Hypovitaminosis D and disease: consequence rather than cause?

In their editorial calling for vitamin D to be put into perspective Harvey and Cooper do not consider the possibility, supportive to their view, that hypovitaminosis D is the consequence rather than the cause of disease.1 We recently completed a study showing unequivocally that serum 25-hydroxyvitamin D is a negative acute phase reactant.

We measured serum C reactive protein and 25-hydroxyvitamin D concentrations before and two days after elective knee or hip surgery in 30 patients. After surgery the mean serum concentration of C reactive protein increased (5.0 (SD 5.5) v 116.0 (81.2) mg/L; P <0.0001), whereas serum 25-hydroxyvitamin D decreased (56.2 (30.3) v 46.0 (27.6) nmol/L; P <0.0006).

These results are consistent with those of two other studies reporting a rapid and noticeable fall in serum 25-hydroxyvitamin D concentration during a systemic inflammatory response.2 3 They seem, however, to contradict the results of two other studies reporting no change in serum 25-hydroxyvitamin D concentration for up to 90 days after an inflammatory insult.4 5 The initial serum samples in these last two studies were, however, all collected after the inflammatory insult,4 5 when serum 25-hydroxyvitamin D is already likely to be at a nadir.2 3 A unifying explanation for the apparently conflicting results of these four studies is that serum 25-hydroxyvitamin D concentration decreases rapidly and dramatically after an inflammatory insult and persists for at least three months.

That serum 25-hydroxyvitamin D is a negative acute phase reactant has implications for acute and chronic diseases. Firstly, serum 25-hydroxyvitamin D is an unreliable biomarker of vitamin D status after an acute inflammatory insult. Secondly, hypovitaminosis D may be the consequence rather than the widely purported cause of a myriad of chronic diseases.1