Part 3 Excitotoxins, Neurodegeneration and Neurodevelopment

Excitotoxins, Neurodegeneration and NeurodevelopmentBy Russell L. Blaylock, M.D



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 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.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.

Unfortunately, for the consumer, the corporate food processors not only continue 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.10 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.11

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.<12 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 ( 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 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.13

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.14

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.15 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).16 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.17

One interesting study found that persons affected by Alzheimer's disease also have widespread destruction of their retinal ganglion cells.18 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.

Part 2 of Excitotoxins, Neurodegeneration and Neurodevelopment

How Excitotoxins Were Discovered

In 1957, two opthalmology 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 Opthalmology 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 statue. 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, including the hippocampus, circumventricular organs, locus cereulus, 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 indogenous. 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 born excitotoxins can add significantly to this accumulation of toxins.