Page 70 - Journal of Special Operations Medicine - Spring 2014

and power. In a large sample of men, serum 25(OH)D provide resilience to mTBI by limiting the inflammatory
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levels were associated with total testosterone even after response following impact. In an animal TBI model,
adjusting for age and body mass index. A follow-up vitamin D deficient rats had elevated levels of inflam-
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study supplemented a subset of those men with 3332IU matory markers at baseline and postinjury compared
vitamin D per day for 1 year. At baseline, both groups with vitamin D sufficient animals. Postinjury treat-
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of men had mean 25(OH)D levels in the deficient range. ment with vitamin D was inferior to maintaining suffi-
However, after 1 year of vitamin D supplementation, cient levels preinjury. Prolonged inflammation is linked
25(OH)D levels were significantly raised as well as all to poor injury outcomes, which has been supported
measures of testosterone. No significant changes oc- by higher levels of inflammatory cytokines measured
curred within the placebo group, supporting the theory within 24 hours of injury correlating with more severe
that vitamin D deficiency inhibits androgen synthesis. brain injury in humans. Vitamin D deficiency restricts
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Emerging evidence strengthens support for the relation- regulation of cytokine production, thereby allowing
ship between vitamin D and testosterone production sustained inflammatory response to injury. This pro-
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by showing that 25(OH)D production occurs in Leydig longed inflammatory response to mTBI increases injury
cells of testes, which are the site of testosterone produc- severity and presents an appropriate target for future
tion. Therefore, Operators with preexisting vitamin D research aimed at minimizing concussive symptoms. As
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deficiency may be at increased risk for deficits in testos- of 2013, no human studies have looked at vitamin D
terone level. status before or after mTBI.

Cognitive Performance and Neuroprotection Vitamin D deficiency likely prolongs mTBI recovery ow-
Vitamin D receptors and metabolizing enzymes have ing to its role in cognitive function and neuroprotection,
been identified in the human brain, establishing sup- While vitamin D status has been not be examined in hu-
port for a role of vitamin D in brain function and de- man mTBI patients, research has established that endo-
velopment. Further research have linked vitamin D crine dysfunction results from mTBI. Altered hormones
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deficiency to increased risk for certain psychiatric and were found in 42% of male veterans who had at least
neurological diseases such as depression, schizophrenia, one mTBI related to blast exposure, compared with no
autism, multiple sclerosis, Alzheimer’s disease, and de- evidence of dysfunction in veterans who had deployed
mentia. 45,46 As a regulator of gene transcription, vitamin but never sustained mTBI. Hormone deficiencies were
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D targets neural genes that affect a variety of behavioral observed most frequently in testosterone and insulin
and biochemical processes. Animal models have shown growth factor I (indicator of growth hormone status).
that vitamin D deficiency slows learning and increases Evidence of endocrine dysfunction following mTBI sug-
anxiety, while human studies have correlated low vi- gests that vitamin D levels may also be altered postinjury,
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tamin D levels with depression and accelerated cogni- raising the question of whether vitamin D deficiency re-
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tive decline. Elevated levels of inflammatory cytokines sults from trauma-related hormonal abnormalities or
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have been correlated with both depression and vitamin whether vitamin D deficiency increases the risk for endo-
D deficiency, suggesting that vitamin D suppresses excess crine dysfunction. Cognitive symptoms linked to vitamin
neural inflammation and maintains cognitive health. D deficiency are similar to those observed in endocrine
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dysfunction and post-concussive syndrome, such as mem-
Due to its role in cognitive function and regulation of ory loss, depression and increased risk for posttraumatic
the inflammatory response, optimal vitamin D status stress disorder (PTSD). 47,54,55 Although vitamin D status
may provide neuroprotection in mild traumatic brain has not been assessed in brain injury, the combination
injury (mTBI). Since chronic vitamin D deficiency has of vitamin D and progesterone has been shown to be an
been linked to a heightened acute inflammatory re- effective treatment for TBI. A human trial treated severe
sponse, vitamin D deficiency at the time of brain injury TBI patients with 200IU/kg (>10,000IU total) vitamin D
could exacerbate secondary damage due to excess in- per day during the first 5 days after injury in combi nation
flammation, worsening postconcussive symptoms and with progesterone. The vitamin D–plus–progesterone
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keeping an Operator from returning to duty. In response treatment group experienced greater recovery compared
to biomechanical forces, mTBI stimulates a cascade of with progesterone alone or placebo, supporting a role of
metabolic events including axonal injury, damaged cel- vitamin D in accelerating brain repair.
lular membranes, disrupted ion exchange, as well as re-
duced cerebral blood flow, inflammation, and cellular Thus, research that monitors vitamin D levels in Op-
death. While the acute release of inflammatory cyto- erators with mTBI is needed, especially considering that
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kines appears to be neuroprotective by promoting tissue vitamin D status may influence symptoms of PTSD and
repair, prolonged inflammation contributes to oxidative has been linked to risk of suicide. Through its association
stress along with neurotoxicity and cellular death. As a with testosterone production, vitamin D deficiency may
key regulator of inflammatory cytokine, vitamin D may contribute to symptoms of PTSD, such as depression,

62 Journal of Special Operations Medicine Volume 14, Edition 1/Spring 2014