Diffuse Alveolar Hemorrhage Associated with Makyo-kanseki-to Administration.

We herein describe the first known case of diffuse alveolar hemorrhage (DAH) associated with the administration of Makyo-kanseki-to, a Chinese herbal drug. A 64-year-old man with bronchial asthma presented with persistent cough. Makyo-kanseki-to was prescribed as an adjunctive treatment for bronchial asthma. Immediately after drug ingestion, the patient expectorated bloody sputum. DAH was diagnosed based on the presence of bilateral ground-glass opacity which was identified on chest computed tomography and bloody bronchoalveolar lavage fluid. We diagnosed that the administration of Makyo-kanseki-to was the responsible medication because the hemorrhage developed immediately after drug ingestion and resolved after the cessation of such medication with no subsequent recurrence.

Drug-induced liver injury: A 2-year retrospective study of 1169 hospitalized patients in a single medical center.

BACKGROUND: Although herbal medicines (HMs) are widely used in Asian and Western countries, medicinal information concerning their hepatic toxicity or interaction with conventional medicines (CMs) is sparse. PURPOSE: The aim of our study was to estimate the prevalence of drug-induced liver injury (DILI) among total inpatients prescribed HMs or CMs. Furthermore, we noted all medications suspected to be associated with hepatotoxicity in the liver injury group during the period of hospitalization. STUDY DESIGN: We retrospectively observed medical records of 1169 inpatients in a single medical center from January 2012 to July 2014. METHODS: Based on a database of the 1169 inpatients at a single medical center, we researched the occurrence rate and type of liver injury according to the criteria of the Council for International Organization of Medical Science (CIOMS). We also utilized a simplified Roussel Uclaf Causality Assessment Method (RUCAM) score for probable causality assessment between drugs and liver injury. RESULTS: Among a total of 1169 inpatients, 13 cases whose baseline LFTs had been in the normal range at admission had abnormal liver parameters at the time of follow-up, and 11 of them (0.94%) were attributed to drugs: 0.43% (5 of 1169) to HMs, 0.43% (5 of 1169) to CMs, and 0.09% (1 of 1169) to combined drug classes. Two of them were found to have liver injury because of pneumonia and sepsis. As for liver injury type, 8 cases were hepatocellular, 2 were cholestatic, and 1 was of mixed pattern. The common causative HMs for hepatotoxicity were Ephedrae Herba and Scutellariae Radix, while CMs included antidepressants, antihistamines, and antibacterials. CONCLUSIONS: We investigated approximate incidence rates and analyzed suspicious drugs associated with liver damage, which revealed a low frequency of liver injury induced by HMs. However, further study, based on a well-designed, long-term, multicenter prospective study, will be required to determine the safety of HMs.

Multi-ingredient, caffeine-containing dietary supplements: history, safety, and efficacy.

PURPOSE: Our objective was to review the history, safety, and efficacy of caffeine-containing dietary supplements in the United States and Canada. METHODS: PubMed and Web of Science databases (1980-2014) were searched for articles related to the pharmacology, toxicology, and efficacy of caffeine-containing dietary supplements with an emphasis on Ephedra-containing supplements, Ephedra-free supplements, and energy drinks or shots. FINDINGS: Among the first and most successful dietary supplements to be marketed in the United States were those containing Ephedra­combinations of ephedrine alkaloids, caffeine, and other phytochemicals. A decade after their inception, serious tolerability concerns prompted removal of Ephedra supplements from the US and Canadian markets. Ephedra-free products, however, quickly filled this void. Ephedra-free supplements typically contain multiple caffeine sources in conjunction with other botanical extracts whose purposes can often be puzzling and their pharmacologic properties difficult to predict. Ingestion of these products in the form of tablets, capsules, or other solid dosage forms as weight loss aids, exercise performance enhancers, or energy boosters have once again brought their tolerability and efficacy into question. In addition to Ephedra-free solid dosage forms, caffeine-containing energy drinks have gained a foothold in the world market along with concerns about their tolerability. IMPLICATIONS: This review addresses some of the pharmacologic and pharmaceutical issues that distinguish caffeine-containing dietary supplement formulations from traditional caffeine-containing beverages. Such distinctions may account for the increasing tolerability concerns affiliated with these products.

Herbal hepatotoxicity and WHO global introspection method.

Herbal hepatotoxicity is a rare but highly disputed disease because numerous confounding variables may complicate accurate causality assessment. Case evaluation is even more difficult when the WHO global introspection method (WHO method) is applied as diagnostic algorithm. This method lacks liver specificity, hepatotoxicity validation, and quantitative items, basic qualifications required for a sound evaluation of hepatotoxicity cases. Consequently, there are no data available for reliability, sensitivity, specificity, positive and negative predictive value. Its scope is also limited by the fact that it cannot discriminate between a positive and a negative causality attribution, thereby stimulating case overdiagnosing and overreporting. The WHO method ignores uncertainties regarding daily dose, temporal association, start, duration, and end of herbal use, time to onset of the adverse reaction, and course of liver values after herb discontinuation. Insufficiently considered or ignored are comedications, preexisting liver diseases, alternative explanations upon clinical assessment, and exclusion of infections by hepatitis A-C, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella zoster virus (VZV). We clearly prefer as alternative the scale of CIOMS (Council for International Organizations of Medical Sciences) which is structured, quantitative, liver specific, and validated for hepatotoxicity. In conclusion, causality of herbal hepatotoxicity is best assessed by the liver specific CIOMS scale validated for hepatotoxicity rather than the obsolete WHO method that is liver unspecific and not validated for hepatotoxicity. CIOMS based assessments will ensure the correct diagnosis and exclude alternative diagnosis that may require other specific therapies.

Continuous reporting of new cases in Spain supports the relationship between Herbalife® products and liver injury.

PURPOSE: Previous publications have linked Herbalife® products to hepatotoxicity. The identification of earlier cases in which the culprit agent could not be established raised the hypothesis of a possible contamination of some specific batches of Herbalife products. METHODS: We searched the Spanish Pharmacovigilance Centres' database of adverse reactions for reports of liver injury associated with the use of Herbalife products from 2003, when the first case was submitted, through September 2010. RESULTS: The search resulted in 20 reports of liver damage (mean age, 49 years; 16 women), with 12 patients (60%) requiring hospitalization. Hepatocellular damage predominated, and nine (53%) of the hepatocellular cases with bilirubin values were jaundiced, fulfilling the Hy's law criteria, which increases the risk for serious outcomes. Two patients experienced a positive rechallenge. One patient developed cirrhosis, whereas all the others recovered. Causality assessment by the Karch and Lasagna modified algorithm showed a category of definite in 1 case, probable in 14, and possible in 5. Analysis of the different Herbalife products that each patient had taken did not enable us to identify any commonly known hepatotoxic ingredient. CONCLUSIONS: Our results support the relationship between the consumption of Herbalife products and hepatotoxicity, underscore the concern regarding the liver-related safety of this dietary supplement, and emphasize the need to establish further regulatory measures.

[Hepatotoxicity associated with the use of Herbalife]. / Lifrarskadi tengdur notkun á Herbalife.

OBJECTIVE: Many herbal products are known to be hepatotoxic. In a recent survey in Iceland concerning adverse reactions related to herbal medicines, Herbalife products were implicated in the majority of the reported cases of hepatotoxicity. METHODS: The clinical presentations of five cases of Herbalife related liver injury during the period of 1999-2008 are analysed. Causality was assessed by using the WHO-UMC system for causality assessment and the RUCAM method. RESULTS: Of the five cases there were four females and one male; median age was 46 years (range 29-78). Herbalife had been used for 1 to 7 months prior to presentation. Four patients presented with a hepatocellular and one with a cholestatic reaction. Median values were for bilirubin 190 micromol/L (range: 26-311; ref. < 20 micromol/L), ALP 407 U/L (range: 149-712; ref. 35-105 U/L) and ALT 24 87 U/L (range: 456-2637; ref. 70 and 45 U/L for males and females, respectively). Liver biopsy was performed in 2 patients and was consistent with toxic hepatitis in both cases. Other causes of hepatitis were excluded by appropriate serological testing and ultrasound. Causality assessment according to RUCAM was probable in three cases and possible in two. Using the WHO-UMC criteria causality was certain in one case, probable in two and possible in two cases. CONCLUSIONS: Hepatotoxicity is probably associated with the use of Herbalife products. Hepatotoxicity due to herbal remedies is an important differential diagnosis in the diagnostic work-up of liver injury.

Perioperative risks and benefits of herbal supplements in aesthetic surgery.

Most medications, herbal preparations, and nutraceutical supplements have notable effects on biochemical pathways and may influence wound healing, coagulation, and cardiovascular function. They can also interact with other drugs. A large portion of the data available regarding the effects of naturopathic medicines is anecdotal. Marketing of certain products may be misleading and potentially harmful, and quality control standards are highly variable. In order to ensure quality control and standardization of products, it is prudent to work with preparations manufactured by companies that adhere to pharmaceutical (good manufacturing practice [GMP]) standards. However, many of these higher-quality products are not readily available to the public over the counter. A large percentage of patients undergoing plastic surgery use one or more herbal medications, but the disclosure of such medications to allopathic providers is often incomplete. In addition, patients may not understand the importance of discontinuing such medications before surgery. The authors review research on the possible benefits and risks of commonly used herbal medications such as arnica montana, St. John's wort, bromelain, echinacea, ginkgo biloba, ephedra, valerian, and others, focusing on their potentially positive or negative impact during the perioperative period of aesthetic surgery. Good communication with surgical patients, including the administration of a presurgical questionnaire to help identify any use of herbal medications, is emphasized.

Vasospasm and stroke attributable to ephedra-free xenadrine: case report.

Following the 2004 ban of ephedra, which was linked to several cases of stroke and myocardial infarction, manufacturers have marketed "ephedra-free" weight loss products that include the active ingredient synephrine. Despite the lack of data on safety and efficacy, synephrine is touted by its promoters as a "safe" alternative to ephedra and is often combined with caffeine, as in the supplement Xenadrine-EFX. We report a case of left middle cerebral artery vasopasm and stroke in a young healthy patient in the setting of Xenadrine-EFX use.

Periconceptional use of weight loss products including ephedra and the association with birth defects.

BACKGROUND: : Weight loss products are frequently used by reproductive-aged women and these products may be taken (inadvertently or intentionally) during pregnancy. This study assessed the association between periconceptional use of weight loss products and major structural birth defects. METHODS: : Mothers of infants with birth defects (case infants) and a random sample of livebirths (control infants) born during the period 1998-2003 in 10 states participated in the National Birth Defects Prevention Study. Adjusted ORs (aORs) for the association between self-reported use of weight loss products and 23 categories of birth defects were calculated. RESULTS: : Mothers of control infants (2.4%) and 2.6% of mothers of case infants reported periconceptional use of weight loss products; 1.2% of mothers of control infants and 1.3% of mothers of case infants reported using an ephedra-containing product. Use of any weight loss product was associated with anencephaly (aOR 2.6; 95% CI: 1.3-5.3), dextro-transposition of the great arteries (aOR 2.1; 95% CI: 1.1-4.3), and aortic stenosis (aOR 3.4; 95% CI: 1.5-7.9). Use of products containing ephedra showed an increased aOR with anencephaly (aOR 2.8; 95% CI: 1.0-7.3), while other weight loss products were associated with dextro-transposition of the great arteries (aOR 1.8; 95% CI: 1.2-2.7), and aortic stenosis (aOR 2.1; 95% CI: 1.3-3.5). CONCLUSIONS: : These results suggest an association between periconceptional use of weight loss products and certain birth defects but the possible mechanism is not clear. This is the first finding of such an association and, because we examined a large number of exposure-outcome associations in a hypothesis-generating analysis, these results might have been due to chance.

[Toxic hepatitis by consumption Herbalife products a case report]. / Hepatitis aguda asociada al consumo de Herbalife a propósito de un caso.

Toxic hepatitis by consumption Herbalife products is an affection poorly documented and with a great impact in the population due to their massive consumption. We present the case of a 63-years-old woman with probable diagnosis of toxic hepatitis secondary to the consumption of nutritional supplements Herbalife. The nutritional supplements based on natural ingredients are of massive consumption worldwide. Because they are recognized like innocuous and of non-controlled comercialization, they lack suitable controls. Although there are reported cases of hepatotoxicity and other side effects induced by these products, there is still not strong evidence to generate a positive reaction of the control organisms. We report a case of acute toxic hepatitis potencially due to the consumption of Herbalife.