)
Collection of 3 to 5 ml of whole blood in heparinized, lead
free curvettes.
2)
Collection of 9 hours of urine. This was
measured from the time the child went to bed until 9 hours later.
It was anticipated that the children were not getting up at
night to urinate and mother would need to watch to catch the first
morning specimen, then determine when is the 9 hour point and
collect additional urine to make the complete collection.
This provided a base line for both blood levels and excretion on
a daily basis.
Just before the first suppository:
1) Collection of 3 to 5 ml of whole blood in heparinized, lead
free curvettes.
2) Insertion of the first suppository in the child’s rectum, high
as possible just before the child goes to sleep, preferably with the
child already in bed.
The morning after the first suppository:
3)
Collection of 9 hours of urine. This was
measured from the time the child went to bed until 9 hours later.
It was anticipated that the children are not getting up at
night to urinate and mother would need to catch the additional urine
to make the complete collection.
The morning before the 10th suppository:
1)
Collection of 3 to 5 ml of whole blood in heparinized, lead
free curvettes.
The morning after the 10th suppository:
Collection of 9 hours of urine:. This was
measured from the time the child went to bed until 9 hours later.
It was anticipated that the children are not getting up at
night to urinate and mother would need to catch the additional urine
to make the complete collection.
The morning of the 19th day:
1) Collection of 3 to 5 ml of whole blood in heparinized, lead
free curvettes.
2)
Collection of 9 hours of urine. This was
measured from the time the child went to bed until 9 hours later.
It was anticipated that the children are not getting up at
night to urinate and mother would need to catch the additional urine
to make the complete collection.
This gave us a determination of equilibrium after no treatment
for 10 days.
The morning of the 30th day:
1)
Collection of 3 to 5 ml of whole blood in heparinized, lead
free curvettes.
The morning of the 30th suppository:
Collection of 9 hours of urine. This was
measured from the time the child went to bed until 9 hours later.
It was anticipated that the children are not getting up at
night to urinate and mother would need to catch the additional urine
to make the complete collection
All specimens were taken to the Laboratory of Dr. Conrado Depratt
at the Institute De Quimica of the Universidad Autonoma de Santo
Domingo.
Results:
Average 20 children test data
Blood lead levels:
Pre study
66.64 mcg/dL
after 10 days of
suppositories
39.09 mcg/dL
after 10 days
without suppositories
61.45 mcg/dL
after 10 more
days on suppositories
83.67 mcg/dL
Urine lead excretion levels
Pre study
4.23 mcg/dL
after 10 days of
suppositories
325.55 mcg/dL
after 10 days
without suppositories
61.445 mcg/dL
after 10 more
days on suppositories
122.71 mcg/ dL
The data clearly demonstrates that EDTA delivered in a rectal
suppository form, effectively removes lead from children with lead
poisoning. The continued high excretion level,
after 10 days without suppositories is of special interest.
Also of special interest is the rebound effect in the blood lead
levels. It’s degree reflecting the high amount
of stored lead in the tissues and bones and the attendant
mobilization effect. Each time the blood lead
level was diminished, additional lead was mobilized from the tissues
and bones.
It
was anticipated that methods to reduce lead intake would be in place
during and after this study. Unfortunately, no
environmental mitigation was even enacted.
Ideally environmental intervention would have been enforced and the
Calcium disodium EDTA rectal suppository therapy would have
continued for a 6-month duration. This
circumstance was not possible.
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