Amino Acid And Protein Requirements: Cognitive Performance ...

Introduction

This chapter addresses amino acid and protein requirements and brain function. A particular focus will be the possibility that central demands for amino acids may modify nutritional requirements when individuals are exposed to extreme environments and other stressors associated with combat and high-intensity military or civilian occupations.

To function adequately, the central nervous system (CNS) requires a number of amino acids found in protein foods. Amino acids such as tryptophan, tyrosine, histidine, and arginine are used by the brain for the synthesis of various neurotransmitters and neuromodulators (Betz et al., 1994). To date, CNS requirements for specific amino acids have not been systematically investigated, perhaps because it has been assumed that brain requirements for precursor amino acids were not critical. Furthermore, appropriate methods of determining whether adequate levels of particular precursors are provided to the CNS by the diet do not exist. Although little information on CNS requirements of specific amine acids is available, results from several lines of related research suggest that the peripheral concentration of particular amine acids can be a factor in the regulation of central neurotransmission, cognitive performance, and mood state. For example, if the amine acid tryptophan is either artificially elevated or lowered, changes in brain function and behavior can occur (Young, 1996). Even in normal humans, acute tryptophan depletion produces transient alterations in mood state (presumably by reducing the CNS concentration of serotonin), in particular increased subjective depression and increased aggression (Young, 1996). In contrast, administration of single doses of pure tryptophan to humans increases sleepiness and may reduce pain sensitivity (Hartmann, 1986; Lieberman et al., 1985). These changes are consistent with the various functions attributed to serotonin in the CNS.

CNS requirements for specific amine acids during periods of undernutrition or when individuals are exposed to highly stressful conditions may be particularly critical. For example, among moderately undernourished, but not highly stressed soldiers participating in a field test of an energy deficient ration, decrements in tryptophan were associated with impaired cognitive performance (Lieberman et al., 1997). Furthermore, a series of studies suggests that supplemental administration of tyrosine increases brain catecholaminergic neurotransmission and has beneficial effects on various behavioral parameters associated with resistance to stress (for a recent review, see Lieberman, 1994). Tyrosine is one of the dietary precursors for the synthesis of the catecholamines, dopamine and norepinephrine. The beneficial neurochemical and behavioral consequences of supplemental tyrosine administration are most readily observed when humans and other animals are exposed to various environmental and psychological stressors (Wurtman et al., 1981).

The Blood-Brain Barrier: A Key Determinant of Brain Nutritional Status

Unlike most other organs, the brain is isolated from the general circulation by the blood-brain barrier (BBB). The nature of the barrier is determined by the special properties of the cerebral vasculature, specifically the epithelial cells of the brain capillaries, which selectively prevent the transport of various substances into the brain (Betz et al., 1994 Pardridge 1977). In general, lipophilic compounds typically can passively cross the BBB, but water soluble compounds, such as amine acids, cannot. The BBB, therefore, must contain special mechanisms for selectively transporting key water soluble compounds, such as essential amine acids, into the brain (Pardridge, 1977; Betz et al., 1994). The special status of the brain with regard to its accessibility to nutritional and other systemic metabolic factors has profound implications for the determination of the nutritional requirements of the CNS. For example, in the periphery, a variety of substances can be used as energy substrates, but the brain must rely almost exclusively on glucose (Pardridge, 1977). In examining the brain's requirements for protein and amino acids, it is essential to keep in mind that many substrates available to other organ systems are not available to the brain as a consequence of the BBB's "protection" of the brain. The protected status of the brain could have important implications under conditions of metabolic stress induced by undernutrition, exposure to adverse environmental conditions, or severe physical stress. It is possible that under such conditions, brain nutrient requirements relative to other organ systems may be proportionally much greater.

Although the brain is protected by the BBB, it still requires a number of substrates for adequate function. The importance of various amino acids as precursors for key brain neurotransmitters is well established, and transport mechanisms exist to provide these to the brain. At least three active transport mechanisms convey amino acids into the brain (Betz et al., 1994). Separate mechanisms exist for transport of the large neutral amino acids (LNAA), basic, and acidic amino acids across the BBB. However, small neutral amino acids like glycine and alanine appear to be actively pumped out of the brain (Betz et al., 1994). These three mechanisms and some of the amino acids that they transport are presented in Table 14-1.

TABLE 14-1

CNS Amino Acid Transport Mechanisms.

Because whole classes of amino acids are actively transported by amino acid-specific carrier mechanisms, compounds from the same class of amino acids actually compete for transport into the brain (Pardridge, 1977). The functional implication of this unique characteristic of the BBB is that the amino acid composition of food is of greater consequence to the brain than perhaps any other organ system. Unlike other organ systems, the brain cannot simply absorb the nutrients it requires from the general circulation but rather only receives those nutrients that are transported across the BBB.

Several of the amino acids that are transported across the BBB and, in some instances, compete for access to the brain, are precursors of important brain neurotransmitters as shown in Table 14-2. There is evidence that most of the neurotransmitters listed in Table 14-2 are, under certain conditions, precursor sensitive; therefore, as the peripheral concentration of any of the precursors varies, there could be consequences with regard to brain metabolism, function, and behavior (for a recent review see Young, 1996).

TABLE 14-2

Amino Acids and Their Neurotransmitter/Neuromodulator Products.

As shown in Table 14-3, these neurotransmitters have a variety of important functions in the brain, regulating or modulating a variety of key CNS functions. Of course, the precise relationship between a neurotransmitter and the behavior of an organism is difficult to summarize and is usually the subject of considerable controversy. Clearly, the functions outlined in Table 14-3 are not only critical in a general way for maintaining the normal behavioral status of an organism, but are also closely related to the ability of that organism to function in stressful conditions. In single nonphysiologic doses, or when administered in special diets, all of the amino acid precursors of the transmitter systems shown in Table 14-3 have been found to alter brain activity.

TABLE 14-3

Putative Functions of Various Neurotransmitter Systems (with Amino Acid Precursors).

This chapter will focus on the large neutral amino acids (LNAAs), tryptophan and tyrosine, because the data on the effects of these neurotransmitter precursors on brain chemistry and behavior is most convincing. Perhaps one of the most critical issues (and most difficult to answer currently) is: Under what, if any, physiological situations will nutrient availability from food affect brain function?