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Vaccines and
Childhood Illnesses:
Beyond Thimerosal
disclosure: no financial conflicts
David Ayoub, MD
Springfield, Illinois
August 5th, 2009
raypoke@mac.com
Aluminum MSDS
Ingestion: Chronic ingestion of aluminum may cause Aluminum Related
Bone Disease or aluminum-induced Osteomalacia with fracturing
Osteodystrophy, microcytic anemia, weakness, fatigue, visual and
auditory hallucinations, memory loss, speech and language impairment
(dysarthria, stuttering, stammering, anomia, hypofluency, aphasia
and eventually, mutism), epileptic seizures (focal or grand mal), motor
disturbance (tremors, myoclonic jerks, ataxia, convulsions, asterixis,
motor apraxia, muscle fatigue), and dementia (personality changes,
altered mood, depression, diminished alertness, lethargy, 'clouding of
the sensorium', intellectual deterioration, obtundation, coma), and
altered EEG.
http://www.sciencelab.com/xMSDS-Aluminum-9922844
“Now the presentations we heard
yesterday clearly demonstrate that
there are huge gaps in our
information about what we know
about the toxicology of aluminum. I
would like to just reiterate what
Neal Halsey said, the differences
between adults and infants, there
appears to be practically no[t] even
animal data never mind human
data.”
May 11th - 12th, 2000
What is aluminum?
•
•
•
•
•
3rd most abundant element
food, water, air, soil, medicine
~8% of earth’s crust
no biological role
a poison
published
1928
Dr Charles T Betts
“All salts of aluminum are poisonous when injected
subcutaneously or intravenously”
Dr. Victor Vaughn, Toxicologist, University of Michigan before US Federal Trade
Commission Hearings on aluminum, 1927
Adjuvant
“agents that act nonspecifically to increase
the specific immune response to an
antigen”
Dictionary of Immunology
(How) do aluminium adjuvants work?
Brewer JM. Immunol Lett. 2006 15;102(1):10-5.
The aluminium compounds, originally identified as adjuvants
over 70 years ago, remain unique in their widespread
application to human vaccines. Given this history, it is
surprising that the physicochemical interactions between
aluminium compounds and antigens are relatively poorly
understood. This has clearly been a contributing factor to
vaccine failures, for example, through inappropriate selection
of aluminium species or buffers. Similarly, the mechanism(s) of
action of aluminium adjuvants are relatively unstudied,
although it appears that these agents fail to fit within the
current principles underlying activation of the immune
response. This review aims to examine recent developments in
our understanding of the physicochemical and biological
aspects of research into aluminium adjuvants
Aluminum Salts Adjuvants
aluminum hydroxide
aluminum phosphate
aluminum sulfate
aluminum hydroxyphosphate sulfate
Number of administered vaccines containing
aluminum increased after Thimerosal reduced
(by 18 months age)
aluminum-containing shots
mercury-containing shots
source: David Ayoub, MD, Prairie Collaborative, Inc
Aluminum content of some vaccines
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•
•
•
•
•
DTaP Infanrix 625 micrograms
Hep B Engerix 250 micrograms
HiB PedVax 225 micrograms
Pediarix 850 micrograms
Prevnar 125 micrograms
DTaP Daptacel 330 micrograms
DTaP Tripedia 170 micrograms
HepB HiB Comvax 225 micrograms
HepB Recombivax 500 micrograms
Hep A Havrix 250 micrograms
HepA-B Twinrix 450 micrograms
Aluminum Exposure Safety Limits
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER F--BIOLOGICS
PART 610 -- GENERAL BIOLOGICAL PRODUCTS STANDARDS
Sec. 610.15 Constituent materials.
(a) Ingredients, preservatives, diluents, adjuvants. An adjuvant shall not be introduced into a
product unless there is satisfactory evidence that it does not affect adversely the safety or potency
of the product. The amount of aluminum in the recommended individual dose of a biological
product shall not exceed:
(1) 0.85 milligrams if determined by assay;
(2) 1.14 milligrams if determined by calculation on the basis of the amount of aluminum compound
added; or
(3) 1.25 milligrams determined by assay provided that data demonstrating that the amount of
aluminum used is safe and necessary to produce the intended effect are submitted to and
approved by the Director, Center for Biologics Evaluation and Research or the Director, Center for
Drug Evaluation and Research (see mailing addresses in 600.2 of this chapter).
"The amount of 15 mg of alum or 0.85 mg aluminum per dose
was selected empirically from data that demonstrated that this
amount of aluminum enhanced the antigenicity and
effectiveness of the vaccine (Joan May, FDA/CBER, personal
communication)."
from NW Baylor, W Egan and Paul Richman,
FDA, CBER; VACCINE; 20 (2002), S18-23
FDA limits NOT based upon safety data!
Aluminum Exposure Defined
2 methods:
acute toxicity:
1) maximum blood levels
chronic toxicity:
2) weight adjusted total
exposures
250 -1225 µg
aluminum in shot
blood volume
50 - 250
µg/kg
Aluminum blood levels
K/DOQI Clinical Practice Guidelines for Bone
Metabolism and Disease in Children With
Chronic Kidney Disease
12.2.b Baseline levels of serum aluminum should be <20 µg/L. (OPINION)
12.2.c If levels of serum aluminum are between 20-60 µg/L, a search for and
elimination of all sources of aluminum should be performed. (OPINION)
12.3 A deferoxamine (DFO) test should be performed if there are elevated serum
aluminum levels (60-200 µg/L) or clinical signs and symptoms of aluminum toxicity
potential aluminum blood levels post
vaccine
newborn: 250 μg/ 250ml blood = 1,000 μg/L
2 month infant*:1225 μg/ 340ml blood = 3,603
μg/L
adult:1225 μg/ 5L blood = 245 μg/L
*70cc/kg blood volume
weight adjusted exposure
“Research indicates that patients with impaired kidney
function, including premature neonates, who receive
parenteral levels of aluminum at greater than 4 to 5
mcg/kg/day accumulate aluminum at levels associated with
central nervous system and bone toxicity. Tissue loading
may occur at even lower rates of administration.”
from: http://www.fda.gov/cder/foi/appletter/2004/19626scs019ltr.pdf
“....I5 and 30 mcg/kg/day of aluminum from TPN solutions. This amount resulted
in tissue loading with aluminum but not in clearly associated disease. Thus, this
rate of aluminum administration could be defined as unsafe. Finally,.....60
mcg/kg/d of aluminum (32). This rate could be considered toxic.”
Gordon Klein, et al 1991
Finally,.....60 mcg/kg/d of aluminum (32). This rate could be
considered toxic.”
Gordon Klein, et al 1991
Al-containing
vaccine
HepB
Energix
DTaP
Infanrix
HiB
Pedvax
PCV
Prevnar
HepA
Havrix
Max dose
(μg)
Max weight
adjusted dose
μg/kg/day
0
3.30 kg
2mo
4.86 kg
4mo
6.54 kg
6mo
7.80 kg
12 mo
10.1 kg
15 mo
10.9 kg
250
250
-
250
250
-
-
625
625
625
-
225
225
225
225
225
-
125
125
125
125
125
-
-
-
-
250
250
1225
975
1225
850
975
875
75.8
252
149
157
84.1
89.4
76.1
625
18 mo
11.5 kg
625
250
Calculating the dose of aluminum exposure
9-11 y/o: 23-55 kg (50-120 lbs)
225 µg/shot x 3 shots= 675 µg total
4-10 µg/kg per shot (12-30 µg/kg total)
Calculating the potential peak blood level
9-11 y/o: 1.6-3.9 L blood volume*
58-140 µg/L potential blood aluminum
*blood volume (70 cc/kg)
Al-containing
content
vaccine
(micrograms)
HepB
Energix
DTaP
Infanrix
HepA
Havrix
PCV
250
625
250
Prevnar
125
HPV
225
total
1475
27-64 µg/kg on day of vaccines
> 800 µg/L blood level
note: This is a smaller dose than
children now receive
MRL violation with just 2 vaccines!
syringe
dissolved by alphahydroxycarboxylic acids
citrate
malate
lactate
interstitial
fluid
blood/lymph
retention
tissue
brain
bone
spleen/liver
myocardium
endocrine
transferrin
ferritin
excretion
urine
Gardasil’s aluminum adjuvant may be solubilized
faster and thus peak serum aluminum levels may
appear higher and sooner than with other
adjuvants
Solubilization of aluminum-containing adjuvants by constituents of
interstitial fluid.
Seeber SJ, White JL, Hem SL. J Parenter Sci Technol. 1991 May-Jun;45(3):156-9.
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiania.
The solubilization of three commercially available aluminum-containing adjuvants by
citrate anion was studied. Amorphous aluminum hydroxyphosphate and boehmite
were both solubilized, however, amorphous aluminum hydroxyphosphate dissolved
significantly faster than boehmite. The results suggest that citrate and other alphahydroxy carboxylate anions in the interstitial fluid are able to solubilize and thereby
facilitate the excretion of aluminum from aluminum-containing adjuvants which are
administered by intramuscular injection. The results also suggest that the release of
antigen following administration may be significantly more rapid from an amorphous
aluminum hydroxyphosphate-adjuvanted vaccine in comparison to a boehmiteadjuvanted vaccine.
blood levels of aluminum after Hep B
vaccine in adults on dialysis: significant
blood levels achieved with inter-individual
variability
toxic
n=17
baseline
In viva absorption of aluminium-containing vaccine
adjuvants using 26Al
RE Flarend SL Hem, JL White. et al. Vaccine 1997:15(12-13);1314-18.
so where is the rest of the aluminum?
78-95% retained in 1 month!
Evidence of aluminum loading in infants receiving intravenous therapy.
Sedman AB, Klein GL, Merritt RJ, Miller NL, Weber KO, Gill WL, Anand H, Alfrey
AC.N Engl J Med. 1985 May 23;312(21):1337-43.
Premies
less than vaccine exposure
average 78% of aluminum still retained in 5 infants exposed for at least
2 weeks (range 60-95%)
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aluminum hydroxide in young adult mice
50 μg/kg per dose x 2 shots
100 μg/kg fully vaccinated
infants: 50-250 μg/kg
Gardasil: 27-64μg/kg
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Behavioral effects of aluminum
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50% reduction in strength/endurance (wire-mesh
hanging)
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138% increase in anxiety(open-field testing)
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increase memory errors (water maze; ns)
20% hair loss at injection site
histopathology
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spinal cord:
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255% increase in apoptosis in spinal cord neurons
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35% reduction in motor neurons in cord
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350% increase astrocytes
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motor cortex neurons
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192% increase in apoptosis
Morin stain for aluminum
myelin
mitochondria
synapses
Are their similarities between aluminum
toxicity and neurodevelopmental disorders?
..............................................47 cases
renal insufficiency
•oral phosphate binders
•contaminated dialysate
•oral antacids
•TPN
•infant formula
normal renal function
•aluminum containing vaccines and MMF .............34 cases
•antacids/TPN/formula ................................................4 cases
85 cases
Progressive encephalopathy in children with chronic renal insufficiency in
infancy. Rotundo A, Nevins TE, Lipton M, Lockman LA, Mauer SM, Michael AF. Kidney Int. 1982
Mar;21(3):486-91.
interval to presentation
n=20
0-156 mo
developmental delay
95%
small head (<-2 sd)
75%
EEG abnormal
94%
seizures
65%
hypotonia
65%
dyskinesia
55%
corticol atrophy/ventriculomegaly
47%
chorea
20%
gait/ataxia
20%
myoclonus
15%
lethargy/dec LOC
15%
weakness
10%
ASD and Aluminum Toxicity
•seizures
•myoclonus
•hypotonia
•motor development
•autonomic/cholinergic dysfunction
•mitochondrial dysfunction
•oxidative stress
•ADD/ADHD
•iron deficiency and anemia
•calcium homeostasis
•bone metabolism/microcephaly
•melatonin, seratonin and sleep disorders
•neuropathology
•immune dysfunction
•systemic infections/ bacterial binding/immunity
Aluminum in Autism Spectrum Disorders
A Random Case Survey
David Ayoub, MD
Anju Usman, MD
October 10, 2007
Fall DAN! Think Tank
Aluminum in Hair
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mean 12.9 µg/g
76.3%
upper limits normal
n-38
Iron: 10.5% above uppe
limits
Manganese: 13.2%
above upper limits
Urinary Provocative Challenge
IV Ca-EDTA
•
n-34, profile with the highest
metals recorded if multiple done
post IV
Ca EDTA
challenge
measuring
urinary metals
Aluminum in Urine
random vs EDTA vs other agents*
mean
410
mean 177.0
97%
0-31
13.9
n-4
n-4
0-21
10.0
18
n-10
n-10
n-34
* DMSA, DMPS, glutathione
Urinary Porphyrins
•First 2 intermediates analyzed
-Uroporphyrin III (UP)-66% elevated
-Hepatocarboxy porphyrin (7cxP)-50% elevated
•Levels expressed as ratio with “upper limits” value
Aluminum
Aluminum
Toxic Metals in Red Cells of Children (ng/ml)
unpublished data from Dr T. Audhya:
n-46
modified from Adams, 2006
n-21
Numerous studies show glutathione
depletion in autistics
Metabolic biomarkers of increased oxidative stress and impaired methylation capacity
in children with autism. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander
JA. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
High cell death
low glutathione
Al(maltol)3
Maltate control
High cell death
Maltate control
Al(maltol)3
B
r
a
i
n
w
e
i
g
Ca
ol
n(
t C
r l
o)
l 3
- 17.4%
p <0.001
oral Al chloride (100mg/kg)
8 weeks
Number of administered vaccines containing
aluminum increased after Thimerosal reduced
(by 18 months age)
aluminum-containing shots
mercury-containing shots
source: David Ayoub, MD, Prairie Collaborative, Inc
Treatment