Caution Regarding Use Of Acetyl DL Leucine

[park_bear]

I want to make sure everyone considering Acetyl DL Leucine is aware of a potential downside.

See here: healthunlocked.com/cure-par...

Please leave any comments at the linked post.

[ghoegap]

Thanks for headsup

[ghoegap]

And what about using acetyl l leucine ( minus the d) ?

[park_bear in reply to ghoegap]

That should be better. Always subject to proof in the clinic.

[Discogs_discogs]

I am trying to wrap my non-scientific head around all of this Information, and I thank you for posting it, Park Bear.

Do I understand correctly that the loss-of-cognition side effect may have been triggered by the D-leucine, but might not be a risk for those who only experiment with L-leucine instead? I remain puzzled.

In any event, I am surprised that a study was published based on only two patients. Two patients is not a study.

[park_bear in reply to Discogs_discogs]

Yes, you understand correctly that the loss-of-cognition side effect may have been triggered by the D-leucine, but might not be a risk for those who only experiment with L-leucine instead.

They labeled their work as a case report rather than as a study.

[Gcf51 in reply to park_bear]

The researchers should run a study with Acetyl-L-leucine. To see if loss-of-cognition still occurs after.

[Rufous2]

I'd add that the loss of cognition might not have been a side effect at all, but simply a coincidence, in which case both enantiomers could be safe.

If one is going to experiment, I think it's "safe to say" N-acetyl-L-leucine (NALL) is the "safer" way to go. If you can find it.

[Discogs_discogs in reply to Rufous2]

I see a dozen different brands of the dietary supplememt L-Leucine for sale on Amazon. However, those are not acetylised forms of L-Leucine. If one takes the normal supplement, L-leucine, this is what Wikipedia tells me happens next:

"Around 40% of dietary L-leucine is converted to acetyl-CoA, which is subsequently used in the synthesis of other compounds. The vast majority of L-leucine metabolism is initially catalyzed by the branched-chain amino acid aminotransferase enzyme, producing α-ketoisocaproate (α-KIC)."

I am not a scientist, but it sounds like the acetylisation of L-leucine changes it. For example:

pubmed.ncbi.nlm.nih.gov/343...

And

biorxiv.org/content/10.1101...

[Rufous2 in reply to Discogs_discogs]

Definitely changes it, and changes how it performs in the body, which is why it's considered a pharmaceutical.

I'm not a scientist either, and unfortunately I don't know any chemists whose brains I can pick. Maybe someone knows the author of this Parkinson's blog? journeywithparkinsons.com He appears to have a background that would lend itself to figuring something like this out.

Edit: his biographical page journeywithparkinsons.com/a...

[AkunaMatata]

Update on the potential cognitive risk: scienceofparkinsons.com/202...

zz, Jan 9th 2025:

"thank you for addressing this topic! I would like to point out that the peer review file for the “ADLL in RBD” paper can be found online in the Supplementary Information section of the original publication. It includes the following additional details about mild cognitive impairment, as quoted from the author’s response to a referee’s query.

“We agree that during the period of ADLL therapy there is a tendency for the MoCA score of patient 1 to worsen. We therefore reinvited (February 2024 – still under ADLL therapy) patient 1 for a new MoCA assessment and the score was 24, which is, by definition of the inclusion criteria, in the range of a mild cognitive impairment. Thus, we cannot rule out that this now 80-year-old RBD patient will develop cognitive impairment in the future. In patient 2 (now 59 years of age), there is also a trend towards lower normal MoCA values during the period of the ADLL therapy. A recent MoCA test (March 2024 – still under ADLL therapy) revealed a score of 28 – this finding is in line with the stated variation in the results of the MoCA screening test.”"

Simon's answer:

"Well spotted ZZ! Bravo indeed. I missed that completely. That is reassuring to know. Thank you so much for sharing your observation. I will make a note of that later tonight on the post."

"Yeah, I was wondering if the D enantiomer was not an “inactive” as the preclinical data suggests. But reader ZZ has just pointed out that the peer reviewer notes for this report are available in the supplementary notes and they address the cognitive issue, noting that patient #2’s MoCA score improved more recently (see elsewhere in the comments here)."

As he notes elsewhere in the article:

"Previous studies have found that acetyl-DL-leucine treatment is associated with improved outcomes in executive function and cognition in elderly individuals (Click here and here to read more about this)."

65 years of use in France at similar doses (1.5 to 4g/day for up to 6 weeks for vertigo) have found no reports of cognitive impairment.