No online current list of potentially life-threatening, hepatotoxic herbs and dietary supplements based on PubMed case reports exists in a summarized tabular form.

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.

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.

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.

A 25-year-old Iranian gentleman was admitted to hospital with severe bloody diarrhoea and abdominal pain. He had similar episodes in the past. On each occasion his symptoms developed following the consumption of the herbal weight loss supplement Hydroxycut Hardcore X. On this admission, a (CT) scan demonstrated bowel wall thickening and peri-colonic fat stranding in the sigmoid colon. On flexible sigmoidoscopy, a continuous length of congested mucosa with multiple small ulcers was seen extending up to the mid-transverse colon, in keeping with ulcerative colitis. Histological analysis of biopsies was taken at the time and confirmed this. He was started on steroids early during his admission but this only provided a transient clinical improvement. The addition of cyclosporine, which was later changed to azathioprine, did not improve his condition either. He therefore underwent an open subtotal colectomy with end ileostomy. He made a slow but steady recovery and was discharged 3 weeks later.

Cigarette smokers have an increased risk for coronary artery disease. Nicotine present in cigarettes can adversely affect the cardiovascular system via stimulation of both sympathetic and parasympathetic neurons. Caffeine, another cardiovascular and central nervous system (CNS) stimulant, is commonly found in Ephedra and Ephedra-free dietary supplements. These caffeine-containing supplements also have been linked to cardiovascular toxicities. Although no longer on the U.S market, Ephedra-containing supplements are another source of cardiovascular and CNS stimulants, namely the ephedrine alkaloids. Together caffeine, nicotine, and ephedrine can individually stress the cardiovascular system, and an overlap of these agents is predicted in smokers and dieters. To understand the collective effects of these stimulants on the heart morphology and ultrastructure, rats were exposed to synthetic combinations of nicotine (0.2 mg/kg/day), ephedrine (0-30 mg/kg/day), and/or caffeine (0-24 mg/kg/day) as well as an extract from a caffeine-containing Ephedra supplement (Metabolife 356). After exposure for 3 days, the hearts were removed and examined for hypersensitivity myocarditis and myocardial necrosis. None of the drugs tested alone affected heart tissue morphology, nor were atypical cardiac cells observed. However, in combination, significant interactions were found between caffeine and ephedrine; the interventricular septum was most susceptible, with a significant increase in atypical cardiac cells observed. Nicotine pretreatment caused greater susceptibility to cardiotoxicity associated with combinations of caffeine + ephedrine or Metabolife, particularly in the left ventricle wall. These results indicate that sympathomimetic combinations present in Ephedra supplements may have produced cardiotoxicity reported in consumers of these products. Moreover, the presence of nicotine exacerbates these toxic effects.

A case of rhabdomyolysis associated with the use of Hydroxycut is reported.

An 18-year-old Caucasian man arrived at an urgent care center complaining of bilateral leg pain and weakness. His creatine kinase (CK) concentration was 13,220 IU/L. He was diagnosed with rhabdomyolysis and instructed to go to the emergency room. He admitted to decreased urine output for four to five days before hospital admission. He had no significant past medical history, and his medications before symptom onset included Hydroxycut four caplets by mouth daily, naproxen sodium 220 mg by mouth as needed for pain, dextroamphetamine saccharate-amphetamine salts (Adderall) 15 mg by mouth once five days prior for a school examination, and hydrocodone-acetaminophen and cyclobenzaprine for pain. His social history revealed a recent increase in his exercise regimen, and his last alcoholic beverage was consumed five days prior. Upon admission, laboratory tests revealed elevated concentrations of CK, serum creatinine (SCr), aspartate transaminase, alanine transaminase (ALT), and alkaline phosphatase. The patient was diagnosed with rhabdomyolysis and treated with intravenous hydration. The patient's leg tenderness was reduced, and he was discharged with instructions to stop Hydroxycut, increase fluid intake, avoid alcohol consumption, and limit physical activity for the next week. Two weeks after hospital discharge, the patient's CK and liver enzyme values returned to normal, excluding ALT and SCr, which remained slightly elevated, and his lower-extremity tenderness fully resolved.

An 18-year-old Caucasian man with no significant medical history developed rhabdomyolysis possibly associated with the ingestion of Hydroxycut in addition to his increased exercise regimen.

Dietary supplements and herbal medicines are gaining popularity in many developed countries.

Although most can be used without any problem, serious toxicities do occur.

Problems can be anticipated when they are used for non-traditional indications, at excessive dose, for prolonged duration, or by patients who are also on multiple modern pharmaceuticals. Problems should also be anticipated when these products claim to be able to relieve symptoms rapidly or when herbs with pronounced pharmacological effects or toxic components are used.

Resuscitation, symptomatic and supportive care are the most important aspects of management of toxicities from these products.

This article reviews when problems with these products can be anticipated and outlines a practical approach to management.

Seizures in persons using dietary supplements (DS) have been reported through the Food and Drug Administration's (FDA) MedWatch system, but not formally reviewed.

Sixty-five cases of DS-associated seizures reported to MedWatch from 1993 to 1999 were obtained through the Freedom of Information Act and independently evaluated by three reviewers for probability of causation based on temporal relationship, biological plausibility, and underlying risk factors. Our aims in this review were 1) to assess the probability of causation in each case; 2) to characterize the patterns of use and types of supplements involved in cases of seizures; and 3) to identify trends that may explain potential risks factors for dietary supplement-related seizures.

Twenty seizures were judged as probably related, 13 possibly related, and 10 as unrelated to DS use. Five cases were not seizures, and 17 cases contained insufficient information. In the 20 probably related cases, 19 involved ephedra, 14 involved herbal caffeine, and in one case, the supplement contained no herbal constituents but an array of elemental salts. Ephedra was also associated with 7 of the 13 possibly related cases, and caffeine was contained in 5 of these supplement products. Creatine, St. John's wort, and ginkgo biloba were other DS implicated in possibly related seizure events. Seizures were associated with hypoglycemia in 3 cases, and secondary to stroke in 2 cases and cardiac arrest in 2 cases. Weight loss (45%) and athletic performance enhancement (30%) were the most often cited reasons for supplement use. In most cases, DS use was within manufacturers' guidelines.

Ephedra was implicated in 27 of 33 DS-associated seizures reported to the FDA over a 7-year period, further underscoring that significant health risks are associated with use of this herbal product.

The metal content of dietary supplements, including 13 ephedra-containing supplements, was studied.

Samples of botanicals (black cohosh, echinacea, goldenseal, kava kava, milk thistle, saw palmetto, Synephrine, and valerian root), ephedra-containing dietary supplements (Amp II, EPH 833, Ephedra, Ephedra 1000, Hydroxycut, Metabolife 356, Metabolift, Ripped Fuel, Ripped Fuel Extreme, Ripped Fuel [ma huang-free], Stacker 2 [two lots], Super Stinger, Virgin Earth, Xenadrine RFA-1 [two lots], Yellow Jacket), and nonprescription reference agents (NoDoz and Primatene) were digested in acid, reacidified, and then spiked with internal standards. Metals were quantified using Environmental Protection Agency quality assurance and quality-control standards 6020 and 200.8. Forty-seven metals were analyzed by inductively coupled plasma-mass spectrometry, with subpart-per-trillion detection limits.

All metals detected were in concentrations below toxic levels or physiological limit levels for the daily doses specified by the products' labeling. Metals found in highest concentrations among all the supplements sampled were sodium, magnesium, calcium, potassium, aluminum, iron, titanium, mercury, strontium, lead, barium, and silver. Of the 27 supplements analyzed, those with the lowest metal concentrations were mostly single-ingredient botanical supplements, while multiple-component, ephedra-containing dietary supplements generally had higher metal concentrations. Significant lot-to-lot variations were found for two ephedra-containing dietary supplements.

None of 47 metals was found in highly toxic amounts in 23 brands of dietary supplements and two nonprescription reference preparations.

Dinitrophenol, a chemical currently used as an insecticide, is known to uncouple mitochondrial oxidative phosphorylation. A component of explosives, it has also been used in the past as a food coloring and clothing dye. In the 1930s, physicians prescribed it for weight loss, but this practice was discontinued when reports of cataracts, deaths, and other adverse outcomes came to light. We describe in our report the overdose and fatality of a teenager who purchased the product as a weight loss dietary supplement by mail order. We also describe a laboratory method that allowed postmortem determination of the dinitrophenol concentration in the victim's serum. Her death, despite prompt medical treatment, underscores the danger of dinitrophenol. The easy accessibility and apparent resurgent interest in dinitrophenol as a weight loss agent is extremely timely and troubling.

Disorders of fuel metabolism as they relate to abnormal fuel intake,abnormal fuel expenditure, and dietary supplements are the focus of this article. The emergency physician should be aware of the medical complications that can occur as a result of starvation states,eating disorders, fad diets, hypermetabolic states, and ergogenic aids. Knowledge and understanding of the complications associated with these disorders will facilitate the diagnosis and management of patients who present to the emergency department with any of the disorders reviewed.

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 use of over-the-counter dietary supplements has risen dramatically, and adverse events can be severe. Physicians should recognize the dangers that ephedrine-containing supplements present and remain vigilant for sympathomimetic symptoms in young, otherwise healthy, patients. This case illustrates how the use of a popular weight-loss supplement by a 27-year-old professional football player apparently resulted in cardiac arrhythmia requiring direct cardioversion.

The International Olympic Committee, the World Anti-Doping Agency, and International Sport Federations have banned and restricted the use of many stimulants including prescription and over-the-counter medications and dietary supplements. In addition to elite athletes, people of all ages use stimulants in attempts to improve athletic performance, alter body composition, and increase levels of energy. Here we introduce a seven-stage model designed to facilitate informed decision-making by individuals taking or thinking of taking stimulants for sport, health, and/or appearance reasons. We review for amphetamines, over-the counter sympathomimetics, and caffeine their performance-enhancing and performance-degrading effects, health benefits and mechanisms of action, medical side effects, and legal, ethical, safety, and financial implications.

The sequencing and annotation of the human genome and the genomes of other model organisms offer new tools and new opportunities for human nutrition research in the 21st century. Basic research continues to be the key foundation for formulating solid nutrition recommendations for the public, but the basis for establishing human nutrient recommendations today suffers because of lack of good biomarkers and because of weak federal funding for nutrition research. In the context of this post-human genome-sequencing era, tantalizing opportunity exists in seven areas-four basic and three applied: 1) identification of molecular biomarkers for nutrient status; 2) characterization of single polynuclear polymorphisms (SNPs) associated with nutrition; 3) development of a national genome array nutrition database; 4) use of models at all phylogenetic levels for nutrition research; 5) application of post-genome-sequencing tools to study diet and human health, including phytonutrients and genetically modified foods; 6) application of these tools to the role of nutrition in pathogenesis of human disease; and 7) development of a funding base for research on exercise and human health.