Optimizing Vitamin D Status Improves Outcomes in
Critical Ill and Injured Patients
Omar K Danner1*, Erin Danielle Danner2 and Leslie Ray Matthews1
1
Department of Surgery, Morehouse School of Medicine, USA
2
College of Arts and Sciences, University of Georgia, USA
*Corresponding author: Omar K Danner, Department of Surgery, Morehouse School of Medicine, USA.
To Cite This Article: Omar K Danner, Optimizing Vitamin D Status Improves Outcomes in Critical Ill and Injured Patients. 2020 - 8(2). AJBSR.
MS.ID.001250. DOI: 10.34297/AJBSR.2020.08.001250.
Received: March 03, 2020; Published: March 16, 2020
Copy Right@ Omar K Danner
This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001250.
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Review Article
Abbreviations: ICU: Intensive Care Unit; BMD: Maximal Bone Density; VDR: Vitamin D Receptors; ARDS: Acute Respiratory Distress Syndrome
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Introduction
In 2008, Giovanucci et al. [1] showed that men with low vitamin
D levels suffered 2.42 times more myocardial infarctions than
those with normal vitamin D status [1]. Alternatively, a sufficient
amount of serum 25-hydroxyvitamin D3, [25(OH)D], appears to
improve the risk of almost every disease of aging. Dobnig et al.
[2] similarly demonstrated people with an inadequate vitamin D
status have twice the likelihood of death over seven years [2,3].
Vitamin D sufficiency, define as serum 25(OH)D levels of 30ng/
mL (75nmol/L) and above, improves various health outcomes,
including bone mineral density, fractures, and colorectal cancer,
based on analysis of observational studies [4]. Vitamin D levels of
21-29ng/mL delineates insufficiency and a concentration of 20ng/
mL or less defines vitamin D deficiency [4]. When vitamin D levels
are inadequate, and particularly fall below17.8ng/mL, mortality risk
increases by as much as 26% from all-cause mortality in the general
population [3,5]. Current data suggests hypovitaminosis D plays a
significant role in the development of numerous common chronic
diseases and inflammatory conditions, including coronary artery
disease, cerebrovascular disease, diabetes mellitus, autoimmune
disorders, such as systemic lupus erythematosus, scleroderma and
multiple sclerosis and 17 different forms of cancer [6-12]. Vitamin
D deficiency is arguably one of the most prevalent but underrated
nutritional deficiency worldwide [6,7]. It continues to be associated
with increased overall mortality risk in several studies [8-12].
Several observational studies on hypovitaminosis D over the past
decade support the persistent existence of a high prevalence of
vitamin D insufficiency and deficiency in as many as 50 to 90%
of hospitalized patients, with a particular predilection in the setting
of critical illness [6-9, 12-14]. Although full elucidation of the role
vitamin D status plays in patients requiring admission to the
intensive care unit (ICU) is an area undergoing active investigation,
epidemiological data supports the findings that vitamin D
sufficiency may decrease the risk of systemic inflammatory from
all causes as well as sepsis in general [12,15]. Investigations by
our group examining the prevalence and effects of insufficient or
deficient serum vitamin D levels on our critically-ill and/or severelyinjured trauma patients revealed increased risk of unfavorable
outcomes when serum vitamin D levels fell below a level of 30ng/
mL (75nmol/mL] in SICU trauma patients who survived their initial
injury and resuscitative efforts [6,16]. According to some of the
world’s leading vitamin D experts, optimal serum levels of 25[OH]D
range between 30 and 50ng/mL. Those individuals with 25 (OH) D3
(calcidiol) levels below 30 ng/mL are considered to have vitamin D
insufficiency as noted above [5,6, 8,15,16] looked at the risk of 30-
day and in-hospital mortality after initiation of critical care services
in patients with severe vitamin D deficiency. There was a 1.9-fold
higher risk of death than in those patients with vitamin D levels
of ≤30ng/mL [7]. Inadequate levels of 25[OH]D in the insufficient
cohort remained a significant predictor of increased likelihood of
mortality, even after multivariate adjustment [7].
Under normal circumstances, vitamin D is a hormone produced
principally by the skin in response to natural sunlight. However,
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when the sun hits the northern hemisphere below 45 degrees
in the spring and summer, it cannot produce UVB rays of the
proper wavelengths from 290 to 315 nm, which is required for
the production of vitamin D in the skin between 10:00 a.m. and
approximately 3:00 p.m. [6,17]. At latitudes of 32 degrees or above,
vitamin D levels are the lowest, particularly during the winter
months and early spring, due to the lack of sunlight at the suitable
wavelength [6,17]. During the fall and winter months, vitamin
D stores decrease by approximately 20 to 30%. Furthermore,
vitamin D deficiency is very common in Western society as it is
nearly impossible to get adequate amounts of vitamin D from diet
alone without purposeful exogenous supplementation [6,7,17].
Therefore, reversal of hypovitaminosis D may not be quick or easy
without supplementation.
There is a suggestion by researchers that vitamin D deficiency
is present in at least 50% to 80% of critically ill patients admitted
to surgical and medical ICUs. Nevertheless, based on the definition
of normal and subtherapeutic vitamin D status, vitamin D
insufficiency in western society may be grossly underestimated
[6-14,16]. The true prevalence and extent of vitamin D deficiency
might be much worse. This understanding is particularly pertinent
considering we have entered the season of increased risk for acute
respiratory illness, where a robust immune system is of paramount
importance for fighting off upper respiratory tract infections. This
underappreciation of vitamin D deficiency may be associated with
increased relative risk of adverse outcomes in fragile and critically
ill patient populations [6-14,16]. In our prior investigations, we
evaluated a cutoff ≥40 ng/mL as a surrogate marker to define
a normal vitamin D level, and levels of <40 ng/mL to represent
a relative insufficiency in our ICU patients [6]. We found higher
25[OH]D levels improved outcomes in surgical ICU patients
[6,8,16]. There is other evidence that supports the body functions
better at this higher vitamin D level. Other authors have suggested
that maximal bone density (BMD) can only be achieved when the
25-hydroxyvitamin D level reaches 40ng/mL or greater [17]. As
fractures are very common in critically injured elderly trauma
patients, achieving adequate vitamin D levels becomes increasingly
important in this fragile, at-risk patient population. Based on prior
observations demonstrating the need for calcidiol levels ≥ 40ng/
mL to adequately suppress serum parathyroid hormone levels
and achieve maximal bone density in the hips and lumbar spine
patients, it is plausible to suggest that higher vitamin D levels may
portend a protective effect in the other severely injured and/or
critically ill individuals [5,6,15,18-20].
To achieve a vitamin D of 30 to 50ng/mL and maintain it long
term, investigators have found that it takes over 4,000 to 5,000
units of 25-(0H) vitamin D supplementation per day [18,20]. This
amounts to over 5 to 10 times the current recommended daily
intake [20]. The importance of this recommendation is that optimal
local concentrations of serum 25-(OH) D ≥30 ng/mL [6,24,25] are
required for optimal paracrine conversion to 1,25-(OH)2-vitamin
D (calcitriol) by macrophages and other immune cells. The serum
concentration needs to be ≥ 30 (>75 nmol/L) [6,7,21-24] to activate
the vitamin D receptors (VDR) that regulates the immune response.
Activation of the VDR by bioactive vitamin D up-regulates the
anti-inflammatory cytokines IL-8 and IL-10, which promotes the
expression of a T-suppressor cell lineage and helps to turn off the
adaptive immune response once the job is complete [23-25]. Thus,
it is understandable that patients with moderate to severe vitamin
D deficiency syndromes are less capable of mounting a successful
immune response to severe insults, injury, and acute viral and
bacterial infections. Furthermore, they have higher risk of ICUrelated septic complications, acute respiratory distress syndrome
(ARDS) and death.
Conclusion
Published data suggests critically-ill patients with inadequate
serum vitamin D stores may enter into a vicious inflammatory cycle
due to low levels of the bioactive form of vitamin D, calcitriol, which
leads to increased production of pro-inflammatory cytokines,
which may not be easily reversed with vitamin D supplementation
[6,8,24]. This review may provide a plausible link between the
excess mortality observed in people during an acute outbreak
of novel acute respiratory syndromes in the general population
and especially patients in the ICU setting who are at a higher risk
of frankly deficient vitamin D levels. Therefore, we recommend
checking serum 25-OH vitamin D levels on all hospitalized
ICU patients, and particularly those with acute respiratory or
unexplained infectious/inflammatory illness. Although it is difficult
to prove clinical effectiveness in the setting of acute infectious
illness, supplementation of vitamin D stores to augment the
immune system using cholecalciferol (Vitamin D3) at doses of 4,000
to 5,000 units daily may not be unreasonable, especially during this
uncharacteristically aggressive flu season, and more so in light of
the worldwide coronavirus [COVID-19] epidemic.
References
1. Giovannucci E, Liu Y, Hollis BW, Rimm EB (2008) 25-hydroxyvitamin
D and risk of myocardial infarction in men: a prospective study. Arch
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2. Dobnig H, Pilz S, Scharnagi H, Renner W, Seelhorst U, et al. (2008)
Independent association of low serum 25-hydroxyvitamin d and
1,25-dihydroxyvitamin D levels with all-cause and cardiovascular
mortality, Arch Intern Med 168(12): 1340-1349.
3. Melamed ML, Michos ED, Post W, Astor B (2008) 25-hydroxyl vitamin
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