Nutrition Support Blog: Dilemmas, Data and Vitamin D
December 6, 2012
I love the word “pleiotropic.” Pleiotropic does not refer to the time period after the Mesozoic era, nor is it a new type of fitness training. The term pleiotropy comes from the Greek pleion, meaning "more", and trepein, meaning "to turn, to convert" and is usually used to refer to a gene, hormone, or in nutritional sciences, a vitamin that has an influence on many diverse targets.
I first noticed the word pleiotropic in reference to the wide variety of biological responses of vitamin D. We now realize that the actions of vitamin D are not limited to calcium absorption and bone health, but also influence cellular growth, proliferation, apoptosis, anti-inflammatory processes and a number of critical immune functions. A large number of observational studies have revealed the association between vitamin D deficiency and inflammatory, malignant and infectious diseases, even overall mortality.
The latest abstracts for the annual meeting of the Society of Critical Care Medicine (SCCM) were recently released, and several abstracts reported a significant increase in ICU morbidity, mortality and/or length of stay in patients that were deficient, compared to patients sufficient in vitamin D.1 Two abstracts were notable in that vitamin D levels were checked prior to admission in patients for sepsis and coronary artery bypass.2,3 In both cases pre-existing vitamin D deficiency appeared to be a predictor of poor outcome in the ICU/CCU.
Of course, the obvious problem is that observational studies do not allow us to know if the vitamin D deficiency causes increased morbidity and mortality, or if it is simply that illness and inflammatory conditions decrease serum vitamin D (see my Blog from Feb 28th on observational studies http://www.healthsystem.virginia.edu/pub/dietitian/inpatient/dh/nutrition-support-team-blog/nutrition-support-blog-wet-sidewalks-cause-it-to-rain)
We know that even relatively modest stress (by surgical/trauma standards) of an elective arthroscopic knee surgery decreased serum levels of vitamin D by approximately 40% within 48 hours, and the decreased serum vitamin D remained low for some time after this single insult.3 The new SCCM abstracts are interesting because they look at pre-admission vitamin D levels, but there is still no way to control for pre-admission chronic illness, inflammatory conditions or overall nutrition status that may have influenced both vitamin D levels and ICU outcome.
The dilemma is that we are still not sure if we should be routinely supplementing vitamin D in the ICU. We currently have no way to know for sure if the decreased serum vitamin D in stress is an adaptive or protective response to stress, similar to serum iron (see my previous blog). There is a need for randomized studies to determine if outcomes are improved by providing supplemental vitamin D. The interventional trials of vitamin D supplementation in non-ICU patients suggest that very large, infrequent doses of vitamin D did not improve outcome, and may even have caused net harm.4,5 Before we start “repleting” low serum levels of vitamin D in critically ill patients, we need data to drive this--if we should supplement in the ICU, when to start, and how much to give.
Until we have better data about vitamin D supplementation in the ICU, I do recommend that you start practicing your use of the word pleiotropic. Perhaps about how improved nutrition status has pleiotropic benefits ….skin integrity, muscle mass, functional status, immune function and even mood. Can’t get much more pleiotropic than that!
1. Critical Care Medicine, Volume 40(12) Supplement 1 pgs. C1-C4,i-vi,1-5 December 2012.
2. Abstract 24 Moromizato T, et al. Pre-hospital vitamin D deficiency and sepsis in the critically ill. Critical Care Medicine, Volume 40(12) Supplement 5 December 2012.
3. Abstract 38 Moromizato T, et al. Pre-hospital serum vitamin D levels and mortality following coronary artery bypass grafting. Critical Care Medicine, Volume 40(12) Supplement 5 December 2012.
4. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O'Reilly DS, Blackwell S, Kinsella J, McMillan DC, Wallace AM. 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 May;93(5):1006-11.
5. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-22.
6. Murdoch DR, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC, Florkowski CM, Livesey JH, Camargo CA, Scragg R. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012; 308(13):1333-1339.
“The lyf so short, the craft so long to lerne.” --Geoffrey Chaucer