HERBALIFE® ASSOCIATED SEVERE HEPATOTOXICITY IN A PREVIOUSLY HEALTHY WOMAN.

Lately there has been an increased consumption of herbal preparations, distributed as nutritional supplements, often claimed to be 'natural' and harmless. However, as their use is not subjected to strict pre-marketing testing and regulations, their ingredients are not clearly defined and there is no quality control or proof of their effectiveness and safety. A growing body of references accentuate their harmful effects, in particular hepatotoxicity, which varies from minimal hepatogram changes to fulminant hepatitis requiring liver transplantation. This case report describes liver damage that was highly suspected to originate from Herbalife® products consumption. We excluded alcohol, viral, metabolic, autoimmune and neoplastic causes of liver lesions, as well as vascular liver disease, but we noticed a connection between the use of Herbalife® products and liver damage. The exact mechanism of liver damage in our patient was not determined. After removing the Herbalife® products, liver damage resolved and there was no need to perform liver biopsy. Taking into consideration the growing consumption of herbal products and their potential harmfulness, we consider that more strict regulations of their production process and sale are necessary, including exact identification of active substances with a list of ingredients, toxicologic testing and obligatory side effect report.

Clinically Relevant Herb-Drug Interactions: Past, Present, and Future (8/11)

In this lecture divided into 11 chapters, Dr. Gurley explains about the factors that contribute to herbal interactions, pharmacodynamic mechanisms, pharmacokinetic Interactions; identify factors that contribute to the risk for herb-drug interactions, and describes how new technologies in supplements and drugs may impact herb-drug interaction.

Ephedra alkaloid contents of Chinese herbal formulae sold in Taiwan.

Consumption of Ephedra alkaloids is prohibited in-competition by the World Anti-Doping Agency (WADA). In Taiwan, colds are often treated with Chinese herbal formulae containing Herba Ephedrae. We screened products sold in Taiwan and preliminarily assessed their relationships with WADA threshold violations. Fifty-six concentrated powder products, including 19 Chinese herbal formulae that contained Herba Ephedrae, were collected. The content of Ephedra alkaloids, namely ephedrine (E), methylephedrine (ME), norpseudoephedrine (NPE; cathine), pseudoephedrine (PE), and norephedrine (NE; phenylpropanolamine), was determined using a validated high-performance liquid chromatography method. The results revealed that the phenotypic indicators of the collected products, E/PE and E/total ratios, were 1.52-4.70 and 0.49-0.72, respectively, indicating that the Herba Ephedrae species in these products was probably E. sinica or E. equisetina, but not E. intermedia. The contents of E, ME, NPE, PE, and NE and the total alkaloid contents in the daily doses of the products were 0.45-34.97, 0.05-4.87, 0.04-3.61, 0.15-12.09, and 0.01-2.00 mg and 0.68-53.64 mg, respectively. The alkaloid contents followed a relatively consistent order (E > PE > ME ≈ NPE > NE), even for products from different manufacturers. We calculated that single doses of 50.0% and 3.6% of the products would result in the WADA thresholds of E and NPE being exceeded, respectively. Our data provide critical information for athletes and medical personnel, who should be wary of using complex Chinese herbal formulae in addition to over-the-counter products.

Hypervitaminosis A inducing intra-hepatic cholestasis--a rare case report.

The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease.

Cardiovascular toxicities of performance-enhancing substances in sports.

Athletes commonly use drugs and dietary supplements to improve athletic performance or to assist with weight loss. Some of these substances are obtainable by prescription or by illegal means; others are marketed as supplements, vitamins, or minerals. Nutritional supplements are protected from Food and Drug Administration regulation by the 1994 US Dietary Supplement Health and Education Act, and manufacturers are not required to demonstrate proof of efficacy or safety. Furthermore, the Food and Drug Administration lacks a regulatory body to evaluate such products for purity. Existing scientific data, which consist of case reports and clinical observations, describe serious cardiovascular adverse effects from use of performance-enhancing substances, including sudden death. Although mounting evidence led to the recent ban of ephedra (ma huang), other performance-enhancing substances continue to be used frequently at all levels, from elementary school children to professional athletes. Thus, although the potential for cardiovascular injury is great, few appropriately designed studies have been conducted to assess the benefits and risks of using performance-enhancing substances. We performed an exhaustive OVID MEDLINE search to Identify all existing scientific data, review articles, case reports, and clinical observations that address this subject. In this review, we examine the current evidence regarding cardiovascular risk for persons using anabolic-androgenic steroids including 2 synthetic substances, tetrahydrogestrinone and androstenedione (andro), stimulants such as ephedra, and nonsteroidal agents such as recombinant human erythropoietin, human growth hormone, creatine, and beta-hydroxy-beta-methylbutyrate.

Toxicity and drug interactions associated with herbal products: ephedra and St. John's Wort.

Health care providers are being increasingly confronted with the use of herbal medications by their patients. It is imperative that patients be questioned regarding herbal preparation use and that health care providers become familiar with these agents. Research into the active components and mechanisms of action of various herbals is ongoing [350]. Long-range studies need to be performed to follow patients for efficacy or toxicity in chronic use [351,352]. Adverse reactions to herbal remedies should be reported to the FDA MedWatch at http://www.fda.gov/medwatch. As withany therapeutic agent, risk of use must always be weighed against potential benefits.

Beliefs and social norms about ephedra onset and perceived addiction among college male and female athletes.

In Spring 2003, a qualitative approach was used to investigate relevant beliefs and norms associated with ephedra initiation and perceived addiction to the drug among 43 primarily minority athletes, attending a historically Black university in the southwestern region of the United States, who self-identified as past users. In general, participants stated that their second ephedra use event occurred on the same day as or the day after initiation. The majority of participants perceived that addiction was established by routine and eccentric behavior. Male athletes stated they used ephedra for improved athletic performance while females stated they used the drug for weight loss. Male participants stated it is difficult to quit ephedra use because of the resulting decrease in athletic performance, sickness, and weight gain. Female athletes were more concerned with their appearance. These findings are important in determining the early extent to which addiction is self-identified.

Safety of ephedra: lessons learned.

The safe use of ephedra represents the best possible outcome of a convergence of variables, some with troubling potential outcomes. Commercially used ephedra and its products is prepared from Ephedra spp. and as such is subject to a variety of influences (including differences in species and strain; growth, harvest and storage conditions) all of which may influence the content of constituents (which may, in turn, affect the absorption, distribution, and metabolism of active constituents) and taken together, influences the net pharmacological effect. Further, as a natural substance with an easily perceived and desirable (i.e. weight-loss) pharmacological effect, ephedra is also susceptible to a variety of adulterants, both economic and efficacious. All of the foregoing represent potential for misadventure before ephedra even reaches the consumer. The consumer introduces a constellation of variables as well, including, but not limited to, acute and chronic diseases, inborn errors in metabolism, simultaneous use of prescription and over-the-counter drugs, dietary supplements, alcohol, illicit substances and certain foods (e.g. chocolate, caffeinated drinks), all or some of which may exert synergistic, additive or even antagonistic influences on the desired physiologic outcome. The foregoing not withstanding, the majority of the published nonclinical and clinical studies, and history of use, support the safety of ephedra at the proposed use levels. However, the reports of adverse events submitted to FDA raise concern about the risk associated with ephedra without establishing a direct causal relationship. Given the foregoing, how best can a decision on safety be made? Should the question actually be "can ephedra be as toxic as reported?"

The combination therapy of Ephedra herb and Loxoprofen caused gastric lesions in mice.

The combination therapy of a Kampo formula and an analgesic-antipyretic agent is often used for the common cold in Japan. We investigated the effect of such a combination therapy, using the Ephedra herb, which is a common ingredient of Kakkon-to and Mao-to, and Loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), on fever induced in an experimental model of mice under strong stress. The combination therapy of Ephedra herb and Loxoprofen caused gastric mucosal lesions and loss of body weight. It is considered that this combination therapy should be avoided because of its adverse effects.