of both excitatory and inhibitory neurotransmitters might contribute to their potential effects in outcomes of TBI.

A list of human studies (years 1990 and beyond) evaluating the effectiveness of BCAAs in providing resilience or treating TBI or related diseases or conditions (i.e., subarachnoid hemorrhage, intracranial aneurysm, stroke, anoxic or hypoxic ischemia, epilepsy) in the acute phase is presented in Table 8-1; this also includes supporting evidence from animal models of TBI. The occurrence or absence of adverse effects in humans is included if reported by the authors.

USES AND SAFETY

The Estimated Average Requirements (EARs) for leucine, isoleucine, and valine are 34, 15, and 19 mg/kg/day, respectively (IOM, 2005). Using the recommended intake for a 70 kg individual as a reference, the actual mean daily intake in the United States for each of the BCAAs is approximately threefold higher for men and approximately twofold higher for women (IOM, 2005). BCAA-enriched protein or amino acid mixtures or BCAAs alone have been used in a variety of metabolic disorders, such as chronic liver disease, encephalopathy, sepsis, and others, usually in an effort to reduce the uptake of aromatic amino acids by the brain and to raise low circulating levels. BCAA supplements are marketed to healthy individuals with claims that they enhance muscle mass, reduce soreness after exercise, and reduce central fatigue, although peer-reviewed research data rarely support these claims (Wagenmakers, 1999). A previous Institute of Medicine (IOM) committee considered the addition of higher amounts of specific amino acids, including BCAAs, to rations used during short-term, high-intensity combat operations. That committee found no evidence to recommend the addition of specific amino acids to those rations (IOM, 2006). As a result of claims for fitness benefits, athletes and military personnel striving to enhance physical performance may have BCAA intakes even higher than those of the general public. A survey by Lieberman et al. (2010) found that 23 percent of military personnel involved in combat arms and 47 percent of those in Special Forces were taking protein or amino acid supplements.

A 2005 IOM report found no studies of adverse events associated with normal diets containing BCAAs or with infused supplemental doses up to 9.75 g, but there was no Tolerable Upper Intake Level (UL) determined because of the lack of dose-response data. Studies of acute or chronic oral administration of BCAAs have reported no adverse effects, even at a high single dose of 60 grams (Fernstrom, 2005). The outcomes of interest measured in these studies were related to physical performance, phenylketonuria, hepatic cirrhosis, and neurological and psychiatric diseases. It is, however, difficult to assess whether some of the outcomes that were not regarded as adverse effects would present a concern in a military setting. As an example, after examining one of the studies reporting no adverse effects, the committee concluded that excessive intake of BCAAs may be deleterious; in that study, oral doses of 10, 30, and 60 grams of BCAAs caused small increases in spatial recognition memory latency in healthy human subjects, but no changes in visual information processing or pattern recognition (Gijsman et al., 2002). The authors attributed the increased latency to a reduced ratio of (tyrosine+phenylalanine) to BCAAs, resulting in reduced transport of tyrosine and phenylalanine across the BBB, and hence reduced dopamine synthesis.



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