Clinical Evidence of Acetyl-L-Carnitine Efficacy in the Treatment of Acute Ischemic Stroke: A Pilot Clinical Trial.

2022-01
Oxidative medicine and cellular longevity 2022(1)
- Mehrdokht Mazdeh
- Parnaz Abolfathi
- Maryam Sabetghadam
- Younes Mohammadi
- Maryam Mehrpooya

PubMed: 35936217
DOI: 10.1155/2022/2493053

Study Design

Type: Randomized Controlled Trial (RCT)
Population: 69 cases with acute ischemic stroke with the onset of symptoms less than 24 hours not candidates for reperfusion therapy
Methods: randomly assigned to either the ALC group (1000 mg three times per day for three consecutive days) or the matching placebo group
Blinding: Double-blind
Duration: 3 days for treatment, with follow-up to day 90
Funding: Unclear

Background

This study was undertaken to evaluate the influence of oral Acetyl-L-carnitine (ALC) in patients with acute ischemic stroke.

Methods

Sixty-nine cases with acute ischemic stroke with the onset of symptoms less than 24 hours not candidates for reperfusion therapy were randomly assigned to either the ALC group (1000 mg three times per day for three consecutive days) or the matching placebo group. The study outcomes based on intention-to-treat criteria included the change in the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 90, as well as the change in serum levels of the inflammatory and oxidative stress biomarkers over the 3-day treatment protocol.

Results

The NIHSS score and mRS score on day 90 were improved by 5.82 and 0.94 scores, respectively, in the ALC-treated group compared to 2.83 and 0.11 scores, respectively, in the placebo-treated group, which demonstrated the superiority of ALC relative to placebo. By using the multivariable analysis after adjusting for other variables in the model, compared to the group treated with placebo, patients in the ALC group had lower NIHSS score (β: -2.40, 95% CI: -0.69, -4.10 (p = 0.007)) and mRS score (β: -1.18, 95% CI: -0.52, -1.84 (p = 0.001)) 90 days after the intervention. The percentage of patients with a favourable functional outcome at day 90, defined as mRS scores of 0 or 1, was significantly higher in the ALC group in comparison to the placebo group (52.9% versus 28.6%). Further, over the 3-day treatment protocol, in the patients receiving ALC, the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease, while the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine's level showed a significant increase compared to those in patients receiving placebo indicating significant alteration.

Conclusions

Although preliminary, these results suggested that ALC administration during the acute phase of ischemic stroke might be helpful in improving functional and neurological outcomes that are probably linked to its anti-inflammatory and antioxidant properties. Trial Registration. This trial is registered with IRCT20150629022965N17 at Iranian Registry of Clinical Trials (registration date: 25/07/2018).

Research Insights

Acetyl-Carnitine→Improved Modified Rankin Scale Score
The percentage of patients with a favourable functional outcome at day 90, defined as mRS scores of 0 or 1, was significantly higher in the ALC group in comparison to the placebo group (52.9% versus 28.6%).
Effect
Beneficial
Effect size
Large
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Increased Antioxidant Enzyme Levels
the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine's level showed a significant increase
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Increased Superoxide Dismutase Levels
the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine's level showed a significant increase
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Increased Total L-Carnitine Level
the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine's level showed a significant increase
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Increased Total Serum Antioxidant Capacity
the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine's level showed a significant increase
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Reduced Interleukin-6 Levels
the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Reduced Neuron-Specific Enolase Level
the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Reduced Soluble Intercellular Adhesion Molecule-1 Level
the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Reduced Stroke Scale Score
The NIHSS score and mRS score on day 90 were improved by 5.82 and 0.94 scores, respectively, in the ALC-treated group compared to 2.83 and 0.11 scores, respectively, in the placebo-treated group, which demonstrated the superiority of ALC relative to placebo.
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days
Acetyl-Carnitine→Reduced Tumor Necrosis Factor Alpha
the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease
Effect
Beneficial
Effect size
Moderate
Dose
1000 mg three times per day for three consecutive days