Effect of magnesium treatment on vitamin D resistance

镁治疗对维生素 D 抵抗的影响

基本信息

项目摘要

DESCRIPTION (provided by applicant): In the setting of an on-going clinical trial in a population of patients with a history of colorectal adenoma, we are proposing to evaluate the effect of magnesium (Mg) supplementation on serum levels of vitamin D metabolites. Despite food fortification and dietary supplementation, vitamin D insufficiency/deficiency is still relativly common in the US. Many epidemiologic studies consistently found that low vitamin D status was associated with increased risks of non-skeletal chronic diseases including colorectal cancer (CRC). However, randomized clinical trials generated inconsistent results. One striking observation is that a large portion of the inter-person variation in serum 25- hydroxyvitamin D (25(OH)D) levels is unexplained. Further, there is a substantial inter-individual variation in serum 25(OH)D in response to the same dose of vitamin D supplementation. Mg plays a critical role in the synthesis and metabolism of vitamin D. The activities of 3 key enzymes determining 25(OH)D level may be Mg-dependent. Further, Mg deficiency has been implicated in "Mg-dependent vitamin-D-resistant rickets" and Mg supplementation substantially reversed resistance to vitamin D treatment. Very recently, we found intake of Mg significantly interacted with intake of vitamin D in relation to risks of vitamin D deficiency and insufficiency. Furthermore, we found the associations of serum 25(OH)D with mortality, including mortality due to CRC, may be modified by Mg intake, and the reduction in risk associated with high serum concentrations of 25(OH)D appeared primarily among those with Mg intake e median. Our novel finding of Mg-vitamin D interaction may explain some of the variability in 25(OH)D levels and may provide another possible interpretation to explain previous inconsistencies. Very recently, an animal study found the Mg-deficient diet significantly reduced the mRNA of the enzyme that primarily converts 25(OH)D to its active form, 1,25-dihydroxyvitamin D (1,25(OH)D), and significantly increased mRNA expression of the enzyme which mainly converts 25(OH)D to 24,25- dihydroxyvitamin D (24,25(OH)D). Further, a randomized clinical trial of vitamin D supplementation observed changes in vitamin D metabolite conversion with a significant increase in conversion of 25(OH)D to 24,25(OH)D. However, the ratio of serum 24,25(OH)D to serum 25(OH)D was only temporarily and slightly affected by vitamin D supplementation. Furthermore, the initial ratio predicted the efficacy of vitamin D treatment (i.e. rise in 25(OH)D). Based on these findings, we hypothesize that Mg supplementation reduces 24,25(OH)D and the ratio of 24,25(OH)D/ 25(OH)D (two markers of Mg deficiency), and, thus, improves resistance to vitamin D and reduces risk of CRC. To test hypothesis, we propose to measure serum levels of 24,25(OH)D, 25(OH)D, and 1,25 (OH)D in samples collected prior to and at the conclusion of a 12-week Mg intervention in 180 individuals (90 Mg-treatment and 90 placebo). This study will be the first to evaluate the effect of Mg supplementation on resistance to vitamin D and will lay the foundation for future prevention trials.
描述(由申请人提供):在有结直肠腺瘤病史的患者人群中进行的一项正在进行的临床试验中,我们建议评价镁(Mg)补充剂对维生素D代谢物血清水平的影响。尽管食物强化和膳食补充,维生素D不足/缺乏症在美国仍然相对常见。许多流行病学研究一致发现,低维生素D状态与非骨骼慢性疾病(包括结直肠癌(CRC))的风险增加有关。然而,随机临床试验产生了不一致的结果。一个引人注目的观察结果是,血清25-羟基维生素D(25(OH)D)水平的大部分人与人之间的差异是无法解释的。此外,血清25(OH)D在相同剂量的维生素D补充剂的反应中存在显著的个体间差异。镁在维生素D的合成和代谢中起着关键作用。影响25(OH)D水平的3种关键酶活性可能具有镁依赖性。此外,镁缺乏与“镁依赖性维生素D抵抗性佝偻病”有关,补充镁基本上逆转了对维生素D治疗的抵抗。最近,我们发现镁的摄入量与维生素D的摄入量显着相互作用,与维生素D缺乏和不足的风险有关。此外,我们发现血清25(OH)D与死亡率(包括结直肠癌死亡率)的相关性可能会被镁摄入量改变,与高血清25(OH)D浓度相关的风险降低主要出现在镁摄入量中等的人群中。我们的镁-维生素D相互作用的新发现可以解释25(OH)D水平的一些变化,并可能提供另一种可能的解释来解释以前的不一致。最近,一项动物研究发现,缺镁饮食显著降低了主要将25(OH)D转化为其活性形式1,25-二羟基维生素D(1,25(OH)D)的酶的mRNA,并显著增加了主要将25(OH)D转化为24,25-二羟基维生素D(24,25(OH)D)的酶的mRNA表达。此外,一项补充维生素D的随机临床试验观察到维生素D代谢物转化的变化,25(OH)D转化为24,25(OH)D的转化显著增加。然而,血清24,25(OH)D与血清25(OH)D的比值仅暂时和轻微地受到维生素D补充的影响。此外,初始比率预测了维生素D治疗的功效(即, 25(OH)D)。基于这些发现,我们假设镁补充剂降低了24,25(OH)D和24,25(OH)D/ 25(OH)D的比率(镁缺乏的两个标志物),从而提高了对维生素D的抵抗力并降低了CRC的风险。为了检验假设,我们建议测量180名受试者(90名镁治疗者和90名安慰剂治疗者)在12周镁干预之前和结束时收集的样本中24,25(OH)D、25(OH)D和1,25(OH)D的血清水平。这项研究将首次评估镁补充剂对维生素D抵抗的影响,并为未来的预防试验奠定基础。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Martha J. Shrubsole其他文献

Erratum to: Urinary polyphenols and breast cancer risk: results from the Shanghai Women’s Health Study
  • DOI:
    10.1007/s10549-009-0599-3
  • 发表时间:
    2009-10-25
  • 期刊:
  • 影响因子:
    3.000
  • 作者:
    Jianfeng Luo;Yu-Tang Gao;Wong-Ho Chow;Xiao-Ou Shu;Honglan Li;Gong Yang;Qiuyin Cai;Nathaniel Rothman;Hui Cai;Martha J. Shrubsole;Adrian A. Franke;Wei Zheng;Qi Dai
  • 通讯作者:
    Qi Dai
Sa1113: A SINGLE-CELL RESOLUTION, MULTI-OMIC SPATIAL ATLAS OF COLONIC TUMORIGENESIS DRIVEN BY <em>C. DIFFICILE</em> FROM HUMAN COLORECTAL CANCER-ASSOCIATED BIOFILMS
  • DOI:
    10.1016/s0016-5085(22)60740-6
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Nicholas O. Markham;Julia L. Drewes;Jada C. Domingue;Bob Chen;Cody N. Heiser;Molly A. Bingham;Alan J. Simmons;Marisol A. Ramirez;Subhag Kotrannavar;Hannah Lunnemann;Erin Laubacher;Won Jae Huh;Martha J. Shrubsole;Qi Liu;Robert Coffey;Cynthia L. Sears;Ken S. Lau
  • 通讯作者:
    Ken S. Lau
Tissue gene expression analysis approach in a context of high technical and biological heterogeneity
  • DOI:
    10.1186/s13104-025-07383-0
  • 发表时间:
    2025-07-22
  • 期刊:
  • 影响因子:
    1.700
  • 作者:
    Evan Bagley;Souvik Seal;Lauren R. Fanning;Jean-Sebastien Anoma;Tami Crawford;Benjamin G. Vincent;Elizabeth L. Barry;Martha J. Shrubsole;Erin Kirk;John A. Baron;Dale C. Snover;David N. Lewin;Todd A. Mackenzie;Xiaohua Gao;Melissa A. Troester;Alexander V. Alekseyenko;Kristin Wallace
  • 通讯作者:
    Kristin Wallace
Sa1227 BACTERIAL INVASION IN PRECANCEROUS POLYPS FROM THE COLON MOLECULAR ATLAS PROJECT
  • DOI:
    10.1016/s0016-5085(23)01760-2
  • 发表时间:
    2023-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Uswah Siddiqi;Julia L. Drewes;Cynthia L. Sears;Robert J. Coffey;Ken S. Lau;Martha J. Shrubsole;Nicholas O. Markham
  • 通讯作者:
    Nicholas O. Markham
Assessing the role of the gut microbiome at the interface between environmental chemical exposures and human health: Current knowledge and challenges
  • DOI:
    10.1016/j.envpol.2022.120380
  • 发表时间:
    2022-12-15
  • 期刊:
  • 影响因子:
    7.300
  • 作者:
    Anna Maria Campana;Hannah E. Laue;Yike Shen;Martha J. Shrubsole;Andrea A. Baccarelli
  • 通讯作者:
    Andrea A. Baccarelli

Martha J. Shrubsole的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Martha J. Shrubsole', 18)}}的其他基金

Southern Environmental Health Study
南方环境健康研究
  • 批准号:
    10900880
  • 财政年份:
    2023
  • 资助金额:
    $ 5.51万
  • 项目类别:
Colibactin-Producing Escherichia coli as an Environmental Stimulus Shaping Pre-Cancer Progression
产生大肠杆菌素的大肠杆菌作为塑造癌症前期进展的环境刺激物
  • 批准号:
    10518848
  • 财政年份:
    2022
  • 资助金额:
    $ 5.51万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10697366
  • 财政年份:
    2022
  • 资助金额:
    $ 5.51万
  • 项目类别:
Colibactin-Producing Escherichia coli as an Environmental Stimulus Shaping Pre-Cancer Progression
产生大肠杆菌素的大肠杆菌作为塑造癌症前期进展的环境刺激物
  • 批准号:
    10697373
  • 财政年份:
    2022
  • 资助金额:
    $ 5.51万
  • 项目类别:
Southern Environmental Health Study
南方环境健康研究
  • 批准号:
    10336724
  • 财政年份:
    2021
  • 资助金额:
    $ 5.51万
  • 项目类别:
Southern Environmental Health Study
南方环境健康研究
  • 批准号:
    10491875
  • 财政年份:
    2021
  • 资助金额:
    $ 5.51万
  • 项目类别:
Methionine metabolism in esophageal adenocarcinoma carcinogenesis
食管腺癌癌变过程中的蛋氨酸代谢
  • 批准号:
    9193068
  • 财政年份:
    2016
  • 资助金额:
    $ 5.51万
  • 项目类别:
Methionine metabolism in esophageal adenocarcinoma carcinogenesis
食管腺癌癌变过程中的蛋氨酸代谢
  • 批准号:
    9024964
  • 财政年份:
    2015
  • 资助金额:
    $ 5.51万
  • 项目类别:
Reproducibility and validity of microbiomial markers in colorectal cancer
结直肠癌微生物标志物的重现性和有效性
  • 批准号:
    8639073
  • 财政年份:
    2014
  • 资助金额:
    $ 5.51万
  • 项目类别:
Reproducibility and validity of microbiomial markers in colorectal cancer
结直肠癌微生物标志物的重现性和有效性
  • 批准号:
    8788702
  • 财政年份:
    2014
  • 资助金额:
    $ 5.51万
  • 项目类别:

相似海外基金

ICF Mechanical Property Optimisation of Magnesium Alloy Wires for Bioresorbable Vascular Scaffolds for the Treatment of Peripheral Arterial Disease
用于治疗外周动脉疾病的生物可吸收血管支架镁合金丝的 ICF 机械性能优化
  • 批准号:
    MR/Z503897/1
  • 财政年份:
    2024
  • 资助金额:
    $ 5.51万
  • 项目类别:
    Research Grant
Microbiome targeted oral butyrate therapy in Gulf War multisymptom illness
微生物组靶向口服丁酸盐治疗海湾战争多症状疾病
  • 批准号:
    10367805
  • 财政年份:
    2023
  • 资助金额:
    $ 5.51万
  • 项目类别:
Molecular analysis of glutamatergic neurons derived from iPSCs containing PPM1D truncating mutations found in Jansen de Vries Syndrome
Jansen de Vries 综合征中发现的含有 PPM1D 截短突变的 iPSC 衍生的谷氨酸能神经元的分子分析
  • 批准号:
    10573782
  • 财政年份:
    2023
  • 资助金额:
    $ 5.51万
  • 项目类别:
Mechanisms and therapeutic potential of blocking the mitochondrial Mg2+ channel Mrs2 in obesity and NAFLD
阻断线粒体 Mg2 通道 Mrs2 在肥胖和 NAFLD 中的机制和治疗潜力
  • 批准号:
    10679847
  • 财政年份:
    2023
  • 资助金额:
    $ 5.51万
  • 项目类别:
Trial of Zinc Supplements for Young Infants with Clinical Severe Infection in Tanzania
在坦桑尼亚对患有临床严重感染的小婴儿进行锌补充剂试验
  • 批准号:
    10635077
  • 财政年份:
    2023
  • 资助金额:
    $ 5.51万
  • 项目类别:
Novel Pharmacological Treatment for Preeclampsia
先兆子痫的新型药物治疗
  • 批准号:
    10758980
  • 财政年份:
    2023
  • 资助金额:
    $ 5.51万
  • 项目类别:
Hypomagnesemia-related magnesium supplementation and its association with healthcare burden and adverse outcomes in patients with heart failure: a population-based study
低镁血症相关的镁补充剂及其与心力衰竭患者的医疗负担和不良后果的关系:一项基于人群的研究
  • 批准号:
    485924
  • 财政年份:
    2022
  • 资助金额:
    $ 5.51万
  • 项目类别:
    Studentship Programs
Magnesium, mitochondria, and diastolic dysfunction
镁、线粒体和舒张功能障碍
  • 批准号:
    10705354
  • 财政年份:
    2022
  • 资助金额:
    $ 5.51万
  • 项目类别:
Structural basis for allosteric regulation of RyR1
RyR1 变构调节的结构基础
  • 批准号:
    10366087
  • 财政年份:
    2021
  • 资助金额:
    $ 5.51万
  • 项目类别:
Mitigate cisplatin induced acute kidney injury through preservation of vasculature and proximal tubule
通过保护脉管系统和近端小管减轻顺铂引起的急性肾损伤
  • 批准号:
    10644372
  • 财政年份:
    2021
  • 资助金额:
    $ 5.51万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了