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

Abstract

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.

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…Two weeks of oral pre-treatment with ALCAR (75 mg/kg) which readily passes the blood-brain barrier, prevented partly the STZ-icv induced effects in rats, as reflected by an attenuation of the STZ-icv induced decrease in hippocampal but not the cortical CAT activity, and by attenuation of cognitive deficits in the MWM probe but not in the training trials, as well as by inefficiency to restore the neuronal septal damage induced by STZ-icv (Terwel et al 1995). The reason of this discrepancy between the low-to-moderate efficacy in STZ-icv animal models and a consistent efficacy in AD patients, in whom a meta-analysis of 21 double-blind randomized, placebocontrolled studies (3-12 months) showed either improvement or delayed progression of cognitive decline (Montgomery et al 2003), is unclear yet, but could be related to the optimisation of the ALCAR dose and/or treatment length and initiation, in the STZ-icv rat experiments.…”

Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

“…[7][8][9] ALC has been used to manage patients with dementia, in particular Alzheimer's disease, with some success. 10 PLC was found to stimulate energy production in ischemic muscles by increasing citric acid cycle flux and stimulating pyruvate dehydrogenase activity. 11 After 24 weeks of therapy, PLC improved mean maximum walking distance in patients with peripheral arterial obstructive disease.…”

Dietary interventions as a neuroprotective therapy for the delay of the onset of cognitive decline in older adults: Evaluation of the evidence

“…A meta-analysis of 21 double-blind, placebo-controlled prospective, parallel group comparison studies of at least 3 months duration with daily doses of 1.5 -3.0 g/day in MCI and/or mild AD patients reported a significant beneficial effect of ALC compared to placebo on both clinical scales and psychometric tests over a six month period [11]. Meta analyses were conducted on clinical and psychometric tests individually in addition to a combined effect.…”