Adjustment of activity level

Abstract

The present disclosure provides a compound and composition that are effective for the adjustment of the activity level of a subject, and a method for adjusting the activity level of a subject. A composition according to the present disclosure includes at least one substance selected from the group consisting of fumaric acid and salts thereof as an active component.

Description

Adjusting activity levels

[0001] The present disclosure relates to compositions for use in modulating activity levels in a subject. The present disclosure also relates to methods for modulating activity levels in a subject.

[0002] Depression is a common illness, estimated to affect approximately one in 15 people. The main symptoms of depression are mood symptoms such as depressed mood, sadness, anxiety, and irritability; thought disorders such as obsession with trivial matters; physical symptoms such as fatigue, insomnia, and loss of appetite; and behavioral symptoms such as impaired concentration, all of which are interrelated. Furthermore, a depressed state is associated with a decrease in activity, and it has been shown that mental and physical effects can create a negative chain reaction. In other words, it has been found that a decrease in activity due to mental disorders can further amplify mental disorders. For this reason, cognitive behavioral therapy, a form of psychotherapy that reduces stress by influencing perceptions (cognition) and behavior, incorporates behavioral techniques to increase activity.

[0003] Therefore, increasing activity is considered to be an important approach to improving daily rhythms and maintaining physical and mental health.

[0004] A method for increasing activity levels has been proposed in the past, which involves stimulating ganglion cells (intrinsically photosensitive retinal ganglion cells (ipRGCs)) and cone cells, which are photoreceptors present in the retina of animals, including humans, by irradiating them with light (Patent Document 1). ipRGCs play an important role in non-image-forming pathways, such as regulating circadian rhythms and the pupillary light reflex. This method can increase the daily activity time without changing the length of the circadian rhythm cycle itself (see paragraph

[0013] of Patent Document 1).

[0005] On the other hand, with regard to short-chain fatty acids, it has been reported that short-chain fatty acids such as butyric acid and propionic acid and their salts promote sleep, based on the following results: salts of butyric acid and propionic acid significantly increase the average daily resting percentage in Drosophila; and feeding butyric acid salts to mice increases the non-REM sleep percentage during the dark period (active period) and the REM sleep percentage throughout the day and during the dark period (active period) (see Patent Document 2). It has also been reported that administration of short-chain fatty acids (acetic acid, butyric acid, propionic acid) causes a phase shift in the circadian rhythm of peripheral tissues (see Non-Patent Document 1). However, there have been no reports that administration of short-chain fatty acids increases activity levels.

[0006] JP 2019-080620 A JP 2013-082671 A

[0007] Tahara Y, Yamazaki M, Sukigara H, Motohashi H, Sasaki H, Miyakawa H, Haraguchi A, Ikeda Y, Fukuda S, Shibata S. Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue. Sci Rep. 2018;8(1):1395. Tsuji, Naoki, "Usefulness of Zebrafish as Experimental Animals in Medical Research," LABIO21_No55, JAN. 2014, pp. 5-6 (Japanese Association of Laboratory Animals). E. Yamamoto et. al., Effect of fumaric acid on the growth of Lactobacillus delbrueckii ssp. bulgaricus during yogurt fermentation, J Dairy Sci. 2021 Sep;104(9):9617-9626. V. Gokmen & J. Acar, Fumaric acid in apple juice: a potential indicator of microbial spoilage of apples used as raw material: Food Additives & Contaminants: Vol 21, No 7, 2004, p.626-631 (tandfonline.com)

[0008] An object of the present disclosure is to provide a composition for regulating activity level, and a method for regulating activity level.

[0009] In recent years, in vitro testing has been promoted as an alternative to animal testing from an animal welfare perspective. However, there are still some experiments for which in vivo animal testing is essential, such as the study of animal behavioral patterns. Zebrafish have recently been widely adopted internationally as a model animal for addressing this issue, even in the field of drug discovery. As a vertebrate, zebrafish share a high degree of genome homology with mammals, and 82% of human disease-related genes are covered by zebrafish homologs. Furthermore, studies of numerous zebrafish mutants have accumulating evidence that fundamental biological systems are well conserved between zebrafish and humans at the molecular biology level. Consequently, numerous disease models using zebrafish have been established for human genetic diseases, and zebrafish have recently become widely used as a model animal for human disease in medical research. Furthermore, zebrafish are suitable experimental animals for in vivo drug efficacy and toxicity screening in many respects, such as their high fecundity, ease of rearing and management, and the surprisingly rapid completion of organ formation through in vitro fertilization. To date, two clinical trials of compounds obtained through drug discovery screening using zebrafish have been reported, and their superiority as a model animal has been recognized (Non-Patent Documents 2 and 3, etc.).

[0010] Therefore, in order to solve the above-mentioned problems, the present inventors conducted extensive research using in vivo testing methods with zebrafish as a model animal and found that fumaric acid, a low-molecular-weight organic acid, has the effect of increasing activity during the active phase.

[0011] The present disclosure was completed based on these findings and through further research, and includes the following embodiments: (I) Composition for regulating activity level (I-1) A composition for regulating activity level, comprising at least one compound selected from the group consisting of fumaric acid and its salts as an active ingredient. (I-2) The composition for regulating activity level described in (I-1), wherein the composition for regulating activity level is a composition for increasing or enhancing the amount of activity of a subject. (I-3) The composition for regulating activity level described in (I-1) or (I-2), comprising a fermentation product of a fumaric acid-producing bacterium or a processed product thereof, which contains at least one compound selected from the group consisting of fumaric acid and its salts. (I-4) The composition for regulating activity level described in (I-3), wherein the fumaric acid-producing bacterium is at least one lactic acid bacterium selected from the group consisting of Streptococcus thermophilus and Lactiplantibacillus plantarum. (I-5) A composition for adjusting activity level according to any one of (I-1) to (I-4), which is a food or drink, a quasi-drug, a pharmaceutical, or an additive therefor.

[0012] (II) Methods for Adjusting Activity Levels (II-1) A method for adjusting the activity level of a subject, comprising administering to the subject at least one compound selected from the group consisting of fumaric acid and its salts or a composition containing the same. (II-2) The method described in (II-1), wherein the adjustment of the activity level is an increase or enhancement of the activity level. (II-3) The method described in (II-1) or (II-2), wherein the composition is a fermentation product of a fumaric acid-producing bacterium or a processed product thereof. (II-4) The method described in (II-3), wherein the fumaric acid-producing bacterium is at least one lactic acid bacterium selected from the group consisting of Streptococcus thermophilus and Lactiplantibacillus plantarum. (II-5) The method described in any one of (II-1) to (II-4), wherein the subject is a human or a vertebrate other than a human in a healthy or pre-disease state, and wherein the method is a non-therapeutic method for the subject. (II-6) The method described in any one of (II-1) to (II-5), wherein the subject is a vertebrate other than a human.

[0013] (III) Use for producing a composition for regulating activity level (III-1) Use of at least one compound selected from the group consisting of fumaric acid and its salts, or a composition containing same, for producing a composition for regulating activity level. (III-2) The use according to (III-1), wherein the composition for regulating activity level is a composition for increasing or enhancing the activity level of a subject. (III-3) The use according to (III-1) or (III-2), wherein the composition containing at least one compound selected from the group consisting of fumaric acid and its salts is a fermentation product of a fumaric acid-producing bacterium or a processed product thereof. (III-4) The use according to (III-3), wherein the fumaric acid-producing bacterium is at least one lactic acid bacterium selected from the group consisting of Streptococcus thermophilus and Lactiplantibacillus plantarum. (III-5) The use according to any one of (III-1) to (III-4), wherein the composition for adjusting activity is a quasi-drug, a pharmaceutical product, a non-therapeutic food or drink for a healthy or pre-disease state human or a vertebrate animal other than a human, or an additive thereto.

[0014] (IV) Compounds and compositions for use in regulating activity level (IV-1) At least one compound selected from the group consisting of fumaric acid and its salts, or a composition containing the same, for use in regulating activity level. (IV-2) A compound for use according to (IV-1), or a composition containing the same, wherein the activity level regulation is an adjustment to increase or enhance the activity level of a subject. (IV-3) A compound for use according to (IV-1) or (IV-2), or a composition containing the same, wherein the composition containing at least one compound selected from the group consisting of fumaric acid and its salts is a fermentation product of a fumaric acid-producing bacterium or a processed product thereof. (IV-4) A compound for use according to (IV-3), or a composition containing the same, wherein the fumaric acid-producing bacterium is at least one lactic acid bacterium selected from the group consisting of Streptococcus thermophilus and Lactiplantibacillus plantarum. (IV-5) The compound for use according to any one of (IV-1) to (IV-4) or a composition containing the same, wherein the composition is a quasi-drug, a pharmaceutical product, a non-therapeutic food or drink for healthy or pre-disease humans or vertebrates other than humans, or an additive therefor.

[0015] According to the present disclosure, it is possible to adjust the activity level of a subject. More preferably, according to the compounds of the present disclosure, compositions containing the same, or methods using them, the intake of highly safe ingredients can increase the activity level even in situations where the activity level is reduced due to internal factors. This makes it possible to adjust, improve, or maintain the rhythm of one's life. It is also possible to prevent or improve mental and physical disorders caused by reduced activity level. It is also expected to be effective in maintaining or improving the health of people who are not yet ill, and in improving work efficiency.

[0016] The distance traveled (mm) of zebrafish (fumaric acid group: n=12) in an aqueous solution containing fumaric acid was measured over a period of 7 days (168 hours) in Experimental Example 1. The distance traveled (mm) of zebrafish (control group: n=12) in an aqueous solution containing no fumaric acid (control solution) was measured over a period of 7 days (168 hours) in Experimental Example 2.

[0017] (I) Composition for Adjusting Activity The composition for adjusting activity according to the present disclosure (hereinafter also referred to simply as "the composition") is characterized by containing, as an active ingredient, at least one selected from the group consisting of fumaric acid and its salts. Hereinafter, fumaric acid and its salts are collectively referred to as "fumaric acids." The salt of fumaric acid may be any salt that exhibits the effects of the present disclosure and is pharmaceutically acceptable or ingestible, and includes metal fumarate salts (e.g., combined salts of fumaric acid with alkali metals such as sodium, potassium, and lithium; alkaline earth metal fumarate salts (e.g., combined salts of fumaric acid with alkaline earth metals such as magnesium and calcium); hydrogen metal fumarate salts (e.g., combined salts of fumaric acid with hydrogen metals such as sodium hydrogen or potassium hydrogen); and ammonium salts (e.g., ammonium salts, tetramethylammonium salts) of fumaric acid.

[0018] The present composition is used to regulate the activity level of animals, including humans. In this disclosure, the term "subject" refers to an animal subjected to the method of the present disclosure. The target animal is not limited to vertebrates, and examples include fish, birds, amphibians, reptiles (collectively referred to as "non-mammals"), and mammals. Preferred are mammals, such as primates such as humans and chimpanzees; laboratory animals such as rats, mice, and rabbits; livestock animals such as pigs, cows, horses, sheep, and goats; and pets such as dogs and cats, and more preferably humans.

[0019] In this disclosure, the term "modulate" includes the meanings of "regulate" and "control." The term "modulate" also includes the meanings of "increase" or "enhance."

[0020] In addition, in this disclosure, the term "activity amount" includes activity amount in the sense of "activity intensity per unit time" (hereinafter referred to as "activity intensity") and activity amount in the sense of "activity time per day" (hereinafter referred to as "activity time").

[0021] Adjusting "activity intensity" means adjusting the activity intensity of a subject per unit time. Activity intensity can be defined, for example, as the distance traveled or the amount of activity of an animal, and can be evaluated, for example, by placing the subject in a fixed space and measuring the distance traveled using behavioral history analysis software or image processing software. By administering the composition to an animal, activity intensity can be increased compared to a control without administration. The degree of increase in activity intensity is not particularly limited as long as an increase is observed compared to the control, and may be, for example, 1.02 times or more, 1.05 times or more, 1.1 times or more, or 1.2 times or more of the activity intensity of the control.

[0022] Adjusting "activity time" refers to adjusting the length of a subject's daily activity time. Animals have a physiological cycle, commonly referred to as a "circadian rhythm," that fluctuates over an approximately 24-hour period. This activity time is determined to some extent by the animal species, environment, and the length of the light-dark period. For example, nocturnal animals are active during the dark period and rest (sleep) during the light period, while diurnal animals are active during the day and rest (sleep) during the night. Activity time can be evaluated, for example, by placing a subject in a fixed space and measuring the subject's activity over time using behavioral history analysis software. By administering the composition to an animal, the daily activity time can be increased compared to a control without administering the composition, preferably without changing the length of the circadian rhythm period itself. The degree of increase in activity time is not particularly limited, as long as an increase is observed compared to the control, and may be, for example, 1.02 times or more, 1.05 times or more, 1.1 times or more, or 1.2 times or more of the control's activity time.

[0023] This composition can adjust the subject's daily rhythm by adjusting the subject's activity level. Therefore, this composition can be preferably used to increase or enhance the activity level of a subject whose activity level has decreased, thereby improving and maintaining the subject's daily rhythm. Here, "daily rhythm" refers to the rhythm of daily life based on a person's unique circadian rhythm, i.e., their way of life (behavioral rhythm). Specifically, this refers to a rhythm in which each element of life, such as sleep, wakefulness, activity, rest, and eating, repeats at a regular cycle, while being influenced by the environment, based on the circadian rhythm.

[0024] According to the present composition, the subject's physical and mental condition can be adjusted by adjusting the subject's activity level. In particular, since the present composition can increase or enhance the subject's activity level, it is possible to prevent mental and physical disorders caused by a decrease in activity level. Therefore, the present composition can preferably be used, for example, to increase or enhance the activity level of a subject with a decreased activity level, thereby preventing or improving the subject's mental and physical disorders. Note that, as shown in Experimental Example 1, the effects of the present composition are also observed in healthy subjects, and therefore the subject of the present disclosure is not limited to its health state, and includes subjects in healthy, pre-illness, and ill states.

[0025] The present compositions include foods and beverages, quasi-drugs, and pharmaceuticals used to regulate activity levels. Here, the term "foods and beverages" includes non-therapeutic foods and beverages for humans. The term "foods and beverages" also includes food and beverages for non-human animals. The term "pharmaceuticals" also includes pharmaceuticals for humans as well as non-human animals.

[0026] The composition also includes an additive for preparing a food, drink, quasi-drug, or pharmaceutical product used to adjust activity levels. By preparing a food, drink, quasi-drug, or pharmaceutical product using the activity-adjusting composition as an additive, the food, drink, quasi-drug, or pharmaceutical product can be imparted with an activity-adjusting effect. As a result, a food, drink, quasi-drug, or pharmaceutical product for adjusting activity levels that has an activity-adjusting effect can be prepared.

[0027] The origin of the fumaric acids used as the active ingredient of the present composition is not particularly limited, and they may be chemically synthesized or extracted and isolated from natural products (animals, plants, microorganisms, and products produced by them). They may also be extracted and isolated from fermented products prepared using microorganisms (fumaric acid-producing bacteria). Furthermore, the fumaric acids incorporated into the present composition may be crudely purified, regardless of their purity, as long as the effects of the present invention are not impaired. For example, as long as the effects of the present disclosure are not impaired, the fumaric acid-containing fermented product itself prepared using microorganisms or a processed product thereof can be used as the active ingredient of the present composition.

[0028] Here, examples of microorganisms include bacteria capable of producing fumaric acids. In the present disclosure, bacteria capable of producing fumaric acids are collectively referred to as "fumaric acid-producing bacteria." Examples of such fumaric acid-producing bacteria include, but are not limited to, lactic acid bacteria, as long as they have the ability to produce fumaric acids. Examples of such lactic acid bacteria include, but are not limited to, lactic acid bacteria belonging to the Streptococcus genus and Lactiplantibacillus genus. Examples of lactic acid bacteria belonging to the Streptococcus genus include S. thermophilus, and examples of lactic acid bacteria belonging to the Lactiplantibacillus genus include L. plantarum (see, for example, Non-Patent Documents 3 and 4). Fermented products prepared by culturing these lactic acid bacteria contain fumaric acids. Therefore, these fermented products or processed products thereof (collectively referred to as "fumaric acid-containing fermented products") can be used as active ingredients in the present composition, or they can be used as the present composition as they are. The processed product is a processed product of a fermentation product prepared using a fumaric acid-producing bacterium, and includes, without limitation, processed products that have been subjected to various treatments (e.g., concentration treatment, purification treatment, drying treatment, etc.) so that they contain fumaric acids at a high concentration or with a high purity.

[0029] The content of fumaric acids contained in the present composition can be appropriately selected, for example, within the range of 0.1 to 99% by mass, as long as the present composition exerts its activity-regulating effect.

[0030] (A) Application to Foods and Beverages, or Food and Beverage Additives One use form of the present composition includes foods and beverages, and food and beverage additives. The form of the foods and beverages and food and beverage additives is not particularly limited, and may be liquid, semi-liquid (including paste, gel, and sol), or solid, including beverage forms. Foods and beverages also include health foods (including functional foods, nutritional supplements, dietary supplements, health foods with disease risk reduction claims (foods for specified health uses, nutritional functional foods, and foods with functional claims), and foods for patients) as well as other general foods and beverages. Health foods are foods and beverages consumed with the expectation of maintaining or improving health. Supplements are foods and beverages in a formulation in which specific ingredients (fumaric acids) are concentrated. All of these foods and beverages are non-therapeutic foods and beverages not intended for therapeutic purposes.

[0031] Foods and beverages may include, for example, dairy products such as yogurt and cheese, which are produced by subjecting food materials such as milk to microbial fermentation to produce fumaric acids, and koji-fermented foods. Furthermore, supplements may be produced by adding excipients, binders, etc. to the composition, kneading the mixture, and then tableting the mixture; powders (pulverized), pills, capsules, jellies, granules, etc. In addition to fumaric acids, the composition may also contain, as appropriate, food-grade (edible) carbohydrates, proteins, lipids, vitamins, minerals, sugars (e.g., glucose), natural or artificial sweeteners, citric acid, carbonated water, fruit juice, stabilizers, preservatives, binders, thickeners, and / or emulsifiers.

[0032] When the food or drink is a beverage, examples of non-alcoholic beverages include, but are not limited to, mineral water, near water, sports drinks, tea drinks, milk drinks, coffee drinks, fruit juice drinks, vegetable juice drinks, fruit and vegetable juice drinks, carbonated drinks, etc. Beer drinks with an alcohol content of less than 1%, such as non-alcoholic beer, may also be used.

[0033] The term "tea beverage" in the above-mentioned non-alcoholic beverages refers to beverages made by brewing leaves (tea leaves) from the tea plant, an evergreen tree of the Theaceae family, or leaves of plants other than tea plants, or grains, etc., and includes all types of fermented tea, semi-fermented tea, and unfermented tea. Specific examples of tea beverages include Japanese tea (e.g., green tea, barley tea), black tea, herbal tea (e.g., jasmine tea), Chinese tea (e.g., Chinese green tea, oolong tea), roasted green tea, etc. "Milk beverage" refers to beverages made primarily from raw milk, cow's milk, etc., or foods produced using these as raw materials, and includes not only those made from cow's milk, etc., but also those made from processed milk, such as nutrient-enriched milk, flavored milk, and sweetened hydrolyzed milk.

[0034] In the case of foods and beverages for humans, the daily intake per adult can be adjusted to a range of 6 mg / kg or less, converted to the intake of fumaric acid, for example, a range of 20 to 360 mg for an adult weighing 60 kg. The same applies when the composition is formulated in a container divided into daily meals, and the amount of the composition formulated in the container can be, for example, an amount of fumaric acid in the range of 20 to 360 mg for an adult weighing 60 kg, converted to the intake of fumaric acid per daily meal.

[0035] The present composition in the form of a food or beverage can be produced according to standard manufacturing methods for various foods and beverages, except that it includes a step of adding and blending fumaric acids or a composition containing fumaric acids as one of the ingredients (e.g., as an additive for food or beverages).

[0036] (B) Application to Quasi-drugs, Pharmaceuticals, or Their Additives One use form of the composition includes quasi-drugs, pharmaceuticals (hereinafter collectively referred to as "pharmaceuticals, etc."), and their additives. These contain, for example, fumaric acids as active ingredients and can be produced by mixing pharmaceutically acceptable carriers or additives such as carriers, excipients, binders, and diluents according to standard methods. These may be in the form of oral or parenteral administration. Oral administration forms include granules, powders, tablets, pills, capsules, syrups, etc. Parenteral administration forms include injections, infusions, nasal administration preparations, and enteral administration (feeding tube administration). However, they are not limited to these. Oral administration forms are preferred.

[0037] Pharmaceutically acceptable carriers include excipients or diluents. In addition to the carrier, additives such as preservatives, stabilizers, binders, pH adjusters, buffers, thickeners, gelling agents, and antioxidants may be added as needed. These additives are preferably those used in pharmaceutical preparations.

[0038] The pharmaceutical product etc. of the present disclosure may be used in combination with other ingredients that have an activity level adjusting effect, particularly an effect of increasing activity level.

[0039] The dosage of the pharmaceuticals and the like disclosed herein varies depending on factors such as the dosage form, the patient's age and body weight, and the nature or severity of the symptoms to be treated. However, a preferred range of dosage for a typical adult via oral administration per day is, for example, 20 to 360 mg, converted to the dose of fumaric acid, for an adult weighing 60 kg. The dosage may be selected appropriately depending on various conditions, such as the route of administration. The drug may be administered to a patient once a day or in multiple divided doses. The target patient is typically a human, but also includes the aforementioned non-human vertebrates.

[0040] (II) Method for Adjusting Activity A method for adjusting the activity level of a subject according to the present disclosure can be carried out by administering to the subject at least one compound selected from the group consisting of fumaric acid and salts thereof or a composition containing the same. Here, the meanings of "fumaric acid and salts thereof," "composition," "subject," and "adjustment of activity level" are as explained in (I) above, and the descriptions therein can be incorporated by reference herein.

[0041] The "administration" mentioned above includes both oral and parenteral administration. Oral administration is preferred. When the subject is a fish, the fumaric acid compound can be administered by mixing it with feed, or by dissolving it in water in which the fish are kept.

[0042] The method for adjusting activity levels disclosed herein is a non-therapeutic method that does not include a therapeutic method. In other words, subjects to which the method disclosed herein is applied are those who are healthy or in a pre-disease state, but do not include patients in a disease state (disease state). Furthermore, the method for adjusting activity levels disclosed herein can be applied to humans as well as vertebrates other than humans.

[0043] According to the method of the present disclosure (hereinafter referred to as "the method"), the activity level of a subject can be adjusted to adjust the subject's life rhythm. Therefore, the method can be preferably used to increase or enhance the activity level of a subject whose activity level has decreased, thereby improving and maintaining the life rhythm of the subject.

[0044] According to this method, by adjusting the activity level of a subject, the subject's physical and mental state can be adjusted. In particular, this method can increase or enhance the activity level of a subject, thereby preventing physical and mental disorders caused by a decrease in activity level. Therefore, this method can preferably be used, for example, to increase or enhance the activity level of a subject whose activity level has decreased, thereby preventing or improving the physical and mental disorders of the subject.

[0045] (III) Use for producing a composition for adjusting activity level The present disclosure includes the use of fumaric acids or a composition containing the same for producing a composition for adjusting activity level. As described above, an "activity-adjusting composition" is a composition used to adjust the activity level of an animal, including humans, and includes foods and beverages, quasi-drugs, or pharmaceuticals. It also includes additives for preparing the foods and beverages, quasi-drugs, or pharmaceuticals. The meanings of "fumaric acids," "compositions containing the same," and "adjusting activity level" are as explained in (I) above, and the descriptions therein are incorporated herein by reference.

[0046] (IV) Compounds and Compositions for Use in Adjusting Activity Level The present disclosure includes fumaric acids or compositions containing the same for use in adjusting activity level. The meanings of "fumaric acids," "compositions containing the same," and "adjusting activity level" are as explained in (I) above, and the descriptions therein are incorporated herein by reference.

[0047] As described above, in this specification, the terms "comprise" and "contain" encompass the meanings of "consist of" and "consist essentially of."

[0048] The present invention will be described below using experimental examples to aid in understanding the configuration and effects of the present invention. However, the present invention is not limited by these experimental examples. Unless otherwise specified, the following experiments were carried out at room temperature (25±5°C) and atmospheric pressure. Unless otherwise specified, "%" and "parts" in the following descriptions mean "% by mass" and "parts by mass," respectively.

[0049] The materials used in the following experimental examples and their sources are as follows: Fumaric acid: Fujifilm Wako Pure Chemical Industries, Ltd. (product number 069-00652)

[0050] Experimental Example 1: Evaluation of activity using zebrafish (1) Experimental method: Fertilized zebrafish eggs were collected and incubated in a 10 cm dish for 3-4 days (light period: 14 hours, dark period: 10 hours, 26°C) until hatched, yielding larvae. The larvae were divided into a test group (n = 12) and a control group (n = 12), and transferred to wells (1 fish per well) of a 96-square well plate containing each of the aqueous solutions shown in Table 1 (800 μl per well).

[0051] Using Danio Vision (Sophia Scientific Co., Ltd.), the behavior of the larvae was tracked under free-running conditions at 26°C under constant darkness for 7 days, and data on the distance traveled was obtained. Danio Vision is a behavioral analysis system for zebrafish (Danio rerio) used in research fields such as drug discovery, safety pharmacology, behavioral genetics, and circadian rhythms.

[0052] (2) Experimental Results The measurement results for the test and control groups are shown in Figures 1 and 2, respectively. Compared to the control group, the test group tended to have an increased distance traveled (amplitude) during the active phase (see the results for measurement times 50-72 h, 84-96 h, 108-120 h, 132-144 h, and 156-168 h in Figures 1 and 2). Increased distance traveled indicates increased activity and behavior. This confirms that administering fumaric acid to the subjects increases the intensity of activity per unit time during the active phase. Therefore, administration of fumaric acid is expected to stimulate activity during the active phase, thereby contributing to a more dynamic lifestyle.

[0053] Furthermore, compared to the control group, the test group tended to have an increased activity time. As shown in Figures 1 and 2, the test group had a larger movement distance (amplitude) than the control group, particularly at measurement times 108-120 h, 132-144 h, and 156-168 h, which corresponded to the active period, confirming a significant increase in the activity time during the active period.

[0054] The present disclosure provides a composition for adjusting activity level that contains a highly safe active ingredient, thereby making it possible to prevent or improve physical conditions caused by decreased activity, and to support the maintenance or improvement of health and work efficiency in healthy or pre-illness people.

Claims

1. A composition for regulating activity, comprising as an active ingredient at least one compound selected from the group consisting of fumaric acid and its salts.

2. A composition for adjusting activity level as described in claim 1, which is a composition for increasing or enhancing the activity level of a subject.

3. A composition for regulating activity as described in claim 1 or 2, which contains a fermentation product of a fumaric acid-producing bacterium or a processed product thereof, which contains at least one compound selected from the group consisting of fumaric acid and its salts.

4. The composition for regulating activity described in claim 3, wherein the fumaric acid producing bacteria is at least one type of lactic acid bacteria selected from the group consisting of Streptococcus thermophilus and Lactiplantibacillus plantarum.

5. A method for regulating the activity of a subject, comprising administering to the subject at least one compound selected from the group consisting of fumaric acid and its salts, or a composition containing the same.

6. The method according to claim 5, wherein the adjustment of the amount of activity is an increase or enhancement of the amount of activity.

7. The method according to claim 5 or 6, wherein the composition is a fermentation product of a fumaric acid producing bacterium or a processed product thereof.

8. The method according to claim 5 or 6, wherein the subject is a human or non-human vertebrate in a healthy or non-diseased state, and the method is a non-therapeutic method for the subject.