Low 25-hydroxyvitamin D Levels and the Risk of Frailty Syndrome: a Systematic Review and Dose-response Meta-analysis

Background: Vitamin D deficiency and frailty are common with aging. Previous studies examining vitamin D status and frailty have produced mixed results, and in particular, the shape of the association has not been well established. We examined the association between 25-hydroxyvitamin D (25OHD) serum levels and frailty by performing a systematic review and dose-response meta-analysis.

Methods: We searched the PubMed, EMBASE and Cochrane Library databases of Elsevier through February 2017. Cross-sectional and cohort studies that reported adjusted risk ratios with 95% confidence intervals (CI) for frailty with ≥3 categories of 25OHD serum levels were selected. Data extraction was performed independently by two authors. The reported risk estimates for 25OHD categories were recalculated, employing a comprehensive trend estimation from summarized dose-response data.

Results: The pooled risk estimate of frailty syndrome per 25 nmol/L increment in serum 25OHD concentration was 0.88 (95% CI = 0.82-0.95, I = 86.8%) in the 6 cross-sectional studies and 0.89 (95% CI = 0.85-0.94, I = 0.0%) in the 4 prospective cohort studies. Based on the Akaike information criteria (AIC), a linear model was selected (AIC for the nonlinear model: - 5.4, AIC for the linear model: - 6.8 in the prospective cohort studies; AIC for the linear model: - 13.6, AIC for the nonlinear model: - 1.77 in the cross-sectional studies).

Conclusions: This dose-response meta-analysis indicates that serum 25OHD levels are significantly and directly associated with the risk of frailty. Further studies should address the underlying mechanisms to explain this relationship and to determine whether vitamin D supplementation is effective for preventing frailty syndrome.