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Vitamin D and critical illness – many questions and unknowns (DBP etc)– Dec 2018

Vitamin D Deficiency and Supplementation in Critical Illness -The Known Knowns and Known Unknowns

Medscape: Crit Care. 2018;22(276)
Priya Nair; Balasubramaniam Venkatesh; Jacqueline R Center

The burgeoning literature on vitamin D deficiency and supplementation over the past decade or so has generated a greater understanding of some areas but also an appreciation of the many areas of equipoise. This is particularly relevant in the field of critical care with the heterogeneous patient populations, the severity and duration of illness and the frequency of comorbid conditions.

This review aims to summarise the current knowledge base of vitamin D deficiency within the context of critical illness—"the known knowns"—and also highlight the areas of recognised uncertainty—"the known unknowns". It acknowledges the fact that there may well be other knowledge gaps of clinical relevance of which we are currently unaware—"the unknown unknowns".
 Download the PDF from VitaminDWiki

Should we measure free vitamin D levels—the role of DBP (clipped form PDF)

As alluded to above, the majority of circulating 25 hydroxy-D and 1,25(OH)2D is tightly bound to DBP and albumin, with less than 1% circulating in an unbound form. Binding of DBP impairs delivery of 25 hydroxy-D to vitamin D-activating 1-alpha-hydroxylase in target cells. It is therefore the unbound or free form of these metabolites which is active in most cells. As a result, factors affecting DBP alter the interpretation of 25 hydroxy-D levels [54].
Levels of DBP are affected by

  • genetic factors,
  • certain drugs (tenofovir, aspirin, oral contraceptive pill),
  • smoking,
  • hormonal factors,
  • obesity and insulin resistance,
  • end stage liver disease and
  • nephrotic syndrome [54].

It might, therefore, be important clinically to be able to measure the free and bound fractions by using a DBP assay. However, measurement of DBP is not standardized and, as a result, it is difficult to compare the different assays and studies.
Alternatively, free 25 hydroxy-D levels can be directly measured by centrifugal ultrafiltration and a newer commercially available enzyme-linked immunosorbent assay. Centrifugal ultrafiltration is the gold standard but not commonly utilized as it is technically difficult, expensive and requires a very sensitive assay methodology [55].
Gene sequencing has uncovered many variations in the DBP gene. Over 120 variants of DBP have been found and, of these, three main phenotypic variants have been described. The variants have different characteristics that can alter 25 hydroxy-D levels. Powe et al.[56] demonstrated in a randomized, placebo-controlled trial that variations in race altered DBP levels and no change in DBP occurred with replacement of vitamin D. In addition, black subjects were found to have lower DBP levels than non-black subjects, resulting in similar concentrations of estimated bioavailable 25 hydroxy-D.
In critically ill patients, DBP falls during the systemic inflammatory response, which theoretically is related to a fall in 25 hydroxy-D. This was discovered in a study performed on patients undergoing orthopaedic surgery who were found to have elevated acute phase reactants [57].
A study performed on ICU patients showed that bactericidal activity was associated with 25 hydroxy-D concentrations, and DBP was decreased in patients with sepsis in comparison to subjects without sepsis [58]. A paediatric intensive care study found that levels of DBP and total 25 hydroxy-D were lower than those reported in healthy children. The lower DBP levels increased bioavailability of 25 hydroxy-D but the calculated bioavail- able 25 hydroxy-D levels were also inversely associated with illness severity [59].
Therefore, total 25 hydroxy-D might not be a reliable indicator in the critical care situation. Overall, assessing vitamin D status and its activity in ICU patients, the implication of free or bound vitamin all contribute to the complexity of designing trials in this area.
On the other hand, Martucci et al. [60] undertook a post-hoc analysis of the VITdAL-ICU trial patients where DBP was measured in stored samples. They found that high dose cholecalciferol increased both total and bioavailable vitamin D metabolites in a similar way. Calculating free levels, however, did not enhance the ability to predict mortality when compared to 25 hydroxy-D alone, suggesting that there may not be an additional benefit to analyzing free vitamin D levels.

Summary of their questions by VitaminDWiki

What is the level to be achieved?
What dose size is needed to achieve the goal
What is to be tested
How to supplement? Oral, injection
When to measure the outcome? – hours, days, weeks, months

What they appear to have failed to ask:

Should more than a single dose be given? - before AND after surgery
When should other forms be used? - for example gut-friendly if digestive system is operating poorly
When should co-factors be used? - Omega-3, Magnesium, etc


We probably will have to wait a decade for the medical establishment to agree upon a protocol
While waiting many people die, are in the hospital longer, and/or have expensive hospital/rehab bills
I keep 400,000 IU of vitamin D in my car to use in case of an emergency ($2)
I would take 300,000 IU before getting to the hospital, then 100,000 IU the next day
Currently the fastest known ways to get vitamin D into the body are: mouthwash and under the tongue
Those ways take about 12 hours. I am exploring the possibility that inhaling vitamin D might be ~10X faster

Trauma/Surgery and VDBP

Omega-3 often helps as well

Pages in BOTH of the categories: Trauma/Surgery and Omega-3

Created by admin. Last Modification: Wednesday June 19, 2019 16:26:46 GMT-0000 by admin. (Version 12)

Attached files

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11121 Critical care unknowns.pdf admin 31 Dec, 2018 496.20 Kb 605