sam-e causes brain damage?

et_al at my-deja.com et_al at my-deja.com
Wed Oct 11 06:37:43 EST 2000


On Tue, 10 Oct 2000 13:25:33 GMT, larryhoover at my-deja.com wrote:

>In article <2kk5ussv4mi7qf19u78chpa8cmsik54is5 at 4ax.com>,
>  et_al at my-deja.com wrote:
>> On Mon, 09 Oct 2000 14:05:16 GMT, larryhoover at my-deja.com wrote:
snipped
>
>> Low levels of Serotonin or it's precursor L-Tryptophan was long
>> promoted as the cause of depression. It turned out to be much more
>> complicated than that, although 'health' food stores still make big
>> bucks out of that misconception.
>
>I think that an error was made in the assignation of serotonin as "the"
>cause, rather than simply a factor. For some people, tryptophan acts as
>a powerful antidepressant.

Very few I would suggest. I don't have any figures available, but
anecdotaly, I and a lot of others took large doses of L-Tryp during
the 1980s, prior to it being banned. I never met one patient that
derived any benefit from it other than as a sleep inducer.

The placebo effect can trigger remission in 40-70% of those with
mood disorders, so that it acted as a powerful antidepressant in a
few is no surprise. 

>That this is not a universal response is
>more likely due to the heterogeneity of the disorder, suggesting that
>the inappropriateness of the hypothesis is one of restricted
>generalizability from a limited sample. In a more restricted context,
>the hypothesis may very well hold true, if there were some way to
>identify those individuals whose depressions involved tryptophan
>absorption/conversion problems.
>
The problem with this is that there is growing evidence that
antidepressants don't increase brain serotonin levels much beyond
the initial period. 

To quote from the most recent paper on this:

>"Our results show significantly different effects between central and 
>peripheral indices of 5-HTmetabolism according to time and to the 
>antidepressant assessed: (i) an enhancement of total tissue 5-HT 
>levels in the three brain areas studied after steady-state achievement 
>of the 3 antidepressants, (ii) the return to initial values of brain 5-HT 
>levels after repeated administration of the two 5-HT re-uptake inhibitors, 
>consistent with the presence of brain adaptative mechanisms, 
>with a concomitant dramatic decrease of platelet 5-HT content"
Alvarez JC, Sanceaume M, Advenier C, Spreux-Varoquaux  (1999)
"Differential changes in brain and platelet 5-HT concentrations
after steady-state achievement and repeated administration of
antidepressant drugs in mice. "
Eur Neuropsychopharmacol, Dec;10(1):31-6

A further nail in the concept that low serotonin levels contribute
to depression is the considerable success of the French AD
Tianeptine, which is a Selective Serotonin Re-Uptake Enhancer. That
is it increases the ability of serotonin transporters to remove the
neurotransmitter from synapses. 

Incidently, it seems to be effective in many cases where
SSRI/TCA/MAOIs weren't. 

There is an axiom in neuroscience that the messenger is not the
message. Neurotransmitters are very much the messengers.

>> Nor is anxiety now regarded as being due to low GABA levels. And
>> while phenylalanine is still registered as a treatment for some
>> psych disorders, it wasn't all that effective for most patients and
>> is not much used now.
>
>Again, I would invoke the specter of heterogeneity. It worked for some
>people. We just don't have any way of determining, a priori, which ones
>would actually benefit.
>
But we also need to consider the placebo effect.

>> In most of these chemicals, its been the receptors for them, or some
>> other aspect of neuronal 'machinery,' not the levels of the
>> chemicals themselves that have been the causative factor.
>
>For some people. I hope I'm not being too redundant. In rough terms,
>30% of people with major depression obtain no benefit from any receptor-
>active medication. I am one such unfortunate.
>
But that does not mean that your depression isn't the result of some
receptor/neuronal "machinery" dysfunction. It just may be that its
related to a receptor/process for which we don't yet have a
mediating chemical. There are over 100 neurotransmitters. We only
have drugs to alter the states of the affected neurons of a handful
of them.

>> I'd be very surprised if low levels of SAM actually occurred in
>> anyone eating a normal diet, so of itself, its unlikely that any
>> positive effect from SAM-e on depression is due to the correction of
>> a lack of SAM. As with most of these neurotransmitter precursors it
>> is probable that larger than normal brain levels of SAM/SAM-e forces
>> some change in specific neurons.
>
>In fact, if the early literature on the subject is correct (check
>medline, as I did), SAMe was first tried as an antidepressant nutritive
>supplement for the very reason that depressed people were significantly
>more likely to have lower levels of SAMe in their blood than were
>normal controls. SAMe is involved in a number of biochemical pathways,
>not restricted to those which involve the formation of
>neurotransmitters. Chronic stress, for example, invoking activation of
>the HPA axis, would deplete SAMe. The outcome, in susceptible
>individuals, could be depression.
>
>Please note that nothing I have expressed yet raises the issue of
>genetic factors. There is a clear heritability of mood disorders,
>perhaps stronger than nearly all other disorders yet identified which
>have a genetic component. What if a single enzyme in the pathway
>involving SAMe were involved? Would those individuals not benefit from
>supplements? What if a sub-acute malabsorption syndrome limited full
>utilization of dietary factors? Megadoses might be necessary to simply
>normalize blood levels. We don't criticize people who lack intrinsic
>factor (required for absorption of B-12) when they take megadoses of a
>nutrient that is readily found in a good diet. Why couldn't a dietary
>factor be involved in SOME peoples' depressions? Statistically, it has
>been estimated that each person has between 120 and 180 genetic flaws.
>Which ones do you have? Which do I?
>
I don't know enough about SAM-e, or the matters you've referred to
to comment. Nor at the moment do I have the time to study this in
more detail. However, I'll raise one point. Much of what you've
written echoes the literature at the time that the significance of
tryptophan/serotonin was first realised. In the last few years much
of that has been discounted. Probably the same will occur with
SAM-e.

Which is not to suggest that it doesn't work, just that its mode of
action may be other than a simple deficiency.

It is interesting that you've raised the vitamin B-12. In the quick
medline scan I did, there were a few papers that suggested that
SAM-e may overcome a deficiency in this and other B group vitamins,
and that this may account for some, not all, but some of its
antidepressive effect. 

>> In this case its to be hoped that the dose required is less than
>> that which sets in train the Parkinson like side effects.
>
>Indeed. But more than that which leads to the alternative: suicide.
>Let's not forget that depression is a fatal disease.
>
True. But I wouldn't want to be in the position where I had only
depression or Parkinson like symptoms to choose from.

>Regards,
>Larry
>

Ian






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