The aim of this meta-analysis was to assess the evidence of chromium picolinate for reducing body weight. Literature searches were conducted on Medline, Embase, The Cochrane Library, Amed and Ciscom. Nine experts and four manufacturers of commercial preparations containing chromium picolinate were asked to contribute published and unpublished studies. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, validation and the assessment of methodological quality were performed independently by two reviewers. To be included, studies were required to state that they were randomized, double-blind and placebo-controlled, and report on body weight. Ten trials met all inclusion criteria and provided data, which were suitable for statistical pooling. For body weight a significant differential effect was found in favour of chromium picolinate (weighted mean difference: −1.1 kg; 95% confidence interval (CI): −1.8 to −0.4 kg, n=489). Sensitivity analysis suggests that this effect is largely dependent on the results of a single trial (weighted mean difference: −0.9 kg; 95% CI: −2.0 to 0.2 kg, n=335). Three of the reviewed trials reported on adverse events, indicating their absence in the treatment groups. In conclusion, our meta-analysis suggests a relatively small effect of chromium picolinate compared with placebo for reducing body weight. The clinical relevance of the effect is debatable and the lack of robustness means that the result has to be interpreted with caution.
Obesity has become one of the most important avoidable risk factors for morbidity and mortality.1 The risk of developing, for instance, cancer, diabetes or heart disease increases with the degree of overweight in both men and women.2,3,4,5 While recent data from the US National Health and Nutrition Examination Surveys (NHANES) show an increase in the prevalence of obesity from 22.9% in NHANES III (1988–1994) to 30.5% in NHANES 1999–2000,6 figures from the UK suggest an increase from 6–8% in 1980 to 15–16.5% in 1994.7,8 One of the major factors responsible for this phenomenon is a decrease in energy expenditure from physical activity.9,10 These considerations and the notoriously poor compliance with conventional weight management programs emphasize the importance of effective and safe therapeutic options to reduce body weight. It is therefore hardly surprising to see a plethora of slimming aids being marketed.
Chromium picolinate is used as an oral treatment to help reduce body weight and alter body composition. It is an organic compound of trivalent chromium, an essential trace mineral and cofactor to insulin, and picolinic acid, a naturally occurring derivative of tryptophan. Chromium enhances insulin activity and has been the subject of a number of studies assessing its effects in carbohydrate, protein and lipid metabolism.11,12,13 Effects include an increase in lean body mass, a decrease in percentage body fat and an increase in basal metabolic rate.11,14 Chromium picolinate is advocated in the medical literature for reducing body weight15,16,17and preparations are sold as slimming aids in the US and Europe, and through the internet. Whether chromium picolinate is effective for this condition, however, is a matter of debate. The aim of this meta-analysis is to assess the evidence from randomized controlled trials of chromium picolinate for reducing body weight in human subjects.
Systematic literature searches were conducted using the data sources Medline, Embase, The Cochrane Library, Amed and Ciscom. The search terms used were chromium, picolinate, dietary supplements, food supplements and derivatives of these. Each database was searched from its inception until January 2002. Additionally, nine experts and four manufacturers of commercial preparations containing chromium picolinate were contacted and asked to provide published or unpublished trials.18 Hand-searches of relevant medical journals, conference proceedings and of our own files were conducted. The bibliographies of all papers located were searched for further studies. No restrictions regarding the language of publication were imposed.
To be included, studies were required to state that they were randomized, double-blind and placebo-controlled, use monopreparations of chromium picolinate and report on body weight of human subjects. Trials were excluded if patients received chromium picolinate as a multiple intervention concomitantly with other medications, diet or exercise. Data were extracted systematically according to patient characteristics, interventions and results. Methodological quality was evaluated using the scoring system developed by Jadad,19 which quantifies the likelihood of bias inherent in the trials, based on the description of randomization, blinding and withdrawals. The screening and selection of studies, data extraction, validation and the assessment of methodological quality were performed independently by two reviewers (MHP, CS). Disagreements in the evaluation of individual trials were largely due to reading errors and were resolved through discussion.
The mean change of body weight compared with baseline was defined as the primary endpoint and was used to assess the difference between the chromium picolinate and the placebo groups. Means and 95% confidence intervals (CI) were calculated using standard meta-analysis software (RevMan 4.1, Update Software Ltd, Oxford, UK), which uses the inverse of the variance to assign a weight to the mean of the within-study treatment effect. For most studies, however, the information was insufficient to allow us to directly calculate the variance of the preintervention to postintervention change. Studies generally reported data on preintervention mean and standard deviation and postintervention mean and standard deviation, but not the standard deviation of the change. The Cochrane Collaboration suggests imputing the variance of the change by assuming a correlation of 0.4 between preintervention and postintervention values.20 The variance of the change was imputed using this correlation factor and then used to assign a weight to the mean of the within-study treatment effect. Summary estimates of the treatment effect were calculated using a random effects model. The χ2 test for heterogeneity was performed to determine whether the distribution of the results was compatible with the assumption that intertrial differences were attributable to chance variation alone. Publication bias was assessed using a funnel plot whereby effect estimates of the common outcome measure were plotted against trial sample size. Sensitivity analyses were performed to test the robustness of the overall effect.
The literature searches revealed 31 potentially relevant trials, which were reported in 30 articles.21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50 No unpublished studies were found. Fourteen studies were excluded because they were either not randomized, double-blind and placebo-controlled,31,32,33,34,35 did not test a monopreparation of chromium picolinate,36,37,38,39,40 did not report on body weight41,42,43or were published in duplicate.44 Ten trials met all inclusion criteria and provided data for body weight that were suitable for statistical pooling (Table 1). Seven other studies, which were reported in six articles,45,46,47,48,49,50were also included but reported data that were not suitable for statistical pooling (Table 2). None of these trials reported a significant reduction of body weight in participants treated with chromium picolinate compared with placebo. The flowchart (Figure 1) provides an overview of all included and excluded trials.
The result of the meta-analysis for body weight is shown in Figure 2. It suggests a significant reduction in body weight in patients receiving chromium picolinate compared with patients receiving placebo (weighted mean difference: −1.1 kg; 95% confidence interval: −1.8 to −0.4 kg, n=489). The χ2 test for heterogeneity suggests that the distribution of the results was compatible with the assumption that intertrial differences were attributable to chance variation (P=1).
A funnel plot of the mean difference in body weight reduction plotted against trial sample size is shown in Figure 3. Visual inspection implies that studies with a smaller sample size are asymmetrically distributed to the right of the weighted mean difference of all trials. The two largest trials22,23suggesting a mean difference of about 1.2 kg in favour of chromium picolinate more closely reflect the weighted overall estimate. Although too few studies are available for firm statements, the funnel plot is consistent with some degree of publication bias.
Sensitivity analyses were performed to test the robustness of the main analysis. We first tested whether removing the data of one trial,23 which accounted for 58% of the overall effect, would alter the direction of the result. The meta-analysis of these data21,22,24,25,26,27,28,29,30suggests the absence of a differential effect (weighted mean difference: −0.9 kg; 95% CI: −2.0 to 0.2 kg, n=335). Another sensitivity analysis assessed six trials,21,22,23,26,27,30 which all included overweight or obese patients for treatment periods ranging between 6 to 13 weeks (weighted mean difference: −1.1 kg; 95% CI: −1.8 to −0.4 kg, n=385).
This meta-analysis focused on the effect of chromium picolinate on body weight. However, additional data were available in eight other trials,21,22,23,25,26,27,29,30 which were used in a secondary analysis to provide an indication of the effect on percentage body fat and lean body mass. The meta-analysis of these data suggests a nonsignificant effect for lean body mass (weighted mean difference: 0.4 kg; 95% CI: −0.1 to 0.8 kg, n=416) and a significant effect for percentage body fat (weighted mean difference: −1.2%, 95% CI: −1.7 to −0.6%, n=416). The lack of robustness of the effect for percentage body fat is apparent when data from one trial,23 which accounted for 61% of the effect, were removed (weighted mean difference: −0.8%; 95% CI: −1.7 to 0.2%, n=262).
Our meta-analysis suggests a significant differential effect for body weight in favour of chromium picolinate. The size of the effect, however, is of debatable clinical relevance and the result of the main analysis lacks robustness. Therefore, we feel that this finding has to be interpreted with caution.
Two trials22,23 accounted for much of the weight in the main analysis. Both were published by the same author and were among only two other studies, which did not advise on maintaining a habitual dietary pattern as a measure of controlling lifestyle factors. In addition, they were the only studies that did not include a specific weight-training program, while the participants in all other trials were required to perform such a program. It is conceivable that the weight training may have obscured a further possible weight-lowering effect through an increase in lean body mass. This notion, however, is not supported by our data. The differences in study sample size may be of more interest. Both trials22,23 were the largest in the meta-analysis and each included more than 120 participants, while all other trials were of considerably smaller sample size. A possible type II error may have prevented the smaller trials from detecting significant intergroup differences. Therefore, the possibility exists that the two larger trials22,23 found a true effect. None of the other studies — four included less than 30 participants and four others included less than 50 participants — suggest a trend towards a differential effect.
Even if one accepts that the overall result reflects a true specific effect, its size is not impressive. A body weight reduction of 1.1–1.2 kg during an intervention period of 10–13 weeks (i.e. 0.08–0.1 kg/week) seems too small to be clinically meaningful. By comparison, a diet with a provision of 3300 kJ/day (800 kcal/day) achieves a mean weight loss of about 1.5–2.5 kg/week, and a more moderate energy restriction of 5000 kJ/day (1200 kcal/day) would induce a weight loss of 0.5–0.6 kg/week.51
Lifestyle changes including dieting and regular physical exercise are generally regarded as the basis for successful long-term weight loss, and limited evidence exists to support the effectiveness of pharmacotherapeutic options other than orlistat.5,52 The popularity of complementary and alternative medicine,53 however, has created a ready market for nonprescription weight loss products, which are also increasingly sold through the internet. For instance, data from a US survey of a random population sample of 14 679 adults demonstrate the common use of nonprescription weight loss products particularly among young obese women. Interestingly, 8% of women with no excess body weight were also reported to use such products.54 Even though these preparations are popular, they frequently lack evidence of effectiveness55 and some may be associated with severe adverse events. Three of the reviewed trials assessed adverse events45,46,47 and all agree on the total absence of adverse events in participants receiving chromium picolinate. Several other authors also found chromium picolinate to be relatively safe.11,56 However, literature searches on Medline, Embase and Amed identified data suggesting potential risks through chromosome damage.57 These were subsequently not confirmed in animal experiments58 and in studies involving humans.59 Two cases of acute rhabdomyolysis were associated with chromium picolinate in young men who took it as a part of their exercise regimen.60,61 Another case of severe renal impairment in a 33-year-old woman was reported.62 She had self-administered a dose several times higher than the recommended daily allowance. Finally, a 32-year-old man was reported to have ingested 1 mg of chromium picolinate daily for 4 days. He subsequently experienced acute generalized exanthematous pustulosis.63
Despite the fact that all included trials were randomized, double-blind and placebo-controlled, the extent of methodological rigor of these studies was variable. None of the studies scored the maximum possible score on the Jadad scale,19 and one scored as low as two of possible five points.30 Study participants were described as healthy volunteers, athletes and obese patients. In five studies21,22,23,26,27 sufficient information was provided to calculate the body mass index identifying the participants as overweight or obese. Another trial30 classified women as obese who exceeded 20–25% body fat. Four other studies24,25,28,29 included apparently healthy subjects but provided insufficient information to calculate the body mass index. None of these studies suggest a trend towards a differential effect.
Limitations of this meta-analysis pertain to the citation tracking and its potential incompleteness. Although strong efforts were made to locate and retrieve all trials on the subject, it is conceivable that some were not uncovered. The distorting effects on systematic reviews arising from publication bias and location bias are well-documented.64,65,66 This includes suggestions that positive findings may be overrepresented in complementary medicine journals67,68 and that these journals favour positive conclusions at the expense of methodological quality.69 In addition, there is evidence for the tendency of positive findings to be published in English language journals,70 and for some European journals not to be indexed in major medical databases.71 Therefore, the possibility of exaggerated treatment effects exists. Restrictions of literature searches relating to the language of publications and databases are therefore problematic. Databases searched for the purposes of this study included those with a focus on the American and European literature and those that specialize in complementary medicine. There were no restrictions in terms of publication language. We are therefore confident that our strategy has minimized bias. The funnel plot, however, suggests some degree of bias. The two largest trials, which are also the studies that reflect the weighted overall estimate most closely,22,23 report the largest reductions in body weight. It is interesting to note that these studies and five others21,25,26,27,29 were at least partly funded by the same manufacturer of commercially available chromium picolinate preparations.
In conclusion, our meta-analysis suggests a relatively small effect of chromium picolinate compared with placebo for reducing body weight. The clinical relevance of the effect, however, is debatable. The lack of sufficient robustness means that the overall result has to be interpreted with caution.
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Mediterranean Journal of Nutrition and Metabolism (2009)