The Association of Serum Calcium Levels with the Risk of Metabolic Syndrome: A Meta-Analysis of Observational Studies.
INTRODUCTION Although some studies have examined the relationship between serum calcium levels and Metabolic Syndrome (MetS), results remain inconsistent, and a quantitative synthesis is lacking. This meta-analysis aims to consolidate existing evidence and clarify the association between serum calcium levels and MetS risk. METHODS We systematically searched seven databases up to May 1, 2025, for observational studies comparing serum calcium in MetS versus non-MetS groups. A random-effects model was applied to pool Odds Ratios (ORs) and Weighted Mean Differences (WMDs) with 95% Confidence Intervals (CIs). Subgroup analyses, sensitivity analyses, and publication bias assessments were also performed. RESULTS Twenty-three studies (n=67,148) showed a positive association in categorical data analysis (OR=1.79, 95% CI: 1.37-2.34, P<0.0001, I2=82.3%), whereas continuous data did not reveal a significant difference (WMD=0.0107 mmol/L, 95% CI: -0.0078-0.0291, P=0.258, I2=89.4%). Subgroup analysis tentatively suggested a higher MetS risk in elderly (65 years old or older) populations (OR=2.44, 95% CI: 1.70-3.51), though this finding was based on a limited number of studies. Substantial heterogeneity was observed in both analyses. DISCUSSION These findings suggest a potential association between elevated serum calcium and increased MetS risk, which may follow a nonlinear, threshold-like pattern. The observed age-related difference, while notable, should be interpreted with caution given the small number of studies in the elderly subgroup. The inconsistency between categorical and continuous results underscores the need for standardized protocols and further prospective investigations to clarify the nature of this relationship. CONCLUSION Elevated serum calcium may be associated with an increased risk of MetS, with a possibly more pronounced effect suggested in older adults. However, these preliminary observations require validation in well-designed prospective studies with agespecific analyses.