Composition and method for improving mental state of healthy individual under psychological stress

Abstract

To provide a composition capable of improving fatigue and / or discomfort in a healthy individual who perceives fatigue and stress in daily life or who is placed under psychological stress, or to provide a method capable of improving the above-mentioned fatigue and / or discomfort.SOLUTION: Provided is a composition for improving the mental state of a healthy individual under psychological stress, the composition comprising ornithine or a salt thereof as an active ingredient. The healthy individual is a healthy individual who perceives fatigue and stress in daily life. The mental state is fatigue and / or discomfort.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for improving the mental state of a healthy subject who is under psychological stress, and a method for improving the mental state of a healthy subject who is under psychological stress. [Background technology]

[0002] Ornithine has the effect of helping the ornithine cycle, which detoxifies ammonia in the liver. It is also known that the intake of ornithine can suppress the production of cortisol, a stress marker, in the hypothalamus-pituitary-adrenal system. Various studies have been conducted on the improvement of stress, fatigue, etc. by the intake of ornithine. For example, Non-Patent Document 1 discloses that when subjects who showed an increase in salivary cortisol when mental stress was applied and who responded to stress were given ornithine, the increase in cortisol was suppressed and a reduction in fatigue was confirmed by a VAS (Visual Analog Scale) questionnaire. Non-Patent Document 2 discloses that when subjects who had a T score of 50 or more on the fatigue scale and a T score of 50 or less on the vitality scale in the Profile of Mood States were selected and given ornithine, a tendency to suppress cortisol was observed, and feelings of anger and hostility and quality of sleep were improved. Patent Document 1 also discloses that administration of ornithine improves subjective fatigue symptoms as determined by a VAS questionnaire by a subject. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2007 / 040244 [Non-patent literature]

[0004] [Non-Patent Document 1] Saori Akizuki, Takayoshi Kiriyoku. "Ingredients Report: Improvement of stress and skin quality by taking L-ornithine." Food and Development = Food processing and ingredients 48.3 (2013): 97-99. [Non-Patent Document 2] Miyake M, et al.,"Randomised controlled trial of the effects of L-ornithine on stressmarkers and sleep quality in healthy workers." Nutrition journal 13.1(2014): 1-8. Summary of the Invention [Problem to be solved by the invention]

[0005] In recent years, with the spread of COVID-19 and the associated changes in living environment due to the acceleration of digitalization, the number of healthy people who feel fatigue and stress in daily life is increasing.Therefore, it is necessary to improve the mental state of such healthy people, such as fatigue and discomfort, when they are under psychological stress.However, the above-mentioned research on ornithine has not been conducted on healthy people who feel both fatigue and stress in daily life, or on the above-mentioned healthy people under psychological stress, and the effect of ornithine on such healthy people is unknown.

[0006] The present invention has been made in consideration of the above circumstances, and aims to provide a composition capable of improving the fatigue and / or discomfort felt by healthy individuals who are aware of fatigue and stress in their daily lives, or by such healthy individuals who are under psychological stress, or to provide a method capable of improving the fatigue and / or discomfort. [Means for solving the problem]

[0007] Means for Solving the Problems The present inventors have conducted extensive research and found that ornithine or a salt thereof can improve the sense of fatigue and / or discomfort felt by healthy individuals who are aware of fatigue and stress in their daily lives when they are subjected to psychological stress, thereby completing the present invention.

[0008] The present invention provides, for example, the following inventions. [1] A composition for improving the mental state of a healthy person under psychological stress, comprising ornithine or a salt thereof as an active ingredient, The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, The composition, wherein the mental state is fatigue and / or discomfort. [2] The composition described in [1], wherein the psychological stress is psychological stress caused by face-to-face communication. [3] The above-mentioned healthy person, A healthy individual with a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition, and The composition according to [1] or [2], which is for a healthy subject whose salivary cortisol concentration increases by 0.05 nmol / L or more in the Trier Social Stress Test. [4] The composition according to any one of [1] to [3], wherein the fatigue and / or discomfort is at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-lowering, fatigue-lethargic feeling, and tension-anxiety. [5] The composition according to any one of [1] to [4], which is used so as to be ingested or administered at a rate of 1,000 to 2,000 mg per day in terms of ornithine. [6] The composition according to any one of [1] to [5], which is intended to be ingested or administered for 8 or more consecutive days. [7] The composition according to any one of [1] to [6], wherein the fatigue and / or discomfort is fatigue and / or discomfort upon waking up the morning after the day on which the psychological stress is experienced. [8] A method for improving the mental state of a healthy individual subjected to psychological stress, comprising: The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, The mental state is fatigue and / or discomfort, A method comprising having the healthy subject ingest or administer to the healthy subject a composition containing ornithine or a salt thereof as an active ingredient. [9] A method for selecting healthy subjects whose mental state is expected to improve by ingestion or administration of ornithine or a salt thereof when subjected to psychological stress, comprising: The mental state is fatigue and / or discomfort, Selecting healthy subjects having a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition; and selecting healthy subjects whose salivary cortisol concentration increases by 0.05 nmol / L or more by the Trier Social Stress Test.

[10] A method for determining whether or not a healthy individual is expected to have an improved mental state by taking or administering ornithine or a salt thereof when subjected to psychological stress, comprising: The mental state is fatigue and / or discomfort, A fatigue-lethargy T-score of 35 or greater and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition; and Healthy subjects with an increase in salivary cortisol concentration of 0.05 nmol / L or more in the Trier Social Stress Test were A method for determining whether a person is a healthy individual whose mental state is expected to improve by taking or administering ornithine or a salt thereof when the person is under psychological stress.

[11] Ornithine or a salt thereof for use in a therapeutic method for improving the mental state of a healthy subject under psychological stress, The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, The ornithine or a salt thereof, wherein the mental state is fatigue and / or discomfort.

[12] Use of ornithine or a salt thereof in a non-therapeutic method for improving the mental state of a healthy subject under psychological stress, comprising: The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, The use, wherein the mental state is fatigue and / or discomfort.

[13] Use of ornithine or a salt thereof for producing a composition for improving the mental state of a healthy subject under psychological stress, comprising: The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, The use, wherein the mental state is fatigue and / or discomfort.

[14] The method, ornithine or a salt thereof, or use thereof according to any one of [8] to

[13] , wherein the psychological stress is psychological stress caused by face-to-face communication.

[15] The above-mentioned healthy person, A healthy individual with a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition, and The method, ornithine or a salt thereof, or use thereof according to any one of [8] to

[14] , in a healthy subject in which the salivary cortisol concentration increases by 0.05 nmol / L or more as a result of the Trier Social Stress Test.

[16] The method, ornithine or a salt thereof, or use thereof according to any one of [8] to

[15] , wherein the fatigue and / or discomfort is at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-dejection, fatigue-lethargic feeling, and tension-anxiety.

[17] The method, ornithine or a salt thereof, or use according to any of [8] to

[16] , wherein the amount is such that 1,000 to 2,000 mg of ornithine is ingested or administered per day.

[18] The method, ornithine or a salt thereof, or use according to any one of [8] to

[17] , which is to be ingested or administered for 8 or more consecutive days.

[19] The method, ornithine or a salt thereof, or use according to any one of [8] to

[18] , wherein the fatigue and / or discomfort is fatigue and / or discomfort upon waking up the morning after the day on which the psychological stress is exerted.

[20] A composition for improving the mental state of a healthy subject, comprising ornithine or a salt thereof as an active ingredient, The mental state is fatigue and / or discomfort, The composition, wherein the improvement in mental condition is independent of cortisol suppression.

[21] The composition described in

[20] , wherein the healthy subject is a healthy subject subjected to psychological stress.

[22] The composition described in

[21] , wherein the psychological stress is psychological stress caused by face-to-face communication.

[23] The above-mentioned healthy person, A healthy individual with a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition, and The composition according to any one of

[20] to

[22] , which is for a healthy subject whose salivary cortisol concentration increases by 0.05 nmol / L or more in the Trier Social Stress Test.

[24] The composition described in any of

[20] to

[23] , wherein the fatigue and / or discomfort is at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-lowering, fatigue-lethargic feeling, and tension-anxiety.

[25] The composition according to any one of

[20] to

[24] , which is used so as to be ingested or administered at a rate of 1,000 to 2,000 mg per day in terms of ornithine.

[26] The composition according to any one of

[20] to

[25] , which is intended to be ingested or administered for 8 or more consecutive days.

[27] The composition described in any of

[21] to

[26] , wherein the fatigue and / or discomfort is fatigue and / or discomfort upon waking up the morning after the day on which the psychological stress is experienced.

[28] A method for improving the mental state of a healthy individual, comprising: The mental state is fatigue and / or discomfort, The improvement in the mental state is independent of cortisol suppression, A method comprising having the healthy subject ingest or administer to the healthy subject a composition containing ornithine or a salt thereof as an active ingredient.

[29] A method for selecting healthy subjects whose mental state is expected to improve by ingestion or administration of ornithine or a salt thereof, comprising: The mental state is fatigue and / or discomfort, The improvement in the mental state is independent of cortisol suppression, Selecting healthy subjects having a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition; and selecting healthy subjects whose salivary cortisol concentration increases by 0.05 nmol / L or more by the Trier Social Stress Test.

[30] A method for determining whether or not a person is a healthy individual whose mental state can be expected to improve by taking or administering ornithine or a salt thereof, comprising: The mental state is fatigue and / or discomfort, The improvement in the mental state is independent of cortisol suppression, A fatigue-lethargy T-score of 35 or greater and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition; and Healthy subjects with an increase in salivary cortisol concentration of 0.05 nmol / L or more in the Trier Social Stress Test were A method for determining whether a subject is a healthy individual whose mental state is expected to improve by taking or administering ornithine or a salt thereof.

[31] Ornithine or a salt thereof for use in a therapeutic method for improving the mental state of a healthy subject, comprising: The mental state is fatigue and / or discomfort, Ornithine or a salt thereof, wherein the improvement of the mental state is independent of cortisol suppression.

[32] Use of ornithine or a salt thereof in a non-therapeutic method for improving the mental state of a healthy subject, comprising: The mental state is fatigue and / or discomfort, The improvement of the mental state is independent of cortisol suppression.

[33] Use of ornithine or a salt thereof for the manufacture of a composition for improving the mental state of a healthy subject, comprising: The mental state is fatigue and / or discomfort, The improvement of the mental state is independent of cortisol suppression.

[34] The method, ornithine or a salt thereof, or use according to any of

[28] to

[33] , wherein the healthy subject is a healthy subject under psychological stress.

[35] The method, ornithine or a salt thereof, or use thereof according to

[34] , wherein the psychological stress is psychological stress caused by face-to-face communication.

[36] The above-mentioned healthy person, A healthy individual with a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition, and The method, ornithine or a salt thereof, or use thereof according to any one of

[28] to

[35] , in a healthy subject in which the salivary cortisol concentration increases by 0.05 nmol / L or more as a result of the Trier Social Stress Test.

[37] The method, ornithine or a salt thereof, or use thereof according to any of

[28] to

[36] , wherein the fatigue and / or discomfort is at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-dejection, fatigue-lethargic feeling, and tension-anxiety.

[38] The method, ornithine or a salt thereof, or use according to any of

[28] to

[37] , wherein the amount is ingested or administered in an amount equivalent to 1,000 to 2,000 mg per day in terms of ornithine.

[39] The method, ornithine or a salt thereof, or use according to any of

[28] to

[38] , which is to be ingested or administered for 8 consecutive days or more.

[40] The method, or use of ornithine or a salt thereof according to any of

[34] to

[39] , wherein the fatigue and / or discomfort is fatigue and / or discomfort upon waking up the morning after the day on which the psychological stress is exerted. Effect of the Invention

[0009] According to the present invention, it is possible to provide a composition capable of improving the fatigue and / or discomfort felt by healthy individuals who are aware of fatigue and stress in their daily lives, or by such healthy individuals who are under psychological stress, or to provide a method capable of improving the fatigue and / or discomfort. [Brief description of the drawings]

[0010] [Figure 1] 1 is a graph showing the concentration of cortisol in saliva before and after the Trier Social Stress Test (hereinafter also referred to as "TSST") when subjects took an ornithine-containing tablet or a placebo tablet. [Diagram 2] 2 is a graph showing the integrated values ​​of salivary cortisol concentration from 45 minutes before the start of the TSST to 140 minutes after the start of the TSST in FIG. 1. [Diagram 3] This is a graph showing the change in T scores obtained from the Japanese version of the Profile of Mood States second edition-Adult short when subjects took ornithine-containing tablets or placebo tablets, based on 45 minutes before the start of the TSST. (A) is anger-hostility, (B) is confusion-perplexity, (C) is depression-depression, (D) is fatigue-lethargy, (E) is tension-anxiety, (F) is vigor-vitality, (G) is friendliness, and (H) is the change in T scores of the TMD score. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] A composition according to one aspect of this embodiment is a composition for improving the mental state of a healthy individual who is under psychological stress, wherein the healthy individual is a healthy individual who is aware of fatigue and stress in daily life, the mental state is fatigue and / or discomfort, and the composition contains ornithine or a salt thereof as an active ingredient.

[0012] Another aspect of the present embodiment is a composition for improving the mental state of a healthy person, the mental state being fatigue and / or discomfort, the effect of improving the mental state being independent of cortisol suppression, and containing ornithine or a salt thereof as an active ingredient. In the composition, the healthy person may be a healthy person who is under psychological stress. In addition, in the composition, the healthy person may be a healthy person who is aware of fatigue and stress in daily life.

[0013] A method according to yet another aspect of this embodiment is a method for improving the mental state of a healthy individual who is under psychological stress, the healthy individual being a healthy individual who is aware of fatigue and stress in daily life, the mental state being fatigue and / or discomfort, and comprising having the healthy individual ingest or administer to the healthy individual a composition containing ornithine or a salt thereof as an active ingredient.

[0014] A method according to yet another aspect of the present embodiment is a method for improving the mental state of a healthy person, the mental state being fatigue and / or discomfort, the effect of improving the mental state being independent of cortisol suppression, and comprising the healthy person taking or administering a composition containing ornithine or a salt thereof as an active ingredient to the healthy person. In the method, the healthy person may be a healthy person who is under psychological stress. In addition, in the composition, the healthy person may be a healthy person who is aware of fatigue and stress in daily life.

[0015] In this specification, the "psychological stress" may be a psychological stress in daily life. Examples of psychological stress in daily life include a speech in front of a person who does not know the person, mental arithmetic in front of a person who does not know the person, a stress caused by face-to-face communication such as a meeting that requires constant attention, and a stress caused by child rearing that requires constant attention. The "psychological stress" can be experimentally imposed by the Trier Social Stress Test (Kirschbaum C, et al., "The 'Trier SocialStress Test'-a tool for investigating psychobiological stress responses in a laboratory setting." Neuropsychobiology 28.1-2 (1993): 76-81. Hereinafter, also referred to as "TSST"). That is, a healthy subject subjected to the TSST is a healthy subject subjected to a psychological stress. A healthy subject subjected to the TSST can also be said to be a healthy subject subjected to a psychological stress caused by face-to-face communication. Specifically, the TSST may be performed by the method described in the Examples below.

[0016] In the present specification, the term "mental state" refers to a feeling of fatigue and / or discomfort. The feeling of fatigue may be fatigue-apathy. Examples of fatigue-apathy include fatigue, apathy, feeling exhausted, tired, worn out, fed up, and exhausted. The discomfort may be at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-depression, and tension-anxiety. Examples of anger-hostility include feelings of anger, hostility, getting angry, being sulky, feeling extremely angry inside, feeling intense anger, and getting angry easily. Examples of confusion-bewilderment include feelings of confusion, bewilderment, confusion in the head, being unable to concentrate, not being able to organize one's thoughts, being at a loss, and not being sure about things. Examples of depression-depression include feelings of depression, depression, sadness, hopelessness, feeling miserable, being unable to do anything by oneself, feeling worthless, and the like. Examples of tension-anxiety include feelings of tension, anxiety, being on edge, feeling flustered, feeling uneasy, feeling nervous, being worried about things, etc. In the present specification, the effect of "improving discomfort" may also be the effect of "supporting a calm feeling."

[0017] In this specification, "fatigue and / or discomfort" may be evaluated by a T-score for at least one selected from the group consisting of anger-hostility, confusion-perplexity, depression-depression, fatigue-lethargy, tension-anxiety, and Total Mood Disturbance (hereinafter also referred to as "TMD score") obtained by the Profile of Mood States 2nd Edition (Heuchert JP, et al., "POMS: Profile of Mood States Second Edition. Tonawanda", Multi-Health Systems Inc., 2012. Hereinafter also referred to as "POMS2"). The T-score is a score obtained by converting the raw score obtained in POMS2 by a known method so that the average score is 50 and the standard deviation is 10 when the population is Japanese. For example, a high T-score for fatigue-lethargy means a strong sense of fatigue. In this specification, POMS2 may be the Japanese version of the Profile of Mood States second edition-Adult short (Konuma H, et al., "Relationship of the Japanese translation of the profile of mood states second edition (POMS 2) to the first edition (POMS)." Juntendo Medical Journal 61.5 (2015): 517-519.). Specifically, POMS2 may be performed by the method described in the Examples below.

[0018] In the present specification, the term "healthy individual" is not particularly limited, but may be an individual who does not have a chronic physical illness, an individual who does not suffer from a serious illness such as a metabolic disease, etc. Furthermore, the age of the "healthy individual" may be 20 to 60 years old.

[0019] In the present specification, "a healthy person who is aware of fatigue and stress in daily life" includes a healthy person who is easily aware of fatigue and stress in daily life. Examples of a healthy person who is aware of stress in daily life include a healthy person who has subjective symptoms such as nervousness, blushing, and increased heart rate when speaking in front of others, and / or feels stress.

[0020] The composition according to the present embodiment can improve the mental state of a healthy person, for example, the mental state of a healthy person who is aware of fatigue and stress in daily life after a psychological load is applied. The effect of improving the mental state is, for example, 30 minutes after the psychological load is applied, and is more effective until the morning after the day of the psychological load is woken up, and is even more effective when the morning after the day of the psychological load is woken up. The effect of improving the mental state is more effective for anger-hostility and fatigue-lethargy among the mental states. The effect of improving the mental state is particularly effective for anger-hostility and fatigue-lethargy among the mental states when the morning after the day of the psychological load is woken up.

[0021] The above-mentioned improving effect is more effectively achieved in healthy individuals who are aware of fatigue and stress in their daily lives, who have a fatigue-lethargy T score of 35 or more and / or a vigor-vitality T score of 60 or less as assessed by POMS2, and who have a salivary cortisol concentration increased by 0.05 nmol / L or more as assessed by TSST. In this case, the above-mentioned improving effect is more effectively achieved when the healthy individual is a healthy individual who has a fatigue-lethargy T score of 35 or more and a vigor-vitality T score of 60 or less as assessed by POMS2, or a healthy individual who has a salivary cortisol concentration increased by 0.08 nmol / L or more as assessed by TSST, and is particularly effectively achieved when the healthy individual is a healthy individual who has a fatigue-lethargy T score of 35 or more and a vigor-vitality T score of 60 or less as assessed by POMS2, and who has a salivary cortisol concentration increased by 0.08 nmol / L or more as assessed by TSST. The measurement of the cortisol concentration in saliva is performed by a chemiluminescence immunoassay. The evaluation of the fatigue-lethargy T-score and the vigor-vitality T-score by POMS2 may be performed specifically by the method described in the Examples. The TSST may be performed specifically by the method described in the Examples below. The increase in the cortisol concentration in saliva by the TSST may be evaluated, for example, by using the salivary cortisol concentration 45 or more years before the start of the TSST as a baseline, and calculating the difference between the baseline and the maximum salivary cortisol concentration after the TSST. The measurement of the cortisol concentration in saliva and the evaluation of the increase in the cortisol concentration in saliva by the TSST may be performed specifically by the method described in the Examples below.

[0022] It is known that ornithine, depending on the subject of ingestion or administration, can reduce the concentration of cortisol in saliva and suppress the increase in the concentration of cortisol in saliva when placed under psychological stress (for example, Non-Patent Document 2). However, as shown in the examples described below, the composition according to this embodiment can improve the above-mentioned mental state without significantly affecting the concentration of cortisol in the saliva of a healthy person who is aware of fatigue and stress in daily life before and after psychological stress. That is, the composition according to this embodiment can improve the above-mentioned mental state independently of the suppression of cortisol. Therefore, it is considered that the ingestion or administration of the composition according to this embodiment to a healthy person who is aware of fatigue and stress in daily life does not weaken the functions of cortisol, such as glucogenesis in the liver, protein metabolism in muscles, and promotion of metabolism such as fat decomposition in adipose tissue, anti-inflammation, and immunosuppression.

[0023] The content of ornithine or a salt thereof in the composition according to the present embodiment may be 1 to 95% by mass, or 10 to 80% by mass. The composition according to the present embodiment may consist of ornithine or a salt thereof.

[0024] Ornithine includes L-ornithine and D-ornithine, with L-ornithine being preferred.

[0025] The salt of ornithine is not particularly limited, but may be a pharma- ceutically acceptable salt, for example, salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; salts with organic acids such as acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, malic acid, lactic acid, stearic acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, α-ketoglutaric acid, gluconic acid, caprylic acid, etc.; salts with alkali metals such as sodium and potassium; salts with aluminum; salts with zinc; salts with alkaline earth metals such as calcium and magnesium; salts with ammonium such as ammonium and tetramethylammonium; salts with organic amines such as morpholine and piperidine; salts with amino acids such as glycine, L-phenylalanine, L-lysine, L-aspartic acid, and L-glutamic acid. As the salt of ornithine, the salt of L-ornithine is preferred, and L-ornithine hydrochloride is more preferred.

[0026] Ornithine or a salt thereof may be produced by a known chemical synthesis method, may be produced by a known fermentation method, or may be generally commercially available. Examples of the chemical synthesis method include the method described in Zaoral M, et al., Amino-acids and peptides. XXV. Dehydration of derivatives of asparagine and glutamine; A new route to α, γ-diaminobutyricacid, ornithine, and arginine. Collection of Czechoslovak Chemical Communications 24.6 (1959): 1993-2012. Examples of the fermentation method include the method described in JP-A-53-24096 or JP-A-61-119194. Examples of generally commercially available ornithine include L-ornithine hydrochloride, etc., which is commercially available from Kyowa Hakko Bio Co., Ltd.

[0027] The composition according to this embodiment may be a pharmaceutical composition or a food composition.

[0028] When the composition according to the present embodiment is a pharmaceutical composition, it may be orally administered, for example, as a tablet, capsule, powder, granule, liquid or syrup, or parenterally administered, for example, as an injection, infusion or suppository. Parenteral administration includes, for example, intravenous, intraperitoneal, subcutaneous administration, etc. Oral administration is preferred because it can be administered easily.

[0029] When the composition according to the present embodiment is a solid pharmaceutical composition, it may contain pharma- ceutically acceptable excipients, lubricants, binders, disintegrants, coating agents, colorants, surfactants, etc., as necessary. Examples of pharma- ceutically acceptable excipients include starch, lactose, refined sucrose, glucose, microcrystalline cellulose, crystalline cellulose, carboxycellulose, carboxymethylcellulose, carboxyethylcellulose, calcium phosphate, magnesium stearate, gum arabic, etc. Examples of pharma-ceutically acceptable binders include hydroxypropylcellulose, etc. Examples of pharma-ceutically acceptable surfactants include glycerin fatty acid esters, etc.

[0030] When the composition according to the present embodiment is a liquid pharmaceutical composition, it may contain pharma- ceutically acceptable stabilizers, dissolution aids, suspending agents, emulsifiers, buffers, preservatives, and the like, as necessary.

[0031] The dosage of the composition according to this embodiment as a pharmaceutical composition varies depending on the degree to which the patient is aware of fatigue and stress in daily life, mental state, psychological stress, age, body weight, administration method, dosage form, etc., but may be, for example, 1000 to 2000 mg or 1400 to 1800 mg in terms of ornithine administered to an adult per day, and may be administered in a single dose or in several divided doses.

[0032] The administration period of the composition according to this embodiment as a pharmaceutical product is not particularly limited, and may be, for example, administered for 8 or more consecutive days.

[0033] The formulation of the composition according to the present embodiment as a pharmaceutical composition may be carried out by a known method. When the composition according to the present embodiment as a pharmaceutical composition is formulated into a tablet, for example, ornithine or a salt thereof may be granulated by fluidized bed granulation or the like, and the granulated product may be compressed to form a tablet. In the above-mentioned fluidized bed granulation, ornithine or a salt thereof and an excipient may be fluidized and mixed as necessary, or a binder may be sprayed onto ornithine or a salt thereof. In the above-mentioned compression molding, the mixture of the above-mentioned granulated product, surfactant, excipient, etc. may be compressed and molded.

[0034] When the composition according to the present embodiment is a food composition, it may contain ingredients that are acceptable as food, if necessary. The ingredients that are acceptable as food are not particularly limited, but include, for example, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, excipients, coating agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, preservatives, sustained-release regulators, surfactants, dissolving agents, humectants, etc. Examples of excipients that are acceptable as food include starch, lactose, refined white sugar, glucose, microcrystalline cellulose, crystalline cellulose, carboxycellulose, carboxymethylcellulose, carboxyethylcellulose, calcium phosphate, magnesium stearate, gum arabic, etc. Examples of binders that are acceptable as food include hydroxypropylcellulose, etc. Examples of surfactants that are acceptable as food include glycerin fatty acid esters, etc.

[0035] When the composition according to this embodiment is a food composition, it may be in the form of a powder, granules, pellets, tablets, liquid, or the like.

[0036] The composition according to the present embodiment as a food composition may be produced by a known method. When the composition according to the present embodiment as a food composition is formulated into a tablet, for example, ornithine or a salt thereof may be granulated by fluidized bed granulation or the like, and the granulated product may be compressed to form a tablet. In the above-mentioned fluidized bed granulation, ornithine or a salt thereof and an excipient may be fluidized and mixed as necessary, or a binder may be sprayed onto ornithine or a salt thereof. In the above-mentioned compression molding, the mixture of the above-mentioned granulated product, surfactant, excipient, etc. may be compressed and molded.

[0037] The composition according to the present embodiment can also be used as a food additive, and can be added to known foods and beverages.The foods and beverages are not particularly limited, and can be added to, for example, beverages such as juice, soft drinks, tea, and lactic acid bacteria beverages; dairy products such as butter, cheese, yogurt, processed milk, and skim milk; meat products such as ham, sausage, and hamburger; fish paste products such as kamaboko, chikuwa, and satsumaage; egg products such as dashi omelet and egg tofu; confectionery such as cookies, jellies, chewing gum, candy, and snacks; bread; noodles; pickles; smoked products; dried fish; tsukudani; salted products; soups; and seasonings.

[0038] The composition according to the present embodiment as a food additive and a food composition may be orally ingested. The amount of intake varies depending on the ease of awareness of fatigue and stress in daily life, mental state, psychological stress, age, body weight, and the form of food and drink, but for example, an adult may take 1000 to 2000 mg or 1400 to 1800 mg of ornithine per day, and may take it in one dose or in several doses.

[0039] The intake period of the composition according to the present embodiment as a food additive and food composition is not particularly limited, and may be, for example, for 8 consecutive days or more.

[0040] A method according to yet another aspect of this embodiment is a method for selecting healthy subjects whose mental state is expected to improve by ingestion or administration of ornithine or a salt thereof when psychological stress is applied, comprising the steps of: selecting healthy subjects whose mental state is fatigue and / or discomfort, and whose fatigue-lethargy T-score is 35 or more and / or whose vigor-vitality T-score is 60 or less as assessed by POMS2; and selecting healthy subjects whose salivary cortisol concentration increases by 0.05 nmol / L or more as measured by TSST.

[0041] In selecting the healthy subjects, healthy subjects with a fatigue-lethargy T-score of 35 or more and a vigor-vitality T-score of 60 or less as assessed by POMS2, or healthy subjects with an increase in salivary cortisol concentration of 0.08 nmol / L or more as assessed by the TSST may be selected, or healthy subjects with a fatigue-lethargy T-score of 35 or more and a vigor-vitality T-score of 60 or less as assessed by POMS2 and an increase in salivary cortisol concentration of 0.08 nmol / L or more as assessed by the TSST may be selected.

[0042] The method may further include a step of selecting a healthy subject who is aware of fatigue and stress in daily life. In the step, a healthy subject who is aware of fatigue and stress in daily life may be selected by performing at least one selected from the group consisting of physical measurements, measurement of circulatory system parameters, blood tests, blood biochemistry tests, urine tests, and interviews by a doctor, and a healthy subject who has subjective symptoms of being easily fatigued in daily life and subjective symptoms of feeling nervous, blushing, increased heart rate, etc., and / or feeling stressed when speaking in front of others may be selected.

[0043] In the above-mentioned method, the mode of ornithine or its salt and the mode of ornithine or its salt being taken or administered can be the same as that in the composition according to the present embodiment described above.In the above-mentioned method, the measurement of the cortisol concentration in saliva can be carried out by chemiluminescence immunoassay, specifically, can be carried out by the method described in the following examples.

[0044] A further aspect of the method of this embodiment is a method for determining whether or not a healthy subject is one whose mental state can be expected to improve by ingestion or administration of ornithine or a salt thereof when psychological stress is applied, in which a healthy subject whose mental state is fatigue and / or discomfort, whose fatigue-lethargy T-score is 35 or more and whose vigor-vitality T-score is 60 or less as assessed by POMS2, and whose salivary cortisol concentration increases by 0.05 nmol / L or more by TSST is determined to be a healthy subject whose mental state can be expected to improve by ingestion or administration of ornithine or a salt thereof when psychological stress is applied.

[0045] In the above method, the healthy person may be a healthy person who is aware of fatigue and stress in daily life. Whether or not a person is aware of fatigue and stress in daily life may be determined by performing at least one selected from the group consisting of physical measurements, measurement of circulatory system parameters, blood tests, blood biochemistry tests, urine tests, and interviews by a doctor. In addition, a healthy person who has subjective symptoms of being easily fatigued in daily life and subjective symptoms such as tension, blushing, and increased heart rate when speaking in front of others and / or feeling stressed may be a healthy person who is aware of fatigue and stress in daily life.

[0046] In the above-mentioned method, the mode of ornithine or its salt and the mode of ornithine or its salt being taken or administered can be the same as that in the composition according to the present embodiment described above.In the above-mentioned method, the measurement of the cortisol concentration in saliva can be carried out by chemiluminescence immunoassay, specifically, can be carried out by the method described in the following examples.

[0047] A method according to yet another aspect of this embodiment is a method for selecting healthy subjects whose mental state is expected to improve by ingestion or administration of ornithine or a salt thereof, comprising the steps of: selecting a healthy subject whose mental state is fatigue and / or discomfort, whose improvement in the mental state is independent of cortisol suppression, and whose fatigue-lethargy T-score is 35 or more and / or whose vigor-vitality T-score is 60 or less, as assessed by POMS2; and selecting a healthy subject whose salivary cortisol concentration increases by 0.05 nmol / L or more by TSST.

[0048] In selecting the healthy subjects, healthy subjects with a fatigue-lethargy T-score of 35 or more and a vigor-vitality T-score of 60 or less as assessed by POMS2, or healthy subjects with an increase in salivary cortisol concentration of 0.08 nmol / L or more as assessed by the TSST may be selected, or healthy subjects with a fatigue-lethargy T-score of 35 or more and a vigor-vitality T-score of 60 or less as assessed by POMS2 and an increase in salivary cortisol concentration of 0.08 nmol / L or more as assessed by the TSST may be selected.

[0049] The method may further include a step of selecting a healthy subject who is aware of fatigue and stress in daily life. In the step, a healthy subject who is aware of fatigue and stress in daily life may be selected by performing at least one selected from the group consisting of physical measurements, measurement of circulatory system parameters, blood tests, blood biochemistry tests, urine tests, and interviews by a doctor, and a healthy subject who has subjective symptoms of being easily fatigued in daily life and subjective symptoms of feeling nervous, blushing, increased heart rate, etc., and / or feeling stressed when speaking in front of others may be selected.

[0050] In the above-mentioned method, the mode of ornithine or its salt and the mode of ornithine or its salt being taken or administered can be the same as that in the composition according to the present embodiment described above.In the above-mentioned method, the measurement of the cortisol concentration in saliva can be carried out by chemiluminescence immunoassay, specifically, can be carried out by the method described in the following examples.

[0051] A method according to yet another aspect of this embodiment is a method for determining whether or not a healthy subject is one whose mental state can be expected to improve by ingestion or administration of ornithine or a salt thereof, in which a healthy subject is determined to be one whose mental state can be expected to improve by ingestion or administration of ornithine or a salt thereof if the mental state is fatigue and / or discomfort, the improvement in the mental state is independent of cortisol suppression, the T-score for fatigue-lethargy is 35 or more and the T-score for vigor-vitality is 60 or less as assessed by POMS2, and the salivary cortisol concentration increases by 0.05 nmol / L or more by TSST.

[0052] In the above method, the healthy person may be a healthy person who is aware of fatigue and stress in daily life. Whether or not a person is aware of fatigue and stress in daily life may be determined by performing at least one selected from the group consisting of physical measurements, measurement of circulatory system parameters, blood tests, blood biochemistry tests, urine tests, and interviews by a doctor. In addition, a healthy person who has subjective symptoms of being easily fatigued in daily life and subjective symptoms such as tension, blushing, and increased heart rate when speaking in front of others and / or feeling stressed may be a healthy person who is aware of fatigue and stress in daily life.

[0053] In the above-mentioned method, the mode of ornithine or its salt and the mode of ornithine or its salt being taken or administered can be the same as that in the composition according to the present embodiment described above.In the above-mentioned method, the measurement of the cortisol concentration in saliva can be carried out by chemiluminescence immunoassay, specifically, can be carried out by the method described in the following examples. EXAMPLES

[0054] The present invention will be specifically described below based on test examples, but the present invention is not limited to these.

[0055] [Evaluation of the effect of ornithine intake on improving mental state in healthy individuals] <poms2> In the following examples, POMS2 was performed using the Japanese version of the Profile of Mood States second edition-Adult short (Konuma H, et al., "Relationship of the Japanese translation of the profile of mood states second edition (POMS 2) to the first edition (POMS)." Juntendo Medical Journal 61.5 (2015): 517-519.).

[0056] <tsst> In the following examples, the TSST was carried out by the method described in Kirschbaum C, et al., The Trier Social Stress Test - a tool for investigatingpsychobiological stress responses in a laboratory setting, Neuropsychobiology. 1993; 28: 76-81. The interviewer in the TSST was a technically trained actor in order to minimize the difference in psychological load between subjects.

[0057] <Measurement of cortisol concentration in saliva samples> In the measurement of the concentration of cortisol in the saliva samples in the following examples, the saliva samples were collected using Salimetrics Oral Swab (SALIMETRICS) and stored at -80°C after collection. The concentration of cortisol in the saliva samples was measured using a Salivary Cortisol Enzyme Immunoassay Kit (SALIMETRICS). Since cortisol rises rapidly when waking up, then falls, and remains at a relatively stable low level from the afternoon onwards (Izawa S, et al., Assessment of Stress by Using Salivary Cortisol and Protocols for Saliva Sampling, J Occup Saf Health, 2010; 3(2): 119-124), all saliva samples were collected between 12:00 and 18:00 to minimize the influence of the day-night rhythm of cortisol.

[0058] <Ornithine-containing tablets and placebo tablets> In the following examples, as the ornithine-containing tablet, a tablet containing L-ornithine hydrochloride (Kyowa Hakko Bio Co., Ltd.) of 1600mg in terms of L-ornithine is used, and as the placebo tablet, a tablet containing crystalline cellulose instead of L-ornithine hydrochloride is used. The nutritional components per tablet of the ornithine-containing tablet and the placebo tablet are as shown in Table 1 below.

[0059] [Table 1]

[0060] <Selection of subjects> The study targeted healthy men and women (i.e., healthy subjects) aged 20 to 60 years old who did not have any chronic physical illnesses. Subjects who had the following subjective symptoms (1) and (2) were recruited via a preliminary questionnaire. (1) Easily fatigued in daily life (2) When speaking in front of others, you may experience physical symptoms such as nervousness, blushing, or an increased heart rate, and / or feel stressed. Furthermore, among the above subjects, subjects whose salivary cortisol concentration increased when psychological stress was applied by the TSST and who showed reactivity to stress were selected. Ultimately, 55 subjects participated in this study. The POMS2 fatigue-lethargy T-scores of the above 55 subjects were a maximum of 73, a minimum of 38, and an average of 53. The vigor-vitality T-scores were a maximum of 57, a minimum of 32, and an average of 42. In addition, the increase in salivary cortisol concentration in these subjects 30 minutes after the start of the TSST was a maximum of 24.25 nmol / L compared to before the start, a minimum of 0.08 nmol / L, and an average of 4.60 nmol / L.

[0061] <Evaluation of improvement in mental state of subjects under psychological stress due to ornithine intake> (Allocation of subjects to ornithine-containing tablet group and placebo tablet group) The 55 subjects were assigned to an ornithine-containing tablet group or a placebo tablet group by stratified randomization. The factors for stratified randomization were sex, age, baseline salivary cortisol concentration, and maximum salivary cortisol concentration after the TSST, and the assignment was performed using computer-generated random numbers. The assignment of the 55 subjects to the ornithine-containing tablet group or the placebo tablet group was kept secret from all subjects and the TSST interviewers.

[0062] (taking ornithine-containing tablets or placebo tablets) The ornithine-containing tablet intake group and the placebo tablet intake group took the ornithine-containing tablet and the placebo tablet, respectively, once a day for 8 consecutive days. On the 8th day, the intake was performed after visiting the venue where the TSST described below was conducted, and 1 hour before the start of the TSST.

[0063] (Implementation of TSST) The TSST was administered to a group taking ornithine-containing tablets and a group taking a placebo tablet.

[0064] (Measurement of salivary cortisol concentration before and after TSST) The salivary cortisol concentration of the ornithine-containing tablet group and the placebo tablet group was measured 45 minutes, 2 minutes, 21 minutes, 30 minutes, 40 minutes, 50 minutes, 80 minutes, and 140 minutes before the start of the TSST. The measurement results are shown in Figure 1, and the integral value of the salivary cortisol concentration from 45 minutes before the start of the TSST to 140 minutes after the start of the TSST in Figure 1 is shown in Figure 2.

[0065] In Figures 1 and 2, data are expressed as mean ± standard error. In Figure 1, the concentration of cortisol in saliva was compared 45 minutes before the start of TSST with other times by Dunnett's test. In Figures 1 and 2, the comparison between the subject group taking the ornithine-containing tablet and the subject group taking the placebo tablet was performed by unpaired t-test. Dunnett's test and unpaired t-test were performed by SAS (registered trademark) (SAS (registered trademark) 9.4) and SPSS (registered trademark) (Statistics 26). In the Dunnett's test and the unpaired t-test, a significant difference was considered to exist when the P value was less than 0.05. In Figure 1, * and ** indicate that the P value in the Dunnett's test is less than 0.05 and less than 0.01, respectively. In Figure 1, the P value in the unpaired t-test was 0.05 or more at all times. In Figure 2, ns indicates that the P value in the unpaired t-test is 0.05 or more. The ornithine-containing tablet group consisted of n=26, and the placebo tablet group consisted of n=29.

[0066] When comparing the ornithine-containing tablet group and the placebo tablet group, as shown in Figure 1, there was no significant difference in the salivary cortisol concentration at any time, and as shown in Figure 2, there was no significant difference in the integral value of the salivary cortisol concentration. Therefore, it was shown that the ingestion of ornithine-containing tablets does not affect the salivary cortisol concentration of the subjects under the experimental conditions. In both the ornithine-containing tablet group and the placebo tablet group, the salivary cortisol concentration was maximum 30 minutes after the start of the TSST and then decreased.

[0067] (POMS2 before and after TSST) POMS2 was administered to the ornithine-containing tablet group and the placebo tablet group 45 minutes before, 50 minutes after, and 140 minutes after the start of the TSST, and at the time of waking up the next morning after the TSST. The changes in the T scores at each time for anger-hostility, confusion-embarrassment, depression-depression, fatigue-lethargy, tension-anxiety, vigor-vitality, friendliness, and TMD score from 45 minutes before the start of the TSST are shown in Figure 3 and Table 2 below. In Figure 3, "Next Morning" means the time of waking up the next morning.

[0068] In Figure 3 and Table 2, the data are expressed as mean ± standard error. In Figure 3 and Table 2, the comparison of T scores at each time between the ornithine-containing tablet intake group and the placebo tablet intake group was performed by comparing the mean values. For example, if the mean T score of the ornithine-containing tablet intake group was smaller than the mean T score of the placebo tablet intake group, it was determined that there was a high probability that the T score would decrease due to the intake of the ornithine-containing tablet. In Figure 3, the comparison of T scores at each time between the ornithine-containing tablet intake group and the placebo tablet intake group was also performed by the Mann-Whitney U test. The Mann-Whitney U test was performed using SAS (registered trademark) (SAS (registered trademark) 9.4) and SPSS (registered trademark) (Statistics 26). In the Mann-Whitney U test, a significant difference was determined when the P value was less than 0.05. For example, if the mean T-score of the ornithine-containing tablet group was significantly smaller than that of the placebo tablet group, it was determined that the ornithine-containing tablet reduced the T-score. However, a P-value of 0.05 or more does not mean that there is no difference between the T-scores of the two groups. In Figure 3, # and * indicate that the P-values ​​in the Mann-Whitney U test are less than 0.10 and 0.05, respectively. The ornithine-containing tablet group had n=26, and the placebo tablet group had n=29.

[0069] [Table 2]

[0070] As shown in Figure 3(A), the group taking ornithine-containing tablets had lower mean T-scores of anger-hostility 50 minutes and 140 minutes after the start of the TSST, and at the time of waking up the next morning after the TSST, compared to the group taking placebo tablets, and the difference was significant at the time of waking up the next morning after the TSST. Therefore, it was shown that the intake of ornithine-containing tablets is highly likely to improve anger-hostility 50 minutes and 140 minutes after the start of the TSST, and improve anger-hostility at the time of waking up the next morning after the TSST.

[0071] As shown in Figure 3(B), the group taking ornithine-containing tablets had lower mean T-scores for confusion and bewilderment 50 minutes and 140 minutes after the start of the TSST, and upon waking up the next morning after the TSST, compared to the group taking placebo tablets. Therefore, it was shown that the intake of ornithine-containing tablets is likely to improve confusion and bewilderment 50 minutes and 140 minutes after the start of the TSST, and upon waking up the next morning after the TSST.

[0072] As shown in Figure 3(C), the group taking ornithine-containing tablets had lower mean T-scores for depression-depression 50 minutes and 140 minutes after the start of the TSST, and at the time of waking up the next morning after the TSST, compared to the group taking placebo tablets. Therefore, it was shown that the intake of ornithine-containing tablets is likely to improve depression-depression 50 minutes and 140 minutes after the start of the TSST, and at the time of waking up the next morning after the TSST.

[0073] As shown in Figure 3(D), the group taking ornithine-containing tablets had lower mean T-scores of fatigue-lethargy 50 minutes and 140 minutes after the start of TSST, and at the time of waking up the next morning after TSST, compared to the group taking placebo tablets, and the difference was significant at the time of waking up the next morning after TSST. Therefore, it was shown that the intake of ornithine-containing tablets is highly likely to improve fatigue-lethargy 50 minutes and 140 minutes after the start of TSST, and improve fatigue-lethargy at the time of waking up the next morning after TSST.

[0074] As shown in Figure 3(E), the group taking ornithine-containing tablets had lower mean T-scores of tension-anxiety 50 minutes and 140 minutes after the start of the TSST, and when waking up the next morning after the TSST, compared to the group taking placebo tablets. Therefore, it was shown that taking ornithine-containing tablets is likely to improve tension-anxiety 50 minutes and 140 minutes after the start of the TSST, and when waking up the next morning after the TSST.

[0075] As shown in Figure 3(H), the group taking ornithine-containing tablets had lower mean T-scores at 50 and 140 minutes after the start of the TSST, and at the time of waking up the next morning after the TSST, compared to the group taking placebo tablets. Therefore, it was shown that the ingestion of ornithine-containing tablets is likely to improve the TMD scores at 50 and 140 minutes after the start of the TSST, and at the time of waking up the next morning after the TSST.

[0076] [Production Example] The following is an example of a method for producing a tablet containing ornithine and the tablet obtained by the method. First, 3600 g of ornithine hydrochloride (product name: L-ornithine hydrochloride Kyowa, manufactured by Kyowa Hakko Bio Co., Ltd.) and 16 g of tricalcium phosphate (product name: tricalcium phosphate, manufactured by Taihei Chemical Industry Co., Ltd.) were placed in a fluidized bed granulation dryer (manufactured by Freund Corporation: FLO-5A type), and while fluidizing and mixing, a solution of 160 g of hydroxypropyl cellulose (product name: Celny SSL, manufactured by Nippon Soda Co., Ltd.) dissolved in water to a total weight of 1600 g was sprayed onto the mixture. Then, 78 g of glycerin fatty acid ester (product name: Poem TR-FB, manufactured by Riken Vitamin Co., Ltd.) and 90 g of microcrystalline cellulose (product name: Ceolas ST-100, manufactured by Asahi Kasei Chemicals Co., Ltd.) were added to 2832 g of the dried granules and mixed, and the mixture was compressed and molded at a compression molding pressure of 10 kN using a rotary tablet press (Hata Iron Works Co., Ltd.: HT-AP15SS-U) to produce tablets with a diameter of 8 mm, 240 mg, and a tablet hardness of 100 N. Each tablet (240 mg) contains approximately 170 mg of L-ornithine.< / tsst>

Claims

1. A composition for improving the mental state of a healthy person under psychological stress, comprising ornithine or a salt thereof as an active ingredient, The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, The composition, wherein the mental state is fatigue and / or discomfort.

2. The composition according to claim 1 , wherein the psychological stress is a psychological stress caused by face-to-face communication.

3. The healthy subject, A healthy individual with a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less as assessed by the Profile of Mood States 2nd Edition, and The composition according to claim 1 or 2, which is for a healthy subject whose salivary cortisol concentration increases by 0.05 nmol / L or more in the Trier Social Stress Test.

4. 3. The composition according to claim 1 or 2, wherein the feeling of fatigue and / or discomfort is at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-downcast, fatigue-lethargic, and tension-anxiety.

5. The composition according to claim 1 or 2, which is used so as to be ingested or administered in an amount of 1000 to 2000 mg per day in terms of ornithine.

6. The composition of claim 5, which is intended to be ingested or administered for eight or more consecutive days.

7. The composition according to claim 1 or 2, wherein the feeling of fatigue and / or discomfort is a feeling of fatigue and / or discomfort upon waking up the morning after the day on which the psychological stress was experienced.

8. A method for improving the mental state of a healthy individual who is under psychological stress, comprising: The healthy subject is a healthy subject who is aware of fatigue and stress in daily life, the mental state is fatigue and / or discomfort, A method comprising having the healthy subject ingest or administering to the healthy subject a composition containing ornithine or a salt thereof as an active ingredient.

9. A method for selecting a healthy subject whose mental state is expected to improve by ingestion or administration of ornithine or a salt thereof when psychological stress is applied, comprising: the mental state is fatigue and / or discomfort, Selecting healthy subjects having a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition; selecting healthy subjects whose salivary cortisol concentration increases by 0.05 nmol / L or more by the Trier Social Stress Test.

10. A method for determining whether or not a healthy individual is expected to have an improved mental state by taking or administering ornithine or a salt thereof when a psychological stress is applied, comprising: the mental state is fatigue and / or discomfort, A fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less as assessed by the Profile of Mood States 2nd Edition, and Healthy subjects whose salivary cortisol concentration increased by 0.05 nmol / L or more by the Trier Social Stress Test were A method for determining whether a person is a healthy individual whose mental state is expected to improve by taking or administering ornithine or a salt thereof when the person is under psychological stress.

11. A composition for improving the mental state of a healthy subject, comprising ornithine or a salt thereof as an active ingredient, the mental state is fatigue and / or discomfort, The composition, wherein the improvement in mental condition is independent of cortisol suppression.

12. The composition according to claim 11 , wherein the healthy subject is a healthy subject under psychological stress.

13. The composition according to claim 12 , wherein the psychological stress is a psychological stress caused by face-to-face communication.

14. The healthy subject, A healthy individual with a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less as assessed by the Profile of Mood States 2nd Edition, and The composition according to claim 11 or 12, which is for a healthy subject whose salivary cortisol concentration increases by 0.05 nmol / L or more in the Trier Social Stress Test.

15. The composition according to claim 11 or 12, wherein the feeling of fatigue and / or discomfort is at least one selected from the group consisting of anger-hostility, confusion-bewilderment, depression-downcast, fatigue-lethargic, and tension-anxiety.

16. The composition according to claim 11 or 12, which is used so as to be ingested or administered at a dose of 1000 to 2000 mg in terms of ornithine per day.

17. 17. The composition of claim 16, which is intended to be taken or administered for eight or more consecutive days.

18. The composition according to claim 12, wherein the feeling of fatigue and / or discomfort is a feeling of fatigue and / or discomfort upon waking up the morning after the day on which the psychological stress was experienced.

19. 1. A method for improving the mental state of a healthy individual, comprising: the mental state is fatigue and / or discomfort, the improvement in mental state is independent of cortisol suppression; A method comprising having the healthy subject ingest or administering to the healthy subject a composition containing ornithine or a salt thereof as an active ingredient.

20. A method for selecting a healthy subject whose mental state is expected to be improved by the ingestion or administration of ornithine or a salt thereof, comprising: the mental state is fatigue and / or discomfort, the improvement in mental state is independent of cortisol suppression; Selecting healthy subjects having a fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less, as assessed by the Profile of Mood States 2nd Edition; selecting healthy subjects whose salivary cortisol concentration increases by 0.05 nmol / L or more by the Trier Social Stress Test.

21. A method for determining whether or not a person is a healthy individual whose mental state can be expected to be improved by the intake or administration of ornithine or a salt thereof, comprising: the mental state is fatigue and / or discomfort, the improvement in mental state is independent of cortisol suppression; A fatigue-lethargy T-score of 35 or more and / or a vigor-vitality T-score of 60 or less as assessed by the Profile of Mood States 2nd Edition, and Healthy subjects whose salivary cortisol concentration increased by 0.05 nmol / L or more by the Trier Social Stress Test were A method for determining whether a subject is a healthy individual whose mental state is expected to improve by taking or administering ornithine or a salt thereof.

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