Safe interventions to enhance cognitive function in cognitively healthy people would be very valuable for several reasons, including a better quality of life and professional success. While L-carnitine has been reported to enhance cognitive function in some conditions, its efficacy is disputed. The evidence of its efficacy for cognitively healthy people has not previously been systematically reviewed.

To assess the efficacy and safety of L-carnitine for the enhancement of cognitive function in people without cognitive impairment.

We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register, on 4 November 2016. We used the search terms ‘L-carnitine’ or ‘acetyl-L-carnitine’ or ‘propionyl-L-carnitine’ or ‘ALC’ or ‘PLC’ or ‘ALCAR’ or ‘ALPAR’. We ran additional separate searches in several other sources to ensure that we retrieved the most up-to-date results. We also reviewed the bibliographies of the randomised controlled trials identified and contacted the authors and known experts in the field and pharmaceutical companies to identify additional published or unpublished data.

Eligible trials were randomised controlled trials (RCTs) or quasi-RCTs, parallel-group or cross-over, that compared L-carnitine or its derivatives, acetyl-L-carnitine or propionyl-L-carnitine, at any dose and for any length of treatment, with placebo or no treatment in cognitively healthy people of any age and either gender.

We used standard methodological procedures expected by Cochrane. Two review authors independently selected trials and evaluated the methodological quality, then extracted and analysed data from the included trials.

Only two RCTs were eligible. One was a cross-over trial with 18 participants. The other randomised 400 participants to one of four treatments, of which two (L-carnitine and placebo) were relevant to this review, but the exact numbers of participants in these two treatment groups was not reported. All participants were young adults. Methodological details were poorly reported, and we considered the risk of bias in both studies to be unclear. The trials assessed different cognitive outcomes. We could extract cognitive data on approximately 200 participants from one trial. We found no evidence that L-carnitine has any effect on reaction time, vigilance, immediate memory, or delayed recall after three days of treatment. This trial report stated that there was a small number of adverse effects, none of which were serious. The small cross-over trial also reported no effect of L-carnitine on cognition, but did not provide data; no information was provided on adverse effects. We considered the available evidence to be of very low quality for all reported outcomes.

Due to the limited number of included trials, short-term treatment, and inadequate reporting, we were unable to draw any conclusions about the efficacy or safety of L-carnitine for cognitive enhancement in healthy adults. Well-designed, randomised, placebo-controlled trials of L-carnitine for cognition enhancement in cognitively healthy people, with large samples and relatively long-term follow-up, are still needed.

Background

Cognition (or cognitive function) is a term used to describe thinking skills, including attention, memory, and reasoning. Supplements and drugs are sometimes used by healthy people to try to improve cognitive function and perform better at work or while studying. These supplements and drugs are known as cognitive enhancers. L-carnitine, which is found naturally in the diet, especially in meat, but can also be produced in the body, has been suggested as a possible cognitive enhancer. It is sold on its own as a dietary supplement and is found in some mixed supplements or ‘energy drinks’. In this review, we searched for clinical trials in which healthy people taking L-carnitine were compared with similar people taking a dummy pill (placebo). We hoped to learn whether or not L-carnitine improves cognitive function and whether it is associated with side effects.

Results

We found only two trials to include in the review. One trial treated approximately 200 participants with L-carnitine or placebo for three days; the other trial treated only 18 participants with only a single dose of L-carnitine. Both trials included healthy young people with an average age of about 21. The trials measured different aspects of cognition using different tests. The smaller trial was only reported as an abstract, and there was no usable data, although the authors said that they found no evidence of an effect of L-carnitine on cognitive function. Important information was missing from the paper describing the other trial, but we found no evidence that L-carnitine had any effect on any of the aspects of cognition that were measured. Only the report of the larger trial mentioned adverse effects of treatment, which were all described as minor and occurring equally among those receiving L-carnitine and those receiving placebo.

Quality of the evidence

It was difficult to properly assess the quality of the included trials because of poor reporting. We considered there to be a serious risk of bias due to poor study methods, and further uncertainty about the results because the studies were so small. We also considered the studies to be too short to adequately address our research question. Due to these factors, we considered the quality of the evidence to be very low.

Conclusions

Given the limited amount of evidence of very low quality, we were not able to draw any conclusions about the effect of L-carnitine on cognitive function or its safety in healthy people. Larger, better-quality studies conducted over a longer period of time are needed to answer our review question.