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

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.

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.

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).

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.