16 intrauterine programming of ncd 24 olson memori... - DSM

SIGHT AND LIFE | VOL. 25 (2) | 2011 VITAMIN D AND INFLAMMATION 3939> I speculate that the surgery also activated many componentsof the immune system.> Therefore, the fall in plasma 25(OH)D concentrations may beassociated with a rapid uptake of 25-OHD by immune cells,priming innate immune defences in the body.> I speculate that the 25(OH)D results obtained followingsurgery may also be obtained following any infection orinflammatory trauma.> Therefore, the many epidemiological studies showing low25(OH)D concentrations associated with chronic diseasesmay be a consequence of those diseases and not the cause.> A worrying feature of the surgical study was the persistentdepression in plasma 25(OH)D concentration by 20-25% for3 months following surgery.> We also do not know what implications these results havefor children’s vitamin D status, especially where they may beexposed to frequent infections.edge that sunlight could provide vitamin D was first shown byHarriett Chick after World War I, when she demonstrated thatrickets in children could be cured by irradiation with ultra-violetlight. Cholecalciferol is fat-soluble and stores of this compoundare found in adipose tissue. These stores of vitamin D are in equilibriumwith plasma 25(OH)D concentration, which is producedin the liver when cholecalciferol undergoes hydroxylation of carbon-25.(Figure 1) Plasma 25(OH)D has a half-life of approximatelythree weeks and this is longer than all other vitamin D metabolites.2 Further metabolism of 25(OH)D is mostly determinedby calcium metabolism. A fall in plasma calcium concentrationsstimulates the formation of another hydroxylase enzyme in thekidney, which converts 25(OH)D to 1,25(OH)₂D. 1,25(OH)₂D controlsa number of metabolic process that raise plasma calciumconcentrations, either by increasing calcium absorption and/orreleasing calcium from bone. However, the 1α-hydroxylase enzymeand vitamin D receptor is also found in many immune andother cells throughout the body 4 so 1,25(OH)₂D has other, nonclassical,functions. These important functions necessitate amuch tighter control over plasma 1,25(OH)₂D than 25(OH)D concentrationsand the half-life is only four hours. 2 Concentrationsin plasma of 25(OH)D and 1,25(OH)₂D differ almost 1000-fold(nmol/L and pmol/L).Interpretation of plasma25-hydroxy-cholecalciferol concentrationsIn my previous commentary on vitamin D, 5 a major concern wasthe reproducibility of plasma 25(OH)D measurements, interassayvariation and appropriate cut-offs to assess those at riskof vitamin D deficiency. The methodological issues were understudy at that time by the UK Food Standards Agency; the subsequentreport indicates the most reliable methods. The reportalso points out the newly available Reference Material from theNational Institutes of Standards and Technology, which shouldimprove inter-laboratory comparisons. 6 Newer studies willtherefore be better able to assure accuracy; however, the problemof interpretation may, if anything, have worsened if plasmaconcentrations of 25(OH)D are influenced by inflammation. 1 Appropriatecut-offs to assess the risk of vitamin D deficiency arestill not resolved. Deficiency is generally regarded as 50, >80 7 oreven >150 8 nmol/L.In terms of functional vitamin D concentration, some workersconsider it is best to assess the free (ie unbound) concentration inplasma, 9 although this is probably not necessary in most clinicalsettings. 2 Most plasma 25(OH)D circulates bound to vitamin D-binding protein (VDBP; 80 – 90%) and most of the remainder isbound to albumin (10 –20%). Very little 25(OH)D remains free,ie biologically active in plasma (0.02–0.05%). 10,11 VDBP alsobinds to 1,25(OH)₂D but the relative affinity is 10-fold less thanfor 25(OH)D, so the proportion of free plasma 1,25(OH)₂D concentrationsis 10-fold higher compared with 25(OH)D (0.2–0.6%).The concentration of VDBP in plasma is 20-fold higher than thetotal amount of vitamin D metabolites and the physiological consequenceof the large molar excess of circulating VDBP is unclear.Only 5% of the total VDBP capacity is usually occupied by vitaminD compounds; the physiological consequence is thereforethat all circulating vitamin D compounds are protein bound andwill have limited access to target cells. Thus, concentrations offree rather than total forms of 25(OH)D and 1,25(OH)₂D may providea better assessment of functional vitamin D status. 12“Workers suggest that the molarratio of 25(OH)D:VDBP or free 25(OH)Dmay be more useful indices of biologicalactivity in the plasma than thetotal 25(OH)D concentration alone”The influence of variations in the concentration of VDBPon the availability of the free vitamin D metabolites was clearlyshown in a comparative study of patients with idiopathic