The role of Aluminum (Al)
in Medicine and our Environment
In a 1998 statement
the Commission ‚Human Biomonitoring’ of the German
Environmental Protection Agency points out three aspects that
are important in the environmental/medical assessment of aluminum:
1. Human exposure is
inevitable. Al is the third most common element on earth.
2. Al is clearly
neurotoxic 3.
Al has a potential role in the development and pathogenesis of
Alzheimer.
The commission states that to monitor an
exposure, we have three laboratory tests (blood, urine, hair) and the
DFO (Deferoxamine) Test.
In this News Release
we discuss the assessment of urine, before and after provocation. More
under www.microtraceminerals.com
1. Aluminum
Reference Range i.e. the acceptable upper range for unprovoked urine:
The German
Environmental Agency is expecting to reduce urine levels to <15µg/L.
The Mayo Clinic states that a daily
excretion >20 µg/L indicates exposure to aluminum.
We now use a reference range of <40µg/g
creatinine, which is equal to 40 µg/L.
All of the above ranges apply to unprovoked
urine i.e. urine that has not been provoked with any type of chelating
agent.
Clinical Information:
Under normal physiologic conditions, the
usual daily dietary intake of aluminum (5-10 mg) is completely
eliminated. Excretion is accomplished by avid filtration of aluminum
from the blood by the glomeruli of the kidney. Patients in renal
failure (RF) lose the ability to clear aluminum and are candidates for
aluminum toxicity.
A high intake of
dietary aluminum results in an increase in Al-elimination. High
amounts of Al can be found in tea, lemonades, colas and fruit juices
packaged in aluminum cans or aluminum-lined boxes. Zeolite, algae
products, food additives such as aluminum phosphate, antacids and
other medications may contain aluminum, causing an increase in urine
concentration.
Urine aluminum concentrations are likely to
be increased above the reference range in patients with metallic joint
prosthesis. Prosthetic devices produced by Zimmer Company and Johnson
and Johnson typically are made of aluminum, vanadium, and titanium.
This list of products is incomplete, and these products change
occasionally; see prosthesis product information for each device for
composition details.
Avoiding Al seems
more important than we ever expected. Research indicates that
transferrin can bind aluminum, transporting it through the Blood Brain
Barrier. In the brain, Al plays a role in the destruction of nerve
cells. (De Sole P., et al. Possible relationship between Al/ferritin
complex and Alzheimer disease. (Clin. Biochem. 2013; 46: 89-93)
The
Al-concentration of unprovoked urine is a reflection of the intake and
exposure that happened during the last hours prior to sampling.
In the
occupationally exposed, intoxication due to inhaled aluminum is
directly related to the renal Al-excretion.
The European
Environmental Agencies have set a Maximum Contaminant Level (MCL) of
200µg/L for the occupationally exposed.
The US Department of
Health and Human Services, Agency for Toxic Substances and Disease
Registry (ATSDR) does not provide a MCL.
THE MCL ONLY APPLIES
TO UNPROVOKED URINE
Diagnosis
and Therapy of an acute Aluminum-Intoxication / Exposition:
Patients receiving chelation therapy with
desferrioxamine (for iron- or aluminum-overload states) excrete
considerably more aluminum in their urine as they would under normal
conditions.
Cautions
In cases of Al-intoxication, desferrioxamine
elevates serum aluminum to levels >150µg/l. However, this test is not
an acceptable substitute for serum aluminum measurements and is not
recommended for routine aluminum screening.
Falsely increased
urine results may be obtained if the specimen is collected in
nonacid-washed polypropylene collection vessels or if metal caps are
used to seal the container.
Which
chelating agent is useful for the treatment of chronic or subacute
aluminum intoxication?
We compared mean levels of unprovoked urine
(baseline or spot urine) with mean levels of provocation urines
following treatment with commonly used chelating agents.
Table 1:
Comparison of mean aluminum concentration of unprovoked vs. provoked
urines:
Chelating agent(s)
|
# of
Tests
(N)
|
Mean
value
µg/g
crea
|
Max-value
µg/g
crea
|
Test
value
>200µg/g crea
|
Mean
Crea
value
g/L
|
Unprovoked urine
|
2485
|
14
|
1256
|
10
|
1,0
|
DMSA
oral, 500mg
|
249
|
19
|
262
|
2
|
0.62
|
DMPS,
iv
|
2750
|
18
|
390
|
2
|
0.66
|
DMPS iv
+ ZnDTPA iv
|
3320
|
20
|
817
|
2
|
0.69
|
MgEDTA,2,5g Infusion +500mg DMSA
|
78
|
57
|
141
|
0
|
0.54
|
CaEDTA,
1,9g +500mg DMSA
|
95
|
46
|
200
|
0
|
0.64
|
DMSA: Mean values are
slightly higher in the provoked urines, but the aluminum binding of
DMSA and the induced renal excretion seems insignificant.
DMPS i.v.:
Mean values are slightly higher for the provoked urine and about equal
to DMSA values. The aluminum binding and/or renal excretion following
DMPS i.v. seems insignificant.
DMPS i.v. +
ZnDTPA i.v. combination therapy
Mean values for the provoked urines are
slightly higher than those of the DMSA+DMPS urines. The aluminum
binding of the combination treatment, including the renal excretion
seem insignificant.
CaEDTA, 1,9g
i.v. plus 500mg DMSA oral, and/or NaMgEDTA, 2,5g i.v. plus DMSA oral
The mean concentration of 57µg/g crea for
the urines provoked with NaMgEDTA+DMSA and the CaEDTA+DMSA provoked
urines (46µg/g crea) are considerably higher than the mean values for
DMSA, DMPS and the DMPS/ZnDTPA combination treatment.
The mean
concentration for the CaEDTA+DMSA and the NaMgEDTA+DMSA provoked
urines are above our reference range of 40µg/g crea.
Assessment:
By comparing mean concentrations of DMSA,
DMPS and the combination DMPS+ZnDTPA urines, we could not determine an
efficient aluminum binding and renal excretion for any of these
chelating agents. These chelating agents may not be the agents of
choice in the treatment of aluminum overexposure.
The mean
concentration of the urines provoked with CaEDTA+DMSA i.e. MgEDTA+DMSA
show an increase in Al-binding and excretion, with 57µg/g crea for
MgEDTA/DMSA and 46µg/g crea for CaEDTA/DMSA. The difference may be
explained by the application route. CaEDTA is often (wrongly)
injected, whereas NaMgEDTA is applied as an infusion. The fluid volume
may be responsible for the lower creatinine value of the urines
provoked with MgEDTA +DMSA (0.54µg/g crea).
From this data, we cannot safely state that
the EDTAs bind aluminum more effectively, especially in lieu of the
extreme values detected in baseline urines.
Of 2485 tests, we
found 10 exceeding the MCL with a mean concentration of 526µg/g crea!
The maximum level was 1256µg/g crea.
We found maximum
concentrations exceeding the MCL in all provocation urines,
except for the MgEDTA+DMSA urines.
See Table 1.
Important information:
Aluminum is widespread in our environment.
This indicates that great caution has to be taken during sampling. Our
urine containers are metal-free. Make sure you are not re-using sample
containers.
Protocol reminders:
|
|
Patients must empty bladder before
chelation (oral or i.v.) is started. |
|
|
To avoid contamination, we prefer that
patients collect all urine in the bladder for the duration of
the appropriate collection period. |
Urine collection
times:
|
|
DMSA oral: 4h |
|
|
DMPS oral: 3-4h |
|
|
DMPS i.v.: 1-2h |
|
|
EDTA: Infusion time plus 45min.
|
|
|
EDTA+DMSA example: If oral DMSA is provided
1h prior to the start of a 2g EDTA infusion, the collection
time is 1h + infusion time + 45min = 3h45min |
|
|
ZnDTPA+DMPS: 2h |
More information
under
http://www.microtraceminerals.com/en/chelation-newsarticles
Additional
information for chronic or subacute aluminum intoxication/exposure:
Aluminum is,
compared with lead or mercury, relatively nontoxic. No known
physiologic need exists for aluminum.
Approximately 95% of
an aluminum load becomes bound to transferrin and albumin
intravascularly and is then eliminated renally. In healthy subjects,
only 0.3% of orally administered aluminum is absorbed via a healthy
GI. When the GI barrier is bypassed, such as with intravenous infusion
or in the presence of advanced renal dysfunction aluminum has the
potential to accumulate. As an example, with intravenously infused
aluminum, 40% is retained in adults and up to 75% is retained in
neonates. Mayor et al suggested that parathyroid hormone may increase
intestinal absorption of aluminum.
Up to this time, no
biological function has been attributed to this metal, and, more
importantly, aluminum accumulation in tissues and organs results in
their dysfunction and toxicity. Aluminum is absorbed from the GI tract
in the form of oral phosphate-binding agents (aluminum hydroxide),
parenterally via immunizations, via dialysate on patients on dialysis
or total parenteral nutrition (TPN) contamination, via the urinary
mucosa through bladder irrigation, and transdermally in
antiperspirants. Lactate, citrate, and ascorbates facilitate GI
absorption. If a significant load exceeds the body's excretory
capacity, the excess is deposited in various tissues, including bone,
brain, liver, heart, spleen, and muscle.
Aluminum can interfere with chromium, iron,
magnesium, zinc, calcium and copper. An inadequate supply of essential
elements facilitates aluminum uptake. Aluminum absorption in bone is a
risk in children with an inadequate intake of dietary calcium or
vitamin D. Highly stressed patients with an inadequate magnesium
supply are at risk. Leaky gut syndrome or kidney problems support the
aluminum uptake.
Aluminum disrupts
the Vitamin B6 and Vitamin D Metabolism.
Infants should be protected from Aluminum in
nanoparticle form. Vaccines are containing either the
mercury-containing thiomersal or aluminum-compounds.
While aluminum
cannot be avoided, we can reduce Al-uptake by optimizing the body’s
nutritional balance. Providing digestive support in the form of
probiotics helps.
We wish you all the
best. If you find this newsletter informative, let us know.
E.Blaurock-Busch and team
References:
|
|
Bundesgesundhbl., Bd. 41 (6), (1998), 271
|
|
|
http://emedicine.medscape.com/article/165315-overview#a0104
|
|
|
Liu TK, Liu SH,
Chang CH, Yang RS: Concentration of metal elements in the blood and
urine in the patients with cementless total knee arthroplasty. Tohoku
J Exp Med 1998; 185: 253-262
|
|
|
O'Shea S, Johnson DW: Review article:
Addressing risk factors in chronic kidney disease mineral and bone
disorder: Can we influence patient-level outcomes? Nephrology
2009; 14: 416-427
|
|
|
Meyer-Baron M, Schuper M, Knapp G, van
Thriel C: Occupational aluminum exposure: Evidence in support of its
neurobehavioral impact. NeuroToxicology 2007; 28: 1068-1078 |
|