How does aluminum get into our bodies and brains?
Aluminum salts began to be
used as a food preservative in the mid-1880’s and that may be a reason why the
first case of AD was discovered approximately 20 years later in 1907 by Doctor Alzheimer.
The commercialization of aluminum salts, and
products containing aluminum, has resulted in more aluminum being refined and
made available every year. Currently we use aluminum in reduced metal, oxidized
metal, and ionic chemical forms, such as salts. The ionic chemical forms of
aluminum are neurotoxic. The reduced metal form of aluminum must be converted first
by corrosion to the oxidized metal form and then by acidic conditions to the
ionic form in order to become neurotoxic. The oxidized metal and ionic chemical
forms of aluminum are found in a variety of pharmaceuticals, such as antacids, vaccines,
food products, baking powder, drinking water, sunscreens, cosmetics,
antiperspirants, astringents, and fertilizers.
Because of the amount of
drinking water we consume daily, any aluminum in drinking water presents an
opportunity for its absorption and accumulation in the body. The ionic form of aluminum is in drinking
water due to acid-rain freeing bound aluminum from minerals in the ground, city
water departments using alum to clarify drinking water, and mortar lined city
water pipes leaching aluminum into drinking water.
There appeared to be no
connection between aluminum in drinking water and AD until the data were
reevaluated in 1996. This analysis
revealed a correlation between aluminum in drinking water and AD when taking
into consideration the concentration of fluoride and silicic acid as well as
aluminum in the drinking water34.
Fluoride ions facilitate the transfer of aluminum across the blood-brain
barrier increasing aluminum absorption in the brain35, while silicic
acid facilitates aluminum removal from the blood by the kidneys decreasing
aluminum absorption by the brain36-38. Therefore, Watson, drinking water is a common
way that aluminum is ingested, absorbed
by our bodies, and accumulated in our brains and silicic acid slows this
accumulation.
The three points of entry for
aluminum into the body are oral ingestion, inhalation, and absorption through
the skin. We do not know which pathway was
the major source of aluminum in the case of strange death. Due to the lack of proper respiratory
protection, we might assume that inhalation was the point of entry. Inhaled aluminum can take a shortcut to the
brain across the olfactory epithelium cells lining the nasal cavities and then diffusing
through olfactory receptor neurons to enter the brain via both olfactory bulbs39-41. Organic complexes of aluminum have been found
to readily enter the brain via this pathway42. The other two
pathways require that aluminum crosses the blood-brain barrier in order to
enter the brain. Once in the brain, some of the aluminum stays there throughout
life43 inhibiting numerous key enzymes and killing neurons44.
Aluminum in the ionic
form can form complexes with a wide variety of organic and inorganic ligands.
Some of these complexes are optimal for absorption from the gastrointestinal
track into the blood and others are optimal for crossing the blood brain
barrier. Ionic aluminum is like a cloaked assassin using these ligands as disguises
to cross two barriers: between the gut and blood and the blood and brain. The
following organic ligands have an affinity for ionic aluminum and have been
found to be present in the blood at the approximate concentrations indicated:
citrate (ca. 250mM), pyroglutamate (ca.
180mM), glutamate (ca. 10mM), nucleotides ATP, ADP, and AMP (ca. 5mM), and transferrin (ca. 1mM)45.
In addition to these organic ligands there are inorganic ligands that also
have an affinity for ionic aluminum including: fluoride, silicic acid,
hydroxide, and phosphate.
Transferrin receptors are
more numerous in those areas of the brain that have the highest levels of
aluminum accumulation46. For
this reason transferrin has been theorized to be the primary (i.e. 90%)
transporter of aluminum to the brain43,47,48. The problem with this theory is the molecular
weight of the transferrin aluminum complex is four-fold higher than can be
handled by the kidney’s glomerulus45. This means that the rapid changes in urinary
excretion of aluminum seen following exposure to aluminum can’t be accounted
for with such a large transporter. The rest of the previously mentioned ligands
result in aluminum complexes that are small enough to be handled by the
glomerulus of the kidney and are therefore more likely to comprise aluminum’s
cloak. But aluminum can change its disguise when reaching the blood-brain
barrier and possibly transferrin is the best disguise for successfully crossing
this barrier.
Watson had become agitated
with worry. He asked Holmes: “So how
long will it take to get the aluminum I consumed at breakfast out of my body?
“ Holmes’ answer was discouraging: “Once
aluminum is ingested and absorbed 64% will be excreted during the first day but
the rest will be slowly excreted and even after 50 years 4% of what you
ingested with breakfast this morning will remain in some parts of your body43.”
As you can see Watson,
aluminum has the means to get into the brain. But is aluminum normally found in
the brain and is a higher level of aluminum in the brain associated with AD?
How much aluminum is in a
normal brain?
It is calculated that the human brain accumulates aluminum at a rate of
10-70 billionths of a gram of aluminum per gram dry weight of brain per year
during a lifetime. This amount is
consistent with the 0.4 to 5.6mcg aluminum per gram dry weight of brain as
observed by autopsy of different regions of human brains after a normal
lifetime of exposure to aluminum3,49. It now appears likely that this slow aluminum
accumulation may facilitate an increased incidence of a wide range of
neurological diseases including AD50.
Is there more aluminum in
brains of those with AD?
Some people absorb and
accumulate aluminum at higher rates than others and this may account for why
some get AD earlier than others3,51. AD patients younger than 77
years old have a 64% greater gastrointestinal aluminum absorption rate than
age-matched non-AD controls52.
However both AD and non-AD people over 77 have similar high rates of gastrointestinal
aluminum absorption53. These high
rates of gastrointestinal absorption result in faster aluminum accumulation in
elderly brains as compared with middle-age brains28,29. Also aluminum
in the brain is not uniformly distributed.
In the elderly, aluminum is highest in the hippocampus (5.6mcg per gram
dry wt. of brain) and lowest in the corpus callosum (1.5mcg per gram dry wt. of
brain)49.
A meta-analysis of published studies involving 1,208 participants,
including 613 AD patients, revealed that aluminum is significantly higher in
brains, serum, and cerebrospinal fluid of AD patients compared with non-AD participants54.
Therefore Watson, aluminum as the “cloaked assassin” has the means to
get into the brain. But does it have the motive or biochemical motivation to cause
mitochondrial disease, a clinical symptom of AD?
How does aluminum cause
mitochondrial disease?
Mitochondrial disease occurs when the mitochondria of the cell fail to
produce enough energy for cell or organ function. This neuro-metabolic dysfunction
has been theorized to be a factor in the causation of AD55. But it
is hard to tell the difference between a cause and a symptom of a disease. Watson, here is why aluminum is the cause of
mitochondrial disease and mitochondrial disease is not a cause but a symptom of
AD.
Mitochondria are membrane bound organelles inside brain and muscle cells
that produce stored energy in the form of ATP generated by combining oxygen
with nutrients in food. The brain normally consumes 30% of the total energy
produced from these nutrients by the body. This process is called bioenergetics
and it requires using nutrients, such as sugar, to make ATP in a series of
steps called the Krebs cycle (a.k.a. TCA cycle). Aluminum lowers the amount and activity of several
Krebs cycle enzymes involved in ATP production56,57. So aluminum
lowers the efficiency of ATP production in brain. This lowers the amount of energy available to
the brain resulting in mitochondrial disease.
Aluminum facilitates the formation of reactive oxygen species (ROS) by
glial cells in the brain that are toxic to mitochondria and neurons58.
Aluminum also inhibits two enzymes in the Krebs
cycle that are involved in NADH production56,57. NADH is used in the body
for making reduced-glutathione59. Reduced-glutathione reduces
cofactors in the body, such as pyrroloquinoline quinone (PQQ), that in turn
reduce the reactive oxygen species (ROS) that are harmful to mitochondria and
neurons. The inhibition of NADH production
by aluminum decreases reduced-glutathione levels allowing ROS to harm mitochondria and
neurons resulting in mitochondrial disease60.
Therefore Watson, aluminum can cause mitochondrial disease by decreasing
ATP production, increasing ROS production, and preventing cofactors, such as PQQ,
from protecting the mitochondria from oxidative harm by ROS.
How does aluminum impair memory?
Some parts of the brain are more prone to absorb aluminum than others,
possibly due to some cells having more transferrin receptors46. The main aluminum-affected brain regions in
humans, rats, and rabbits exposed to aluminum in their diet include the
entorhinal cortex (EC), hippocampus, and locus coeruleus (LC). The EC and the hippocampal regions (e.g. CA1
pyramidal cell layer) are the regions with most absorbed aluminum in rats
chronically exposed to aluminum in their diet44. These are also
regions of the brain most vulnerable to NFT formation and neuronal death in AD61. In fact the EC is the first area of the brain
to be affected by AD62.
The entorhinal cortex (EC) is a neuronal hub linking the hippocampus
with the neocortex. The hippocampus
plays a key role in declarative memories such as autobiographical, episodic,
and semantic memory and spatial memories including memory formation and
consolidation and memory evolution during sleep. The neocortex is involved with sensory
stimuli, generation of motor commands, spatial reasoning, conscious thought,
and language. A region of the EC (e.g.
layer III) is connected to all regions of the hippocampal formation including
the dentate gyrus, all CA regions, including the CA1 pyramidal cell layer, and
subiculum. These connections are called the perforant pathway. Surgical destruction of the perforant pathway
in rats results in memory impairment44 and surgical destruction of
the perforant pathway in humans results in impairment of short term memory63. Aluminum in the diets of rats results in both
lesions in the perforant pathway and in memory impairment44. Therefore Watson, aluminum, like a surgeon’s
knife, can cause short term memory loss.
