BOX 17-5

Other Research Recommendations

RECOMMENDATION 7-1. Based on the literature from animal and human trials concerning stroke and epilepsy, DoD should consider a clinical trial with TBI patients using an array of antioxidants in combination (e.g., vitamins E and C, selenium, beta-carotene).

RECOMMENDATION 11-1. DoD should conduct animal studies to examine the specific effects of ketogenic diets, other modified diets (e.g., structured lipids, low-glycemic-index carbohydrates, fructose), or precursors of ketone bodies that affect energetics and have potential value against TBI. These animal studies should specifically consider dose, time, and clinical correlates with injury as variables. Results from these studies should be used to design human studies with these various diets to determine if they improve outcome against severe TBI. These studies should include time as a variable to determine whether there is an optimal initiation point and length of use.

RECOMMENDATION 11-2. If these studies show benefits, then DoD should further investigate whether the potential beneficial effect of such ketogenic or modified diets or precursors to ketone bodies applies to concussion/mild and moderate TBI. Before conducting these studies, DoD should consider the feasibility (i.e., how to ensure compliance with a modified diet) of using diets that affect the metabolic energy available, such as ketogenic diets, for the treatment of TBI.

RECOMMENDATION 14-1. Based on positive outcomes in small-animal models of TBI with curcumin and resveratrol, DoD should consider conducting human trials. In addition, other flavonoids (e.g., isoflavones, flavanols, epicatechin, theanine) should be evaluated in animal models of TBI.

RECOMMENDATION 15-1. The committee recommends more animal studies be conducted to determine if vitamin D enhances the beneficial actions of progesterone in the treatment of TBI. If this synergistic effect is confirmed in animals, then studies in humans should be conducted to evaluate the extent to which vitamin D supplementation might improve the efficacy of progesterone treatment.

RECOMMENDATION 15-2. Based on animal studies showing a requirement of vitamin D for the efficacy of progesterone therapy, future animal studies are recommended to test the efficacy of using vitamin D supplements to improve resilience to TBI. Should the data from animal studies support use of this steroid hormone, human trials should be implemented to test the efficacy of vitamin D in populations at high risk for TBI.

RECOMMENDATION 16-2. Future work is needed in both humans and animal models to determine the extent to which chronic preinjury zinc supplementation can improve resilience in the event of a TBI.

BOX 17-6

Future Update of Evidence-Based Guidelines

RECOMMENDATION 2-1. Evidence-based nutrition guidelines specific for severe TBI should be updated. These guidelines should address unique nutritional concerns of severe TBI when different from generic critical illness nutrition guidelines (e.g., meeting energy needs and benefits of specific nutrients, food components, or diets). In addition, current guidelines to manage mild and moderate TBI should include recommendations for nutritional interventions. The guidelines should be developed in a collaborative manner with the various key stakeholders (e.g., American Dietetic Association, Department of Veterans Affairs, DoD).

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