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

非洲裔美国人血液中 25(OH)-维生素 D 水平的优化

• 批准号: 10045657
• 负责人: Sushil K Jain
• 金额: $ 50.72万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10045657
• 关键词: Adverse effects; African American; Analysis of Variance; Animals; Antioxidants; Biological; Biological Availability; Biological Markers; Blood; Chemistry; Cholecalciferol; Clinical; Clinical Trials; Controlled Clinical Trials; Coupled; Cysteine; Data; Development; Diabetes Mellitus; Disease; Dose; Double-Blind Method; Ensure; Fasting; Future; GC gene; GLUT4 gene; Genes; Glutathione; Goals; Grant; Health; Health Hazards; Human; Hydroxylation; Impairment; Incidence; Inflammation; Inflammatory; Ingestion; Insulin Resistance; Kidney Function Tests; Life Style; Link; Liver; Measurable; Mediating; Mediator of activation protein; Medical; Metabolic; Metabolism; Mixed Function Oxygenases; Modeling; Muscle; Natural Products; Nutrient; Obesity; Oral; Outcome; Oxidative Stress; Pain; Pathway interactions; Physiological; Placebo Effect; Placebos; Population; Prediabetes syndrome; Pregnancy Tests; Public Health; Randomized; Randomized Controlled Clinical Trials; Rattus; Recommendation; Regulation; Regulator Genes; Reporting; Research Subjects; Risk; SLC2A1 gene; Safety; Serum; Statistical Data Interpretation; Supplementation; TNF gene; Testing; Therapeutic; Therapeutic Effect; Tissues; Translations; United States National Center for Health Statistics; Up-Regulation; Validation; Visit; Vitamin A; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Whole Blood; capsule; chronic pain; clinical pain; cost; delta opioid receptor; design; dietary supplements; efficacy clinical trial; efficacy trial; epidemiology study; experience; glucose metabolism; health disparity; improved; liver function; liver metabolism; member; mouse model; novel; novel strategies; preclinical study; prevent; side effect; success

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.

优化非洲裔美国人的25（OH）维生素D水平 公共卫生问题：低循环水平为25（OH）维生素D（VD）与许多 非裔美国人（AA）的不利健康状况和健康差异。上病理学高剂量VD 需要补充以消除AA循环25（OH）VD的水平上观察到的差异 和白人主题。但是，最近的研究质疑了高剂量VD的治疗作用 补充。 理由：谷胱甘肽（GSH）是主要的物理抗氧化剂。最近的研究报告，低水平 GSH与动物和人类研究中的25（OH）VD缺陷有关。使用ZDF大鼠的动物研究 25（OH）VD缺乏症的小鼠模型表明，与补充Vd-inone相比 与VD（胆石素） + L-半胱氨酸（LC，A GSH前体）共同补充，导致了改善 GSH状态导致25（OH）VD的循环水平显着升高并降低氧化。 应力，TNF-α和胰岛素抵抗（IR）。 方法：AA的谷胱甘肽水平降低（GSH），并且胰岛素抵抗的高发生率（IR） 和炎症性疾病。该R33应用程序为我们的设计介绍了随机，双盲，安慰剂的设计 对照临床试验测试了与L-半胱氨酸相结合补充VD的假设（A GSH前体）在优化25（OH）VD和GSH [生物学特征]的统计数据方面更为成功。 并简单地降低TNF-α和IR [功能或临床结果]，这表明治疗性更好 与仅在AA受试者中补充VD相比，方法相比。 对公共卫生的影响：这项R33临床试验的成功完成将对 使用GSH前体的未来有效临床试验的设计设计， 较低的VD剂量减少25（OH）VD缺乏/不足，炎症和IR生物标志物。这 开发安全的低成本饮食补充剂，可以改善25-羟基维生素D状态并降低 胰岛素抵抗和炎症将为糖尿病前的治疗带来重大益处 非裔美国人人口中的健康差异，包括慢性疼痛。 该应用对PAR-18-828的反应高度敏感，将复制以前的人类研究并检查 通过将天然产物L-半胱氨酸与VD相结合以优化生物学特征的结果 补充和效率。