Vitamin D deficiency is highly prevalent among critically ill patients, with reported rates ranging from 81.5% to 99%. In addition, multiple studies have found associations between low vitamin D levels and increased risk of adverse events, including prolonged length of stay, infection, and even mortality. We covered one of these studies in a blog.
These associations are suggested to be due to vitamin D’s ability to increase the functioning of various components of the immune system, as shown in multiple in vitro studies. One way in which vitamin D has been shown to stimulate the immune system is through an increase in the production of cathelecidins, which are a family of antimicrobial proteins.
In animals, low cathelecidin levels increase the susceptibility to bacterial infection. In humans, there is only one known cathelecidin, human cathelecidin antimicrobial protein 18 (hCAP18).
There have been very few studies that have measured cathelecidin and vitamin D levels in the critically ill at the same time, and these have shown conflicting results as to how vitamin D status is related to hCAP18. No study has looked at how both cathelecidin and vitamin D levels are related to adverse outcomes among critically ill patients.
Therefore, researchers designed a study to prospectively evaluate the relationship between hCAP18 and vitamin D status in critically ill patients as well as the relationship between these two markers and adverse outcomes in this population.
To do this, they looked at data from 121 critically ill patients admitted to ICUs at Brigham and Women’s Hospital between 2008 and 2012. The patients’ vitamin D and hCAP18 levels were measured the day after being admitted to the ICU.
The researchers then looked to see if these two markers were related and if they were also associated with 90-day mortality and sepsis.
After adjusting for multiple factors, including age and disease severity, their analysis revealed:
- Vitamin D insufficiency, defined as levels below 30 ng/ml, was prevalent in 95% of patients.
- HCAP18 levels were positively correlated with vitamin D levels (p = 0.001).
- Vitamin D levels were significantly lower in patients who died compared to patients who survived (p = 0.03).
- Patients with the lowest hCAP18 levels had 4.49 increased odds of 90-day mortality and sepsis compared to patients with the highest hCAP18 levels.
These results provide a possible explanation as to why critically ill patients with low vitamin D levels suffer more adverse events.
The researchers concluded,
“In this prospective cohort study among critically ill patients, we found that lower total 25D levels were associated with lower hCAP18 levels, which were in turn associated with a greater risk of 90-day mortality. These findings provide a potential mechanistic basis for the commonly observed association between low 25D levels and poor outcomes in critically ill patients.”
They acknowledged the limitations of the study, which included its single-center, observational design. They also cautioned that the association between hCAP18 and sepsis needed to be confirmed in further research, as cathelecidin levels were not measured before the onset of acute illness and therefore the possibility of reverse causation cannot be excluded.
Randomized controlled trials are now needed to determine if improving vitamin D status improves outcomes among critically ill patients.