NEURODEGENERATIVE DISEASES AND ASPARTAME

CHAPTER ONE

AMYOTROPHIC LATERAL SCLEROSIS

ALS is a rapidly progressive and inevitably fatal neurological disease that destroys the neurons responsible for controlling voluntary muscles. The word amyotrophic means "without muscle nourishment," refering to the loss of signals the nerves normally send to the muscles. Lateral means "to the side" and refers to the location of the damage in the spinal cord. Sclerosis means "hardened" and refers to the hardened nature of the spinal cord in advanced ALS. It is often called a motor neuron disease, in reference to the cells that are lost in this disorder.

The muscle-controlling nerve cells, or motor neurons, are divided into two types: the upper and the lower. The upper motor neurons are located in the upper part of the brain and exert some control over the lower motor neurons, which are in the brainstem and the spinal cord. With ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send any messages to the muscles. As the muscles gradually weaken and waste away, they also begin to twitch. Eventually, the ability of the brain to be able to control or start voluntary movement is lost. Individuals with ALS lose their strength and the ability to move their arms, legs and body. As the nerve cells or neurons break down, so do the muscles in the diaphragm and chest wall, causing the individual to lose the ability to breathe without support from a ventilator.

The lower motor neurons are directly attached to muscles through axons. Bundles (nerves) of these axons leave the spinal cord and extend out to the muscles. The function of lower motor neurons is to send "go" signals to muscles. When these cells gradually die, as in individuals with ALS, muscles become progressively weaker and eventually they become paralyzed. The lower motor neurons control most of the body are in the spinal cord. Those that control the muscles of speaking, swallowing and facial expression are bulbar motor neurons located in the brainstem.

Figure 7. In ALS, upper and lower motor neurons degenerate. Upper motor neurons normally send signals to lower motor neurons, which send signals to muscles. Illustration from MD’s ALS Division Publication.

Conventional medicine does not understand the cause of ALS and scientists do not know why this disease strikes some individuals and not others. ALS does not affect a person's ability to see, smell, taste, hear, or recognize touch, and it does not usually impair a person’s thinking or other cognitive abilities, although recent studies have shown a small percentage of patients experience problems with memory or decision-making. There are also signs that some may even develop a form of dementia (Anitei, 2006). 

The cell’s energy supply in the form of ATP is normally produced in the cells via the mitochondria in aerobic cell respiration. This is a metabolic process involving oxygen in the breakdown of glucose. During this breakdown process, free radicals are inadvertantly produced, including two important free radicals, superoxide radical and hydroxyl radical (Eisen, 2000). Of these two, hydroxyl radical is the most potent. The body usually produces these free radicals in minute quantities, however if nothing is done to squelch them, they will accumulate in high concentrations and begin to destroy cells.

The enzyme superoxide dismutase (SOD), a free radical scavenger or antioxidant, catalyzes the dismutation of superoxide into oxygen and hydogen peroxide. SOD is an extremely important antioxidant defense in nearly all cells exposed to oxygen. Normally, SOD deactivates toxins and free radicals that are occuring within all cells. However, it is believed that in individuals with a rare familial form of ALS, there is a defect of SOD within the motor neurons of the spinal cord. When SOD enzymes are at low levels and are exposed to excitotoxins, massive destruction of the motor cells takes place. Excessive amounts of a particular chemical messenger such as aspartate, a neurotoxin, will damage the neurons. Eventually, damage accumulates due to the inability of cells to repair damage as quickly as it arises.

Figure 8. Free Radical Damage to Motor Neurons – Illustration originally published in Geriatrics and Aging: Volume 3, Number 9, November 2000, Pages 26, 27.

At John Hopkins University in Baltimore, Dr. Jeffery Rothstein recently found that ALS patients have a deficiency of glutamate transporter proteins. These are specific proteins that transport free glutamate from the fluid around the neurons into surrounding astrocytes, a star-shaped neuralgia cell of nervous tissue. Under normal conditions, free glutamate would be removed immediately. Rothstein's group found deficiencies of a key protein, GLT-1, in the brains and spinal cords of some patients who had died of ALS. GLT-1, or glutamate transporter 1, is a protein whose usual job is to clear away excess glutamate (Rothstein, 1996).

The damage caused by the loss of the glutamate transporter does not happen all at once. Dr. Rothstein found that when he applied a glutamate transport blocker to a spinal cord slice in a culture, glutamate levels rose to high levels that persisted for weeks. The neurons appeared normal within the first few weeks; however, as time progressed, he began to see the motor neurons slowly dying (Rothstein, 2004).

Figure 9. When a neuron is damaged, it can no longer control the muscle, as it should. Illustration from ALS Association.

This data suggest that ALS is a disease wherein the glutamate transporter protein is not present, causing a rise in glutamate and aspartate within the spinal cord. Eventually, high concentrations of glutamate and aspartate destroy the large motor neurons in the spinal cord.

 

 

 

 

 

 

CHAPTER TWO

PARKINSON’S DISEASE

Excitotoxic stimulation due to the ingestion of Aspartame creates powerful insults to the brain, whereas individuals can develop clinical manifestations of Parkinson's disease. The depletion of the neurotransmitter dopamine, resulting from the obliteration of enzyme sites by the flood of these excitotoxins, further complicates this condition.

Parkinson's disease is a complex chronic brain disorder resulting primarily from the progressive death of a specific group of nerve cells in a layer of a region of the substantia nigra. This region is in the midbrain and consists of a layer of large pigmented nerve cells that produce dopamine. Also affected is the basal ganglia, made up of a group of nuclei associated with motor and learning functions in the midbrain.

 

Figure 10. Basal Ganglia and related structures of the brain. Illustration from About.com – Senior Health

 

Parkinson's disease is one of a group of motor system disorders which result in the loss of dopamine-producing brain cells. The four primary symptoms of this disease are tremors, rigidity of the limbs, bradykinesia (extreme slowness in movement), impaired balance and coordination. As the individual’s condition worsens, they may have difficulty walking, talking, or completing other simple tasks. Parkinson’s usually affects people over the age of 50; however, since the approval of Aspartame in cold soft drinks, there has been a remarkable rise in the percentage of individuals who are exhibiting early onset of this disease. In the progression of this disease, the shaking or tremors, which affects the majority of the individuals, may begin to interfere with daily activities.  Other symptoms may include depression and other emotional changes, difficulty in swallowing, chewing, speaking, urinary problems or constipation, skin problems and sleep disruptions.  There are currently no blood or laboratory tests that have been demonstrated to help in early diagnosis.  A neurological examination is all that is available today for individuals seeking help. Another challenge for the individual is finding a doctor that will give them a diagnosis for their symptoms.  The disease can be difficult to diagnose accurately and doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases.

There is substantial evidence to show Parkinson's disease is a disorder whose cause appears to be related to excitotoxicity by Aspartame (Blaylock, 1997; Choi 1992; Kurland, 1988). The combination of aspartate and phenylalanine in Aspartame destroys the cells in the brain pertaining to this disease. These excitotoxins cause these brain cells to generate enormous amounts of free radicals. Aspartic acid is 40% of the Aspartame molecule and can exacerbate these destructive changes in the brains of individual with Parkinson’s disease. The additional toxins created by Aspartame are DKP, aspartate, methanol, formaldehyde and formic acid, all adding to this injury (Bowen, 2000).

Dr. Hyman Jacob Roberts M.D. F.A.C.P., F.C.C.P., director of the Palm Beach Institute for Medical Research has authored 18 texts and has had more than 240 original articles and letters published, most dealing with diagnostic difficulties, metabolic and neurological problems due to Aspartame poisoning or, as he has coined the term, "Aspartame Disease" (Roberts, 2001). He noted in all of his findings dealing with Parkinson’s disease that there is an alteration of serotonin and dopamine concentrations in the brain by phenylalanine and aspartate. The enzyme, phenylalanine hydroxylase converts phenylalanine to tyrosine and then to dihydroxyphenylalanine (DOPA) and then precursor to dopamine. DOPA can cross the sympathetic neuronal membranes and reach the blood stream. It then becomes a source for the synthesis of tissue catecholamines (dopamine, epinephrine, and norepinephrine), even in the absence of tyrosine hydroxylase, a primary regulator in catecholamine biosynthesis. However, there is a reduction of brain dopamine in the presence of high concentrations of phenylalanine and recent evidence demonstrates oral Aspartame creates formaldehyde as the phenylalanine accumulates within the cells, damaging proteins and destroying the cell’s DNA (Congressional Record-Senate, 1985). In addition, chronic exposure to excess phenylalanine and aspartic acid can decrease the levels of serotonin and other neurotransmitters within several other regions of the brain (Roberts, 1995).

As aspartate overexcites the cortical glutamate cells, it produces parkinsonism a group of nervous disorders similar to Parkinson's disease, marked by muscular rigidity, tremor, and impaired motor control due to the use of certain drugs or frequent exposure to toxic chemicals (Lynch & Guttmann, 2002). The cortical glutamate cells connect to the nigrostriatal neurons lying deep in the brain. Dr. Roberts claims, "It is sort of like lightning hitting the power line outside your house and burning up all of the appliances connected to that line." The power line represents the cortical glutamate neurons and the appliances, the nigrostriatal system.

 Aspartic acid is a recognized source of this damage to the basal ganglia area where Parkinson’s disease degeneration occurs (Bowen, 2002). As in the case with methyl alcohol, the molecular structure of Aspartame makes the aspartic acid damage 5000 times more potent than from free aspartic acid on a milligram per milligram basis. When dopamine, a neurotransmitter necessary to let the brain circuitry function normally, is no longer produced in sufficient amounts in neural tissue, reduction in its concentration within the brain will lead to Parkinson's disease (Bowen, 2000).

Because phenylalanine isolate competes with all other amino acids at the enzyme sites in the brain, it decreases dopamine production making Parkinson symptoms much worse (Bowen, 2000).

  The first step in dopamine synthesis in the brain is to have the amino acid tyrosine decarboxylated to tyramine, usually replacing a carboxyl group with hydrogen. Phenylalanine isolate also competitively inhibits the active site on the decarboxylase enzyme (Bowen, 2005). When the tyrosine is not decarboxylated to tyramine the dopamine levels in the brain plummet considerably. Chronic exposure to excess phenylalanine can decrease the levels of serotonin and other neurotransmitters within several regions of the brain (Wurtman, 1987).

The methyl alcohol derived from Aspartame also plays a role in Parkinson’s disease. It has been reported that methyl alcohol appears to cause Parkinson’s through postsynaptic dysfunction by interfering with dopamine reuptake at nerve terminals (Indakoetxea, Lopez de Munain, Marti-Masso, & Linazasoro, 1990). Insufficient levels of dopamine from the neurons of the substantia nigra synapsing on neurons in the striatum are believed to be responsible for the primary symptoms of Parkinson's. Individuals with Parkinson’s disease use L-Dopa to try to increase the dopamine levels; however, the use of Aspartame can completely defeat this therapeutic endeavor (Gold, 2002).

 

 

CHAPTER THREE

ALZHIEMER’S DISEASE

While conventional medicine has dedicated substantial efforts to study the cause and cure of Alzheimer’s disease and on the formation of amyloid plaques and neurofibrillary tangles that are thought to contribute to the degradation of the neurons in the brain and the symptoms of Alzheimer's disease, Aspartame is not on the list to investigate. In an individual with Alzheimer's disease, there is an accumulation of amyloid plaques between neurons in the brain. Amyloid is a general term for protein fragments that the body produces normally. Beta-amyloid found in senile plaques (or neuritic plaques) is a fragment of a protein that is snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques (Blaylock, 1997).

Perhaps the accumulation of this abnormal protein is just a result of this disease rather than the cause. Something else is injuring the neurons causing them to acquire amyloid protein (Blaylock, 1997).

 

Figure 11. Degenerative changes in an Alzheimer’s-diseased brain. The senile plaques deposited between the neurons consist mainly of the protein beta-amyloid. Illustration from American Health Assistance Foundation.

 

With age, the brain normally shrinks due to the death of brain cells. There is also loss of the myelin (fatty insulation) surrounding the fiber pathway within the white matter of the brain. However, the brain does not lose neurological function just because humans age. The brain is capable of functioning neurologically until we die (Duara, 1984). What scientists do know and see in an aging brain is the presence and progressive accumulation of an "age pigment" called lipofuscin. This is a yellow-brown pigment known to collect in neurons of the elderly. However, the accumulation of lipofuscin does not appear to affect mental function.

The cause of Alzheimer’s can be attributed to many events in an individual’s life, including a severe blow to the head, high fevers, or a chronic subdural hematoma (a large collection of blood in the brain). However, most cases of Alzheimer’s present as a long, gradual, and silent loss of neurons over many years, rather than a massive loss over a short period of time.

The hippocampus of the temporal lobe is the area of the brain that is responsible for new memories, and in Alzheimer’s patients, it is the area that shows the most extensive damage. Researchers are not sure whether the mechanism that retrieves new memories breaks down or rather the inability to store the new memories as they are created is the problem. Eventually, long-term memories will begin to fade along with whatever new memories are made.

Neuritic or senile plaques and neurofibrillary tangles are microscopic bodies found throughout the brains of patients with dementia, chronic dementia, and Alzheimer’s disease. However, these two microscopic injuries or inclusions have also been found in the brains of normal elderly persons. There is growing evidence that these lesions are not the cause of Alzheimer’s disease, but rather the corollary of it (Blaylock, 1997). These lesions develop because of the death of neurons, but do not cause the neurons to actually die (Trojanowski, 1999).

The neurons where these neurofibrillary tangles are located are neurons with glutamate receptors. The frontal and parietal cortex and the hippocampus of the temporal lobes are heavily concentrated with these neurofibrillary (age) tangles and plaques. These are the areas where most of the damage and neuron deaths occur. Viewing these neurofibrillary tangles under the electron microscope, scientists see a mass of twisted fibrils found within the dying neuron. They appear as clusters of paired strands twisted upon each other. These are called, paired helical filaments. Glutamate and aspartate are found in the highest concentration of any other amino acids within these neurofibrillary tangles (Blaylock, 2006). The number of neurofibrillary tangles determines the degree of dementia.

In 1985, two scientists, Umberto De Boni and D.R.C. McLachlan, were working with spinal cord cells that were exposed to excitotoxins in tissue culture (DeBoni & Crapper-McLachlan, 1978), and discovered that prolonged exposure to glutamate or aspartate resulted in the formation of paired helical filaments identical to those seen in the brains with Alzheimer’s disease (DeBoni & McLachlan, 1985).

Senile or neuritic plaque is a darkly staining buildup of abnormal brain cell fragments located outside the neuron and in the same areas as the neurofibrillary tangles. What the two scientists found in the core of these plaques was the protein beta-amyloid not usually found in the brain. Although neuroscientists believe that Alzheimer’s disease is a disorder resulting from the accumulation of this abnormal protein in the brain cells, they can not explain why it only accumulates in certain neurons that contain glutamate receptors and not others.

One indicator of Alzheimer's disease is the accumulation of amyloid plaques between nerve cells in the brain. Because the beta-amyloid stimulates an abnormal flow of calcium into the interior of the neuron, it makes a glutamate-sensitive neuron even more sensitive to excitotoxins (aspartate and glutamate), which allows the neuron to be excited to death. Therefore, these findings show that high concentrations of glutamate and aspartate in neuritic plaque are causing these neurons to die (Blaylock, 1997).

There are specific types of proteins found in high concentrations in the brains of individuals with Alzheimer’s disease. The immunological staining test that is done to determine the degree of concentration of these proteins is ALZ-50. Exposing cultures of normal neurons from the hippocampus to high concentrations of glutamate below that which can kill neurons showed a marked increased in the modification of the color of these neurons. Apparently, concentrations of glutamate and aspartate can also increase the immunoreactive staining, which lead researchers to believe that lower concentrations of food excitotoxins, such as Aspartame, can result in the same specific immunoreactive stain changes seen in Alzheimer’s disease (Blaylock, 1997; Mattson, 1990).

Wanting to retest the results, Umberto De Boni and D.R.C. McLachlan then added glutamate-blocking drugs to the culture medium and the results showed the effects caused by the glutamate and aspartate were completely blocked, suggesting that the excitotoxin was causing the destruction. These researchers showed that by exposing neurons to glutamate or aspartate they could induce paired helical filaments almost identical to those seen in individuals suffering with naturally occurring Alzheimer’s disease. The destruction was dose-dependent, showing that the higher the level of excitotoxins, the greater the damage (Sindou, 1992). Researchers also noted that the beta-amyloid acted through all three subtypes of glutamate receptors, NMDA, quisqualate, and kainite (Blaylock, 1997).

These findings proved that glutamate and aspartate can induce the same immunoreactive proteins found in Alzheimer’s disease, and once the neurons begin to destruct, they create abnormal proteins in the form of beta-amyloid. The effect is dose-dependent; the amount of excitotoxins determines the level of beta-amyloid protein present. This in turn, can further enhance the toxicity of glutamate and aspartate. The more plaques that are formed, such as beta-amyloid, the more sensitive surviving neurons are to the excitotoxins.

What this all means is that if an individual unknowingly has the beginnings of Alzheimer’s disease and consumes Aspartame found in diet soda, sugar-free candies, artificial sweetener, medication, supplementation, or any other products, they have subjected themselves to further exposure of excitotoxins that will accelerate the process that leads to full-blown Alzheimer’s disease. Below, shown in Table 1, you see the progress of 129 Aspartame consumers with what was diagnosed as Aspartame-associated memory loss.

 

Table 1: FDA Data on 129 consumers with Aspartame-associated memory loss

SEX	INDIVIDUALS	PERCENTAGE
Female	109	84.5%
Male	20	15.5%
RACE	INDIVIDUALS	PERCENTAGE
White	43	33.3%
Nonwhite	0	0%
Unknown	86	66.7%
AGE GROUPS (years)	INDIVIDUALS	PERCENTAGE
1-19	6	4.7%
20-29	11	8.5%
30-39	28	21.7%
40-49	21	16.3%
50-59	13	10.1%
60+	12	9.3%
Unknown	38	29.4%

Note. Dr. Linda Tollefson (FDA’s Assistant Commissioner for Science) provided information on 129 consumers who complained to the FDA about memory loss while using Aspartame products. Chart Illustration from Aspartame Disease: An Ignored Epidemic -- by Dr. HJ Roberts, MD, FACP, FCCP.

 

One of the most important advancements in medical technology has been the positron emission tomography (PET). It is the fastest-growing and accepted nuclear medicine tool in medicine today and is noninvasive. Its scanning technique utilizes small amounts of radioactive positrons (positively charged particles) to visualize body function and metabolism. Physicians first used PET to obtain information about brain function, and to study brain activity in various neurological diseases and disorders including stroke, epilepsy, Alzheimer's disease, Parkinson's disease, and Huntington's disease. Doctors are able to evaluate patients for cancers of the head and neck, lymph system, skin, lungs, colon, breast, and esophagus. PET can also evaluate heart muscle function in patients with coronary artery disease or cardiomyopathy.

Because of PET, scientists can actually watch the brain function and metabolize glucose for energy. With all this new technology, doctors have confirmed their beliefs that Alzheimer’s disease does not happen overnight as a result of sudden loss of massive amounts of neurons, but rather as a creeping death of the brain over decades (Blaylock, 1997). PET has allowed the scientists to rule out certain preconceptions of how Alzheimer’s disease is caused. It was once believed that infectious malformed proteins, prions, could infect the brain and cause a slow die-off of cells that would lead to Alzheimer’s disease (Whitehouse, 1986). However, there seems to be a problem with this hypothesis. Prions tend to affect widespread areas of the brain rather than selected sites and they found symptoms not related to Alzheimer’s disease. The theory of abiotrophy is not convincing because only very specific brain cells are seen dying and other cells adjacent to these dying cells are completely healthy. Something is targeting the neurons, and that something can distinguish these neurons from others. Moreover, that something may be an environmental neurotoxin causing these neurons to die.

Excitotoxins, such as aspartate and glutamate, excite the brain rather than calm it down (Blaylock, 1997; 2005). They stimulate the formation of free radicals within exposed neurons that, in turn, can trigger the release of even higher levels of glutamate within the brain. This results in even greater damage and shows us that once this cascade of damage begins, it becomes self-generating (Breitner, 1994). It is important to keep in mind that most studies that are done to understand how excitotoxins (glutamate and aspartate) affect neurons in the brain and their toxic effects are executed by using very high doses. The reason for this is that technology today to detect low level damage requires special equipment and researchers may not have the specialized tools to observe the effect of prolonged exposure to lower doses. Nevertheless, they do know that neurons exposed to low dosages of excitotoxins in a dose-dependent manner in rat hippocampal and septal cell cultures produced identical changes in the dendrites of neurons seen in an individual with Alzheimer’s disease (Mattson, 1992). Unlike most animal studies, where glutamate and aspartate are used over short terms to produce results of excitotoxin damage, human exposure may persist over decades, even a lifetime (Mattson, Cheng, Davis, Bryant, Lieberburg, & Rydel, 1992). People consume foods containing glutamate and aspartate without any knowledge of its ability to kill.

Glutamate and aspartate are commonly used as metabolic fuels and as neurotransmitters, however, when the concentration of these excitotoxins elevates to a crisis level and are not carefully regulated, toxic amounts will build up and destroy specific neurons. To prevent glutamate accumulation from happening, the brain has a pump system that pumps excess glutamate found in the extracellular fluid around the neurons into the surrounding glial cells. As it enters the glial cells, there are special enzymes that deactivate the glutamate from producing any further damage. When this protective system fails due to the lack of ATP, the glutamate begins to accumulate and stimulate the receptors on the surface of the cell membrane, which allows calcium to pour into the cell damaging the mitochondria (Blaylock, 1997).

When the brain begins to deplete its ATP the body experiences hypoglycemia or low blood sugar. The brain uses more glucose in twenty minutes of deep concentration than the body does in one hour of physical activity and consumes over 25% of all the glucose used in the body. Under normal conditions, the brain absorbs twice as much glucose as it uses. This offers a large measure of protection under conditions where the brain’s energy needs are greatly increased, such as with seizures and during the early stages of brain injury or when excitotoxins deplete the brain of ATP. Unfortunately, it cannot store this energy and when the brain becomes hypoglycemic, it begins to fail rapidly. When there is a lack of sugar to the brain, then designated parts of the brain begin to die. These same areas of the brain are also destroyed when large dosages of excitotoxins are introduced.

 

Figure 12. Areas of the brain affected by Alzheimer’s and other dementias. These areas of the brain are most sensitive to excitotoxins damage. Illustration from Nucleus Medical Art.

 

The brain damage caused by severe hypoglycemia in the presence of Aspartame is a result of the failure of these protective mechanisms and not from a lack of fuel to the brain cells themselves (Lindvall, 1988). Scientists have also noted the same damage to the brain if oxygen is removed. It appears that what ever the cause of the energy failure, the result is identical. Glutamate accumulates in the brain in high levels and destroys glutamate–sensitive neurons (Benveniste, 1984). However, the reversal of this situation can actually protect the brain and herein lies a huge misunderstanding.

Aspartame and MSG are flavor enhancements that are often used to prepare foods that have few or close to zero amounts of carbohydrates. If an individual is consuming Aspartame and/or glutamate-laden foods, and other foods containing carbohydrates, the fuel from the carbohydrates will protect the neurons from hypoglycemic destruction. However, most individuals using Aspartame as an artificial sweetener are primarily concerned about not consuming carbohydrates. A diet soda or NutraSweet® /Equal® packet used in sweetening coffee or other consumable products are usually void of carbohydrates or have very low levels to assist with feeding the brain the necessary fuel it needs to function. Therefore, there is no protection to the neurons to help them with the needed energy to stay afloat as they begin to swell up with calcium and begin to burst.

While glucose can reduce the amount of neuron damage caused by high doses of glutamate and aspartate, the protection is not complete. Cellular damage still occurs, but to a much lesser degree. Chronic exposure to high levels of glutamate or aspartate will cause less brain injury when an individual is consuming adequate levels of carbohydrates; nevertheless, accumulative damage over many years may be substantial.

 

Figure 13. When there is enough energy or ATP within the neuron, they are resistant to excitotoxins. However, when the energy or ATP runs out, the neurons become vulnerable at even low dosages. Illustration by Dr. Russell L. Blaylock, M.D.

 

There are many deleterious consequences to a decreased ATP production including increased free radical production and oxidative stress. Cytochrome oxidase is an oxidizing enzyme found in the mitochondria (Parker, 1990). It is extremely important in cellular respiration as an agent of electron transfer from certain cytochrome molecules to oxygen molecules. Individuals with Alzheimer’s disease have neurons that are defective in the delivery of glucose to the brain. Recently, it has been demonstrated that there is a 50% reduction of cytochrome oxidase in platelets of patients with Alzheimer's disease. The deficiency of this key energy-metabolizing enzyme could reduce energy stores and could contribute to brain dysfunction and neurodegenerative processes associated with Alzheimer’s disease (Mutisya, Bowling & Beal, 1994). In Parkinson’s disease, an enzyme that is predominately deficient in the mitochrondria is Complex I (Schapira, Cooper, Dexter, Clark, Jennery & Marshen, 1990). There are a number of studies that show a decrease in complex I activity in peripheral tissues affected by Parkinson’s disease (Schapira, et al. 1990). Mitochondrial ATP production is a foundation for health and it is necessary for physical strength, stamina and consciousness. Because the mitochondria produce most of the currency used by the body, cells with a high metabolic rate, such as heart muscle cells, may contain many thousands of mitochondria while other cells may contain only dozens. Even subtle deficits in mitochondrial function can cause weakness, fatigue, and cognitive difficulties. Excitotoxins that create neurotoxicity can strongly interfere with mitochondrial function and are potent poisons (Cooper & Schapira, 1997).

The pyruvate decarboxylation reaction links glycolysis and the citric acid cycle. This reaction is the conversion of pyruvate into acetyl CoA. The pyruvate decarboxylation reaction is catalyzed by the pyruvate dehydrogenase complex. In 1985, Dr. Kwan-Fu Rex Sheu and his coworkers produced evidence that the pyruvate dehydrogenase complex is inhibited in calcium-loaded cerebrocortical mitochondria. Impairment of mitochondrial function happens because of calcium-loading and is one of the significant events that leads to neuronal death after an ischemic insult. Pyruvate dehydrogenase is an important metabolic enzyme found to be deficient with Alzheimer’s disease. Once again, without ATP to bail the calcium out of the swelling neurons due to aspartate and other excitotoxins holding the calcium channel open, it is inevitable that the neuron will be excited, expand and explode (Lai, DiLorenzo, Sheu & Rex, 1988).

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