1: Acetyl L-Carnitine and Mild Cognitive Decline
Int Clin Psychopharmacol. 2003 Mar;18(2):61-71.
Meta-analysis of double blind randomized controlled clinical trials of Acetyl-L-Carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease.
The efficacy of Acetyl-L-Carnitine (gamma-trimethyl- beta-acetylbutyrobetaine (Alcar) in mild cognitive impairment (MCI) and mild (early) Alzheimer's disease (AD) was investigated with a meta-analysis of double-blind, placebo-controlled prospective, parallel group comparison studies of at least 3 months duration. The duration of the studies was 3, 6 or 12 months and the daily dose varied between studies from 1.5-3.0 g/day. An effect size was calculated to reflect the results of the variety of measures used in the studies grouped into the categories of clinical tests and psychometric tests. The effect sizes from the categories were integrated into an overall summary effect size. The effect size for the Clinical Global Impression of Change (CGI-CH) was calculated separately. Meta-analysis showed a significant advantage for Alcar compared to placebo for the integrated summary effect [ES =0.201, 95% confidence interval (CI)=0.107-0.295] and CGI-CH (ES =0.32, 95% CI=0.18-0.47). The beneficial effects were seen on both the clinical scales and the psychometric tests. The advantage for Alcar was seen by the time of the first assessment at 3 months and increased over time. Alcar was well tolerated in all studies.
2: Acetyl-L-Carnitine and Alzheimer's Dementia
Curr Med Res Opin. 1990;11(10):638-47.
Double-blind, placebo controlled study of Acetyl-L-Carnitine in patients with Alzheimer's dementia.
A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g Acetyl-L-Carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the Acetyl-L-Carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the Acetyl-L-Carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that Acetyl-L-Carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.
3: Clinical Study Reviews:
A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurological units following a strict selection criteria: age, Mini Mental State Examination (MMSE) Global Deterioration Scale and Geriatric Depression Scale (GDS). After the initial screening and enrollment, the trial was run for 150 days in four phases:
Phase T0 (placebo treatment for 30 days), phases T1 and T2 (L-acetylcarnitine (LAC) 1500 mg/day for 90 days), phase T3 (further 30 days of placebo treatment). Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances, or emotional affective and relational behavior. The outcome of phase T3 enabled the authors to estimate the possible favorable effects persisting after termination of L-acetylcarnitine therapy. The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC treatment improved the items tested: the total score and the memory index increased significantly and the favorable effect persisted after LAC was discontinued. The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy, and the positive results were confirmed by the Hamilton Rating Scale (p < 0.0001). The behavioral-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment (p < 0.0004); the same trend was observed in the scores for instability and negative feeling. No significant adverse drug reaction occurred during the trial. In conclusion, the statistical analysis of the data from this single-blind, multichannel trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment. Other reports indicate that this drug may be effective in the treatment of dementia.