excitotoxins, glutamate, glutamine and the Blood Brain Barrier

[Guest guest]

I couldn't agree with you more. Another MAJOR problem with our society

is the addictive behavior that people display, even in eating. You tell

someone that a substance is good for them, and they consume imbalanced,

unnaturally high amounts of it. Sometimes we miss the forest for the

trees, and I would admit that I did here. The fact is that seaweed from

pure sources IS a wonderful natural chelator. BUT, as practitioners, we

have the obligation to posit with our patients the caveat that too much

of it is NOT a good thing. One other thing, also to remember, I think,

is to think twice before recommending it to patients suffering from

neuro-degenerative diseases.

 

Thanks, and your wisdom is appreciated.

 

Yehuda

 

On Tue, 22 Feb 2005 13:16:13 +0000 " mike Bowser "

<naturaldoc1 writes:

>

> In the end it comes down to balance. We need to take a serious look

> at the

> modern diet as we no longer are consuming natural foods. Our

> commercial ag

> system has a lot to do with the changing of nutritional profiles of

> our

> food. We are getting more and more screwed up food. Glutamate as

> an

> additive known as MSG is problematic (different chemical) in food

> but I

> still do not see enough other concern for the amino acid glutamate,

> which is

> important for our well being.

> Mike W. Bowser, L Ac

>

> >Yehuda L Frischman <

> >

> >

> >Re: excitotoxins, glutamine, glutamine and the Blood

> Brain

> >Barrier

> >Tue, 22 Feb 2005 00:57:03 -0800

> >

> >

> >Dear Mike, George and alon,

> >

> >I did some research in respect to your concerns, particularly as to

> the

> >distinction between glutamine, which as a major fuel source for the

> brain

> >and and body(as a matter of fact, is the most abundant Amino Acid

> in the

> >body), readily crosses the Blood Brain Barrier, as George

> mentioned, and

> >glutamate, which does not easily cross the Blood Brain Barrier.

> And even

> >if you want to dispute the glutamine/glutamate cycle, glutamate has

> >other ways of getting into the brain anyway! There are 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. Glutamate actually

> is an

> >important neurotransmitter in the hypothalamus. But careful

> regulation of

> >blood levels of glutamate is critical, since high

> bloodconcentrations of

> >glutamate increase hypothalamic levels as well, and exposure to MSG

> >damages 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. Furthermore, 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 recent studies have shown

> 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 would be the case when individuals

> consume, on

> >a daily basis, foods high in the excitotoxins - MSG (seaweed) ,

> aspartame

> >(Nutrasweet) and L- cysteine(food additives). Though experiments

> cited

> >by defenders of MSG safety were conducted to test the efficiency

> of the

> >BBB acutely, these did not explore the chronic, long term

> bombardment of

> >the BBB by them . 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 to the traditional

> >Oriental diet as well, but certainly not in as high

> concentrations.(I

> >would be glad to cite the references if anyone requests)

> >

> >Furthermore, studies have 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, creating a vicious cycle.

> >

> >

> >Yehuda

> >

> >

> >On Mon, 21 Feb 2005 17:56:57 +0000 " mike Bowser "

> ><naturaldoc1 writes:

> > >

> > > This edition was published in 2005 and shows a very interesting

> > > relationship

> > > between plants/bacteria that produce glutamate and animals that

> > > consume this

> > > and change it into glutamine. Their is a cycle here. This

> reminds

> > > me of

> > > glucose or oxygen and that plants produce it and we consume it.

> I

> > > guess we

> > > have a need for them after all.

> > > Mike W. Bowser, L Ac

> > >

> > > >George Mandler <gmandler

> > > >

> > > >

> > > >Re: excitotoxins and glutamine vs glutamine

> > > >Mon, 21 Feb 2005 08:12:32 -0500

> > > >

> > > >

> > > >

> > > >On Feb 21, 2005, at 12:37 AM, mike Bowser wrote:

> > > >

> > > > >

> > > > > Something here does not seem right. In my biochem text it

> is

> > > > > mentioned

> > > > > (4th ed of Principles of Biochemistry by Lehninger) that

> > > pathways are

> > > > > discussed for glutamine production from glutamate.

> > > >

> > > >Yeah but that textbook is probably circa 1999?? so our bodies

> now

> > > work

> > > >differently in 2005 and the later textbooks reflect these

> > > physiological

> > > >changes. ;-) ;-)

> > > >

> > > >No glutamine/glutamate is a cycle. One gets converted to the

> other

> > > and

> > > >vice versa. I don't think you can get glutamate across a

> membrane,

> > > so

> > > >glutamate is used intracellulary and glutamine extracellulary...

> > > >

> > > >--george

> > > >

> > > > >

> > > > >> Yehuda L Frischman <

> > > > >>

> > > > >>

> > > > >> excitotoxins and glutamine vs glutamine

> > > > >> Sun, 20 Feb 2005 15:14:44 -0800

> > > > >>

> > > > >>

> > > > >> Yehuda

> > > > >> Are you saying that glutamate (i.e. the salt of glutamine)

> is

> > > more

> > > > >> harmful than glutamine? Glutamine in the major source of

> > > nutrition for

> > > > >> the gut and is a necessary excitatory amino acid for the

> brain.

> > > We

> > > > >> need

> > > > >> both excitatory and inhibitory systems and precursors. Very

> high

> > > > >> doses on

> > > > >> glutamine are often recommended in nutritional medicine both

> > > for the

> > > > >> gut

> > > > >> and brain.

> > > > >>

> > > > >>

> > > > >>

> > > > >>

> > > > >> Dear Alon,

> > > > >>

> > > > >> Rather than answer your question personally, let me defer

> to Dr.

> > > > >> Russell

> > > > >> Blaylock, board certified neurosurgeon, whose major work on

> > > > >> excitotoxins

> > > > >> I mentioned in an earlier post and who is quoted on the

> site:

> > > > >> http://www.mercola.com:

> > > > >>

> > > > >>

> > > > >>

> > > > >> Is

> > > Glutamine

> > > > >> Supplementation Helpful or Harmful?

> > > > >>

> > > > >> Dr. Mercola's Comment:

> > > > >>

> > > > >> Glutamine is an amino acid that makes up the majority of our

> > > skeletal

> > > > >> muscle. There is some controversy over whether oral

> glutamine

> > > > >> supplementation is toxic or helpful to healthy people. In a

> past

> > > > >> article,

> > > > >> Dr. Robert Crayhon expressed the view of many natural

> medicine

> > > > >> experts,

> > > > >> " After reviewing the literature, I am unconvinced that

> > > high-dose oral

> > > > >> glutamine supplementation is toxic to neurons in healthy

> > > persons. "

> > > > >>

> > > > >> However, Dr. Russell Blaylock, a board-certified

> neurosurgeon

> > > and

> > > > >> author

> > > > >> of the highly recommended Excitotoxins: The Taste that Kills

> > > wrote in

> > > > >> to

> > > > >> me with another viewpoint and his response is below.

> > > > >>

> > > > >>

> > > > >>

> > >

> ----

> > > > >> ---

> > > > >> -------

> > > > >>

> > > > >> By Russell L. Blaylock, M.D.

> > > > >> Advanced Nutritional Concepts, LLC.

> > > > >>

> > > > >> Dr. Robert Crayhon posted comments on this site indicating

> that

> > > I was

> > > > >> terribly mistaken in my caution concerning the use of

> glutamine

> > > and

> > > > >> that

> > > > >> he had consulted several " cell biologists " who were also

> > > concerned

> > > > >> with

> > > > >> my statements on glutamine safety. In fact it was stated

> that I

> > > > >> apparently did not understand that glutamine was not an

> > > excitotoxin

> > > > >> and

> > > > >> was not converted into an excitotoxin.

> > > > >>

> > > > >> Of course, I never stated glutamine was an excitotoxin, but

> I

> > > do state

> > > > >> that it is converted into the excitotoxin glutamate within

> > > neurons.

> > > > >> Numerous recent studies as well as Siegel’s Basic

> Neurochemistry

> > > > >> textbook

> > > > >> emphatically state that the major source of glutamate is

> from

> > > > >> glutamine

> > > > >> in the brain. Normally, when the brain finishes using

> glutamate

> > > for

> > > > >> chemical communication between brain cells at the synapse

> the

> > > > >> glutamate

> > > > >> is taken up by surrounding glial cells and changed by the

> enzyme

> > > > >> glutamine synthease into glutamine, where it is stored.

> > > > >>

> > > > >> The Problem With Excitotoxins

> > > > >>

> > > > >>

> > > > >> The glutamine is then transported to the neuron and by the

> > > enzyme

> > > > >> glutaminase, it is converted to glutamate--the potential

> > > excitotoxin.

> > > > >> I

> > > > >> say potential because unless it accumulates outside the

> brain

> > > cell it

> > > > >> is

> > > > >> harmless.

> > > > >>

> > > > >> This is the major source of glutamate within the brain.

> > > Excitotoxins

> > > > >> are

> > > > >> usually amino acids, such as glutamate and aspartate. These

> > > special

> > > > >> amino

> > > > >> acids cause particular brain cells to become excessively

> > > excited, to

> > > > >> the

> > > > >> point they will quickly die. Excitotoxins can also cause a

> loss

> > > of

> > > > >> brain

> > > > >> synapses and connecting fibers. Food-borne excitotoxins

> include

> > > such

> > > > >> additives as MSG, aspartame, hydrolyzed protein and soy

> protein

> > > > >> extract.

> > > > >>

> > > > >> In two recent studies it was found that the amount of

> glutamine

> > > in the

> > > > >> brain could predict the brain damage seen both in pediatric

> > > brain

> > > > >> injuries and brain damage secondary to seizures. Adding

> large

> > > amounts

> > > > >> of

> > > > >> glutamine to the diet increases significantly brain levels

> of

> > > > >> glutamine

> > > > >> and, hence, glutamate. Another study found that by adding

> > > glutamine to

> > > > >> the diet of animals exposed to another powerful excitotoxin

> > > called

> > > > >> quinolinic acid, brain cell damage was increased

> significantly.

> > > > >> Quinolinic acid is known to accumulate in the brain in most

> > > cases of

> > > > >> viral brain infection as seen with HIV dementia and viral

> > > > >> encephalitis.

> > > > >>

> > > > >> Glutamine and Liver Toxicity

> > > > >>

> > > > >>

> > > > >> Individuals with liver toxicity tend to accumulate ammonia

> in

> > > their

> > > > >> blood

> > > > >> and brain. Until recently, it was assumed that it was the

> > > ammonia that

> > > > >> caused liver disease-associated brain injury and that

> glutamine

> > > was

> > > > >> protective.

> > > > >>

> > > > >> Newer studies indicate that actually it is the glutamine

> that is

> > > > >> causing

> > > > >> the brain’s injury. Increasing glutamine in the diet would

> > > > >> significantly

> > > > >> aggravate this damage.

> > > > >>

> > > > >> Free Radicals in the Brain

> > > > >>

> > > > >>

> > > > >> Glutamine accumulation has also been found in Alzheimer’s

> > > disease,

> > > > >> Huntington’s disease and high levels of brain glutamine have

> > > been

> > > > >> associated with a worse prognosis in Lou Gehrig’s disease.

> > > Likewise,

> > > > >> recent studies have shown that high brain glutamine levels

> > > increase

> > > > >> brain

> > > > >> levels of free radicals and impair the ability of brain

> > > mitochondria

> > > > >> to

> > > > >> produce energy. When the brain produces low energy,

> > > excitotoxins,

> > > > >> such as

> > > > >> glutamate, become even more toxic. It has been shown that

> the

> > > reason

> > > > >> for

> > > > >> glutamine toxicity under these conditions is because it is

> > > converted

> > > > >> to

> > > > >> the excitotoxin--glutamate.

> > > > >>

> > > > >> Glutamine and Multiple Sclerosis

> > > > >>

> > > > >>

> > > > >> Of particular concern is the finding that people with

> multiple

> > > > >> sclerosis

> > > > >> have increased levels of the enzyme glutaminase (the enzyme

> that

> > > > >> converts

> > > > >> glutamine into glutamate) in areas of nerve fiber damage.

> High

> > > levels

> > > > >> of

> > > > >> glutamine in the diet would increase glutamate levels near

> these

> > > > >> injured

> > > > >> areas magnifying the damage. It has been shown that

> > > excitotoxicity

> > > > >> plays

> > > > >> a major role in multiple sclerosis by destroying the cells

> > > > >> (oligodendrocytes) that produce myelin.

> > > > >>

> > > > >> Glutamine and Pregnant Women

> > > > >>

> > > > >>

> > > > >> Another area of concern would be pregnant women. Glutamine

> > > passes

> > > > >> through

> > > > >> the placenta and may actually be concentrated in the baby’s

> > > blood,

> > > > >> producing very high levels. Glutamate plays a major role in

> the

> > > > >> development of the baby’s brain. Excess glutamate has been

> > > shown to

> > > > >> cause

> > > > >> significant impairment of brain development in babies and

> can

> > > lead to

> > > > >> mental retardation.

> > > > >>

> > > > >> When to Use Glutamine

> > > > >>

> > > > >>

> > > > >> The major use for high-dose glutamine would be to repair

> > > > >> gastrointestinal

> > > > >> injury. In such cases, I would recommend short-term use

> only.

> > > Those

> > > > >> with

> > > > >> a history of the following conditions should avoid

> glutamine,

> > > even for

> > > > >> short-term use:

> > > > >>

> > > > >> Stroke

> > > > >> Neurodegenerative disease

> > > > >> Pregnancy

> > > > >> Malignancy

> > > > >> Recent vaccinations

> > > > >> ADHD

> > > > >> Hypoglycemia

> > > > >> Autism

> > > > >> Multiple sclerosis

> > > > >> Other neurological disorders

> > > > >>

> > > > >> Glutamine has recently been shown to produce extreme

> > > hypoglycemia,

> > > > >> even

> > > > >> more so than leucine, which is known to produce fatal

> > > hypoglycemia in

> > > > >> infants.

> > > > >>

> > > > >> The reason Chinese Restaurant Syndrome is not seen with

> > > glutamine

> > > > >> challenge is that the glutamate receptors in the lungs and

> > > esophagus

> > > > >> are

> > > > >> stimulated by glutamate, not glutamine. The glutamine must

> be

> > > > >> converted

> > > > >> first and this occurs primarily in the brain.

> > > > >>

> > > > >> The only safe situation for glutamine use is in the vigorous

> > > athlete.

> > > > >> Glutamine is used as a muscle fuel, so that vigorous

> exercise

> > > will

> > > > >> consume most of the glutamine before it can accumulate in

> the

> > > brain. I

> > > > >> would still avoid long-term use in high doses. I would

> caution

> > > > >> readers to

> > > > >> avoid excess glutamine, especially in the above named

> > > conditions and

> > > > >> situations.

> > > > >>

> > > > >>

> > > > >> Yehuda Frischman

> > > > >>

> > > > >>

> > > > >> " When you see someone doing something wrong, realize that

> it was

> > > > >> brought

> > > > >> before

> > > > >> you because you did something similar. Therefore, instead of

> > > judging

> > > > >> him, judge yourself. "

> > > > >>

> > > > >> The Baal Shem Tov Hakodesh

> > > > >>

> > > > >>

> > > > >>