trauma (reviewed in De Bandt and Cynober, 2006). Of these, four reported no beneficial effect on nitrogen balance, whereas three found positive results. The number of patients in each study tended to be small (ranging from 5 to 101, mean = 31) and the patients were heterogeneous in terms of type and severity of trauma.

A prospective, randomized controlled study of patients undergoing curative hepatic resection found that perioperative oral nutrition including BCAAs resulted in higher serum erythropoietin concentrations than a control diet (for patients who did not have hepatitis). The authors suggested that higher erythropoietin concentrations might provide protection from ischemic injury (Ishikawa et al., 2010).

When BCAAs were added as additional therapy to the ketogenic diet of children with refractory epilepsy, 13 out of 17 benefited, with a 50–100 percent seizure reduction compared to the ketogenic diet alone (Evangeliou et al., 2009). The authors suggested that BCAAs may not only increase the effectiveness of the ketogenic diet, but that the diet could be more easily tolerated by the patients because of the change in the ratio of fat to protein.

Animal Studies

Cole and colleagues reported that brain-injured mice exhibited cognitive improvement when treated with BCAA-supplemented drinking water (each BCAA at a concentration of 100 mM), beginning two days after injury (Cole et al., 2010). The injury was a 20 millisecond pressure pulse of saline to the dura, and hippocampal-dependent cognition was assessed using a conditioned fear response. Responses diminished by approximately 50% in the injured mice compared to sham controls, whereas injured mice drinking BCAA-supplemented water behaved no differently from controls. In addition to behavioral assessments, Cole et al. (2010) analyzed synaptic function in vitro. The excitatory postsynaptic potentials generated in hippocampal slices from injured mice were diminished compared to sham controls, but incubating the slices with BCAAs at concentrations of 100 μM fully restored synaptic function (Cole et al., 2010).


Leucine and other essential amino acids are necessary, and their benefit in increasing protein synthesis and lean body mass is well documented. However, there are not yet compelling data to support a recommendation to supplement rations with BCAAs to ameliorate or treat TBI. There is some indication from a pilot study that BCAAs might act synergistically with a ketogenic diet in epilepsy, one of the many possible sequelae of TBI.

The only randomized clinical trial (Ott et al., 1988) suggests that intravenous infusion of BCAAs may be beneficial for maintaining positive nitrogen balance following TBI, but the influence of BCAAs on morbidity and mortality was not reported. There is one encouraging animal study in which mice supplemented with BCAAs (dissolved in water at 100 mM) showed improvements in cognition and diminished excitatory potentials in hippocampal slices (Cole et al., 2010). Taken altogether, however, there is not enough evidence from animal studies to support initiating research in humans.

Because a large percentage of military personnel take BCAAs as supplements to their diets, BCAAs should be included in the dietary intake assessments of TBI patients in medical treatment facilities to identify preinjury nutritional intake and status, as well as nutritional intake during the various stages of treatment. The data could be used to establish potential relationships between preinjury nutritional intake/status and recovery progress.

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