Excitotoxics (long) and Neuroendocrine Damage

[OPIRG]

In          article           <16C1DCB70.SIMMS at vmd.cso.uiuc.edu>,
SIMMS at vmd.cso.uiuc.edu       writes:    
>      In      article <1993Jul30.154752.1 at vms.ocom.okstate.edu> 
banschbach at vms.ocom.okstate.edu writes:

>>Adults handle these amino acid imbalances fairly well  with  no
>>permanent damage.

The major areas of excitotoxic action are the arcuate nucleus  of
the hypothalamus, and the neurohypophysis (median eminence (ME)).
Without these neurons, or  with  substantial  necrosis  in  these
areas,  is  it unreasonable to expect interference with endocrine
function?

Given the major hormone that is effected  (Gonadotropin-releasing
Hormone  (GnRH)),and what it is responsible for, I don't think it
is unreasonable to predict/suspect that  chronic  adult  exposure
could  have  some kind of suppressive effect on, for example, the
control of ovulation in females, and the  control  of  libido  in
males,  given  what  GnRH does. Also, Terry, Epelbaum, and Martin
(1981) found immediate and persistant supression of  rhythmic  GH
secretion,  and  rapid  and transient release of prolactin, as an
effect of acute MSG exposure in adult male rats.  I'm no biochem-
ist,  but  it seems to me that this is not going to have *no* ef-
fect on behavior, for one,  particularly  certain  drive-oriented
behaviors.

>> Headaches and dizzyness are the main problems.   For  children
>>under the  age of 9 though, chronic exposure to phenylalanine,
>>aspartic acid or glutamic acid if they can  not  prevent  blood
>>level spikes from occuring after eating foods or beverages with
>>high amounts of these amino acids could  cause  permanant  brain
>>damage.

Yes.

<snip>

>>Just like PKU, only a very small population will not be able to
>>handle aspartic acid or glutamic acid but for these people, too
>>much aspartic acid (nutrasweet) or  glutamic  acid  (Monosodium
>>glutamate,  MSG)  before the age of 9 could cause serious ir-
>>reversiable brain damage.  This is why MSG is no longer allowed
>>in baby foods.

<Questions from Laura deleted to save bandwidth>

>>Laura, the placenta acts as a buffer to protect the  fetus  from
>>potential harm.   Even if the fetus has the genetic defect that
>>causes PKU and the mother drinks diet coke with nutrasweet,  the
>>placenta  will  protect the fetus from any elevation in maternal
>>blood levels of phenylalanine that may occur.  Humans have eaten
>>foods that are naturally high in phenylalanine, aspartic acid or
>>glutamic and the placenta has developed  metabolic  defenses to
>>protect  the  fetus.   It doesn't work as well against alcohol or
>>cocaine though.

Or thalidomide. Or a host of other componds. Or, if John Olney is
correct,  and  the literature bears him out, glutamate and aspar-
tate. And Madeline Price was adamant when I spoke with her a  few
weeks back, that aspartic acid can easily pass both the gut wall,
and the placenta. So spiking *can* occur, according to some medi-
cal researchers.

>>... aspartic acid, glutamic acid or  phenyalanine  blood  spikes
>>which  then cause an imbalance in brain neurotransmitters levels
>>are similiar to those  that  occur  in  adults.   Dizzyness  and
>>headaches  after consuming  food or beverages that contain high
>>amounts of these amino acids.

Both Glu and Asp have neurotransmitter functions in the mammalian
brain.  But I hadn't heard that phenylalanine is now considered a
putative neurotransmitter. Could you elaborate on this? (I rather
doubt it could be, given that anyone with PKU would automatically
be missing a neurotransmitter. Which seems *highly* unlikely.

>>An  occasional  jolt  of  aspartic  acid,   glutamic   acid   or
>>phenylalanine isn't going to hurt even a child who can not regu-
>>late the blood levels of these amino acids.

I'm afraid I'm going to have to disagree with you on that:  Olney
and others have clearly shown that acute spiking can cause severe
necrosis in the arcuate and the ME, within hours of exposure,  in
fetal  brain,  as  well as neonatal brain tissue. Check out Olney
(1988), see attached.

>> It's the chronic exposure during the first 9 years  of  life
>>that  leads  to  permanent  alterations in synapse formation that
>>spell real trouble (mental retardation).

The major affected areas are CVO's - circumventricular organs, and they
are  not in  areas  involved in cognition. The damaged areas govern
neuroendocrine functioning. Other effected areas include the visual
system in developing brain.

No doubt, however, chronic exposure is bound to have some form of
effect,  and likely at a lower dose than is needed to cause acute
damage.

>>A child who has an averse reaction to drinking  beverages  with
>>nutrasweet  or  consuming foods with a high MSG content (usually
>>soup) should not be exposed to either  MSG  or  nutrasweet  on  a
>>regular basis.  An older child can tell you that they don't feel
>>good after consuming nutrasweet or MSG but a  baby  can't.   MSG
>>and nutrasweet should never be added to infant foods.

Absolutely - well said!

>>Marty B.

%%  edited version of paper on excitotoxic 
%%  food  additives follows

*****************************************************************************
NEUROTOXIC  FOOD  ADDITIVES: A Call for Caution 

Copyright, C. Dianne Murray, 1992

Monosodium glutamate (or MSG),  Apartame,  and  hydrolysed  plant
protein  (HVP), all compounds containing free glutamate (Glu) and
aspartate (Asp), are excitotoxic food  additives  (Olney,  1988).
Despite  Glu's  and  Asp's proven neurotoxic and neuroteratogenic
effects, their use as additives remain mostly unregulated, except
for  MSG's in baby foods (Olney, 1988).  MSG and HVP are added to
processed and some restaurant foods to enhance flavors; aspartame
is  a  sugar substitute, widely used in diet drinks and desserts.
HVP is subject to no legal regulation and is now widely  used  in
products as a substitute for MSG (Olney, 1984,1988).

Glu and Asp are  the  active  compounds  in  MSG  and  Aspartame,
respectively  (Olney,  1984).  They are amino acids necessary for
protein formation, and they act as  excitatory  neurotransmitters
in  the  mammalian  CNS  (Carlson, 1985). Glutamate is one of the
most widely distributed excitatory neurotransmitters in  the  CNS
of  mammals  - glutamate receptors are distributed throughout the
brain (Carlson, 1985). Other excitatory amino acid receptors  in-
clude the n-methyl-d aspartate (NMDA) receptor, the most abundant
receptor in the mammalian brain,  according  to  Carlson  (1985).
The  NMDA receptor is the site of binding for aspartate.  Several
subtypes of glutamate receptors exist (Stewart, et. al., 1990).

Excitatory neurotransmitters are necessary to life, yet, in large
doses,  they are toxic. Excitotoxicity occurs when an substantial
excess of an excitatory compound (e.g. Glu or Asp), or an excito-
toxin  (e.g.  domoic  acid),  is  available to post-synaptic mem-
branes, causing too rapid and frequent depolarization and  firing
of  a neuron, and its subsequent death (Olney, 1988).  Excitotox-
ins include amino acids such as  glutamate,  aspartate,  cysteine
(Olney and Ho, 1970), and kainic acid, as well as their structur-
al analogues (such as domoic acid, a  food  poison  analogous  to
kainic acid and glutamate (Stewart, et. al, 1990)).

The blood-brain barrier protects the brain from  the  effects  of
most toxins circulating in the blood (Olney, 1988) but excitotox-
ins circumvent this protective system; they act on  some  of  the
circumventricular  organs  (CVO's),  areas  which lie outside the
blood-brain barrier, specifically the median eminence and the ar-
cuate  nucleus  of the hypothalamus, the pituitary gland, and the
area postrema (Olney, 1988). Different species exhibit  different
susceptibilities  to  Glu and Asp.; humans are the most sensitive
tested (Olney, 1984, 1988)). Sensitivity depends, in part, on ex-
posure,  and  exposure on uptake across the gut wall. Humans' are
very sensitive because they have the most  efficient  gut  uptake
for  these compounds; high levels of circulating excitotoxins are
thus quickly achieved after consumption. (Olney, 1988). Individu-
als show differences in susceptibility to excitotoxins.

Glu and Asp cause neuron death  in  developing  animals.  Age  is
negatively  correlated  with  sensitivity  to excitotoxins in the
diet, thus fetuses and infants are most  at  risk.  Olney  (1988)
found  effects within 4 hrs. of oral MSG administration in infant
mice. The effects of oral and subcutaneous doses of Glu  and  MSG
to  infants  are  summarized in Table 1. Similar effects would be
expected for Aspartame, since Aspartame is 50% Asp, and Asp expo-
sure  has been shown to cause similar neurological damage, mainly
in the arcuate nucleus of the hypothalamus (ANH), the median