Creatine

Military personnel are using creatine in the form of dietary supplements to increase strength and muscle mass. In the context of TBI, the committee found good evidence of improvements in cognition and behavior from trials with creatine in children and adolescents. Although this evidence comes from long-term studies, treatment with creatine was started early after injury and may have influenced disease processes during the acute phase. In fact, creatine is thought to maintain mitochondrial energetics and improve cerebral vascular function, both of which are disrupted during the acute phase of TBI. The military is urged to resolve questions about whether these results can be extrapolated to adults and about the timing of administration and optimal dose.

Ketogenic Diet

Results from studies of children with epilepsy suggest that ketogenic diets (or other modified diets that increase levels of ketone bodies) might be therapeutic for TBI. It is hypothesized that ketogenic diets might provide an alternative source of energy and reduce dependence on glucose, whose metabolism is impaired after TBI. There are, however, concerns about the feasibility of these diets in the TBI context, where meeting nutritional needs is important, especially early after injury; adherence to ketogenic diets by patients might also be difficult once they are outside a hospital setting.

Magnesium

Magnesium has a role in inhibiting the actions of the excitatory neurotransmitter glutamate by regulating calcium entry into the postsynaptic neuron, a process intimately related to a TBI event. Despite this seemingly neuroprotective action, there is no clear evidence that magnesium supplementation will affect TBI outcomes. The committee offered no recommendation for supplementing with or conducting further research on magnesium. The window of opportunity for magnesium use in the treatment of TBI is a critical issue that remains to be addressed. The military should follow the results from current magnesium trials, which will evaluate potential benefits of magnesium when administered one to two hours after the onset of brain damage.

N-3 Fatty Acids

Despite surveys indicating that n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) are being taken as dietary supplements by military personnel, it has been suggested that the n-3 fatty acid status of the active duty military population might be low. Because it is well documented that fish oil supplementation decreases inflammation, n-3 fatty acids are the subject of many studies evaluating their health benefits and elucidating their mechanism of action. The ratio of n-3:n-6 composition may affect cell membrane fluidity, thickness, or other characteristics. Although animal models and human studies on other brain injuries suggest they may provide benefits, there has been no human trial evaluating the effects of n-3 fatty acids on resilience to or treatment of TBI.

Polyphenols

Polyphenols are a heterogeneous group of compounds widely found in nature that have been evaluated for their benefits to health when consumed either singly or in combination,



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