Updated September 21, 2024
As of September 21, 2024 we found one new paper showing that acetyl-L-carnitine treatment lowered serum markers of oxidative stress in a small sample of people living with ALS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604350/. Since our TOE Mechanisms grade was already an A, this did not result in any grade changes.
Updated June 30, 2026
As of June 2026, we found 1 new interesting paper PMC13077999. This described a hypothesis-free two-sample Mendelian randomisation (MR) analysis of the concentration of 575 plasma/serum metabolites, to determine which might be linked to risk of ALS. Acetyl-L-carnitine was identified as being significantly protective against ALS. This did not change our TOE grades. We are carefully watching the new ALCALS trial which we do expect to influence our TOE grades. Results from this trial are expected September 2027 (NCT06126315).
Updated June 17, 2024
Since our review, we found a new published retrospective case control study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576701/. This shows that treatment with acetyl-l-carnitine at 1.5g/d (but not 3g/d) was associated with significant survival benefits. We thus change our TOE Cases grade from C to A. We continue to watch for a phase 3 trial of acetyl-l-carnitine to verify the benefits seen in the previous small phase 2 trial and this new case control study.
Key Information
Click on any letter grade below for more info:
Preclinical Trials Grade:
D
Published: Jul 2020
There are good theoretical mechanisms for carnitines, some preclinical evidence for LC and ALCAR, and a single clinical trial that suggested ALCAR could slow disease progression in PALS. All three carnitines appear to be well-tolerated, generally safe, and inexpensive. We believe that there is a need for future clinical trials of carnitines in PALS to further elucidate their efficacy. Until there is further data, we cannot endorse any of these supplements as a definite way to slow ALS progression; however, oral ALCAR at 1000mg three times daily (3000 mg total daily dose) appears to be a theoretically promising supplement available for PALS whom would like to self-experiment.
Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans
Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)
Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans
Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS
Grade F: Implausible; would violate known principles or laws of biology
Grade U: No useful information was found for this category
Grade A: Two or more peer-reviewed publications reporting benefits in well-designed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade B: One peer-reviewed publication reporting benefits in a well-designed study.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)
Grade F: The only studies available show no benefit
Grade U: No useful information was found for this category
Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits
Grade B: More than one unpublished report of benefit with validated diagnosis and benefits
Grade C: One unpublished report of benefit with validated diagnosis and benefits
Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits
Grade F: The only reports available show no benefit
Grade U: No useful information was found for this category
Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials
Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial
Grade D: One or more peer-reviewed publications reporting benefits in a flawed trial.
Flawed trials means those in which there are identifiable problems with patient selection, randomization, blinding, controls or follow-up. These have ‘high or unclear risk of bias’ according to published criteria. Well-designed trials are those that have ‘low risk of bias’.
Grade F: The only trials available show no benefit
Grade U: No useful information was found for this category
Grade A: No exposed patients appear to have experienced harms
Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade B (oral): More than 0% but less than10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D (intravenous): More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade U: No useful information was found for this category
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