Excitotoxics (long) and Neuroendocrine Damage
wcsbeau at superior.carleton.ca
Thu Aug 12 07:11:27 EST 1993
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
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
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
>> 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
>>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
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-
>>... 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
>>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!
%% 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
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