Androgenic steroids in Over-the-Counter dietary Supplements: Analysis for association with adverse health effects.

From 2012 to 2013, approximately 16 New York residents reported vague, nonspecific adverse health effects which included fatigue, loss of scalp hair, and muscle aches. One patient was hospitalized for liver damage. An epidemiological investigation identified a common factor among these patients; the consumption of B-50 vitamin and multimineral supplements from the same supplier. To investigate whether these nutritional supplements might have been responsible for the adverse health effects observed, comprehensive chemical analyses of marketed lots of the supplements were performed. To determine presence of organic components and contaminants, organic extracts of samples were prepared and analyzed using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), liquid chromatography high-resolution mass spectrometry (LC-HRMS), and nuclear magnetic resonance (NMR). These analyses revealed the presence of significant levels of methasterone (17ß-hydroxy-2α,17α-dimethyl-5α-androstane-3-one), an androgenic steroid and schedule III-controlled substance; dimethazine, an azine-linked dimer of methasterone; and methylstenbolone (2,17α-dimethyl-17ß-hydroxy-5α-androst-1-en-3-one), a related androgenic steroid. Methasterone and extracts of certain supplement capsules were identified as highly androgenic in luciferase assays by using an androgen receptor promoter construct. This androgenicity persisted for several days after cell exposure to the compounds. The presence of these components in implicated lots were associated with adverse health effects and the hospitalization of one patient and the presentation of symptoms of severe virilization in a child. These findings underscore the need for more rigorous oversight of the nutritional supplement industry.

Profiles of phytoestrogens in human urine from several Asian countries.

Intake of a diet rich in phytoestrogens has been associated with a decreased risk for hormone-dependent cancers in humans. Biomonitoring of phytoestrogens in human urine has been used to assess the intake of phytoestrogens. Although studies have reported phytoestrogen levels in urine specimens from the United States and Japan, little is known of human intake of phytoestrogens in other Asian countries. In this study we determined the concentrations of seven phytoestrogens, namely, enterolactone, enterodiol, daidzein, equol, O-desmethylangolensin (O-DMA), genistein, and coumestrol, in 199 human urine samples from three Asian countries, Vietnam (Hanoi and Ho Chi Minh), Cambodia (Phnom Penh), and India (Chennai and Kolkata), using a simple, sensitive, and reliable liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method. The residue levels of phytoestrogens in urine samples from the three Asian countries were compared with the concentrations in 26 urine samples from Japan (Ehime) and 16 urine samples from the United States (Albany), analyzed in this study. Among the phytoestrogens analyzed, isoflavones such as daidzein and genistein were predominant in urine samples from Vietnam; samples from Cambodia and India contained higher concentrations of enterolactone than isoflavones. Urinary concentrations of isoflavones in samples from Hanoi, Vietnam, were notably higher than the concentrations in samples from Cambodia, India, and the United States and similar to the concentrations in samples from Japan. The lowest concentrations of daidzein and the highest concentrations of enterolactone were found in urine samples from India. Concentrations of equol and O-DMA, which are microbial transformation products of daidzein (produced by gut microflora), were notably high in urine samples from Hanoi, Vietnam. The ratios of the concentration of equol or O-DMA to that of daidzein were significantly higher in samples from Hanoi than from Japan, indicating high biotransformation efficiency of daidzein by the population in Hanoi. High concentrations of equol, in addition to isoflavones, in urine have been linked to reduced breast cancer risk in previous studies, and, thus, the Vietnamese population may have potential protective effect against breast cancer. This study suggests that the dietary intake and profiles of phytoestrogens vary considerably, even among Asian countries.

Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure.

Reports of toxicity secondary to Kratom are rare and lack of diagnostic testing in human specimens has prevented confirmatory explanation of observed clinical effects. We present a novel case of serious human toxicity following Kratom use confirmed via quantitative analysis of urine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. A 64 year-old male was witnessed to have a seizure at home following kratom consumption. Upon arrival to the emergency department (ED), the patient was unresponsive. While in the ED, the patient sustained a second seizure. He was intubated to protect his airway. The remainder of his hospital course was uneventful. A urine specimen was collected shortly after admission and sent for analysis. The mitragynine concentration in the urine was 167 ± 15 ng/ml. We report a rare case of Kratom toxicity characterized by a seizure and coma confirmed by urinary analysis of mitragynine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. The proposed mechanism for this reaction is unclear but suggested mechanisms include adenosine binding or stimulation of adrenergic and/or serotonergic receptors similar to tramadol.