The following is the third and final piece of a three part series that comprises a white paper report on Nutritional Protection Against Excitotoxins. In this series we explore the importance of nutrition in protecting the body and brain from harmful toxins and free radicals. To read the complete report on Nutritional Protection, click to download. This is for reference only, all rights are reserved.
Research now shows us that as we age our cells, including neurons, lose a significant amount of their ability to generate energy. Most cells generate the majority of their energy from electrons passing through a series of enzymatic reactions within the mitochondria, known as the electron transport chain. These electrons are derived from the breakdown of glucose in the kreb’s cycle.
The various steps in energy generation by the electron transport chain have been designated Complex I through V as listed in the table below:
Electron Transport Chain:
- Complex I-NADH – Ubiquinone oxidoreductase
- Complex II – Succinate: ubiquinone oxidoreductase
- Complex III – ubiquinonl: ferricytochrome c oxidoreductase
- Complex IV – ferrocytochrome c: oxygen oxidoreductase
- Complex V – ATP synthease
Anything that blocks one of these enzymatic steps severely interferes with the cells’ ability to produce energy, primarily in the form of ATP. But to better understand how energy deficits occur we must go back one more step.
Even before energy production declines another process begins to develop as we age — the cells begin to accumulate free radicals in larger amounts. We know that free radicals can damage cell membranes, intracellular components, and even the DNA itself. One reason for all of this increase in free radicals is the reduction in the cell’s protection mechanisms. For example, we know that all cells contain three antioxidant enzymes–glutathione, catalase, and superoxide dismustase — as well as a multitude of scavenging vitamins and minerals (Vitamins C, E, K, beta carotene, selenium, magnesium, and zinc). Even co-enzyme Q10 acts as a powerful free radical scavenger and a regenerator of antioxidants vitamin C and E.
As we age, there is a progressive decline in reduced glutathione, as well as the other antioxidants, within the cellular environment. 3 This is partly due to the increased production of several oxygen radicals, such superoxide and the hydroxide radical, which in essence overwhelm the antioxidant enzymes. A combinatimon of decreased availability of the antioxidant enzymes, depletion of the dietary antioxidants, and increased generation of free radicals puts all cells at considerable risk of serious injury or death.
In humans, we know that lipid peroxidation, a process of free radical injury to cell membrane lipids, results in the accumulation of “age” pigments within the brain called lipofuscin. Animals fed diets low in vitamin E develop a dramatic increase in these “age” pigments. 4 Vitamin E supplementation dramitically reduces brain lipofuscin.
One of the early finding in Parkinson’s disease, is a dramatic fall in the glutathione levels within the neurons of the primary area of the brain affected, the substantia nigra. This is accompanied by a buildup of peroxides and the dangerous hydroxide radical. Iron accumulation within the affected neurons act as powerful free radical generators as well. A recent study also indicated that there may be an accumulation of copper in addition to iron. 5 Copper, too, is a powerful generator of free radicals. Interestingly, iron is also known to be increased in the frontal lobes in cases of Alzheimer’s disease. 6 And, as one could expect, there is an increase in lipid peroxidation in cases of Alzheimer’s disease. Microscopically, free iron seems to concentrate in and around the neuritic plaques common to Alzheimer’s disease patients.
The buildup of free radical within the neurons with aging not only affects energy production (complex I is especially sensitive to damage by free radicals) but also produces sever damage to the mitochondrial DNA. 7 Cells posses two types of genetic material. One found in the nucleus (most think of this) and another within the mitochondria. The latter is responsible for reproduction of the mitochondria within the cell.
Damage to the mitochondrial DNA affects only the involved mitochondria and not the genetics of the cell itself. But, when that mitochondria reproduces itself the defect is passed on to the new mitochondria as well. In today’s time, we know that there is a growing list of diseases caused by mitochondrial dysfunction. We know that many of these diseases do not present themselves until later childhood or even adulthood. The explanation for this may lie in the fact that until greater than 60% of the mitochondria are affected no disease occurs. That may take many years or even decades.
It is known that mitochondrial DNA mutates at a rate ten times that of chromosomal DNA. 8 Most likely this is because the former lacks histones and repair enzymes. An interesting study was done by Dr. Allen C. Bowling that demonstrated an age dependent impairment of electron transport chain enzymes in the primate cortex. 9 They found that complex I and IV in the brain were especially vulnerable to age-related damage; these are the same two complexes damaged in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disorder. A portion of these two complexes are encoded in the mitochondrial DNA. Complex II, III, and V were preserved, this is not surprising, since they are encoded by the chromosomal DNA only. Complex I is known to be very sensitive to destruction by the hydroxl radical and complex IV to peroxide.
It is also important to note that glutamate not only damages the microtubules within the dendrites, even in lower doses, but it also damages the DNA as well. 10 Dr. S.E. Shepard, in a recent study, found that aspartame (NutraSweet), when nitrosated in the stomach, shows a significant mutagenicity, 11 causing damage to the genetic structure of the cell. In fact, they found that the nitrosated aspartame was quite toxic to cells themselves.
Protection For Our Neurons Against Free Radicals
Since the primary defect causing neurons to have difficulty generating energy is related to free radical generation, our primary concern should be to restore the cell’s ability to combat these accumulating free radicals. There are several things we can do.
Multiple Vitamins Vs. Single Antioxidant Vitamins:
It is better to take several different types of antioxidants. There are many different types of free radical–peroxides, hydroxide radical, superoxide, and singlet oxygen. The antioxidants each specialize in removing specific types of free radical. For example, vitamin E scavenges in the propagation phase of lipid peroxidation. But, for most forms of vitamin E, it does so only in the lipid fractions of the cell, that is the fatty membranes. Water soluble vitamin E appears to concentrate in the cytosol of the cell as well. Coezyme Q10, on the other hand, blocks both the initiation as well as the propagation of lipid peroxidation.
Vitamin C and beta carotene block free radicals within the watery parts of the cells (cytosol) and in the space out the cell (extracellular space) but not in the lipid membranes. It is also important to note that vitamin C and coenzyme Q10 can recycle vitamin E, thereby restoring its antioxidant function. 12 Glutathione also recycles vitamin C.
It is for these reasons that the antioxidant vitamins and minerals should be taken in combination. Clinical studies confirm this.
Free Radical Generators
We must emphasize that all excitotoxins — glutamate, aspartate, and L-cysteine–stimulate large amounts of free radicals within exposed neurons. In all cases, we know that excess excitotoxic stimulation results in the buildup of free radicals within the involved neurons. Catherine Bergeron has stated that the best theory for excitotoxity in ALS was that it initiated oxidative stress and the arachidonic cascade (by phospholipase A2), therefore generating large concentrations of free radicals in the anterior horn cells of the spinal cord. 13 In time, this results in the progressive death of motor nuerons and the onset of progressive weakness.
There are many similar scenarios carried out in the other neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases. In all cases, it has been shown that excess excitotoxic stimulation results in the buildup of free radicals within the involved neurons, eventually overwhelming the cell’s ability to neutralize these harmful items.
Stimulation of Mitochondrial Energy Production
Once we have corrected the problem of excess free radical generation, we are still left with damaged mitochondria that lack the ability to produce a sufficient amount of energy for normal functioning and survival. Research has shown that there is a growing list of mitochondrial diseases that are being recognized. Up until just recently, treatment for these diseases were hopeless. What changed this was the realization that these are metabolic defects and that by manipulating the cell’s metabolism one could correct some of these defects.
Early treatment involved the use of riboflavin and L-carnitine. The end results were surprising. Many patients became functionally independent for the first time.
Enter Coenzyme Q10
Research has shown us that certain mitochondrial toxins can mimic these type of disorders. Dr. Flint Beal conducted a study, using animals, and found that if the animals were given a mitochondrial toxin they developed lesions deep in their brains. 14 However, if the animals were treated beforehand with the coenzyme Q-10 the lesions could be prevented.
Conclusion
It is becoming extremely evident that most if not all of the neurodegenerative diseases of the central nervous system begin with an impaired energy production system. This in return, leaves the neuron vulnerable to excitotoxin injury. By using nutritional products to increase mitochondrial energy production this final destructive step in prevented.
If you missed Part One: “Bad Eicosanoids” or Part Two: “Omega 3 Fatty Acids” of this series, click the corresponding title to view. Don’t forget to place your order for high quality BioVeda supplements that may help mitigate the potential damage that bad eicanosoids may be causing on your brain and body.
Krill Oil : Top Notch Antioxidant Protection — krill oil contains the unique antioxidant which may protect you from damaging free radicals. Past evidence has shown us that phospholipids are the safest and most effective carriers of DHA and EPA. Sadly though, standard fish oils and some low quality krill oil brands lack the phospholipid complex. Instead they contain omega-3 in the free-triglyceride form. This is less beneficial form. Phospholipids are the building blocks of your cell membranes; they regulate cellular transport and act like the “gate keepers of the cell.” This means that they protect the cell membrane from free radical attacks. If that’s not enough important facts, the most dominant phospholipid in krill oil is phosphatidyl choline, which is slightly composed of choline. Choline has been shown to be crucial in brain development, learning and memory. We also know that choline is important for fetal and infant brain development. Choline is the much needed neurotransmitter acetylcholne (this sends nerve signals to the brain) and trimethylglycine, a highly acclaimed liver protecter.
Fish Oil: EPA/ DHA is an essential fatty acid which stands for docosahexaenoic acid and eicosapentaenoic acid. This essential fatty acid is an Omega 3 fat, which is usually found in cold water fish. EPA/ DHA are highly unsaturated fat because they contain 6 and 5 double bond’s on their long structural chain. These polyunsaturated fats play a very important role with the function of our bodies. EPA and DHA are vital nutrients and may be taken to maintain healthy function of the following: Brain and Retina- DHA is a building block of tissue in the brain and retina of the eye. It helps with forming neural transmitters, such as phosphatidylserine, which is important for brain function. DHA is found in the retina of the eye and taking DHA may be necessary for maintaining healthy levels of DHA for normal eye function. Mega EPA/DHA is something everyone can benefit from!
Cell Manna: Complete Cellular Whole Food Support – Cell Manna is unlike any other product on the market due to its anti-aging benefits. With over 80 different ayurvedic and Korean herbs, this product’s key benefits are anti-aging, hormonal balance, and overall harmony. Cell Manna was created to provide the nutrients to the cells within the body. We call this micro nutrition which is used to feed specific cells you are targeting (ex. Liver, kidney, etc.). Taken by itself it is an overall rejuvenator for every cell within the body.
CoQ Support: CoQ10 has been available for decades, but now there is an amazing new form of Co Q10 called ubiquinol. Why is this so beneficial? CoQ10 is one of the key elements in the aging process and free radical production. These free radicals are oxygen atoms deficient in electrons that become highly reactive. This in turn causes potential damage to your tissues and DNA. If there was something you could do to limit the free radical production, then you could change the aging process. One nutrient that can help you do just that is Co Q10. The problem is your body requires the reduced form of Co Q10 (ubiquinol) to help you limit free radical production. If you’re younger than 25 years old, this isn’t an issue because your body is capable of converting Co Q10 from the oxidized to the reduced form. but, if you’re older, your body becomes more and more challenged to convert the oxidized Co Q10 to ubiquinol. Another very important reason for using a Co Q10 supplement is to help boost your body’s cellular energy production. Co Q10 helps facilitate the production of adenosine triphosphate (ATP), the energy “currency for all your cells. But if you’re over 25, you need the reduced form of Co Q10, ubiquinol, to efficiently do this. So even if you do your best to eat a healthy diet, your body’s ability to produce Co Q10 and convert it to ubiquinol declines over time.
*These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.
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