Serum cholecalciferol may be a better marker of vitamin D status than 25-hydroxyvitamin D
Medical Hypothesis, Feb 2018 DOI: https://doi.org/10.1016/j.mehy.2017.12.017
Rolf Jorde. G. Grimnes
Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway and Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
- Most (perhaps all?) cells can process vitamin D – no trip through liver and kidney is required
- Unprocessed vitamin D does not stay around long ( half life approx. 1 day)
- The effect of non-daily dosing is difficult to notice with standard blood tests
- The study states that there are 6 possible circulating forms of Vitamin D
- Only one of which is measured by the standard vitamin D test
- Free vitamin D
- DBP-bound vitamin D
- Free 25(OH)D
- DBP-bound 25(OH)D
- Free 1,25(OH)2D
- DBP-bound 1,25(OH)2D
Questions by the founder of VitaminDWiki
- Where does unprocessed Vitamin D hide?
- Why does weekly dosing sometimes give more benefits than daily dosing?
Are the additional benefits due to tissue processing?
Does tissue processing happen faster than liver-kidney processing?
- How much processing of oral vitamin D is done by tissues? (some studies believe up to 90%)
- How much processing of injected vitamin D is done by tissues
Especially in cases of poorly functioning liver or kidney
- How much of the processing by tissues end up back in the blood stream?
- Half life of 25(OH)D varies with the existing level and the source of the Vitamin D – Why?
- Does the half-life of free vitamin D also vary with level and source?
- Direct application of vitamin D topically provides much more skin benefits than oral
Might topical application of vitamin D inside the respiratory tract provide similar benefits?
See also VitaminDWiki
- Response to Vitamin D varies with Vitamin D Binding Protein gene – RCT May 2018
- Behind the scenes of vitamin D binding protein - more than vitamin D binding – Oct 2015
- Vitamin D dose size needed – VitD testing tells only a portion of the story – Jan 2016
PDF of uncorrected manuscript is available free at Sci-Hub 10.1016/j.mehy.2017.12.017
Vitamin D is produced in the skin upon sun-exposure or obtained through the diet. Vitamin D is hydroxylated to 25-hydroxyvitamin D (25(OH)D) in the liver and to the active form 1,25-dihydroxyvitamin D (1,25(OH)2D) in the kidneys. To exert its effect 1,25(OH)2D has to bind to the nuclear vitamin D receptor VDR. Lack of vitamin D leads to rickets in children and to osteomalacia in adults. 25(OH)D is used as a marker of a subject’s vitamin D status. Low serum 25(OH)D levels are associated with a number of diseases, risk factors for disease and increased mortality. However, intervention studies with vitamin D have generally been disappointing.
Many, if not most cells have the hydroxylases necessary for intra-cellular activation of vitamin D. It is likely that more vitamin D diffuses or are transported into the cells than 25(OH)D and 1,25(OH)2D, and accordingly, most of the 1,25(OH)2D that bind to the VDR are derived from intra-cellular hydroxylation of vitamin D.
Therefore, our hypothesis is that serum vitamin D is a better marker of a subject’s vitamin D status than 25(OH)D. Since the half-life in serum for vitamin D is approximately one day, giving vitamin D weekly or monthly will result in short-lived serum vitamin D peaks with periods of vitamin D deficiency in between. On the other hand, serum 25(OH)D, which has a half-life of weeks, will show high and stable serum levels throughout. Important vitamin D effects may have been missed in studies with intermittent dosing, and vitamin D in intervention trials should be given daily. Likewise, in epidemiological studies and clinical practice 25(OH)D has uniformly been used as marker. This may lead to gross misclassification of individuals that do not have a stable influx of vitamin D from sun-exposure or diet. In epidemiological studies serum vitamin D should be measured as well as 25(OH)D, and in clinical practice a 25(OH)D measurement should be interpreted in view of recent sun-exposure and diet history.