TABLE 15-1 Relevant Data Identified for Vitamin D


Type of Injury/Insult

Type of Study and Subjects



Tier 1: Clinical trials

None found





Tier 2: Observational studies

Buell et al., 2010


Prospective cohort study (Nutrition and Memory in Elders)


25(OH)D insufficiency (10–20 ng/mL) was associated with twice the risk of stroke (ORb=2.29, 95% CIc: 1.09–4.83, p=0.03). But the association with stroke was not significant after stratifying for presence or absence of dementia.

na=318 patients ≥ 60 years old

Compared to patients taking sufficient levels (> 20 ng/mL) of 25(OH)D, deficient (< 10 ng/mL) patients had higher geometric mean white matter hypersensitivity (WMH) volume (p=0.004), higher WMH grade (p=0.02), and higher prevalence of large vessel infarcts (p < 0.01).

Tier 3: Animal studies

None found





a n: sample size.

b OR: relative risk.

c CI: confidence interval.

Although the roles of vitamin D in the CNS are not well understood, it appears that its function is largely mediated by VDR. This member of the steroid-thyroid nuclear receptor family is widely expressed in both the human and rodent cortex, spinal cord, amygdala, hypothalamus, cerebellum, mesopontine area, and diencephalon. VDR is particularly high in the hippocampus, a region of the brain associated not only with learning and memory, but also with emotion (Eyles et al., 2005). When the hormonal form of vitamin D associates with VDR in the nucleus, this complex can combine with the retinoic acid receptor RXR to produce heterodimers. Together, these two nutrients (vitamin D in the form of 1,25(OH)2-D3 and vitamin A in the form of 9-cis-retinoic acid) and their respective nuclear receptors (VDR and RXR) bind to specific sequences of DNA known as vitamin D response elements (VDREs). Binding of this complex to VDREs in the 5′-flanking region of vitamin D–responsive genes results in the regulation of gene transcription in the CNS, where it is now believed to participate in cell proliferation and neuronal differentiation and neuronal function (Levenson and Figueirôa, 2008).

Table 15-1 includes limited supporting evidence (1990 and later) from human studies on vitamin D supplementation for CNS injuries. Any adverse effects in humans are also listed.


The current Recommended Dietary Allowance (RDA) for vitamin D is 600 International Units (IU) per day for both male and female adults up to the age of 70 (IOM, 2010). At age 70, the RDA increases to 800 IU. There are a number of considerations to take into account when applying these recommendations to military populations and others at risk for

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