Excitotoxins, Neurodegeneration and Neurodevelopment
By Russell L. Blaylock, M.D
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. As stated, 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 would be expected to increase hypothalamic levels as well. One of the earliest and most consistent findings with exposure to MSG is damage to an area of the hypothalamus 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 other 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.44 This would be the situation seen when individuals consume, on a daily basis, foods high in the excitotoxins - MSG, aspartame and L-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 continuous 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.45 But, not only is the adjacent brain vulnerable, but the openings act as points of entry, eventually exposing the entire brain to potentially toxic levels of glutamate. Several clinicians have remarked that their MS patients 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.46
Recently, it has been shown that not only can free radicals open the blood-brain barrier, but excitotoxins can as well.47 In fact, glutamate receptors have been demonstrated on the barrier itself.49 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, creating a vicious cycle.
Thursday, August 7, 2008
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