|
1
|
Gupta RC, Doss RB. Toxicity Potential of Nutraceuticals. Methods Mol Biol 2025; 2834:197-230. [PMID: 39312167 DOI: 10.1007/978-1-0716-4003-6_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
During the past few decades and especially during and after the COVID-19 pandemic, the use of nutraceuticals has become increasingly popular in both humans and animals due to their easy access, cost-effectiveness, and tolerability with a wide margin of safety. While some nutraceuticals are safe, others have an inherent toxic potential. For a large number of nutraceuticals, no toxicity/safety data are available due to a lack of pharmacological/toxicological studies. The safety of some nutraceuticals can be compromised via contamination with toxic plants, metals, mycotoxins, pesticides, fertilizers, drugs of abuse, etc. Knowledge of pharmacokinetic/toxicokinetic studies and biomarkers of exposure, effect, and susceptibility appears to play a pivotal role in the safety and toxicity assessment of nutraceuticals. Interaction studies are essential to determine efficacy, safety, and toxicity when nutraceuticals and therapeutic drugs are used concomitantly or when polypharmacy is involved. This chapter describes various aspects of nutraceuticals, particularly their toxic potential, and the factors that influence their safety.
Collapse
Affiliation(s)
- Ramesh C Gupta
- Department of Toxicology, Murray State University, Breathitt Veterinary Center, Hopkinsville, KY, USA.
| | - Robin B Doss
- Department of Toxicology, Murray State University, Breathitt Veterinary Center, Hopkinsville, KY, USA
| |
Collapse
|
|
2
|
Björnsson ES. The Epidemiology of Newly Recognized Causes of Drug-Induced Liver Injury: An Update. Pharmaceuticals (Basel) 2024; 17:520. [PMID: 38675480 PMCID: PMC11053599 DOI: 10.3390/ph17040520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/12/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence and prevalence of drug-induced liver injury appear to be increasing globally, for example, with the introduction of checkpoint inhibitors. Several reviews have been published in the last decade on the epidemiology of DILI, both among hospitalized patients and in the general population, as well as from retrospective and prospective studies on DILI. Most of these reviews have not focused on newly recognized agents that have recently changed the landscape of DILI. Apart from liver injury associated with antibiotics, oncological agents, particularly checkpoint inhibitors, are increasingly being recognized as causing liver injury. The type of liver injury associated with these agents is not idiosyncratic but rather an indirect type of injury. Furthermore, recently, COVID-19 vaccines and green tea extract have been found to lead to liver injury. Checkpoint inhibitors have revolutionized the treatment of many malignancies, such as malignant melanoma, lung cancer, and renal cancer. Via the activation of T cells, they can increase immune activity against malignant cells, but at the same time, they can decrease immune tolerance and therefore lead to immune-related adverse effects in many organs. The most common adverse effect in clinical practice is liver injury. A recent prospective study demonstrated an 8% frequency of DILI due to the use of checkpoint inhibitors among patients with malignant melanoma and renal cancer. This rate is much higher than observed with drugs, leading to idiosyncratic liver injury. Shortly after the implementation of the worldwide vaccination program against COVID-19, several case reports were published on suspected vaccination-induced autoimmune-like hepatitis occurring shortly after the vaccination. At first, these reports were met with skepticism, but currently, around 100 reports have been published, and cases of positive recurrence have been reported. The clinical, biochemical, immunological, and histological features are indistinguishable from classic autoimmune hepatitis (AIH). These reactions are very similar to drug-induced autoimmune-like hepatitis (DI-ALH) due to drugs such as nitrofurantoin, minocycline, and infliximab, which do not relapse after a short course of corticosteroids, which is the general rule in classic autoimmune hepatitis (AIH). Green tea extract has been found to be a well-documented cause of acute hepatocellular liver injury with jaundice. A strong HLA association has been reported, showing a high prevalence of HLA-B*35:01 among patients suffering from green tea-induced liver injury. Overall, 3% of patients recruited in the DILIN study were supplemented with green tea extract as one of the ingredients. In a prospective population-based study from Iceland, green tea was implicated in approximately 8% of patients with DILI.
Collapse
Affiliation(s)
- Einar Stefan Björnsson
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The National University Hospital of Iceland, Faculty of Medicine, University of Iceland, Hringbraut, 101 Reykjavik, Iceland
| |
Collapse
|
|
3
|
Sigurdarson SS, Kristjansson M, Bjornsson ES. Hepatocellular Jaundice due to Hydroxycut in Monozygotic Twins. J Clin Exp Hepatol 2024; 14:101294. [PMID: 38144897 PMCID: PMC10733688 DOI: 10.1016/j.jceh.2023.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/10/2023] [Indexed: 12/26/2023] Open
Abstract
Liver injury associated with the use of a number of different of herbal and dietary supplements are increasingly recognized. It is though often unclear which of the sometimes multiple ingredients are responsible for the liver injury. Several case reports have been published on suspected liver injury due to Hydroxycut, which is a multi-ingredient supplement often used to induce weight loss. However, the hepatotoxic potential of Hydroxycut has though been disputed, and steatotic liver disease has also been implicated in patients who are found to have elevated liver enzymes while on Hydroxycut. We report clinically apparent liver injury with jaundice associated with the use of Hydroxycut in monozygotic twins with remarkably similar type of liver injury. Both had the genotype HLA-B 35:01 allele, a risk factor for green-tea extract induced liver injury, which is included in Hydroxycut.
Collapse
Affiliation(s)
| | - Mar Kristjansson
- Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland
| | - Einar S. Bjornsson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland
| |
Collapse
|
|
4
|
Jeon YG, Kim YY, Lee G, Kim JB. Physiological and pathological roles of lipogenesis. Nat Metab 2023; 5:735-759. [PMID: 37142787 DOI: 10.1038/s42255-023-00786-y] [Citation(s) in RCA: 84] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 03/15/2023] [Indexed: 05/06/2023]
Abstract
Lipids are essential metabolites, which function as energy sources, structural components and signalling mediators. Most cells are able to convert carbohydrates into fatty acids, which are often converted into neutral lipids for storage in the form of lipid droplets. Accumulating evidence suggests that lipogenesis plays a crucial role not only in metabolic tissues for systemic energy homoeostasis but also in immune and nervous systems for their proliferation, differentiation and even pathophysiological roles. Thus, excessive or insufficient lipogenesis is closely associated with aberrations in lipid homoeostasis, potentially leading to pathological consequences, such as dyslipidaemia, diabetes, fatty liver, autoimmune diseases, neurodegenerative diseases and cancers. For systemic energy homoeostasis, multiple enzymes involved in lipogenesis are tightly controlled by transcriptional and post-translational modifications. In this Review, we discuss recent findings regarding the regulatory mechanisms, physiological roles and pathological importance of lipogenesis in multiple tissues such as adipose tissue and the liver, as well as the immune and nervous systems. Furthermore, we briefly introduce the therapeutic implications of lipogenesis modulation.
Collapse
Affiliation(s)
- Yong Geun Jeon
- Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea
| | - Ye Young Kim
- Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea
| | - Gung Lee
- Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea
| | - Jae Bum Kim
- Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea.
| |
Collapse
|
|
5
|
de Carvalho Machado C, Dinis-Oliveira RJ. Clinical and Forensic Signs Resulting from Exposure to Heavy Metals and Other Chemical Elements of the Periodic Table. J Clin Med 2023; 12:2591. [PMID: 37048674 PMCID: PMC10095087 DOI: 10.3390/jcm12072591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 03/19/2023] [Accepted: 03/28/2023] [Indexed: 03/31/2023] Open
Abstract
Several heavy metals and other chemical elements are natural components of the Earth's crust and their properties and toxicity have been recognized for thousands of years. Moreover, their use in industries presents a major source of environmental and occupational pollution. Therefore, this ubiquity in daily life may result in several potential exposures coming from natural sources (e.g., through food and water contamination), industrial processes, and commercial products, among others. The toxicity of most chemical elements of the periodic table accrues from their highly reactive nature, resulting in the formation of complexes with intracellular compounds that impair cellular pathways, leading to dysfunction, necrosis, and apoptosis. Nervous, gastrointestinal, hematopoietic, renal, and dermatological systems are the main targets. This manuscript aims to collect the clinical and forensic signs related to poisoning from heavy metals, such as thallium, lead, copper, mercury, iron, cadmium, and bismuth, as well as other chemical elements such as arsenic, selenium, and fluorine. Furthermore, their main sources of occupational and environmental exposure are highlighted in this review. The importance of rapid recognition is related to the fact that, through a high degree of suspicion, the clinician could rapidly initiate treatment even before the toxicological results are available, which can make a huge difference in these patients' outcomes.
Collapse
Affiliation(s)
- Carolina de Carvalho Machado
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Ricardo Jorge Dinis-Oliveira
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- TOXRUN—Toxicology Research Unit, University Institute of Health Sciences (IUCS), CESPU, 4585-116 Gandra, Portugal
- UCIBIO-REQUIMTE-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
- MTG Research and Development Lab, 4200-604 Porto, Portugal
| |
Collapse
|
|
6
|
Intharuksa A, Denduangboripant J, Chansakaow S, Thongkhao K, Sukrong S. HPLC and DNA barcoding profiles for identification of the selected twelve Mucuna species and its application for detecting prohibited aphrodisiac Mucuna products. Heliyon 2023; 9:e14130. [PMID: 36915514 PMCID: PMC10006835 DOI: 10.1016/j.heliyon.2023.e14130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/11/2023] [Accepted: 02/23/2023] [Indexed: 03/04/2023] Open
Abstract
Aphrodisiac herbal products originated from various plants including Mucuna species. In Thai folklore, Mucuna macrocarpa Wall. and M. pruriens (L.) DC. have long been consumed and utilized for their aphrodisiac properties. Consumption of these plants can lead to serious adverse effects caused by l-dopa. The plants have been legally banned for use as foods, dietary supplements, or nutraceuticals by the FDA of several countries. To protect consumers, methods for the identification of illicit plants or herbal products are needed. This study aimed to identify the selected twelve Mucuna species and examine the aphrodisiac herbal products containing M. macrocarpa and M. pruriens by using HPLC analysis of l-dopa coupled with DNA barcoding profiles of ITS, matK, rbcL, and trnH-psbA. The results showed that l-dopa could be found not only in the seeds of M. macrocarpa and M. pruriens but also in associated allied Mucuna species. Then, a DNA barcode was introduced to support in HPLC profiling to identify the plants. DNA barcodes of twelve Mucuna species found in Thailand were established and used to reconstruct a phylogenetic tree. In this study, ITS2 sequences showed the highest interspecific variability and could be used to differentiate all Mucuna species. The results of ITS2 sequence coupled with HPLC analysis revealed that all the purchased aphrodisiac products originated from M. pruriens only. Therefore, the integration of HPLC analysis and DNA barcoding profile was an efficient method for the identification of prohibited Mucuna species for safety monitoring of herbal supplements and protecting customer safety. Regulatory agencies should raise awareness and restrain the use of these commercial products.
Collapse
Affiliation(s)
- Aekkhaluck Intharuksa
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University Suthep Road, Suthep, Mueang, Chiang Mai, 50200, Thailand
| | | | - Sunee Chansakaow
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University Suthep Road, Suthep, Mueang, Chiang Mai, 50200, Thailand
| | - Kannika Thongkhao
- School of Languages and General Education, Walailak University, Nakhon Si Thammarat 80160, Thailand.,Center of Excellent in Marijuana, Hemp and Kratom, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Suchada Sukrong
- Center of Excellence in DNA Barcoding of Thai Medicinal Plants, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10300, Thailand
| |
Collapse
|
|
7
|
Vuppalanchi R, Ghabril M. Review article: clinical assessment of suspected drug-induced liver injury and its management. Aliment Pharmacol Ther 2022; 56:1516-1531. [PMID: 36282208 DOI: 10.1111/apt.17246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/10/2022] [Accepted: 09/25/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND Idisyncratic drug-induced liver injury (DILI) is a rare instance of liver injury after exposure to an otherwise safe drug or herbal or dietary supplement. DILI can be associated with significant morbidity and mortality. Furthermore, it is an important consideration in drug development due to safety concerns. AIMS AND METHODS To highlight pearls and pitfalls to aid clinicians in diagnosing DILI and surmising the management options. We also share the best practices from personal insights developed from decades long participation in the causality assessment committee meetings of the DILI Network. RESULTS DILI lacks a diagnostic test and is currently diagnosed through a process of exclusion of competing aetiologies of liver injury. This requires a high degree of suspicion to consider the possibility of DILI, skill in ruling out the obvious and less obvious competing liver insults, and an understanding of the expected phenotypes of DILI. The facets of DILI cover multiple aspects, including the latency, liver injury pattern, course of injury, and associated autoimmune or immuno-allergic features. Care for patients with DILI is geared towards stopping the offending drug and symptom management that include the use of corticosteroids in select cases. CONCLUSION The diagnosis of DILI is challenging and is primarily made through a carefully crafted patient interview, temporal relationship with the implicated drug or supplement, and exclusion of competing aetiology. LiverTox is a useful resource for clinicians to review the literature and recognise the likelihood of the implicated agent in causing DILI.
Collapse
Affiliation(s)
- Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| |
Collapse
|
|
8
|
Zovi A, Langella R, Nisic A, Vitiello A, Musazzi UM. Liver injury and dietary supplements: Does hydroxycitric acid trigger hepatotoxicity? JOURNAL OF INTEGRATIVE MEDICINE 2022; 20:473-475. [PMID: 35710615 DOI: 10.1016/j.joim.2022.05.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 05/11/2022] [Indexed: 06/15/2023]
Abstract
Rising rates of obesity has increased the global use of herbal supplements intended to control weight. However, taking these preparations without appropriate medical supervision could increase the risk of manifestation of side effects, especially at the hepatic level. In literature, different cases of acute liver injury consequent to the use of food supplements containing Garcinia cambogia and hydroxycitric acid are reported. This letter aims to review the most recent literature that analysed the herb-induced liver disease due to the use of hydroxycitric acid, from the first alert coming from the European Food and Drug Administration in 2009, to the last recent European food alerts from 2020 to 2021. It is noteworthy that in some cases it demonstrated the relationship between hydroxycitric acid and hepatotoxicity. Therefore, there is a need to draw more attention to the relationship between a safe use and a more awareness in the intake of these supplements, to preserve the safety of the consumers who increasingly purchase food supplements, products that have only nutritive properties and are never curative.
Collapse
Affiliation(s)
- Andrea Zovi
- Department of Pharmaceutical Sciences, University of Milan, Via G. Colombo, Milan 71-20133, Italy
| | - Roberto Langella
- Italian Society of Hospital Pharmacy (SIFO), SIFO Secretariat of the Lombardy Region, Via Carlo Farini, 81, Milan 20159, Italy.
| | - Andrea Nisic
- Regional Pharmacovigilance Center, Lombardy Region, Piazza Città di Lombardia, 1, Milan 20124, Italy
| | - Antonio Vitiello
- Pharmaceutical Department, USL Umbria 1, Via Guerriero Guerra, 21, Perugia 06127, Italy
| | - Umberto M Musazzi
- Department of Pharmaceutical Sciences, University of Milan, Via G. Colombo, Milan 71-20133, Italy
| |
Collapse
|
|
9
|
Le TT, McGrath SR, Fasinu PS. Herb-drug Interactions in Neuropsychiatric Pharmacotherapy - A Review of Clinically Relevant Findings. Curr Neuropharmacol 2022; 20:1736-1751. [PMID: 34370637 PMCID: PMC9881059 DOI: 10.2174/1570159x19666210809100357] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/23/2021] [Accepted: 08/04/2021] [Indexed: 11/22/2022] Open
Abstract
The management of neuropsychiatric disorders relies heavily on pharmacotherapy. The use of herbal products as complimentary medicine, often concomitantly, is common among patients taking prescription neuropsychiatric drugs. Herb-drug interaction, a clinical consequence of this practice, may jeopardize the success of pharmacotherapy in neuropsychiatry. Besides the wellknown ability of phytochemicals to inhibit and/or induce drug-metabolizing enzymes and transport proteins, several phytoconstituents are capable of exerting pharmacological effects on the central nervous system. This study reviewed the relevant literature and identified 13 commonly used herbal products - celery, echinacea, ginkgo, ginseng, hydroxycut, kava, kratom, moringa, piperine, rhodiola, St. John's wort, terminalia/commiphora ayurvedic mixture and valerian - which have shown clinically relevant interactions with prescription drugs used in the management of neuropsychiatric disorders. The consequent pharmacokinetic and pharmacodynamic interactions with orthodox medications often result in deleterious clinical consequences. This underscores the importance of caution in herb-drug co-medication.
Collapse
Affiliation(s)
- Tram T. Le
- School of Pharmacy, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC, 27501, USA;
| | - Sarah R. McGrath
- School of Pharmacy, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC, 27501, USA;
| | - Pius S. Fasinu
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA,Address correspondence to this author at the Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Tel/Fax: +1 205 934 4565; E-mail:
| |
Collapse
|
|
10
|
Soares PF, Fernandes MTCF, Souza ADS, Lopes CM, Dos Santos DAC, Oliveira DPR, Pereira MG, Prado NMDBL, Gomes GSDS, Santos G, Paraná R. Causality imputation between herbal products and HILI: An algorithm evaluation in a systematic review. Ann Hepatol 2022; 25:100539. [PMID: 34555512 DOI: 10.1016/j.aohep.2021.100539] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 02/04/2023]
Abstract
Algorithms can have several purposes in the clinical practice. There are different scales for causality imputation in DILI (Drug-Induced Liver Injury), but the applicability and validity of these for the HILI (Herb-Induced Liver Injury) evaluation is questionable for some scales. The purpose of the study was to determine the clinical and demographic profile of the patients with HILI, and the main algorithmic scales used in its causality assessment. The methodology was a systematic review of articles in English, Spanish, or Portuguese language, from 1979 to 2019, involving humans, with descriptors related to HILI. Qualitative and quantitative statistical analysis were performed. As a result, from a total of 60 articles, 203 HILI reports were selected: 59.9% were women, similar with other studies, and the average age was 45.8 years. Jaundice was the most frequent symptom and regarding the type of lesion, the hepatocellular was the most frequent. In regard to HILI severity, 3.0% were severe and 7.6% were fatal or required liver transplantation. In 72.3% of the cases, the most used algorithm was RUCAM (Roussel Uclaf Causality Assessment Method). The conclusion of the study is that RUCAM was the most used algorithm for causality assessment in HILI. The patients were predominantly female, jaundice was the main symptom, and HILI is reversible in the majority of cases.
Collapse
Affiliation(s)
- Pedro Felipe Soares
- School Medicine of Bahia- University Federal of Bahia, Av. Rector Miguel Calmon, S/N - Vale do Canela, 40110-100, Salvador - BA, Brazil.
| | | | | | - Caio Medina Lopes
- Faculty of Pharmacy - University Federal of Bahia, Salvador, BA, Brazil.
| | | | | | | | | | | | - Genário Santos
- Sciences of Health Post Graduation Program - University Federal of Bahia, Salvador, BA, Brazil.
| | - Raymundo Paraná
- School Medicine of Bahia- University Federal of Bahia, Av. Rector Miguel Calmon, S/N - Vale do Canela, 40110-100, Salvador - BA, Brazil.
| |
Collapse
|
|
11
|
Anto EJ, Syahputra RA, Silitonga HA, Situmorang PC, Nugaraha SE. Oral acute toxicity study extract ethanol of balakka fruit (Phyllanthus emblica). PHARMACIA 2022. [DOI: 10.3897/pharmacia.69.e81280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Phyllanthus emblica (PE) is a plant widely found in Indonesia, especially in Sumatra island, and in India. This study followed the OECD No. 420. The groups were divided based on gender, male and female rats. Male rats were divided into 6 groups, which were male/female control, male/female 2000 mg/kgBW, and male/female 5000 mg/kgBW. This study revealed that the ethanol extract of Phyllanthus emblica (EEPE) doses of 2000 mg/kgBW and 5000 mg/kgBW did not cause histological changes in the heart, liver, testes, ovaries, and kidneys, and did not cause changes to the hematological parameters, kidney biochemical parameters, liver biochemical parameters, and electrolyte parameters both in male and female rats. The results show that the LD50 of EEPE is higher than 5000 mg/kgBW. In short, this study provides information regarding the antioxidant activity and the safe use of EEPE. The LD50 of extract ethanol of Phyllanthus emblica is higher than 5000 mg/kgBW.
Collapse
|
|
12
|
Knapik JJ, Trone DW, Steelman RA, Farina EK, Lieberman HR. Adverse effects associated with use of specific dietary supplements: The US Military Dietary Supplement Use Study. Food Chem Toxicol 2022; 161:112840. [PMID: 35093428 DOI: 10.1016/j.fct.2022.112840] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 01/11/2022] [Accepted: 01/25/2022] [Indexed: 12/15/2022]
Abstract
Dietary supplements (DSs) are used by 50% of Americans and 70% of United States military service members (SMs); some have adverse effects (AEs). This cross-sectional investigation examined AEs associated with specific DSs. A stratified random sample of SMs from the Air Force, Army, Marine Corps, and Navy was obtained. Volunteers completed a questionnaire reporting AEs for 96 generic and 62 specific DSs. The highest prevalence (≥1 AE) in specific DS categories was 35% prohormones, 33% weight loss supplements, 26% pre/post workout supplements, 14% herbal products, 12% multivitamin/multiminerals, 11% protein/amino acids, 9% muscle building supplements, 7% other DSs, 6% joint health products, and 5% individual vitamins/minerals. Specific DSs of concern (with proportion reporting AEs) included: Libido Max® (35%), Hydroxycut Hardcore® (33%), OxyElite® (33%), Roxylean® (31%), Growth Factor 9® (30%), Super HD® (29%), Hydroxycut Advanced® (29%), Lipo 6® (28%), The Ripper® (27%), Test Booster® (27%), Xenadrine Xtreme Thermogenic® (27%), C4 Extreme® (26%), and C4 Origional® (25%). Products marketed for weight loss, use before/after workout, and prohormones had the highest AE prevalence. DSs can contain substances with independent/additive AEs and/or interact with other ingredients or prescribed medications. Methods described here could provide a continuous surveillance system detecting dangerous DSs entering the market.
Collapse
Affiliation(s)
- Joseph J Knapik
- Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Natick, MA, 01760, USA.
| | - Daniel W Trone
- Naval Health Research Center, Building 329, Ryne Rd, San Diego, CA, 92152, USA
| | - Ryan A Steelman
- Army Public Health Center, 8252 Blackhawk Rd, Aberdeen Proving Ground, MD, 21010, USA
| | - Emily K Farina
- Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Natick, MA, 01760, USA
| | - Harris R Lieberman
- Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Natick, MA, 01760, USA
| |
Collapse
|
|
13
|
Hoofnagle JH, Bonkovsky HL, Phillips EJ, Li YJ, Ahmad J, Barnhart H, Durazo F, Fontana RJ, Gu J, Khan I, Kleiner DE, Koh C, Rockey DC, Seeff LB, Serrano J, Stolz A, Tillmann HL, Vuppalanchi R, Navarro VJ. HLA-B*35:01 and Green Tea-Induced Liver Injury. Hepatology 2021; 73:2484-2493. [PMID: 32892374 PMCID: PMC8052949 DOI: 10.1002/hep.31538] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/25/2020] [Accepted: 08/16/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Herbal supplements, and particularly multi-ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea-associated liver injury. APPROACH AND RESULTS Among 1,414 patients enrolled in the U.S. Drug-Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15-448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% confidence interval [CI], 58-87) of green tea cases, but only 15% (95% CI, 10-20) caused by other supplements and 12% (95% CI, 10-14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5-11.5). CONCLUSIONS Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01, suggesting that it is idiosyncratic and immune mediated.
Collapse
Affiliation(s)
- Jay H Hoofnagle
- Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD
| | - Herbert L Bonkovsky
- National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD
- Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | | | - Yi-Ju Li
- Duke Clinical Research Institute, Duke University, Durham, NC
| | - Jawad Ahmad
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Huiman Barnhart
- Duke Clinical Research Institute, Duke University, Durham, NC
| | - Francisco Durazo
- University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA
| | - Robert J Fontana
- Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI
| | - Jiezhun Gu
- Duke Clinical Research Institute, Duke University, Durham, NC
| | - Ikhlas Khan
- National Center for Natural Products Research, University of Mississippi, University, MI
| | - David E Kleiner
- The Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC
| | - Leonard B Seeff
- Department of Medicine, Einstein Healthcare Network, Philadelphia, PA
| | - Jose Serrano
- Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD
| | - Andrew Stolz
- Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA
| | - Hans L Tillmann
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, NC
| | - Raj Vuppalanchi
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
| | - Victor J Navarro
- Department of Medicine, Einstein Healthcare Network, Philadelphia, PA
| |
Collapse
|
|
14
|
Andueza N, Giner RM, Portillo MP. Risks Associated with the Use of Garcinia as a Nutritional Complement to Lose Weight. Nutrients 2021; 13:450. [PMID: 33572973 PMCID: PMC7911601 DOI: 10.3390/nu13020450] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/23/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023] Open
Abstract
Nowadays, obesity is one of the great nutritional problems facing public health. The prevalence of this pathology has increased in a worrying way over recent years, currently reaching epidemic proportions. In this context, nutritional supplements are presented as a therapeutic alternative to which more and more people are turning to. Nutritional supplements to lose weight based on the Garcinia plant, specifically on Garcinia cambogia, are commonly used. The active principle of this plant to which these properties have been attributed, is hydroxycitric acid (HCA). The aim of the present review is to gather reported data concerning the effectiveness of nutritional supplements based on Garcinia extracts on weight loss and their possible negative effects. Contradictory results have been observed regarding the effectiveness of the supplements. While statistically significant weight loss was observed in some studies, no changes were found in others. Regarding safety, although Garcinia supplements have been revealed as safe in the vast majority of the studies carried out in animal models and humans, some cases of hepatotoxicity, serotonin toxicity and mania have been reported. In conclusion, the results suggest that Garcinia-based supplements could be effective in short-term weight loss, although the data are not conclusive. In addition, the safety of the complement should be further studied.
Collapse
Affiliation(s)
- Naroa Andueza
- Nutrition and Obesity Group, Department of Pharmacy and Food Science, Lucio Lascaray Research Institute, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain;
| | - Rosa M. Giner
- Department of Pharmacology, Faculty of Pharmacy, University of Valencia, 46100 Burjassot, Spain;
- Spanish Agency of Food Safety and Nutrition (AESAN), 28014 Madrid, Spain
| | - Maria P. Portillo
- Nutrition and Obesity Group, Department of Pharmacy and Food Science, Lucio Lascaray Research Institute, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain;
- Spanish Agency of Food Safety and Nutrition (AESAN), 28014 Madrid, Spain
- Bioaraba Health Research Institute, 01009 Vitoria, Spain
- CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain
| |
Collapse
|
|
15
|
Jędrejko K, Lazur J, Muszyńska B. Risk Associated with the Use of Selected Ingredients in Food Supplements. Chem Biodivers 2021; 18:e2000686. [PMID: 33410585 DOI: 10.1002/cbdv.202000686] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 01/05/2021] [Indexed: 12/30/2022]
Abstract
This review focuses on four new product categories of food supplements: pre-workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to 'camouflage' stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti-Doping Agency.
Collapse
Affiliation(s)
- Karol Jędrejko
- Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmaceutical Botany, Medyczna 9 Street, PL, 30-688, Kraków, Poland
| | - Jan Lazur
- Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmaceutical Botany, Medyczna 9 Street, PL, 30-688, Kraków, Poland
| | - Bożena Muszyńska
- Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmaceutical Botany, Medyczna 9 Street, PL, 30-688, Kraków, Poland
| |
Collapse
|
|
16
|
Graf C, Elmassry M, Chu VM, Pawar D, Tijani L. Plexus Slim®-Induced Immune Thrombocytopenic Purpura. Cureus 2020; 12:e11413. [PMID: 33312809 PMCID: PMC7725491 DOI: 10.7759/cureus.11413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Primary immune thrombocytopenic purpura (ITP) is a common cause of thrombocytopenia. Due to the many possible precipitating factors, the diagnostic approach can be complex in nature. Much of the published literature on drug-induced ITP (DITP) report on quinine-induced thrombocytopenia. Here we present a case of the proposed dietary cause of DITP by the weight loss supplement Plexus® which contains two potential thrombocytopenia-causing compounds, garcinia cambogia fruit extract, and chromium polynicotinate. This case highlights how a thorough patient history, including evaluation of supplement use and dietary habits, can be of the utmost importance in the workup of ITP.
Collapse
|
|
17
|
Philips CA, Ahamed R, Rajesh S, George T, Mohanan M, Augustine P. Comprehensive review of hepatotoxicity associated with traditional Indian Ayurvedic herbs. World J Hepatol 2020; 12:574-595. [PMID: 33033566 PMCID: PMC7522561 DOI: 10.4254/wjh.v12.i9.574] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/16/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
With growing antipathy toward conventional prescription drugs due to the fear of adverse events, the general and patient populations have been increasingly using complementary and alternative medications (CAMs) for managing acute and chronic diseases. The general misconception is that natural herbal-based preparations are devoid of toxicity, and hence short- and long-term use remain justified among people as well as the CAM practitioners who prescribe these medicines. In this regard, Ayurvedic herbal medications have become one of the most utilized in the East, specifically the Indian sub-continent, with increasing use in the West. Recent well-performed observational studies have confirmed the hepatotoxic potential of Ayurvedic drugs. Toxicity stems from direct effects or from indirect effects through herbal metabolites, unknown herb-herb and herb-drug interactions, adulteration of Ayurvedic drugs with other prescription medicines, and contamination due to poor manufacturing practices. In this exhaustive review, we present details on their hepatotoxic potential, discuss the mechanisms, clinical presentation, liver histology and patient outcomes of certain commonly used Ayurvedic herbs which will serve as a knowledge bank for physicians caring for liver disease patients, to support early identification and treatment of those who present with CAM-induced liver injury.
Collapse
Affiliation(s)
- Cyriac Abby Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India.
| | - Rizwan Ahamed
- Gastroenterology and Advanced GI Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Sasidharan Rajesh
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Tom George
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Meera Mohanan
- Anesthesia and Critical Care, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Philip Augustine
- Gastroenterology and Advanced GI Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| |
Collapse
|
|
18
|
Ferreira GDSA, Watanabe ALC, Trevizoli NDC, Jorge FMF, Diaz LGG, Couto CDF, Lima LVD, Raupp DRL, Araujo BED. Acute Liver Failure Caused by Use of Fat Burner: A Case Report. Transplant Proc 2020; 52:1409-1412. [PMID: 32192741 DOI: 10.1016/j.transproceed.2020.01.072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 01/10/2020] [Indexed: 02/07/2023]
Abstract
Acute liver failure is a rare condition consisting of abrupt and extensive hepatocyte injury, leading to significant liver dysfunction associated with a high mortality. Liver transplantation is the most effective treatment in severe cases. The most common cause of acute liver failure in Western countries is drug-induced liver injury caused by prescription drugs and herbal and dietary supplements. Thermogenics, or fat burners, are a category of dietary supplements that claim to increase the resting metabolic rate, leading to weight loss. There are previous reports of acute liver failure associated with specific thermogenic formulations. We report the case of a 36-year-old male patient who developed jaundice 7 days after he started taking a thermogenic dietary supplement (Thermo Gun), with progressive deterioration of hepatic function and development of hepatic encephalopathy 19 days after the beginning of the symptoms. He had a Model for End-Stage Liver Disease score of 38 and fulfilled 4 of the King's College Criteria for poor prognosis in patients with acute liver failure. He underwent liver transplantation, receiving a graft from a cadaveric donor, and is alive with good liver graft function 2 years after the transplant. No possible causes for acute liver injury were identified other than the use of the supplement, which contained N-acetyl-L-tyrosine; 1,3,7-trimenthylxanthine; white willow; and 1-hydroxypholedrine. We found no previous reports in the literature of acute liver failure associated with those particular substances. This manuscript is compliant with the Helsinki Congress and the Istanbul Declaration.
Collapse
|
|
19
|
Vilas-Boas V, Gijbels E, Jonckheer J, De Waele E, Vinken M. Cholestatic liver injury induced by food additives, dietary supplements and parenteral nutrition. ENVIRONMENT INTERNATIONAL 2020; 136:105422. [PMID: 31884416 DOI: 10.1016/j.envint.2019.105422] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 12/05/2019] [Accepted: 12/13/2019] [Indexed: 06/10/2023]
Abstract
Cholestasis refers to the accumulation of toxic levels of bile acids in the liver due to defective bile secretion. This pathological situation can be triggered by drugs, but also by ingredients contained in food, food supplements and parenteral nutrition. This paper provides an overview of the current knowledge on cholestatic injury associated with such ingredients, with particular emphasis on the underlying mechanisms of toxicity.
Collapse
Affiliation(s)
- Vânia Vilas-Boas
- Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
| | - Eva Gijbels
- Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
| | - Joop Jonckheer
- Department of Intensive Care, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Elisabeth De Waele
- Department of Intensive Care, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Mathieu Vinken
- Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
| |
Collapse
|
|
20
|
Oketch-Rabah HA, Roe AL, Rider CV, Bonkovsky HL, Giancaspro GI, Navarro V, Paine MF, Betz JM, Marles RJ, Casper S, Gurley B, Jordan SA, He K, Kapoor MP, Rao TP, Sherker AH, Fontana RJ, Rossi S, Vuppalanchi R, Seeff LB, Stolz A, Ahmad J, Koh C, Serrano J, Low Dog T, Ko R. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep 2020; 7:386-402. [PMID: 32140423 PMCID: PMC7044683 DOI: 10.1016/j.toxrep.2020.02.008] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 02/04/2020] [Accepted: 02/12/2020] [Indexed: 02/07/2023] Open
Abstract
As part of the United States Pharmacopeia's ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)."
Collapse
Key Words
- ADME, Absorption, distribution, metabolism, and excretion
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- AUC, area under the curve
- Bw, body weight
- C, Catechin
- CAM, causality assessment method
- CG, (+)‐catechin‐3‐gallate
- CIH, Concanavalin A-induced hepatitis
- CMC, chemistry, manufacturing, and controls
- COMT, catechol‐O‐methyltransferase
- Camellia sinensis
- ConA, Concanavalin A
- DILI, drug‐induced liver injury
- DILIN, Drug‐Induced Liver Injury Network
- DO, Diversity Outbred
- DS, Dietary Supplement
- DSAE, JS3 USP Dietary Supplements Admission Evaluations Joint Standard-Setting Subcommittee
- Dietary supplements
- EC, (–)‐epicatechin
- ECG, (‐)‐epicatechin‐3‐gallate
- EFSA, European Food Safety Authority
- EGC, (–)‐epigallocatechin
- EGCG, (–)‐epigallocatechin‐3‐gallate
- FDA, United States Food and Drug Administration
- GC, (+)‐gallocatechin
- GCG, (–)‐gallocatechin‐3‐gallate
- GT(E), green tea or green tea extract
- GT, green tea
- GTE, green tea extract
- GTEH, EP Green Tea Extract Hepatotoxicity Expert Panel
- Green tea
- Green tea extract
- HDS, herbal dietary supplement
- HPMC, Hydroxypropyl methylcellulose
- Hepatotoxicity
- LD50, lethal dose, median
- LFT(s), liver function test(s)
- LT(s), Liver test(s)
- Liver injury
- MGTT, Minnesota Green Tea Trial
- MIDS, multi-ingredient dietary supplement
- MRL, maximum residue limit
- NAA, N-acetyl aspartate
- NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases
- NIH, National Institutes of Health
- NOAEL, no observed adverse effect level
- NTP, National Toxicology Program
- OSM, online supplementary material
- PAs, Pyrrolizidine Alkaloids
- PD-1, Programmed death domain-1
- PDGTE, powdered decaffeinated green tea extract
- PK/PD, pharmacokinetics and pharmacodynamics
- RUCAM, Roussel Uclaf Causality Assessment Method
- SIDS, single-ingredient dietary supplement
- TGF-beta, Transforming growth factor beta
- USP, United States Pharmacopeia
- γ-GT, Gamma-glutamyl transferase
Collapse
Affiliation(s)
- Hellen A. Oketch-Rabah
- U.S. Pharmacopeial Convention, Rockville, MD, USA
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Amy L. Roe
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Vice Chair, (USP GTEH EP, 2015-2020 cycle)
| | - Cynthia V. Rider
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Herbert L. Bonkovsky
- U.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle)
- Section on Gastroenterology & Hepatology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Gabriel I. Giancaspro
- U.S. Pharmacopeial Convention, Rockville, MD, USA
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Victor Navarro
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
| | - Mary F. Paine
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA
| | - Joseph M. Betz
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Robin J. Marles
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Steven Casper
- U.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle)
| | - Bill Gurley
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Scott A. Jordan
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Kan He
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Mahendra P. Kapoor
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Theertham P. Rao
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Averell H. Sherker
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Liver Diseases Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Blvd., Bethesda, MD, USA
| | - Robert J. Fontana
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Simona Rossi
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
| | | | - Leonard B. Seeff
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
| | - Andrew Stolz
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
| | - Jawad Ahmad
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
| | - Christopher Koh
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Liver Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, 10 Center Drive, Building 10, Rm 9B-16, Bethesda, MD, 20892,USA
| | - Jose Serrano
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Liver Diseases Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Blvd., Bethesda, MD, USA
| | - Tieraona Low Dog
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
| | - Richard Ko
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Chair (USP GTEH EP, 2015-2020 cycle)
| |
Collapse
|
|
21
|
Khetpal N, Mandzhieva B, Shahid S, Khetpal A, Jain AG. Not All Herbals are Benign: A Case of Hydroxycut-induced Acute Liver Injury. Cureus 2020; 12:e6870. [PMID: 32190438 PMCID: PMC7057255 DOI: 10.7759/cureus.6870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Dietary supplements do not need prior Food and Drug Administration (FDA) approval before they are sold to the public per Dietary Supplement Health and Education Act of 1994 (DSHEA). Reporting serious dietary supplement related adverse reactions is voluntary. Hydroxycut is a brand of dietary supplements that are marketed as a popular weight loss product that contains multiple herbal constituents. Due to its potential hepatotoxic effects, FDA issued a warning in 2009 and recommended that consumers discontinue use of Hydroxycut. Hydroxycut was recalled from the market but a reformulated herbal mix is now available again. We are presenting a case of acute liver injury associated with Hydroxycut. The prominent pattern of liver injury is severe hepatocellular injury with the striking elevation of the aminotransferase levels and minimal abnormalities in alkaline phosphatase levels. It can sometimes cause severe hepatocellular necrosis.
Collapse
Affiliation(s)
| | | | - Sonia Shahid
- Internal Medicine, Karachi Medical and Dental College, Karachi, PAK
| | - Akash Khetpal
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | | |
Collapse
|
|
22
|
Yousaf MN, Chaudhary FS, Hodanazari SM, Sittambalam CD. Hepatotoxicity associated with Garcinia cambogia: A case report. World J Hepatol 2019; 11:735-742. [PMID: 31772720 PMCID: PMC6856022 DOI: 10.4254/wjh.v11.i11.735] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 09/28/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
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.
Collapse
Affiliation(s)
- Muhammad Nadeem Yousaf
- Department of Medicine, Medstar Union Memorial Hospital, Baltimore, MD 21218, United States.
| | - Fizah S Chaudhary
- Department of Internal Medicine, American University of Barbados, Wildey 11100, Barbados
| | | | - Charmian D Sittambalam
- Department of Medicine, Medstar Union Memorial Hospital, Baltimore, MD 21218, United States
| |
Collapse
|
|
23
|
Riebensahm C, Ka D, Sow A, Semmo N, Wandeler G. A closer look at the spectrum of drug-induced liver injury in sub-Saharan Africa. Expert Rev Clin Pharmacol 2019; 12:875-883. [PMID: 31269818 DOI: 10.1080/17512433.2019.1638251] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Introduction: Drug-induced liver injury (DILI) has become the most frequent cause of acute liver failure in high-income countries. However, little is known about the determinants of DILI in sub-Saharan Africa (SSA), where the prescription of antimicrobials and the use of potentially hepatotoxic traditional medicine are common. Areas covered: Based on an extensive literature search, we summarize current data available on the epidemiology and risk factors of DILI in SSA. We discuss the most likely causes of DILI in the region, including antimicrobial therapies and traditional medicine. We also highlight research gaps as well as barriers to diagnosis and management of the condition, and explore ways to address these important challenges. Expert opinion: DILI is underestimated in SSA and several factors challenge its early diagnosis, including lack of information on the causes of DILI in the region, sub-optimal knowledge about the condition among clinicians, and structural difficulties faced by health care systems. In order to better prevent the occurrence of DILI and its complications, it is crucial to enhance awareness among health care providers and patients, adapt drug prescription habits and regulations, and improve current knowledge on the main risk factors for DILI, including host genetic and environmental determinants.
Collapse
Affiliation(s)
- Carlotta Riebensahm
- Division of Hepatology, Bern University Hospital, University of Bern , Bern , Switzerland
| | - Daye Ka
- Division of Hepatology, Bern University Hospital, University of Bern , Bern , Switzerland.,Department of Infectious Diseases, Hôpital Fann , Dakar , Senegal
| | - Abdoul Sow
- Division of Hepatology, Bern University Hospital, University of Bern , Bern , Switzerland.,Division of Gastroenterology and Hepatology, Hôpital Principal , Dakar , Senegal
| | - Nasser Semmo
- Division of Hepatology, Bern University Hospital, University of Bern , Bern , Switzerland
| | - Gilles Wandeler
- Department of Infectious Diseases, Hôpital Fann , Dakar , Senegal.,Department of Infectious Diseases, Bern University Hospital, University of Bern , Bern , Switzerland
| |
Collapse
|
|
24
|
Hydroxycitrate: a potential new therapy for calcium urolithiasis. Urolithiasis 2019; 47:311-320. [PMID: 30915494 DOI: 10.1007/s00240-019-01125-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 03/04/2019] [Indexed: 02/07/2023]
Abstract
Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.
Collapse
|
|
25
|
Farrington R, Musgrave IF, Byard RW. Evidence for the efficacy and safety of herbal weight loss preparations. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2019; 17:87-92. [PMID: 30738773 DOI: 10.1016/j.joim.2019.01.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Accepted: 12/14/2018] [Indexed: 12/19/2022]
Abstract
Rising rates of obesity across the globe have been associated with an increase in the use of herbal preparations for weight control. However, the mechanisms of action for these substances are often not known, as is the potential for interaction with other herbal preparations or prescription pharmaceutical drugs. To investigate the reported efficacy and safety of herbal weight loss preparations, we conducted a review of the literature focusing on herbs that are most commonly used in weight loss preparations, specifically, Garcinia cambogia, Camellia sinensis, Hoodia gordonii, Citrus aurantium and Coleus forskohlii. There was no clear evidence that the above herbal preparations would cause sustained long-term weight loss in humans in the long term. Serious illness and even death have occasionally resulted from the use of herbal weight loss preparations. Few clinical trials have been undertaken to evaluate the efficacy and/or safety of herbal weight loss preparations. In addition, potential issues of herb-herb and herb-drug interactions are often not considered. Regulation of these products is much less rigorous than for prescription medications, despite documented cases of associated hepatotoxicity.
Collapse
Affiliation(s)
- Rachael Farrington
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia 5005, Australia.
| | - Ian F Musgrave
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Roger W Byard
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia 5005, Australia; Forensic Science SA, Adelaide, South Australia 5000, Australia
| |
Collapse
|
|
26
|
Finding the bad actor: Challenges in identifying toxic constituents in botanical dietary supplements. Food Chem Toxicol 2018; 124:431-438. [PMID: 30582954 DOI: 10.1016/j.fct.2018.12.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 12/11/2018] [Accepted: 12/17/2018] [Indexed: 12/14/2022]
Abstract
Botanical-derived dietary supplements have widespread use in the general population. The complex and variable nature of botanical ingredients and reports of adverse responses have led to concern for negative human health impacts following consumption of these products. Toxicity testing of the vast number of available products, formulations, and combinations is not feasible due to the time and resource intensive nature of comprehensive testing. Methods are needed to assess the safety of a large number of products via more efficient frameworks. Identification of toxicologically-active constituents is one approach being used, with many advantages toward product regulation. Bioassay-guided fractionation (BGF) is the leading approach used to identify biologically-active constituents. Most BGF studies with botanicals focus on identifying pharmacologically-active constituents for drug discovery or botanical efficacy research. Here, we explore BGF in a toxicological context, drawing from both efficacy and poisonous plant research. Limitations of BGF, including loss of mixture activity and bias toward abundant constituents, and recent advancements in the field (e.g., biochemometrics) are discussed from a toxicological perspective. Identification of active constituents will allow better monitoring of market products for known toxicologically-active constituents, as well as surveying human exposure, two important steps to ensuring the safety of botanical dietary supplements.
Collapse
|
|
27
|
Crescioli G, Lombardi N, Bettiol A, Marconi E, Risaliti F, Bertoni M, Menniti Ippolito F, Maggini V, Gallo E, Firenzuoli F, Vannacci A. Acute liver injury following Garcinia cambogia weight-loss supplementation: case series and literature review. Intern Emerg Med 2018; 13:857-872. [PMID: 29802521 DOI: 10.1007/s11739-018-1880-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 05/17/2018] [Indexed: 02/07/2023]
Abstract
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.
Collapse
Affiliation(s)
- Giada Crescioli
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy.
| | - Niccolò Lombardi
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy
| | - Alessandra Bettiol
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy
| | - Ettore Marconi
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy
| | - Filippo Risaliti
- Division of General Medicine 2, New Hospital "Santo Stefano", Prato, Italy
| | - Michele Bertoni
- Division of General Medicine 2, New Hospital "Santo Stefano", Prato, Italy
| | | | - Valentina Maggini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Referring Center for Phytotherapy, Tuscany Region Careggi, University Hospital, Florence, Italy
| | - Eugenia Gallo
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Referring Center for Phytotherapy, Tuscany Region Careggi, University Hospital, Florence, Italy
| | - Fabio Firenzuoli
- Referring Center for Phytotherapy, Tuscany Region Careggi, University Hospital, Florence, Italy
| | - Alfredo Vannacci
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy
| |
Collapse
|
|
28
|
Teschke R, Wolff A, Eickhoff A, Danan G. Is obesity rather than the dietary supplement used for weight reduction the cause of liver injury? JGH Open 2018; 2:152-157. [PMID: 30483581 PMCID: PMC6152465 DOI: 10.1002/jgh3.12057] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 04/17/2018] [Accepted: 04/23/2018] [Indexed: 02/06/2023]
Abstract
Acute liver injury has been attributed to dietary supplements (DS) used for weight loss, but their causal role was much questioned, and obesity as an alternative cause of the liver injury remained unclear. A comprehensive search of the Medline database was conducted with terms that included "DS," "liver injury," "obesity," "obesity-related liver diseases," and "nonalcoholic steatohepatitis." For each term, we focused on the first 50 publications. We undertook a manual search to identify additional reports. Underlying liver diseases and other health issues are common in patients taking DS for weight reduction. These include obesity or morbid obesity, as well as complex metabolic disorders complicated by excess morbidity and mortality due to associated liver diseases. Among these are nonalcoholic fatty liver disease with potential progression to nonalcoholic steatohepatitis and cirrhosis, often classified as cryptogenic with a rare risk of hepatocellular carcinoma. With the exception of hepatocellular carcinoma, these obesity-related liver diseases were observed to varying degrees in patients, and some even required a liver transplant. This raises the question whether the liver injury that occurred in these patients is due to DS consumed for weight loss or to the underlying obesity-related liver diseases. This analysis showed that, in many instances, the causal role of obesity has been neglected. Obesity-associated liver diseases should be considered as differential diagnosis of liver injury in obese patients using DS.
Collapse
Affiliation(s)
- Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and HepatologyKlinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/MainHanauGermany
| | - Albrecht Wolff
- Department of GastroenterologyGeorg August UniversityGöttingenGermany
| | - Axel Eickhoff
- Department of Internal Medicine II, Division of Gastroenterology and HepatologyKlinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/MainHanauGermany
| | - Gaby Danan
- Pharmacovigilance ConsultancyParisFrance
| |
Collapse
|
|
29
|
Hepatotoxicity Associated with Use of the Weight Loss Supplement Garcinia cambogia: A Case Report and Review of the Literature. Case Reports Hepatol 2018; 2018:6483605. [PMID: 29721342 PMCID: PMC5867608 DOI: 10.1155/2018/6483605] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 01/03/2018] [Accepted: 01/31/2018] [Indexed: 12/21/2022] Open
Abstract
The use of herbal and dietary supplements for weight loss is becoming increasingly common as obesity is becoming major health problem in the United States. Despite the popularity of these natural supplements, there are no guidelines for their therapeutic doses and their safety is always a concern. Garcinia cambogia extract with its active ingredient “hydroxycitric acid” is a component of many weight loss regimens. It suppresses fatty acid biosynthesis and decreases appetite. However, its prolonged use in weight maintenance is unknown. Here we describe a case of acute hepatitis after the use of Garcinia cambogia for weight loss.
Collapse
|
|
30
|
Abstract
By the turn of the twenty-first century, the use of nutraceuticals became increasingly popular in both humans and animals due to their easy access, cost-effectiveness, and tolerability with a wide margin of safety. While some nutraceuticals are safe, others have a toxic potential. For a large number of nutraceuticals, no toxicity/safety data are available due to a lack of pharmacological/toxicological studies. The safety of some nutraceuticals can be compromised via contamination with toxic plants, metals, mycotoxins, pesticides, fertilizers, drugs of abuse, etc. Knowledge of pharmacokinetic/toxicokinetic studies appears to play a pivotal role in safety and toxicity assessment of nutraceuticals. Interaction studies are essential to determine efficacy, safety, and toxicity when nutraceuticals and therapeutic drugs are used concomitantly. This chapter describes various aspects of nutraceuticals, particularly their toxic potential, and the factors influencing their safety.
Collapse
|
|
31
|
Vitalone A, Di Sotto A, Mammola CL, Heyn R, Miglietta S, Mariani P, Sciubba F, Passarelli F, Nativio P, Mazzanti G. Phytochemical analysis and effects on ingestive behaviour of a Caralluma fimbriata extract. Food Chem Toxicol 2017; 108:63-73. [PMID: 28713048 DOI: 10.1016/j.fct.2017.07.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 06/16/2017] [Accepted: 07/12/2017] [Indexed: 12/22/2022]
Abstract
Caralluma fimbriata Wall. is currently used as a "natural slimming" food supplement, likely due to its content in pregnane glycosides. In the present study, a commercially available Caralluma fimbriata extract (Slimaluma®; CFE, 100 mg/kg) has been evaluated for its ability to affect the ingestive behaviour in female rats, also with reference to the modulation of the brain neuropeptides NPY and ORX.The interference of CFE with α-amylase and lipase enzymes has been investigated in vitro, as possible peripheral mechanism of action. Also, the chemical composition of CFE has been assessed by NMR and spectrophotometric analysis. Results from in vivo study showed that CFE induced effects neither on blood parameters, nor on liver and gut histomorphology. Interestingly, a reduction in body weight gain with an increase in water intake and hypothalamic levels of NPY and ORX peptides were found. Phytochemical analysis, showed CFE contained about 12% of pregnane glycosides and 1.3% of polyphenols. Present results suggest possible effects of C. fimbriata on ingestive behaviour, likely mediated by central and peripheral mechanisms.
Collapse
Affiliation(s)
- Annabella Vitalone
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| | - Antonella Di Sotto
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Caterina Loredana Mammola
- Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy
| | - Rosemarie Heyn
- Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy
| | - Selenia Miglietta
- Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy
| | - Paola Mariani
- Department of General and Specialized Surgery "P. Stefanini", Sapienza University of Rome, V.le Del Policlinico 155, 00161 Rome, Italy
| | - Fabio Sciubba
- Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| | - Francesca Passarelli
- Department of Molecular Medicine and of Medical Surgical Sciences and Biotechnology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| | - Paola Nativio
- Department of Molecular Medicine and of Medical Surgical Sciences and Biotechnology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| | - Gabriela Mazzanti
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| |
Collapse
|
|
32
|
Zaidan J, Tabet R, Karam B, Daneshvar F, Raza M, Bekheit S. Asystole caused by Hydroxycut Hardcore: A case report and literature review. Ann Noninvasive Electrocardiol 2017; 23:e12479. [PMID: 28653348 DOI: 10.1111/anec.12479] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 05/23/2017] [Indexed: 11/28/2022] Open
Abstract
Obesity is a rising epidemic worldwide driving people to search for remedy through nonconventional therapies. Hydroxycut products are popular supplements used as weight loss aids. Many reports revealed serious adverse effects related to their ingestion. We report the case of a 37-year-old healthy male patient who presented following an episode of syncope. On telemetry, he manifested recurrent sinus node arrests, including a symptomatic 24 s sinus pause. The patient admitted to taking Hydroxycut Hardcore for 10 days previously. After discontinuation of the drug, his symptoms completely resolved. This is the first case of Hydroxycut-associated syncope secondary to bradyarrhythmia.
Collapse
Affiliation(s)
- Julie Zaidan
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY, USA
| | - Rabih Tabet
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY, USA
| | - Boutros Karam
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY, USA
| | - Farshid Daneshvar
- Department of Cardiovascular Medicine, Staten Island University Hospital, Staten Island, NY, USA
| | - Mohammed Raza
- Department of Cardiovascular Medicine, Staten Island University Hospital, Staten Island, NY, USA
| | - Soad Bekheit
- Department of Cardiovascular & Electrophysiology Medicine, Staten Island University Hospital, Staten Island, NY, USA
| |
Collapse
|
|
33
|
Xing S, Sharp LK, Touchette DR. Weight loss drugs and lifestyle modification: Perceptions among a diverse adult sample. PATIENT EDUCATION AND COUNSELING 2017; 100:592-597. [PMID: 27847132 DOI: 10.1016/j.pec.2016.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 09/26/2016] [Accepted: 11/08/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVES Explore how adults from diverse racial and socioeconomic backgrounds perceive the use of weight loss drugs (prescription, over-the counter, herbals and supplements) and lifestyle modification. METHODS Individual, face-to-face, semi-structured interviews were conducted with persons presenting to an academic hospital-affiliated outpatient pharmacy serving ethnic minorities and low income individuals. RESULTS Fifty persons were interviewed, including 21 African Americans, 11 Hispanics and 17 low-income individuals (annual income <$20,000), of whom 33 self-reported as overweight or obese. Ever-users (14/50) and nonusers (36/50) of weight loss drugs expressed a belief in the importance of diet and exercise, but were not necessarily doing so themselves. Fear of side effects and skepticism towards efficacy of drugs deterred use. Some expressed concern over herbal product safety; others perceived herbals as natural and safe. Drugs were often viewed as a short-cut and not a long-term weight management solution. CONCLUSION A range of concerns related to the safety and efficacy of weight loss drugs were expressed by this lower income, ethnically diverse population of underweight to obese adults. PRACTICE IMPLICATIONS There is need and opportunity for healthcare providers to provide weight loss advice and accurate information regarding the safety and efficacy of various types of weight loss approaches.
Collapse
Affiliation(s)
- S Xing
- University of Illinois at Chicago Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL, 833 South Wood St (MC 871), 60612-7230, USA.
| | - L K Sharp
- University of Illinois at Chicago Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL, 833 South Wood St (MC 871), 60612-7230, USA.
| | - D R Touchette
- University of Illinois at Chicago Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL, 833 South Wood St (MC 871), 60612-7230, USA.
| |
Collapse
|
|
34
|
Abstract
The increase in the use of herbal and dietary supplements (HDSs) over the last decades has been accompanied by an increase in the reports of HDS-associated hepatotoxicity. The spectrum of HDS-induced liver injury is diverse and the outcome may vary from transient liver test increases to fulminant hepatic failure resulting in death or requiring liver transplant. There are no validated standardized tools to establish the diagnosis, but some HDS products have a typical clinical signature that may help to identify HDS-induced liver injury.
Collapse
Affiliation(s)
- Ynto S. de Boer
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
,Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Averell H. Sherker
- Liver Diseases Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| |
Collapse
|
|
35
|
Adike A, Smith ML, Chervenak A, Vargas HE. Hydroxycut-related Vanishing Bile Duct Syndrome. Clin Gastroenterol Hepatol 2017; 15:142-144. [PMID: 27151488 DOI: 10.1016/j.cgh.2016.04.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 04/21/2016] [Accepted: 04/26/2016] [Indexed: 02/07/2023]
Affiliation(s)
- Abimbola Adike
- Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Phoenix, Arizona
| | - Maxwell L Smith
- Department of Pathology, Mayo Clinic Arizona, Phoenix, Arizona
| | - Amy Chervenak
- Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Phoenix, Arizona
| | - Hugo E Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Phoenix, Arizona.
| |
Collapse
|
|
36
|
Lunsford KE, Bodzin AS, Reino DC, Wang HL, Busuttil RW. Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation. World J Gastroenterol 2016; 22:10071-10076. [PMID: 28018115 PMCID: PMC5143754 DOI: 10.3748/wjg.v22.i45.10071] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 07/06/2016] [Accepted: 08/05/2016] [Indexed: 02/06/2023] Open
Abstract
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, however, 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.
Collapse
|
|
37
|
Abstract
Drug-induced liver injury (DILI) remains a significant clinical challenge and is the leading cause of acute liver failure in most countries. An aging population that uses more medications, a constant influx of newly developed drugs and a growing risk from unfamiliar herbal and dietary supplements will make DILI an increasing part of clinical practice. Currently, the most effective strategy for disease management is rapid identification, withholding the inciting agents, supportive care and having a firm understanding of the expected natural history. There are resources available to aid the clinician, including a new online "textbook" as well as causality assessment tools, but a heightened awareness of risk and the disease's varying phenotypes and good history-taking remain cornerstones to diagnosis. Looking ahead, growing registries of cases, pharmacoepidemiology studies and translational research into the mechanisms of injury may produce better diagnostic tools, markers for risk and disease, and prevention and therapeutics.
Collapse
Affiliation(s)
- Tanvir Haque
- Department of Medicine and Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Eizaburo Sasatomi
- Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Paul H Hayashi
- Department of Medicine and Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| |
Collapse
|
|
38
|
Knapik JJ, Trone DW, Austin KG, Steelman RA, Farina EK, Lieberman HR. Prevalence, Adverse Events, and Factors Associated with Dietary Supplement and Nutritional Supplement Use by US Navy and Marine Corps Personnel. J Acad Nutr Diet 2016; 116:1423-1442. [DOI: 10.1016/j.jand.2016.02.015] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Accepted: 02/12/2016] [Indexed: 01/17/2023]
|
|
39
|
Brown AC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2016; 107:472-501. [PMID: 27402097 DOI: 10.1016/j.fct.2016.07.001] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 06/30/2016] [Accepted: 07/01/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND No online current list of potentially life-threatening, hepatotoxic herbs and dietary supplements based on PubMed case reports exists in a summarized tabular form. METHODS Documented case reports of herbs or dietary supplements (DS; includes herbs) appearing to contribute to liver injury were used to create an online "DS Toxic Table" of potentially hepatotoxic herbs and dietary supplements (PubMed, 1966 to June, 2016, and cross-referencing). The spectrum of DS induced liver injuries (DSILI) included elevated liver enzymes, hepatitis, steatosis, cholestasis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, veno-occlusive disease, acute liver failure requiring a liver transplant, and death. RESULTS Over the past 50 years, approximately 21 herbs (minus germander and usnic acid that are no longer sold) and 12 dietary supplements (minus the nine no longer sold and vitamin A & niacin due to excess intake) posed a possible risk for liver injures in certain individuals. The herbs with the most number of reported publications (but not cases studies) in descending order, were germander, black cohosh, kava extract, and green tea extract. CONCLUSION These online DS Toxic Tables will contribute to continued Phase IV post marketing surveillance to detect possible liver toxicity cases and serve to forewarn consumers, clinicians, and corporations.
Collapse
Affiliation(s)
- Amy Christine Brown
- Department of Complementary and Alternative Medicine, John A. Burns School of Medicine, 651 Ilalo Street, MEB 223, University of Hawaii at Manoa, Honolulu, HI, 96813, USA.
| |
Collapse
|
|
40
|
Frenzel C, Teschke R. Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation. Int J Mol Sci 2016; 17:E588. [PMID: 27128912 PMCID: PMC4881436 DOI: 10.3390/ijms17050588] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 03/31/2016] [Accepted: 04/11/2016] [Indexed: 12/13/2022] Open
Abstract
Herb induced liver injury (HILI) and drug induced liver injury (DILI) share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM) rarely causes elevated liver tests (LT). However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method) is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.
Collapse
Affiliation(s)
- Christian Frenzel
- Department of Medicine I, University Medical Center Hamburg Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, 63450 Hanau, Germany.
| |
Collapse
|
|
41
|
García-Cortés M, Robles-Díaz M, Ortega-Alonso A, Medina-Caliz I, Andrade RJ. Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics. Int J Mol Sci 2016; 17:537. [PMID: 27070596 PMCID: PMC4848993 DOI: 10.3390/ijms17040537] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 03/17/2016] [Accepted: 03/25/2016] [Indexed: 02/07/2023] Open
Abstract
Dietary supplements (DS) are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI) is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. The aim of this manuscript is to report a tabular listing with a description of DS associated with hepatotoxicity as well as review the phenotype and severity of DSILI. Natural remedies related to hepatotoxicity can be divided into herbal product-induced liver injury and DS-induced liver injury. In this article, we describe different DS associated with liver injury, some of them manufactured DS containing several ingredients (Herbalife™ products, Hydroxycut™, LipoKinetix™, UCP-1 and OxyELITE™) while others have a single ingredient (green tea extract, linoleic acid, usnic acid, 1,3-Dimethylamylamine, vitamin A, Garcinia cambogia and ma huang). Additional DS containing some of the aforementioned ingredients implicated in liver injury are also covered. We have also included illicit androgenic anabolic steroids for bodybuilding in this work, as they are frequently sold under the denomination of DS despite being conventional drugs.
Collapse
Affiliation(s)
- Miren García-Cortés
- Servicio de Farmacología Clíınica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), 29010 Málaga, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain.
| | - Mercedes Robles-Díaz
- Servicio de Farmacología Clíınica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), 29010 Málaga, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain.
| | - Aida Ortega-Alonso
- Servicio de Farmacología Clíınica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), 29010 Málaga, Spain.
| | - Inmaculada Medina-Caliz
- Servicio de Farmacología Clíınica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), 29010 Málaga, Spain.
| | - Raul J Andrade
- Servicio de Farmacología Clíınica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), 29010 Málaga, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain.
| |
Collapse
|
|
42
|
Avigan MI, Mozersky RP, Seeff LB. Scientific and Regulatory Perspectives in Herbal and Dietary Supplement Associated Hepatotoxicity in the United States. Int J Mol Sci 2016; 17:331. [PMID: 26950122 PMCID: PMC4813193 DOI: 10.3390/ijms17030331] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 02/16/2016] [Accepted: 02/16/2016] [Indexed: 01/06/2023] Open
Abstract
In the United States (US), the risk of hepatotoxicity linked to the widespread use of certain herbal products has gained increased attention among regulatory scientists. Based on current US law, all dietary supplements sold domestically, including botanical supplements, are regulated by the Food and Drug Administration (FDA) as a special category of foods. Under this designation, regulatory scientists do not routinely evaluate the efficacy of these products prior to their marketing, despite the content variability and phytochemical complexity that often characterizes them. Nonetheless, there has been notable progress in the development of advanced scientific methods to qualitatively and quantitatively measure ingredients and screen for contaminants and adulterants in botanical products when hepatotoxicity is recognized.
Collapse
Affiliation(s)
- Mark I Avigan
- Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
| | - Robert P Mozersky
- Office of Dietary Supplement Products, Center for Food Safety and Applied Nutrition, 5100 Paint Branch Parkway, College Park, MD 20740, USA.
| | | |
Collapse
|
|
43
|
Abstract
CONTEXT Drug-induced liver injury (DILI) represents a diverse set of responses following exposure to any manufactured or naturally occurring chemical compound. Drug-induced liver injury is of major concern owing to the ever increasing number of compounds introduced into the market for treatment of various diseases as well as the increasing popularity of herbals, which lend themselves to self-medication but are not rigorously regulated. OBJECTIVE To provide an overview of the prevalence, classification, and diagnosis of DILI with emphasis on pathogenesis and the role of a liver biopsy. To focus on the most common, emerging, and herbal agents that cause DILI with emphasis on the histologic pattern of injury observed. DATA SOURCES A review of the literature was drawn from the PubMed (US National Library of Medicine) repository, textbooks, and online databases. All figures were taken from cases seen at our tertiary referral center, which is 1 of 12 participating sites in the National Institutes of Health-funded Drug-Induced Liver Injury Network. CONCLUSIONS Drug-induced liver injury due to prescription, over-the-counter, and herbal products is a major cause of liver disease in the United States and around the world. Diagnosis of DILI is challenging because there is no single clinical, laboratory, or histologic feature specific to DILI. Accurate diagnosis requires establishing a causal relationship with the suspected agent and excluding competing causes of liver injury. The liver biopsy is an essential component in the management of DILI by offering clues to the underlying pathogenesis, providing prognostic information, and guiding therapy.
Collapse
Affiliation(s)
| | | | - Romil Saxena
- From the Department of Pathology and Laboratory Medicine (Drs Fisher and Ms Saxena)
| |
Collapse
|
|
44
|
Salacinski AJ, Howell SM, Hill DL, Mauk SM. The Acute Effects of Nonstimulant Over-the-Counter Dietary Herbal Supplements on Resting Metabolic Rate. J Diet Suppl 2015; 13:368-77. [PMID: 26317375 DOI: 10.3109/19390211.2015.1036191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Weight loss supplements are widely advertised and highly sought out products. Many supplements claim to increase body fat utilization, increase resting metabolic rate (RMR), and to improve body composition by decreasing total body fat composition. Therefore, the purpose of this study was to determine the acute effect of nonstimulant herbal supplements on RMR and substrate utilization. METHODS Ten female and 16 male participants (mean age 23.7 ± 3.9 years; mean weight 79.2 ± 18.2 kg) completed a random-repeated measures crossover study. Participants completed a total of three RMRs by either ingesting a placebo (P) or one of two supplements [raspberry ketones (R) or metabolic activator blend (MAB)] 2 hours prior to testing. RESULTS No significant difference was found for RMR for P vs. MAB (p = .130), vs. R (p = .588), and MAB vs. R (p = .636). No significant difference was found for respiratory quotient for P vs. MAB (p = .056), vs. R (p = .149), and MAB vs. R (p = .764). No significant difference was found for substrate utilization: percent carbohydrate utilization, P vs. MAB (p = .052), P vs. R (p = .124), and MAB vs. R (p = .680); and percent fat utilization, P vs. MAB (p = .052), P vs. R (p = .120), and MAB vs. R (p = .749). CONCLUSIONS Therefore, nonstimulant weight loss supplements may not be beneficial for weight loss, or an increase of fat utilization.
Collapse
Affiliation(s)
- Amanda J Salacinski
- a Department of Kinesiology and Physical Education , Northern Illinois University , DeKalb , IL , USA
| | - Steven M Howell
- a Department of Kinesiology and Physical Education , Northern Illinois University , DeKalb , IL , USA
| | - Danielle L Hill
- a Department of Kinesiology and Physical Education , Northern Illinois University , DeKalb , IL , USA
| | - Steven M Mauk
- a Department of Kinesiology and Physical Education , Northern Illinois University , DeKalb , IL , USA
| |
Collapse
|
|
45
|
Zheng EX, Navarro VJ. Liver Injury from Herbal, Dietary, and Weight Loss Supplements: a Review. J Clin Transl Hepatol 2015; 3:93-8. [PMID: 26357638 PMCID: PMC4548352 DOI: 10.14218/jcth.2015.00006] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Revised: 03/23/2015] [Accepted: 03/30/2015] [Indexed: 12/11/2022] Open
Abstract
Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury.
Collapse
Affiliation(s)
- Elizabeth X. Zheng
- Correspondence to: Elizabeth X. Zheng, Department of Hepatology, Einstein Healthcare Network, 5401 Old York Road, Suite 505, Philadelphia, PA 19141, USA.Tel: +1‐215‐456‐8242, Fax: +1‐215‐456‐8058, E‐mail:
| | | |
Collapse
|
|
46
|
Haimowitz S, Hsieh J, Shcherba M, Averbukh Y. Liver failure after Hydroxycut™ use in a patient with undiagnosed hereditary coproporphyria. J Gen Intern Med 2015; 30:856-9. [PMID: 25666208 PMCID: PMC4441672 DOI: 10.1007/s11606-014-3153-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 11/19/2013] [Accepted: 12/12/2014] [Indexed: 11/26/2022]
Abstract
We report the case of a young male presenting with cholestatic liver failure. After an extensive workup, the etiology of the liver failure was determined to be due to hereditary coprophorphyria (HCP). The inciting event was the use of Hydroxycut™, an over-the-counter supplement to promote weight loss that has been reported to cause oxidative liver injury in vulnerable populations. Although HCP is a rare cause of cholestatic liver failure, it is treatable if diagnosed correctly and in a timely manner. In this clinical vignette, we discuss a case that highlights the genetic susceptibility to disease that can be unmasked by environmental exposures. We also review the relevant literature on Hydroxycut™ and how it can affect hepatic function.
Collapse
|
|
47
|
Araujo JL, Worman HJ. Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut. BMJ Case Rep 2015; 2015:bcr-2015-210303. [PMID: 25948859 DOI: 10.1136/bcr-2015-210303] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts.
Collapse
Affiliation(s)
- James L Araujo
- Department of Medicine, Columbia University, New York, New York, USA
| | - Howard J Worman
- Department of Medicine, Columbia University, New York, New York, USA Department of Pathology and Cell Biology Columbia University, New York, New York, USA
| |
Collapse
|
|
48
|
Teschke R, Eickhoff A. Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps. Front Pharmacol 2015; 6:72. [PMID: 25954198 PMCID: PMC4407580 DOI: 10.3389/fphar.2015.00072] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 03/18/2015] [Indexed: 12/19/2022] Open
Abstract
Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.
Collapse
Affiliation(s)
- Rolf Teschke
- Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt MainFrankfurt, Germany
| | | |
Collapse
|
|
49
|
Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology 2015; 148:517-532.e3. [PMID: 25500423 DOI: 10.1053/j.gastro.2014.12.004] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 12/02/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023]
Abstract
Herbal products have been used for centuries among indigenous people to treat symptoms and illnesses. Recently, their use in Western countries has grown significantly, rivaling that of prescription medications. Currently, herbal products are used mainly for weight loss and bodybuilding purposes but also to improve well-being and symptoms of chronic diseases. Many people believe that because they are natural, they must be effective and safe; however, these beliefs are erroneous. Few herbal products have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary. Moreover, current highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant. Herbal products are no safer than conventional drugs and have caused liver injury severe enough to require transplantation or cause death. Furthermore, their efficacy, safety, and claims are not assessed by regulatory agencies, and there is uncertainty about their reported and unreported contents. We review the history of commonly used herbal products, as well as their purported efficacies and mechanisms and their adverse effects.
Collapse
Affiliation(s)
| | - Herbert L Bonkovsky
- Liver Digestive & Metabolic Disorders Laboratory, Carolinas HealthCare System, Charlotte, North Carolina
| | - Victor J Navarro
- Jefferson Medical College, Einstein Healthcare Network, Philadelphia, Pennsylvania
| | - Guqi Wang
- Carolinas HealthCare System, Charlotte, North Carolina
| |
Collapse
|
|
50
|
Stickel F, Shouval D. Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol 2015; 89:851-65. [DOI: 10.1007/s00204-015-1471-3] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 02/05/2015] [Indexed: 12/15/2022]
|