Tran Buu N, Okoniewski Richard, Spink Barbara C, LeMaster David M, Aldous Kenneth M, Spink David C
Wadsworth Center, New York State Department of Health, Albany, NY 12237, USA; Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, USA.
Wadsworth Center, New York State Department of Health, Albany, NY 12237, USA.
Steroids. 2023 May;193:109199. doi: 10.1016/j.steroids.2023.109199. Epub 2023 Feb 14.
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 (17β-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-17β-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.
2012年至2013年期间，约16名纽约居民报告了模糊的、非特异性的健康不良影响，包括疲劳、脱发和肌肉疼痛。一名患者因肝损伤住院。一项流行病学调查确定了这些患者的一个共同因素；他们都服用了来自同一供应商的B-50维生素和多种矿物质补充剂。为了调查这些营养补充剂是否可能是观察到的健康不良影响的原因，对市售批次的补充剂进行了全面的化学分析。为了确定有机成分和污染物的存在，制备了样品的有机提取物，并使用气相色谱-质谱联用仪（GC-MS）、液相色谱-串联质谱联用仪（LC-MS/MS）、液相色谱高分辨率质谱联用仪（LC-HRMS）和核磁共振仪（NMR）进行分析。这些分析揭示了大量甲睾酮（17β-羟基-2α,17α-二甲基-5α-雄甾烷-3-酮）的存在，甲睾酮是一种雄激素类固醇，属于第三类管制物质；二甲嗪，甲睾酮的一种嗪连接二聚体；以及甲基司坦唑醇（2,17α-二甲基-17β-羟基-5α-雄甾-1-烯-3-酮），一种相关的雄激素类固醇。通过使用雄激素受体启动子构建体，在荧光素酶测定中，甲睾酮和某些补充剂胶囊的提取物被鉴定为具有高度雄激素活性。细胞接触这些化合物后，这种雄激素活性持续了几天。在涉案批次中发现这些成分与健康不良影响、一名患者住院以及一名儿童出现严重男性化症状有关。这些发现强调了对营养补充剂行业进行更严格监管的必要性。
