5 replies to this topic

[Mixter]

Question. Could it be true for ANY neurotransmitter (and any
direct precursors as well as supps/medication that increase
its availability) that, if you take a lot of any of those over a
long time, you'll always end up with sensitization due to
(over)growth of the synaptic receptors for that neurotransmitter?

May it be true for choline (and all the cholinergic smart drugs)?

I've researched a bit and found no studies for or against it, but
probably only because it hasn't been researched yet.

I've already read the cholinic-adrenergic hypothesis thread, very interesting.

Huge difference between that problem and the speculative choline sensitization would be, for
adrenergic imbalance, you could supplement with low-dose hydrocortisone (prescribed, after
ACTH test), and/or take DHEA, licorice and other adrenal support things.

IF choline sensitization is a possible issue (i.e. stimulating the growth of
ACh receptors by long-term cholinergic usage), THEN

1) "getting off" choline would have some serious implications and precautions, i.e. like
getting off SSRIs, which according to all the descriptions, wouldn't be my idea of fun

2) Choline, and even more so, Cholinergics would HAVE TO be cycled in that case, at least
as taken by healthy individuals with no major choline deficiency. If there could be
something like a 'choline addiction', I don't want to know the long-term issues of it...

I don't mean to scare by this, I just thought about it for several days no,
and haven't seen it investigated anywhere before. If someone can show
that this concern is mostly or all nonsense, all the better. [thumb]

[ I believe this is a generally interesting issue, but the reason on how I came thinking about
this, is that for the first time, I used cholinergics three months in a row (studying) instead of
cycling or occasional 1-week use (several years before, with good results).

I've used an avg. of 800mg Choline, 150-200mg alpha-GPC, with 100mg Piracetam all the
time, and some days going up to 300mg Piracetam and adding standard dose of hydergine or
nicergoline. (Btw, especially the nicergoline combination is very interesting and powerful in
terms of enhanced memory, thinking speed, sharpened senses and emotions and stress
response for me, but I don't use both ergot's more than occasionally to avoid sensitization.)

And yes, plus the other standard supps/necessary omegas and vitamins along with that, but
not really combined with other nootropics. Anyhow after 3 months, I started feeling funny,
noticing a lot in my brain going on (even the physically increased circulation was noticeable),
seldomly garbled thoughts but most of the time much faster thinking, but especially my
emotional and general perception subjectively improved to a state of a few years back,
to a state of before a lot of mostly work related stress (well, maybe just plain aging, since
I'm approaching 30) worsened them a bit.

Now, when I decided stopping all the supps for a while at that noticeable point
(i.e. reduce all nootropics to just 100mg choline, then no choline), I felt a noticeable negative
difference, which has to be due to choline/cholinergic lack: subjective breath depression,
tiredness, quite bad in concentrating/doing strenuous mental work without choline, spacy
feeling, and too low blood pressure (< 110/70) / pulse (< 60) for my taste.

EDIT: PS: In my case, that weird was feeling simply too low blood pressure/pulse, i.e.
I experimentally went for a small amount of candy and 1L diet coke (ewww), then
only 30 mins. exercise, this instantly stopped ALL the symptoms that I had for
several days, that not even went with reducing choline to almost zero. So, probably
a safe bet that it was nothing but low blood pressure.

Doesn't mean that very low blood pressure, esp. combined with excessive vasodilation
can also be quite dangerous (and likely if you're already a low-blood pressure type like
me) - worst case is shock. Again, I'm not saying choline and vasodilators are evil, just
that there are basic precautions to take like with everything else...

But what I actually was talking about, choline resistance/sensitization is a different
issue and I still have no clue whether it may or may not be a (negative) issue... ]

My point of all this is: Choline supplementation is definitely good and I'll continue it,
it supports/even 'repairs' brain structures, apart from methylation effects and many other
beneficial aspects. BUT if sensitization (growth of ACh receptors) is an issue within even 3
months, and why should it not be with any neurotransmitter(?), it's a BAD idea to over-do
this (even if it doesn't offset adrenergic imbalance) in the long-term without pauses.

IF so, even normal choline supplementation alone should perhaps be cycled (maybe a 3
weeks on, 1 week off cycle is enough or so), if you plan taking it for a really long time.

These are just my $.02, happy about all suggestions/comments

Edited by mixter, 04 February 2007 - 03:39 PM.

[wild2side]

Very interesting.. considering this is the exact same issue i have been dealing with and thinking about for the past week or so.

My story is similar to yours. Have been taking l-pyroglutamic acid (100mg) and a-GPC choline (750-1000mg) for about 3 months (have cycled once or twice, but mostly steady dosing for a month on end). It was great at first (all the things you'd want in a nootropic). But after sometime i started to notice tendency towards depression, more impulsiveness, lack of concentration (possibly due to impulsiveness), apathy, and so on.

A week ago i stopped taking the pyroglutamic acid, and now just use bacopa and fish oils. However, i am still dosing as much as 1000mg of choline to keep from falling asleep and/or do any kind of mental work (i.e. studying).

I've ordered oxiracetam and some centro to see if i could combat the previous problems with l-pyroglutamic acid.. however, im starting to see that it may not be such a good idea.

Im wondering if slowly lowering choline intake will restore my old balance. Because i am not finding that the increase choline intake is benefiting me, because i am relying on it just to stay somewhat mentally focused, and even so, i find reading comprehension and fact memorization to be more difficult.

[xanadu]

Has anyone considered the opposite possibility? Perhaps people might develop a tolerance to choline sups? The second poster sounds like he may have developed just such a tolerance.

[wild2side]

That could be a possibility.. however, to me it seems not so much an issue of tolerance, but of deficiency.
Since pyroglutamic acid increases activity of choline, I've altered to amount of choline my body takes in, produces, and uses, to a point where it requires continuous supplementation.

I will wait and see if this effect will slowly taper off.

[wild2side]

Just wanted to report that my worry has substantially subsided. Today (my 6th day since stopping pyroglutamic acid supplementatoin), i feel much better on just a single dose of 250mg of a-GPC. A few more days and i will end it entirely. The 3 month supplementation has basically resulted in a residue effect.