traumatic brain injury (TBI). First, the current RDAs for vitamin D were developed under conditions of minimal sun exposure (IOM, 2010), and therefore do not factor in the vitamin D synthesized in the skin through exposure to sunlight. More importantly, the Institute of Medicine (IOM) set the current RDA for vitamin D at a level found to be sufficient to maintain bone health and normal calcium metabolism in healthy people, the only outcome found to be associated with vitamin D status. It is not known whether the dietary vitamin D requirement for optimal brain function under normal or injured conditions should be different.

Median estimates of vitamin D intake from foods are below the Estimated Average Requirements (EARs) of 400 IU recently established by the IOM. However, vitamin D also is synthesized in the skin, and therefore vitamin D status is not accurately reflected exclusively by dietary intake. Using National Health and Nutrition Examination Survey (NHANES) data from 2000 to 2006, levels of 25-hydroxyvitamin D in serum, a depiction of total vitamin D exposure, were above 50 nmol/mL, the level identified as meeting the needs of most of the population. The IOM concluded that the population of North America, with the possible exception of the aging population and those with dark skin, is meeting its needs for vitamin D.

NHANES (2005–2006) data show that 37 percent of the U.S. population reported using vitamin D supplements. This is likely to be predominantly in the form of multivitamin supplements or as an adjunct to calcium supplementation. The current Tolerable Upper Intake Level (UL) for adults is 4,000 IU. Excess dietary intake of vitamin D has been shown to cause vitamin D intoxication, which leads to hypercalcemia and, eventually, soft tissue calcification and resultant renal and cardiovascular damage.

EVIDENCE INDICATING EFFECT ON RESILIENCE

Human Studies

There have been no clinical trials to address the possibility that vitamin D supplementation may promote resilience to subsequent TBI. However, human data (in elderly populations) does indicate that failure to maintain adequate vitamin D nutriture is associated with diminished neurocognitive health. For example, plasma 25-hydroxy vitamin D concentrations of less than 20 ng/mL in individuals 65–99 years of age were associated with increased prevalence of dementia, and concentrations below 10 ng/mL were associated with increased cranial indicators (detected via magnetic resonance imaging [MRI]) of cerebrovascular disease such as white matter hyperintensity volume and large vessel infarcts (Buell et al., 2010).

Animal Studies

Maintaining adequate vitamin D nutrition prior to injury may be critical for post-TBI treatment with progesterone, the only agent that has thus far shown therapeutic benefit in randomized, placebo-controlled clinical trials. This possibility is based on a 2009 study conducted in aged rats (Cekic et al., 2009): vitamin D–replete animals showed a 50 percent reduction in spontaneous locomotor activity following contusion to the medial frontal cortex, but progesterone treatment fully restored activity. Rats deficient in vitamin D exhibited a similar reduction in locomotor activity following contusion, but treatment with either progesterone alone or vitamin D alone had no restorative effect. Although treatment with progesterone plus vitamin D did completely restore locomotor activity, the possible efficacy



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