Optimization of Blood Levels of 25(OH)-vitamin D in African Americans

非裔美国人25(OH)维生素D水平的优化 公共卫生问题：循环中低水平的25(OH)维生素D(VD)与许多 非洲裔美国人(AA)的不良健康状况和健康差距。超生理学大剂量VD 需要补充以消除在AA中观察到的循环25(OH)VD水平的差异 和白人受试者。然而，最近的研究对大剂量VD的治疗效果提出了质疑 补充。 原理：谷胱甘肽(GSH)是一种主要的生理性抗氧化剂。最近的研究报告说，低水平的 在动物和人类研究中，谷胱甘肽与25(OH)VD缺陷有关。ZDF大鼠的动物实验研究 而25(OH)VD缺乏的小鼠模型表明，与单独补充VD相比， 与VD(胆钙化醇)L-半胱氨酸(LC，谷胱甘肽前体)共补充导致改善 GSH状态导致循环中25(OH)VD水平显著升高，氧化作用降低 应激、肿瘤坏死因子-α和胰岛素抵抗(IR)。 研究方法：再障患者的谷胱甘肽(GSH)水平降低，胰岛素抵抗(IR)的发生率也较高 和炎症性疾病。这个R33应用程序展示了我们设计的随机、双盲、安慰剂- 补充血管性痴呆联合L-半胱氨酸(A)的临床对照试验 GSH前体)更成功地优化了25(OH)VD和GSH[生物标志]的状态 同时降低肿瘤坏死因子-α和IR[功能或临床结果]，提示更好的治疗方法 在AA受试者中与单独补充VD的方法进行比较。 对公众健康的影响：这项R33临床试验的成功完成将对 使用GSH前体和辅助剂检查联合补充剂的未来疗效临床试验的设计 较低的VD剂量可减少25(OH)VD缺乏/不充分、炎症和IR生物标志物。这个 开发一种安全、低成本的膳食补充剂，可以改善25-羟基维生素D的状况并减少 胰岛素抵抗和炎症将在治疗糖尿病前期和 非洲裔美国人的健康差距，包括慢性疼痛。 这个应用程序对PAR-18-828高度响应，将复制以前的人类研究并检查 天然产物L-半胱氨酸与VD相结合优化其生物学特征的结果 补充剂和功效。

Optimization of 25(OH) vitamin D levels in African Americans Public Health Issue: Low circulating levels of 25(OH) vitamin D (VD) have been correlated with many adverse health conditions and health disparities in African Americans (AA). Supraphysiological high-dose VD supplementation is required to eliminate the differences observed in the levels of circulating 25(OH)VD in AA and white subjects. However, recent studies have questioned the therapeutic effects of high-dose VD supplementation. Rationale: Glutathione (GSH) is a major physiological antioxidant. Recent studies report that low levels of GSH are linked to 25(OH)VD deficiencies in both animal and human studies. Animal studies using ZDF rats and a mouse model of 25(OH)VD deficiency have shown that, compared to supplementation with VD-alone, co-supplementation with VD (cholecalciferol) + L-cysteine (LC, a GSH precursor) led to an improvement in GSH status that resulted in significant increases in circulating levels of 25(OH)VD and reduced oxidative stress, TNF-α, and insulin resistance (IR). Approach: AA have reduced levels of glutathione (GSH), as well as a high incidence of insulin resistance (IR) and inflammatory disorders. This R33 application presents our design for a randomized, double-blind, placebo- controlled clinical trial to test the hypothesis that supplementation with VD in combination with L-cysteine (a GSH precursor) is more successful at optimizing the statuses of 25(OH)VD and GSH [biological signatures] and simultaneously decreasing TNF-α and IR [functional or clinical outcomes], suggesting a better therapeutic approach compared with supplementation with VD alone in AA subjects. Impact on Public Health: The successful completion of this R33 clinical trial will have a significant impact on the design of future efficacy clinical trials examining co-supplementation using a GSH precursor coupled with lower VD doses to reduce 25(OH)VD deficiency/inadequacy, inflammation, and IR biomarkers. The development of a safe, low-cost dietary supplement that can improve 25-hydroxy vitamin D status and reduce insulin resistance and inflammation would provide significant benefits in the treatment of pre-diabetes and health disparities, including chronic pain, in the African American population. This application, which is highly responsive to PAR-18-828, will replicate previous human studies and examine the outcome of biological signatures by combining the natural product L-cysteine with VD to optimize its supplementation and efficacy.