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Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis^1,2

¹ From the University of Connecticut Schools of Medicine (NS) and Pharmacy (WLB and CIC), Farmington and Storrs, CT, and the Departments of Medicine (NS) and Drug Information (WLB and CIC), Hartford Hospital, Hartford, CT

² Address reprint requests and correspondence to CI Coleman, University of Connecticut School of Pharmacy Hartford Hospital, 80 Seymour Street, Hartford, CT 06102-5037. E-mail: ccolema{at}harthosp.org.

	ABSTRACT

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Background: Several clinical trials have investigated the impact of glucomannan on plasma lipids, body weight, fasting blood glucose (FBG), and blood pressure (BP), but have yielded conflicting results and had only modest sample sizes.

Objective: The objective was to perform a meta-analysis of randomized controlled trials of glucomannan to better characterize its impact on plasma lipids, FBG, body weight, and BP.

Design: A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Library, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through November 2007. A random-effects model was used to calculate the weighted mean difference (WMD) and 95% CIs as the difference between the mean for the glucomannan and control groups. Standard methods for assessing statistical heterogeneity and publication bias were used.

Results: Fourteen studies (n = 531) met the inclusion criteria. The use of glucomannan significantly lowered total cholesterol [weighted mean difference (WMD): –19.28 mg/dL; 95% CI: –24.30, –14.26], LDL cholesterol (WMD: –15.99 mg/dL; 95% CI: –21.31, –10.67), triglycerides (WMD: –11.08 mg/dL; 95% CI: –22.07, –0.09), body weight (WMD: –0.79 kg; 95% CI: –1.53, –0.05), and FBG (WMD: –7.44 mg/dL; 95% CI: –14.16, –0.72). The use of glucomannan did not appear to significantly alter any other study endpoints. Pediatric patients, patients receiving dietary modification, and patients with impaired glucose metabolism did not benefit from glucomannan to the same degree.

Conclusions: Glucomannan appears to beneficially affect total cholesterol, LDL cholesterol, triglycerides, body weight, and FBG, but not HDL cholesterol or BP.

	INTRODUCTION

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More than 50 million Americans are thought to suffer from the metabolic syndrome, which is characterized by a group of metabolic risk factors occurring in a single individual, including but not limited to abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance or glucose intolerance (1). Patients with the metabolic syndrome are at increased risk of coronary heart disease, stroke, and peripheral vascular disease as well as type 2 diabetes mellitus. According to the American Heart Association, the primary goal for the management of patients with the metabolic syndrome is to reduce their risk of cardiovascular disease and type 2 diabetes through smoking cessation and by reducing LDL cholesterol, blood pressure, body mass index, and glucose to recommended levels (1).

Glucomannan is a soluble fiber derived from Amorphophallus konjac and is available in numerous over-the-counter products such as Lipozene. Like other soluble fiber (oats, guar gum, pectin, and psyllium), glucomannan has been touted for its potential beneficial effects on the risk of coronary heart disease (2). Glucomannan is thought to prolong gastric emptying time, which increases satiety, reduces body weight, decreases the ingestion of foods that increase cholesterol and glucose concentrations, reduces the postprandial rise in plasma glucose, suppresses hepatic cholesterol synthesis, and increases the fecal elimination of cholesterol containing bile acids (2).

Several clinical trials (3-19) have investigated the impact of glucomannan on total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, body weight, fasting blood glucose (FBG), systolic blood pressure (SBP), or diastolic blood pressure (DBP), but have yielded conflicting results and had only modest sample sizes. Although previous meta-analyses assessing the effects of soluble fibers on these same endpoints have been published, none have evaluated glucomannan. Therefore, we conducted a meta-analysis of randomized controlled trials of glucomannan to better characterize its impact on various characteristics of the metabolic syndrome.

	METHODS

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Data sources
A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Library, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through November 2007. A search strategy using the Medical Subject Headings (MeSH) and the text keywords konjac, mannan, konjac-mannan, konjac flour, glucomannan, glucomannano, konjaku, konnyaku, conjac, devil's tongue, voodoo lily, snake palm, Amorphophallus konjac, Amorphophallus rivieri, and Araceae was used. This search was then limited to clinical trials. No language restrictions were imposed. In addition, a manual search of references from reports of clinical trials or review articles was performed to identify relevant trials. When applicable, efforts were made to contact investigators for clarification or additional data.

Study selection
Only randomized controlled trials of glucomannan that reported efficacy data on at least one of the following components of the metabolic syndrome were included in the analysis: total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, body weight, FBG, SBP, or DBP. Both parallel and crossover trials were eligible for inclusion; however, crossover trials had to have a washout period of 2 wk to be included in the meta-analysis. Studies using an active control were excluded.

Validity assessment
Because they are inherent controls of bias, randomization and double-blinding were used to assess the methodologic quality of included trials.

Data abstraction
Through use of a standardized data abstraction tool, 2 reviewers independently collected data; disagreements were resolved through discussion. The following information was obtained from each trial: author identification, year of publication, study design, the abovementioned methodologic quality criteria, source of study funding, study population (including study inclusion and exclusion criteria), sample size, duration of patient follow-up, glucomannan dose and formulation used, use of concurrent dietary modification, effects on lipid variables (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), body weight, FBG, SBP, and DBP.

Statistical analysis
The mean change in lipid, glucose, body weight, and blood pressure variables from baseline was treated as a continuous variable and the weighted mean difference (WMD) was calculated as the difference between the mean in the glucomannan and control groups. A DerSimonian and Laird random-effects model (a variation on the inverse variance method, which incorporates an assumption that the different studies are estimating different, yet related, treatment effects) was used in calculating the WMD and its 95% CI. For parallel trials, net changes in each of these study variables were calculated as the difference (glucomannan minus control) in the changes (baseline minus follow-up) in these mean values (also referred to as the change score). For crossover trials, net changes were calculated as the mean difference in values at the end of the glucomannan and control periods. Because variances for net changes were not reported directly for most studies, they were calculated from CIs, P values, or individual variances for intervention and control groups or periods. For parallel trials in which variance for paired differences was reported separately for each group, we calculated a pooled variance for net change using standard methods. When the variance for paired differences was not reported, we calculated it from variances at baseline and at the end of follow-up. As suggested by Follmann et al (20), we assumed a correlation coefficient of 0.5 between initial and final values. We assumed equal variances during the trial and between intervention and control groups.

The statistical analysis was performed by using STATSDIRECT statistical software (version 2.4.6; StatsDirect Ltd, Cheshire, United Kingdom), and MIX statistical software (freely accessible at www.mix-for-meta-analysis.info). A P value <0.05 was considered statistically significant for all analyses, except where otherwise specified.

Statistical heterogeneity was addressed using the Q Statistic, where a P value < 0.10 was considered representative of significant statistical heterogeneity. Visual inspection of funnel plots and Egger's weighted regression statistics were used to assess for the presence of publication bias. To assess the potential effect of any publication bias on the meta-analysis results, the Trim and Fill method was used, which uses funnel plot symmetry to estimate the number of "missing" studies and the magnitudes of their effects. It then re-estimates the overall effect size after imputing any potentially "missing" studies into the meta-analysis to determine whether the results of the original analysis were markedly affected by publication bias.

Studies of poorer methodologic quality, such as open-label or crossover trials, may exhibit inaccurate treatment effects. Excluding them may result in increased internal validity but could reduce the external validity of the analysis. In addition, the selection of a random-effects rather than a fixed-effects model in a meta-analysis is controversial. The use of a random-effects model in the calculation of CIs results in wider intervals and thus a more conservative estimate of treatment effects when compared with a fixed-effects model. To reconcile these issues, sensitivity analysis was conducted whereby the meta-analysis was reanalyzed excluding studies that were not double-blinded, excluding crossover studies, and finally using a fixed-effects model (Mantel-Haenszel methodology). We also conducted a sensitivity analysis excluding the study by Venter et al (15), which uses a glucomannan product that may have also contained another pharmacologically active soluble fiber (pectin) and was limited to studies using total daily doses of 3 (ie, the minimum recommended dose of soluble fiber by the Food and Drug Administration) (21) and 10 g glucomannan/d (ie, the maximum practical dose of soluble fiber) (22). Additionally, subgroup analyses were performed whereby the effects of glucomannan on study endpoints were assessed separately in subjects with impaired glucose metabolism [type 2 diabetes mellitus or impaired glucose tolerance (IGT)], in obese subjects, in adults, and in children and in studies using or not using concurrent dietary modifications.

	RESULTS

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The initial search yielded 3109 potential literature citations. Of these, only 24 were clinical trials in humans. On review of references from identified studies, an additional 5 studies potentially meeting our inclusion criteria were identified, bringing the total number of studies for full-text review to 29. Fifteen of the 29 studies were excluded for the reasons given in Figure 1. Of note, the study by Vita et al (17) met all the inclusion criteria but could not be included because measures of variation around effect were not provided and could not be estimated from the data provided. Two other studies (18, 19) did not meet our criteria for inclusion because of the lack of a washout period of adequate duration.

View larger version (23K): [in this window] [in a new window]   FIGURE 1.. Flow diagram of trial identification, inclusion, and exclusion. *Data from the study by Zhang et al (14) was excluded from this analysis because of concerns regarding errors in data reporting. DBP, diastolic blood pressure; FBG, fasting blood glucose; SBP, systolic blood pressure.

Table 1

Figure 2

Table 2

View larger version (50K): [in this window] [in a new window]   FIGURE 2.. Effect of glucomannan on characteristics of the metabolic syndrome. A: Total cholesterol (n = 286 glucomannan, n = 273 control); B: LDL cholesterol (n = 146 glucomannan, n = 148 control); C: HDL cholesterol (n = 138 glucomannan, n = 140 control); D: Triglycerides (n = 301 glucomannan, n = 287 control); E: Body weight (n = 186 glucomannan, n = 193 control); F: Fasting blood glucose (n = 61 glucomannan, n = 62 control). A DerSimonian and Laird random-effects model was used in calculating the weighted men difference and its 95% CI. To convert values for cholesterol from mg/dL to mmol/g, multiply by 0.0286; to convert values for triglycerides from mg/dL to mmol/g, multiply by 0.01129. *Study reported separate analyses of 2 heterogeneous and mutually exclusive patient populations; thus, each analysis was treated as a separate study in this meta-analysis.

The results of subgroup and sensitivity analyses are presented in Table 2. Similar benefits in pediatric patients compared with adults (or the base-case analysis) were not seen. In addition, it appears that glucomannan does not have as robust an effect on triglycerides in patients with impaired glucose metabolism or when used in conjunction with dietary modification, the benefits of glucomannan on weight loss are enhanced by dietary modification, and patients with impaired glucose metabolism do not reap the hypoglycemic benefits of glucomannan. After the exclusion of studies that used a double-blind methodology, the analyses for triglycerides and FBG went from being of borderline statistical significance to borderline nonsignificance; however, because the effect size estimates for both analyses remained relatively constant, these changes were likely a result of decreased statistical power. No other subgroup or sensitivity analyses resulted in changes in overall study conclusions.

	DISCUSSION

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In this meta-analysis of 14 randomized controlled trials, patients receiving glucomannan had statistically significantly lower total cholesterol, LDL cholesterol, triglycerides, body weight, and FBG after treatment than did control patients; however, the use of glucomannan did not appear to alter HDL cholesterol or either systolic or diastolic blood pressure. Our analysis could only show trends toward benefits with glucomannan in children. We also found that glucomannan does not have as robust an effect on triglycerides in patients with impaired glucose metabolism or when used in conjunction with dietary modification, that the benefits of glucomannan on weight loss are enhanced by dietary modification, and that patients with impaired glucose metabolism do not reap the hypoglycemic benefits of glucomannan. Because of the smaller number of studies included in the abovementioned subgroup analyses, they should be interpreted with caution and considered hypothesis-generating only.

It would appear that the greatest potential cardiovascular benefits from glucomannan are due to its effect on lipids. Studies have shown that for each 1-mg/dL reduction in a patient's LDL-cholesterol concentration, their relative risk of having a coronary heart disease event is decreased by 1%. Thus, the 16-mg/dL reduction in LDL cholesterol seen in our meta-analysis with glucomannan is not only statistically significant, but likely is also clinically significant (23).

Glucomannan is not the only soluble fiber believed to reduce the risk of cardiovascular disease risk by altering plasma lipids. Two previous meta-analyses (22, 24) evaluated the hypocholesterolemic effects of pectin, psyllium, oats, and guar gum with reductions in total and LDL cholesterol ranging from 7% to 15% and 7% to 10%, respectively, along with a detrimental but small effect on HDL cholesterol. These effects on total cholesterol, LDL cholesterol, and HDL cholesterol are similar to those observed in our meta-analysis, which suggests that this may be a class effect of soluble fibers. Interestingly, whereas previous meta-analyses did not demonstrate reductions in triglycerides with soluble fibers other than glucomannan, our meta-analysis showed a statistically significant 11-mg/dL reduction. The reason behind glucomannan's ability to preferentially lower triglycerides compared with other soluble fibers is not known, but may be related to its higher viscosity and thus its greater ability to alter the metabolic pathways of hepatic cholesterol and lipoprotein metabolism (2).

Glucomannan is commonly touted in the United States as an effective over-the-counter weight-loss supplement (25, 26). In studies lasting a mean of 5.2 wk, our meta-analysis found that there was a statistically significant but small reduction in weight of 0.79 kg (1%) with glucomannan. While studied over a slightly longer period of time, orlistat (Alli) the only over-the-counter weight-loss treatment approved by the Food and Drug Administration (FDA), has been shown to decrease body weight by 5% in the first 16 wk of treatment (27). Therefore, based on current data, glucommanan's effect on weight could be described as mild, as could its effects on FBG.

Only a limited number of studies have evaluated the short-term safety and tolerability of glucomannan. On the basis of the available data, glucomannan appears to be well tolerated; adverse gastrointestinal effects such as loose stools, flatulence, diarrhea, and abdominal discomfort are the most commonly reported (15). Of potential greater concern are case reports of esophageal obstruction resulting from swelling of glucomannan tablets that have been reported in the literature (28). In response to these and similar cases related to glucomannan containing "jelly cup type candies," the FDA issued warnings about consuming certain products containing glucomannan stating they felt it posed a serious choking risk, particularly to infants, children, and the elderly (29). A paucity of data exist on the long-term safety of glucomannan.

Some limitations of this meta-analysis should be noted. First, we included both crossover and parallel studies. Crossover studies are often subject to additional biases and are thus thought to have a lower internal validity than an equivalent parallel study, particularly when studies have insufficient washout periods. Although we believed that it was advantageous to include crossover trials to provide additional power to our meta-analysis, we did not include trials that did not explicitly state the presence and duration of the washout period or studies that had a washout period <2 wk in duration. In addition, we conducted sensitivity analysis whereby we reanalyzed our results including only those studies that used the more rigorous parallel design. No noteworthy changes in any of the study endpoints were noted after conducting this sensitivity analysis, which strengthened our confidence in the conclusions of the meta-analysis. Second, as with any meta-analysis, the potential for publication bias is a concern. Publication bias is defined as "the tendency on the parts of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings." Although visual inspection of our meta-analysis’ funnel plot could not rule out the presence of publication bias, a review of Egger's weighted regression statistics and Trim and Fill analyses showed that it was unlikely that publication bias significantly affected our study results.

	CONCLUSIONS

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Glucomannan appears to beneficially affect total cholesterol, LDL cholesterol, triglycerides, body weight, and FBG, but not HDL cholesterol or blood pressure. Larger individual studies following patients for longer periods of time and evaluating both safety and efficacy are warranted and needed.

	ACKNOWLEDGMENTS

 
The authors’ responsibilities were as follows—NS, WLB, and CIC: responsible for analyzing the data, interpreting the data and results, and writing the manuscript; and WLB and CIC: responsible for formulating the research question, conducting the literature search, interpreting the data and results, and writing the manuscript. We certify that none of the material in this manuscript was previously published, and we have no conflicts to declare germane to this manuscript.

	REFERENCES

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