The authors concluded that chitosan had modest total cholesterol-lowering benefits in patients with hypercholesterolaemia. Although the recommendations for further research seem appropriate, the reliance on a small number of small-sized trials, along with the potential for publication bias and unexplained variation amongst the trials, mean that the reliability of the authors' conclusion is uncertain.

To evaluate the impact of chitosan on serum lipids in patients with hypercholesterolaemia.

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and the Natural Medicines Comprehensive Database were searched without language restriction up to May 2008. Search terms were reported. Reference lists of relevant studies and review articles were scanned for further trials. Investigators were contacted for additional data or clarification.

Placebo-controlled randomised controlled trials (RCTs) of patients with hypercholesterolaemia treated with chitosan were eligible for inclusion in the review. Eligible trials had to report on at least one lipid outcome (total cholesterol; low density lipoprotein; high density lipoprotein; or triglycerides). Crossover trials were included if they had a wash-out period of at least four weeks; or, where this was not met, they were treated as parallel trials with data collected only from the first phase. Trials with multiple treatment arms were included by reporting each pair-wise comparison separately and dividing the placebo sample equally across the comparisons.

All trials included patients with mild to moderate hypercholesterolemia. The dosage of chitosan ranged from 1.2g/day to 6.75g/day. Placebos were reported as unknown, lactose, starch, or cellulose. One trial included additional counselling and one trial included diet modification.

Two reviewers independently selected trials for inclusion.

The authors referred to the use of methodological quality criteria, but this was not fully reported. It appeared that blinding was assessed, along with sample size and follow-up duration.

Two reviewers independently carried out the quality assessment. Disagreements were resolved by discussion, or by reference to a third reviewer.

Data were extracted on mean (baseline to follow-up) differences in total cholesterol, low-density lipoprotein and high-density lipoprotein fractions, and triglyceride concentrations. For parallel trials, the net change represented the difference (chitosan minus placebo) in the change (baseline minus follow-up) in mean value (change score). In crossover trials, the net change was the mean difference in values at the end of the treatment periods. Variances for net changes were calculated from confidence intervals (CIs), p-values, or individual variances for trial groups. In parallel trials, the variance for paired differences was extracted or calculated. One crossover trial was included as a parallel trial as there was no wash-out period, taking into account only the data from the first phase.

Two reviewers independently carried out the data extraction. Disagreements were resolved by discussion, or by reference to a third reviewer.

Weighted mean differences (WMD) and 95% confidence intervals were pooled in a random-effects meta-analysis (DerSimonian and Laird). Statistical heterogeneity was assessed using the I² statistic. Publication bias was assessed using funnel plots and Egger's weighted regression.

Six placebo-controlled RCTs (n=416 patients) were included in the review. Sample sizes ranged from 40 to 97 patients Four trials were double-blinded and two were single blinded. Follow-up ranged from four to 16 weeks.

Pooled results showed a statistically significant reduction in total cholesterol following treatment with chitosan (WMD -11.59mg/dL, 95% CI -21.45 to -1.73). There were no statistically significant treatment effects for low-density lipoprotein, high-density lipoprotein, or triglycerides. Heterogeneity was substantial in the analysis of total cholesterol (I²=69.5%) and moderate in the high-density lipoprotein analysis (I²=26.1%).

Publication bias could not be ruled out.

Chitosan had modest total cholesterol-lowering benefits in patients with hypercholesterolaemia.

The review question was clear and was supported by replicable inclusion criteria. A number of literature sources were searched and attempts were made to minimise language bias. There was no apparent search for unpublished material, and the authors were unable to rule out publication bias in their formal analysis. The review process was conducted with adequate attempts to minimise error and bias.

Although the authors appeared to refer to using wider quality assessment criteria, the results reported were limited, which made it difficult to judge the overall reliability of findings. The chosen method of synthesis appeared to be appropriate given the substantial heterogeneity. However, despite substantial heterogeneity, there was no reported exploration of this in sub-group analysis.

Reliance on a small number of small-sized trials, along with the potential for publication bias, unexplained variation amongst the trials, and limited quality results, means that the reliability of the authors' conclusion is uncertain. The research recommendations seem appropriate.

Practice: The authors stated that, in the absence of adequate data on potential harms, clinicians should be cautious in prescribing chitosan. In particular, patients with allergies or religious aversions to shellfish should avoid use of this treatment.

Research: The authors stated that larger randomised controlled trials are needed to evaluate the impact of chitosan on other lipoproteins. Additionally, exploration of the concomitant use of this treatment with other lipid-lowering medications should be investigated, along with an exploration of differential effects of various forms of chitosan, and the impact of an established diet in addition to chitosan.

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.