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Matusak M, Aljabban J, Wirtz M, Agni R, Spengler E. Cholestasis Linked to Bodybuilding Supplements: Exploring the Risks of Contamination. Case Reports Hepatol 2024; 2024:5112461. [PMID: 38826497 PMCID: PMC11142851 DOI: 10.1155/2024/5112461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 10/26/2023] [Accepted: 04/22/2024] [Indexed: 06/04/2024] Open
Abstract
Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male recreational bodybuilder who presented with muscle cramping, fatigue, and diffuse itching in the setting of bodybuilding supplement use. Labs showed cholestatic liver injury, and liver biopsy revealed bland cholestasis and sinusoidal dilation. He was diagnosed with anabolic-androgenic steroid-induced liver injury. He was symptomatically managed with plasmapheresis for debilitating pruritus. This case highlights drug-induced liver injury as a complication of bodybuilding supplement use containing unlabeled anabolic-androgenic steroids. Sports medicine providers should inquire on herbal and dietary supplement use and be aware of potential contaminants.
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Affiliation(s)
- Mark Matusak
- Department of Family Medicine, University of Wisconsin Hospital and Clinics, Madison, USA
| | - Jihad Aljabban
- Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, USA
| | - Mark Wirtz
- Department of Family Medicine, University of Wisconsin Hospital and Clinics, Madison, USA
| | - Rashmi Agni
- Department of Pathology, University of Wisconsin Hospital and Clinics, Madison, USA
| | - Erin Spengler
- Department of Gastroenterology and Hepatology, University of Wisconsin Hospital and Clinics, Madison, USA
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2
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Carty J, Navarro VJ. Dietary Supplement-Induced Hepatotoxicity: A Clinical Perspective. J Diet Suppl 2024; 22:58-77. [PMID: 38528750 DOI: 10.1080/19390211.2024.2327546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
The consumption of dietary supplements (DS) has resulted in a significant and escalating number of cases involving liver injury. It is crucial for clinicians and consumers to be well informed about the adverse effects of such products, leading to their discontinuation and timely reporting of any harmful cases. This article delves into the clinical perspective of DS-related hepatotoxicity, highlighting key concepts such as a systematic diagnostic approach. The discussion extends to notable examples of both currently popular and potential future dietary supplements, such as garcinia cambogia, turmeric, and ashwagandha, accompanied by an overview of recent findings. Causality assessment tools play a crucial role in establishing a connection between these products and instances of liver injury, with consideration of the advantages and disadvantages associated with their use. Fostering a comprehensive understanding of regulatory standards, coupled with a solid foundation of knowledge of DS, will prove instrumental in preventing DS-related hepatotoxicity. Achieving this goal requires collaborative efforts from both consumers and clinicians.
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Affiliation(s)
- Jordan Carty
- Department of Medicine, Jefferson Einstein Medical Center, Philadelphia, PA, USA
| | - Victor J Navarro
- Department of Medicine, Jefferson Einstein Medical Center, Philadelphia, PA, USA
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Abstract
Herbal and dietary supplements represent a multi-billion-dollar industry reportedly used by over half of American adults. However, these products are not regulated by the Federal Drug Agency and contain a wide range of contaminants, leading to over 50,000 adverse events each year. This review aims to highlight the widespread use and current regulatory status of herbal and dietary supplements, identify the presentation and diagnostic dilemmas faced with liver injury, and discuss the most common agents implicated in herbal and dietary supplement hepatotoxicity.
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Affiliation(s)
- Jonathan Kwong-Shing Lin
- Division of Digestive and Liver Disease, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887, USA
| | - Shannan R. Tujios
- Division of Digestive and Liver Disease, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887, USA
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Conway K, Ferstl C, Kumar M. Dietary supplement adulteration - knowledge, attitudes, and practices of California health care professionals: A cross-sectional survey study. PATIENT EDUCATION AND COUNSELING 2023; 114:107824. [PMID: 37290282 DOI: 10.1016/j.pec.2023.107824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/08/2023] [Accepted: 05/24/2023] [Indexed: 06/10/2023]
Abstract
OBJECTIVE To assess knowledge, attitudes, and practices surrounding dietary supplements (DS) among California health care professionals (HCPs) and assess factors contributing to the frequency with which HCPs discuss DS with patients. METHODS In this cross-sectional study, an online questionnaire was distributed to HCPs in California from December 2021-April 2022 via professional membership email listservs. RESULTS Among 514 HCPs, overall knowledge of DS did not vary significantly by professional group, and 90% had received little to no DS education. Pharmacists (OR = 0.328, p = 0.0001) and those with less reported DS education (OR = 0.58, p = 0.0045; OR = 0.075, p = 0.0097) had a decreased likelihood of initiating conversations about DS more frequently. Females (OR = 2.5, p < 0.0001) and those with a higher knowledge score (OR = 1.2, p = 0.0297) had an increased likelihood of initiating conversations about DS more frequently. CONCLUSIONS HCPs acknowledge the clinical significance of DS adulteration and would benefit from additional informational resources to reduce the adverse effects associated with adulterated supplements. PRACTICE IMPLICATIONS HCPs initiate more conversations about DS use when they are more informed and will gain from staying up to date on DS-related information to encourage more patient communication.
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Affiliation(s)
- Kimberly Conway
- California Department of Public Health, Sacramento, USA; California Epidemiologic Investigation Service (Cal-EIS) Fellowship, Sacramento, USA.
| | - Carrie Ferstl
- California Department of Public Health, Sacramento, USA.
| | - Madhur Kumar
- California Department of Public Health, Sacramento, USA.
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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.
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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
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6
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Gurley BJ, McGill MR, Koturbash I. Hepatotoxicity due to herbal dietary supplements: Past, present and the future. Food Chem Toxicol 2022; 169:113445. [PMID: 36183923 PMCID: PMC11404749 DOI: 10.1016/j.fct.2022.113445] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/20/2022] [Accepted: 09/23/2022] [Indexed: 11/26/2022]
Abstract
Dietary supplements (DS) constitute a widely used group of products comprising vitamin, mineral, and botanical extract formulations. DS of botanical or herbal origins (HDS) comprise nearly 30% of all DS and are presented on the market either as single plant extracts or multi-extract-containing products. Despite generally safe toxicological profiles of most products currently present on the market, rising cases of liver injury caused by HDS - mostly by multi-ingredient and adulterated products - are of particular concern. Here we discuss the most prominent historical cases of HDS-induced hepatotoxicty - from Ephedra to Hydroxycut and OxyELITE Pro-NF, as well as products with suspected hepatotoxicity that are either currently on or are entering the market. We further provide discussion on overcoming the existing challenges with HDS-linked hepatotoxicity by introduction of advanced in silico, in vitro, in vivo, and microphysiological system approaches to address the matter of safety of those products before they reach the market.
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Affiliation(s)
- Bill J Gurley
- National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Mitchell R McGill
- Department of Environmental Health Sciences, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Igor Koturbash
- Department of Environmental Health Sciences, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
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Assis MHD, Alves BC, Luft VC, Dall'alba V. LIVER INJURY INDUCED BY HERBAL AND DIETARY SUPPLEMENTS: A POOLED ANALYSIS OF CASE REPORTS. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:522-530. [PMID: 36515339 DOI: 10.1590/s0004-2803.202204000-84] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 08/03/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The intake of dietary supplements and medicinal plants is very popular worldwide. However, these products are not innocuous, and their intake can cause severe damage to health, especially liver injury. OBJECTIVE This study aims to describe the clinical cases of dietary supplements-induced liver injury (DSILI) and herb-induced liver injury (HILI), identifying the main products involved and the clinical outcomes related to them. METHOD A literature search was performed in PubMed, EMBASE, Google Scholar, and LILACS databases, using the search terms: "Chemical and Drug-Induced Liver Injury", "Dietary Supplements" and "Herbal" and their synonyms. RESULTS 189 articles were included in the study, totaling 428 clinical cases of drug-induced liver injury. The most frequent agents of liver injury were Herbalife® products, associated with 50 cases, Polygonum multiflorum, with 25 cases, Hydroxycut® products, and green tea, both associated in 19 cases, and Oxyelite Pro® and kava tea, both associated with 16 cases. Most individuals required hospitalization (82.6%) and an important number of cases evolved to death (3.6%), liver transplantation (8.9%), or chronic liver disease (1.9%). CONCLUSION The indiscriminate use of dietary supplements and herbal products was associated with an alarming number of cases of liver injury. The mechanisms through which each of the products causes liver damage still need to be better understood, but this review is a warning about the risk associated with the use of products considered harmless by a large part of the population.
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Affiliation(s)
- Michelle Hoff de Assis
- Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Curso de Graduação em Nutrição, Porto Alegre, RS, Brasil
| | - Bruna Cherubini Alves
- Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Porto Alegre, RS, Brasil
| | - Vivian Cristine Luft
- Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Curso de Graduação em Nutrição, Porto Alegre, RS, Brasil
- Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Epidemiologia, Porto Alegre, RS, Brasil
- Hospital de Clínicas de Porto Alegre, Serviço de Nutrição e Dietética; Porto Alegre, RS, Brasil
| | - Valesca Dall'alba
- Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Curso de Graduação em Nutrição, Porto Alegre, RS, Brasil
- Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Porto Alegre, RS, Brasil
- Hospital de Clínicas de Porto Alegre, Serviço de Nutrição e Dietética; Porto Alegre, RS, Brasil
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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.
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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:
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9
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Rao A, Rule JA, Hameed B, Ganger D, Fontana RJ, Lee WM. Secular Trends in Severe Idiosyncratic Drug-Induced Liver Injury in North America: An Update From the Acute Liver Failure Study Group Registry. Am J Gastroenterol 2022; 117:617-626. [PMID: 35081550 PMCID: PMC10668505 DOI: 10.14309/ajg.0000000000001655] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 01/03/2022] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Idiosyncratic drug-induced liver injury (DILI) is the second leading cause of acute liver failure (ALF) in the United States. Our study aims were to characterize secular trends in the implicated agents, clinical features, and outcomes of adults with DILI ALF over a 20-year period. METHODS Among 2,332 patients with ALF enrolled in the ALF Study Group registry, 277 (11.9%) were adjudicated as idiosyncratic DILI ALF (INR ≥ 1.5 and hepatic encephalopathy) through expert opinion. The 155 cases in era 1 (January 20, 1998-January 20, 2008) were compared with the 122 cases in era 2 (January 21, 2008-January 20, 2018). RESULTS Among 277 cases of DILI ALF, 97 different agents, alone or in combination, were implicated: antimicrobials, n = 118 (43%); herbal/dietary supplements (HDS), n = 42 (15%); central nervous system agents/illicit substances, n = 37 (13%); oncologic/biologic agents, n = 29 (10%); and other, n = 51 (18%). Significant trends over time included (i) an increase in HDS DILI ALF (9.7% vs 22%, P < 0.01) and decrease in antimicrobial-induced DILI ALF (45.8% vs. 38.5%, P = 0.03) and (ii) improved overall transplant-free survival (23.5%-38.7%, P < 0.01) while the number of patients transplanted declined (46.4% vs 33.6%, P < 0.03). DISCUSSION DILI ALF in North America is evolving, with HDS cases rising and other categories of suspect drugs declining. The reasons for a significant increase in transplant-free survival and reduced need for liver transplantation over time remain unclear but may be due to improvements in critical care, increased NAC utilization, and improved patient prognostication.
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Affiliation(s)
- Ashwin Rao
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Jody A. Rule
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Bilal Hameed
- Division of Gastroenterology and Hepatology, University of California San Francisco School of Medicine, San Francisco, California, USA
| | - Daniel Ganger
- Division of Gastroenterology and Hepatology, Northwestern Medicine, Chicago, Illinois, USA
| | - Robert J. Fontana
- Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - William M. Lee
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Lua PL, Roslim NA, Ahmad A, Mansor M, Aung MMT, Hamzah F. Complementary and Alternative Therapies for Weight Loss: A Narrative Review. J Evid Based Integr Med 2021; 26:2515690X211043738. [PMID: 34496677 PMCID: PMC8436299 DOI: 10.1177/2515690x211043738] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Despite various strategies, overweight and obesity problems are still increasingly prevalent worldwide with serious health outcomes. Consequently, the continuous demand for more effective, safe and acceptable therapies for reducing body weight is also escalating—including complementary and alternative therapies (CATs). The aim of this review is to provide a summary of the most commonly- and recently-used CATs, with evaluation of their safety and efficacy for weight loss. Electronic scientific databases such as Scopus, PubMed and EBSCO Host were explored for articles that reported CATs for overweight and obesity treatment from 2015 to December 2019. Only systematic reviews, meta-analysis and randomized controlled trials (RCTs) published in English were included. Studies whereby CATs were not utilized for reducing body weight were excluded. Eight systematic reviews and meta-analyses and 11 additional RCTs with 765 participants (50.2% overweight and 49.8% obese) related to hypnotherapy, acupuncture and dietary supplements met the inclusion criteria. Their results suggested that spirulina, chitosan, probiotic, EPA + DHA, vitamin D, fiber, and herbal extract supplementation may all provide small reductions in body weight (ranging from 1-10 kg). Interestingly, hypnotherapy and acupuncture reported significantly greater reduction in body weight compared with placebo (p < 0.001 and p < 0.0001, respectively). Nonetheless, the evidence is still relatively limited and not encouraging to provide a definitive conclusion due to the methodological shortcomings and the presence of adverse events in chitosan and fiber supplementation. Hence, studies of this nature need to be further replicated and improved to corroborate the efficacy and safety of the CATs to combat weight issues.
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Affiliation(s)
- Pei Lin Lua
- Faculty of Pharmacy, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
| | - Nurul Afiedia Roslim
- Faculty of Pharmacy, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
| | - Aryati Ahmad
- Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
| | - Mardiana Mansor
- Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
| | - Myat Moe Thwe Aung
- Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
| | - Farrahdilla Hamzah
- Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
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Januszko P, Lange E. Nutrition, supplementation and weight reduction in combat sports: a review. AIMS Public Health 2021; 8:485-498. [PMID: 34395698 PMCID: PMC8334642 DOI: 10.3934/publichealth.2021038] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 06/29/2021] [Indexed: 11/18/2022] Open
Abstract
Nutrition is the aspect closely connected to physical activity and may affect body composition, sports performance and post-workout regeneration. Using an appropriate diet plan is a proven method to optimize performance improvements in combat sports. In the majority of combat sports athletes are classified according to their body mass in order to minimize differences between competitors. Many athletes induce weight loss in order to gain an advantage over their opponents. The review was undertaken to provide safe, evidence-based protocols helping athletes in weight reduction without negative effects on sports performance. The nutritional requirements for combat sports athletes, sports supplements, gradual and rapid weight reduction strategies are discussed in this review.
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Affiliation(s)
- Paulina Januszko
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, SGGW, Warsaw, Poland
| | - Ewa Lange
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, SGGW, Warsaw, Poland
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12
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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: 58] [Impact Index Per Article: 14.5] [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.
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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
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13
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Cho T, Wang X, Yeung K, Cao Y, Uetrecht J. Liver Injury Caused by Green Tea Extract in PD-1 -/- Mice: An Impaired Immune Tolerance Model for Idiosyncratic Drug-Induced Liver Injury. Chem Res Toxicol 2021; 34:849-856. [PMID: 33617238 DOI: 10.1021/acs.chemrestox.0c00485] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Idiosyncratic drug-induced liver injury (IDILI) is an idiosyncratic drug reaction that is specific to an individual and can lead to liver failure and even death. The mechanism of IDILI remains poorly understood, but most IDILI appears to be immune-mediated. We have developed the first validated animal model by using a PD-1-/- mouse model in combination with anti-CTLA-4 to block immune checkpoints and impair immune tolerance. Treatment of these mice with drugs that cause IDILI in humans led to delayed-onset liver injury with characteristics similar to IDILI in humans. The current study investigates the effects of green tea extract, a weight-loss dietary supplement that has been reported to cause IDILI in humans. Green tea extracts contain a highly variable content of catechins including (-)-epigallocatechin gallate, the major catechin in green tea formulations. If the liver injury caused by green tea extract in humans is immune-mediated, it may occur in our impaired immune tolerance model. Female PD-1-/- mice treated with anti-CTLA-4 antibody and green tea extract (500 mg/kg), a dose that is considered a no-observed-adverse-effect level for liver in rodents, produced a delayed onset increase in serum alanine transaminase levels and an increase in hepatic CD8+ T cells. In contrast, the response in male PD-1-/- mice was less pronounced, and there was no evidence of liver injury in wild-type mice. These findings are consistent with the hypothesis that the IDILI caused by green tea extract is immune-mediated and is similar to IDILI caused by medications that are associated with IDILI.
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Affiliation(s)
- Tiffany Cho
- Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada
| | - Xijin Wang
- Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada
| | - Karen Yeung
- Temerty Faculty of Medicine, Department of Immunology, University of Toronto, Toronto, Ontario M5S 3M2, Canada
| | - Yanshan Cao
- Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada
| | - Jack Uetrecht
- Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada
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14
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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.
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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
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15
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Yergaliyev KA, Aveling EL, Lee RM, Austin SB. Lessons for Local Policy Initiatives to Address Dietary Supplement Use Among Adolescents: A Qualitative Study of Stakeholders' Perceptions. J Adolesc Health 2020; 67:550-556. [PMID: 32387096 DOI: 10.1016/j.jadohealth.2020.03.026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 02/10/2020] [Accepted: 03/07/2020] [Indexed: 11/30/2022]
Abstract
PURPOSE Weight-loss and muscle-building dietary supplements can have adverse health consequences for youth. At a time, when the Food and Drug Administration is considering increasing oversight of dietary supplements, this study aimed to explore community stakeholders' perceptions about the use of and access to such supplements among adolescents and to identify challenges and opportunities to engage stakeholders with policy initiatives to curtail youth access to supplements at the local level. METHOD We conducted 32 key informant semistructured interviews in four municipalities in Massachusetts with purposefully selected participants representing three categories of community stakeholders who could contribute to policy agenda setting at the local level: policy professionals, youth service providers, and young adults aged 18-25 years who used weight-loss or muscle-building supplements as minors. Interviews were audio-recorded, transcribed, deidentified, and analyzed using thematic analysis approach, facilitated by Dedoose software. RESULTS Community stakeholders reported wide availability and easy access to dietary supplements. Most participants were unaware of health risks. Many stakeholders did not perceive the use of these products as an issue impacting youth in their communities. The challenges identified in engaging stakeholders were competing concerns on the policy agenda, limited capacity of stakeholders, and uncertainty about who is accountable for the problem. CONCLUSION This study indicates the need for complementary, multipronged approaches at the municipal level to address the problem of weak regulation and easy access to potentially dangerous weight-loss and muscle-building supplements for youth.
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Affiliation(s)
- Kuanysh A Yergaliyev
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; SDU Business School, Suleyman Demirel University, Almaty, Kazakhstan.
| | - Emma-Louise Aveling
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Rebekka M Lee
- Department of Social and Behavior Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - S Bryn Austin
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; Department of Social and Behavior Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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16
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Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72:671-722. [PMID: 31863477 DOI: 10.1002/hep.31065] [Citation(s) in RCA: 520] [Impact Index Per Article: 104.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Cara L Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David Adams
- Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - David N Assis
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nanda Kerkar
- Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York, NY
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX
| | - John M Vierling
- Medicine and Surgery, Baylor College of Medicine, Houston, TX
| | | | - Mohammad H Murad
- Mayo Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, MN
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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17
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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.
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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.
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18
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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)."
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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
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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)
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19
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Zheng E, Sandhu N, Navarro V. Drug-induced Liver Injury Secondary to Herbal and Dietary Supplements. Clin Liver Dis 2020; 24:141-155. [PMID: 31753247 DOI: 10.1016/j.cld.2019.09.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The use of herbal and dietary supplements (HDS) is increasing in the United States and worldwide. Its significant association with liver injury has become a concern, particularly because rates of hepatotoxicity caused by HDS are increasing. There are variety of HDS available, ranging from multi-ingredient substances, to anabolic steroids for bodybuilding purposes, to individual ingredients for purposes of supplementing a diet. This article reviews the impact of liver injury cause by HDS and explores the hepatotoxic potential of such products and their individual ingredients.
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Affiliation(s)
- Elizabeth Zheng
- Columbia University Medical Center, 622 West 168th Street, PH-14-406, New York, NY 10032, USA
| | - Naemat Sandhu
- Einstein Medical Center, 5401 Old York Road, Klein Building Suite 505, Philadelphia, PA 19141, USA
| | - Victor Navarro
- Einstein Medical Center, 5401 Old York Road, Klein Building Suite 505, Philadelphia, PA 19141, USA.
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20
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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.
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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
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21
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Abnormal Liver Enzymes. Gastroenterol Nurs 2019; 41:497-507. [PMID: 30418344 DOI: 10.1097/sga.0000000000000346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Abnormal liver enzymes are frequently encountered in primary care offices and hospitals and may be caused by a wide variety of conditions, from mild and nonspecific to well-defined and life-threatening. Terms such as "abnormal liver chemistries" or "abnormal liver enzymes," also referred to as transaminitis, should be reserved to describe inflammatory processes characterized by elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Although interchangeably used with abnormal liver enzymes, abnormal liver function tests specifically denote a loss of synthetic functions usually evaluated by serum albumin and prothrombin time. We discuss the entities that most commonly cause abnormal liver enzymes, specific patterns of enzyme abnormalities, diagnostic modalities, and the clinical scenarios that warrant referral to a hepatologist.
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22
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23
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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.
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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
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24
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Risks associated with fat burners: A toxicological perspective. Food Chem Toxicol 2019; 123:205-224. [DOI: 10.1016/j.fct.2018.10.051] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 10/16/2018] [Accepted: 10/22/2018] [Indexed: 12/18/2022]
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25
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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.
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26
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Skinner CM, Miousse IR, Ewing LE, Sridharan V, Cao M, Lin H, Williams DK, Avula B, Haider S, Chittiboyina AG, Khan IA, ElSohly MA, Boerma M, Gurley BJ, Koturbash I. Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments. Food Chem Toxicol 2018; 122:21-32. [PMID: 30282009 DOI: 10.1016/j.fct.2018.09.067] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 09/18/2018] [Accepted: 09/28/2018] [Indexed: 02/07/2023]
Abstract
Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging clinical problem. In this study, we investigated the liver and heart toxicity of HDS OxyELITE-PRO™ New Formula (OEP-NF), a dietary supplement marketed for weight loss and performance enhancement that was recently withdrawn from the market. Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and hepatotoxic risks following both short- and long-term administration schedules. Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in 40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF for eight weeks, while not exhibiting significant effects on body weights, significantly altered hepatic gene expression, increased the number of apoptotic and mast cells in the heart and affected cardiac function. The degree of toxicity in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of other hepato- and cardiotoxicity cases associated with HDS ingestion, argue strongly for introduction of quality standards and pre-marketing safety assessments for multi-ingredient HDS.
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Affiliation(s)
- Charles M Skinner
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Isabelle R Miousse
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Laura E Ewing
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Vijayalakshmi Sridharan
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA.
| | - Maohua Cao
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA.
| | - Haixia Lin
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - D Keith Williams
- Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Bharathi Avula
- National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
| | - Saqlain Haider
- National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
| | - Amar G Chittiboyina
- National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
| | - Ikhlas A Khan
- National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
| | - Mahmoud A ElSohly
- ElSohly Laboratories, Inc. (ELI), Phyto Chemical Services, Inc. (PSI), 5 Industrial Park Drive, Oxford, MS 38655, USA.
| | - Marjan Boerma
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Bill J Gurley
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
| | - Igor Koturbash
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
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Ganger DR, Rule J, Rakela J, Bass N, Reuben A, Stravitz RT, Sussman N, Larson AM, James L, Chiu C, Lee WM. Acute Liver Failure of Indeterminate Etiology: A Comprehensive Systematic Approach by An Expert Committee to Establish Causality. Am J Gastroenterol 2018; 113:1319. [PMID: 29946176 PMCID: PMC9252260 DOI: 10.1038/s41395-018-0160-2] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 05/15/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES In the United States, the Acute Liver Failure Study Group (ALFSG) registry lists approximately 11% of cases as of indeterminate etiology (IND-ALF) as determined by the respective local site principal investigator (PI). Traditionally, IND-ALF has prompted concern that other viruses or toxins might be implicated. We hypothesized that many IND- ALF cases would have an identifiable etiology upon further investigation. Improving the identification process should reduce the number of truly indeterminate cases. METHODS Specific definitions for each etiology ("etiology-specific algorithms") were developed by a Causality Adjudication Committee that included six reviewers (each with 20 or more years of experience). Of 2718 patients with ALF, 303 initially deemed IND-ALF by site PIs underwent committee review guided by the algorithms. Acetaminophen (APAP) protein adducts were measured in sera when available, additional HEV testing was performed, and viral sequences sought by microarray analysis and metagenomic next-generation sequencing (mNGS). Study sites were asked to provide liver biopsy and/or explant reports and to update serological findings not reported previously. RESULTS Nearly half (142, 46.9%) of the 303 IND-ALF cases could be reassigned to a single, defined etiology and rated as highly likely or probable; 11 additional cases, upon review, did not meet ALF criteria. Amongst reassigned etiologies, 45 were previously unrecognized APAP, 34 autoimmune hepatitis (AIH), 24 drug-induced liver injury (DILI), 13 various viral causes, 12 ischemia, and 14 miscellaneous other etiologies. The remaining 150, deemed true IND-ALF, represented just 5.5%. CONCLUSIONS The indeterminate etiology in ALF includes patients with a diagnosis that is discernible after closer examination. Revision of etiologic diagnoses of indeterminate cases using added testing and expert opinion is useful in understanding all aspects of ALF.
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Affiliation(s)
- Daniel R. Ganger
- Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jody Rule
- Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jorge Rakela
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Nathan Bass
- Department of Medicine, UCSF San Francisco, San Francisco, CA, USA
| | - A Reuben
- Medical University of South Carolina, Charleston, SC, USA
| | - RT Stravitz
- Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA
| | - Norman Sussman
- Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA
| | - Anne M. Larson
- Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA
| | - Laura James
- Section of Pediatric Pharmacology and Toxicology, Arkansas Children’s Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Charles Chiu
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA,UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA,Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA
| | - William M. Lee
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Austin SB, Liu SH, Tefft N. Could a tax on unhealthy products sold for weight loss reduce consumer use? A novel estimation of potential taxation effects. Prev Med 2018; 114:39-46. [PMID: 29842920 DOI: 10.1016/j.ypmed.2018.05.022] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 05/04/2018] [Accepted: 05/22/2018] [Indexed: 01/31/2023]
Abstract
Abuse of widely available, over-the-counter (OTC) drugs and supplements such as diet pills, laxatives, and diuretics by adolescents for weight control is well-documented, yet manufacturers and retailers can sell them to minors without restriction. The aim of our study was to estimate the effect of added taxation of OTC drugs and dietary supplements sold for weight loss on household purchases of these products. With data from 60,538 U.S. households in the 2012 waves of the Nielsen/IRi National Consumer Panel (NCP) and the Nielsen/IRi Retail Scanner (NRS) datasets, we conducted analyses in 2017 to tally annual quantities and expenditures on OTC drugs or dietary supplements making weight-loss, cleanse/detox, or diuretic claims. We estimated the percent reduction in household purchases due to a simulated 20% added tax on each category. Among the 14,151 households reporting at least one purchase in the three claims categories, a 20% higher average price of weight-loss products was associated with a 5.2% lower purchases of those products. Among households with children ages 12 to 17 years old present, purchases were 17.5% lower, and among households with a daughter present, purchases were 10.3% lower. Taxation may be an effective public health strategy to reduce purchasing of potentially dangerous OTC drugs and supplements sold for weight loss, especially for households that include children ages 12-17 years old or a daughter.
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Affiliation(s)
- S Bryn Austin
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA; Strategic Training Initiative for the Prevention of Eating Disorders based at Harvard T.H. Chan School of Public Health and Boston Children's Hospital, Boston, MA, USA.
| | - Selena Hua Liu
- Strategic Training Initiative for the Prevention of Eating Disorders based at Harvard T.H. Chan School of Public Health and Boston Children's Hospital, Boston, MA, USA; Department of Nutrition, Simmons College, Boston, MA, USA
| | - Nathan Tefft
- Department of Economics, Bates College, Lewiston, ME, USA
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29
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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.
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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
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30
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Licata A, Minissale MG. Weight-loss supplementation and acute liver failure: the case of Garcinia Cambogia. Intern Emerg Med 2018; 13:833-835. [PMID: 30032342 DOI: 10.1007/s11739-018-1912-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 07/12/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Anna Licata
- Internal Medicine, Internal Medicine and Hepatology, Department of and Medical Specialities (DIBIMIS), University of Palermo, Piazza Delle Cliniche 2, 90127, Palermo, Italy.
| | - Maria Giovanna Minissale
- Internal Medicine, Internal Medicine and Hepatology, Department of and Medical Specialities (DIBIMIS), University of Palermo, Piazza Delle Cliniche 2, 90127, Palermo, Italy
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31
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Liu Y. Incorporation of absorption and metabolism into liver toxicity prediction for phytochemicals: A tiered in silico QSAR approach. Food Chem Toxicol 2018; 118:409-415. [DOI: 10.1016/j.fct.2018.05.039] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 04/05/2018] [Accepted: 05/16/2018] [Indexed: 02/06/2023]
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32
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Roytman MM, Poerzgen P, Navarro V. Botanicals and Hepatotoxicity. Clin Pharmacol Ther 2018; 104:458-469. [DOI: 10.1002/cpt.1097] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 04/18/2018] [Accepted: 04/19/2018] [Indexed: 01/06/2023]
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Ramachandran A, Visschers RGJ, Duan L, Akakpo JY, Jaeschke H. Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives. J Clin Transl Res 2018. [PMID: 30873497 PMCID: PMC6261533 DOI: 10.18053/jctres.04.201801.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area. Relevance for patients:This review focuses on the role of mitochondrial dysfunction in liver injury mechanisms of clinically important drugs like acetaminophen, diclofenac, rifampicin, isoniazid, amiodarone and others. A better understanding ofthe mechanisms in animal models and their translation to patients will be critical for the identification of new therapeutic targets.
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Affiliation(s)
- Anup Ramachandran
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States
| | - Ruben G J Visschers
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States
| | - Luqi Duan
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States
| | - Jephte Y Akakpo
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States
| | - Hartmut Jaeschke
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States
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Abstract
Chinese medicine and herb medicine though used to treat liver diseases are an important cause of liver injury. Many phytochemicals have the potential to injure the liver, some in a dose-related fashion and more often in an idiosyncratic fashion, meaning occurrence is uncommon to rare in the population using these treatments. As is the case with pharmaceuticals, the phytochemicals are usually tolerated despite either no or mild transient subclinical injury but rarely in some susceptible patients cause moderate to severe liver injury which is likely mediated by the adaptive immune system.
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Affiliation(s)
- Neil Kaplowitz
- USC Research Center for Liver Disease, USC Keck School of Medicine, Los Angeles, CA, 90033, USA.
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35
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Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, Frutos MJ, Galtier P, Gott D, Gundert-Remy U, Lambré C, Leblanc JC, Lillegaard IT, Moldeus P, Mortensen A, Oskarsson A, Stankovic I, Waalkens-Berendsen I, Woutersen RA, Andrade RJ, Fortes C, Mosesso P, Restani P, Arcella D, Pizzo F, Smeraldi C, Wright M. Scientific opinion on the safety of green tea catechins. EFSA J 2018; 16:e05239. [PMID: 32625874 PMCID: PMC7009618 DOI: 10.2903/j.efsa.2018.5239] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The EFSA ANS Panel was asked to provide a scientific opinion on the safety of green tea catechins from dietary sources including preparations such as food supplements and infusions. Green tea is produced from the leaves of Camellia sinensis (L.) Kuntze, without fermentation, which prevents the oxidation of polyphenolic components. Most of the polyphenols in green tea are catechins. The Panel considered the possible association between the consumption of (-)-epigallocatechin-3-gallate (EGCG), the most relevant catechin in green tea, and hepatotoxicity. This scientific opinion is based on published scientific literature, including interventional studies, monographs and reports by national and international authorities and data received following a public 'Call for data'. The mean daily intake of EGCG resulting from the consumption of green tea infusions ranges from 90 to 300 mg/day while exposure by high-level consumers is estimated to be up to 866 mg EGCG/day, in the adult population in the EU. Food supplements containing green tea catechins provide a daily dose of EGCG in the range of 5-1,000 mg/day, for adult population. The Panel concluded that catechins from green tea infusion, prepared in a traditional way, and reconstituted drinks with an equivalent composition to traditional green tea infusions, are in general considered to be safe according to the presumption of safety approach provided the intake corresponds to reported intakes in European Member States. However, rare cases of liver injury have been reported after consumption of green tea infusions, most probably due to an idiosyncratic reaction. Based on the available data on the potential adverse effects of green tea catechins on the liver, the Panel concluded that there is evidence from interventional clinical trials that intake of doses equal or above 800 mg EGCG/day taken as a food supplement has been shown to induce a statistically significant increase of serum transaminases in treated subjects compared to control.
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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.
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37
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Tujios SR, Lee WM. Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy. Liver Int 2018; 38:6-14. [PMID: 28771932 PMCID: PMC5741491 DOI: 10.1111/liv.13535] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 07/27/2017] [Indexed: 12/11/2022]
Abstract
Acute liver failure (ALF) requires urgent attention to identify etiology and determine prognosis, in order to assess likelihood of survival or need for transplantation. Identifying idiosyncratic drug-induced liver injury (iDILI) may be particularly difficult, but the illness generally follows a subacute course, allowing time to assess outcome and find a liver graft if needed. Not all drugs that cause iDILI lead to ALF; the most common are antibiotics including anti-tuberculous medications, non-steroidal anti-inflammatory agents and herbal and dietary supplements (HDS). Determining causality remains challenging particularly if altered mentation is present; identifying the causative agent depends in part on knowing the propensity of the drugs that have been taken in the proper time interval, plus excluding other causes. In general, iDILI that reaches the threshold of ALF will more often than not require transplantation, since survival without transplant is around 25%. Treatment consists of withdrawal of the presumed offending medication, consideration of N-acetylcysteine (NAC), as well as intensive care. Corticosteroids have not proven useful except perhaps in instances of apparent autoimmune hepatitis caused by a limited number of agents. Recently developed prognostic scoring systems may also aid in predicting outcome in this setting.
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Affiliation(s)
- Shannan R Tujios
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - William M Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
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38
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Risk of Liver Injury Associated with Green Tea Extract in SLIMQUICK(®) Weight Loss Products: Results from the DILIN Prospective Study. Drug Saf 2017; 39:749-54. [PMID: 27189593 DOI: 10.1007/s40264-016-0428-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Herbal and dietary supplements (HDS) have been increasingly recognized as a cause for acute liver injury (Navarro et al. Hepatology 60(4):1399-1408, 2014; Bailey et al. J Nutr 141:261-266, 2011). HDS products frequently contain numerous ingredients, and are marketed under various product names. A perusal of marketed weight loss products indicates that green tea extract (GTE) is a common ingredient in many. We aimed to describe the course and outcome of six patients who developed liver injury attributed to SLIMQUICK(®) weight loss products. METHODS Patients with suspected drug-induced liver injury were enrolled in a prospective study of the Drug-Induced Liver Injury Network (DILIN) and causality was assessed by a panel of hepatologists. During the period under study, 6 of 1091 cases of liver injury were attributed to a SLIMQUICK(®) product and were assigned causality scores of probable, highly likely, or definite. RESULTS Six cases of acute liver injury attributed to SLIMQUICK(®) products were enrolled in the DILIN prospective study between 2007 and 2011. All were women aged 22 to 58 years. Two had a normal body weight and four were mildly obese (body mass index 22.9-32.2 kg/m(2)). All were taking SLIMQUICK(®) products for weight loss and no patient reported prior use. Laboratory tests revealed a hepatocellular pattern of injury, with initial alanine aminotransferase (ALT) levels above 1000 U/L in all but one patient. Three patients were hospitalized and one underwent successful liver transplantation. No patients died of liver injury. GTE and/or its component catechins were listed among the ingredients for five of the six products. CONCLUSIONS SLIMQUICK(®) products can lead to severe acute hepatocellular liver injury, which may result in transplantation. Given the frequency of GTE as a component in weight loss products, this ingredient should be studied further as a possible cause for liver injury.
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39
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Miousse IR, Skinner CM, Lin H, Ewing LE, Kosanke SD, Williams DK, Avula B, Khan IA, ElSohly MA, Gurley BJ, Koturbash I. Safety assessment of the dietary supplement OxyELITE™ Pro (New Formula) in inbred and outbred mouse strains. Food Chem Toxicol 2017; 109:194-209. [PMID: 28843594 DOI: 10.1016/j.fct.2017.08.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 08/18/2017] [Accepted: 08/20/2017] [Indexed: 12/12/2022]
Abstract
Herbal dietary supplements have gained wide acceptance as alternatives to conventional therapeutic agents despite concerns regarding their efficacy and safety. In 2013, a spate of severe liver injuries across the United States was linked to the dietary supplement OxyELITE Pro-New Formula (OEP-NF), a multi-ingredient product marketed for weight loss and exercise performance enhancement. The principal goal of this study was to assess the hepatotoxic potential of OEP-NF in outbred and inbred mouse models. In an acute toxicity study, significant mortality was observed after administering 10X and 3X mouse-equivalent doses (MED) of OEP-NF, respectively. Increases in liver/body weight ratio, ALT and AST were observed in female B6C3F1 mice after gavaging 2X and 1.5X MED of OEP-NF. Similar findings were observed in a 90-day feeding study. These alterations were paralleled by altered expression of gene- and microRNA-signatures of hepatotoxicity, including Cd36, Nqo1, Aldoa, Txnrd1, Scd1 and Ccng1, as well as miR-192, miR-193a and miR-125b and were most pronounced in female B6C3F1 mice. Body weight loss, observed at week 1, was followed by weight gain throughout the feeding studies. These findings bolster safety and efficacy concerns for OEP-NF, and argue strongly for implementation of pre-market toxicity studies within the dietary supplement industry.
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Affiliation(s)
- Isabelle R Miousse
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
| | - Charles M Skinner
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
| | - Haixia Lin
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
| | - Laura E Ewing
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
| | - Stanley D Kosanke
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Heartland Veterinary Pathology Services, PLLC, Oklahoma City, OK, USA.
| | - D Keith Williams
- Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
| | - Bharathi Avula
- National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
| | - Ikhlas A Khan
- National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
| | - Mahmoud A ElSohly
- ElSohly Laboratories, Inc. (ELI) and Phyto Chemical Services, Inc. (PSI), 5 Industrial Park Drive, Oxford, MS 38655, USA.
| | - Bill J Gurley
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72223, USA.
| | - Igor Koturbash
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
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Wong LL, Lacar L, Roytman M, Orloff SL. Urgent Liver Transplantation for Dietary Supplements: An Under-Recognized Problem. Transplant Proc 2017; 49:322-325. [PMID: 28219592 DOI: 10.1016/j.transproceed.2016.11.041] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Accepted: 11/16/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized. RESULTS Of 2408 adult cases, 625 were characterized as a drug-induced liver injury. The majority of cases (n = 300) were due to acetaminophen toxicity, but the fourth highest category was due to HDS (n = 21). Of these 21 cases caused by HDS, 13 did not list the specific agent responsible, mean age was 36 years, and all cases occurred after 2007. There probably are more cases because 25% of all LT cases in the study did not list a specific reason for liver failure and 20% of all drug-induced liver failure did not list a specific drug. CONCLUSIONS Herbal/supplement use is the fourth most common cause of drug-induced AHN requiring LT, albeit an underestimation of the problem. Detailed questioning of patients and their support systems regarding herbal/supplement use and better reporting are imperative to further define this problem and identify products that have the potential to lead to liver failure.
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Affiliation(s)
- L L Wong
- Department of Surgery, University of Hawaii, John A. Burns School of Medicine, Honolulu, Hawaii.
| | - L Lacar
- University of Hawaii, Honolulu, Hawaii
| | - M Roytman
- Liver Center, Queens Medical Center, Honolulu, Hawaii
| | - S L Orloff
- Division of Abdominal Organ Transplantation/Hepatobiliary Surgery, Oregon Health and Sciences University, Portland VA Medical Center, Portland, Oregon
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Austin SB, Yu K, Tran A, Mayer B. Research-to-policy translation for prevention of disordered weight and shape control behaviors: A case example targeting dietary supplements sold for weight loss and muscle building. Eat Behav 2017; 25:9-14. [PMID: 27118415 DOI: 10.1016/j.eatbeh.2016.03.037] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 02/23/2016] [Accepted: 03/30/2016] [Indexed: 11/29/2022]
Abstract
New approaches to universal eating disorders prevention and interventions targeting macro-environmental change are greatly needed, and research-to-policy translation efforts hold promise for advancing both of these goals. This paper describes as a policy-translation case example an academic-community-government partnership of the Strategic Training Initiative for the Prevention of Eating Disorders, Multi-Service Eating Disorders Association, and the office of Massachusetts Representative Kay Khan, all based in Massachusetts, USA. The partnership's research-to-policy translation project focused on dietary supplements sold for weight loss and muscle building, which have been linked with serious injury and death in consumers. Youth and people of all ages with eating disorders and body dysmorphic disorder may be especially vulnerable to use these products due to deceptive promises of fast and safe weight loss and muscle gain. The research-to-policy translation project was informed by a triggers-to-action framework to establish the evidentiary base of harm to consumers, operationalize policy solutions to mitigate harm through legislation, and generate political will to support action through legislation introduced in the Massachusetts legislature to restrict sales of weight-loss and muscle-building dietary supplements. The paper concludes with lessons learned from this unique policy translation effort for the prevention of disordered weight and shape control behaviors and offers recommendations for next steps for the field to advance research and practice for universal, macro-environmentally targeted prevention.
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Affiliation(s)
- S Bryn Austin
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA.
| | - Kimberly Yu
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA
| | - Alvin Tran
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Beth Mayer
- Multi-Service Eating Disorders Association, Newton, MA, USA
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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.
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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
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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.
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The Dangerous Mix of Adolescents and Dietary Supplements for Weight Loss and Muscle Building: Legal Strategies for State Action. JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE 2016; 21:496-503. [PMID: 25248073 DOI: 10.1097/phh.0000000000000142] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Adolescents use dietary supplements marketed for weight loss or muscle building, but these are not recommended by physicians. These products are often ineffective, adulterated, mislabeled, or have unclear dosing recommendations, and consumers have suffered injury and death as a consequence. When Congress passed the Dietary Supplement Health and Education Act, it stripped the Food and Drug Administration of its premarket authority, rendering regulatory controls too weak to adequately protect consumers. State government intervention is thus warranted. This article reviews studies reporting on Americans' use of dietary supplements marketed for weight loss or muscle building, notes the particular dangers these products pose to the youth, and suggests that states can build on their historical enactment of regulatory controls for products with potential health consequences to protect the public and especially young people from unsafe and mislabeled dietary supplements.
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Zheng E, Navarro V. Daño hepático debido al uso de suplementos nutricionales y de herbolario: revisión de componentes individuales. Clin Liver Dis (Hoboken) 2016; 8:S30-S33. [PMID: 31041093 PMCID: PMC6490225 DOI: 10.1002/cld.597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 02/08/2016] [Indexed: 02/04/2023] Open
Affiliation(s)
- Elizabeth Zheng
- Del Department of HepatologyEinstein Medical CenterPhiladelphiaPA, EE. UU
| | - Víctor Navarro
- Del Department of HepatologyEinstein Medical CenterPhiladelphiaPA, EE. UU
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Heidemann LA, Navarro VJ, Ahmad J, Hayashi PH, Stolz A, Kleiner DE, Fontana RJ. Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case Series. Dig Dis Sci 2016; 61:2741-8. [PMID: 27142670 PMCID: PMC4982804 DOI: 10.1007/s10620-016-4181-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 04/20/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIM Herbal and dietary supplement (HDS) hepatotoxicity is increasingly being reported in the USA. This case series describes the presenting clinical features and outcomes of seven patients with liver injury attributed to OxyELITE Pro enrolled in the Drug-Induced Liver Injury Network (DILIN) study. METHODS The 6-month outcomes of patients with hepatotoxicity attributed to OxyELITE Pro enrolled in the DILIN prospective registry between 2004 and 2015 are presented. RESULTS Six of the seven patients (86 %) presented in 2013 with symptoms of hepatitis and acute hepatocellular injury. The median duration of OxyELITE Pro use was 18 weeks (range 5-102 weeks). Median age was 36 years (range 28-62), 86 % were female, and 43 % were Asian. One patient had rash, none had eosinophilia, and three had antinuclear antibody reactivity. The median peak ALT was 2242 U/L, alkaline phosphatase 284 U/L and bilirubin 15.0 mg/dL. Six patients (86 %) were hospitalized, three developed acute liver failure and two underwent liver transplantation. DILIN causality scores for OxyELITE Pro were definite in 1, highly likely in 3, probable in 2, and possible in 1. Four of the five patients without liver transplant recovered completely within 6 months, while one patient had mild residual ALT elevations. CONCLUSIONS Seven cases of severe acute hepatocellular injury attributed to OxyELITE Pro are reported. These results reinforce the need to assess for HDS supplement use in patients presenting with unexplained acute hepatitis and point to the need for additional regulatory oversight of HDS products.
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Affiliation(s)
- Lauren A Heidemann
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI
| | - Victor J Navarro
- Department of Medicine, Einstein Healthcare Network, Philadelphia, PA
| | - Jawad Ahmad
- Department of Medicine, Icahn School of Medicine at Mount Sinai Medical Center, New York, NY
| | | | - Andrew Stolz
- University of Southern California, Los Angeles, CA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Robert J. Fontana
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI
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Chatham-Stephens K, Taylor E, Chang A, Peterson A, Daniel J, Martin C, Deuster P, Noe R, Kieszak S, Schier J, Klontz K, Lewis L. Hepatotoxicity associated with weight loss or sports dietary supplements, including OxyELITE Pro™ - United States, 2013. Drug Test Anal 2016; 9:68-74. [PMID: 27367536 DOI: 10.1002/dta.2036] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 06/25/2016] [Accepted: 06/26/2016] [Indexed: 12/14/2022]
Abstract
In September 2013, the Hawaii Department of Health (HDOH) was notified of seven adults who developed acute hepatitis after taking OxyELITE Pro™, a weight loss and sports dietary supplement. CDC assisted HDOH with their investigation, then conducted case-finding outside of Hawaii with FDA and the Department of Defense (DoD). We defined cases as acute hepatitis of unknown etiology that occurred from April 1, 2013, through December 5, 2013, following exposure to a weight loss or muscle-building dietary supplement, such as OxyELITE Pro™. We conducted case-finding through multiple sources, including data from poison centers (National Poison Data System [NPDS]) and FDA MedWatch. We identified 40 case-patients in 23 states and two military bases with acute hepatitis of unknown etiology and exposure to a weight loss or muscle building dietary supplement. Of 35 case-patients who reported their race, 15 (42.9%) reported white and 9 (25.7%) reported Asian. Commonly reported symptoms included jaundice, fatigue, and dark urine. Twenty-five (62.5%) case-patients reported taking OxyELITE Pro™. Of these 25 patients, 17 of 22 (77.3%) with available data were hospitalized and 1 received a liver transplant. NPDS and FDA MedWatch each captured seven (17.5%) case-patients. Improving the ability to search surveillance systems like NPDS and FDA MedWatch for individual and grouped dietary supplements, as well as coordinating case-finding with DoD, may benefit ongoing surveillance efforts and future outbreak responses involving adverse health effects from dietary supplements. This investigation highlights opportunities and challenges in using multiple sources to identify cases of suspected supplement associated adverse events. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
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Affiliation(s)
- Kevin Chatham-Stephens
- EIS officer, 1600 Clifton Road NE MS C-09, Atlanta, GA.,Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Ethel Taylor
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Arthur Chang
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Amy Peterson
- Division of Integrated Biosurveillance, Armed Forces Health Surveillance Center
| | - Johnni Daniel
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Colleen Martin
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Patricia Deuster
- Department of Military and Emergency Medicine, Uniformed Services University
| | - Rebecca Noe
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Stephanie Kieszak
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Josh Schier
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
| | - Karl Klontz
- Office of Analytics and Outreach, Center for Food Safety and Applied Nutrition, Food and Drug Administration
| | - Lauren Lewis
- Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention
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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: 55] [Impact Index Per Article: 6.1] [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.
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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.
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49
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Smith RJ, Bertilone C, Robertson AG. Fulminant liver failure and transplantation after use of dietary supplements. Med J Aust 2016; 204:30-2. [PMID: 26763816 DOI: 10.5694/mja15.00816] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 10/16/2015] [Indexed: 01/02/2023]
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50
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Zheng E, Navarro V. Liver injury due to herbal and dietary supplements: A review of individual ingredients. Clin Liver Dis (Hoboken) 2016; 7:80-83. [PMID: 31041035 PMCID: PMC6490262 DOI: 10.1002/cld.541] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 01/25/2016] [Accepted: 02/08/2016] [Indexed: 02/04/2023] Open
Affiliation(s)
- Elizabeth Zheng
- Department of HepatologyEinstein Medical CenterPhiladelphiaPA
| | - Victor Navarro
- Department of HepatologyEinstein Medical CenterPhiladelphiaPA
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