Vitamin D and executive functioning: Are higher levels better?

Objectives: Insufficiency of 25-hydroxyvitamin D has been associated with cognitive impairment, particularly worse executive functioning. However, it remains unclear whether supratherapeutic levels (>= 100 nmol L-1) are associated with even better performance than sufficient levels (defined as >= 50 nmol L-1 or even >= 75 nmol L-1). The current investigation sought to examine this question. Method: Healthy adults (n=142) were tested on four measures of executive functioning, including verbal fluency, digit span backward, CANTAB (R) Spatial Working Memory, and One Touch Stockings of Cambridge. A measure of attention (digit span forward) and memory (CANTAB (R) Verbal Recognition) were also assessed. Based on blood 25-hydroxyvitamin D [25(OH)D] levels, participants were divided into four groups: insufficient (<50 nmol L-1), low sufficient (50 to <75 nmol L-1), high sufficient (75 to <100 nmol L-1), and supratherapeutic (>= 100 nmol L-1). Relationships between vitamin D status and cognition were assessed by analyses of covariance and hierarchical multiple regression, adjusted for age, education, sex, body mass index, mood, and physical activity level. Multivariate regression spline analyses were utilized to investigate nonlinearity. Results: Performance on verbal fluency, but not other measures, differed by vitamin D status, analysis of covariance (ANCOVA), F(3, 127) =2.70, p =.048; d=0.50. Specifically, participants with supratherapeutic levels provided a greater number of words (M=16.1, SE=1.0) than those with insufficient (M=12.0, SE=1.0; p =.007, d=0.78), low (M=13.4, SE=0.7; p =.026, d=0.51), and high sufficient levels (M=13.9, SE=0.9; p =.080, d=0.42). Similarly, vitamin D status was a significant independent predictor of verbal fluency (p =.025, d=0.40). Spline analyses revealed that there is a positive, near-linear association between verbal fluency and 25(OH)D levels up to and exceeding 100 nmol L-1. Discussion: Supratherapeutic levels of vitamin D were associated with significantly better performance on verbal fluency. Importantly, commonly used cutoff levels and sufficiency categories have been based on bone health and optimal levels for cognition are unknown. These findings suggest that levels exceeding 100 nmol L-1 may be optimal for at least some aspects of executive functioning.