Composition for increasing efficiency of consumption of cognitive resources

Abstract

The purpose of the present invention is to provide a novel composition for increasing the efficiency of consumption of cognitive resources. The present invention provides a composition for increasing the efficiency of consumption of cognitive resources, said composition containing at least one substance selected from the group consisting of cacao polyphenol, theobromine, and caffeine as an active ingredient. The composition may be in a unit intake form, and one or more of the unit intake forms may contain the daily effective intake amount of cacao polyphenol, theobromine, and / or caffeine for a human. The composition is preferably a food.

Description

Composition for improving cognitive resource consumption efficiency REFERENCE TO RELATED APPLICATIONS

[0001] This application benefits from the priority of an earlier Japanese application, Patent Application No. 2023-102349 (filing date: June 22, 2023), the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a composition for improving the efficiency of cognitive resource consumption.

[0003] It is empirically known that performing multiple tasks simultaneously results in lower performance and achievement on each task compared to performing a single task. This decline in performance during multiple tasks is thought to be caused by interference from the simultaneous performance of other tasks (e.g., the dual-task interference effect), which reduces the cognitive resource capacity available for performing the target task (Non-Patent Document 1). Cognitive resources are the brain resources required to perform cognitive tasks, and their capacity is finite. For example, dual-task interference occurs when two tasks compete for a limited cognitive resource capacity, and it has been shown that the lateral prefrontal cortex is involved in this phenomenon (Non-Patent Document 2).

[0004] Recent research has shown that cognitive resources can be used efficiently by suppressing their consumption. For example, it has been reported that professional soccer players, a physical sport, can efficiently control foot movements by significantly reducing the consumption of cognitive resources in the motor cortex of the brain (Non-Patent Document 3).

[0005] Y Jono et al., Japanese Journal of Health Promotion and Physical Therapy, Vol. 3, No. 2:47-51(2013)K Watanabe and S Funahashi, Nature Neuroscience, 17(4), 601-611 (2014)E Naito and S Hirose, Front. Hum. Neurosci., Sec. Motor Neuroscience, Volume 8, Article 594 (2014)

[0006] The present invention aims to provide a composition for improving the efficiency of cognitive resource consumption.

[0007] The present invention provides the following: [1] A composition for improving the efficiency of cognitive resource consumption or an agent for improving the efficiency of cognitive resource consumption, comprising one or more active ingredients selected from the group consisting of cocoa polyphenols, theobromine, and caffeine. [2] The composition or agent described in [1] above, which is in a unit intake form. [3] The composition or agent described in [2] above, in which one or more unit intake forms contain cocoa polyphenols, theobromine, and / or caffeine in amounts effective for a human to consume per day. [4] The composition or agent described in any of [1] to [3] above, which contains cocoa polyphenols, theobromine, and caffeine as active ingredients. [5] The composition or agent described in [3] or [4] above, in which the effective daily intake of cocoa polyphenols for a human is 450 to 850 mg. [6] The composition or agent described in any of [3] to [5] above, in which the effective daily intake of theobromine for a human is 100 to 300 mg. [7] The composition or agent according to any one of [3] to [6] above, wherein the effective daily intake of caffeine for a human is 15 to 35 mg. [8] A composition for improving the efficiency of cognitive resource consumption or an agent for improving the efficiency of cognitive resource consumption, comprising non-fat cocoa as an active ingredient. [9] The composition or agent according to [8] above, which is in a unit intake form.

[10] The composition or agent according to [9] above, wherein one or more unit intake forms contain an effective daily intake of non-fat cocoa for a human.

[11] The composition or agent according to any one of [8] to

[10] above, wherein the effective daily intake of non-fat cocoa for a human is 7 to 30 g.

[12] The composition or agent according to any one of [1] to

[11] above, which is ingested or administered before engaging in a cognitive task requiring attention.

[13] The composition or agent according to any one of [1] to

[12] above, which is in the form of a food, a medicine, or a supplement.

[14] The composition or agent according to any one of [1] to

[13] above, for maintaining and / or improving the efficiency of performance, judgment, attention, thinking, or understanding when performing a cognitive task.

[15] The composition or agent according to any one of [1] to

[14] above, for maintaining and / or improving the productivity and / or work efficiency of mental work involving the consumption of cognitive resources.

[16] A method for improving the efficiency of cognitive resource consumption, comprising ingesting or administering to a subject in need thereof an effective amount of cocoa polyphenols, theobromine and / or caffeine or non-fat cocoa, or a composition comprising some or all of these.

[17] Use of a composition comprising cocoa polyphenols, theobromine and / or caffeine or non-fat cocoa, or some or all of these, as an agent for improving the efficiency of cognitive resource consumption or in a method for improving the efficiency of cognitive resource consumption.

[0008] The compositions of [1] and [8] above may be referred to herein as "the compositions of the present invention," and the agents of [1] and [8] above may be referred to herein as "the agents of the present invention."

[0009] The active ingredients of the compositions and agents of the present invention are advantageous in that they provide compositions and agents for improving the efficiency of cognitive resource consumption that are highly safe and can be taken continuously over a long period of time without the risk of side effects.

[0010] Figure 1 shows the regions where a significant interaction was observed in brain activity during the Stroop task (corresponding to -logP > 1.301, family-wise error corrected p < 0.05). In the figure, "L_46_ROI" indicates the left dorsolateral prefrontal cortex, and "L_PF_ROI" indicates the left inferior parietal lobule. Figure 2 is a graph showing the difference in contrast estimates during the Stroop task as a function of time (early and late) after test food ingestion. In the figure, "L_46_ROI" indicates the left dorsolateral prefrontal cortex, "L_PF_ROI" indicates the left inferior parietal lobule, "Contrast of Early. Stroop-Late. Stroop" indicates the difference in brain activity during the Stroop task, calculated by subtracting the contrast estimate from the second Stroop task (late) from the contrast estimate from the first Stroop task (early). "R" indicates test food R, and "S" indicates test food S. Specific Description of the Invention

[0011] The compositions and agents of the present invention contain one or more active ingredients selected from the group consisting of cocoa polyphenols, theobromine, and caffeine. The compositions and agents of the present invention also contain non-fat cocoa content as an active ingredient. In this specification, "cocoa polyphenols, theobromine, and / or caffeine" and "non-fat cocoa content" are sometimes referred to as "active ingredients of the present invention."

[0012] In the present invention, "cocoa polyphenols" refers to polyphenols contained in cocoa, i.e., cocoa-derived polyphenols. Therefore, typically, cocoa polyphenol extracts or purified products extracted (including crude extracts) or purified (including crudely purified) from the cocoa plant or processed products thereof can be used as active ingredients in the present invention. Examples of components constituting cocoa polyphenols include monomers such as catechin and epicatechin, and oligomers (dimers or higher) formed by polymerization of catechin, such as procyanidin B2, procyanidin B5, procyanidin C1, and cinnamtannin A2. In the present invention, processed products containing cocoa polyphenols (e.g., processed cocoa bean products such as cocoa mass, defatted cocoa mass, cocoa powder, and ground cocoa beans) can also be incorporated as cocoa polyphenols into the compositions and agents of the present invention. The various forms of cocoa polyphenols described above can be used alone or in combination in the compositions and agents of the present invention.

[0013] In the present invention, "theobromine" refers to theobromine contained in cacao, i.e., theobromine derived from cacao. Therefore, typically, theobromine extract or purified product obtained by extraction (including crude extraction) or purification (including crude purification) from cacao plants or processed products thereof can be used as the active ingredient of the present invention.

[0014] In the present invention, "caffeine" refers to caffeine contained in cacao, i.e., cacao-derived caffeine. Therefore, typically, a cacao caffeine extract or purified product extracted (including crude extraction) or purified (including crude purification) from a cacao plant or a processed product thereof can be used as an active ingredient of the present invention.

[0015] In the present invention, examples of the cacao plant or processed products thereof that can be used as raw materials for cocoa polyphenols, theobromine, and / or caffeine, or processed products containing cocoa polyphenols, theobromine, and / or caffeine, include various parts of the plant or processed cocoa beans, such as cacao bark, cacao leaves, cocoa beans, cocoa nibs, cocoa shells, cocoa mass, defatted cocoa mass, and cocoa powder. Cocoa mass is obtained by grinding cocoa beans, and defatted cocoa mass can be obtained by removing fats and oils from the cocoa mass. The method for removing fats and oils is not particularly limited and can be carried out using known methods such as pressing. Cocoa powder can be obtained by pulverizing the defatted cocoa mass. Furthermore, when extracting from a cacao plant or processed products thereof, it is preferable to use cocoa nibs, cocoa mass, or cocoa powder that have been subjected to a micronization process such as grinding or pulverization, in terms of extraction efficiency. In the present invention, the term "cacao plant" may intentionally or unintentionally include substances other than the cacao plant. Furthermore, when extracting cacao plants or processed products thereof as raw materials, substances other than the cacao plant may also be intentionally or unintentionally included. Furthermore, cacao mass and cocoa powder may also intentionally or unintentionally include substances other than the cacao plant.

[0016] Methods for extracting cocoa polyphenols from cocoa plants or processed products thereof are known. For example, cocoa polyphenol-containing compositions can be prepared according to the methods described in Japanese Patent Application Laid-Open Nos. 2009-183229 and 2011-93807. Theobromine and caffeine can also be extracted from cocoa plants or processed products thereof using known extraction methods to prepare theobromine- and / or caffeine-containing compositions. In these methods, the extraction solvent is not particularly limited, but water, hot water, or alcohol (e.g., ethanol) can be used. Extraction can also be performed under acidic conditions with the addition of hydrochloric acid or the like. Furthermore, methods for purifying cocoa polyphenols, theobromine, and / or caffeine from cocoa plants or processed products thereof can be used using known methods, such as synthetic adsorbents, ion exchange resins, ultrafiltration, and activated clay treatment, without particular limitation.

[0017] For efficient administration or ingestion of cocoa polyphenols, it is preferable to use a composition containing cocoa polyphenols at a high concentration in the present invention. In this case, a cocoa polyphenol-enriched composition obtained according to known methods (e.g., JP 2009-183229 A and JP 2011-93807 A) can be used in the present invention. For example, when a cocoa polyphenol extract is used in the compositions and agents of the present invention, the extract can have a total cocoa polyphenol content of 40% or more, preferably 69.8% or more.

[0018] The content of cocoa polyphenols in the compositions and agents of the present invention can be determined arbitrarily depending on the purpose, use, form, dosage form, symptoms, body weight, etc., and the present invention is not limited thereto. However, the content (solid content equivalent) relative to the total amount can be determined as follows: That is, the lower limit of the cocoa polyphenol content in the compositions and agents of the present invention (not less than or exceeding) can be 0.5% by mass, preferably 1% by mass, more preferably 2%, 3%, 4%, or 5% by mass. The upper limit of the content (not more than or less than) can be 100% by mass, preferably 99% by mass, more preferably 90%, 80%, 70%, or 60% by mass. These lower and upper limits can be arbitrarily combined, and the content range can be, for example, 0.5 to 100% by mass (preferably 1 to 99% by mass, more preferably 2 to 90% by mass or 5 to 60% by mass).

[0019] In the present invention, the cocoa polyphenol content can be measured by the Folin-Ciocalteu method. The Folin-Ciocalteu method is a measurement method based on the oxidation-reduction of phenols, and can be performed according to the method established by the Chocolate Industry Fair Trade Commission. In the measurement, the polyphenol content can be calculated using commercially available epicatechin as a standard substance.

[0020] The theobromine content in the compositions and agents of the present invention can be determined arbitrarily depending on the purpose, use, form, dosage form, symptoms, body weight, etc., and the present invention is not limited thereto. However, the content (in terms of solid content) can be determined as follows relative to the total amount. That is, the lower limit of the theobromine content in the compositions and agents of the present invention (not less than or exceeding) can be 0.1% by mass, preferably 0.5% by mass, more preferably 1%, 2%, 3%, or 4% by mass. The upper limit of the content (not more than or less than) can be 100% by mass, preferably 99% by mass, more preferably 90%, 80%, 70%, or 60% by mass. These lower and upper limits can be arbitrarily combined, and the content range can be, for example, 0.1 to 100% by mass (preferably 0.5 to 99% by mass, more preferably 1 to 90% by mass or 2 to 60% by mass).

[0021] In the present invention, the theobromine content can be measured by high performance liquid chromatography (HPLC).

[0022] The caffeine content in the compositions and agents of the present invention can be determined arbitrarily depending on the purpose, use, form, dosage form, symptoms, body weight, etc., and the present invention is not limited thereto. However, the content (in terms of solid content) can be determined as follows relative to the total amount. That is, the lower limit of the caffeine content in the compositions and agents of the present invention (not less than or exceeding) can be 0.01% by mass, preferably 0.05% by mass, more preferably 0.1%, 1%, 2%, or 3% by mass. The upper limit of the content (not more than or less than) can be 100% by mass, preferably 99% by mass, more preferably 90%, 80%, 70%, or 60% by mass. These lower and upper limits can be arbitrarily combined, and the content range can be, for example, 0.01 to 100% by mass (preferably 0.05 to 99% by mass, more preferably 0.1 to 90% by mass or 1 to 60% by mass).

[0023] In the present invention, the caffeine content can be measured by high performance liquid chromatography (HPLC).

[0024] The present invention also provides a composition for improving cognitive resource consumption efficiency and an agent for improving cognitive resource consumption efficiency, each containing non-fat cocoa as an active ingredient. The content of non-fat cocoa in the compositions and agents of the present invention, which contain non-fat cocoa as an active ingredient, can be determined arbitrarily depending on the purpose, use, form, dosage form, symptoms, body weight, etc., and the present invention is not limited thereto. However, the content (solid content equivalent) relative to the total amount can be determined as follows: That is, the lower limit of the non-fat cocoa content in the compositions and agents of the present invention (above or beyond) can be 1% by weight, preferably 5% by weight, more preferably 10%, 20%, 30%, or 40% by weight. The upper limit of the content (below or below) can be 100% by weight, preferably 99% by weight, more preferably 90%, 80%, 70%, or 60% by weight. These lower and upper limits can be combined in any desired manner, and the range of the content can be, for example, 1 to 100% by mass (preferably 5 to 90% by mass, 10 to 90% by mass, or 40 to 90% by mass). In this specification, "fat-free cocoa content" is synonymous with "defatted cocoa mass."

[0025] In the present invention, "cognitive resources" are also referred to as cognitive resources, attention resources, neural resources, attention resources, or brain resources, and refer to brain resources required for performing cognitive tasks, which are consumed by performing cognitive tasks. In the present invention, the capacity of cognitive resources is finite. Here, "cognitive tasks" refers to tasks performed using cognitive functions, including the performance of cognitive tasks (including cognitive tasks requiring attention). Cognitive tasks requiring attention may be cognitive function tests, such as the Stroop task (synonymous with the Stroop test). The Stroop task is a representative test used to evaluate executive functions, which are the ability to appropriately control attention and behavior to perform a certain goal under conditions in which cognitive conflict occurs when competing stimuli are presented.

[0026] In the present invention, "improving the efficiency of cognitive resource consumption" means reducing the consumption of resources required to perform cognitive tasks, and includes suppressing the increase in the consumption of resources required to perform cognitive tasks, as well as maintaining the consumption of resources required to perform cognitive tasks.

[0027] As shown in the examples below, the active ingredients of the compositions and agents of the present invention, cocoa polyphenols, theobromine, and / or caffeine, suppress and / or reduce increased brain activity in activated regions involved in attention maintenance, working memory, response inhibition, and / or attention control during cognitive task performance. Therefore, the compositions and agents of the present invention can be used to suppress and / or reduce increased brain activity during cognitive task performance, where the brain activity can be brain activity involved in attention maintenance, working memory, response inhibition, and / or attention control. For example, the compositions and agents of the present invention can be used to maintain and / or improve the efficiency of performance, judgment, attention, thinking, or understanding during cognitive task performance, and / or to maintain and / or improve the productivity and / or work efficiency of mental tasks that require the consumption of cognitive resources.

[0028] Here, brain activity correlates with the consumption of cognitive resources in performing cognitive tasks (Front. Hum. Neurosci., Sec. Motor Neuroscience, Volume 8 (2014), Front. Hum. Neurosci., 17 April 2013, Sec. Cognitive Neuroscience, Volume 7 (2013)). That is, increased brain activity indicates increased consumption of cognitive resources in performing cognitive tasks. On the other hand, decreased brain activity (including suppression of increases in brain activity) indicates decreased consumption of cognitive resources in performing cognitive tasks (including suppression of increases in cognitive resource consumption), and therefore decreased brain activity indicates improved efficiency of cognitive resource consumption. Therefore, the compositions and agents of the present invention can be used to improve the efficiency of cognitive resource consumption.

[0029] According to the examples described below, the active ingredients of the compositions and agents of the present invention, i.e., cocoa polyphenols, theobromine and / or caffeine, or non-fat cocoa, do not affect performance in cognitive tasks, but suppress increases in brain activity in activated areas involved in maintaining attention, working memory, response inhibition and / or attention control during the performance of cognitive tasks. This suggests that these effects are based on different mechanisms, namely, the exertion of cognitive function and the improvement of the efficiency of cognitive resource consumption.

[0030] The improvement of cognitive resource consumption efficiency can be evaluated by the suppression of the increase in brain activity during cognitive task performance.Such brain regions can be regions whose activity increases during cognitive task performance, such as the left dorsolateral prefrontal cortex and the left inferior parietal lobule.The suppression of the increase in brain activity can be evaluated as an improvement in cognitive resource consumption efficiency when the brain activity of a subject performing a cognitive task after taking the active ingredient of the present invention is smaller than the brain activity of the subject performing the cognitive task before taking the active ingredient of the present invention.The suppression of the increase in brain activity can also be evaluated by dividing the cognitive task performance into the first half and the second half based on the elapsed time since taking the active ingredient of the present invention, and subtracting the brain activity of the second half from the brain activity of the first half, and the larger the difference in brain activity, the greater the improvement in cognitive resource consumption efficiency can be evaluated.Therefore, when the difference in brain activity of a subject performing a cognitive task after taking the active ingredient of the present invention is larger than the difference in brain activity of the subject performing the cognitive task before taking the active ingredient of the present invention, the improvement in cognitive resource consumption efficiency can be evaluated. Alternatively, the efficiency of cognitive resource consumption can be evaluated as improved when the difference in brain activity during a cognitive task performed by a subject after ingestion of the active ingredient of the present invention is, for example, about 1.1 times or more, more preferably about 1.15 times or more, even more preferably about 1.2 times or more, even more preferably about 1.25 times or more, particularly preferably about 1.3 times or more, and even more particularly preferably about 1.35 times or more, about 1.4 times or more, or about 1.5 times or more, compared to the difference in brain activity during a cognitive task performed by the subject before ingestion.

[0031] Brain activity can be measured by known methods, such as electroencephalography (EEG) and magnetoencephalography (MEG), which measure electrical neural activity in the brain, and functional near-infrared spectroscopy (fNIRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), which measure changes in local cerebral blood flow. In the fMRI method, a functional magnetic resonance imaging (fMRI) device can be used to measure local oxygen metabolism and blood flow dynamics as a surrogate marker of brain activity, as a blood oxygenation-level-dependent (BOLD) signal (Glover GH., Neurosurg Clin N Am., 2011;22(2):133-139).

[0032] In the present invention, subjects for which the efficiency of cognitive resource consumption is improved include humans and non-human mammals (e.g., pets such as dogs and cats, and livestock such as cows and horses), preferably humans. In the present invention, subjects for which the efficiency of cognitive resource consumption is improved also include healthy individuals.

[0033] The compositions and agents of the present invention can be provided in the form of pharmaceuticals and quasi-drugs (e.g., pharmaceutical compositions), foods (e.g., food compositions), feeds (e.g., feed compositions), etc., and can be implemented according to the description below.

[0034] The active ingredients of the present invention, cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa, can be orally administered to humans and non-human animals. Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using pharmaceutically acceptable carriers using techniques commonly used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, flavorings, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc.

[0035] In the present invention, cocoa polyphenols, theobromine and / or caffeine, or non-fat cocoa content can be incorporated into pharmaceuticals or quasi-drugs. The cocoa polyphenol content in the pharmaceuticals or quasi-drugs can be, for example, 0.1% by mass, 10% by mass, 20% by mass, or 30% by mass at lower limits, and 95% by mass, 80% by mass, 70% by mass, or 50% by mass at upper limits. These lower and upper limits can be arbitrarily combined, and the cocoa polyphenol content (in terms of solids content) in the pharmaceuticals or quasi-drugs can be, for example, 0.1 to 95% by mass, 10 to 80% by mass, or 20 to 70% by mass. The theobromine content in a pharmaceutical or quasi-drug can be, for example, 0.01% by mass, 0.1% by mass, 10% by mass, 20% by mass, or 30% by mass at its lower limit, and 95% by mass, 80% by mass, 70% by mass, or 50% by mass at its upper limit. These lower and upper limits can be arbitrarily combined, and the theobromine content (in terms of solid content) in a pharmaceutical or quasi-drug can be, for example, 0.01 to 95% by mass, 0.1 to 95% by mass, 10 to 80% by mass, or 20 to 70% by mass. The caffeine content in a pharmaceutical or quasi-drug can be, for example, 0.01% by mass, 0.1% by mass, 10% by mass, 20% by mass, or 30% by mass at its lower limit, and 95% by mass, 80% by mass, 70% by mass, or 50% by mass at its upper limit. These lower and upper limits can be arbitrarily combined, and the caffeine content (in terms of solid content) in a pharmaceutical or quasi-drug can be, for example, 0.01 to 95% by mass, 0.1 to 95% by mass, 10 to 80% by mass, or 20 to 70% by mass. The content of fat-free cocoa in a pharmaceutical or quasi-drug product can be, for example, a lower limit (not less than or exceeding) of 1%, 5%, 10%, 20%, or 30% by weight, and an upper limit (not more than or less than) of 100%, 99%, 90%, 80%, or 70% by weight.These lower and upper limits can be combined in any desired manner, and the range of the fat-free cocoa content (in terms of solids content) in a drug or quasi-drug can be, for example, 1 to 100% by mass, 5 to 99% by mass, 10 to 99% by mass, or 20 to 99% by mass. The drug or quasi-drug can be provided in the form of a pharmaceutical composition.

[0036] When the active ingredients of the present invention, cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa component, are provided as a food product, the cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa component, can be directly incorporated into the food product, and the food product contains an effective amount of the cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa component. Here, "containing an effective amount" of cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa component refers to a content such that the cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa component, when ingested in a normally consumed amount, is ingested in the ranges described below. Furthermore, the term "food" is used to encompass health foods, functional foods, nutritional supplements, health-claimed foods (e.g., foods for specified health uses, foods with nutrient functions, foods with functional claims), foods for special dietary uses (e.g., foods for infants, foods for pregnant women, foods for the sick), and supplements.

[0037] The form or shape of the "food" is not particularly limited, and it may be a food or supplement consumed daily, a drink, a semi-liquid or gel-like form (e.g., liquid diet), or a solid form, but examples include foods whose main ingredient is cocoa beans, preferably an oil-and-fat processed composition, and more preferably an oil-and-fat processed food such as chocolate. Furthermore, by making it into a semi-solid composition containing the active ingredient of the present invention, it can be ingested by humans and non-human mammals who have impaired chewing and swallowing functions and are unable to take orally orally administer the drug.

[0038] As described above, in order to efficiently ingest cocoa polyphenols, theobromine, and / or caffeine, the cocoa polyphenols, theobromine, and / or caffeine can be directly used in the present invention, or a composition containing high concentrations of cocoa polyphenols, theobromine, and / or caffeine (e.g., defatted cocoa mass) can be used in the present invention. Therefore, foods and supplements made primarily from cocoa beans are preferably those containing high concentrations of cocoa polyphenols, theobromine, and / or caffeine, more preferably oil-processed compositions containing high concentrations of cocoa polyphenols, theobromine, and / or caffeine, and even more preferably chocolate containing high concentrations of cocoa polyphenols, theobromine, and / or caffeine. An oil-and-fat processed composition (particularly chocolate) containing high concentrations of cocoa polyphenols, theobromine, and / or caffeine can be produced by using, as a raw material, a cocoa-derived material (e.g., cocoa nibs, cocoa mass, defatted cocoa mass, cocoa powder, ground cocoa beans) and / or a cocoa extract (e.g., cocoa nib extract) having a high cocoa polyphenol, theobromine, and / or caffeine content. In the present invention, a so-called high-cocoa chocolate containing high concentrations of cocoa polyphenols, theobromine, and / or caffeine can be used as the composition and agent of the present invention, and the cocoa content in the chocolate can be 55% by mass or more (preferably 70% by mass or more).

[0039] Here, the content of cocoa polyphenols, theobromine and / or caffeine in foods and supplements is not particularly limited as long as intake of cocoa polyphenols, theobromine and / or caffeine is possible. However, from the viewpoint of efficient intake of cocoa polyphenols, theobromine and / or caffeine, the content in an oil-and-fat processed composition such as chocolate is, for example, 1.0 to 50% by mass (preferably 1.0 to 15% by mass, more preferably 1.2 to 12% by mass, even more preferably 1.4 to 9% by mass, even more preferably 1.5 to 10% by mass) of cocoa polyphenols per solid content of the composition. can be 1.6 to 7% by mass, particularly preferably 1.8 to 5% by mass, theobromine can be 0.4 to 50% by mass (preferably 0.4 to 40% by mass, more preferably 0.5 to 30% by mass, even more preferably 0.6 to 20% by mass, even more preferably 0.5 to 10% by mass, particularly preferably 0.6 to 5% by mass), and caffeine can be 0.05 to 50% by mass (preferably 0.05 to 15% by mass, more preferably 0.06 to 10% by mass, even more preferably 0.07 to 7% by mass, even more preferably 0.08 to 5% by mass, particularly preferably 0.09 to 2% by mass). Furthermore, the content of fat-free cocoa content in foods and supplements is not particularly limited as long as intake of fat-free cocoa content is possible, but from the viewpoint of efficient intake of fat-free cocoa content, the content of fat-free cocoa content in an oil-processed composition such as chocolate can be, for example, 1 to 100% by mass (preferably 5 to 90% by mass, more preferably 10 to 90% by mass, even more preferably 20 to 90% by mass, still more preferably 30 to 90% by mass, and particularly preferably 40 to 90% by mass) based on the solid content of the composition.

[0040] The food provided by the present invention includes fat-and-oil processed foods, such as chocolate, whose main ingredient is cocoa beans. Here, fat-and-oil processed foods are used to refer to fat-and-oil based confectioneries processed using cocoa nibs, cocoa mass, cocoa powder, cocoa butter, fats, and the like. The term "fat-and-oil based confectioneries" as used herein does not refer to chocolate, semi-chocolate, or chocolate products as defined in the Fair Competition Code for Labeling of Chocolates, a rule approved by the Japan Fair Trade Commission, but also includes all types of fat-and-oil based confectioneries, such as tempered and non-tempered fat creams and chocolates made with cocoa substitutes, which do not fall under the aforementioned rules. The fat-and-oil based confectioneries of the present invention can be prepared according to conventional methods, except for the incorporation of cocoa polyphenols, theobromine, and / or caffeine, or the incorporation of non-fat cocoa. For example, the fat-and-oil based confectioneries of the present invention can be produced by mixing the ingredients of the confectioneries, followed by a refining (fine-graining) process using a roll mill, a conching process, and optionally a tempering process, a molding process, an aging process, and the like.

[0041] The foods provided by the present invention are not limited to oil- and fat-processed foods, as long as they contain the active ingredients cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa. Examples include starch-based foods such as bread, biscuits, noodles, crackers, and nutritional bars; various confectioneries such as candy, chewing gum, gummy candies, and snacks; milk and dairy products such as milk, processed milk, ice cream, fermented milk (e.g., yogurt), dairy drinks, cheese, butter, and cream; desserts such as pudding, jelly, bavarois, and mousse; beverages such as non-alcoholic and alcoholic beverages; processed meat products such as ham and sausage; processed fish products such as kamaboko (fish paste), chikuwa (fish cake), and fish sausage; processed fruit products such as jams and purees; and seasonings such as roux and sauces. Cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa, can be appropriately incorporated at an appropriate stage in the manufacturing process depending on the characteristics and purpose of each food.

[0042] The pharmaceuticals and foods of the present invention can be ingested or administered to mammals in need thereof (for example, humans, mice, rats, rabbits, dogs, cats, cows, horses, pigs, monkeys, etc.).

[0043] For example, when cocoa polyphenols, theobromine, and / or caffeine are orally ingested as foods, the amount of cocoa polyphenols ingested by a human per day (based on solids) can be adjusted to 250 to 1000 mg (preferably 400 to 900 mg, more preferably 450 to 850 mg, even more preferably 450 to 850 mg, even more preferably 550 to 750 mg, and particularly preferably 600 to 700 mg), 80 to 500 mg of theobromine (preferably 90 to 400 mg, more preferably 100 to 300 mg, even more preferably 130 to 260 mg, even more preferably 150 to 240 mg, and particularly preferably 170 to 220 mg), and 12 to 55 mg of caffeine (preferably 13 to 45 mg, more preferably 15 to 35 mg, even more preferably 17 to 33 mg, even more preferably 18 to 32 mg, and particularly preferably 20 to 30 mg). Alternatively, the cocoa polyphenols, theobromine, and / or caffeine may be orally ingested in the form of cocoa mass, in which case, the daily intake of an adult (based on solids) ranges from 5 to 30 g (preferably 10 to 25 g). Alternatively, the cocoa polyphenols, theobromine, and / or caffeine may be orally ingested in the form of non-fat cocoa, in which case, the daily intake of an adult (based on solids) ranges from 7 to 30 g (preferably 11 to 27 g). In the present invention, the cocoa polyphenols, theobromine, and / or caffeine may be orally ingested in the form of processed fats and oils, such as chocolate. When high-cocoa chocolate with a cocoa content of 70% or more and a total content of cocoa polyphenols, theobromine, and caffeine of 2% or more is orally ingested, the daily intake of an adult can be 4 to 40 g (preferably 20 to 30 g). In any of the above cases, the intake amount of the active ingredients of the present invention, i.e., cocoa polyphenols, theobromine, and / or caffeine, as well as the intake period described below, are applicable whether the composition and agent of the present invention are used for non-therapeutic or therapeutic purposes, and in the case of therapeutic purposes, "intake" can be read as "administration."

[0044] When the active ingredient of the present invention is provided as a feed (for example, pet food or livestock feed), it can be provided in accordance with the above description of food.

[0045] The composition and agent of the present invention may be used in combination with other orally ingestible compositions or agents without limitation. For example, the composition and agent of the present invention may be used in combination with a material or composition that is expected to improve the efficiency of cognitive resource consumption, thereby further enhancing the effect of improving the efficiency of cognitive resource consumption.

[0046] The composition and agent of the present invention may be started to be taken before the expected date and time of improving the efficiency of cognitive resource consumption. Examples of the expected date and time of improving the efficiency of cognitive resource consumption include before engaging in a cognitive task (e.g., a cognitive task requiring attention), for example, within 1 hour, 45 minutes, 30 minutes, 15 minutes, 5 minutes, or 1 minute before engaging in the task.

[0047] The compositions and agents of the present invention may be provided as compositions containing a daily amount of cocoa polyphenols, theobromine, and / or caffeine, or non-fat cocoa, effective for improving the efficiency of cognitive resource consumption. In this case, the compositions and agents of the present invention may be packaged so that the effective daily amount can be ingested, and the form thereof is not particularly limited as long as the effective daily amount can be ingested.

[0048] Typically, the compositions and agents of the present invention can be provided in unit intake forms, and a subject can ingest one or more unit intake forms to obtain a daily effective intake. Here, "unit intake form" refers to a form containing a predetermined amount of active ingredient suitable for a single intake, including processed forms such as blocks, plates, sticks, tablets, and capsules, as well as packaged forms. For example, assuming a daily effective intake (recommended intake) of cocoa polyphenols of 600 mg and a unit intake form of a chocolate bar containing 120 mg of cocoa polyphenols, it is recommended that the subject consume five of the chocolate products per day. Furthermore, assuming a daily effective intake (recommended intake) of theobromine of 200 mg and a unit intake form of a chocolate bar containing 40 mg of theobromine, it is recommended that the subject consume five of the chocolate products per day. Furthermore, assuming that the effective daily intake (recommended intake) of caffeine is 25 mg and the unit intake form is a bar-shaped chocolate product containing 5 mg of caffeine, it is recommended that the subject consume five bars of the chocolate product per day.Furthermore, assuming that the effective daily intake (recommended intake) of fat-free cocoa is 17 g and the unit intake form is a bar-shaped chocolate product containing 5 g of fat-free cocoa, it is recommended that the subject consume four bars of the chocolate product per day.

[0049] When the composition and agent of the present invention are provided in a unit intake form, it is desirable to provide information on the intake amount so that the effective intake amount for one day can be taken. Furthermore, when the effective intake amount for one day is provided in multiple unit intake forms, for convenience of intake, multiple unit intake forms corresponding to the effective intake amount for one day can be provided as a set, or even multiple unit intake forms corresponding to the effective intake amount for multiple days can be provided as a set. For example, in the above chocolate product example, 25 bars of chocolate product (which may be individually wrapped) corresponding to the effective intake amount for five days can be provided as a set (which may be packaged in a container).

[0050] When the composition and agent of the present invention are provided in a packaged form, it is desirable that the package has instructions regarding the amount of intake so that a daily effective intake can be taken, or that a document with such instructions is provided together with the composition and agent. Furthermore, when a daily effective intake is provided in multiple packages, multiple packages containing a daily effective intake can be provided as a set for convenience of intake.

[0051] The packaging form for providing the composition and agent of the present invention is not particularly limited as long as it specifies a certain amount, and examples include wrapping paper, bags, pouches, soft bags, paper containers, cans, bottles, capsules, and other containers that can accommodate the composition and agent of the present invention.

[0052] The compositions and agents of the present invention can exert their effects by being taken once, and to further enhance their effects, they can be taken continuously for at least one week, preferably for two weeks or more, more preferably for three weeks or more, even more preferably for four weeks or more, and even more preferably for one month or more. Here, "continuously" means taking them every day, or taking them at least once every two days. When the compositions and agents of the present invention are provided in unit intake forms, a set of unit intake forms corresponding to an effective intake amount for a certain period (e.g., one week or one month) for continuous intake may be provided.

[0053] The food of the present invention may be labeled with a claim regarding the improvement of the efficiency of cognitive resource consumption. In this case, in order to make the labeling easy for consumers to understand, the food of the present invention may be labeled with, for example, some or all of the following claims: - Contributes to efficient brain utilization - Contributes to maintaining and / or improving the efficiency of performance, judgment, attention, thinking, and understanding when performing cognitive tasks - Maintains and / or improves the productivity and / or work efficiency of mental work that consumes cognitive resources - Optimizes the allocation of cognitive resources when multitasking - Prevents the depletion of cognitive resources - Has excellent effects in saving and preserving cognitive resources

[0054] Another aspect of the present invention provides a method for improving the efficiency of cognitive resource consumption, comprising ingesting or administering to a subject (e.g., a human or non-human mammal) in need thereof an effective amount of cocoa polyphenols, theobromine, and / or caffeine, or a composition comprising some or all of these. The method of the present invention can be carried out according to the description of the compositions and agents of the present invention.

[0055] Another aspect of the present invention provides use of a composition comprising cocoa polyphenols, theobromine and / or caffeine, or non-fat cocoa, or some or all of these, for the manufacture of an agent for improving the efficiency of cognitive resource consumption, as an agent for improving the efficiency of cognitive resource consumption, or in a method for improving the efficiency of cognitive resource consumption. The use of the present invention can be carried out according to the description of the composition and agent of the present invention and the method of the present invention.

[0056] According to yet another aspect of the present invention, there is provided a composition comprising cocoa polyphenols, theobromine and / or caffeine, or non-fat cocoa, or some or all of these, for use in improving the efficiency of cognitive resource consumption. These inventions can be carried out according to the description of the compositions and agents of the present invention and the methods of the present invention.

[0057] The methods and uses of the present invention may be used in mammals, including humans, and are intended to be both therapeutic and non-therapeutic. As used herein, "non-therapeutic" does not include surgical, therapeutic, or diagnostic procedures for humans (i.e., medical procedures for humans), and specifically does not include methods of surgical, therapeutic, or diagnostic procedures for humans performed by a physician or a person under the direction of a physician.

[0058] The present invention will be described in more detail based on the following examples, but the present invention is not limited to these examples.

[0059] Example 1: Evaluation of the effects of high-cocoa chocolate on the brain through human trials (1) Methods A. Selection of subjects Subjects were selected to meet all of the following inclusion criteria and not to violate any of the exclusion criteria.

[0060] <Inclusion criteria> (1) Individuals who have received a full explanation of the purpose and content of this study, are competent to consent, fully understand the purpose, and volunteer voluntarily and agree to participate in writing. (2) Healthy men and women aged 30 to 50 at the time of consent acquisition.

[0061] <Exclusion criteria> (1) Those who have taken medicines, quasi-drugs (excluding topical medications) and / or supplements five or more days a week in the month prior to screening, and those who plan to take them five or more days a week during the study period. (2) Those who have a serious disease such as cranial nerve disease, liver disease, kidney disease, heart disease, circulatory system disease, malignant tumor, etc., or those with a history of such a disease. (3) Those who have seizures (loss of consciousness, coma, convulsions, etc.) due to nervous system disease, color vision abnormalities, diabetes, arrhythmia, or those with a history of such a disease. (4) Those with food allergies. (5) Those who cannot consume bitter chocolate (dark chocolate). (6) Those who consume excessive alcohol (an average of 60g or more per day in terms of alcohol). (7) Those who smoke. (8) Those who work day and night shifts and those who work night shifts during the study period. (9) Those who have significantly low task performance in the cognitive function test at screening. (10) Those who were unable to complete the measurement in the autonomic nervous function test at screening. (11) Left-handed (12) Persons using internal or external life support devices (cardiac pacemakers, neurological pacemakers, etc.). (13) Persons with metal foreign bodies in their bodies (arterial clips, metal pins from fracture treatment, etc.). (14) Persons using metal bridges for orthodontics. (15) Persons with tattoos or permanent makeup. (16) Persons currently engaged in or previously engaged in metal processing or other occupations that frequently involve handling metal. (17) Persons with mental disorders or claustrophobia. (18) Persons with hearing, speech, or grip impairment. (19) Persons with impaired body temperature regulation or sweating. (20) Persons unable to maintain a supine position for more than one consecutive hour. (21) Persons who have participated in other clinical research within one month prior to obtaining consent to participate in this study, or who plan to participate in other clinical research during the study period. (22) Pregnant or potentially pregnant persons, breastfeeding persons, or persons planning or hoping to become pregnant during the study period. (23) Other persons who the study director or co-investigator deems unsuitable as subjects.

[0062] A screening test was conducted on 55 healthy Japanese men and women who had given written consent and wished to participate in the study. Based on the results of the screening test, 33 people who met the inclusion criteria and did not violate the exclusion criteria were selected as subjects and were equally assigned to two groups: a group that consumed test food R (n = 17) and a group that consumed test food S (n = 16).

[0063] B. Preparation of Test Foods Test food chocolates (25 g each) of Test Food R (hereinafter sometimes simply referred to as "R") and Test Food S (hereinafter sometimes simply referred to as "S") shown in Table 1 were prepared as test foods. Test Food R (100 parts by mass) contained 35 parts by mass of non-fat cocoa (non-fat components in cocoa mass excluding cocoa butter). Test Food S (100 parts by mass) contained 12 parts by mass of the same non-fat cocoa as Test Food R, with the remainder replaced by cellulose and dextrin. In other words, Test Food R contained approximately three times the amount of non-fat cocoa (defatted cocoa mass) as Test Food S.

[0064]

[0065] C. Analysis of test food components The contents of the main components in the test foods were analyzed by the Japan Food Research Laboratories using the analytical methods shown in Table 2. The analysis results are shown in Table 3. Based on the analysis results, the intake of the main components per test (per 25g test food) was calculated. The intake amounts are shown in Table 4.

[0066]

[0067]

[0068]

[0069] D. Test Method: A placebo-controlled, randomized, double-blind, crossover study was conducted on subjects. The test food R intake group (R group) and the test food S intake group (S group) were given a single dose of one test food (25 g) of each test food. Next, brain activity during the subjects' cognitive tasks (traffic light tasks) was measured using a functional magnetic resonance imaging (fMRI) device (task fMRI). Specifically, 20 minutes after ingestion of the test food, the first task fMRI (Early) was performed for 15 minutes, followed by a 10-minute break and a second task fMRI (Late) for 15 minutes.

[0070] The fMRI device used was a 3 Tesla MRI device (SIEMENS Prisma, Erlangen, Germany).

[0071] The subjects were administered both non-Stroop and Stroop traffic light tasks. The non-Stroop task required selective attention to focus on the traffic light among images of pedestrians, traffic lights, and arrows. The Stroop task required selective attention to focus on the traffic light among images of pedestrians, traffic lights, and arrows. It required response inhibition when the color of the traffic light and the meaning of the letters on the image were inconsistent (a cognitive task requiring attention). Specifically, subjects held a pushbutton device in their right hand and were instructed to press the button corresponding to the letter (red or blue) displayed on the image as quickly and accurately as possible when the image was presented, regardless of the color (red or blue) of the traffic light in the stimulus image. The non-Stroop or Stroop task was randomly presented on a computer display, and subjects responded by pressing the button.

[0072] Statistical analysis was performed on brain activity (fMRI data) during Stroop task and non-Stroop task performance. The platform and software used for statistical analysis are shown in Table 5.

[0073]

[0074] Specifically, the type of test food (R and S) and the time elapsed since ingestion (Early and Late) were used as factors to compare interactions. That is, the difference in brain activity between the first task fMRI (R.Early) and the second task fMRI (R.Late) when ingestion of test food R was compared with the difference in brain activity between the first task fMRI (S.Early) and the second task fMRI (S.Late) when ingestion of test food S was compared ([R.Early > R.Late] > [S.Early > S.Late]). Of the subjects, 7 were excluded from the valid analysis at the discretion of the study manager, so the data of the 26 subjects who were valid analysis subjects were analyzed.

[0075] (2) Results The results are shown in Figures 1 and 2.

[0076] Figure 1 shows statistical maps of BOLD (blood oxygenation-level-dependent) signal changes (contrast estimates) superimposed on brain surface images. Figure 1 shows significant brain activity interactions between the left dorsolateral prefrontal cortex (L_46_ROI), which is involved in sustained attention, working memory, and response inhibition, and the left inferior parietal lobule (L_PF_ROI), which is involved in higher brain functions such as attention control, during the Stroop task. However, no brain regions showed significant interactions during non-Stroop task performance.

[0077] Figure 2 is a graph showing the difference in brain activity during the Stroop task [Early - Late], calculated by subtracting the contrast estimate from the second Stroop task (Late) from the contrast estimate from the first Stroop task (Early). Figure 2 shows that in both the left dorsolateral prefrontal cortex (L_46_ROI) and the left inferior parietal lobule (L_PF_ROI), ingestion of test food R decreased activity in the late phase, whereas ingestion of test food S increased activity in the late phase. Furthermore, in both of these regions, ingestion of test food R showed a significantly higher difference in brain activity during the Stroop task compared to ingestion of test food S.

[0078] On the other hand, no significant interactions were observed in the performance (correct response rate, incorrect response rate, no response rate, and average reaction time) of the cognitive task (traffic light task) of the fMRI task due to the type of test food (R and S) or the time elapsed since ingestion (Early and Late) in either the Stroop task or the non-Stroop task, and equivalent task performance was maintained regardless of the intake of any of the test foods.

[0079] In the left dorsolateral prefrontal cortex and left inferior parietal lobule, areas whose activity increases with response inhibition and attention control, brain activity decreased over time with ingestion of high-cocoa chocolate (test food R), indicating that ingestion of high-cocoa chocolate reduces the consumption of cognitive resources used for response inhibition and attention control in the later part of the task (late).On the other hand, brain activity increased over time with ingestion of test food S, indicating that in order to maintain task performance, more cognitive resources are required for response inhibition and attention control in the later part of the task (late) compared to the earlier part (early) when ingestion of test food S is taken.

[0080] According to the present invention, it is possible to provide a composition derived from natural cocoa beans, which is highly safe and contributes to improving the efficiency of cognitive resource consumption in the person who consumes it, and a method for producing a food product containing the composition.

Claims

1. A composition for improving the efficiency of cognitive resource consumption, comprising as an active ingredient one or more selected from the group consisting of cocoa polyphenols, theobromine and caffeine.

2. The composition of claim 1 in unit dosage form.

3. The composition of claim 2, wherein one or more unit dosage forms contain an effective daily intake amount of cocoa polyphenols, theobromine and / or caffeine for humans.

4. The composition according to claim 1 or 3, comprising cocoa polyphenols, theobromine and caffeine as active ingredients.

5. The composition according to claim 3, wherein the effective daily intake amount of cocoa polyphenols for humans is 450 to 850 mg.

6. The composition according to claim 3, wherein the effective daily intake of theobromine for humans is 100 to 300 mg.

7. The composition according to claim 3, wherein the effective daily intake of caffeine for humans is 15 to 35 mg.

8. A composition for improving the efficiency of cognitive resource consumption, comprising non-fat cocoa as an active ingredient.

9. The composition of claim 8, which is in unit dosage form.

10. The composition of claim 9, wherein one or more unit dosage forms comprise an effective daily serving of non-fat cocoa for a human.

11. The composition of claim 10, wherein the effective daily intake of non-fat cocoa for a human is from 7 to 30 grams.

12. The composition described in claim 1 or 8, which is ingested or administered prior to engaging in a cognitive task requiring attention.

13. The composition according to claim 1 or 8, which is a food product, a medicine or a supplement.

14. A composition according to claim 1 or 8 for maintaining and / or improving the efficiency of performance, judgment, attention, thinking or understanding during the performance of a cognitive task.

15. A composition according to claim 1 or 8 for maintaining and / or improving productivity and / or work efficiency in mental work involving the consumption of cognitive resources.

16. A method for improving the efficiency of cognitive resource consumption, comprising ingesting or administering to a subject in need thereof a composition comprising effective amounts of cocoa polyphenols, theobromine and / or caffeine or non-fat cocoa, or any or all of these.

17. Use of cocoa polyphenols, theobromine and / or caffeine or non-fat cocoa content, or a composition comprising any or all of these, for the manufacture of an agent for improving the efficiency of consumption of cognitive resources, as an agent for improving the efficiency of consumption of cognitive resources, or in a method for improving the efficiency of consumption of cognitive resources.

Images