Hypersensitivity pneumonitis associated with inhalation of catechin-rich green tea extracts.

A 51-year-old man presented with fever and fatigue after 3.5 months of antituberculosis therapy. High-resolution computed tomography of his chest revealed new ground-glass opacities and poorly defined centrilobular nodules. He had undergone catechin inhalation for 1 month. We diagnosed hypersensitivity pneumonitis (HP) based on the clinical course, bronchoscopy and a challenge test. Cases of HP due to inhalation of extracted catechin powder are rare. Although it has many known positive attributes, it is necessary to be aware that catechin can cause HP.

Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review.

Globally, people are struggling with obesity. Many effective, nonconventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful.

Green tea polyphenols supplementation and Tai Chi exercise for postmenopausal osteopenic women: safety and quality of life report.

BACKGROUND: Evidence suggests that both green tea polyphenols (GTP) and Tai Chi (TC) exercise may benefit bone health in osteopenic women. However, their safety in this population has never been systematically investigated. In particular, there have been hepatotoxicity concerns related to green tea extract. This study was to evaluate the safety of 24 weeks of GTP supplementation combined with TC exercise in postmenopausal osteopenic women, along with effects on quality of life in this population. METHODS: 171 postmenopausal women with osteopenia were randomly assigned to 4 treatment arms for 24 weeks: (1) Placebo (500 mg starch/day), (2) GTP (500 mg GTP/day), (3) Placebo + TC (placebo plus TC training at 60 min/session, 3 sessions/week), and (4) GTP + TC (GTP plus TC training). Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, and total bilirubin at baseline and every 4 weeks. Kidney function (urea nitrogen and creatinine), calcium, and inorganic phosphorus were also assessed at the same times. Qualify of life using SF-36 questionnaire was evaluated at baseline, 12, and 24 weeks. A mixed model of repeated measures ANOVA was applied for analysis. RESULTS: 150 subjects completed the study (12% attrition rate). The compliance rates for study agents and TC exercise were 89% and 83%, respectively. Neither GTP supplementation nor TC exercise affected liver or kidney function parameters throughout the study. No adverse event due to study treatment was reported by the participants. TC exercise significantly improved the scores for role-emotional and mental health of subjects, while no effect on quality of life was observed due to GTP supplementation. CONCLUSIONS: GTP at a dose of 500 mg/day and/or TC exercise at 3 hr/week for 24 weeks appear to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. TC exercise for 24 weeks (3 hr/wk) significantly improved quality of life in terms of role-emotional and mental health in these subjects. ClinicalTrials.gov identifier: NCT00625391.

[Severe hepatitis caused by green tea intoxication in a child. Case report]. / Hepatitis grave producida por intoxicación con té verde en un niño. Presentación de un caso.

Herb-induced liver injury is a type of adverse drug reaction related to using herbal medicine, and now is a segment of druginduced liver injury. The use of herbal products has increased significantly, because it is generally regarded as safe and natural by the public. In the United States, the incidence reaches 9 % and, in the countries of Asia, 19-63 % of the total cases of druginduced liver injury. Green tea is obtained from the leaves of the Camellia sinensis. Freshly harvested leaves are stabilized by dry heating to inactivate the polyphenol enzyme and then dried quickly. Its consumption has increased in recent years and has been reported with hepatotoxic reactions. We present a case of severe hepatitis related to the consumption of green tea in a 2-year-old child.

El daño hepático inducido por hierbas es una reacción adversa relacionada con el uso de medicina herbaria, incluida en el grupo de daño hepático inducido por drogas. El uso terapéutico de hierbas medicinales es cada vez más frecuente por la creencia de que los productos naturales o hierbas son siempre seguros. En Estados Unidos, la incidencia de toxicidad alcanza un 9 % y, en países de Asia, un 19-63 % de los casos totales de daño hepático inducido por drogas. El té verde es obtenido de las hojas de la Camellia sinensis. Las hojas recién cosechadas son estabilizadas por calentamiento en seco para inactivar la enzima polifenol y luego se secan rápidamente. Su consumo ha aumentado en los últimos años, y se han documentado reacciones hepatotóxicas. Se presenta un caso de hepatitis aguda grave asociada al consumo de té verde en un niño de 2 años.

[Liver injury induced by "natural remedies": an analysis of cases submitted to the Spanish Liver Toxicity Registry]. / Hepatotoxicidad secundaria a "productos naturales": análisis de los casos notificados al Reigstro Español de Hepatotoxicidad.

BACKGROUND: toxic liver damage associated with the use of natural remedies is a growing health problem. OBJECTIVES: to analyze the demographics, and clinical and epidemiological characteristics of patients developing liver injury related to these remedies. PATIENTS AND METHODS: all DILI cases associated with the use of herbal remedies (HR) or dietary supplements (DS) submitted to the Spanish Registry were analyzed. Type of liver damage, severity, and outcome were specifically evaluated. RESULTS: thirteen cases out of 521 DILI cases (2%) submitted to the Spanish Liver Toxicity Registry between 1994 and 2006 were related to HR/DS, which ranked as the 10th therapeutic group with a greater number of cases and above pain killers, anxiolytics, and antipsychotic drugs. Nine patients (69%) were female (mean age 45 years). Nine cases (69%) had jaundice at presentation. The predominating type of liver damage was hepatocellular (12; 92%), and 31% of cases exhibited the common features of hypersensitivity. Camellia sinensis (3, 23%) was the main causative herb, followed by Rhamnus purshianus and isoflavones (Fitosoja(R), Biosoja(R)) (2 cases each, 15%). Three cases (23%) were rechallenged with the offending product. CONCLUSIONS: the incidence of hepatic damage related to HR/DS is not so rare, the most common profile of affected patients being a woman with acute hepatocellular hepatitis. Low suspicion regarding the putative role of herbs in hepatotoxicity makes diagnosis more difficult, and probably increases the incidence of inadvertent rechallenge in these patients.

Doxorubicin cardiotoxicity and Camellia sinensis cardioprotection determined by speckle-tracking echocardiography

Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells

Update of green tea interactions with cardiovascular drugs and putative mechanisms.

Many patients treated with cardiovascular (CV) drugs drink green tea (GT), either as a cultural tradition or persuaded of its putative beneficial effects for health. Yet, GT may affect the pharmacokinetics and pharmacodynamics of CV compounds. Novel GT-CV drug interactions were reported for rosuvastatin, sildenafil and tacrolimus. Putative mechanisms involve inhibitory effects of GT catechins at the intestinal level on influx transporters OATP1A2 or OATP2B1 for rosuvastatin, on CYP3A for sildenafil and on both CYP3A and the efflux transporter p-glycoprotein for tacrolimus. These interactions, which add to those previously described with simvastatin, nadolol and warfarin, might lead, in some cases, to reduced drug efficacy or risk of drug toxicity. Oddly, available data on GT interaction with CV compounds with a narrow therapeutic index, such as warfarin and tacrolimus, derive from single case reports. Conversely, GT interactions with simvastatin, rosuvastatin, nadolol and sildenafil were documented through pharmacokinetic studies. In these, the effect of GT or GT derivatives on drug exposure was mild to moderate, but a high inter-individual variability was observed. Further investigations, including studies on the effect of the dose and the time of GT intake are necessary to understand more in depth the clinical relevance of GT-CV drug interactions.

Dietary Supplements, Isotretinoin, and Liver Toxicity in Adolescents: A Retrospective Case Series.

Isotretinoin is the most effective acne therapy available, but has the potential for a number of adverse side effects, including transaminitis. The iPLEDGE isotretinoin program recommends avoiding some herbals and supplements due to potential side effects. However, little is known about the effects of protein supplements on the liver, particularly in patients taking isotretinoin. We designed a retrospective chart review to evaluate the symptoms, diagnosis, treatment, and outcome of patients on or preparing to take isotretinoin therapy who were concurrently ingesting protein or herbal supplementation and who developed transaminitis. In 100% (8/8) of cases, dietary supplementation was determined to be at least a possible cause of elevated liver transaminases. In 75% (6/8) of cases, dietary supplement appears to be the most likely cause at some point in their evaluation. Most of our patients' elevations in aspartate aminotransferase and/or alanine aminotransferase were likely caused by supplementation with protein, creatine, or herbal extracts, rather than prescribed isotretinoin or tetracycline antibiotics for acne. Hence, dietary supplementation may cause liver function abnormalities. As supplement usage appears common in teenagers, clinicians should consider counseling their patients to avoid these products, particularly when prescribing known hepatotoxic drugs.

Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements.

The safety of green tea infusions and green tea extract (GTE)-based products is reviewed regarding catechins. Epigallocatechin 3-gallate (EGCG), the major catechin present in green tea, is suspected of being responsible for liver toxicity reported in humans consuming food supplements. Intake of EGCG with green tea infusions and GTE-based beverages is up to about 450mg EGCG/person/day in Europe and higher in Asia. Consumption of green tea is not associated with liver damage in humans, and green tea infusion and GTE-based beverages are considered safe in the range of historical uses. In animal studies, EGCG's potency for liver effects is highly dependent on conditions of administration. Use of NOAELs from bolus administration to derive a tolerable upper intake level applying the margin of safety concept results in acceptable EGCG-doses lower than those from one cup of green tea. NOAELs from toxicity studies applying EGCG with diet/split of the daily dose are a better point of departure for risk characterization. In clinical intervention studies, liver effects were not observed after intakes below 600mg EGCG/person/day. Thus, a tolerable upper intake level of 300mg EGCG/person/day is proposed for food supplements; this gives a twofold safety margin to clinical studies that did not report liver effects and a margin of safety of 100 to the NOAELs in animal studies with dietary administration of green tea catechins.

An intervention study on the effect of matcha tea, in drink and snack bar formats, on mood and cognitive performance.

Matcha tea is gaining popularity throughout the world in recent years and is frequently referred to as a mood-and-brain food. Previous research has demonstrated that three constituents present in matcha tea, l-theanine, epigallocatechin gallate (EGCG), and caffeine, affect mood and cognitive performance. However, to date there are no studies assessing the effect of matcha tea itself. The present study investigates these effects by means of a human intervention study administering matcha tea and a matcha containing product. Using a randomized, placebo-controlled, single-blind study, 23 consumers participated in four test sessions. In each session, participants consumed one of the four test products: matcha tea, matcha tea bar (each containing 4g matcha tea powder), placebo tea, or placebo bar. The assessment was performed at baseline and 60min post-treatment. The participants performed a set of cognitive tests assessing attention, information processing, working memory, and episodic memory. The mood state was measured by means of a Profile of Mood States (POMS). After consuming the matcha products compared to placebo versions, there were mainly significant improvements in tasks measuring basic attention abilities and psychomotor speed in response to stimuli over a defined period of time. In contrast to expectations, the effect was barely present in the other cognitive tasks. The POMS results revealed no significant changes in mood. The influence of the food matrix was demonstrated by the fact that on most cognitive performance measures the drink format outperformed the bar format, particularly in tasks measuring speed of spatial working memory and delayed picture recognition. This study suggests that matcha tea consumed in a realistic dose can induce slight effects on speed of attention and episodic secondary memory to a low degree. Further studies are required to elucidate the influences of the food matrix.

Evaluation of Safety and Antioxidant Activity of Yellow Tea (Camellia sinensis) Extract for Application in Food.

The article presents an evaluation of the safety of yellow tea (Camellia sinensis) extract consumption and its antioxidant activity in an animal model. Wistar rats were exposed through diet to 2, 6, and 10 g yellow tea extract/kg feed for 90 days. No signs of toxicity and no differences in mean body weight gain in the treated and control rats were recorded throughout the experiment. No statistically significant differences in hematology findings and clinical chemistry parameters were observed between controls and treated groups. Microscopic examination of tissue sections revealed no pathology attributable to yellow tea extract intake. Lipid peroxidation level in the liver was slightly increased in medium-dose males and high-dose females and decreased in two female groups receiving 2 and 6 g/kg of the extract tested. Content of carbonyl groups in protein, as well as the basal level of DNA damage, was not changed. In a majority of rats, the activity of antioxidant enzymes was increased except superoxide dismutase in high-dose groups, glutathione peroxidase in high-dose females, glutathione reductase in low- and mid-dose groups, and glutathione S-transferase in mid-dose females and high-dose males. It could be concluded that rats tolerated well dietary treatment with yellow tea extract up to 0.8 g/kg b.w./day for 90 days. Results showed that yellow tea extract at the doses tested did not demonstrate adverse effects and improved the antioxidant status in the liver of rats.

Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea.

Despite an ancient reputation for potential phytotherapeutic effects and innocuity, traditional herbal medicine has previously been implicated in severe adverse events. Exolise is an 80% ethanolic dry extract of green tea (Camellia sinensis) standardized at 25% catechins expressed as epigallocatechin gallate, containing 5-10% caffeine. It has been available in France, Belgium, Spain and the United Kingdom since 1999, as an adjuvant therapy for use in weight loss programmes. In various studies, green tea has to date been considered useful for its potential hepatic protective properties. In this study, we report a case of fulminant hepatitis during self-medication with Exolise, requiring liver transplantation.

La actividad antibacteriana de Camellia sinensis comparada con propóleo frente al Streptococcus mutans / Antibacterial activity of Camellia sinensis versus propolis against Streptococcus mutans

RESUMEN Introducción: El té verde (Camellia sinensis) y el propóleo presentan flavonoides, que inhiben el crecimiento, metabolismo y la coagregación del Streptococcus mutans, principal agente causal de la caries dental. Objetivo: Evaluar la actividad antibacteriana in vitro del extracto etanólico del té verde (Camellia sinensis) al 10 por ciento y 20 por ciento comparado con extracto etanólico de propóleo al 10 por ciento y 20 por ciento, frente al crecimiento de cepas de Streptococcus mutans (ATCC 25175). Métodos: Estudio experimental in vitro, longitudinal, prospectivo y comparativo. El universo estuvo constituido por 90 discos de difusión y la muestra por 15 discos embebidos en té verde (Camellia sinensis) o propóleo a diferentes concentraciones, clorhexidina acuosa al 0,12 por ciento y agua destilada. El tamaño de muestra se calculó por fórmula de comparación de medias, después de realizar un estudio piloto. Se colocaron los discos de difusión embebidos en las sustancias sobre agar Mueller Hinton, sembrado con Streptococcus mutans (ATCC 25175), haciendo medición del ancho de los halos inhibitorios a las 24 y 48 h. Se aplicaron pruebas de comparación no paramétricas de Kruskal Wallis y la prueba rangos de Wilcoxon. Resultados: El máximo ancho de halo inhibitorio logrado por clorhexidina acuosa al 0,12 por ciento, extracto etanólico de té verde (Camellia sinensis) al 20 por ciento y extracto etanólico de propóleo al 20 por ciento fue a las 24 h con valores de 10,64 mm ± 0,924 mm, 6,82 mm ± 0,982 mm y 8,36 mm ± 1,286 mm, respectivamente. El extracto etanólico de té verde (Camellia sinensis) al 20 por ciento, presentó diferencias estadísticamente significativas respecto al extracto etanólico de propóleo al 20 por ciento, tanto a las 24 h (p= 0,013), como a las 48 h (p= 0,011). Conclusiones: Frente al crecimiento de cepas de Streptococcus mutans (ATCC 25175), el extracto etanólico de propóleo al 20 por ciento presenta mayor actividad antibacteriana respecto al extracto etanólico de té verde (Camellia sinensis) al 10 por ciento y 20 por ciento, actividad que disminuye con el paso del tiempo(AU)

ABSTRACT Introduction: Green tea (Camellia sinensis) and propolis contain flavonoids which inhibit the growth, metabolism and co-aggregation of Streptococcus mutans, the main causative agent of dental caries. Objective: Evaluate the antibacterial activity in vitro of 10 percent and 20 percent green tea (Camellia sinensis) ethanolic extract versus 10 percent and 20 percent propolis ethanolic extract against the growth of Streptococcus mutans (ATCC 25175) strains. Methods: An in vitro experimental prospective longitudinal comparative study was conducted. The study universe was 90 diffusion disks and the sample was 15 disks soaked up in green tea (Camellia sinensis) or propolis at various concentrations, 0.12 percent aqueous chlorhexidine and distilled water. Sample size was estimated by the comparison of means formula after conducting a pilot study. The diffusion disks soaked up in the substances were placed on Mueller Hinton agar planted with Streptococcus mutans (ATCC 25175) and the width of the inhibition haloes was measured at 24 h and 48 h. Nonparametric Kruskal-Wallis comparison tests and the Wilcoxon rank test were performed. Results: The maximum width of the inhibition halo achieved by 0.12 percent aqueous chlorhexidine, 20 percent green tea (Camellia sinensis) ethanolic extract, and 20 percent propolis ethanolic extract at 24 h was 10.64 mm ± 0.924 mm, 6.82 mm ± 0.982 mm and 8.36 mm ± 1.286 mm, respectively. The 20 percent green tea (Camellia sinensis) ethanolic extract showed statistically significant differences with respect to the 20 percent propolis ethanolic extract, both at 24 h (p= 0.013) and at 48 h (p= 0.011). Conclusions: The 20 percent propolis ethanolic extract displays greater antibacterial activity against the growth of Streptococcus mutans (ATCC 25175) strains than the 10 percent and 20 percent green tea (Camellia sinensis) ethanolic extract. This activity decreases with the passing of time(AU)

Chinese green tea and acute hepatitis: a rare yet recurring theme.

A previously healthy 16-year-old girl presented with signs of acute hepatitis. On initial enquiry, she had not taken any prescribed or 'over-the-counter' medications, and there was no recent travel history. Further investigations revealed no viral, autoimmune or metabolic cause of hepatitis. Only following specific questioning did she reveal that she had, in the preceding 3 months, regularly consumed internet ordered Chinese green tea, which contained Camellia sinensis. After ceasing green tea consumption, there was a rapid and sustained recovery of her hepatitis. The authors discuss the probable cause of herbal tea in this case of acute hepatitis, and the importance of awareness of this rare yet recurring theme for patients and clinicians alike.

High concentration of epigallocatechin-3-gallate increased the incidences of arrhythmia and diastolic dysfunction via ß2-adrenoceptor.

Epigallocatechin-3-gallate (EGCG) is the major and most potent representative in green tea, which has been proved to modulate myocardial contractility. Whether EGCG has some negative effects on cardiac function is not known. In the present study, we investigated the effects of EGCG at different doses on cardiac contraction and explored whether ß2 -adrenoceptor (ß2 AR) was involved in EGCG-induced cardiac effects. Isolated rat hearts were mounted on the Langendorff system and perfused with different concentrations of EGCG in low or normal calcium Krebs-Henseleit (KH) buffer. The contraction of hearts was measured. Ventricular myocytes were cultured with EGCG and isoprenaline (ISO, 10(-7) M) for 12 h. ICI118,551 (55 nM) was used to inhibit ß2 AR. Cardiomyocyte shortening, viability, and responsiveness to ISO (10(-9) M) were measured. EGCG dose dependently enhanced contractility of perfused heart in low calcium KH buffer. In the normal calcium KH buffer, EGCG at low dose (20 µM) increased heart contraction, while at high dose (50 µM), it increased the incidences of arrhythmia and diastolic dysfunction. In isolated ventricular myocytes, EGCG at the concentration of 0.001 to 1.0 µΜ did not affect their contraction. However, the responsiveness to ISO and the survival of myocytes were increased by EGCG (0.01 µM). The increased responsiveness was partially abolished by ICI118,551. The data obtained in this study demonstrated that EGCG at low dose conferred cardioprotection, yet at high dose increased the incidences of arrhythmia and diastolic dysfunction. ß2 AR was involved in EGCG-induced cardiac effects.

Herbal hepatotoxicity: analysis of cases with initially reported positive re-exposure tests.

BACKGROUND: Positive re-exposure tests are diagnostic hallmarks for hepatotoxicity. OBJECTIVE: To test validity of positive re-exposures in herb induced liver injury. METHODS: We searched Medline database for cases of herb induced liver injury with positive re-exposures and analysed 34 cases for positive re-exposure test criteria of baseline alanine aminotransferase< 5N before re-exposure, and re-exposure alanine aminotransferase ≥ 2× baseline alanine aminotransferase. Re-exposure test was negative, if baseline alanine aminotransferase< 5N combined with re-exposure alanine aminotransferase< 2× baseline alanine aminotransferase, or if baseline alanine aminotransferase≥ 5N regardless of the re-exposure alanine aminotransferase including no available re-exposure alanine aminotransferase result. RESULTS: In 21/34 cases (61.8%), criteria for a positive re-exposure were fulfilled, with negative tests in 6/34 cases (17.6%) or uninterpretable ones in 7/34 cases (20.6%). Confirmed positive re-exposure tests established potential of herb induced liver injury for Aloe, Chaparral, Chinese herbal mixtures, Chinese Jin Bu Huan, Chinese Syo Saiko To, Germander, Greater Celandine, Green tea, Kava, Mistletoe, Polygonum multiflorum, and Senna, with up to 4 case reports per herb. CONCLUSIONS: Among 34 cases of herb-induced liver injury with initially reported positive re-exposure tests, 61.8% of the cases actually fulfilled established test criteria and provided firm diagnoses of herb induced liver injury by various herbs.