Non-therapeutic use of aronia extract for enhancing executive function

Abstract

The present invention relates to the field of food supplementation, in particular to the field of nutraceuticals, more in particular to the use of an Aronia berry extract and compositions thereof. More specifically, the invention relates to the non-therapeutic use of an Aronia berry extract or composition thereof for improving executive function parameters, mental wellbeing and / or memory in healthy human subjects.

Description

[0001] Non-therapeutic use of aronia extract for enhancing executive function

[0002] Field of the invention

[0003] The present invention relates to the field of food supplementation, in particular to the field of nutraceuticals, more in particular to the use of an Aronia berry extracts and compositions thereof. More specifically, the present invention relates to the non-therapeutic use of an Aronia berry extract or composition comprising such extract for improving overall brain health. In particular, the invention relates to the non-therapeutic use of an Aronia berry extract or composition thereof for improving executive function parameters, mental wellbeing and / or memory in healthy human subjects.

[0004] Background to the invention

[0005] Cognitive and mental health are important for overall wellbeing and quality of life. Cognitive function is essential for daily functioning, because it encompasses the mental processes that allow individuals to carry out everyday activities effectively, ranging from social interactions to performing household tasks. In addition, various cognitive skills, including executive function and memory, have shown to play an important role in academic and work performance. Impairments in any of these functions can significantly impact an individual's independence and productivity, but also affect mental wellbeing. In turn, mental wellbeing is important for optimal cognitive functioning, as high levels of stress can have a negative effect on cognitive performance including impaired attention, executive function and memory.

[0006] Aronia melanocarpa berries (black chokeberries) contain high concentrations of anthocyanins. Anthocyanins such as cyanidin-3-glycosides are able to cross the blood-brain barrier, where they are able to exert direct beneficial effects in the brain, such as increasing the density of nervous fibers, and protection against oxidative stress and inflammation. Previously, it was found that Aronia Melanocarpa extract supplementation could improve attention and psychomotor control in healthy individuals (WO2018146255A1). Therefore, an important approach to improve specific cognitive performance outcomes would be to increase the intake of anthocyanins or natural components containing these compounds through supplementation. However, cognitive functions are diverse and can be categorized into several main domains each with their own distinct functions, including attention and psychomotor speed, executive function, memory, and social cognition. Consequently, the effects of the same intervention are likely to differ across these domains. So far, protective effects of aronia have been shown with regard to memory (Lee et al. 2016), but only in relation to (age-related) memory impairment or cognitive decline. Since cognitive decline significantly impacts brain function, any effects shown in individuals experiencing cognitive decline or memory impairment cannot simply be extrapolated to healthy individuals.

[0007] Until now, data about the effects of Aronia Melanocarpa berry extract on executive function parameters, mental wellbeing and memory in healthy human subjects is lacking. Therefore, it was unexpected that such characteristics of cognitive and mental health could be improved by Aronia Melanocarpa berry extract in a healthy population.

[0008] Summary of the invention

[0009] In a first aspect, the present invention provides the non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract for improving executive function parameters, mental wellbeing and / or memory in healthy human subjects.

[0010] In an embodiment, improving executive function parameters comprises: improving manipulation of visuospatial information, improved spatial working memory, improved spatial awareness, improving strategy making, improving strategic planning, improving strategic thinking, improving strategic planning with less errors, improving strategic thinking with less errors, improving problem solving, improving response inhibition, improving high level thinking, improving reasoning, improving retention, improving decision making, improving mental flexibility, and / or improving planning.

[0011] In another embodiment, improving mental wellbeing comprises: improving quality of life, improving emotional wellbeing, improving pleasantness, improving arousal, improving mood, reducing stress, and / or improving emotion.

[0012] In another specific embodiment, improving memory comprises: improving visual associative learning, improving visual matching ability, improving (short-term visual) recognition, improving visual memory, improving episodic memory performance, improving learning capacity, improving encoding, improving recall efficiency, improving visual memory, improving task accuracy, improving learning efficacy, reducing error making, reducing mistake making, improving memory scores, improving remembering of pattern locations, and / or improving delayed memory.

[0013] In yet another embodiment, the Aronia berry extract comprises an anthocyanin, preferably cyanidin-3-O-glycoside, more preferably selected from the list comprising: cyanidin-3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, cyanidin-3-xyloside, or any combination thereof. In a particular embodiment, the Aronia berry extract comprises at least 10% (w / w) anthocyanins, preferably at least 15% (w / w) anthocyanins, more preferably at least 20% (w / w) anthocyanins, even more preferably at least 25% (w / w) anthocyanins.

[0014] In another particular embodiment, in case cyanidin-3-galactoside is present, said Aronia berry extract comprises at least 30% (w / w), preferably at least 40% (w / w) cyanidin-3-galactoside, more preferably at least 50% (w / w), most preferably at least 60% (w / w) of the total amount of cyanidin-3-O-glycoside.

[0015] In yet another embodiment, the Aronia berry extract comprises at least about 5% (w / w) cyanidin-3-galactoside, preferably at least about 10% (w / w) cyanidin-3-galactoside, more preferably at least about 15% (w / w) cyanidin-3-galactoside (w / w) of the total amount of the extract.

[0016] In a further embodiment, the composition comprises about and between 1 mg to 1000 mg of Aronia berry extract, such as more than 1 mg and less than 750 mg, about and between 5 mg to 750 mg, about and between 15 and 500 mg, about and between 30 mg to 250 mg, or about and between 65 to 150 mg of Aronia berry extract.

[0017] In a specific embodiment, the composition comprises about and between 1 mg to 500 mg of anthocyanin, preferably about and between 10 mg to 300 mg, more preferably about and between 15 mg to 200 mg of anthocyanin.

[0018] In another specific embodiment, the composition further comprises one or more compounds selected from a group comprising: caffeine, taurine, theanine, inositol, guarana, magnesium, melatonin, ribose, carnitine, co-enzyme Q10, alpha-glycerophosphocholine, alpha-lipoic acid, luteolin-7-glucoside, luteolin, quercetin, xylose lutein, zeaxanthin, astaxanthin, meso-zeaxanthin, beta-carotene, zinc, copper, vitamin B1 , vitamin B6, vitamin B12, vitamin A, vitamin C, vitamin D, vitamin E, omega-3 fatty acids, and / or anti-oxidants.

[0019] In yet another embodiment, the Aronia berry extract is an Aronia melanocarpa berry extract. In a particular embodiment, said composition is an oral composition.

[0020] In another particular embodiment, said composition is in the form of a pill, powder, capsule, tablet, gel, gummy, beverage, chewing gum, chewable tablet, lozenge or troche. Brief of the

[0021] With specific reference now to the figures, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the different embodiments of the present invention only. They are presented in the cause of providing what is believed to be the most useful and readily description of the principles and conceptual aspects of the invention. In this regard no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention. The description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

[0022] Figure 1. Between and total errors on the spatial working memory test following AME and placebo supplementation. (A) The number of between errors after AME supplementation were significantly lower compared to placebo. (B) The number of total errors after AME supplementation were significantly lower compared to placebo. AME: aronia melanocarpa extract.

[0023] Figure 2. Spatial working memory after AME and placebo supplementation. The number of errors were significantly lower after AME supplementation compared to placebo. AME: aronia melanocarpa extract.

[0024] Figure 3. Memory scores on the paired associated learning task. (A) Location recall of paired patterns in the memory task increased significantly after AME supplementation compared to placebo. (B) The number of errors decreased significantly after AME supplementation compared to placebo. AME: aronia melanocarpa extract.

[0025] Figure 4. Affect grid scores. AME supplementation showed a trend towards an increased Affect Grid Pleasantness (A) and Arousal (B) in men. AME: aronia melanocarpa extract.

[0026] Detailed

[0027]

[0028] The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous. As used in the specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. By way of example, "a compound" means one compound or more than one compound.

[0029] The term "about" or "approximately" as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of + / -10% or less, preferably + / -5% or less, more preferably + / - 1 % or less, and still more preferably + / -0.1 % or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier "about" or "approximately" refers is itself also specifically, and preferably, disclosed.

[0030] The overall objective of the present invention is to provide a composition for non-therapeutic use to improve specific aspects of cognitive and mental health, in particular cognitive skills including executive function and memory, but also the mental wellbeing of subjects. These aspects are all part of overall brain health and are important to maintain a person’s overall wellbeing.

[0031] As mentioned hereinbefore, it was surprisingly found that an Aronia berry extract or a composition comprising said Aronia berry extract has beneficial effects on executive function parameters, mental wellbeing and / or memory, in particular in healthy individuals. In particular, as described in examples 1 and 2, six weeks of aronia extract supplementation resulted in improvements in executive function, mental wellbeing and memory parameters.

[0032] In a first aspect, the present invention provides the non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract for improving executive function parameters, mental wellbeing and / or memory in healthy human subjects.

[0033] In the context of the present invention, the term “non-therapeutic use” is to be understood as a non-therapeutic method, including uses of products or technologies that are not intended to treat or prevent a medical condition. In healthy individuals, it refers to the uses of products or technologies that are intended to enhance or optimize non-disease related conditions, such as memory, executive function, mood or other aspects of mental or physical wellbeing. Substances or compounds can also be used non-therapeutically in the context of cosmetic treatment.

[0034] As an example, an Aronia berry extract or composition comprising such an extract can be administered to a subject in an effective dosage, and optionally repeating said dosage, until a beneficial effect has occurred, without specifically treating a disease or ailment. Accordingly, the beneficial effect can also be a cosmetically beneficial effect. As used herein, the term “extract” refers to all active substances separated from a natural ‘raw material’ product by an appropriate solvent such as but not limited to ethanol, oil or water wherein all or nearly all of the solvent is evaporated after the extraction process. Extracts of Aronia berries may comprise fibers, vitamins, minerals, and other natural substances with antioxidant, lipid-lowering, and antiproliferative properties. The extract of the present invention contains all extracts and purified substances obtained in each step of extraction or purification, a diluted solution thereof, a concentrate or a dried product. Extracts may be in the form of tinctures, absolutes, syrups, or in powder form.

[0035] As used herein and unless otherwise specified, the term “composition” refers to the identity of all different, individual substances, compounds or elements (e.g. agents, modulators, regulators, etc.) that constitute the composition, in combination with the Aronia berry extract. It can be a solution, mixture, an emulsion, a suspension, liquid, aqueous or non-aqueous composition prepared according to a specific procedure. Some components impart specific properties to the composition when it is put into use.

[0036] In particular, as defined herein, the term “composition” is used in the context of an Aronia berry extract that is further processed in a form that is particularly suitable for administration to a subject. Wherein the Aronia berry extract is a pure extract form that can be administered or used as a dried powder, tincture, absolute or syrup, the composition according to the invention can be processed in a more user-friendly dosage such as a capsule or pill for use. Therefore, when reference is made to a “composition”, it comprises an Aronia extract according to the invention and one or more compound to obtain such a composition. Accordingly, the terms “extract” and “composition” can be used interchangeably. For example, when reference is made to the non-therapeutic use of the Aronia berry extract, it is also meant to include the composition according to the invention, and vice versa, unless otherwise stated.

[0037] A particular object of the present invention relates to the non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract for improving executive function parameters.

[0038] In the context of the present invention, the term “executive function” is to be understood as a set of complex mental processes and cognitive abilities required for goal directed behavior. It includes skills such as transitioning between thinking and acting on different concepts, implementing strategic thinking for problem-solving and decision making, setting goals and developing plans to achieve those goals, and the ability to suppress inappropriate responses. Executive function is one of the main domains of cognitive function.

[0039] In a further embodiment, improving executive function parameters comprises: improving manipulation of visuospatial information, improved spatial working memory, improved spatial awareness, improving strategy making, improving strategic planning, improving strategic thinking, improving strategic planning with less errors, improving strategic thinking with less errors, improving problem solving, improving response inhibition, improving high level thinking, improving reasoning, improving retention, improving decision making, improving mental flexibility, and / or improving planning.

[0040] Executive function parameters can be assessed using different methods such as behavioral / neuropsychological testing batteries as disclosed in the methods section. Other suitable methods include questionnaires, rating scales, and functional neuroimaging.

[0041] Executive function can be assessed by various tests, measuring different components. One example is the spatial working memory test, which gives outcomes on errors and strategy scores. Spatial working memory is an important component of executive function and includes parameters such as the ability to remember and manipulate spatial information.

[0042] In the context of the present invention, it was shown that the claimed extracts and compositions improve spatial working memory (see example 1 and 2). Spatial working memory tests are a validated read-out for amongst others the executive function parameters retention and the manipulation visuospatial information. These outcomes are linked to mental flexibility, spatial awareness, problem solving and decision making. Accordingly, it can be concluded that the extract and compositions of the present invention are capable of improving spatial working memory, retention, manipulation of visuospatial information, mental flexibility, spatial awareness decision making and problem solving.

[0043] In a particular embodiment, the use of an Aronia berry extract or a composition comprising Aronia berry extract can improve or reduce at least one executive function parameter selected from the above-mentioned list by at least 0.1%, such as at least 0.5%, at least 1.0%, at least 1.5%, preferably at least 2.0%, more preferably at least 2.5%, particularly preferably at least 3.0%, and most preferably at least 4.0% when compared to untreated subjects.

[0044] Where in the context of the present invention for a particular parameter, a comparison with untreated subjects is made, this is meant to be a comparison of said parameter in individuals being administered the extracts or compositions according to the invention, versus the same parameter in individuals not being administered the extracts or compositions of the invention. In another particular embodiment, the use of an Aronia berry extract or a composition comprising said Aronia berry extract can improve or reduce at least one executive function parameter selected from the above-mentioned list of symptoms by at least 5%, such as at least 10%, at least 15%, at least 20%, preferably at least 25%, more preferably at least 30%, and most preferably at least 40%, when compared to untreated subjects. Another object of the present invention relates to the non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract for improving mental wellbeing parameters.

[0045] In the context of the present invention, the term ‘mental wellbeing’ is to be understood as a state of mental health. This does not merely include the absence of mental disorders, but also emotional, social and psychological wellbeing. It helps determine a person’s ability to cope with stress, manage emotions, and build and maintain social relationships. In another embodiment, improving mental wellbeing comprises: improving quality of life, improving emotional wellbeing, improving pleasantness, improving arousal, improving mood, reducing stress, and / or improving emotion.

[0046] In another particular embodiment, the present invention relates to the non-therapeutic use of an Aronia berry extract or a composition comprising Aronia berry extract to improve one or more mental wellbeing parameters selected from the group comprising: emotional stability, social functioning, and self-perception.

[0047] Mental wellbeing parameters can be assessed using validated self-reported questionnaires or rating scales, including the affect grid, as described in the methods section. Other methods include clinical interviews or physiological measures.

[0048] In the context of the present invention, it was shown that the claimed extracts and compositions increased affect grid scores (example 2). The affect grid is a two-dimensional single item mood scale, that assesses the degree of pleasantness and arousal. Pleasantness reflects the individual’s subjective evaluation of how positive or negative their current emotional state feels (how content or happy they feel). Arousal on the affect grid is reflects the current level of physiological and psychological activation or energy (how awake, alert, or stimulated they feel). An increase in pleasantness and arousal on this grid indicates a shift towards higher energy and more positive mood states, which contribute to emotional wellbeing and thereby support overall mental wellbeing.

[0049] In a specific embodiment, the use of an Aronia berry extract or a composition comprising Aronia berry extract can improve or reduce at least one mental wellbeing parameter selected from the above-mentioned list by at least 0.1%, such as at least 0.5%, at least 1.0%, at least 1.5%, preferably at least 2.0%, more preferably at least 2.5%, particularly preferably at least 3.0%, and most preferably at least 4.0% when compared to untreated subjects.

[0050] In another embodiment, the use of an Aronia berry extract or a composition comprising Aronia berry extract can improve or reduce at least one mental wellbeing function parameter selected from the above-mentioned list of parameters by at least 5%, such as at least 10%, at least 15%, at least 20%, preferably at least 25%, more preferably at least 30%, and particularly preferably at least 40%, when compared to untreated subjects.

[0051] Without being bound by theory, there is a close relationship between mental wellbeing and sleep quality. Poor mental health including stress can result in sleep disturbances, such as prolonged sleep latency, reduced sleep duration and an increased number of times waking up during the night. Improving mental wellbeing parameters can therefore also result in enhanced sleep quality. Enhanced mental wellbeing has been associated with less daytime naps, less trouble falling asleep and better overall sleep quality.

[0052] In the context of this invention, improving sleep quality can be defined as decreased sleep onset latency, decreased sleep latency, improved sleep efficiency, decreased sleep disturbance, decreased wake after sleep onset, decreased number of awakenings, improved ratio of sleep stages, decreased medication use, decreased daytime dysfunction, feeling more rested / refreshed, feeling less sleepy after waking up and increased sleep duration.

[0053] Therefore, in an embodiment, the present invention also relates to the non-therapeutic use of an Aronia berry extract or a composition comprising Aronia berry extract to improve parameters of sleep quality.

[0054] A further object of the present invention relates to the non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract to improve memory parameters. In the context of the present invention, the term ‘memory’ is to be understood as the processes involved in encoding, storage and retrieval of information. Memory can be categorized into different types of memory, such as sensory memory, short-term memory and long-term memory.

[0055] In another specific embodiment, improving memory comprises: improving visual associative learning, improving visual matching ability, improving (short-term visual) recognition, improving visual memory, improving episodic memory performance, improving learning capacity, improving encoding, improving recall efficiency, improving visual memory, improving task accuracy, improving learning efficacy, reducing error making, reducing mistake making, improving memory scores, improving remembering of pattern locations, and / or improving delayed memory.

[0056] Memory can be assessed using different methods such as neuropsychological tests, behavioral tests and self-reported measures.

[0057] In the context of the present invention, it was shown that the claimed extracts and compositions improved the first attempt memory score and location recall on the paired associated learning task (example 2). This task is designed to measure outcomes within the memory domain, that give an indication of visual memory and new learning. Therefore, it can be concluded that the extract and compositions of the present invention are capable of improving visual associative learning, episodic memory, encoding, recall efficiency, visual memory, task accuracy and learning efficacy.

[0058] In a particular embodiment, the use of an Aronia berry extract or a composition comprising Aronia berry extract can improve or reduce at least one memory parameter selected from the above-mentioned list by at least 0.1%, such as at least 0.5%, at least 1.0%, at least 1.5%, preferably at least 2.0%, more preferably at least 2.5%, particularly preferably at least 3.0%, and most preferably at least 4.0% when compared to untreated subjects.

[0059] In another particular embodiment, the use of an Aronia berry extract or a composition comprising Aronia berry extract can improve or reduce at least one memory parameter selected from the above-mentioned list of symptoms by at least 5%, such as at least 10%, at least 15%, at least 20%, preferably at least 25%, more preferably at least 30%, and particularly preferably at least 40%, when compared to untreated subjects.

[0060] The non-therapeutic use of the extract or composition according to the invention is specifically directed to human subjects, in particular healthy human subjects. In the context of the present invention, the term healthy human subject is to be understood as an individual that is not diagnosed with cognitive decline, memory loss, memory impairment, or any other form of cognitive impairment.

[0061] In an embodiment, the healthy human subject is an adult, in particular an adult between the age of 18 to about 75 years, about and between 18 to 55 years. Alternatively, about and between 55 to 75 years. More in particular about and between 18 to 45 years, and even more in particular about and between 18 and 35 years.

[0062] Within the context of the present invention, the term "subject" or “individual” or “participant” refers to a human, in particular a healthy human.

[0063] In an embodiment, the composition according to the invention is used for human and / or animal consumption.

[0064] The blood brain barrier (BBB) is a highly selective semipermeable membrane that separates the central nervous system from the circulation. It prevents harmful substances from entering the brain while supplying it with essential nutrients. A compromised BBB function has been associated with the development of neurological and psychiatric disorders and stress responses. By maintaining the brain’s internal homeostasis, the BBB plays an important role in cognitive function and mental wellbeing. In a specific embodiment, the improvement in executive function, mental wellbeing and / or memory is accompanied by an improved blood brain barrier function.

[0065] The present application relates to the non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract. Aronia berries contain a large amount of flavonoids (polyphenolic compounds) such as anthocyanins. In the following paragraphs, concentrations of anthocyanins and other compounds are disclosed and relate to concentrations in the Aronia berry extract. One skilled in the art will understand that final concentrations in the composition comprising the Aronia extract will deviate proportionally to the amount of extract used in the composition.

[0066] As used herein, the term “anthocyanin” also termed “anthocyans” refers to a group of pigments that belong to the flavonoid family synthesized via the phenylpropanoid pathway. Anthocyanins are water-soluble vacuolar pigments that are present in all tissues of higher plants, including leaves, stems, roots, flowers, and fruits and depending on their pH, may appear red, purple, blue, or black. Flavonoid compounds such as anthocyanins protect plants against insects and external stress, and act as antioxidants to prevent damage by active oxygen. In particular, when these anthocyanins are ingested by animals or humans, they can exert various beneficial functions, including anti-oxidant action, anti-inflammatory effects, improving cardiovascular health, and protecting against eye diseases.

[0067] In a specific embodiment, the Aronia berry extract comprises an anthocyanin, preferably cyanidin-3-O-glycoside, more preferably selected from the list comprising: cyanidin-3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, cyanidin-3-xyloside, or any combination thereof.

[0068] In a specific embodiment, the extract or composition according to the invention comprises cyanidin-3-galactoside in combination with cyanidin-3-glucoside; alternatively cyanidin-3-galactoside in combination with cyanidin-3-arabinoside; alternatively cyanidin-3-galactoside in combination with cyanidin-3-xyloside; alternatively cyanidin-3-glucoside in combination with cyanidin-3-arabinoside; alternatively cyanidin-3-glucoside in combination with cyanidin-3-xyloside; alternatively cyanidin-3-arabinoside in combination with cyanidin-3-xyloside; alternatively cyanidin-3-galactoside in combination with cyanidin-3-glucoside, cyanidin-3-xyloside; alternatively cyanidin-3-galactoside in combination with cyanidin-3-arabinoside, cyanidin-3-xyloside; alternatively cyanidin-3-glucoside in combination with cyanidin-3-arabinoside, cyanidin-3-xyloside; alternatively cyanidin-3-galactoside in combination with cyanidin-3-glucoside, cyanidin-3-arabinoside, cyanidin-3-xyloside. In a particular embodiment, the Aronia berry extract comprises at least 10% (w / w), anthocyanins, preferably at least 15% (w / w) anthocyanins, more preferably at least 20% (w / w) anthocyanins, even more preferably at least 25% (w / w) anthocyanins.

[0069] In a specific embodiment, the Aronia berry extract comprises about and between 1% to about 50% (w / w), preferably about and between 5% to about 40% (w / w), more preferably about and between 10% to about 35% (w / w), most preferably about and between 15% and about 30% (w / w) of anthocyanin.

[0070] In another specific embodiment, the Aronia berry extract comprises about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% (w / w) of anthocyanins.

[0071] In another particular embodiment, in the case that cyanidin-3-galactoside is present, said Aronia berry extract comprises at least 30% (w / w) cyanidin-3-galactoside, preferably at least 40% (w / w), more preferably at least 50% (w / w), most preferably at least 60% (w / w) of the total amount of cyanidin-3-O-glycoside.

[0072] In a specific embodiment, in the case that cyanidin-3-galactoside is present in the Aronia berry extract, then cyanidin-3-galactoside comprises about and between 25% to about 100% (w / w), preferably about and between 35% to about 90% (w / w), more preferably about and between 40% to about 80% (w / w), most preferably about and between 50% and about 70% (w / w) of the total amount of cyanidin-3-O-glycoside.

[0073] In another specific embodiment, in the case that cyanidin-3-galactoside is present in the Aronia berry extract or a composition comprising said Aronia berry extract, then cyanidin-3-galactoside comprises about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% (w / w) of the total amount of cyanidin-3-O-glycoside.

[0074] In yet another embodiment, the Aronia berry extract comprises at least about 5% (w / w) cyanidin-3-galactoside, preferably at least about 10% (w / w) cyanidin-3-galactoside, more preferably at least about 15% (w / w) cyanidin-3-galactoside (w / w) of the total amount of the extract.

[0075] In a specific embodiment, the Aronia berry extract comprises about and between 5% to about 80% (w / w), preferably about and between 10% to about 70% (w / w), more preferably about and between 15% to about 60% (w / w), most preferably about and between 20% and about 50% (w / w) cyanidin-3-galactoside of the total amount of the extract. In another specific embodiment, the Aronia berry extract comprises about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% (w / w) cyanidin-3-galactoside of the total amount of the extract.

[0076] In a particular embodiment, the Aronia berry extract comprises at least about 3% (w / w), at least about 5% (w / w) cyanidin-3-glucoside, preferably at least about 10% (w / ) cyanidin-3-glucoside, more preferably at least about 15% (w / w) cyanidin-3-glucoside (w / w) of the total amount of the extract.

[0077] In a specific embodiment, the Aronia berry extract comprises about and between 5% to about 80% (w / w), preferably about and between 10% to about 70% (w / w), more preferably about and between 15% to about 60% (w / w), most preferably about and between 20% and about 50% (w / w) cyanidin-3-glucoside of the total amount of the extract.

[0078] In another specific embodiment, the Aronia berry extract comprises about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% (w / w) cyanidin-3-glucoside of the total amount of the extract.

[0079] In a further embodiment, the extract of the invention comprises:

[0080] • at least 10% anthocyanins;

[0081] • of which at least 25% cyanidin-3-O-glycosides; and

[0082] • of which at least 50% cyanidin-3-galactoside.

[0083] In a further embodiment, the extract of the invention comprises:

[0084] • at least 20% anthocyanins;

[0085] • of which at least 25% cyanidin-3-O-glycosides; and

[0086] • of which at least 50% cyanidin-3-galactoside.

[0087] In another embodiment, the composition comprises about and between 1 mg to 1000 mg of Aronia berry extract, such as more than 1 mg and less than 750 mg, about and between 5 mg to 750 mg, about and between 15 and 500 mg, about and between 30 mg to 250 mg, or about and between 65 to150 mg of Aronia berry extract.

[0088] In a further embodiment, the composition comprises at least 15 mg of Aronia berry extract, such as at least 30 mg, at least 50 mg, at least 100 mg, at least 125 mg or at least 200 mg of Aronia berry extract. In an even further embodiment, the composition according to the invention comprises about 5 mg, 10 mg, 15 mg, 25 mg, 50 mg, 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg of Aronia berry extract.

[0089] In a specific embodiment, the composition comprises about and between 1 mg to 500 mg of anthocyanin, preferably about and between 10 mg to 300 mg, more preferably about and between 15 mg to 200 mg of anthocyanin.

[0090] In another embodiment, the composition comprises at least 5 mg of anthocyanin, such as at least 10 mg, at least 15 mg, at least 20 mg, at least 30 mg or at least 40 mg of anthocyanin. In an even further embodiment, the composition according to the invention comprises about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg of anthocyanin.

[0091] In a specific embodiment, the composition of the invention comprises an Aronia berry extract comprising about 16% or about 25% of anthocyanin.

[0092] A non-limiting example of a composition according to the invention comprises about 65 mg of Aronia berry extract of which about 16 mg is anthocyanin.

[0093] Another non-limiting example of a composition according to the invention comprises about 200 mg of Aronia berry extract of which about 50 mg is anthocyanin.

[0094] Another non-limiting example of a composition according to the invention comprises about 250 mg of Aronia berry extract of which about 60 mg is anthocyanin.

[0095] Another non-limiting example of a composition according to the invention comprises about 300 mg of Aronia berry extract of which about 75 mg is anthocyanin.

[0096] Another non-limiting example of a composition according to the invention comprises about 750 mg of Aronia berry extract of which about 180 mg is anthocyanin.

[0097] In some embodiments, the compositions may further comprise optionally one or more of a protein source, a free amino acid, a carbohydrate source, a fat source, a vitamin, a mineral, or an anti-oxidant. In another specific embodiment, the composition further comprises one or more compounds selected from a group comprising: caffeine, taurine, theanine, inositol, guarana, magnesium, melatonin, ribose, carnitine, co-enzyme Q10, alpha-glycerophosphocholine, alpha-lipoic acid, luteolin-7-glucoside, luteolin, quercetin, xylose lutein, zeaxanthin, astaxanthin, meso-zeaxanthin, beta-carotene, zinc, copper, vitamin B1 , vitamin B6, vitamin B12, vitamin A, vitamin C, vitamin D, vitamin E, omega-3 fatty acids, and / or anti-oxidants.

[0098] As used herein, the term “anti-oxidants” refers to molecules that can inhibit oxidation. Suitable anti-oxidants that can be in the composition are but not limited to resveratrol, selenium, lycopene and curcumin.

[0099] In yet another embodiment, said Aronia berry extract is an Aronia melanocarpa berry extract. The extract according to the invention can be obtained by extracting, isolating and fractionating whole Aronia berries with or without the seeds, using extraction, separation and fractionation methods known in the art, and can be extracted according to various extraction solvents and extraction methods. Exemplary methods for preparing Aronia berry extracts derived from Aronia melanocarpa may be found in KR101978336B1. Following such extraction methods, extracts in the form of a powder may be obtained. Alternatively, an extract in accordance with the present invention may also be in the form of a juice concentrate of Aronia berries with or without the seeds, wherein said juice concentrate may be a standardized concentrate.

[0100] As an illustrative example, an Aronia berry extract is prepared using a method comprising the following steps:

[0101] a) immersing Aronia berries with an extraction solution being water or an extraction solution essentially made of an alcoholic solution comprising at least 25% alcohol by weight, for example ethanol, for a period of time of at least 4 hours;

[0102] b) recovering the resultant extraction solution from end of step a);

[0103] c) immersing Aronia berries from step a) with a new extraction solution, which composition is similar to that defined hereabove, for a period of time of at least 4 hours; d) recovering the extraction solution from end of step c);

[0104] e) collecting the resultant extraction solutions respectively from step b) and step c); f) vacuum distillating the resultant solution from step e), for example at 70°C., so as to yield a concentrate comprising from 30% to 40% by weight of solids; and

[0105] g) drying the resultant concentrate from end of step f, for example by spraying at 70°C, so as to yield an extract as particles comprising from 10% to 40% by weight of anthocyanin content. The solution for extracting the Aronia berry extract may include a crude extract, a polar solvent extract, or a non-polar solvent soluble extract, preferably a polar solvent extract. In addition, the polar solvent-soluble extract may be water or an organic solvent such as but not limited to methanol, n-propyl alcohol, isopropyl alcohol, and t-butyl alcohol. Or a mixture thereof.

[0106] In an embodiment, the extract or composition according to the invention can be administered in multiple doses per day and more specifically at least once, twice, three times, four times a day, preferably in at least one or two doses per day.

[0107] In a preferred embodiment, the composition is administered on a regimen of one intake per day.

[0108] In a particular embodiment, the composition is administered on a regimen of one intake per day comprising about 65 mg of Aronia berry extract, with about 16 mg of anthocyanin.

[0109] In a particular embodiment, the composition is administered on a regimen of three intakes per day wherein each intake comprises about and between 150 mg to 500 mg of Aronia berry extract, in particular about 250 mg of Aronia berry extract.

[0110] In another particular embodiment, the composition is administered on a regimen of three intakes per day wherein each intake comprises about and between 15 mg to 500 mg, preferably 60 mg of anthocyanins.

[0111] In another embodiment, the composition can also be administered on in one intake per day wherein said composition comprises about 750 mg of Aronia extract of which about 180 mg anthocyanins.

[0112] In a particular embodiment, said composition is an oral composition.

[0113] The composition is administered as a supplement to the diet of an individual multiple times a week, more specifically once, twice, three times, four times, five times, six times, seven times a week, preferably daily.

[0114] In an embodiment, the composition is administered to the individual consecutively for a number of days until a beneficial effect is achieved. For example, the composition can be administered to the individual daily for at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 or more consecutive days. As another example, the composition can be administered to the individual for a longer period, such as a period of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 years.

[0115] In a particular embodiment, the composition is administered to the individual for at least 1 week, such as at least 2 weeks, at least 3 weeks, at least 4 weeks, preferably at least 1 weeks. In another embodiment, the composition is administered at least 3 months, for example a period of 3 months to 1 year, and preferably for at least 6 months.

[0116] The above examples of administration do not require continuous daily administration with no interruptions. Instead, there may be some short breaks in the administration, such as a break of two to four days during the period of administration. The ideal duration of the administration of the composition can be determined by those of skill in the art.

[0117] The compositions for non-therapeutic use of the present invention, can be prepared in any known or otherwise effective dosage or product form suitable for use in providing to systemic delivery of the Aronia extract compounds to the site of interest, which would include both nonpharmaceutical dosage forms as well as nutritional product forms. For example, the extracts can be formulated along with common excipients, diluents, or carriers, and formed into oral tablets, capsules, sprays, mouth washes, lozenges, treated substrates (e.g., oral or topical swabs, pads, or disposable, non-digestible substrate treated with the compositions of the present invention); oral liquids (e.g., suspensions, solutions, emulsions), powders, or any other suitable dosage form.

[0118] Non-limiting examples of suitable excipients, diluents, and carriers can be: fillers and extenders such as starch, sugars, mannitol, and silicic derivatives; binding agents such as carboxymethyl cellulose and other cellulose derivatives, alginates, gelatin, and polyvinyl pyrolidone; disintegrating agents such as calcium carbonate and sodium bicarbonate; surface active agents such as acetyl alcohol, glycerol monostearate; adsorptive carriers such as kaolin and bentonite ; carriers such as propylene glycol and ethyl alcohol, and lubricants such as talc, calcium and magnesium stearate, and solid polyethyl glycols.

[0119] The compositions are preferably administered as oral dosage forms. For example, the composition may be selected from the group consisting of food compositions, dietary supplements, nutritional compositions, nutraceuticals, powdered nutritional products to be reconstituted in a liquid before consumption, food additives, medicaments, beverages and drinks. Preferred dosage or product forms in this respect include oral tablets, capsules, oral liquids as well as powders to be reconstituted in a liquid or to be used in for example but not limited to bakery matrices such as bread, cookies and biscuits; and dairy products such as butter, cheese, milk, and yoghurt.

[0120] In another particular embodiment, said composition is in the form of a pill, powder, capsule, tablet, gel, gummy, beverage, chewing gum, chewable tablet, lozenge, or troche.

[0121] In a preferred embodiment, the composition is in the form of a pill or capsule. In another embodiment, the composition is in the form of a powder to be reconstituted in or sprinkled over food matrices. Suitable food matrices to reconstitute are but not limited to liquids such as water, milk, juices; gels such as grape jelly, emulsions such as mayonnaise, fibrous materials such as fruits and vegetables, crystals such as sugars, porous structures such as marshmallows and much more.

[0122] In another particular embodiment, the present invention provides a method for improving executive function parameters, mental wellbeing and / or memory in healthy human subjects, the method comprising administering an Aronia berry extract or a composition comprising an Aronia berry extract to the subject. Example 1 - Effects on executive function in healthy individuals after intake of 160 mg Aronia berry extract

[0123] Methods

[0124] The study was a randomized, double-blind, placebo-controlled, cross-over trial consisting of two study groups and a pre- and post-test day in both study arms. The study population consisted of healthy adults with a body mass index (BMI) between 25-35 kg / m2, which have no specific signs of cognitive decline.

[0125] Participants ingested, in random order, capsules containing 160 mg of Aronia Melanocarpa extract (AME) or placebo (cellulose) capsules for six weeks, separated by a 12-week washout period.

[0126] Participants underwent measurements in the morning in a fasted state in a room with controlled temperature at 22°C. During test visits, executive function tests (Multitasking test and Spatial Working Memory test) were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) system. CANTAB is a validated and computerized assessment tool that is designed to evaluate various aspects of cognitive function.

[0127] Results

[0128] On the spatial working memory test, significantly less errors (20% less between errors and 20% less total errors) were observed after six weeks of AME supplementation compared to placebo (Fig. 1A, B; both p=0.006). This shows improvements in the executive function parameters retention and manipulation of visuospatial information. Improvements in the retention and manipulation of visuospatial information indicate mental flexibility, and spatial awareness, leading to better problem-solving skills and practical applications in daily life Example 2 - Effects on executive function, mental wellbeing and memory in healthy young adults after intake of 65 mg Aronia berry extract

[0129] Methods

[0130] Apparently healthy young adults aged 18-35 years without cognitive decline with a body mass index (BMI) between 18 and 30 kg / m2were included in the study. The study was designed as a randomized, double-blind, placebo-controlled cross-over trial, where each participant was randomly allocated to receive either six weeks of Aronia Melanocarpa extract (AME) or placebo, separated by a six-week wash-out period.

[0131] The study product consisted of capsules containing 65 mg of AME or placebo (cellulose). Participants were instructed to ingest one capsule daily before breakfast.

[0132] All study visits were arranged in the morning while participants were in a fasted state, and each visit for the same participant took place at the same time of day. During the test visits, outcomes of cognitive function were measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) system. Mood was assessed using the Affect Grid, which is a two-dimensional single item mood scale, assessing the degree of pleasantness and arousal as perceived by the study participants at the end of the interventions.

[0133] Results

[0134] After six weeks of AME intake, the number of errors on the spatial working memory test was significantly lower compared to placebo (Fig. 2; p=0.003). This shows that AME intake was able to significantly improve spatial working memory, which is an important component of executive function. It involves the ability to remember and manipulate spatial information and plays a key role in decision-making and problem-solving.

[0135] Improvements were also seen on the paired associated learning task, which is part of the memory domain. AME supplementation significantly increased the participants' ability to correctly recall the location of paired patterns on their very first try in the memory task (Fig. 3A; p=0.049). This is a cognitive measure linked to visual associative learning and episodic memory, reflecting better encoding and recall efficiency. AME supplementation also significantly decreased errors compared to the placebo group when the number of times a subjects chooses the incorrect box were measured (Fig 3B; p=0.045). The intervention thus led to a statistically significant improvement in visual memory, task accuracy and learning efficacy. In male participants, AME supplementation showed a trend towards an increased Affect Grid pleasure (Fig 4A; p=0.081) and arousal (Fig 4B; p=0.140). The pleasantness dimension specifically measures the self-reported positivity in their mood, while the arousal dimension specifically measures the current level of physiological and psychological activation or energy (how awake, alert, or stimulated they feel). Together these trends suggest both an increase in arousal and pleasantness, suggesting elevated mood towards a more excited state after AME intervention in men.

[0136] References

[0137] Lee HY, Weon JB, Jung YS, Kim NY, Kim MK, Ma CJ. Cognitive-Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice.

[0138] Evidence-Based Complement Altern Med. 2016; 2016: 1-8.

Claims

Claims1. Non-therapeutic use of an Aronia berry extract or a composition comprising said Aronia berry extract for improving executive function parameters, mental wellbeing and / or memory in healthy human subjects.

2. Non-therapeutic use according to claim 1, wherein improving said executive function parameters comprises: improving manipulation of visuospatial information, improved spatial working memory, improved spatial awareness, improving strategy making, improving strategic planning, improving strategic thinking, improving strategic planning with less errors, improving strategic thinking with less errors, improving problem solving, improving response inhibition, improving high level thinking, improving reasoning, improving retention, improving decision making, improving mental flexibility, and / or improving planning.

3. Non-therapeutic use according to any one of claims 1 to 2, wherein improving said mental wellbeing comprises: improving pleasantness improving quality of life, improving emotional wellbeing, improving arousal, improving mood, reducing stress, and / or improving emotion.

4. Non-therapeutic use according to any one of claims 1 to 3, wherein improving said memory comprises: improving visual associative learning, improving visual matching ability, improving (short-term visual) recognition, improving visual memory, improving episodic memory performance, improving learning capacity, improving encoding, improving recall efficiency, improving visual memory, improving task accuracy, improving learning efficacy, reducing error making, reducing mistake making, improving memory scores, improving remembering of pattern locations, and / or improving delayed memory.

5. Non-therapeutic use according to claims 1 to 4, wherein said Aronia berry extract comprises an anthocyanin, preferably cyanidin-3-O-glycoside, more preferably selected from the list comprising: cyanidin-3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, cyanidin-3-xyloside or any combination thereof.

6. Non-therapeutic use according to any one of claims 1 to 5, wherein said Aronia berry extract comprises at least 10% (w / w), anthocyanins, preferably at least 15% (w / w) anthocyanins, more preferably at least 20% (w / w) anthocyanins, even more preferably at least 25% (w / w) anthocyanins.

7. Non-therapeutic use according to claim 5, wherein in the case that cyanidin-3-galactoside is present, said Aronia berry extract comprises at least 30% (w / w) cyanidin-3-galactoside, preferably at least 40% (w / w), more preferably at least 50% (w / w), most preferably at least 60% (w / w) of the total amount of cyanidin-3-O-glycoside.

8. Non-therapeutic use according to any one of claims 1 to 7, wherein said Aronia berry extract comprises at least about 5% (w / w) cyanidin-3-galactoside, preferably at least about 10% (w / w) cyanidin-3-galactoside, more preferably at least about 15% (w / w) cyanidin-3-galactoside (w / w) of the total amount of the extract.

9. Non-therapeutic use according to any one of claims 1 to 8, wherein said composition comprises about and between 1 mg to 1000 mg of Aronia berry extract, such as more than 1 mg and less than 750 mg, about and between 5 mg to 750 mg, about and between 15 and 500 mg, about and between 30 mg to 250 mg, or about and between 65 to150 mg of Aronia berry extract.

10. Non-therapeutic use according to any one of claims 1 to 9, wherein said composition comprises about and between 1 mg to 500 mg of anthocyanin, preferably about and between 10 mg to 300 mg, more preferably about and between 15 mg to 200 mg of anthocyanin.

11. Non-therapeutic use according to any one of claims 1 or 10, wherein said composition further comprises one or more compounds selected from a group comprising: caffeine, taurine, theanine, inositol, guarana, magnesium, melatonin, ribose, carnitine, co-enzyme Q10, alpha-glycerophosphocholine, alpha-lipoic acid, luteolin-7-glucoside, luteolin, quercetin, xylose lutein, zeaxanthin, astaxanthin, meso-zeaxanthin, beta-carotene, zinc, copper, vitamin B1 , vitamin B6, vitamin B12, vitamin A, vitamin C, vitamin D, vitamin E, omega-3 fatty acids, and / or anti-oxidants.

12. Non-therapeutic use according to any one of claim 1 to 11, wherein said Aronia berry extract is an Aronia melanocarpa berry extract.

13. Non-therapeutic use according to any one of claims 1 to 12, wherein said composition is an oral composition.

14. Non-therapeutic use according to any one of claims 1 to 13, wherein said composition is in the form of a pill, powder, capsule, tablet, gel, gummy, beverage, chewing gum, chewable tablet, lozenge or troche.

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