I found this study very interesting especially the conclusion for those in prodromal PD - iRBD. Study was just on two people but with 100% sucess, I am all ears. I have had the same effect with my diet (dream change and almost elimination of all REM movements)
Abstract
Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson’s disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic “Parkinson-Disease-related-Pattern (PDRP)”-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient’s FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD.
Very interesting. "Results of the cognitive screening test MoCA stayed in the normal range for patient 2, whereas patient 1 showed a trend of decrease in the MoCA score and developed a mild cognitive impairment during the study. In respect to the exploration of the olfactory function, the TDI sum-score slightly increased over time with ADLL therapy, but remained still in the anosmic range"
"Here we describe the effects of long-term therapy with ADLL in two subjects suffering from iRBD, hyposmia and cardiac sympathetic denervation—a prodromal phenotype of PD and DLB3,4. The beneficial effects of an oral administration of ADLL were reflected in three—therapy-responsive—outcome measures: (1) a marked decline in the subjectively assessed clinical severity of the RBD phenotype (disappearance of aggressive dream content, reduction of dream enactment); (2) a stabilization or reversal of the slow, progressive decline of specific striatal DAT-SPECT binding ratios; and (3) a stabilization or reversal of the expression of the PDRP, an indicator of the progressive metabolic impairment in the CNS of iRBD and PD—as measured by FDG-PET. On the other hand, long-term therapy with ADLL failed to change the anosmic status of both patients.
The decrease of severity of the RBD-phenotype already after 3 weeks of ADLL therapy may be due to a functional improvement of neurons in circuits controlling REM sleep atonia and dream content15."
....
"In conclusion, the reduction of the severity of the RBD phenotype may reflect a symptomatic effect. The observed changes in the two objective imaging progression markers, however, raise the possibility that ADLL treatment slowed the progression to the PD phenotype, i.e., it might reflect a disease-modifying effect of ADLL in prodromal PD. Thus, these results support further explorations whether ADLL may have disease-modifying properties in prodromal PD. They also provide a compelling rationale for a placebo-controlled trial in iRBD patients with bioactive acetyl-l-leucine."
So 2 patients. The DAT scans looked positive. One patient developed MCI during treatment. It looks like we can buy Acetyl-DL-leucine by the pound. Interesting. Thanks!
Interesting, but I think I'd stay away from the DL version of N acetyl-leucine. Most studies are using just the purified L form, probably for the reasons detailed in this paper; journals.plos.org/plosone/a...
"In conclusion, firstly, the L-enantiomer–which is the pharmacologically active form in models of acute vertigo–has different pharmacokinetics when administered with the D-enantiomer as the racemate (N-acetyl-DL-leucine) compared to administration as the purified L-enantiomer. Secondly, we found evidence for an accumulation of the D-enantiomer, which would be exacerbated by chronic dosing of the racemate, with unknown and possibly unwanted deleterious effects on cell function. Thirdly, the results of this study, taken together with the regulatory guidelines of the FDA [17] and the EMA [18], strongly supports the research and development of isolated N-acetyl-L-leucine."
It does sound like a promising molecule for those with balance issues.
Thanks. Odd that, if I read the original post and study correctly, they used the "D", but it is moot for me anyway. Like WhyRBD , I have curtailed my violent dreams with some combination of diet and lifestyle and supplements. Based on what I could glean from the study, I am having more success than those two taking Acetyl-DL-leucine.
Actually, they addressed this in the discussion part of the paper;
"Our report has obvious limitations. Due to regulations on “individual cases of off-label use” we investigated only two iRBD patients with open label ADLL therapy without a placebo control. We used the available racemate of ADLL instead of the bioactive enantiomer acetyl-L-leucine, which is not currently available25."
Apparently they couldn't get acetyl-L-leucine and concluded by saying;
"Thus, these results support further explorations whether ADLL may have disease-modifying properties in prodromal PD. They also provide a compelling rationale for a placebo-controlled trial in iRBD patients with bioactive acetyl-L-leucine."
Wonder how long it will take for such a trial to take place? Let me know if you find a reliable source for acetyl-L-leucine. 😁
Definately an option for those suffering with iRBD and have difficult time with diet. Results in weeks is a huge relief to those that are jumping out of bed. The effect of smell is small price to pay if one regains their night and sleep. Research does show if frequency and intensity are reduced, phenoconversion rate is reduced. This appears to be consistent through multiple studies. What is interesting to me is what could be the common denominator between this amino acid and diet allowing them both to deliver the same results. My diet, in a two year study at UF, did improve my condition. Delaying PD and LBD is a big deal.
So this is a chemically modified form of the amino acid Leucine? Interesting medical application. I take HMB a metabolite of leucine to increase muscle strength and to prevent sarcopenia. I'm now popping out of chairs without pushing off. Has really helped me to add HMB and BCAAs to my diet, being careful not to have them too close to medication as they will compete.
Acetyl-L-leucine is mostly being trialed in lysosomal storage diseases, as described in the originally linked study;
"Acetyl-leucine (AL) has been found to have symptomatic and disease-modifying effects in animal models of lysosomal storage disorders (LSD), including Niemann-Pick disease type C (NPC) and GM2 gangliosidosis6,7. Several formal LSD clinical trials with the active L-enantiomer, including our recent double-blind, placebo-controlled crossover phase 3 trial in NPC8, found that N-acetyl-L-leucine had rapid beneficial effects on neurological signs and symptoms and an excellent safety profile8,9,10."
"Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD."
"Collectively, these data suggest that idiopathic Parkinson’s disease and other synucleinopathies exhibit remarkably similar features of LSDs (lysosomal storage disorders) at both the genetic and biochemical level, indicating an overlap in the pathogenesis of these disorders."
"Lysosomal function has a central role in maintaining neuronal homeostasis, and, accordingly, lysosomal dysfunction has been linked to neurodegeneration and particularly to Parkinson’s disease (PD).""Recent studies have also highlighted the bidirectional link between Parkinson’s disease and lysosomal storage diseases (LSD); evidence includes the presence of α-synuclein inclusions in the brain regions of patients with LSD and the identification of several lysosomal genes involved in LSD as genetic risk factors to develop PD."
So, is there a mechanistic link between RBD-reducing diets and acetyl-L-leucine's effects on RBD? Maybe..... but maybe they work on different pathways, in which case it would probably make sense to take acetyl-leucine in addition to a successful diet, much like acetyl-leucine is being used with miglustat in Niemann-Pick disease for a synergistic affect.
Why do drastically different diets/supplements work for different people? Do they all have some underlying connection to each other, and/or the lysosome, that's not readily apparent? Are there different sub-types of RBD? How is genetics involved? There are just so many variables, it makes my head hurt! 🥴 AI, anyone?
Interesting that it's already a drug that's used for vertigo:
"ADLL is commercially available under the trade name Tanganil® in France. It has been registered for the indication “vertigo” since 1960. The drug contains the racemate of acetyl-leucine, i.e., the inactive D-form and the bioactive enantiomer, the L-form of acetyl-leucine in equal parts. "
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
A nightime story some of you might find entertaining.
Encouraging results from the phase-I trial! The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in PD
A shot of hope
REM Sleep Disorder
REM sleep disorder 
