United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts.

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)."

Improving natural product research translation: From source to clinical trial.

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

Hepatotoxicity due to hydroxycut: a case series.

OBJECTIVES: Muscletech Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada) was a popular weight-loss supplement that was recalled by the manufacturer in May 2009 on the basis of reports of hepatotoxicity associated with this supplement. We sought to characterize the clinical presentation of Hydroxycut-associated liver injury and to adjudicate these cases for causal association with Hydroxycut. METHODS: We assessed the causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study. RESULTS: Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized, and three of eight patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database, including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting, and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed eight cases as definite, five highly likely, two probable, and two were considered to be possible. CONCLUSIONS: Hydroxycut has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight-loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated.

Antiplasmodial activity of extracts and quassinoids isolated from seedlings of Ailanthus altissima (Simaroubaceae).

Extracts and isolated compounds from seedlings of Ailanthus altissima, were assessed for antiplasmodial activity in vitro. Two quassinoids, ailanthone and 6alpha-tigloyloxychaparrinone, isolated from the active extracts showed activity against both chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum in vitro. Only ailanthone demonstrated low toxicity against the Vero cell line (kidney cells from the African green monkey). This is the first report of the isolation and antiplasmodial activity of 6alpha-tigloyloxychaparrinone from this species.