(plus other dietary/supplement info) Re: Lithium side effects/Inositol??

[Chinzilla]

one of the earliest effects of lithium is the observation that it inhibits an
enzyme called IMP or inosine monophosphatase. inositol phosphates are
secondary messengers that cause certain responses in the body. hormones, for
example, often use the secondary messenger pathway to elicit a bodily response
and therefore is able to influence a 'global' effect in the body.

lithium was originally thought to work by inhibiting inositol phosphate
formation and therefore blunting the signaling caused by inositol phosphates.
if you are taking inositol supplements maybe the docs may wonder how this will
affect effectiveness of lithium. however, a recent (1997) scientific paper
suggests that this may not actually be how lithium exerts its antimanic effect
- they found that valproic acid (depakote) does not influence inositol levels
yet valproic acid has antimanic properties. lithium and valproic acid work in
different mechanisms towards relieving manic depression and the effect on
inositol may be part of how lithium works but it is obviously not the total
contribution towards antimania.

i for one caution with supplementing the diet with massive doses of certain
amino acids (like glutamine, tyrosine, tryptophan, glycine) or other dietary
supplements that we can get in health stores simply because you are flooding
your body with abnormally large doses of only one kind of 'nutrient' and the
body has its ways of either responding/compensating or shutting down other
things that might cause more problems. for example, the cells in our bodies
'share' amino acid transporters. see it as 'carpooling', where a bunch of
amino acids take the same car to come into your cell. all amino acids which are
essential (we cannot make it from other nutrient precursors and must get it
from diet) share a little group of cars. if you flood your body with one or two
amino acids, automatically you deprive yourself of the rest because the excess
amino acids start inhibiting internalization of other amino acids. in
addition, you have to realize that many of these amino acids are
neurotransmitters by themselves (like glutamate or glycine) or are precursors
to neurotransmitters (like tyrosine and tryptophan)

i see the trend of people taking huge doses of vitamins and nutrients etc., and
i dont think most realize that this can be very dangerous when you dont know
how you are affecting your body. The derivatives of vitamins D and A, for
example, have often been used in cancer cell studies because these vitamins
stimulate cell growth, and in excess doses are able to transform cells from
normal to abnormal.

really talk with your doctor before taking any supplements in excess. just
because something is 'naturally' in our bodies doesnt mean its safe to take in
large amounts. thats why even our bodies monitor carefully how much it makes of
its own stuff.

jane

[TRex765849]

I had an interesting/scary experience relating to supplements lately. I've
been on Neurontin for the past 4.5 months and doing very well with it.
However, about a week and a half ago I started feeling like the meds were
losing their effectiveness. It also so happens that I had started
supplementing a pretty high dosage of zinc as a SODase (fights free radicals)
to help my immune system, etc. Well, to experiment, I stopped taking the zinc
and I started to feel better within 2 days. Now this is all very annecdotal
and unscientific, but I came across this article that might explain possibly
why I had this effect. It seems that zinc acts on the GABA receptors in the
brain--the same ones the GABApentin affect. Could it be that the high zinc I
was taking was competing with the Gabapentin for the GABA receptors in the
brain? Food for thought.

Be Well

--T

--------------------------

Neurobiol Dis 1997;4(3-4):137-169

Zinc metabolism in the brain: relevance to human neurodegenerative
disorders.

Cuajungco MP, Lees GJ

Department of Psychiatry and Behavioural Science, University of Auckland
School of Medicine, New Zealand.

Zinc is an important trace element in biology. An important pool of zinc
in the brain is the one present in synaptic vesicles in a
subgroup of glutamatergic neurons. In this form it can be released by
electrical stimulation and may serve to modulate responses
at receptors for a number of different neurotransmitters. These include
both excitatory and inhibitory receptors, particularly the
NMDA and GABA(A) receptors. This pool of zinc is the only form of zinc
readily stained histochemically (the chelatable zinc
pool), but constitutes only about 8% of the total zinc content in the
brain. The remainder of the zinc is more or less tightly bound
to proteins where it acts either as a component of the catalytic site of
enzymes or in a structural capacity. The metabolism of
zinc in the brain is regulated by a number of transport proteins, some
of which have been recently characterized by gene cloning
techniques. The intracellular concentration may be mediated both by
efflux from the cell by the zinc transporter ZrT1 and by
complexing with apothionein to form metallothlonein. Metallothionein may
serve as the source of zinc for incorporation into
proteins, including a number of DNA transcription factors. However, zinc
is readily released from metallothionein by disulfides,
increasing concentrations of which are formed under oxidative stress.
Metallothionein is a very good scavenger of free radicals,
and zinc itself can also reduce oxidative stress by binding to thiol
groups, decreasing their oxidation. Zinc is also a very potent
inhibitor of nitric oxide synthase. Increased levels of chelatable zinc
have been shown to be present in cell cultures of immune
cells undergoing apoptosis. This is very reminiscent of the zinc
staining of neuronal perikarya dying after an episode of ischemia
or seizure activity. Thus a possible role of zinc in causing neuronal
death in the brain needs to be fully investigated.
intraventricular injections of calcium EDTA have already been shown to
reduce neuronal death after a period of ischemia.
Pharmacological doses of zinc cause neuronal death, and some estimates
indicate that extracellular concentrations of zinc could
reach neurotoxic levels under pathological conditions. Zinc is released
in high concentrations from the hippocampus during
seizures. Unfortunately, there are contrasting observations as to
whether this zinc serves to potentiate or decrease seizure
activity. Zinc may have an additional role in causing death in at least
some neurons damaged by seizure activity and be involved
in the sprouting phenomenon which may give rise to recurrent seizure
propagation in the hippocampus. In Alzheimer's disease,
zinc has been shown to aggregate beta-amyloid, a form which is
potentially neurotoxic. The zinc-dependent transcription
factors NF-kappa B and Sp1 bind to the promoter region of the amyloid
precursor protein (APP) gene. Zinc also inhibits
enzymes which degrade APP to nonamyloidogenic peptides and which degrade
the soluble form of beta-amyloid. The changes
in zinc metabolism which occur during oxidative stress may be important
in neurological diseases where oxidative stress is
implicated, such as Alzheimer's disease, Parkinson's disease, and
amyotrophic lateral sclerosis (ALS). Zinc is a structural
component of superoxide dismutase 1, mutations in which give rise to one
form of familiar ALS. After HIV infection, zinc
deficiency is found which may be secondary to immune-induced cytokine
synthesis. Zinc is involved in the replication of the
HIV virus at a number of sites. These observations should stimulate
further research into the role of zinc in neuropathology.

Publication Types:

Review
Review, tutorial

PMID: 9361293, UI: 98027199