Carnitine for fatigue in multiple sclerosis: Cochrane systematic review

Abstract

Assessed as up to date: 2011/10/28

Background

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients.

Objectives

To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose.

Search methods

A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied.

Selection criteria

Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included.

Data collection and analysis

Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up.

Main results

The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported.

Authors' conclusions

There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

Author(s)

Tejani Aaron M, Wasdell Michael, Spiwak Rae, Rowell Greg, Nathwani Shabita

Summary

Carnitine for fatigue in patients with multiple sclerosis (MS)

Fatigue  is commonly associated with multiple sclerosis and leads to significant disability and loss of quality of life. Several kind of interventions have been carried out, but definitive evidence on their relative efficacy and tolerability are not available.  As quite recently it has been hypothesised a relationship between low carnitine levels in the blood and fatigue, and several studies showed that supplementation with carnitine produced improvement in fatigue symptoms. The Authors decided to perform a systematic review to assess the possible efficacy of carnitine in improving fatigue and to identify any adverse events in relapsing-remitting and secondary progressive MS patients. Most of the studies did not meet the inclusion criteria of methodological  quality, but one with the enrollement of  36 patients for 12-month intervention  with carnitine associated with amantadine, another drug commonly used to improve fatigue.

From this report, it is unclear if carnitine supplementation in MS patients improves fatigue, reduces the disability that results from fatigue or improves quality of life. It is also unclear if the use of carnitine for MS related fatigue is safe.

Reviewer's Conclusions

Implications for practice

There is insufficient evidence at this time to determine if carnitine has any clinically important, positive impact on fatigue in MS patients. In addition, there is insufficient evidence that the use of carnitine to treat fatigue in MS patients is safe. Clinicians should advise their patients that the effect (both beneficial and harmful) of carnitine to treat fatigue associated with MS remains unknown at this time.

Implications for research

To really prove or disprove carnitine’s role in treating MS related fatigue, research is needed based on good design principles (i.e. randomized controlled trials using a parallel group prospective design, patients randomized into at least two arms (carnitine and placebo), employing double blind/double-dummy procedures, testing the success of blinding after the trial, have adequate allocation concealment, a trial duration of at least one year, and outcomes that should include those listed in our hierarchy of outcomes that was used in this review). The ongoing RCT incorporates design similar to this and will provide key information when published in 2013.

In addition, it is essential that minimally clinically important differences (MCID) be identified for common fatigue measurement scales using distribution or anchor-based methods. Without identified MCID for these outcome measures, clinicians will not be able to use the data in practice from the above mentioned RCTs.

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