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Excitotoxins, neurodegeneration
and neurodevelopment

By Dr Russell L. Blaylock, MD

A growing number of clinicians and basic scientists 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 amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, Huntington's disease and olivopontocerebellar degeneration.'

An enormous amount of both clinical and experimental evidence has
accumulated over the past decade, supporting this basic premise.' Yet, the FDA still refuses to recognise the immediate and long term danger to the public caused by the practice of allowing various excitotoxins to be added to the food supply; excitotoxins such as MSG (monosodium glutamate), hydrolysed vegetable protein and aspartame. The amount of these neurotoxins added to our food has increased enormously since their 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 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, hydrolysed vegetable protein and natural flavouring are used to enhance the taste of food, while aspartame is an artificial sweetener.

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 flavouring, 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, the animals experience full toxicity, i.e., the excitotoxins are synergistic.

Also, liquid forms of excitotoxins, as found 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 levels in the blood.

So, what are excitotoxins?

These are substances, usually acidic amino acids, that react with specialised 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. MSG is the sodium salt of glutamate. This amino acid is a normal neurotransmitter in the brain. In fact, it is the neurotransmitter most commonly used by the brain. Defenders of MSG and aspartame usually ask how a substance that is used normally by the brain could cause harm. It is because glutamate, as a neurotransmitter, exists in the extracellular fluid only in very, very small concentrations?no more than 8 to 12 uM [micromoles/litre]. When the concentration of this transmitter rises above this level, the neurons begin to fire abnormally. At higher concentrations, the cells undergo a specialised process of delayed cell death known as "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 die suddenly 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 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 fullblown disorder if not for their exposure to high levels of foodborne excitotoxin additives. Some might only have had a very mild form of the disease, if not for the exposure. Likewise, foodborne excitotoxins may be harmful to those suffering from strokes, head injury and HIV infection, and certainly should not be used in a hospital setting.

The discovery of excitotoxins

In 1957, two opthalmology residents, Lucas and Newhouse, were conducting an experiment on mice to study a particular eye disorder.' 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 was not as severe as in the newborns. The results of their experiment were published in the Archives of Opthalmology and soon forgotten. For 10 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 given to 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." 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 and adrenal, as well as reproductive dysfunction.
Physiologically, they demonstrated multiple endocrine deficiencies,
including of TSH, growth hormone, LH, FSH and ACTH. When Dr Olney examined the animals' brains, he discovered discrete lesions of the arcuate nucleus as well as less severe destruction of other hypothalamic nuclei.

Since this early observation, monosodium glutamate and other excitatory substances have become standard tools in studying the function of the hypothalamus. Recent studies showed that glutamate is the most important neurotransmitter in the hypothalamus.' Later studies indicated that the damage by monosodium glutamate was much more widespread, affecting the hippocampus, circumventricular organs, locus ceruleus, amygdala, limbic system, subthalamus and striatum.6 More recent molecular studies disclosed the mechanism of this destruction in some detail.'

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 specialised 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.

Countering the FDA's spin on MSG safety

In July 1995, the Federation of American Societies for Experimental Biology (FASEB) conducted a definitive study for the US Food and Drug Administration (FDA) on the question of safety of MSG.' The FDA wrote a very deceptive summary of the report in which it 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 summarised, in detail, my criticism of this widely reported FDA deception in the revised paperback edition of my book, "Excitotoxins: The Taste That Kills", by analysing exactly what the report said and failed to say.' For example, it never said that MSG did not aggravate neurodegenerative diseases. What it 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.

Unfortunately for the consumer, the corporate food processors not only
continue to add MSG to our foods but go to great lengths to disguise these harmful additives. For example, they use such names as "hydrolysed vegetable protein", "vegetable protein", "textured protein", "hydrolysed plant protein", "soy protein extract", "caseinate","yeast extract" and "natural flavouring". We know experimentally that when these excitotoxin taste?enhancers are added together, they become much more toxic than is seen individually.'' In fact, excitotoxins in subtoxic concentrations can be fully toxic to specialised brain cells when used in combination. Frequently on supermarket shelves I see processed foods, 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 who have 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."

In the case of amyotrophic lateral sclerosis (ALS), we know that consumption of red meats, and especially MSG itself, can significantly elevate blood glutamate to levels much higher than seen in the normal population." Similar studies, as far as I am aware, have not been conducted in patients with Alzheimer's or Parkinson's disease. But, as a general rule, I would certainly suggest that persons 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
monosodium glutamate. Glutamate is a naturally occurring amino acid found in varying concentrations in many foods. Defenders of MSG safety allude to this fact in their defence. 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 utilised 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 as stated, based on present knowledge, is in the case of ALS. Also, the tomato plant contains several powerful antioxidants known to block glutamate toxicity."

Hydrolysed vegetable protein is a common food additive and may contain at least two excitotoxins: glutamate and cysteic acid. Hydrolysed vegetable protein is made by a chemical process that breaks down the vegetable's protein structure purposefully to free the glutamate as well as aspartate, another excitotoxin. This brown, powdery substance is used to enhance the flavour of foods, especially meat dishes, soups and sauces, Despite the fact that some health food manufacturers have attempted to sell the idea that this flavour 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 hydrolysed vegetable protein as by using MSG or aspartate.

Source: Medical Sentinel, vol.4, no. 6, Nov-Dec, 1999

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