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

基本信息

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
项目类别：
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

项目摘要

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.

非洲裔美国人 25(OH) 维生素 D 水平的优化公共卫生问题：25(OH) 维生素 D (VD) 循环水平低与许多疾病相关非裔美国人 (AA) 的不良健康状况和健康差异。需要补充以消除 AA 中循环 25(OH)VD 水平的差异然而，最近的研究对高剂量 VD 的治疗效果提出了质疑。化。理由：谷胱甘肽 (GSH) 是一种主要的生理抗氧化剂，最近的研究表明谷胱甘肽水平较低。在使用 ZDF 大鼠的动物研究中，GSH 与 25(OH)VD 缺乏有关。 25(OH)VD 缺乏症小鼠模型表明，与单独补充 VD 相比，联合补充 VD（胆钙化醇）+ L-半胱氨酸（LC，GSH 前体）可改善 GSH 状态导致 25(OH)VD 循环水平显着增加并减少氧化压力、TNF-α 和胰岛素抵抗 (IR)。方法：AA 会降低谷胱甘肽 (GSH) 水平，并且会增加胰岛素抵抗 (IR) 的发生率该 R33 应用展示了我们的随机、双盲、安慰剂设计。对照临床试验检验了补充 VD 与 L-半胱氨酸（a GSH 前体）在优化 25(OH)VD 和 GSH [生物特征] 的状态方面更加成功同时降低 TNF-α 和 IR [功能或临床结果]，表明更好的治疗方法与 AA 受试者中单独补充 VD 相比。对公众健康的影响：本次R33临床试验的成功完成将对公众健康产生重大影响未来疗效临床试验的设计，检查使用 GSH 前体与降低 VD 剂量以减少 25(OH)VD 缺乏/不足、炎症和 IR 生物标志物。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 状态并减少胰岛素抵抗和炎症将为糖尿病前期和糖尿病的治疗提供显着的益处。非裔美国人的健康差异，包括慢性疼痛。该应用程序对 PAR-18-828 高度响应，将复制之前的人体研究并检查通过将天然产物 L-半胱氨酸与 VD 相结合来优化其生物特征的结果补充和功效。