Hypovitaminosis D and disease: consequence rather than cause?

Abstract

chemical pathologist and honorary professor of laboratory medicine, Jenna L Waldron senior clinical scientist, Helen L Ashby specialist registrar in chemical pathology and metabolic medicine, Michael P Cornes senior clinical scientist, Julia Bechervaise academic FY2, Cyrus Razavi academic FY2, Osmond L Thomas consultant orthopaedic surgeon, Sanjiv Chugh consultant orthopaedic surgeon, Shreeram Deshpande consultant orthopaedic surgeon, Clare Ford consultant clinical scientist New Cross Hospital, Wolverhampton WV10 0QP, UKIn 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 et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr 2011;93:1006-11. 3 Louw JA, Werbeck A, Louw ME, Kotze TJ, Cooper R, Labadarios D. Blood vitamin concentrations during the acute-phase response. Crit Care Med 1992;20:934-41. 4 Newens K, Filteau S, Tomkins A. Plasma 25-hydroxyvitamin D does not vary over the course of a malarial infection. Trans Roy Soc Trop Med Hyg 2006;100:41-4. 5 Barth JH, Field HP, Mather AN, Plein S. Serum 25 hydroxy-vitamin D does not exhibit an acute phase reaction after acute myocardial infarction. Ann Clin Biochem 2012;49:399-401.

Author response—vitamin D deficiency and systemic inflammation in bronchiectasis

“…4 Importantly, the study to which Dr Shee refers showed an effect of systemic inflammation on 25-hydroxyvitamin D (25-OHD) concentrations after major surgery, resulting in a mean CRP rise of 116 mg/l and a mean fall in 25-OHD of 10 nmol/l. 5 In our study and in the Wilson et al study, stable patients with bronchiectasis had a mean CRP level of 6 mg/l. It is unclear whether such low-level systemic inflammation can also affect circulating 25-OHD levels, but it is unlikely to be solely responsible for the degree of vitamin D deficiency observed in our population.…”

Vitamin D deficiency and risk of acute lung injury in severe sepsis and severe trauma: a case-control study

“…Higher vitamin D levels may, in certain situations, paradoxically increase the pathogen burden [39] leading to a worsening of pro-inflammatory stress in the lung and thence to ALI/ARDS. Another, more likely, interpretation for our primary findings is that low levels of vitamin D are not associated with development of ALI/ARDS and are potentially epiphenomena of severity and/or chronicity of illness [40]. In the current study, when cases and controls were rigorously matched for severity of illness using APACHE II scores and other clinical characteristics, no association between ALI/ARDS and 25-OHD levels was apparent.…”

Cord blood vitamin D and the risk of acute lower respiratory infection in Indigenous infants in the Northern Territory

“…As the climate and time spent outdoors are likely to be similar for urban and remote participants, risk factors other than exposure to sunlight require further investigation. Interestingly, vitamin D has also been found to be a negative acute phase reactant that is depleted after an inflammatory insult 25 . Lower vitamin D levels seen among remote participants may therefore be the result, rather than a cause, of their high burden of infection.…”