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Protein and brain function

Protein and brain function

Balance is what the body Protei, and healthy sources Protein and brain function all Pfotein macronutrients: fat, protein, and carbohydrates. Molecule key for synapse strengthening. This isn't to say that to stay alert, you ought to eat mostly protein.

Protein and brain function -

K,L Summary of EPM test results. L Mean total distance in each group. Error bars and dots indicate SD and scores of individual mice, respectively. NPD, normal protein diet; LPD, low protein diet; EPM, elevated plus maze; PAT, passive avoidance test; Veh, vehicle; p.

A previously described quantification method for amino acids 11 was used in this study with minor modifications. The plasma sample was mixed with the internal standard solution stable isotope-labeled amino acids in water and deproteinized with acetonitrile.

Frozen brain tissue was powdered using a Multi-Beads Shocker Yasui Kikai, Osaka, Japan and homogenized in an ice-cold methanol aqueous solution containing L-phenyl- d 5 -alanine was used to calculate recovery of the pretreatment procedure.

The homogenate was further mixed with water and chloroform, and its upper phase was dried up. The residual was dissolved with water, and mixed with the internal standard solution. Plasma albumin and total protein and glucose measurements were conducted on a chemical analyzer DRI-CHEMV: FUJIFILM, Tokyo, Japan.

The elevated plus maze EPM consisted of two open Each individual mouse was placed in the center area facing an open arm and allowed to freely explore the maze for 8 min.

The behavior of the animals was recorded, tracked, and analyzed with the SMART 3. The following parameters were evaluated: number of entries into the closed vs. open arms, distance traveled cm within the closed and opened arms, and time spent in the closed and opened arms.

The EPM test was conducted on day 28 and day 60 in Experiment 1 and on day 36 in Experiment 2 during the dark period. The passive avoidance test PAT was performed using a step-through cage Muromachi Kikai, Tokyo, Japan consisting of white and black compartments separated by a sliding door.

During the training trial, mice were placed in the white compartment, the door was opened, and the step-through latency was recorded. When the mice entered the dark compartment with its four paws on the grid floor, an electric foot shock 1 mA was delivered through stainless-steel rods for 1 s. After 24 h, a probe test was performed using the same procedure without any foot shock.

The step-through latency time to enter the dark compartment was recorded up to a maximum of s in Experiment 1 and s in Experiment 2 as the cut-off latency. The PAT was conducted on days 29 and 30 in Experiment 1 and on days 37 and 38 in Experiment 2 during the dark period.

Statistical analyses were performed using GraphPad Prism 6 Software. First, we examined whether LPD intake affected brain function in aged mice through behavioral experiments. The PAT was used to investigate the learning and memory activities of mice.

The EPM is considered to be a reliable indicator of anxiogenic behavior and depends upon the assumption that mice inherently prefer the closed arms of the maze to the open arms.

We observed the number of entries in the open arms and total distance in the EPM, which are given in Figures 1E—H. These results indicate that LPD induced cognitive function decline and agitation and disinhibition behavior in aged mice.

Next, we hypothesized that LPD leads to low concentrations of EAAs in the plasma and brain, thereby inducing neurotransmitter depletion in the brain, resulting in cognitive dysfunction and behavioral abnormalities. To identify the concentrations of EAAs and neurotransmitters, we quantified these concentrations in the plasma and brain of the NPD and LPD groups.

Plasma levels of EAAs Val, Leu, Ile, Lys, Met, Thr, Trp, and Phe and non-essential amino acids Tyr and Pro in the LPD group were significantly lower than those in the NPD group Figure 2A , Supplementary Table 2.

The LPD group also exhibited significantly lower levels of EAAs Val, Leu, Ile, Lys, and Thr , non-essential amino acids, and neurotransmitters [especially aspartate Asp , GABA, glutamate Glu , glycine Gly , dopamine, norepinephrine, and serotonin] in the brain than the NPD group Figure 2B , Supplementary Table 3.

However, the concentrations of plasma albumin and total protein and glucose were not different between the LPD and NPD groups Supplementary Figure 1. Figure 2. The concentrations of amino acids and neurotransmitters in the plasma and brain were decreased by LPD.

A Radar charts of amino acids in aged B6 mice. The average of each amino acid concentration as normalized values in the plasma left and prefrontal cortex area PFC area; right are expressed.

B Mean neurotransmitter concentrations in the PFC area after sacrifice in each group. Finally, we hypothesized that the flux of EAAs from the blood to the brain would be important for maintaining neurotransmitters. Thus, we conducted oral administration of seven EAAs Val, Leu, Ile, Lys, Phe, His, and Trp , which are a source of neurotransmitters.

To examine the importance of the flux of EAAs into the brain, we compared the effects of administering EAAs in the form of C1 control against C2 or C2, which is composed of EAAs with high fluxes into the brain based on a previous report 12 Table 1.

Both C1 and C2 EAAs ameliorated the changes in agitation and disinhibition behavior indicated by a reversal of the changes in the total distance traveled on day 28 and the number of entries in the open arms on day 60 in the EPM Figures 1F,G. In addition, C2 ameliorated the step-through latency in the PAT Figure 1C , confirming the importance of fluxes of EAAs into brain for cognitive function.

While C2 intake once per day was enough to ameliorate cognitive decline Figures 1I,J , C2 intake twice per day was needed to ameliorate agitation and disinhibition behavior Figure 1K.

Moreover, C2 reversed the concentrations of Glu and dopamine in the brain Figure 2B. However, there was no difference among the groups in the total distance in the EPM Figure 1L. Here, we demonstrated the importance of protein and amino acid nutrition for maintaining brain function.

In this study, protein malnutrition in aged mice caused behavioral abnormalities as well as physiological alterations in the brain, including decreased neurotransmitter and plasma amino acid levels. These findings are in accordance with previous clinical studies showing the possibility that chronic protein malnutrition leads to cognitive dysfunction 7 , 8.

In this study, the changes induced by LPD were reversed by EAA supplementation, suggesting the importance of EAA nutrition in the brain and behavior. This is the first study to report the phenotype of protein malnutrition and EAA supplementation in aged mice. In this study, LPD mice showed a significantly decreased passive avoidance response compared to NPD mice, indicating that LPD in aged mice was associated with learning and memory impairment.

The PAT is one of the most widely used tests for fear learning and memory. Furthermore, LPD mice showed an increase in the proportion of time spent in the open arms of the EPM, indicating that those mice had agitation and disinhibition potentially caused by the LPD.

Furthermore, similar to rTg mice 16 — 18 , LPD mice showed increased total distance moved, indicating hyperactive behavior in a new environment. Interestingly, LPD mice showed decreased amino acid concentrations in the blood and brain. Since EAAs in the blood enter the brain via the blood-brain barrier BBB , both blood and brain EAAs can conceivably be influenced by food intake.

Most neurotransmitters are synthesized from amino acids. For example, dopamine and norepinephrine are synthesized from tyrosine, which is a metabolite of Phe.

Glu is synthesized from branched-chain amino acids or glutamine Gln , which are derived from the blood via the BBB.

Despite the slow flux of Leu into the brain, which is With age, the synthesis of these neurotransmitters is known to decline in humans and mice 20 — Furthermore, the amount of neurotransmitters, including dopamine, norepinephrine, acetylcholine, Glu, serotonin and GABA, and the levels of their synthetic enzymes are known to be lower in patients with AD than in healthy people 21 , Dopamine and norepinephrine are monoamines that are associated with cognitive function, particularly working memory In this study, LPD mice exhibited decreased concentrations of GABA, Glu, Gly, dopamine, norepinephrine, serotonin and Asp, which might be associated with behavioral abnormalities.

In this study, we used seven essential amino acids Val, Leu, Ile, Lys, Phe, His, and Trp that can be a source of neurotransmitters in the brain to make two EAA mixtures of different compositions.

We hypothesized that the rate of amino acid influx to the brain 12 would be important and set C1 as the composition that is the reciprocal of what easily passes through the brain. In contrast, C2 was composed to directly match the ratios of the brain influx rate of the different EAAs.

Although both C1 and C2 reversed the behavioral changes in the EPM, only C2 reversed the behavioral change in the PAT. C2 but not C1 improved the LPD-induced learning and memory behavior deficits and elevated the Glu concentration. The C2 mix is mainly composed of Leu, Phe, and Lys, which are potential substrates for synthesizing Glu in brain cells Glu is known to be an important neurotransmitter that triggers de novo spine growth 26 and is involved in learning and memory ability Glu restoration could be one of the key mechanisms connecting behavior and nutrition.

The details of the link between the decreased amino acid and neurotransmitter concentrations and behavioral abnormalities must be further examined in the future.

Also, in this study, only male mice were fed a LPD for 2 months. The effects with shorter- and longer-term LPD feeding to behaviors are to be investigated in the future.

And whether the similar results will be obtained in female mice, which have estrus cycle that affect animal behaviors including emotion-related behaviors, social behaviors, and cognition, would be a future research question.

Several reports have indicated that the amount of protein consumed by the elderly is not sufficient 28 — Oral issues such as decreased appetite with age 32 , 33 , dysphagia 34 , reduced muscle strength required for meat consumption 35 , 36 , and periodontal disease 37 are noted as causes.

In addition, aging of the digestive organs and gastric acid secretion decrease in the elderly 38 , suggesting a decrease in digestive function to efficiently absorb the ingested protein. Although some nutritional epidemiological studies suggest the relationships between dietary protein deficiency and cognitive decline 7 — 10 , it is yet to be demonstrated whether the EAA supplementation could affect cognitive ability in humans.

Future clinical trials to examine the effects of EAA supplemental intake to cognitive ability in the elderly are needed. This study may shed light on the roles of EAAs in relation to the brain function of aged people. Although further research is necessary to illustrate the detailed mechanism and clinical effectiveness, EAA ingestion could be one possible solution for maintaining healthy brain function.

In this work, we investigated the association between protein intake and cognitive function in aged mice, showing that LPD resulted in learning disabilities, disinhibition, and hyperactive behavior. LPD intake may conceivably cause low blood amino acid levels, resulting in neurotransmitter deficiency in the brain.

The addition of seven EAAs Val, Leu, Ile, Lys, Phe, His, and Trp that can be a source of neurotransmitters to the LPD reversed some of the changes in behavior and neurotransmitter concentrations.

Further studies elucidating the connection between brain function and protein and amino acid nutrition are necessary. The animal study was reviewed and approved by Animal Study Ethics Committe of Ajinomoto Co.

HS, MT-Y, YT, KS, KN, MH, and AK: concept and design of the study. HS, MT-Y, NK, KM, SU, MK, MN, SK, and MI: data acquisition and analysis. HS, YT, KN, and AK: drafting the manuscript and figure.

All authors read and approved the final version of the manuscript. The authors declare that this study received funding from Ajinomoto Co. The funder was involved in the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit it for publication.

HS, MT-Y, NK, KM, SU, MK, MN, SK, MI, KS, KN, AK are employed by Ajinomoto Co. We are grateful to Takahiro Shimizu and Takashi Mashima WDB Eureka, Tokyo, Japan , Kohei Tsumaki WDB, Tokyo, Japan for technical assistance.

Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement.

doi: PubMed Abstract CrossRef Full Text Google Scholar. El-Hayek YH, Wiley RE, Khoury CP, Daya RP, Ballard C, Evans AR, et al. Tip of the iceberg: assessing the global socioeconomic costs of Alzheimer's disease and related dementias and strategic implications for stakeholders.

J Alzheimers Dis. Crous-Bou M, Minguillón C, Gramunt N, Molinuevo JL. Alzheimer's disease prevention: from risk factors to early intervention. Alzheimers Res Ther. Nes M, Sem SW, Rousseau B, Bjørneboe GE, Engedal K, Trygg K, et al. Dietary intakes and nutritional status of old people with dementia living at home in Oslo.

Eur J Clin Nutr. PubMed Abstract Google Scholar. Sanders CL, Wengreen HJ, Schwartz S, Behrens SJ, Corcoran C, Lyketsos CG, et al. Nutritional status is associated with severe dementia and mortality: The Cache County dementia progression study.

Alzheimer Dis Assoc Disord. Thomas DE, Chung-A-On KO, Dickerson JW, Tidmarsh SF, Shaw DM. Tryptophan and nutritional status of patients with senile dementia. Psychol Med. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population.

La Rue A, Koehler KM, Wayne SJ, Chiulli SJ, Haaland KY, Garry PJ. Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr. Roberts RO, Roberts LA, Geda YE, Cha RH, Pankratz VS, O'Connor HM, et al. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia.

CrossRef Full Text Google Scholar. Fernando WMADB, Rainey-Smith SR, Gardener SL, Villemagne VL, Burnham SC, Macaulay SL, et al. Associations of dietary protein and fiber intake with brain and blood amyloid-β. Shimbo K, Oonuki T, Yahashi A, Hirayama K, Miyano H. Rapid Commun Mass Spectrom.

Smith QR. Transport of glutamate and other amino acids at the blood-brain barrier. The phenomenon of peripheral modulation of brain serotonin occurs as a consequence of both the previously noted competition of the LNAA for transport across the BBB and the selective uptake by muscle of the branchedchain amine acids following a carbohydrate meal.

Following consumption of carbohydrate, which elicits the secretion of insulin, the concentration of the branched-chain amine acids in the plasma falls as they move into muscle, while tryptophan levels remain relatively unchanged. Therefore, since more tryptophan is available for transport by the LNAA carrier mechanism, tryptophan transport to the brain increases and more tryptophan is available for the synthesis of serotonin.

In humans, it has been established that changes in the protein:carbohydrate ratio of foods can alter plasma tryptophan levels in the same way as in experimental animals Lieberman et al. To date, an association of changes in protein and carbohydrate intake with changes in behavior has not been clearly established, but several behavioral functions have been shown to be sensitive to substantial changes in plasma tryptophan levels.

When tryptophan is administered in pure form or in higher than physiologic concentrations in meals, or is artificially lowered by administering tryptophan-free meals, substantial changes in a variety of behavioral parameters can be observed.

One of the most frequently documented effects of tryptophan administration is an increase in self-reported mental fatigue. Tryptophan's effects on arousal and alertness appear to be similar to those produced by mild over-the-counter sedatives such as antihistamines. These effects have been documented with self-reported mood questionnaires Figure and by polysomnography Hartmann and Greenwald, ; Lieberman et al.

The hypnotic-like effects observed in humans after tryptophan administration are consistent with reports implicating brain serotonin neurons in the regulation of alertness.

Although tryptophan is clearly not as potent as prescription hypnotic drugs, it was sold as an over-the-counter, natural sleep aid until several years ago. It was withdrawn from the market when a large number of cases of a rare disease called eosinophilia-myalgia syndrome EMS were seen in individuals who were taking it.

The exact cause of the disease has never been conclusively demonstrated, although it has been suggested that a contaminant was present in the tryptophan produced by one manufacturer.

Source: more Another well-established effect of tryptophan relates to the role of serotonin in the regulation of mood, in particular, level of depression. Most antidepressant drugs increase serotonergic neurotransmission, although many have other central effects as well.

Consistent with this role of serotonin in the brain, it appears that single meals that are deficient in tryptophan have substantial acute effects on self-reported level of depression. A series of studies have been conducted in several laboratories to examine the effects of specially formulated tryptophan-free meals on mood state.

These studies have consistently observed substantial increases in depression when these low- tryptophan meals are ingested Young, when measured with standard self-reported mood questionnaires in normal individuals, as shown in Figure Smith et al.

Effects of a single tryptophan deficient meal on self-reported depression and plasma tryptophan levels of healthy volunteers. Source: Adapted from Smith et al.

Tryptophan-deficient meals also affect the level of aggression displayed by normal volunteers. When normal individuals are classified as belonging to a high-aggressive personality type based on standardized personality questionnaires, administration of tryptophan-deficient meals increases not only aggressive mood state, but also the level of aggressive behavior overtly displayed Figure Cleare and Bond, Administration of a high- tryptophan meal to such individuals decreases aggressive mood and behavior Cleare and Bond, Effects of tryptophan-depleted and -supplemented meals on subjective and objective measures of aggression among normal, high-trait aggressive volunteers.

Tryptophan has also been reported to decrease pain sensitivity in animal models, normal humans, and patients suffering from certain clinical conditions where pain is present Lieberman et al.

The changes in aggression and pain induced by artificially altering plasma levels of tryptophan are consistent with data implicating serotonin in the regulation of aggression and pain sensitivity.

Overall, there is little doubt that substantial variations in plasma tryptophan levels can have a major impact on the behavior of humans and other animals. However, it should be noted that the doses of tryptophan that have been shown to be unequivocally psychoactive may produce changes in brain tryptophan that are larger than those produced by any food that increases or decreases brain serotonin.

Currently, the smallest change in levels of plasma or brain tryptophan that will have an impact on brain function or behavior is unknown. Therefore, it is not currently possible to determine whether nutritional requirements for tryptophan are in any way related to brain demands for this amino acid.

Another amino acid that has been extensively examined for behavioral effects is tyrosine, the precursor of three neurotransmitters: norepinephrine, dopamine, and epinephrine see Table Tyrosine is not typically considered to be an essential amino acid since it can be synthesized by humans from phenylalanine; however, it has been suggested by some investigators that the brain may not be able to synthesize sufficient tyrosine from phenylalanine to meet its needs Pardridge, Tyrosine is generally found in larger quantities than tryptophan in most protein foods.

Since tyrosine is a LNAA, it competes with tryptophan and the other LNAAs for transport across the BBB. Under certain conditions, it appears that administration of tyrosine can affect brain neurotransmission. Specifically, it has been hypothesized that when central catecholaminergic neurons are very active as occurs during exposure to acute stress , they will become precursor sensitive Wurtman et al.

Although these neurons are not normally believed to be affected by the availability of tyrosine, they may require additional tyrosine to function optimally when they are firing frequently Lieberman, ; Wurtman et al.

Norepinephrine is believed to play a critical role in the response of the brain to acute stress. Exposure to heat, cold, cardiovascular stressors, and electric shock all produce significant increases in brain catecholaminergic activity Stone, Central noradrenergic neurons seem to be critical for regulating key behavioral parameters such as attention, arousal level, and mood state Lieberman, Although norepinephrine appears to be particularly critical for the brain's résponse to stress, another brain catecholamine, dopamine, also appears to be involved in certain aspects of the acute response to various stressors.

The neurochemical consequences of exposure to stress and the effects of supplemental tyrosine under such conditions have been examined in animal models.

Two recent studies examined the effects of a combination of cold and restraint stress on release of norepinephrine in the rat hippocampus Luo et al. The technique of microdialysis was used to assess norepinephrine release since it permits continuous assessment of neurotransmitter release in vivo from a specific brain region Ungerstedt et al.

Figure illustrates the effects of stress and supplemental tyrosine under these conditions. The combination of cold and restraint stress substantially increased the release of norepinephrine in the hippocampus over baseline levels; when animals were pretreated with tyrosine, the magnitude of the increase was substantially amplified Lieberman and Shukitt-Hale, To evaluate the hypothesis that supplemental tyrosine can prevent some adverse behavioral and physiological effects of exposure to various acute stressors, a number of animal and human studies have been conducted for reviews, see Lieberman, ; Owasoyo et al.

In general, the results of these studies suggest that tyrosine administration, particularly when the stress is severe, will have beneficial effects on the ability of the organism to function adequately. Testing conditions, in min intervals, are specified on the x-axis.

Source: Adapted from more In some of the initial studies, rats were exposed to foot shock, and their spontaneous behavior was assessed Lehnert et al.

In these studies, rats that were pretreated with tyrosine were more active and appeared to be less debilitated following exposure to the stressor. In other animal studies in which high doses of tyrosine were administered, learning and memory, as well as other aspects of performance in the cold and under high-altitude conditions, were improved Ahlers, et al.

In addition, tyrosine has been shown to have beneficial effects in animals exposed to heat stress by reducing immobility, the dependent measure in the Porsolt swim test Yeghiayan, in press; Figure In human studies, tyrosine has been found to have positive effects on cognitive performance during exposure to a combination of cold and high-altitude stress as well as cold stress alone Banderet and Lieberman, ; Shurtleff et al.

Tyrosine also appears to enhance performance of individuals exposed to psychological stress Figure Deijen and Orlebeke, These human studies are consistent with neurochemical and behavioral studies of animals that also suggest that tyrosine has beneficial effects on the ability of animals to cope with acute stress and can improve performance on tasks requiring attention and learning.

Although not directly addressing the issue of dietary requirements for tyrosine, these studies indicate that there may be an increased CNS requirement for this amino acid during periods of intense stress. Effect of heat stress and tyrosine on performance of rats in the Porsolt swim test.

Increased immobility mean difference in immobility indicates inability of the animal to respond appropriately to the heat stressor. Source: Adapted from Yeghiayan, in more Source: Adapted from Deijen and Orlebeke Several years ago, as part of a U.

Army Research Institute of Environmental Medicine USARIEM field study of an experimental lightweight ration, the relationship between plasma amino acid levels and mental performance was assessed.

The light weight ration tested, termed the Ration, LightWeight RLW , was intended to be the sole source of nutrition for soldiers operating without logistical support for up to 30 days Askew et al. The ration was nutritionally balanced but calorie energy deficient since it provided only 2, kcal of energy per day.

In this study, which was conducted under temperate climatic conditions, the RLW was compared with the standard Army field ration—the Meal, Ready-to-Eat MRE-Version VI.

The macronutrient intake of soldiers consuming the two types of rations, as well as the actual mean daily energy expenditure of the soldiers in each group can be found in Table The individuals receiving the RLW ration had a substantial daily energy deficit of over 1, kcal, while the control group's energy intake was only several hundred kcal below their daily energy expenditure level.

At the start and conclusion of the study, two standard tests of cognitive performance previously shown to be sensitive to the effects of nutritional parameters simple visual reaction time and four-choice visual reaction time were administered to the soldiers.

In addition, on the same day that performance was assessed, blood samples were drawn and plasma amino acids determined. Plasma levels of both tryptophan and tyrosine were reduced substantially Figures and over the course of the study among the soldiers consuming the RLW ration.

To ascertain whether changes in plasma levels of either tryptophan or tyrosine were related to behavioral function during this field study, changes in the ratio of tryptophan and tyrosine to the other LNAAs were computed and correlated with changes in performance. Plasma ratios are believed to be a better indicator of transport of amine acids across the BBB than absolute levels of an amine acid because of the previously noted competition of similar amine acids for a common carrier Pardridge, There were significant correlations between both types of performance and the tryptophan to other LNAAs ratio but not the tyrosine ratio Figure Lieberman et al.

This indicates that under conditions of undernutrition, tryptophan may be the best indicator of changes in mental performance. Therefore, maintaining adequate tryptophan levels may be particularly important when the optimal amino acid content of field rations is under consideration.

This is consistent with the data discussed above, indicating that decrements in plasma tryptophan induced by administration of a single tryptophan-deficient meal can substantially increase depression and aggression and alter arousal in normal volunteers Cleare and Bond, ; Smith et al.

Although a significant correlation between tyrosine levels and performance was not observed during this field study, the research was conducted in a relatively nonstressful environment, not under conditions where the influence of tyrosine on central catecholamines is likely to be important.

Mean Daily Nutrient Intakes of the Standard Field Ration and Lightweight Ration Groups for 30 Days of a Field Study. Plasma tryptophan levels in soldiers consuming either a lightweight ration or standard field rations the MRE over the course of a day field study conducted in a temperate climate.

Source: Adapted from Lieberman et al. Plasma tyrosine levels in soldiers consuming either a lightweight ration or standard field rations the MRE over the course of a day field study conducted in a temperate climate.

Relationship between changes in plasma: tryptophan ratio and two tests of cognitive performance in soldiers consuming either a lightweight ration or standard field rations the MRE over the course of a day field study conducted in a temperate climate. Maintenance of appropriate plasma concentration of at least one amine acid, tryptophan, the precursor of serotonin, is essential for optimal brain function and cognitive performance.

Substantial decreases or increases in the typical levels of tryptophan present in the plasma will substantially disrupt normal behavior and brain function. Reduced plasma tryptophan increases depression and aggression, while increases in this amine acid induce drowsiness and decrease pain sensitivity.

The optimal range for plasma and brain tryptophan levels has not been established in humans or any other species, nor has the daily requirement for this amine acid been determined with respect to its effects on brain function.

Administration of tyrosine, precursor of the catecholamines including norepinephrine, has been shown to prevent some of the adverse neurochemical and behavioral effects of exposure to acute stress.

Optimal plasma and brain levels of this amine acid may be less critical than that of tryptophan, except under stressful conditions. Of course, such conditions are of great relevance to the development of optimal military rations. The possible importance of other amine acids such as histidine, arginine, or threonine to the regulation of behavior is currently not known.

Given the importance of optimal cognitive function to soldiers and the documented relationship between several amine acids and brain function, studies to quantify CNS requirements for specific amine acids under conditions of metabolic, environmental, and psychological stress are required.

Such studies could provide the basis for optimizing the amine acid content of field rations intended for use in extremely stressful combat conditions. Development of methods to evaluate CNS requirements for specific amine acids under normal and adverse circumstances is also necessary.

Consideration should be given to conducting further animal research using techniques such as microdialysis to assess release of brain transmitters under various environmentally and nutritionally stressful conditions, including undernutrition, thermal stress, hypoxia, and psychological stress. A recent consensus report by an international working group on protein and amine acid requirements concluded that ''Amine acid requirements at all ages require further investigation.

Such studies should include consideration of amine acid use for processes other than protein deposition" Working Group, Given the importance of the neurotransmitter precursors for the CNS, it is recommended that some of these functional measures be behavioral.

Specifically, functional outcome measures based on behavioral and other CNS end points should be considered as potentially critical measures of amine acid and protein requirements, particularly when the amine acid in question is known to affect brain function.

When humans are exposed to stressors such as extreme environmental conditions, intense exercise, or psychological stress, the importance of brain requirements for amino acids may be relatively greater than under optimal physiological conditions. ROBERT NESHEIM: I will take one question if anybody has a quick one, and then I think we need to take a break.

GERALD COMBS: Since tryptophan is the least abundant amino acid in most proteins and would be the most constant, its relationship to total protein would be more nearly the same than any other amino acid.

Do you think that might be part of the reason why it was the only one that was correlated with function? HARRIS LIEBERMAN: It is hard to say, because tryptophan has other unique characteristics.

I think the fact that it is precursor dependent with regard to variations in protein to carbohydrate ratio, could also be an important factor. But, yes, it is quite possible. You are right there. Harris R. Lieberman, U. Army Research Institute of Environmental Medicine, Natick, MA Turn recording back on.

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Show details Institute of Medicine US Committee on Military Nutrition Research. Contents Hardcopy Version at National Academies Press. Search term. Lieberman 1 Introduction This chapter addresses amino acid and protein requirements and brain function. 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.

TABLE CNS Amino Acid Transport Mechanisms. TABLE Putative Functions of Various Neurotransmitter Systems with Amino Acid Precursors. Tryptophan Tryptophan is the rarest of the essential amino acids found in food and, as noted above, is the precursor of serotonin.

Figure Effects of a single tryptophan deficient meal on self-reported depression and plasma tryptophan levels of healthy volunteers. Figure Effects of tryptophan-depleted and -supplemented meals on subjective and objective measures of aggression among normal, high-trait aggressive volunteers.

Tyrosine Another amino acid that has been extensively examined for behavioral effects is tyrosine, the precursor of three neurotransmitters: norepinephrine, dopamine, and epinephrine see Table Figure Effect of heat stress and tyrosine on performance of rats in the Porsolt swim test.

Changes in Amino Acids During Field Studies: Undernutrition and Mental Performance Several years ago, as part of a U. TABLE Mean Daily Nutrient Intakes of the Standard Field Ration and Lightweight Ration Groups for 30 Days of a Field Study.

Figure Plasma tryptophan levels in soldiers consuming either a lightweight ration or standard field rations the MRE over the course of a day field study conducted in a temperate climate. Figure Plasma tyrosine levels in soldiers consuming either a lightweight ration or standard field rations the MRE over the course of a day field study conducted in a temperate climate.

Figure Relationship between changes in plasma: tryptophan ratio and two tests of cognitive performance in soldiers consuming either a lightweight ration or standard field rations the MRE over the course of a day field study conducted in a temperate climate.

Author's Conclusion and Recommendations Maintenance of appropriate plasma concentration of at least one amine acid, tryptophan, the precursor of serotonin, is essential for optimal brain function and cognitive performance.

References Ahlers, S. Thomas, J. Schrot, and D. Tyrosine and glucose modulation of cognitive deficits. Marriott, editor. Institute of Medicine.

Washington, D. Askew, E. Munro, M. Sharp, S. Siegel, R. Popper, M. Rose, R. Hoyt, K. Reynolds, H. Lieberman, D. Engell, and C. Nutritional status and physical and mental performance of soldiers consuming the Ration, Lightweight or the Meal, Ready-to-Eat military field ration during a 30 day field training exercise RLW Technical Report No.

Natick, Mass. Army Research Institute of Environmental Medicine. Banderet, L. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans.

Brain Res. Betz, A. Goldstein, and R. Blood-brain-cerebrospinal fluid barriers. Siegel, editor. New York: Raven Press;. Cleare, A. Effects of alterations in plasma tryptophan levels on aggressive feelings. Psychiatry 51 12 The effect of tryptophan depletion and enhancement on subjective and behavioral aggression in normal male subjects.

Deijen, J. Effect of tyrosine on cognitive function and blood pressure under stress. Fernstrom, H. Brain tryptophan concentrations and serotonin synthesis remain responsive to food consumption after the ingestion of sequential meals. Fernstrom, J. Brain serotonin content: Physiological dependence on plasma tryptophan levels.

Science Hajak, G. Huether, J. Blanke, M. Blömer, C. Freyer, B. Poeggler, A. Reimer, A. Rodenbeck, M. Schulz-Varszegli, and E. The influence of intravenous l-tryptophan on plasma melatonin and sleep in men. Hartmann, E. Effect of l-tryptophan and other amino acids on sleep.

Objectives: To Prohein the association of Immune-boosting foods intake ffunction different sources with cognitive decline. Protein and brain function Our analysis included 3, Protein and brain function aged 55—93 years from the China Health and Nutrition Survey. Cognition was assessed in, and Diet intake was assessed using weighing methods in combination with h dietary recalls for three consecutive days at each survey. Results: Participants consumed quintile 1: 0. Can lack Funcction protein affect brain function and Energizing natural supplements brian RELATED: Protein: The Profein Story. The brain Energizing post-workout meals composed of mostly water and fatty acids. It relies on a steady stream of glucose for energy, burning through a large amount of this simple sugar each day. The brain is a finicky eater, liking mainly glucose or nothing. Protein and brain function

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