Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.     

Hepatoxicity associated with weight-loss supplements： A case for better post-marketing surveillance

There is a growing number of case reports of hepatoxicity from the widely marketed weight-loss supplement Hydroxycut, which contains the botanical ingredient Garcinia cambogia. These case reports may substantially undercount the true magnitude of harm. Based on the past experience with harmful dietary supplements, US regulators should assume the more precautionary approach favored by Canada and Europe. Lacking effective adverse event surveillance for supplements, or the requirements to prove safety prior to coming to the market, case reports such as those summarized here assume added importance.     

Acute liver injury following <Emphasis Type="Italic">Garcinia cambogia</Emphasis> weight-loss supplementation: case series and literature review

Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb–drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.     

Hepatotoxicity associated with Garcinia cambogia: A case report

BACKGROUND Herbal supplements(HS) for weight loss are perceived to be "safe" and"natural", as advertised in ads, however, hepatotoxicity can be associated with consumption of some HS. Use of HS may be missed, as the patient may not report these unless specifically asked about these products, since they are often not thought of as medications with potential side effects or interaction potential.CASE SUMMARY We reported a case of a 21-year-old female with morbid obesity who presented with abdominal pain for 1 wk associated with nausea, vomiting, anorexia and myalgias. She denied smoking tobacco, drinking alcohol, usage of illicit drugs,hormonal contraceptives, or energy drinks. There was no significant past medical or family illnesses. Her laboratory workup revealed acute liver failure. The workup for possible etiologies of acute liver failure was unremarkable. She was using a weight loss herbal supplement "Garcinia cambogia" for 4 wks. This case demonstrates the association of acute liver failure with Garcinia cambogia.CONCLUSION Medical reconciliation of HS should be performed in patients with suspected acute liver failure and early discontinuation of HS can prevent further progression of drug induced hepatoxicity.     

Rhabdomyolysis in response to weight-loss herbal medicine

The authors report rhabdomyolysis following the ingestion of weight-loss herbal medicine in an otherwise healthy 54-year-old woman. Three hours after ingestion of the herbal medicine, the patient suffered chest pain that continued for 2 hours and resolved gradually. Laboratory investigation showed the presence of rhabdomyolysis with peak serum creatine kinase (CK) of 1028 IU/L, which gradually decreased and normalized after the herbal medicine was discontinued. The pharmacological effects of the active ingredients of the herbal medicine, ma huang (ephedrine), guarana (active alkaloid caffeine), chitosan, Gymnena sylvestre, Garcinia cambogia (50% hydroxycitric acid), and chromium, are discussed, and similar case reports are reviewed. The elevation of CK in this case is of concern, as it may denote that muscle breakdown may be one of the mechanisms of weight loss in these herbal remedies. Further studies are needed to investigate their effects on muscle bulk or CK. Physicians should be aware of the potential side effects of many herbal medicines. It may be advisable to measure serum CK enzyme for patients who admit using weight-loss herbs.     

Complementary therapies for reducing body weight: a systematic review

The prevalence of obesity is increasing at an alarming rate and a plethora of complementary therapies are on offer claiming effectiveness for reducing body weight. The aim of this systematic review is to critically assess the evidence from randomized controlled trials (RCTs) and systematic reviews of complementary therapies for reducing body weight. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until January 2004. Hand-searches of relevant medical journals and bibliographies of identified articles were conducted. There were no restrictions regarding the language of publication. Trial selection, quality assessment and data abstraction were performed systematically and independently by two authors. Data from RCTs and systematic reviews, which based their findings on the results of RCTs, were included. Six systematic reviews and 25 additional RCTs met our inclusion criteria and were reviewed. The evidence related to acupuncture, acupressure, dietary supplements, homeopathy and hypnotherapy. Except for hypnotherapy, Ephedra sinica and other ephedrine-containing dietary supplements the weight of the evidence is not convincing enough to suggest effectiveness. For these interventions, small effects compared with placebo were identified. In conclusion, our findings suggest that for most complementary therapies, the weight of the evidence for reducing body is not convincing. Hypnotherapy, E. sinica and other ephedrine-containing dietary supplements may lead to small reductions in body weight. However, the intake of E. sinica and ephedrine is associated with an increased risk of adverse events. Interventions suggesting positive effects in single RCTs require independent replication.     

Green tea extract:A potential cause of acute liver failure

The use of herbal products has increased significantly in recent years.Because these products are not subject to regulation by the Food and Drug Administration and are often used without supervision by a healthcare provider,the indication for and consumption of these supplements is quite variable.Moreover,their use is generally regarded as safe and natural by the lay-public.Unfortunately,there has been an increase in the number of reported adverse events occurring with the use of herbal products.We present a case of acute impending liver failure in an adolescent male using a weightloss product containing green tea extract.Our case adds to the growing concern surrounding the ingestion of green tea extract and serves to heighten healthcare provider awareness of a potential green tea extract hepatotoxicity.Despite the generally touted benefits of green tea as a whole,clinical concern regarding its use is emerging and has been linked to its concentration in multiple herbal supplements.Interestingly,the suspected harmful compounds are those previously proposed to be advantageous for weight-loss,cancer remedy,and anti-inflammatory purposes.Yet,we emphasize the need to be aware of not just green tea extract,but the importance of monitoring patient use of all dietary supplements and herbal products.     

Endocrinology trial design: adverse event reporting in randomised controlled trials of recombinant human GH in GH-deficient adults

We have evaluated the reporting of withdrawals due to adverse effects and specific adverse effects in randomised controlled trials of recombinant human GH in adults. A systematic review was carried out of randomised controlled trials of the clinical effectiveness of recombinant human GH in adults with GH deficiency in relation to impact on quality of life. Trials were identified from searching electronic databases, bibliographies of related articles and consulting experts. There was reporting of withdrawals due to adverse effects and specific adverse effects. Rates of oedema and arthralgia were reported in included trials. Seventeen randomised controlled trials, published between 1990 and 1999, met the inclusion criteria for the review. Nine trials reported data on the effectiveness of GH on quality of life in adults. Only five trials (29%) reported both withdrawals from the study because of adverse events and specific adverse events with numbers per study arm and per type. Six further trials (35%) reported either withdrawal details or specific adverse event details or partial data on specific adverse events. Six trials (35%), however, did not report information on either withdrawals or specific adverse events. Ten of the 17 studies (59%) reported the number of patients who withdrew from the study due to adverse events per study arm and type of adverse event per study arm. Seven of the 17 trials (41%) reported the number of specific adverse events per study arm and six (35%) reported the type per study arm. The reporting of adverse events in randomised controlled trials of GH is variable and not consistent across trials. It is not possible to assess the impact that adverse events may have had on unblinding patients, and therefore the extent to which the effects of GH may have been overestimated. Therefore those conducting endocrinology trials in the future need to pay attention to the reporting of withdrawals due to adverse events and specific adverse events.     

Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review

Abstract. Asplund K (Umeå and Stockholm, Sweden). Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review (Review). J Intern Med 2002; 251: 372–392. Do antioxidant vitamins, in regular food or as food supplements, protect against myocardial infarction and stroke? In this systematic literature review on the effects of antioxidant vitamins in the primary prevention of cardiovascular disorders, studies with ischaemic heart disease, stroke or combined cardiovascular events as end‐points have been included. Studies on the effects of antioxidant vitamins on intermediary end‐points (such as blood lipids and blood pressure) and as secondary prevention in patients with manifest cardiovascular disease are reviewed in a conventional manner. In observational studies (case–control or cohort design), people with high intake of antioxidant vitamins by regular diet or as food supplements generally have a lower risk of myocardial infarction and stroke than people who are low‐consumers of antioxidant vitamins. The associations in observation studies have been shown for carotene, ascorbic acid as well as tocopherol. In randomized controlled trials, however, antioxidant vitamins as food supplements have no beneficial effects in the primary prevention of myocardial infarction and stroke. Serious adverse events have been reported. After an initial enthusiasm for antioxidants in the secondary prevention of cardiovascular disease, recent reports from of several large randomized trials have failed to show any beneficial effects. Thus, the apparent beneficial results of high intake of antioxidant vitamins reported in observational studies have not been confirmed in large randomized trials. The discrepancy between different types of studies is probably explained by the fact that supplement use is a component in a cluster of healthy behaviour. Antioxidant vitamins as food supplements cannot be recommended in the primary or secondary prevention against cardiovascular disease.     

Acute liver injury induced by weight-loss herbal supplements

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.     

A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity

This review focuses on the efficacy and safety of effective herbal medicines in the management of obesity in humans and animals. PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to December 30, 2008. The search terms were ＂obesity＂ and （＇herbal medicine＂ or ＂plant＂, ＂plant medicinal＂ or ＂medicine traditional＂） without narrowing or limiting search elements. All of the human and animal studies on the effects of herbs with the key outcome of change in anthropometric measures such as body weight and waist-hip circumference, body fat, amount of food intake, and appetite were included. In vitro studies, reviews, and letters to editors were excluded. Of the publications identified in the initial database, 915 results were identified and reviewed, and a total of 77 studies were included （19 human and 58 animal studies）. Studies with Cissus quadrangularis （CQ）, Sambucus nigra, Asparagus officinalis, Garcinia atroviridis, ephedra and caffeine, Slimax （extract of several plants including Zingiber officinale and Bofutsushosan） showed a significant decrease in body weight. In 41 animal studies, significant weight loss or inhibition of weight gain was found. No significant adverse effects or mortality were observed except in studies with supplements containing ephedra, caffeine and Bofutsushosan. In conclusion, compounds containing ephedra, CQr ginseng, bitter melon, and zingiber were found to be effective in the management of obesity. Attention to these natural compounds would open a new approach for novel therapeutic and more effective agents.     

Weight loss intervention trials in women with breast cancer: a systematic review

Obesity has been associated with poor health outcomes in breast cancer survivors. Thus, weight loss is recommended for overweight and obese survivors. We systematically reviewed studies (published up to July 2013) that evaluated behaviourally based, weight loss interventions in women with breast cancer exclusively. Completed randomized trials, single‐arm trials and ongoing trials were reviewed. Within‐group and between‐group differences for weight loss were extracted, as was data on secondary outcomes, i.e. clinical biomarkers, patient‐reported outcomes, adverse events. Ten completed randomized trials, four single‐arm trials and five ongoing trials were identified. Statistically significant within‐group weight loss was observed over periods of 2 to 18 months in 13 of the 14 trials, with six randomized and two single‐arm trials observing mean weight loss ≥5%. Clinical biomarkers, psychosocial and patient‐reported outcomes were measured in a small number of studies. No serious adverse events were reported. Only two trials assessed maintenance of intervention effects after the end‐of‐intervention and none reported on cost‐effectiveness. The studies included in this review suggest that weight loss is feasible to achieve and is safe in women following treatment for breast cancer. Future studies should assess (and be powered for) a range of biomarker and patient‐reported outcomes, and be designed to inform translation into practice.     

On the Use of Herbal Medicines in Management of Inflammatory Bowel Diseases: A Systematic Review of Animal and Human Studies

Because of potential adverse events and lack of effectiveness of standard therapies, the use of complementary and alternative medicines (CAM), particularly of herbal therapies, for inflammatory bowel disease (IBD) is increasing. Results from the use of herbal therapies for managing IBD are promising, and no serious adverse events have been reported from them. Herbal therapies show their benefit in managing IBD by different mechanisms such as immune system regulation, antioxidant activity, inhibition of leukotriene B4, inhibition of nuclear factor-kappa B (NF-κB), and antiplatelet activity. In this paper, all reported herbal therapies established in animal IBD models or used for managing human IBD are systematically reviewed and their possible mechanisms of action discussed. Conducting clinical trials with high quality and validity (randomized, double blinded, controlled, on a large number of patients) to obtain more conclusive results about the use of herbal therapies in IBD is recommended.     

Acute liver failure associated with Garcinia cambogia use

Millions of Americans regularly use herbal supplements, but many are unaware of the potential hidden dangers. Numerous supplements have been associated with hepatotoxicity and, indeed dietary/herbal supplements represent an increasingly common source of acute liver injury. We report a case of acute liver failure requiring liver transplantation associated with the use of Garcinia cambogia, a supplement widely promoted for weight loss. When patients present with acute hepatitis or liver failure from an unknown etiology, a careful history of supplement use should be performed.     

Hypothalamic regulatory pathways and potential obesity treatment targets

With an ever-growing population of obese people as well as comorbidities associated with obesity, finding effective weight loss strategies is more imperative than ever. One of the challenges in curbing the obesity crisis is designing successful strategies for long-term weight loss and weight-loss maintenance. Currently, weight-loss strategies include promotion of therapeutic lifestyle changes (diet and exercise), pharmacological therapy, and bariatric surgery. This review focuses on several pharmacological targets that activate central nervous system pathways that normally limit food intake and body weight. Though it is likely that no single therapy will prove effective for everyone, this review considers several recent pre-clinical targets, and several compounds that have been in human clinical trials.     

Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force

Background: Overweight and obesity in adults are common and adversely affect health. Purpose: To summarize effectiveness and harms of primary care-relevant weight-loss interventions for overweight and obese adults. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to September 2010; systematic reviews for identifying trials before 2005. Study Selection: Two investigators appraised 6498 abstracts and 648 articles. Clinical trials were included if control groups received minimal interventions. Articles were rated as good, fair, or poor by using design-specific criteria. Data Extraction: One investigator abstracted study characteristics and findings for good- and fair-quality studies; a second checked them. Data Synthesis: Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants after 12 to 18 months, with more treatment sessions associated with greater loss. Limited data suggest weight-loss maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in 3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin resulted in less weight loss. Data on effects of weight-loss treatment on long-term health outcomes (for example, death and cardiovascular disease) were insufficient. Weight-loss treatment reduced diabetes incidence in participants with prediabetes. Effects on intermediate outcomes (for example, lipids and blood pressure) were mixed and small. Data on serious medication harms were insufficient. Medications commonly caused withdrawals due to gastrointestinal symptoms. Limitations: Few studies reported health outcomes. Behaviorally based treatments were heterogeneous and specific elements were not well-described. Many studies could not be pooled because of insufficient reporting of variance data. Medication trials had high attrition, lacked postdiscontinuation data, and were inadequately powered for rare adverse effects. Conclusion: Behaviorally based treatments are safe and effective for weight loss and maintenance. Primary Funding Source: Agency for Healthcare Research and Quality.