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
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 .
Levels of DBP are affected by
- genetic factors,
- certain drugs (tenofovir, aspirin, oral contraceptive pill),
- hormonal factors,
- obesity and insulin resistance,
- end stage liver disease and
- nephrotic syndrome .
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 .
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. 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 .
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 . 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 .
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.  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.
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
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 and surgery category listing has
244 items along with related searches
- Severe sepsis may be prevented by 400,000 IU of vitamin D – RCT 2023
- Critically ill children – randomized clinical trial to give single doses of up to 400,000 IU of vitamin D – 2019
- Vitamin D loading doses reduce ICU mortality by 30 percent – meta-analysis April 2017
- Children in Intensive Care need Vitamin D loading dose of 10000 IU per kg (nearing a consensus) - Oct 2016
- All ICU patients with good vitamin D level survived, none who died had a good level – April 2018
- ICU cost reduced by at least 27,000 dollars if get high dose vitamin D in first week - April 2017
- Off topic: Improving your health BEFORE surgery (prehabilitation) helps your recovery - 2018
- Prehabilitation would include getting optimal levels of vitamin D before surgery
Pages in BOTH of the categories: Trauma/Surgery and Mortality
- Ventilator-associated pneumonia death rate cut in half by Vitamin D injection (300,000 IU) – RCT July 2017
- Low Vitamin D when entering ICU is deadly (acute kidney injury in this case) – Aug 2017
- Increased Hospital, Sepsis deaths if low vitamin D – March 2014
- Vitamin D and Glutamine reduced Trauma Center deaths by half – March 2017
- Half of Swiss emergency patients had low vitamin D: length of stay, mortality, etc. – May 2016
- Chance of dying in hospital cut in half by just 10 ng higher level of Vitamin D – April 2016
- ICU patients 30 percent less likely to die if have enough vitamin D – meta-analysis Nov 2016
- Hospital ICU added high dose vitamin D - malpractice lawsuit costs dropped from 26 million dollars to ZERO - Oct 2016
- Vitamin D and exercise after hip fracture surgery – far fewer deaths – July 2016
- Radio frequency ablation survival doubled with even modest levels of vitamin D – Feb 2016
- ICU death rate reduced 3X when a single dose of vitamin D changed the PTH – Nov 2015
- Risk of death within 90 days of ICU decreased by 16 percent for 1 nanogram extra vitamin D – June 2014
- ICU survival increased with vitamin D single loading dose - JAMA Sept 2014
- Vitamin D intervention increased by 20 percent the survival of critically ill patients- RCT June 2014
- Hospital or ICU death about twice as likely if low vitamin D – March 2014
- 3X more likely to die within 3 months of being in ICU for 2 days if less than 20 ng vitamin D – Sept 2013
- Chance of dying within 1 month of entering hospital is 45 percent higher if low vitamin D – July 2013
- More sepsis deaths when active vitamin D (Calcitrol) was low – May 2013
- Off topic: Use of ICU in month before death has increased to almost 30 pcnt – Feb 2013
- Almost 6X more likely to die after coronary bypass if vitamin D deficient – Dec 2012
- Critically ill 70 percent more likely to die if vitamin D less than 15ng – Jan 2011
Pages in BOTH of the categories: Trauma/Surgery and Omega-3
- Omega-3 supplements taken before and after surgery actually helped – RCT Nov 2018
- ICU length of stay reduced when supplement with Omega-3 – meta-analysis July 2018
- 3 days of Omega-3 before cardiac surgery reduced risk of post-op bleeding by half – RCT March 2018
- Omega-3 benefits in surgery and ICU including via IV - March 2016
- Omega-3 reduced time in hospital and atrial fibrillation after cardiac surgery – meta-analysis May 2016
- 2.7 fewer days in hospital after surgery if had taken Omega-3 (19 RCT) – meta-analysis – June 2017
- Sepsis: 4 fewer days in ICU if add Omega-3 – meta-analysis of 12 RCT – June 2017
- Cognitive decline after traumatic brain injury reduced by Omega-3 (mice) – Nov 2016
- Football Brain injuries prevented by Omega-3 – RCT Jan 2016
- Omega-3 should be cost-effective to reduce days in ICU – simulation June 2015