Sutherland Joshua P, Zhou Ang, Hyppönen Elina
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Nutrients. 2024 Dec 26;17(1):38. doi: 10.3390/nu17010038.
: Falls are a major public health concern. Daily vitamin D supplementation is a proposed fall prevention strategy; however, safety concerns have arisen from some clinical trials showing increased fall risk when using higher vitamin D dosing methods. The relationship between vitamin D and falls may be influenced by factors, such as inflammation, which can alter the balance of essential nutrients like vitamin D and retinol, potentially affecting motor function. We use a genetic epidemiological approach to explore the association of inflammation, vitamin D, and fall risk. We included 307,082 UK Biobank participants and conducted observational and Mendelian randomization (MR) analyses to investigate associations between 25-hydroxyvitamin D [25(OH)D] and fall risk, with analyses including restriction to participants who had fallen and had inflammation as defined by CRP ≥ 5 mg/L. In the observational analysis, CRP was associated with a higher (per 5 mg/L CRP increase OR = 1.06, 95% CI 1.05-1.07) and 25(OH)D with a lower odds of falls. The association between 25(OH)D concentrations and fall risk was non-linear ( < 0.001), reflecting a plateauing of the association at higher concentrations. There was an interaction between 25(OH)D and CRP on their association with the odds of falls ( = 0.009). In participants with CRP ≥ 5 mg/L, the association was U-shaped, and the fall risk was elevated for both 25(OH)D < 25 nmol/L and ≥ 100 nmol/L ( < 0.004). The association between high 25(OH)D and falls was most pronounced for participants with CRP ≥ 20 mg/L (≥ 100 nmol/L vs. 50-74.99 nmol/L: OR = 2.40, 95% CI, 1.50-3.86). Genetically predicted higher 25(OH)D was not associated with fall risk in the overall population, but a suggestive association with fall risk was seen in participants who had fallen and had CRP > 20 mg/L (926 cases; OR = 1.20, 95% CI, 1.00-1.44). Our study suggests that inflammation might modify the vitamin D and fall risk relationship. Both low and high 25(OH)D levels are associated with more falls in individuals with chronic inflammation, with supporting evidence seen in both observational and MR analyses. This may provide insight into the increased fall risk following high-dose vitamin D supplementation in clinical trials, warranting further research.
跌倒问题是一个重大的公共卫生关注点。每日补充维生素D是一种预防跌倒的策略；然而，一些临床试验引发了安全担忧，这些试验表明采用较高剂量维生素D的给药方法时跌倒风险会增加。维生素D与跌倒之间的关系可能受到炎症等因素的影响，炎症会改变维生素D和视黄醇等必需营养素的平衡，从而可能影响运动功能。我们采用基因流行病学方法来探究炎症、维生素D与跌倒风险之间的关联。我们纳入了307,082名英国生物银行的参与者，并进行了观察性分析和孟德尔随机化（MR）分析，以研究25-羟基维生素D [25(OH)D]与跌倒风险之间的关联，分析对象限定为已经跌倒且炎症水平由CRP≥5 mg/L定义的参与者。在观察性分析中，CRP与较高的跌倒几率相关（每增加5 mg/L CRP，OR = 1.06，95% CI 1.05 - 1.07），而25(OH)D与较低的跌倒几率相关。25(OH)D浓度与跌倒风险之间的关联是非线性的（< 0.001），这反映出在较高浓度时该关联趋于平稳。25(OH)D和CRP在与跌倒几率的关联上存在交互作用（= 0.009）。在CRP≥5 mg/L的参与者中，这种关联呈U形，25(OH)D < 25 nmol/L和≥100 nmol/L时跌倒风险均升高（< 0.004）。对于CRP≥20 mg/L的参与者，高25(OH)D与跌倒之间的关联最为明显（≥100 nmol/L vs. 50 - 74.99 nmol/L：OR = 2.40，95% CI，1.50 - 3.86）。在总体人群中，基因预测的较高25(OH)D水平与跌倒风险无关，但在已经跌倒且CRP > 20 mg/L的参与者中观察到与跌倒风险有提示性关联（926例；OR = 1.20，95% CI，1.00 - 1.44）。我们的研究表明，炎症可能会改变维生素D与跌倒风险之间的关系。在患有慢性炎症的个体中，低水平和高水平的25(OH)D都与更多的跌倒相关，观察性分析和MR分析均提供了支持证据。这可能有助于解释临床试验中高剂量补充维生素D后跌倒风险增加的现象，值得进一步研究。
