Acetate supplementation attenuates neuro inflammation

I read recently about a trial of acetate supplementation as a treatment for Post Lyme Disease Treatment Syndrome--and particularly the fatigue and brain fog symptoms associated with that syndrome. The symptoms are almost identical to those of CFS/ME and appear to be associated with epigenetic changes and resulting neuro-inflammation (and in fact, post-Lyme probably is a subset of CFS/ME with a known etiology). In the research article below the researchers discovered that acetate supplementation positively affects the epigenetic problems and affords relief to the symptoms.
Other similar articles discuss the fact that acetate supplementation attenuates neuro-inflammation (a condition that seems by many accounts to be present in CFS/ME).

I communicated with one of the researchers who advised me that they used oral glyceryl triacetate (Triacetin). She advised me that studies have also been conducted on treating Canavans Disease using this particular acetate form.

I have set out links to the particular research publications below. I am interested in everyone's comments. This may be something that proves very useful to us sufferers in the future. I am also interested in where to obtain pharmaceutical grade (if there is such a grade) or even food grade Triacetin (its actually a food additive rated safe by the USDA) to give it a DIY try.
Jim

UND scientists pursue treatment for the lingering effects of Lyme disease
http://blogs.und.edu/uletter/2017/01/und-scientists-pursue-treatment-for-the-lingering-effects-of-lyme-disease/

Dietary Acetate Supplementation Attenuates Neuroinflammation
https://www.researchgate.net/publication/260283803_Dietary_Acetate_Supplementation_Attenuates_Neuroinflammation

Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-9-249

Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain.
https://www.ncbi.nlm.nih.gov/pubmed/16002461
 

Hip

Well-Known Member
@Hip, have any idea where to find this substance?
Can't seem to find it anywhere as a retail product, but several places sell it wholesale.

I have looked under the synonyms of:

triacetin
glyceryl triacetate
E1518 (EU food additive name)
A1518 (Australian food additive name)
Enzactin (pharmaceutical drug name for triacetin)
CAS number 102-76-1
 
Can't seem to find it anywhere as a retail product, but several places sell it wholesale.

I have looked under the synonyms of:

triacetin
glyceryl triacetate
E1518 (EU food additive name)
A1518 (Australian food additive name)
Enzactin (pharmaceutical drug name for triacetin)
CAS number 102-76-1

Thanks for these posts. Can you tell me where it is available wholesale?
I may buy a small amount and try a DIY experiment with it.

Thanks
 

Hip

Well-Known Member
Thanks for these posts. Can you tell me where it is available wholesale?
I may buy a small amount and try a DIY experiment with it.
Unless you are a company (or pretend that you are one), wholesalers will not usually deal with you. I've tried to obtain items from wholesalers myself, but they will often ask you for a link to your company website and so forth.

You can find wholesalers here.
 
Got some Triacetin. Will begin non scientific, non placebo controlled, non peer reviewed trial of one (me)acetate supplementation program. I'll let everyone know how it goes.
 

Hip

Well-Known Member
From the Lyme acetate paper:
When acetate is supplied by a single oral dose of glyceryl triacetate (GTA),
  • brain acetyl-CoA levels increase by 2.2-fold,
  • it reduces neuroglia activation by 40 to 50%,
  • increases histone acetylation,
  • and is anti-inflammatory with regard to reducing IL-1β
in a rat model of neuroinflammation.
(The bullets I added for clarity).


The rat oral dose used in that study was 6 grams of triacetin per kg of body weight:
rats were treated daily with either GTA [glyceryl triacetate] or water (6 g/kg body weight) by oral gavage.
Using the rat-to-human conversion factor of 6.2, by my calculations that equates to a human dose of 0.97 grams per kg body weight. So for an 80 kg adult human, that would be a daily dose of 78 grams of triacetin.

78 grams seems like a very high dose (assuming I got my calculations right).


It says in this FDA webpage that rat doses of 10 grams per kg per day results in testicular atrophy in male rats and uterine discoloration in female rats. But 5 grams per kg per day was safe for rats.
 
I checked the doses given to babies in the Canavan disease trials and found the amounts to be quite high as well. (high dose trial 4.5 grams per kg per day). I do find it somewhat alarming that such high amounts of Triacetin may be needed to achieve the results in your bullet points above. I'm experimenting with about 10-15 grams per day of liquid acetate (mixed into water). That should be safe, but perhaps insufficient to prompt the desired symptom relief.
 

Hip

Well-Known Member
I'm experimenting with about 10-15 grams per day of liquid acetate (mixed into water). That should be safe, but perhaps insufficient to prompt the desired symptom relief.
The rat oral dose of 10 grams per kg per day that led to testicular atrophy equates to a human dose of 1.6 grams per kg per day, by my calculation, which for an 80 kg human would be an oral dose of 128 grams a day.

But according to the FDA webpage I referred to earlier, this testicular atrophy did not appear at rat oral doses of 5 grams per kg per day, which equates to 64 grams a day for an 80 kg human.

It's hard to say whether we can extrapolate from rats to humans, but if we can, then 64 grams a day would seem to be the upper limit for safety.



Though I am slightly confused by the following statement on that FDA webpage:
. It is recognized that at an even higher feeding level (10 g per kg per day) male rats developed testicular atrophy and female rats, uterine discoloration. However, such a level which would amount to 50 g or more for an infant and 600 g for an adult per day, is vastly higher than would be possible in the consumption of foods to which acetostearins are added for functional purposes.
Because by my calculation, a rat dose of 10 g per kg per day equates to 128 grams per day for an adult human, not 600 grams as they say. My calculation is based on the rat-to-human conversion factor of 6.2, given on page 7 of this document.


(Like many people, I used to think that animal and human mg per kg body weight drug doses were the same, so that if in an animal study they used a dose of X mg/kg, then the same X mg/kg dose would also apply to humans. Obviously the human daily dose will be higher than the animal one, due to humans having larger body weight compared to most lab animals like rats and mice, but other than that, I assumed the mg/kg would be the same.

But this is not the case: the mg/kg dose is quite a bit smaller in humans compared to rats, mice and guinea pigs, because our metabolic rate and various other factors is much slower than these rodents. So you have to first use the conversion factors detailed in the above link.)
 
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