Supplementary Material for: Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study

Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging techniques have led investigators to explore peripheral GSH as a possible pathological signature of oxidative stress-associated brain changes. In a preclinical model of GSH deficiency, we found a correlation between whole brain and peripheral GSH levels. We found that the naturally occurring isothiocyanate sulforaphane increased blood GSH levels in healthy human subjects following 7 days of daily oral administration. In parallel, we explored the potential influence of sulforaphane on brain GSH levels in the anterior cingulate cortex, hippocampus, and thalamus via 7-T magnetic resonance spectroscopy. A significant positive correlation between blood and thalamic GSH post- and pre-sulforaphane treatment ratios was observed, in addition to a consistent increase in brain GSH levels in response to treatment. This clinical pilot study suggests the value of exploring relationships between peripheral GSH and clinical/neuropsychological measures, as well as the influences sulforaphane has on functional measures that are altered in neuropsychiatric disorders.

精神分裂症及其他神经精神障碍仍有待开发基于发病机制的干预手段。过量氧化应激日益被认为参与脑疾病的病理生理过程，多项研究均报道了主要抗氧化剂谷胱甘肽（glutathione, GSH）水平降低。由于通过成像技术评估脑内氧化应激相关变化存在技术局限性，研究者转而探索将外周谷胱甘肽作为氧化应激相关脑改变的潜在病理特征。在谷胱甘肽缺乏的临床前模型中，我们发现全脑与外周谷胱甘肽水平存在相关性。我们发现，健康人体受试者经每日口服给药7天后，天然存在的异硫氰酸酯萝卜硫素可升高血液谷胱甘肽水平。与此同时，我们通过7特斯拉磁共振波谱技术，探究了萝卜硫素对前扣带回皮层、海马体及丘脑内脑谷胱甘肽水平的潜在影响。结果显示，萝卜硫素给药前后血液与丘脑谷胱甘肽水平的比值呈显著正相关，同时脑内谷胱甘肽水平在给药后呈现一致性升高。这项临床预试验表明，探索外周谷胱甘肽与临床/神经心理学指标之间的关联，以及萝卜硫素对神经精神障碍中受损的功能指标的影响，具有重要研究价值。