Catcancer.eu2

Review Article
Dietary supplements for body-weight reduction: a systematicreview1,2 ABSTRACT
tions such as type 2 diabetes, heart disease, cancer, and osteoar- Background: Compliance with conventional weight-management
thritis of weight-bearing joints increases with body weight (2–5), programs is notoriously poor, and a plethora of over-the-counter and these conditions lead to substantial economic costs in the slimming aids are sold with claims of effectiveness.
total health care budget (6). One factor responsible for over- Objective: The objective of the study was to assess the evidence
weight and obesity is a continuous decrease in energy expendi- from rigorous clinical trials, systematic reviews, and meta-analyses ture from physical activity during recent decades (7, 8). Com- on the effectiveness of dietary supplements in reducing body weight.
pliance with conventional weight-management programs is Design: The study was a systematic review. Literature searches were
notoriously poor, which indicates a need for safe, effective, and conducted on Medline, Embase, Amed, Cinahl, and the Cochrane acceptable therapeutic options. It is therefore not surprising to Library until March 2003. Hand searches of medical journals, the see the marketing of a plethora of over-the-counter slimming aids authors’ own files, and bibliographies of identified articles were with claims of effectiveness (9, 10). The aim of this systematic conducted. There were no restrictions regarding the language of review is to critically assess the evidence from rigorous clinical publication. The screening of studies, selection, validation, data trials, systematic reviews, and meta-analyses on the effective- extraction, and the assessment of methodologic quality were per- ness of dietary supplements in reducing body weight.
formed independently by the 2 reviewers. To be included, trials wererequired to be randomized and double-blind. Systematic reviews andmeta-analyses of dietary supplements were included if they were based on the results of randomized, double-blind trials.
Results: Five systematic reviews and meta-analyses and 25 addi-
Systematic literature searches were conducted to identify all tional trials were included and reviewed. Data on the following randomized clinical trials (RCTs), systematic reviews, and meta- dietary supplements were identified: chitosan, chromium picolinate, analyses of dietary supplements for body weight reduction. Data Ephedra sinica, Garcinia cambogia, glucomannan, guar gum, sources were Medline, Embase, Amed, Cinahl, and the Cochrane hydroxy-methylbutyrate, plantago psyllium, pyruvate, yerba maté, Library. The search terms used were dietary supplements, food and yohimbe. The reviewed studies provide some encouraging data supplements, herbal products, phytotherapy, overweight, obe- but no evidence beyond a reasonable doubt that any specific dietary sity, weight loss, slimming, and derivatives of these. Each data- supplement is effective for reducing body weight. The only excep- base was searched from its inception until March 2003. Hand tions are E. sinica– and ephedrine-containing supplements, which searches of relevant medical journals and of the authors’ own have been associated with an increased risk of adverse events.
files were conducted. The bibliographies of all articles located Conclusions: The evidence for most dietary supplements as aids in
were searched for further studies. There were no restrictions reducing body weight is not convincing. None of the reviewed di- regarding the language of publication (11).
etary supplements can be recommended for over-the-counter To be included, trials were required to state that they were Am J Clin Nutr 2004;79:529 –36.
randomized and double-blind. Systematic reviews and meta-analyses of dietary supplements were included if based on the KEY WORDS
Overweight, obesity, weight reduction, com- results of randomized, double-blind trials. Studies assessing plementary medicine, alternative medicine, herbal medicine, dietary acute effects only were excluded. All studies were selected ac- supplements, chitosan, guar, chromium, ephedra, psyllium, garcinia cording to defined criteria, and data were validated and extractedin a systematic manner. Methodologic quality was evaluated byusing the system developed by Jadad et al (12). The screening and INTRODUCTION
selection of studies, data extraction, validation, and the assessment The number of persons whose body weight is greater than their of methodologic quality were performed independently by the 2 ideal is increasing, particularly in developed countries. In theUnited States, for instance, more than half of the adult population 1 From Complementary Medicine, Peninsula Medical School, Universi- must now be classified as overweight or obese. On the basis of a ties of Exeter and Plymouth, Exeter, United Kingdom.
normal body mass index (BMI; in kg/m2) ranging from 18.5 to Address reprint requests and correspondence to MH Pittler, Complemen- tary Medicine, Peninsula Medical School, Universities of Exeter and Ply- 24.9, 31% of the US adult population is obese (BMI ͧ 30), and mouth, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom. E-mail: an additional 34% is overweight (BMI ͧ 25; 1). Excess body weight is one of the most important risk factors for all-cause morbidity and mortality. The likelihood of developing condi- Accepted for publication September 24, 2003.
Am J Clin Nutr 2004;79:529 –36. Printed in USA. 2004 American Society for Clinical Nutrition reviewers. Disagreements in the evaluation of studies were largely All 3 trials that reported on adverse events and an additional trial due to reading errors and were resolved through discussion.
using niacin-bound chromium (Table 1) reported no adverseevents in patients receiving chromium.
Ephedra sinica
Five systematic reviews and meta-analyses based on the re- E. sinica, or ma-huang, is an evergreen shrub native to central sults of double-blind RCTs and 25 additional double-blind RCTs Asia (50). Ephedrine, the primary active constituent of the bo- met all inclusion criteria. The identified evidence relates to tanical E. sinica, has been studied alone and in combination with ayurvedic herbal preparations, chitosan, chromium picolinate, caffeine. A systematic review of 5 double-blind trials, including Ephedra sinica, Garcinia cambogia, glucomannan, guar gum, 2 trials whose format as randomized or nonrandomized is not hydroxy-methylbutyrate, plantago psyllium, pyruvate, yerba clear, concluded that the combination of ephedrine and caffeine maté, and yohimbe (Tables 1 and 2).
is effective for reducing body weight and appears to outweigh therisks (Table 2) (38). The most rigorous review to date (39) as- Ayurvedic preparations
sessed human studies with ͧ 8 wk of follow-up and concluded We identified one double-blind RCT assessing ayurvedic that E. sinica and ephedrine promote a modest short-term weight herbal preparations (13). Included patients whose body weight loss of Ȃ0.9 kg/mo more than does placebo (Table 2). The in- was ͧ 20% greater than their ideal according to the Life Insur- take of those supplements, however, is associated with a 2.2- to ance Corporation of India received daily either indistinguishable 3.6-fold increase in odds of psychiatric, autonomic, or gastroin- placebo or ayurvedic preparations (Table 1) plus 750 mg testinal symptoms and heart palpitations. Because of safety Triphala/d. Patients in the treatment group experienced a reduc- concerns, the FDA is now taking several regulatory actions tion in body weight ranging between 7.9 and 8.2 kg, which with regard to ephedra and ephedrine-containing supplements differed significantly from the reduction seen with placebo.
Chitosan
Garcinia cambogia
Chitosan is a cationic polysaccharide, which is produced from Hydroxycitric acid is obtained from extracts of G. cambogia chitin, a substance derived from the exoskeleton of crustaceans.
and has been shown to inhibit citrate cleavage enzyme, suppress It is promoted as a remedy to reduce fat absorption (41), and data de novo fatty acid synthesis and food intake, and decrease body from preclinical studies exist to support this notion (42– 44).
weight gain (20). We identified a double-blind RCT, which However, data from our meta-analysis of 5 double-blind RCTs, tested the effects of 3 g G. cambogia extract/d, which contained which included patients who were described as either obese, 50% hydroxycitric acid, in patients with an average BMI of 32 overweight, or having 10 –25% excess body weight, indicated (20). The results suggest the absence of a significantly greater serious methodologic limitations of the clinical evidence (36).
weight loss in the treatment group than in the placebo group. Two The meta-analysis concluded that the effectiveness of chitosan further double-blind RCTs report effects in favor of treatment for body-weight reduction is not established beyond a reasonable with G. cambogia compared with placebo (Ramos et al, unpub- doubt. We identified 5 further double-blind RCTs (Table 1) as- lished observations; cited in 20, 21). This is supported by a trial sessing overweight or obese patients that had been published testing the effects of hydroxycitric acid (22). Other double-blind since the meta-analysis. Overall, the evidence available in the RCTs, however, that tested G. cambogia extract– or hydroxy- literature indicates that there is considerable doubt that chitosan citric acid– containing combination preparations with or without is effective for reducing body weight in humans. Adverse events dietary alterations (Kaats et al, unpublished observations; cited most frequently included gastrointestinal symptoms such as con- in 20, 23–25) report conflicting results. Overall, the evidence for stipation and flatulence (Tables 1 and 2).
G. cambogia is not compelling. Adverse events are reported inthe reviewed trials and are listed in Table 1.
Chromium picolinate
Glucomannan
Chromium, an essential trace mineral and cofactor to insulin, enhances insulin activity and has been the subject of studies Glucomannan is a component of konjac root, derived from assessing its effects in carbohydrate, protein, and lipid metabo- Amorphophallus konjac C. Koch. Its chemical structure is sim- lism (45– 47). Reported effects include an increase in lean body ilar to that of galactomannan from guar gum (see below) and mass, a decrease in percentage body fat, and an increase in the comprises a polysaccharide chain of glucose and mannose (53).
basal metabolic rate (19, 45, 48). Chromium picolinate is an We identified one double-blind RCT including patients with organic compound of trivalent chromium and picolinic acid, a body weight ͧ20% over their ideal (26). The report suggests naturally occurring derivative of tryptophan. Our meta-analysis significantly greater weight loss in the treatment group than in the included 10 double-blind RCTs (Table 2). The results suggest a placebo group. There were no adverse events in the treatment relatively small reduction of 1.1–1.2 kg (ie, 0.08 – 0.2 kg/wk) group. Independent replication of this trial is warranted.
compared with placebo during an intervention period of 6 –14 wkin patients with an average BMI of 28 –33 (37). By comparison, a diet with a provision of 3300 kJ/d achieves a mean weight loss Whether guar gum, a dietary fiber derived from the Indian of Ȃ1.5–2.5 kg/wk, and a more moderate energy restriction to cluster bean (Cyamopsis tetragonolobus), is effective in lower- 5000 kJ/d results in a weight loss of 0.5– 0.6 kg/wk (49). There- ing body weight was assessed in our meta-analysis (40). Twenty fore, it seems that the observed effect with chromium picolinate double-blind, placebo-controlled RCTs were included, and the is, although statistically significant, not clinically meaningful.
data from 11 trials were statistically pooled. The results of the DIETARY SUPPLEMENTS FOR BODY-WEIGHT REDUCTION TABLE 1
Randomized, double-blind trials of dietary supplements for body-weight reduction1
flatulence, stoolbulkiness,bloating, nausea,heartburn consume a 5000-kJ/ddiet; exercise wasencouraged TABLE 1 (Continued)
mass decreaseand P ҃ 0.06for lean massincrease 1 NR, not reported; NA, not applicable.
2 Quantification of the likelihood that bias is inherent in a trial, based on the description of randomization, blinding, and withdrawals (12).
3 n randomly assigned/n analyzed.
4 Unpublished observations, cited in reference 20.
meta-analysis suggest that guar gum is not effective in reducing spect to fat mass (27, 28), while at least a trend toward an increase body weight. The agreement between the individual RCTs con- in lean body mass was reported from all trials, including those in firms the overall result of the meta-analysis. Adverse events which it is unclear whether the patients and care providers were reported in the reviewed trials predominately relate to the gas- blinded. Thus, there are encouraging data that require further independent replication. Only 2 of the 4 trials provided data onadverse events (54), and they reported no such events in patients Hydroxy-methylbutyrate
treated with ␤-hydroxy-␤-methylbutyrate.
␤-Hydroxy-␤-methylbutyrate is a metabolite of leucine that has shown anticatabolic actions through inhibiting protein break- Plantago psyllium
down (54). ␤-Hydroxy-␤-methylbutyrate is available as a dietarysupplement and is primarily used by bodybuilders as a supportive Psyllium is a water-soluble fiber derived from the husks of ripe measure to induce changes in body composition. The searches seeds from Plantago ovata (50). We identified one double-blind yielded 4 RCTs reported in 3 articles (54, 27, 28). Two double- RCT, which included patients with type 2 diabetes and a mean blind RCTs reported significant intergroup differences with re- BMI of 29 (29). There were no significant changes in body DIETARY SUPPLEMENTS FOR BODY-WEIGHT REDUCTION TABLE 2
Systematic reviews and meta-analyses of dietary supplements for body-weight reduction1
to change theireating habitsand to exerciseregularly hypertension (7),upper gastrointestinalsymptoms (88),headache (16), 1 RCTs, randomized controlled trials; NR, not reported; NA, not applicable.
2 n randomly assigned/n analyzed.
3 Not defined in original trials.
4 Data from double-blind, placebo-controlled trials are presented; it is unclear whether 2 of the 5 studies were randomized.
5 Data from all identified studies are presented.
6 Data from controlled trials are presented.
weight in either the treatment or placebo group. The authors results of that study indicated that this combination preparation report excellent tolerance of psyllium.
might potentially be effective in lowering body weight. Adverseevents were not reported.
Pyruvate
Pyruvate is generated in the body via glycolysis, and supple- mentation with pyruvate seems to enhance exercise performance Yohimbe (Pausinystalia yohimbe) is a tall evergreen tree that and improve measures of body composition (55, 56). Two is native to Central Africa. Yohimbine, an ␣-2 receptor antago- double-blind RCTs, which included patients with BMIs of ͧ25, nist, is the main active constituent of the ground bark of P. assessed the effects of pyruvate supplementation (30, 31). None yohimbe. Most clinical studies relate to the effects of this isolated of these studies reported significantly greater effects on weight constituent of yohimbe bark. We identified 3 double-blind RCTs, reduction than were seen with placebo. One (30) reported a which included patients who were Œ 15–20% over their ideal significant body-weight reduction of 1.2 kg from baseline, while body weight or had a BMI ranging between 28 and 48 (33–35).
both reported significant reductions in fat mass and percentage These trials report conflicting results (Table 1). At present, there- body fat from baseline. Considering the evidence available from fore, it is unclear whether yohimbine is effective in reducing rigorous clinical trials, the case of pyruvate as an aid to body- body weight. Few adverse events were reported.
composition changes and weight loss is weak. No adverse eventsare reported in one trial, and the other did not report on adverseevents (Table 1).
DISCUSSION
The data from published double-blind RCTs, systematic re- Yerba maté
views, and meta-analyses are encouraging in some cases, but Yerba maté (Ilex paraguariensis) is an evergreen tree that is they provide little convincing evidence that any specific dietary native to South America. In a combination preparation also con- supplement is effective in reducing body weight. The only ex- taining guarana (Paullinia cupana) and damiana (Turnera dif- ceptions are E. sinica– and ephedrine-containing dietary supple- fusa), it was tested in patients with a BMI of 26 –30 (32). I. ments. These remedies, however, have been associated with an paraguariensis and in particular P. cupana contain relatively increased risk of adverse events. The relative paucity of compel- large amounts of caffeine and have been shown by ultrasound ling evidence to suggest the effectiveness of dietary supplements scanning to prolong gastric emptying time (32). The descriptive in weight loss confirms the findings of earlier reviews (57).
Lifestyle changes including dieting and regular physical ex- of the evidence involved a degree of judgment in some cases, ercise are the basis for successful long-term weight loss, and which is another potential source of bias. However, we used a limited evidence exists to support the effectiveness of pharma- standard scale (12) to assess important criteria of methodologic cotherapeutic options other than orlistat and sibutramine (58, quality. This scale was also used in 4 of the 5 systematic reviews 59). Notoriously poor compliance with conventional weight- and meta-analyses. The methodologic quality of the evidence management programs and the popularity of complementary and was combined in an informal process with the type of evidence alternative medicine have created a ready market for nonpre- (eg, RCT or meta-analysis) and the volume of evidence to pro- scription weight-loss products. Data from a US survey of a ran- duce an indication of weight. This process of appraising the dom population sample of almost 15 000 adults, for instance, clinical evidence was performed independedntly by the 2 review- showed the common use of nonprescription weight-loss prod- ucts, particularly among young obese women. It is interesting In conclusion, according to our findings, the evidence for most that 8% of women with no excess body weight were also reported dietary supplements as aids in reducing body weight is not con- vincing. None of the reviewed dietary supplements can be rec- Although these preparations are popular, given the lack of convincing data on effectiveness (60), even minor adverse events MP was responsible for the conception and design of the study. MP and EE shift the delicate risk-benefit balance against their use. There is were responsible for the drafting of the manuscript, critical revision of the no convincing evidence, for instance, that guar gum is more manuscript for important intellectual content, and for final approval of the effective than placebo (Table 2), whereas adverse events such as manuscript. Neither of the authors had any conflicts of interest.
diarrhea, nausea, and flatulence were severe enough for 3% of thepatients in trials included in our meta-analysis to withdraw.
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Source: http://catcancer.eu/young-vital/datos/19-Dietary-supplements-for-body---weight.pdf