Food Additive Excitotoxins and Degenerative Brain Disorders
In Harmony Holistic Stress Relief
by Russell L.
Blaylock, MD
How Excitotoxins Were Discovered
The FDA's
Response
The
Corporate Response
Conclusion
References
There are a growing number of clinicians and basic scientists who are
convinced that a group of compounds called excitotoxins play a critical role in
the development of several neurological disorders including migraines,
seizures, infections, abnormal neural development, certain endocrine disorders,
neuropsychiatric disorders, learning disorders in children, AIDS dementia,
episodic violence, lyme borreliosis, hepatic encephalopathy, specific types of
obesity, and especially the neurodegenerative diseases, such as ALS,
Parkinson's disease, Alzheimer's disease, Huntington's disease, and
olivopontocerebellar degeneration.(
1)
An enormous amount of both clinical and experimental evidence has
accumulated over the past decade supporting this basic premise.(
2) Yet, the FDA still refuses
to recognize the immediate and long term danger to the public caused by the
practice of allowing various excitotoxins to be added to the food supply, such
as monosodium glutamate (MSG), hydrolyzed vegetable protein, and aspartame.*
The amount of these neurotoxins added to our food has increased enormously
since their first introduction. For example, since 1948 the amount of MSG added
to foods has doubled every decade. By 1972, 262,000 metric tons were being
added to foods. Over 800 million pounds of aspartame have been consumed in
various products since it was first approved. Ironically, these food additives
have nothing to do with preserving food or protecting its integrity. They are
all used to alter the taste of food. MSG, hydrolyzed vegetable protein, and
natural flavoring are used to enhance the taste of food so as to mask
disagreeable taste and magnify desired taste. Aspartame is an artificial
sweetener that goes by various brand names such as NutraSweet and Equal.
These toxins (excitotoxins) are not present in just a few foods, but rather
in almost all processed foods. In many cases they are being added in disguised
forms, such as natural flavoring, spices, yeast extract, textured protein, soy
protein extract, etc. Experimentally, we know that when subtoxic levels of
excitotoxins are given to animals in divided doses, they experience full
toxicity, i.e., they are synergistic. Also, liquid forms of excitotoxins, as
occurs in soups, gravies and diet soft drinks are more toxic than that added to
solid foods. This is because they are more rapidly absorbed and reach higher
blood levels.
So, what is an excitotoxin? These are substances, usually acidic amino
acids, that react with specialized receptors in the brain in such a way as to
lead to destruction of certain types of neurons. Glutamate is one of the more
commonly known excitotoxins, but over seventy have thus far been identified.
MSG is the sodium salt of glutamate. Glutamate is a normal neurotransmitter in
the brain. In fact, it is the most commonly used neurotransmitter by the brain.
Defenders of MSG and aspartame use, usually say: How could a substance that is
used normally by the brain cause harm? This is because, glutamate, as a
neurotransmitter, exists in the extracellular fluid only in very, very small
concentrations --- no more than 8 to 12uM. When the concentration of this
transmitter rises above this level, the neurons begin to fire abnormally. At
higher concentrations, the cells undergo this specialized process of delayed
cell death, excitotoxicity. That is, they are excited to death.
It should also be appreciated that the effects of excitotoxin food additives
generally are not dramatic. Some individuals may be especially sensitive and
develop severe symptoms and even sudden death from cardiac irritability; but,
in most instances, the effects are subtle and develop over a long period of
time. While the food additives, MSG and aspartame, are probably not direct
causes of the neurodegenerative diseases, such as Alzheimer's dementia, Parkinson's
disease, or amyotrophic lateral sclerosis (ALS), they may well precipitate
these disorders and certainly worsen their pathology as we shall see. It may be
that many people with a propensity for developing one of these diseases would
never develop a full blown disorder had it not been for their exposure to high
levels of food borne excitotoxin additives. Some may have had a very mild form
of the disease had it not been for the exposure. Likewise, food borne
excitotoxins may be harmful to those suffering from strokes, head injury and
HIV infection, and certainly should not be used in a hospital setting.
How
Excitotoxins Were Discovered
In 1957, two ophthalmology residents, Lucas and Newhouse, were conducting an
experiment on mice to study a particular eye disorder.(
3) During the course of this
experiment, they fed newborn mice MSG and discovered that all demonstrated
widespread destruction of the inner nerve layer of the retina. Similar
destruction was also seen in adult mice but not as severe as the newborns. The
results of their experiment was published in the
Archives of Ophthalmology
and soon forgotten.
For ten years prior to this report, large amounts of MSG were being added
not only to adult foods but also to baby foods in doses equal to those of the
experimental animals.
Then in 1969, Dr. John Olney, a neuroscientist and neuropathologist working
out of the Department of Psychiatry at Washington University in St. Louis,
repeated Lucas and Newhouse's experiment.(
4) His lab assistant noticed
that the newborn of MSG exposed mice were grossly obese and short in stature.
Further examination also demonstrated hypoplastic organs, including pituitary,
thyroid, adrenal as well as reproductive dysfunction. Physiologically, they
demonstrated multiple endocrine deficiencies, including TSH, growth hormone,
LH, FSH, and ACTH. When Dr. Olney examined the animal's brain, he discovered
discrete lesions of the arcuate nucleus as well as less severe destruction of
other hypothalamic nuclei.
Recent studies have shown that glutamate is the most important
neurotransmitter in the hypothalamus.(
5) Since this early
observation, monosodium glutamate and other excitatory substances have become
the standard tool in studying the function of the hypothalamus. Later studies
indicated that the damage by monosodium glutamate was much more widespread and
included such areas as the hippocampus, circumventricular organs, locus
ceruleus, amygdala-limbic system, subthalamus, and striatum.(
6)
More recent molecular studies have disclosed the mechanism of this destruction
in some detail.(
7) Early
on, it was observed that when neurons
in vitro were exposed to glutamate
and then washed clean, the cells appeared perfectly normal for approximately an
hour, at which time they rapidly underwent cell death. It was discovered that
when calcium was removed from the medium, the cells continued to survive.
Subsequent studies have shown that glutamate, and other excitatory amino acids,
attach to a specialized family of receptors (NMDA, kainate, AMPA and
metabotrophic) which in turn, either directly or indirectly, opens the calcium
channel on the neuron cell membrane, allowing calcium to flood into the cell.
If unchecked, this calcium will trigger a cascade of reactions, including free
radical generation, eicosanoid production, and lipid peroxidation, which will
destroy the cell.
With this calcium triggered stimulation, the neuron
becomes very excited, firing its impulses repetitively until the point of cell
death, hence the name excitotoxin. The activation of the calcium channel
via the NMDA type receptors also involves other membrane receptors such as the
zinc, magnesium, phencyclidine, and glycine receptors.
In many disorders connected to excitotoxicity, the source of the glutamate
and aspartate is endogenous. We know that when brain cells are injured they
release large amounts of glutamate from surrounding astrocytes, and this
glutamate can further damage surrounding normal neuronal cells. This appears to
be the case in strokes, seizures and brain trauma. But, food borne excitotoxins
can add significantly to this accumulation of toxins.
The FDA's
Response
In July 1995, the Federation of American Societies for Experimental Biology
(FASEB) conducted a definitive study for the FDA on the question of safety of
MSG.(
8) The FDA wrote a
very deceptive summary of the report in which they implied that, except
possibly for asthma patients, MSG was found to be safe by the FASEB reviewers.
But, in fact, that is not what the report said at all. I summarized, in detail,
my criticism of this widely reported FDA deception in the revised paperback
edition of my book,
Excitotoxins: The Taste That Kills, by analyzing
exactly what the report said, and failed to say.(
9) For example, it never
said that MSG did not aggravate neurodegenerative diseases. What they said was,
there were no studies indicating such a link. Specifically, that no one has
conducted any studies, positive or negative, to see if there is a link. A vital
difference.
What we find is that there are many gaps in our knowledge concerning the toxicity
of food additive excitotoxins. For example, virtually no long term studies have
been done on the neuroendocrine effects of chronic excitotoxin additive feeding
in humans. Likewise, there are no studies of regionally distributed brain
levels of glutamate, aspartate and cysteine following chronic excitotoxin
feeding. Most important, there are no studies of the effect of these
excitotoxins on the physiology of the nervous system under conditions of low
brain energy supply. In examining the research literature, virtually all
studies of this problem, other than behavioral effects, are centered on
microscopic pathologic changes and not functional alterations of either the
neurons themselves or of the entire brain itself. This is of vital importance,
since we know that neurons can have severely altered function without
pathological change as seen on either light or electron microscopy. Several
studies have been done that demonstrate significant alteration in brain
neurochemistry with acute MSG exposure.(
10,11)
The
Corporate Response
Unfortunately, for the consumer, the corporate food processors not only
continued to add MSG to our foods, but they have gone to great links to
disguise these harmful additives. For example, they use such names as
hydrolyzed vegetable protein, vegetable protein, textured protein, hydrolyzed
plant protein, soy protein extract, caseinate, yeast extract, and natural
flavoring. We know experimentally that when these excitotoxin taste enhancers
are added together they become much more toxic than is seen individually.(
12) In fact, excitotoxins in
subtoxic concentrations can be fully toxic to specialized brain cells when used
in combination. Frequently, I see processed foods on supermarket shelves,
especially frozen or diet foods, that contain two, three or even four types of
excitotoxins. We also know, as stated, that excitotoxins in liquid forms are
much more toxic than solid forms because they are rapidly absorbed and attain
high concentration in the blood. This means that many of the commercial soups,
sauces, and gravies containing MSG are very dangerous to nervous system health,
and should especially be avoided by those either having one of the above
mentioned disorders, or who are at a high risk of developing one of them. They
should also be avoided by cancer patients and those at high risk for cancer,
because of the associated generation of free radicals and lipid peroxidation.(
13)
In the case of ALS, we know that consumption of red meats and especially MSG
itself, can significantly elevate blood glutamate, much higher than is seen in
the normal population.(
14)
Similar studies, as far as I am aware, have not been conducted in patients with
Alzheimer's disease or Parkinson's disease. But, as a general rule, I would
certainly suggest that person's with either of these diseases avoid MSG
containing foods as well as red meats, cheeses, and pureed tomatoes, all of
which are known to have higher levels of glutamate.
It must be remembered that it is the glutamate molecule that is toxic in
MSG. Glutamate is a naturally occurring amino acid found in varying
concentrations in many foods. Defenders of MSG safety allude to this fact in
their defense. But, it is free glutamate that is the culprit. Bound glutamate,
found naturally in foods, is less dangerous because it is slowly broken down
and absorbed by the gut, so that it can be utilized by the tissues, especially
muscle, before toxic concentrations can build up. Therefore, a whole tomato is
safer than a pureed tomato. The only exception to this based on present
knowledge, is in the case of ALS. Also, the tomato plant contains several
powerful antioxidants known to block glutamate toxicity.(
15)
Hydrolyzed vegetable protein is a common food additive and may contain at
least two excitotoxins, glutamate and cysteic acid. Hydrolyzed vegetable
protein is made by a chemical process that breaks down the vegetable's protein
structure to purposefully free the glutamate, as well as aspartate, another
excitotoxin. This brown powdery substance is used to enhance the flavor of
foods, especially meat dishes, soups, and sauces. Despite the fact that some
health food manufacturers have attempted to sell the idea that this flavor
enhancer is "all natural" and "safe" because it is made
from vegetables, it is not. It is the same substance added to processed foods.
Experimentally, one can produce the same brain lesions using hydrolyzed
vegetable protein as by using MSG or aspartate.(
16)
A growing list of excitotoxins are being discovered, including several that
are found naturally. For example, L-cysteine is a very powerful excitotoxin.
Recently, it has been added to certain bread dough and is sold in health food
stores as a supplement. Homocysteine, a metabolic derivative, is also an
excitotoxin.(
17)
Interestingly, elevated blood levels of homocysteine has recently been shown to
be a major, if not the major, indicator of cardiovascular disease and stroke.
Equally interesting, is the finding that elevated levels have also been
implicated in neurodevelopmental disorders, especially anencephaly and spinal
dysraphism (i.e., neural tube defects).(
18) It is thought that this
is the protective mechanism of action associated with the use of the prenatal
vitamins B12, B6, and folate when used in combination. It remains to be seen if
the toxic effect is excitatory or by some other mechanism. If it is excitatory,
then unborn infants would be endangered as well by glutamate, aspartate (part
of the aspartame molecule), and the other excitotoxins. Recently, several
studies have been done in which it was found that all Alzheimer's patients
examined had elevated levels of homocysteine.(
19)
One interesting study found that persons affected by Alzheimer's disease
also have widespread destruction of their retinal ganglion cells.(
20) Interestingly, this is
the area found to be affected when Lucas and Newhouse first discovered the
excitotoxicity of MSG. While this does not prove that dietary glutamate and
other excitotoxins cause or aggravate Alzheimer's disease, it is powerful
circumstantial evidence. When all of the information known concerning
excitatory food additives is analyzed, it is hard to justify continued approval
by the FDA for the widespread use of these food additives.
Conclusion
In this brief discussion of a most complicated and evolving subject, I have
had to omit several important pieces of the puzzle. For example, I have said
little about the functional components of the receptor systems, the glutamate
transporter and its relation to ALS and Alzheimer's dementia, receptor decay
with aging and disease, membrane effects of lipid peroxidation products,
membrane fluidity, effects of chronic inflammation on the glutamate/free
radical cycle, stress hormones and excitotoxicity, the role of insulin excess
on the eicosanoid system, or the detailed physiology of the glutamatergic
system. I have also only briefly alluded to the toxicity of aspartame and
omitted its strong connection to brain tumor induction.
But, I have tried to show the reader that there is a strong connection
between dietary and endogenous excitotoxin excess and neurological dysfunction
and disease. Many of the arguments by the food processing industry have been
shown to be false. For example, that dietary glutamate does not enter the brain
because of exclusion by the blood-brain barrier, has been shown to be wrong,
since glutamate can enter by way of the unprotected areas of the brain such as
the circumventricular organs. Also, as we have seen, chronic elevations of
blood glutamate can breech the intact blood-brain barrier. In addition, there
are numerous conditions under which the barrier is made incompetent.
As our knowledge of the pathophysiology and biochemistry of the neurodegenerative
diseases increases, the connection to excitotoxicity has become stronger.(
21) This is especially so
with the interrelationship between excitotoxicity and free radical generation
and declining energy production with aging. Several factors of aging have been
shown to magnify this process. For example, as the brain ages its iron content
increases, making it more susceptible to free radical generation. Also, aging
changes in the blood brain barrier, microvascular changes leading to impaired
blood flow, free radical mitochondrial injury to energy generating enzymes, DNA
adduct formation, alterations in glucose and glutamate transporters and free
radical and lipid peroxidation induced alterations in the neuronal membranes
all act to make the aging brain increasingly susceptible to excitotoxic injury.
Over a lifetime of free radical injury due to chronic stress, infections,
trauma, impaired blood flow, hypoglycemia, hypoxia and poor antioxidant defenses
secondary to poor nutritional intake, the nervous system is significantly
weakened and made more susceptible to further excitotoxic injury. We know that
a loss of neuronal energy generation is one of the early changes seen with the
neurodegenerative diseases. This occurs long before clinical disease develops.
But, even earlier is a loss of neuronal glutathione functional levels.
A word about ascorbic acid: Few are aware of the importance of adequate ascorbate
levels for CNS function and neural protection against excitotoxicity. We are
finding out that ascorbic acid plays a vital role in neurobehavioral regulation
and the dopaminergic system as well, which may link ascorbate supplementation
to improvements in schizophrenia.
Our knowledge of this process opens up new avenues for treatment as well as
prevention of excitotoxic injury to the nervous system. For example, there are
many nutritional ways to improve CNS antioxidant defenses and boost neuronal energy
generation, as well as improve membrane fluidity and receptor integrity. By
using selective glutamate blocking drugs or nutrients, one may be able to alter
some of the more devastating effects of Parkinson's disease. For example, there
is evidence that dopamine deficiency causes a disinhibition (overactivity) of
the subthalamic nucleus and that this may result in excitotoxic injury to the
substantia nigra.(
22) By
blocking the glutamatergic neurons in this nucleus, one may be able to reduce
this damage. There is also evidence that several nutrients can significantly
reduce excitotoxicity. For example, combinations of coenzyme Q10 and
niacinamide have been shown to protect against striatal excitotoxic lesions.
Methylcobolamine, phosphotidylserine, picnogenol and acetyl-L-carnitine all
protect against excitotoxicity as well.
Of particular concern is the toxic effects of these excitotoxic compounds on
the developing brain. It is well recognized that the immature brain is four
times more sensitive to the toxic effects of the excitatory amino acids as is
the mature brain. This means that excitotoxic injury is of special concern from
the fetal stage to adolescence. There is evidence that the placenta concentrates
several of these toxic amino acids on the fetal side of the placenta.
Consumption of aspartame and MSG containing products by pregnant women during
this critical period of brain formation is of special concern and should be
discouraged. Many of the effects, such as endocrine dysfunction and complex
learning, are subtle and may not appear until the child is older. Other
hypothalamic syndromes associated with early excitotoxic lesions include immune
alterations and violence dyscontrol.
Over 100 million American now consume aspartame products and a greater
number consume products containing one or more excitotoxins. There is
sufficient medical literature documenting serious injury by these additives in
the concentrations presently in our food supply to justify warning the public
of these dangers. The case against aspartame is especially strong.
Footnote
* See FDA position papers at
http://www.fda.gov/opacom/backgrounders/msg.html and
http://www.fda.gov/bbs/topics/ANSWERS/ANS00772.html.
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Dr. Blaylock is a neurological surgeon in Jackson, Mississippi, and a
member of the Editorial Board of the Medical Sentinel.
E-mail: russell@mail.misnet.com.
Originally published in the Medical Sentinel 1999;4(6):212-215. Copyright
©1999 Association of American Physicians and Surgeons (AAPS).
http://aapsonline.org/jpands/hacienda/article27.html
