• Before any definitive conclusions can be made about efficacy, the route and timing of administration and dosage are key considerations that investigators need to optimize in study designs.

  • Investigators should consider synergistic and antagonistic effects with nutrients, dietary supplements, food components, or other substances in the diets of military personnel.

Although not related to nutrition specifically, the committee thought it important to mention the significance of appropriate methodologies. There are still substantial deficiencies in the biomarkers and animal models currently used. On that point, the committee made two general recommendations: first, to continue to develop better animal models, and second, to identify biomarkers of both injury and improved brain function.

There also is a need to assess the nutritional status of military personnel to determine whether there are nutrients that need to be added to the diets of military personnel to main­tain optimal readiness and mission performance goals. The committee found there are not enough nutritional assessments of military personal conducted in various settings, specifi­cally during deployments.

In addition to providing protein and energy after severe injury, there are other nutri­tional interventions that are promising but for which many questions persist about exact protocols (e.g., dosage, time, and route of administration), and more research is critically needed in order to provide optimal treatment to military members with TBI. For example, based on recent reports that mortality and morbidity of TBI patients are affected by early feeding, the committee strongly supports elucidation of the best practices during the early postinjury period. Fundamental questions remain, however, about the appropriate serum levels of glucose and insulin to be achieved within the first 24 hours after severe TBI. More information is also needed on the best nutrition goals for the two weeks following that period. In addition to these urgent questions about protein and energy needs shortly after injury, research gaps also were identified in other promising areas. Based on the existing evidence from animal and human research studies, the nutritional interventions selected for review by the committee were energy and protein provision, antioxidants (e.g., vitamins E and C), polyphenols (e.g., flavonoids, resveratrol, and curcumin), branched-chain amino acids, choline, creatine, ketogenic and similar modified diets, magnesium, n-3 fatty acids, vitamin D, and zinc. Chapter 4 describes how these nutrition interventions were selected. For some of the selected nutrients, such as resveratrol, studies have demonstrated benefits of the nutrient in animal models of TBI or brain injury. However, there are as yet no clinical trials that confirm similar beneficial effects in humans. For other nutrients, such as creatine, there are human trials with promising results that could be extended to military personnel. In other cases, such as magnesium, choline, and n-3 fatty acids, human trials are under way, and the military should review those studies as the results are made public.

The committee recognizes the need for the Department of Defense (DoD) to prioritize the research recommendations. Although there will undoubtedly be other criteria that will be used to guide such ranking, the committee offers here its reflections on the prioritization of research based on its opinions about the likelihood of positive results for lessening the effects of TBI. Research on interventions for which human trials to explore efficacy in improving the outcomes of TBI already exist or are ongoing have been presented as “most promising research” (Box 17-4). Research on interventions for which animal studies in TBI or human studies in associated conditions have shown improvements in outcomes is presented as “other research” (Box 17-5). Although the research recommendations are directed to DoD as the sponsor of this study, the committee recognizes that this research agenda would entail

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