19 replies to this topic

[health_nutty]

As I understand it, ALCAR increases acetylcholine by acting as an acetyl donor. Is there any food or supplement that also acts as an acetyl donor (other acetylated aminos I'm guessing would). Is there anything really cheap like some kind of vinegar?

[chrono]

That's a fairly esoteric question; I doubt you'll get many answers (though if anyone else has been reviewing ACh biosynthesis, I hope they'll speak up! ). Glucose and pyruvate are the primary donors, then ALCAR. Acetic and citric acids play a very small role.

I wouldn't bother with the acids, unless there's absolutely no other drawback to supplementing them. I've seem some pyruvates around fairly cheaply, but I don't know if exogenous administration will raise acetylcholine, or if it might have other negative consequences. I'll do sub pubmed-ing this week to see, as it's an interesting possibility.

Edited by chrono, 14 July 2010 - 02:30 AM.

[health_nutty]

That's a fairly esoteric question; I doubt you'll get many answers (though if anyone else has been reviewing ACh biosynthesis, I hope they'll speak up! ). Glucose and pyruvate are the primary donors, then ALCAR. acetic and citric acidS play a very small role.

I wouldn't bother with the acids, unless there's absolutely no other drawback to supplementing them. I've seem some pyruvates around fairly cheaply, but I don't know if exogenous administration will raise acetylcholine, or if it might have other negative consequences. I'll do sub pubmed-ing this week to see, as it's an interesting possibility.

Yesterday I started up taking apple cider vinegar again to try this out. You know, my tolerance to Piracetam seems improved. No negative side effects yesterday on a moderate dose of 800mg three times a day. Of course I had to taint the experiment because my free bottle of "Instant Focus" arrived yesterday afternoon.

[recitative]

You could also try drinking kombucha for acetic acid.

That's a fairly esoteric question; I doubt you'll get many answers (though if anyone else has been reviewing ACh biosynthesis, I hope they'll speak up! ). Glucose and pyruvate are the primary donors, then ALCAR. acetic and citric acidS play a very small role.

I wouldn't bother with the acids, unless there's absolutely no other drawback to supplementing them. I've seem some pyruvates around fairly cheaply, but I don't know if exogenous administration will raise acetylcholine, or if it might have other negative consequences. I'll do sub pubmed-ing this week to see, as it's an interesting possibility.

Yesterday I started up taking apple cider vinegar again to try this out. You know, my tolerance to Piracetam seems improved. No negative side effects yesterday on a moderate dose of 800mg three times a day. Of course I had to taint the experiment because my free bottle of "Instant Focus" arrived yesterday afternoon.

[Curiouser]

What about N-acetyl cysteine? Does anyone know if that donates to Ach?

[chrono]

I'm not sure about NAC. My understanding from the ACh biosynthesis papers I've read is that it must be a molecule with an acetyl group which the enzyme carnitine acetyltransferase is able to utilize (to transfer the acetyl group to CoA, then on to choline via ChAT). So I don't think it can be just any molecule with an acetyl group.

Though most of the good research on this subject seems to have been done in the 70s and 80s, so the list I've given definitely shouldn't be considered comprehensive.

@health_nutty: I saw you recommend vinegar in another thread. Is this having a definitive effect for you? Based on the research, I expected this to be a pretty poor performer compared to ALCAR, based on the fact that it's utilized much less preferably by CarAT. OTOH, I've heard that ALCAR has a ceiling bioavailability of like 2g, while it might be possible to get enough vinegar into your system to compensate for the poor utilization. How much are you taking?

But as you've noted, the Instant Focus product has 100mg of Alpha GPC in it. Based on my own experience, GPC is a very effective choline precursor, especially when combined with ALCAR.

Edited by chrono, 14 July 2010 - 08:45 PM.

[health_nutty]

I'm taking a tablespoon 3 times a day of ACV. I know I tainted the experiement by starting Instant Focus. However, I was feeling better in the first morning I tried vinegar even before taking the Instant focus. We'll see what happens when my bottle of instant focus runs out.

I'm also taking 2g of ALCAR daily, but I have been taking that consistently for a couple of weeks.

Edited by health_nutty, 14 July 2010 - 09:13 PM.

[chrono]

I'm thinking of trying this as well, just for another data point. Is ACV...nasty? lol

[health_nutty]

I'm thinking of trying this as well, just for another data point. Is ACV...nasty? lol

Don't ask me I have I high bad taste tolerance. But more seriously, if you drink it with a glass of water it doesn't taste bad at all (you should drink it dilluted in water anyways so it won't erode the enamel on your teeth or bother your stomach).

[distinct]

I'm thinking of trying this as well, just for another data point. Is ACV...nasty? lol

Don't ask me I have I high bad taste tolerance. But more seriously, if you drink it with a glass of water it doesn't taste bad at all (you should drink it dilluted in water anyways so it won't erode the enamel on your teeth or bother your stomach).

I like ACVs taste quite a bit. In the summer, a tbsp or two diluted in water with a touch of wild honey and ice is delicious.

[chrono]

I like ACVs taste quite a bit. In the summer, a tbsp or two diluted in water with a touch of wild honey and ice is delicious.

I tried it straight for the first time last night, and immediately started looking at capsuled options. Tried it this way today, and it's very tolerable. Being cold definitely helps.

With regard to its applicability to ACh synthesis, it's looking pretty unlikely. Ingested acetic acid is indeed used as a substrate for acetyl-CoA, but most of this seems to take place in the body, as part of the TCA/Krebs cycle.

Acetic acid administered orally is immediately absorbed; uptake then occurs in liver and peripheral tissues. It is metabolized via acetyl-CoA in the tricarboxylic acid cycle in liver and skeletal muscle

Haven't found any other free references, but several mentions of its very rapid metabolism, and trouble making it to the brain. Perhaps some of the acetyl-CoA crosses the BBB, but that's not my impression so far.

1 tablespoon of ACV contains about 0.75g acetic acid. If we assume that most of this is used for physiological processes, the chance for making a significant contribution to ACh synthesis seems slim. I think I'll keep taking it, because it seems to have some other nice benefits, so I'll watch for an effect with piracetam.

Edited by chrono, 16 July 2010 - 02:27 AM.

[recitative]

Here is a simple recipe for a vinaigrette:

apple cider vinegar
flax seed oil
lecithin (this thickens it, but don't use too much or it will be too thick)
agave
spices: tumeric, kelp, cayenne
fresh herbs if you have them, mashed up garlic is also tasty.

I would not suggest that this would have any nootropic effect, but I do think it is healthy. I have salads with it about three or four times a week, with subtle variations.

[chrono]

So far, I could only find one good paper about pantothenic acid (B5)/pantethine:

Effects of ethanol and pantothenic acid on brain acetylcholine synthesis. [free PDF]
Rivera-Calimlim L, Hartley D, Osterhout D.
Department of Pharmacology, University of Rochester

1. Measurements of brain acetylcholine (ACh) synthesis from precursor [14C]-pyruvate, pantothenic acid (PA) concentration in the brain, and blood ethanol (EtOH) concentration were made in rats treated with either ethanol (5-6 g kg-1 body wt daily) alone or ethanol with PA supplementation (100-200 mg kg-1 body wt daily). EtOH with or without PA was administered orally by either Lieber-Decarli liquid diet for 4 weeks and 4 months or by oral intubation for 1 and 4 days. Matched controls were given either ethanol-free liquid diet or saline. 2. ACh synthesis in the brain of rats treated with ethanol alone for 4 months was significantly (P less than 0.01) inhibited. PA concentration of the brain was diminished to 7.0% of the control value. 3. PA concentration in the brain of rats treated with ethanol plus PA for 4 months was three times that of rats treated with ethanol alone. ACh synthesis in rats with ethanol and PA supplementation was also significantly (P less than 0.01) higher. 4. There was no difference in blood EtOH concentration between rats treated with ethanol with or without PA supplement. 5. The EtOH effect on ACh synthesis and PA concentration in the brain was observed in the chronic treatments but not in the acute treatments. 6. Data suggest that chronic ethanol exposure may decrease ACh synthesis by depleting PA, a precursor for the synthesis of acetyl CoA. Acetyl CoA is an essential substrate for ACh synthesis.

Acetylcholine (ACh) synthesis in the rat brain of control (saline-treated) (open columns), ethanol (closed columns) and ethanol plus pantothenic acid supplement (hatched columns) treatments for the duration of four months (a), four weeks (b), four days ©, and 1 day (d).

But as this paper also showed that the ethanol-induced ACh deficit was caused by B5 depletion, I'm not sure the fact that supplemental B5 corrects it is really applicable to our question.

The paper does mention that earlier work by the author demonstrated ACh was increased in a more general way:

Previous studies have shown that PA, the precursor of CoA, increased brain ACh synthesis from ['4C]-pyruvate in both in vitro and in vivo experiments in aged rats (Rivera-Calimlim, 1981). Likewise, it was shown that brain ACh synthesis of diet-induced PA-deficient rats was significantly diminished (Rivera-Calimlim, 1981).

RIVERA-CALIMLIM, L. (1981). Pantothenic acid and brain acetylcholine. Clin. Pharmacol. Ther., 35, 269.

However, I was completely unable to find this paper. No mention in medline. Volume 35 of Clinical Pharmacology & Therapeutics is actually from 1984, and this paper is not listed in that volume, or volume 29-30 from 1981. No luck searching through the author's papers, or google scholar. Maybe I can find something the next time I'm at a library with a hard copy of this journal.

I've read a few of the pantethine experiences posted here, and if anything, they do sound like it's increasing acetylcholine (or at least, not decreasing it). I'm inclined to think my previous concern about CoA inhibition of ChAT might be a non-issue. I have yet to get the full text for the original research, but it's from the early 70s and probably not very comprehensive. It's entirely possible that the inhibition only affects the rate of ChAT activity and not the amount, or that the extra acetyl-CoA offsets the effect.

So, I think it's definitely worth experimenting with. As I'm having piracetam trouble right now, and my current cocktail of ALCAR + Hup A + alpha GPC is having some weird effects, I might give it a try myself.

Edited by chrono, 20 July 2010 - 04:51 AM.

[Raccoon]

Nice timing.

Lately I had to decrease the vinegar dose. Couple day's ago in the morning I had running thought's. Nothing bad really, but enough to light the yellow light for me. I haven't had those in couple of years and last time when it happened I had a bad flu. Overdoing it also lessens my apettite so vinegar is doing something...

With a small dose the effect's are overall good for me. Definietly there is some stimulation, mood lift, but also my skin starting to get better, the eyewhites are more clean, inflammation went down, digestion much better - just like in the standard "quack statements" from alternative health sites. Now i'm baffled...

For me vinegar for years had the unhealthy food stigma, because old wives tale that it destroys blood. Where i live there is a wide spread idea of not overdoing pickled food and vinegar but I never found anything to support that in pubmed. Does acetic acid do something bad to the erythrocytes that I don't know?

I know also from experience that it improves the effects of yerba mate (weak imao). Also look at the russians and slavians. They drink vodka with much fat and pickled food (fish, cucumbers, onions, mushrooms) and vinegar is know hangover antidote in japan. Years of observation?

Is there only acetyl donoring choline involved?
Methylation and acetylation are important body processes. What with Krebs cycle?

Found an interesting article, but not very scientific: http://www.naturodoc...shi_vinegar.htm

Edited by Raccoon, 06 August 2010 - 09:07 AM.

[chrono]

Lately I had to decrease the vinegar dose. Couple day's ago in the morning I had running thought's. Nothing bad really, but enough to light the yellow light for me. I haven't had those in couple of years and last time when it happened I had a bad flu. Overdoing it also lessens my apettite so vinegar is doing something...

I'm pretty unconvinced about the possibility that vinegar raises ACh, but am always willing to be wrong For clarification, how long have you been taking it, and what dose? The above seems to imply that it's been at least a while, and that you only developed racing thoughts once. This implies to me that something else may have been the cause?

For some further discussion of the metabolic effects of vinegar, see these threads:

Apple Cider Vinegar ...a cheap version of Metformin?
Apple cider vinegar attenuates lipid profile in normal/diabetic rats

[Primal]

what's the state-of-the-art for acetyl group donors? 

[abelard lindsay]

I wrote an essay on this very topic!   The idea was to focus on optimizing the PDHC complex which generates acetyl-COA.  Basically Pyruvate and B-Vitamins.

 

http://optimalperfor...-puzzle-part-1/

 

 

Edited by abelard lindsay, 10 July 2014 - 12:24 AM.

[Primal]

Also can acetyl donors act against sirtuins deacetylation http://www.longecity...st-methylation/ to accelerate aging?

[Primal]

I wrote an essay on this very topic!   The idea was to focus on optimizing the PDHC complex which generates acetyl-COA.  Basically Pyruvate and B-Vitamins.

 

http://optimalperfor...-puzzle-part-1/

 

 

 

So you think B1 and B5 would be to acetylation what B9 and B12 are to methylation? Any other cofactors?  

 

zinc and NAD+ are cofactors only for deacetylation? any other cofactors for deacetylation?

Edited by Primal, 10 July 2014 - 12:56 AM.

[Primal]

 

I wrote an essay on this very topic!   The idea was to focus on optimizing the PDHC complex which generates acetyl-COA.  Basically Pyruvate and B-Vitamins.

 

http://optimalperfor...-puzzle-part-1/

 

 

 

So you think B1 and B5 would be to acetylation what B9 and B12 are to methylation? Any other cofactors?  

 

zinc and NAD+ are cofactors only for deacetylation? any other cofactors for deacetylation?

 

 

http://www.longecity...on/#entry680984