TOXIC ADDITIVES IN YOUR FOOD AND DRINK....NOT JUST ANOTHER SCARE

[Guest guest]

Not Just Another Scare: Toxin Additives in Your Food and Drink

 

Russell L. Blaylock, M.D.

 

There are a growing number of clinicians and basic 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. 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,

usually 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 is 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

links to disguise these harmful additives. For example, they use such

names a 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 of 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.

 

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. Neuroscientist 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.

 

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.

 

And, 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.

 

The Blood-Brain Barrier

 

One of the MSG industry's chief arguments for the safety of their

product is that glutamate in the blood cannot enter the brain because

of the blood-brain barrier (BBB), a system of specialized capillary

structures designed to exclude toxic substance from entering the

brain. There are several criticisms of their defense. For example, it

is known that the brain, even in the adult, has several areas that

normally do not have a barrier system, called the circumventricular

organs. These include the hypothalamus, the subfornical organ,

organium vasculosum, area postrema, pineal gland, and the

subcommisural organ. Of these, the most important is the

hypothalamus, since it is the controlling center for all

neuroendocrine regulation, sleep wake cycles, emotional control,

caloric intake regulation, immune system regulation and regulation of

the autonomic nervous system. Interestingly, it has recently been

found that glutamate is the most important neurotransmitter in the

hypothalamus. Therefore, careful regulation of blood levels of

glutamate is very important, since high blood concentrations of

glutamate can easily increase hypothalamic levels as well. One of the

earliest and most consistent findings with exposure to MSG is damage

to an area known as the arcuate nucleus. This small hypothalamic

nucleus controls a multitude of neuroendocrine functions, as well as

being intimately connected to several other hypothalamic nuclei. It

has also been demonstrated that high concentrations of blood

glutamate and aspartate (from foods) can enter the so-

called " protected brain " by seeping through the unprotected areas,

such as the hypothalamus or circumventricular organs.

 

Another interesting observation is that chronic elevations of blood

glutamate can even seep through the normal blood-brain barrier when

these high concentrations are maintained over a long period of time.

This, naturally, would be the situation seen when individuals

consume, on a daily basis, foods high in the excitotoxins - MSG,

aspartame and cysteine. Most experiments cited by the defenders of

MSG safety were conducted to test the efficiency of the BBB acutely.

In nature, except in the case of metabolic dysfunction (Such as with

ALS), glutamate and aspartate levels are not normally elevated on a

daily basis. Sustained elevations of these excitotoxins are peculiar

to the modern diet. (And in the ancient diets of the Orientals, but

not in as high a concentration.)

 

An additional critical factor ignored by the defenders of excitotoxin

food safety is the fact that many people in a large population have

disorders known to alter the permeability of the blood-brain barrier.

The list of condition associated with barrier disruption include:

hypertension, diabetes, ministrokes, major strokes, head trauma,

multiple sclerosis, brain tumors, chemotherapy, radiation treatments

to the nervous system, collagen-vascular diseases (lupus), AIDS,

brain infections, certain drugs, Alzheimer's disease, and as a

consequence of natural aging. There may be many other conditions also

associated with barrier disruption that are as yet not known.

 

When the barrier is dysfunctional due to one of these conditions,

brain levels of glutamate and aspartate reflect blood levels. That

is, foods containing high concentrations of these excitotoxins will

increase brain concentrations to toxic levels as well. Take for

example, multiple sclerosis. We know that when a person with MS has

an exacerbation of symptoms, the blood-brain barrier near the lesions

breaks down, leaving the surrounding brain vulnerable to excitotoxin

entry from the blood, i.e. the diet. But, not only is the adjacent

brain vulnerable, but the openings act as a points of entry,

eventually exposing the entire brain to potentially toxic levels of

glutamate. Several clinicians have remarked on seeing MS patients who

were made worse following exposure to dietary excitotoxins. I have

seen this myself.

 

It is logical to assume that patients with the other

neurodegenerative disorders, such as Alzheimer's disease, Parkinson's

disease, and ALS will be made worse on diets high in excitotoxins.

Barrier disruption has been demonstrated in the case of Alzheimer's

disease.

 

Recently, it has been shown that not only can free radicals open the

blood-brain barrier, but excitotoxins can as well. In fact, glutamate

receptors have been demonstrated on the barrier itself. In a

carefully designed experiment, researchers produced opening of the

blood-brain barrier using injected iron as a free radical generator.

When a powerful free radical scavenger (U-74006F) was used in this

model, opening of the barrier was significantly blocked. But, the

glutamate blocker MK-801 acted even more effectively to protect the

barrier. The authors of this study concluded that glutamate appears

to be an important regulator of brain capillary transport and

stability, and that overstimulation of NMDA (glutamate) receptors on

the blood-brain barrier appears to play an important role in

breakdown of the barrier system. What this also means is that high

levels of dietary glutamate or aspartate may very well disrupt the

normal blood-brain barrier, thus allowing more glutamate to enter the

brain, sort of a vicious cycle.

 

Relation to Cellular Energy Production

 

Excitotoxin damage is heavily dependent on the energy state of the

cell. Cells with a normal energy generation systems that are

efficiently producing adequate amounts of cellular energy, are very

resistant to such toxicity. When cells are energy deficient, no

matter the cause - hypoxia, starvation, metabolic poisons,

hypoglycemia - they become infinitely more susceptible to excitotoxic

injury or death. In fact, even normal concentrations of glutamate are

toxic to energy deficient cells.

 

It is known that in many of the neurodegenerative disorders, neuron

energy deficiency often precedes the clinical onset of the disease by

years, if not decades. This has been demonstrated in the case of

Huntington disease and Alzheimer's disease using the PET scanner,

which measures brain metabolism. In the case of Parkinson's disease,

several groups have demonstrated that one of the early deficits of

the disorder is an impaired energy production by the complex I group

of enzymes from the mitochondria of the substantia nigra. (Part of

the Electron Transport System.) Interestingly, it is known that the

complex I system is very sensitive to free radical damage.

 

Recently, it has been shown that when striatal neurons (Those

involved in Parkinson's and Huntington's diseases.) are exposed to

microinjected excitotoxins there is a dramatic, and rapid fall in

energy production by these neurons. CoEnzyme Q10 has been shown, in

this model, to restore energy production but not to prevent cellular

death. But when combined with niacinamide, both cellular energy

production and neuron protection is seen. I would recommend for those

with neurodegenerative disorders, a combination of CoQ10, acetyl-L

carnitine, niacinamide, riboflavin, methylcobalamin, and thiamine.

 

One of the newer revelation of modern molecular biology, is the

discovery of mitochondrial diseases, of which cellular energy

deficiency is a hallmark. In many of these disorders, significant

clinical improvement has been seen following a similar regimen of

vitamins combined with CoQ10 and L-carnitine. Acetyl L-carnitine

enters the brain in higher concentrations and also increases brain

acetylcholine, necessary for normal memory function. While these

particular substances have been found to significantly boost brain

energy function they are not alone in this important property.

Phosphotidyl serine, Ginkgo Biloba, vitamin B12, folate, magnesium,

Vitamin K and several others are also being shown to be important.

 

While mitochrondial dysfunction is important in explaining why some

are more vulnerable to excitotoxin damage than others, it does not

explain injury in those with normal cellular metabolism. There are

several conditions under which energy metabolism is impaired. For

example, approximately one third of Americans suffer from what is

known as reactive hypoglycemia. That is, they respond to a meal

composed of either simple sugars or carbohydrates that are quickly

broken down into simple sugars (a high glycemic index.) by secreting

excessive amounts of insulin. This causes a dramatic lowering of the

blood sugar.

 

When the blood sugar falls, the body responds by releasing a burst of

epinephrine from the adrenal glands, in an effort to raise the blood

sugar. We feel this release as nervousness, palpitations of our

heart, tremulousness, and profuse sweating. Occasionally, one can

have a slower fall in the blood sugar that will not produce a

reactive release of epinephrine, thereby producing few symptoms. This

can be more dangerous, since we are unaware that our glucose reserve

is falling until we develop obvious neurological symptoms, such as

difficulty thinking and a sensation of lightheadedness.

 

The brain is one of the most glucose dependent organs known, since it

has a limited ability to burn other substrates such as fats. There is

some evidence that several of the neurodegenerative diseases are

related to either excessive insulin release, as with Alzheimer's

disease, or impaired glucose utilization, as we have seen in the case

of Parkinson's disease and Huntington's disease.

 

It is my firm belief, based on clinical experience and physiological

principles, that many of these diseases occur primarily in the face

of either reactive hypoglycemia or " brain hypoglycemia " . In at least

two well conducted studies it was found that pure Alzheimer's

dementia was rare in those with normal blood sugar profiles, and that

in most cases Alzheimer's patients had low blood sugars, and high CSF

(cerebrospinal fluid) insulin levels. In my own limited experience

with Parkinson's and ALS patients I have found a disproportionately

high number suffering from reactive hypoglycemia.

 

I found it interesting that several ALS patients have observed an

association between their symptoms and gluten. That is, when they

adhere to a gluten free diet they improve clinically. It may be that

by avoiding gluten containing products, such as bread, crackers,

cereal, pasta ,etc, they are also avoiding products that are high on

the glycemic index, i.e. that produce reactive hypoglycemia. Also,

all of these food items are high in free iron. Clinically,

hypoglycemia will worsen the symptoms of most neurological disorders.

We know that severe hypoglycemia can, in fact, mimic ALS both

clinically and pathologically. It is also known that many of the

symptoms of Alzheimer's disease resemble hypoglycemia, as if the

brain is hypoglycemic in isolation.

 

In studies of animals exposed to repeated mild episodes of hypoxia

(lack of brain oxygenation), it was found that such accumulated

injuries can trigger biochemical changes that resemble those seen in

Alzheimer's patients. One of the effects of hypoxia is a massive

release of glutamate into the space around the neuron. This results

in rapid death of these sensitized cells. As we age, the blood supply

to the brain is frequently impaired, either because of

atherosclerosis or repeated syncopal episodes, leading to short

periods of hypoxia. Hypoglycemia produces lesions very similar to

hypoxia and via the same glutamate excitotoxic mechanism. In fact,

recent studies of diabetics suffering from repeated episodes of

hypoglycemia associated with over medication with insulin,

demonstrate brain atrophy and dementia.

 

Again, it should be realized that excessive glutamate stimulation

triggers a chain of events that in turn triggers the generation of

large numbers of free radical species, both as nitrogen species and

oxygen species. Once this occurs, especially with the accumulation of

the hydroxyl ion, destruction of the lipid components of the

membranes occurs, as lipid peroxidation. In addition, these free

radicals damage proteins and DNA as well. The most immediate DNA

damage is to the mitochondrial DNA, which controls protein expression

within that particular cell and its progeny. It is suspected that at

least some of the neurodegenerative diseases, Parkinson's disease in

particular, are inherited in this way. But more importantly, it may

be that accumulated damage to the mitochondrial DNA secondary to

progressive free radical attack (somatic mitochondrial injury) is the

cause of most of the neurodegenerative diseases that are not

inherited. This would result from an impaired reserve of antioxidant

vitamins/minerals and enzymes, increased cellular stress, chronic

infection, free radical generating metals and toxins, and impaired

DNA repair enzymes.

 

It is estimated that the number of oxidative free radical injuries to

DNA number about 10,000 a day in humans. Normally, these injuries are

repaired by special repair enzymes. It is known that as we age these

repair enzymes decrease or become less efficient. Also, some

individuals are born with deficient repair enzymes from birth as, for

example, in the case of xeroderma pigmentosum. Recent studies of

Alzheimer's patients also demonstrate a significant deficiency in DNA

repair enzymes and high levels of lipid peroxidation products in the

affected parts of the brain. It is also important to realize that the

hippocampus of the brain, most severely damaged in Alzheimer's

dementia, is one of the most vulnerable areas of the brain to low

glucose supply as well as low oxygen supply. That also makes it very

susceptible to glutamate toxicity.

 

Another interesting finding is that when cells are exposed to

glutamate they develop certain inclusions (cellular debris) that not

only resembles the characteristic neurofibrillary tangles of

Alzheimer's dementia, but are immunologically identical as well.

Similarly, when experimental animals are exposed to the chemical

MPTP, they not only develop Parkinson's disorder, but the older

animals develop the same inclusions (Lewy bodies) as see in human

Parkinson's.

 

Eicosanoids and Excitotoxins

 

It is known that one of the destructive effects triggered by

excitotoxins is the release of arachidonic acid from the cell

membrane and the initiation of the eicosanoid reactions. Remember,

glutamate primarily acts by opening the calcium pore, allowing

calcium to pour into the cell's interior. Intracellular calcium in

high concentrations initiates the enzymatic release of arachidonic

acid from the cell membrane, where it is then attacked by two enzymes

systems, the cyclooxygenase system and the lipooxgenase system. These

in turn produce a series of compounds that can damage cell membranes,

proteins and DNA, primarily by free radical production, but also

directly by the " harmful eicosanoids. "

 

Biochemically, we know that high glycemic carbohydrate diets, known

to stimulate the excess release of insulin, can trigger the

production of " harmful eicosanoids. " We should also recognize that

simple sugars are not the only substances that can trigger the

release of insulin. One of the more powerful triggers includes

certain amino acids, including leucine, alanine, and taurine.

Glutamine, while not acting as an insulin trigger itself, markedly

potentiates insulin release by leucine. This is why, except under

certain situations, individual " free " amino acids should be avoided.

 

It is known that excitotoxins can also stimulate the release of

these " harmful eicosanoids. " So that in the situation of a

hypoglycemic individual, they would be subjected to production of

harmful eicosanoids directly by the high insulin levels, as well as

by elevated glutamate levels. Importantly, both of these events

significantly increase free radical production and hence, lipid

peroxidation of cellular membranes. It should be remembered that

diets high in arachidonic acid, such as egg yellows, organs meats,

and liver, may be harmful to those subjected to excessive excitotoxin

exposure.

 

And finally, in one carefully conducted experiment, it was shown that

insulin significantly increases glutamate toxicity in cortical cell

cultures and that this magnifying effect was not due to insulin's

effect on glucose metabolism. That is, the effect was directly

related to insulin interaction with cell membranes. Interestingly,

insulin increased toxic sensitivity to other excitotoxins as well.

 

The Special Role of Flavanoids

 

Flavonoids are diphenylpropanoids found in all plant foods. They are

known to be strong antioxidants and free radical scavengers. There

are three major flavonols - quercetin, Kaempferol, and myricetin, and

two major flavones - luteolin and apigenin. Seventy percent of the

flavonoid intake in the average diet consist of quercetin, the main

source of which is tea (49%), onions (29%), and apples (7%).

Fortunately, flavonoids are heat stable, that is, they are not

destroyed during cooking. Other important flavonoids include

catechin, leucoanthocyanidins, anthocyanins, hesperedin and

naringenin.

 

Most interest in the flavonoids stemmed from their ability to inhibit

tumor initiation and growth. This was especially true of quercetin

and naringenin, but also seen with hesperetin and the isoflavone,

genistein. There appears to be a strong correlation between their

anticarcinogenic potential and their ability to squelch free

radicals. But, in the case of genistein and quercetin, it also has to

do with their ability to inhibit tyrosine kinase and phosphoinositide

phosphorylase, both necessary for mammary cancer and glioblastoma (a

highly malignant brain tumor) growth and development.

 

As we have seen, there is a close correlation between insulin,

excitotoxins, free radicals and eicosanoid production. Of particular

interest, is the finding that most of the flavonoids, especially

quercetin, are potent and selective inhibitors of delta-5-

lipooxygenase enzyme which initiates the production of eicosanods.

Flavones are also potent and selective inhibitors of the enzyme

cyclooxygenase (COX) which is responsible for the production of

thromboxane A2, one of the " harmful eicosanoids " . The COX-2 enzymes

is associated only with excitatory type neurons in the brain and

appears to play a major role in neurodegeneration.

 

One of the critical steps in the production of eicosanoids is the

liberation of arachidonic acid from the cell membrane by

phospholipase A2. Flavonones such as naringenin (from grapefruits)

and hesperetin (citrus fruits) produce a dose related inhibition of

phospholipase A2 (80% inhibition), thereby inhibiting the release of

arachidonic acid. The non-steroidal anti-inflammatory drugs act

similarly to block the production of inflammatory eicosanoids.

 

What makes all of this especially interesting is that recently, two

major studies have found that not only can non-steroidal anti-

inflammatories slow the course of Alzheimer's disease, but they may

prevent it as well. But, these drugs can have significant side

effects, such as GI bleeding, liver and kidney damage. In high doses,

the flavonoids have shown a similar ability to reduce " harmful

eicosanoid " production and should have the same beneficial effect on

the neurodegenerative diseases without the side effects. Also, these

compounds are powerful free radical scavengers and would be expected

to reduce excitotoxicity as well.

 

But, there is another beneficial effect. There is experimental, as

well as clinical evidence, that the flavonoids can reduce capillary

leakage and strengthen the blood brain barrier. This has been shown

to be true for rutin, hesperedin and some chalcones. Rutin and

hesperedin have also been shown to strengthen capillary walls. In the

form of hesperetin methyl chalcone, the hesperedin molecule is

readily soluble in water, significantly increasing its absorbability.

Black currents have the highest concentration of hesperetin of any

fresh fruit, and in a puree form, is even more potent.

 

The importance of these compounds again emphasizes the need for high

intakes of fruits and vegetables in the diet, and may explain the low

incidence of many of these disorders in strict vegetarians, since

this would supply a high concentration of flavonoids, carotenoids,

vitamins, minerals, and other antioxidants to the body. Normally, the

flavonoids from fruits and vegetables are only incompletely absorbed,

so that relatively high concentrations would be needed to attain the

same therapeutic levels seen in these experiments. Juice Plus allows

us to absorb high, therapeutic concentrations of these flavonoids by

a process called cryodehydration. This process removes the water and

sugar from fruits and vegetable but retains their flavonoids in a

fully functional state. Also the process allows one to consume large

amounts of fruits and vegetables that would be impossible with the

whole plant.

 

Iron and Health

 

For decades we, especially women, have been told that we need extra

iron for health -that it builds healthy blood. But, recent evidence

indicates that iron and copper may be doing more harm than good in

most cases. It has been well demonstrated that iron and copper are

two of the most powerful generators of free radicals. This is because

they catalyze the conversion of hydrogen peroxide into the very

powerful and destructive hydroxyl radical. It is this radical that

does so much damage to membrane lipids and DNA bases within the cell.

It also plays a major role in the oxidation of LDL-cholesterol,

leading to heart attacks and strokes.

 

Males begin to accumulate iron shortly after puberty and by middle

age have 1000mg of stored iron in their bodies. Women, by contrast,

because of menstruation, have only 300 mg of stored iron. But, after

menopause they begin to rapidly accumulate iron so that by middle age

they have about 1500 mg of stored iron. It is also known that the

brain begins to accumulate iron with aging. Elevated iron levels are

seen with all of the neurodegenerative diseases, such as Alzheimer's

dementia, Parkinson's disease, and ALS. It is thought that this iron

triggers free radical production within the areas of the brain

destroyed by these diseases. For example, the part of the brain

destroyed by Parkinson's disease, the substantia nigra, has very high

levels of free iron.

 

Normally, the body goes to great trouble to make sure all iron and

copper in the body is combined to a special protein for transport and

storage. But, with several of these diseases, we see a loss of these

transport and storage proteins. This is where flavonoids come into

play. We know that many of the flavonoids (especially quercitin,

rutin, hesperidin, and naringenin) are strong chelators of iron and

copper. In fact, drinking iced tea with a meal can reduce iron

absorption by as much as 87%. But, flavonoids in the diet will not

make you iron deficient.

 

Phosphotidyl serine and Excitotoxity

 

Recent clinical studies indicate that phophotidyl serine can

significantly improve the mental functioning of a significant number

of Alzheimer's patients, especially during the early stages of the

disease. We know that the brain normally contains a large

concentration of phosphotidyl serine. Interestingly, this compound

has a chemical structure similar to L-glutamate, the main excitatory

neurotransmitter in the brain. Binding studies show that phosphotidyl

serine competes with L-glutamate for the NMDA type glutamate

receptor. What this means is that phosphotidyl serine is a very

effective protectant against glutamate toxicity. Unfortunately, it is

also very expensive.

 

The Many Functions of Ascorbic Acid

 

The brain contains one of the highest concentrations of ascorbic acid

in the body. Most are aware of its function in connective tissue

synthesis and as a free radical scavenger. But, ascorbic acid has

other functions that make it rather unique. Ascorbic acid in solution

is a powerful reducing agent where it undergoes rapid oxidation to

form dehydroascorbic acid. Oxidation of this compound is accelerated

by high ph, temperature and some transitional metals, such as iron

and copper. The oxidized form of ascorbic acid can promote lipid

peroxidation and protein damage. This is why it is vital that you

take antioxidants together, since several, such as vitamin E (as D-

alpha-tocopherol) and alpha-lipoic acid, act to regenerate the

reduced form of the vitamin.

 

In man, we know that certain areas of the brain have very high

concentrations of ascorbic acid, such as the nucleus accumbens and

hippocampus. The lowest levels are seen in the substantia nigra.

These levels seem to fluctuate with the electrical activity of the

brain. Amphetamine acts to increase ascorbic acid concentration in

the corpus striatum (basal ganglion area) and decrease it in the

hippocampus, the memory imprint area of the brain. Ascorbic acid is

known to play a vital role in dopamine production as well.

 

One of the more interesting links has been between the secretion of

the glutamate neurotransmitter by the brain and the release of

ascorbic acid into the extracellular space. This release of ascorbate

can also be induced by systemic administration of glutamate or

aspartate, as would be seen in diets high in these excitotoxins . The

other neurotransmitters do not have a similar effect on ascorbic acid

release. This effect appears to be an exchange mechanism. That is,

the ascorbic acid and glutamate exchange places. Theoretically, high

concentration of ascorbic acid in the diet could inhibit glutamate

release, lessening the risk of excitotoxic damage. Of equal

importance is the free radical neutralizing effect of ascorbic acid.

 

There is now substantial evidence that ascorbic acid modulates the

electrophysiological as well as behavioral functioning of the brain.

It also attenuates the behavioral response of rats exposed to

amphetamine, which is known to act through an excitatory mechanism.

In part, this is due to the observed binding of ascorbic acid to the

glutamate receptor. This could mean that ascorbic acid holds great

potential in treating disease related to excitotoxic damage. Thus

far, there are no studies relating ascorbate metabolism in

neurodegenerative diseases. There is at least one report of ascorbic

acid deficiency in guineas pigs producing histopathological changes

similar to ALS.

 

It is known that as we age there is a decline in brain levels of

ascorbic acid. When accompanied by a similar decrease in glutathione

peroxidase, we see an accumulation of H202 and hence, elevated levels

of free radicals and lipid peroxidation. In one study it was found

that with age not only does the extracellular concentration of

ascorbic acid decrease but the capacity of the brain ascorbic acid

system to respond to oxidative stress is impaired as well.

 

In terms of its antioxidant activity, vitamin C and E interact in

such a way as to restore each others active antioxidant state.

Vitamin C scavenges oxygen radicals in the aqueous phase and vitamin

E in the lipid, chain breaking, phase. The addition of vitamin C

suppresses the oxidative consumption of vitamin E almost totally,

probably because in the living organism the vitamin C in the aqueous

phase is adjacent to the lipid membrane layer containing the vitamin

E.

 

When combined, the vitamin C was consumed faster during oxidative

stress than the vitamin E. Once the vitamin C was totally consumed,

the vitamin E began to be depleted at an accelerated rate. N-acetyl-L-

cysteine and glutathione can reduce vitamin E consumption as well,

but less effectively than vitamin C. The real danger is when vitamin

C is combined with iron. Recent experiments have shown that such

combinations can produce widespread destruction within the striate

areas of the brain. This is because the free iron oxidizes the

ascorbate to produce the powerful free radical hydroxyascorbate.

Alpha-lipoic acid acts powerfully to keep the ascorbate and

tocopherol in the reduced state (antioxidant state). As we age, we

produce less of the transferrin transport protein that normally binds

free iron. As a result, older individuals have higher levels of free

iron within their tissues, including brain.

 

Conclusion

 

In this discussion, I tried to highlight some of the more pertinent

of the recent findings related to excitotoxicity in general and

neurodegenerative diseases specifically. In no way is this an all

inclusive discussion of this topic. There are many areas I had to

omit because of space, such as alpha-lipoic acid, an antioxidant that

holds great promise in combatting many of these diseases. Also, I did

not go into detail concerning the metabolic stimulants, the

relationship between exercise and degenerative nervous system

diseases, the protective effect of methycobalamin, and the various

disorders related to excitotoxins.

 

I also purposely omitted discussions of magnesium to keep this paper

short. It is my experience, that magnesium is one of the most

important neuroprotectants known. I would encourage those who suffer

from one of the excitotoxin related disorders to avoid, as much as

possible, food borne excitotoxin additives and to utilize the

substances discussed above. The fields of excitotoxin research, in

combination with research on free radicals and eicosanoids, are

growing very rapidly and new information arises daily. Great promise

exist in the field of flavonoid research as regards many of these

neurodegenerative diseases as well as in our efforts to prevent

neurodegeneration itself.

 

A recent study has demonstrated that aspartame feeding to animals

results in an accumulation of formaldehyde within the cells, with

evidence of significant damage to cellular proteins and DNA. In fact,

the formaldehyde accumulated with prolonged use of aspartame. With

this damning evidence, one would have to be suicidal to continue the

use of aspartame sweetened foods, drinks and medicines. The use of

foods containing excitotoxin additives is especially harmful to the

unborn and small children. By age 4 the brain is only 80% formed. By

age 8, 90% and by age 16 it is fully formed, but still undergoing

changes and rewiring (plasticity). We know that the excitotoxins have

a devastating effect on formation of the brain (wiring of the brain)

and that such exposure can cause the brain to be " miswired. " This may

explain the significant, almost explosive increase in ADD and ADHD.

Glutamate feeding to pregnant animals produces a syndrome almost

identical to ADD. It has also been shown that a single feeding of MSG

after birth can increase free radicals in the offspring's brain that

last until adolescence. Experimentally, we known that infants are 4X

more sensitive to the toxicity of excitotoxins than are adults. And,

of all the species studied, cats, dogs, primates, chickens, guinea

pigs, and rats, humans are by far the most sensitive to glutamate

toxicity. In fact, they are 5x more sensitive than rats and 20x more

sensitive than non-human primates.

 

I have been impressed with the dramatic improvement in children with

ADD and ADHD following abstention from excitotoxin use. It requires

care monitoring of these children. Each time they are exposed to

these substances, they literally go bonkers. It is ludicrous, with

all we know about the destructive effects of excitotoxins, to allow

our children and ourselves to continue on this destructive path.