Low 25-hydroxyvitamin D levels and the risk of frailty syndrome: a systematic review and dose-response meta-analysis

Abstract

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, I² = 86.8%) in the 6 cross-sectional studies and 0.89 (95% CI = 0.85-0.94, I² = 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.

Keywords: 25-hydroxyvitamin D; Cohort studies; Cross-sectional studies; Dose-response; Elderly; Frailty; Meta-analysis; Systematic review; Vitamin D.

Fig. 1

Flow diagram for the search strategy and study selection process

Fig. 2

Study-specific risk ratios and 95% confidence intervals of frailty syndrome risk according to study-specific serum levels of 25-hydroxyvitamin D (25OHD). Depending on available information, the median, midpoints or means of the categories were used for defining study-specific serum levels of 25OHD (nmol/L). CS, cross-sectional study; CO, prospective cohort studies

Fig. 3

Forest plots of the risk ratios (RRs) of frailty syndrome per 25 nmol/L increment in serum 25-hydroxyvitamin D concentration using a random-effects analysis. The squares represent study-specific RR (the square sizes are proportional to the weight of each study in the overall estimate); the horizontal lines represent 95% confidence intervals (CIs), and the diamond represents the overall RR estimate with 95% CI

Fig. 4

Risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) for the dose-response relationship between serum 25-hydroxyvitamin D concentrations (nmol/L) and risk of frailty syndrome among the populations. a, cross-sectional studies; b, prospective cohort studies. The solid and long-dashed lines represent the estimated RRs and their 95% CIs, respectively. The short-dashed line represents the non-linear relationship