EXCITOT0XINS - By Dr. Russell L. Blaylock, MD
(Author of the excellent book: Excitotoxins: The Taste That Kills)
There are a growing number of Clinicians and Scientists who are convinced that excitotoxins play a critical role in the development of several neurological disorders, including migraines, seizures, infections, abnormal neural development, certain endocrine disorders, specific types of obesity, and especially the neurodegenerative diseases; a group of diseases which includes: 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 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 MSG, hydrolyzed vegetable protein, and aspartame (NutraSweet and Equal – the blue packets).
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 that it tastes better. Aspartame is an artificial sweetener.
The public must be made aware that 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 (below toxic levels) of excitotoxins are given to animals, they experience full toxicity. 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 amino acids, that react with specialized receptors in the brain in such a way as to lead to destruction of certain types of brain cells. 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 most commonly used neurotransmitter by the brain. Defenders of MSG and aspartame use, often say: “How could a substance that is used normally by the brain cause harm?” This is because, glutamate, as a neurotransmitter, is used by the brain only in very, very small concentrations - no more than 8 to 12ug. When the concentration of this transmitter rises above this level the neurons begin to fire abnormally. At higher concentrations, the cells undergo a specialized process of cell death.
The brain has several elaborate mechanisms to prevent accumulation of MSG in the brain. First is the blood-brain barrier, a system that impedes glutamate entry into the area of the brain cells. But, this system was intended to protect the brain against occasional elevation of glutamate of a moderate degree, as would be found with un-processed food consumption. It was not designed to eliminate very high concentrations of glutamate and aspartate consumed daily, several times a day, as we see in modern society. Several experiments have demonstrated that under such conditions, glutamate can by-pass this barrier system and enter the brain in toxic concentrations. In fact, there is some evidence that it may actually be concentrated within the brain with prolonged exposures. There are also several conditions under which the blood-brain barrier (BBB) is made incompetent. Before birth, the BBB is incompetent and will allow glutamate to enter the brain. It may be that for a considerable period after birth the barrier may also incompletely developed as well. Hypertension, diabetes, head trauma, brain tumors, strokes, certain drugs, Alzheimer's disease, vitamin and mineral deficiencies, severe hypoglycemia, heat stroke, electromagnetic radiation, ionizing radiation, multiple sclerosis, and certain infections can all cause the barrier to fail. In fact, as we age the barrier system becomes more porous, allowing excitotoxins in the blood to enter the brain. So there are numerous instances under which excitotoxin food additives can enter and damage the brain.
Finally, recent experiments have shown that glutamate and aspartate (as in aspartame) can open the barrier itself. Another system used to protect the brain against environmental excitotoxins, is a system within the brain that binds the glutamate molecule (called the glutamate transporter) and transports it to a special storage cell (the astrocyte) within a fraction of a second after it is used as a neurotransmitter. This system can be overwhelmed by high intakes of MSG, aspartame and other food excitotoxins. It is also known that excitotoxins themselves can cause the generation of numerous amounts of free radicals and that during the process of lipid peroxidation (oxidation of membrane fats) a substance is produced called 4-hydroxynonenal. This chemical inhibits the glutamate transporter, thus allowing glutamate to accumulate in the brain. Excitotoxins destroy neurons partly by stimulating the generation of large numbers of free radicals. Recently, it has been shown that this occurs not only within the brain, but also within other tissues and organs as well (liver and red blood cells). This could, from all available evidence, increase all sorts of degenerative diseases such as arthritis, coronary heart disease, and atherosclerosis, as well as induce cancer formation. Certainly, we would not want to do something that would significantly increase free radical production in the body. It is known that all of the neurodegenerative disease, such as Parkinson's disease, Alzheimer's disease, and ALS, are associated with free radical injury of the nervous system.
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 MSG and aspartame are probably not causes of the neurodegenerative diseases, such as Alzheimer's dementia, Parkinson's disease, or amyotrophic lateral sclerosis, they may well precipitate these disorders and certainly worsen their effects. 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.
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. The FDA wrote a very deceptive summery 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. 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. In other words it has not been looked at -.a vital difference.
Unfortunately for the consumer, the corporate food processors not only continue to add MSG to our foods, but they have gone to great lengths to disguise these harmful additives. For example, they use such names as hydrolyzed vegetable protein, vegetable protein, hydrolyzed plant protein, caseinate, yeast extract, and natural flavoring. We know experimentally, as stated, when these excitotoxin taste enhancers are added together they become much more toxic. 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 food, that contain two, three or even four types of excitotoxins. We also know that excitotoxins in a liquid form 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 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.
In the case of ALS, amyotrophic lateral sclerosis, 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. 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 high levels of glutamate. It must be remembered that it is the glutamate molecule that is toxic in MSG (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 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, in the case of tomatoes, the plant contains several powerful antioxidants known to block glutamate toxicity.
Hydrolyzed vegetable protein should not be confused with hydrolyzed vegetable oil. The oil does not contain appreciable concentration of glutamate, it is an oil. 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. A growing list of excitotoxins is 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. 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 (neural tube defects). It is thought that this is the protective mechanism of action 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. Recent studies have shown that persons affected by Alzheimer's disease also have widespread destruction of their retinal ganglion cells. 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 makes one very suspicious. One could argue a common intrinsic etiology for central nervous system neuronal damage and retinal ganglion cell damage, but these findings are disconcerting enough to warrant further investigations.
EXCITOTOXINS - By Dr. George Grant
The Free Radical Connection
It is interesting to note that many of the same neurological diseases associated with excitotoxic injury are also associated with accumulations of toxic free radicals and destructive lipid enzymes. For example, the brains of Alzheimer's disease patients have been found to contain high concentration of lipolytic enzymes, which seems to indicate accelerated membrane lipid peroxidation, again caused by free radical generation. In the case of Parkinson's disease, we know that one of the early changes is the loss of glutathione from the neurons of the striate system, especially in a nucleus called the substantia nigra. It is this nucleus that is primarily affected in this disorder. Accompanying this, is an accumulation of free iron, which is one of the most powerful free radical generators known. One of the highest concentrations of iron in the body is within the globus pallidus and the substantia nigra. The neurons within the latter are especially vulnerable to oxidant stress because the oxidant metabolism of the transmitter-dopamine- can proceed to the creation of very powerful free radicals. That is, it can auto-oxidize to peroxide,which is normally detoxified by glutathione. As we have seen, glutathione loss in the substantia nigra is one of the earliest deficiencies seen in Parkinson's disease. In the presence of high concentrations of free iron, the peroxide is converted into the dangerous and very powerful free radical, hydroxide. As the hydroxide radical diffuses throughout the cell, destruction of the lipid components of the cell takes place, a process called lipid peroxidation. Using a laser microprobe mass analyzer, researchers have recently discovered that iron accumulation in Parkinson's disease is primarily localized in the neuromelanin granules (which gives the nucleus its black color). It has also been shown that there is dramatic accumulation of aluminum within these granules. Most likely, the aluminum displaces the bound iron, releasing highly reactive free iron. It is known that even low concentrations of aluminum salts can enhance iron-induced lipid peroxidation by almost an order of magnitude. Further, direct infusion of iron into the substantia nigra nucleus in rodents can induce a Parkinsonian syndrome, and a dose related decline in dopamine. Recent studies indicate that individuals having Parkinson's disease also have defective iron metabolism.
Another early finding in Parkinson's disease is the reduction in complex I enzymes within the mitochondria of this nucleus. It is well known that the complex I enzymes are particularly sensitive to free radical injury. These enzymes are critical to the production of cellular energy. When cellular energy is decreased, the toxic effect of excitatory amino acids increases dramatically, by as much as 200 fold. In fact, when energy production is very low, even normal concentrations of extracellular glutamate and aspartate can kill neurons. One of the terribly debilitating effects of Parkinson's disease is a condition called " freezing up", a state where the muscle are literally frozen in place. There is recent evidence that this effect is due to the unopposed firing of a special nucleus in the brain (the subthalamic nucleus). Interestingly, this nucleus uses glutamate for its transmitter. Neuroscientists are exploring the use of glutamate blocking drugs to prevent this disorder.
And finally, there is growing evidence that similar free radical damage, most likely triggered by toxic concentrations of excitotoxins, causes ALS. Several studies have demonstrated lipid peroxidation product accumulation within the spinal cords of ALS victims. Iron accumulation has also been seen in the spinal cords of ALS victims. Besides the well known reactive oxygen species, such as super oxide, hydroxyl ion, hydrogen peroxide, and singlet oxygen, there exist a whole spectrum of reactive nitrogen species derived from nitric oxide, the most important of which is peroxynitrate. These free radicals can attack proteins, membrane lipids and DNA, both nuclear and mitochondrial, which makes these radicals very dangerous.
It is now known that glutamate acts on its receptor via a nitric oxide mechanism. Overstimulation of the glutamate receptor can result in accumulation of reactive nitrogen species, resulting in the concentration of several species of dangerous free radicals. There is growing evidence that, at least in part, this is how excess glutamate damages nerve cells.
In a multitude of studies, a close link has been demonstrated between excitotoxity and free radical generation. Others have shown that certain free radical scavengers (anti-oxidants), have successfully blocked excitotoxic destruction of neurons. For example, vitamin E is known to completely block glutamate toxicity in vitro (in culture). Whether it will be as efficient in vivo (in a living animal) is not known. But, it is interesting in light of the recent observations that vitamin E slows the course of Alzheimer's disease, as had already been demonstrated in the case of Parkinson's disease. There is some clinical evidence, including my own observations, that vitamin E also slows the course of ALS as well, especially in the form of D- Alpha-tocopherol. I would caution that anti-oxidants work best in combination and when use separately can have opposite, harmful, effects. That is, when antioxidants, such as ascorbic acid and alpha tocopherol, become oxidized themselves, such as in the case of dehydroascorbic acid, they no longer protect, but rather act as free radicals themselves. The same is true of alpha-tocopherol.
Taking the vitality pack + Provex Plus (or CV) + Cell Wise is highly recommended to neutralize those free radicals.
We know that there are four main endogenous sources of oxidants:
1. Those produced naturally from aerobic metabolism of glucose.
2. Those produced during phagocytic cell attack on bacteria, viruses, and parasites, especially with chronic infections.
3. Those produced during the degradation of fatty acids and other molecules that produce H2O2 as a by-product. (This is important in stress, which has been shown to significantly increase brain levels of free radicals.) And 4. Oxidants produced during the course of p450 degradation of natural toxins.
As we have seen, one of the major endogenous sources of free radicals is from exposure to free iron. Unfortunately, iron is one mineral heavily promoted by the health industry, and is frequently added to many foods, especially breads and pastas. Copper is also a powerful free radical generator and has been shown to be elevated within the substantia nigra nucleus of Parkinsonian brains.
When free radicals are generated, the first site of damage is to the cell membranes, since they are composed of polyunsaturated fatty acid molecules known to be highly susceptible to such attack. The process of membrane lipid oxidation is known as lipid peroxidation and is usually initiated by the hydroxal radical. We know that one's diet can significantly alter this susceptibility. For example, diets high in omega 3-polyunsaturated fatty acids (fish oils and flax seed oils) can increase the risk of lipid peroxidation experimentally. Contrawise, diets high in olive oil, a monounsaturtated oil, significantly lowers lipid peroxidation risk. From the available research.The beneficial effects of omega 3-fatty acid oils in the case of strokes and heart attacks probably arises from the anticoagulant effect of these oils and possibly the inhibition of release of arachidonic acid from the cell membrane. But, olive oil has the same antithrombosis effect and anticancer effect but also significantly lowers lipid peroxidation.
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