The ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 is predictive of 25-hydroxyvitamin D3 response to vitamin D3 supplementation

24,25-Dihydroxyvitamin D (24,25VD) is a major catabolite of 25-hydroxyvitamin D (25VD) metabolism, and may be physiologically active. Our objectives were to: (1) characterize the response of serum 24,25VD3 to vitamin D3 (VD3) supplementation; (2) test the hypothesis that a higher 24,25VD3 to 25VD3 ratio (24,25:25VD3) predicts 25VD3 response.Serum samples (n = 160) from wk 2 and wk 6 of a placebo-controlled, randomized clinical trial of VD3 (28,000 IU/wk) were analyzed for serum 24,25VD3 and 25VD3 by mass spectrometry.Serum 24,25VD3 was highly correlated with 25VD3 in placebo- and VD3-treated subjects at each time point (p < 0.0001). At wk 2, the 24,25:25VD3 ratio was lower with VD3 than with placebo (p = 0.035). From wk 2 to wk 6, the 24,25:25VD3 ratio increased with the VD3 supplement (p < 0.001) but not with placebo, such that at wk 6 this ratio did not significantly differ between groups. After correcting for potential confounders, we found that 24,25:25VD3 at wk 2 was inversely correlated to the 25VD3 increment by wk 6 in the supplemented group (r = −0.32, p = 0.02) but not the controls.There is a strong correlation between 24,25VD3 and 25VD3 that is only modestly affected by VD3 supplementation. This indicates that the catabolism of 25VD3 to 24,25VD3 rises with increasing 25VD3. Furthermore, the initial ratio of serum 24,25VD3 to 25VD3 predicted the increase in 25VD3. The 24,25:25VD3 ratio may therefore have clinical utility as a marker for VD3 catabolism and a predictor of serum 25VD3 response to VD3 supplementation.

► Serum 24,25-dihydroxyvitamin D3 (24,25VD3) response to vitamin D3 (VD3) supplement.
► Serum 24,25VD3 correlated strongly with 25-hydroxyvitamin D3 (25VD3).
► Initial ratio of serum 24,25VD3 to 25VD3 predicted the increase in 25VD3.
► 24,25:25VD3 ratio reflects 25VD3 catabolism and response to VD3 supplement.