Threshold effect of serum 25-hydroxyvitamin D on Anemia risk in U.S. adults aged 45 years and older.

Background

While previous studies have reported conflicting linear or U-shaped associations between vitamin D and anemia, evidence regarding the specific dose-response relationship in middle-aged and older adults remains limited. This study aimed to identify the threshold effect of serum 25-hydroxyvitamin D [25(OH)D] on anemia risk in U.S. adults aged ≥ 45 years.

Methods

We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. A total of 9,306 participants were included. Anemia was defined according to WHO hemoglobin thresholds. Survey-weighted multivariate logistic regression and restricted cubic spline (RCS) models, together with segmented regression, were used to assess the association and identify inflection points.

Results

The prevalence of anemia was 13.3%. In the fully adjusted survey-weighted model, higher serum 25(OH)D levels were independently associated with a lower risk of anemia. RCS analysis revealed a significant non-linear association (P for non-linearity < 0.001), identifying a threshold of 64.57 nmol/L (bootstrap 95% CI: 64.45-64.69). Below this threshold, each 1 nmol/L increment in serum 25(OH)D was associated with approximately 2% lower odds of anemia (OR = 0.98, 95% CI: 0.97-0.99, P < 0.001); at or above this threshold, the association plateaued, with no significant further effect on anemia risk (OR = 1.00, 95% CI: 1.00-1.01, P = 0.64).

Conclusion

In U.S. adults aged ≥ 45 years, the protective association between serum 25(OH)D and anemia appears to exhibit a threshold around 64.57 nmol/L, below which lower levels were associated with progressively higher anemia risk. These findings are hypothesis-generating and merit confirmation in prospective and interventional studies.