NZ705719A - Acute cognitive and mood effects of plant polysaccharides in adult human subjects - Google Patents

Abstract

Use of a dietary supplement for improving mood, learning, memory, reducing stress, anxiety or mental fatigue, or any combination thereof in a human subject; wherein a nutritionally effective amount of the dietary supplement is administered to the human subject in an amount sufficient to improve mood, learning, memory, reduce stress, anxiety, mental fatigue, or any combination thereof, and wherein the human subject has been identified by the use of one or more tests as being in need of improvement in mood, learning, memory, reduction of stress, anxiety, or mental fatigue, or any combination thereof. , learning, memory, reduce stress, anxiety, mental fatigue, or any combination thereof, and wherein the human subject has been identified by the use of one or more tests as being in need of improvement in mood, learning, memory, reduction of stress, anxiety, or mental fatigue, or any combination thereof.

Description

ACUTE COGNITIVE AND MOOD EFFECTS OF PLANT POLYSACCHARIDES IN ADULT HUlVLAN SUBJECTS Technical Field of the Invention The present ion relates in general to the field of dietary supplements, and more particularly, to a y supplement comprising plant polysaccharides that has a beneficial effect on cognitive performance and mood in —aged adults. ound Art Without limiting the scope of the invention, its ound is described in connection with health effects of plant polysaccharides including dietary ments thereof.

US. Patent No. 7,157,431 issued to Mcanalley et a1. (2007) discloses compositions of plant ydrates for dietary supplements and nutritional support for promotion and maintenance of good health. Defined nutritionally effective amounts of one to eleven essential saccharides, glyconutrients, are used in various inventive compositions as dietary supplements. The dietary composition herein can include phytonutrients, ns, minerals, herbal extracts, and other non-toxic nutrients. The glyconutritional dietary supplement herein provides essential saccharides which are the building blocks of glycoproteins. These compositions, when administered orally or topically, have been found to improve the well being of mammals suffering from a variety of disorders.

Disclosure of the Invention The present invention bes the beneficial health effects of dietary ments containing plant polysaccharides. More specifically, the present invention details improved cognitive performance and mood in middle-aged adults following administration of a plant polysaccharide containing dietary supplement.

In one embodiment, the instant invention provided a method for improving cognition, mood, learning, memory, reducing stress, anxiety, -fatigue, modifying or, or any combinations thereof in a human subject comprising the steps of: fying the human subject in need of improvement of cognition, mood, learning, memory, reduction of , anxiety, mental-fatigue, modifying behavior, or any combinations thereof and administering a nutritionally effective amount of a dietary ment in an amount sufficient to improve cognition, mood, learning, memory, reduce stress, anxiety, mental-fatigue, modifying behavior, or any combinations thereof. In one aspect of the instant invention, the dietary supplement is adapted for oral administration and is in the form of a , is dissolved in a liquid, is encapsulated, or any combinations thereof.

The method, as described hereinabove, further comprises the steps of: (i) performing one or more tests to assess the cognition, memory, mood, stress and anxiety level, or any combinations thereof in the human subject prior to the administration of the dietary supplement to ine a baseline or pre—test level for the human subject, (ii) performing one or more tests to assess the ion, , mood, stress and anxiety level, or any combinations thereof in the human subject at one or more specified time-points after the administration of the dietary supplement to determine a post-test level for the human subject, and (iii) comparing the baseline and the post- test levels to ine uation, termination, or modification of the administration of the dietary supplement in the human subject.

In another , the human subject may suffer from one or more heart conditions, diabetes, head/brain injury, neurological conditions, neurodegenerative conditions, psychiatric conditions, or any combinations thereof In yet another aspect, the stress or the anxiety arises from one or more stress disorders, Post Traumatic Stress Disorder (PTSD), phobias, psychological traumas, or any combinations thereof In another aspect, the dietary supplement ates one or more adverse effects d by central s system drugs, alcohol abuse, or any combinations thereof The method, described above, further comprises the step of measuring blood glucose levels prior to and after administration of the dietary supplement. In another aspect, the dietary supplement does not cause an elevated blood glucose level in the subject and the dietary supplement may be administered simultaneously or sequentially in one or a combination of dosage forms. In yet another aspect, the dietary supplement may be stered aneously or sequentially with one or more drugs, vitamins, other nutritional supplements, or any combinations thereof.

The dietary supplement described in the method hereinabove ses: (i) a nutritionally effective amount of isolated and purified ated mannose and (ii) a nutritionally effective amount of at least five isolated and purified saccharides selected from: galactose, glucose, mannose, xylose, N—acetylneuraminic acid, , N—acetylgalactosamine, N— acetylglucosamine, arabinose, glucuronic acid, uronic acid, iduronic acid and arabinogalactan.

A method for improving cognition, mood, learning, memory, ng stress, anxiety, mental- fatigue, modifying behavior, or any combinations thereof in a human subject without elevation of blood glucose levels is described in another embodiment of the instant invention. The method comprises the steps of: identifying the human subject in need of improvement of cognition, mood, ng, memory, reduction of stress, anxiety, mental-fatigue, modifying behavior, or any combinations thereof and stering a ionally effective amount of a dietary supplement in an amount sufficient to improve cognition, mood, learning, memory, reduce stress, anxiety, mental-fatigue, modifying behavior, or any combinations thereof. In one aspect, the dietary supplement is adapted for oral administration. In another aspect, the dietary supplement is a powder, is dissolved in a liquid, is ulated, or any combinations thereof. In yet another aspect, the method comprises the step of measuring blood glucose levels prior to and after stration of the y supplement and the step of terminating the administration of the dietary supplement in case of an ally elevated blood glucose levels.

The method, as described hereinabove, further ses additional steps, these include: (i) performing one or more tests to assess the cognition, memory, mood, stress and anxiety level, or any combinations thereof in the human subject prior to the administration of the dietary supplement to determine a baseline or st level for the human subject, (ii) performing one or more tests to assess the cognition, memory, mood, stress and anxiety level, or any combinations f in the human subject at one or more specified time-points after the administration of the dietary supplement to determine a est level for the human subject, and (iii) comparing the baseline and the est levels to determine continuation, termination, or modification of the administration of the dietary supplement in the human subject. In one aspect, the human subject may suffer from one or more heart conditions, diabetes, head/brain injury, neurological conditions, neurodegenerative conditions, psychiatric ions, or any combinations thereof. In another aspect, the stress or the anxiety arises from one or more stress disorders, Post Traumatic Stress Disorder (PTSD), phobias, psychological s, or any combinations thereof. In yet another aspect, the dietary supplement alleviates one or more adverse effects induced by central nervous system drugs, alcohol abuse, or any combinations thereof.

The dietary supplement of the method of the present invention may be administered simultaneously or sequentially in one or a combination of dosage forms and with one or more drugs, vitamins, other nutritional ments, or any ations thereof. The dietary supplement comprises: (i) a ionally effective amount of isolated and purified acetylated mannose and a nutritionally effective amount of at least five ed and purified saccharides 2012/034752 selected from: galactose, glucose, mannose, xylose, N—acetylneuraminic acid, fucose, N— acetylgalactosamine, N-acetylglucosamine, arabinose, glucuronic acid, galacturonic acid, ic acid and ogalactan. In a related aspect the at least five isolated and purified saccharides further comprise glucosamine and rhamnose.

In yet another embodiment, the present invention discloses a method for improving cognition, mood, learning, , reducing stress, anxiety, mental-fatigue, modifying behavior, or any combinations thereof in a human subject without elevation of blood glucose levels sing the steps of: identifying the human subject in need of improvement of cognition, mood, learning, memory, reduction of stress, anxiety, mental-fatigue, modifying behavior, or any combinations thereof and administering a nutritionally effective amount of a dietary supplement in an amount sufficient to improve cognition, mood, learning, memory, reduce stress, anxiety, mental-fatigue, modifying behavior, or any combinations thereof. The dietary supplement disclosed herein comprises: a nutritionally effective amount of isolated and purified acetylated mannose and a nutritionally effective amount of at least five ed and purified saccharides selected from: galactose, e, mannose, xylose, N—acetylneuraminic acid, fucose, N-acetylgalactosamine, N—acetylglucosamine, arabinose, glucuronic acid, galacturonic acid, iduronic acid and ogalactan.

Description of the gs For a more complete understanding of the features and advantages of the present ion, reference is now made to the detailed description of the invention along with the accompanying figures and in which: is a schematic representation of the test protocol showing the running order for the testing day in hours; is a plot showing the participants tive ratings of mental fatigue post ent; and is a plot showing the effects of polysaccharides, placebo and sucrose on blood glucose levels. ption of the Invention While the making and using of s embodiments of the present invention are discussed in detail below, it should be appreciated that the present invention provides many applicable inventive concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussed herein are merely illustrative of specific ways to make and use the invention and do not delimit the scope of the invention.

To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as “ 3’ (C a an” and “the” are not intended to refer to only a ar entity, but include the general class of which a specific example may be used for illustration. The terminology herein is used to be specific embodiments of the invention, but their usage does not delimit the ion, except as outlined in the claims.

As used herein, the term “carbohydrate” is used hangeably with the terms “saccharide”, “polysaccharide”, “oligosaccharide” and ” the definitions of which are well known in the art of carbohydrate chemistry. Although the itions of the invention are intended to include at least one of the eleven essential saccharides, it should be noted that the saccharides can be in the form of mono-, oligo- and/or polysaccharides, e.g. a composition containing gum tragacanth and guar gum will be considered as containing galacturonic acid, fucose, xylose, arabinose, se, mannose and galactose. Therefore, by controlling the amount of particular gums in a given dietary supplement, one can control the amount of the respective saccharides in said dietary supplement.

Although the present invention includes the above cited eleven essential saccharides, it should be noted that other saccharides, nutritional compounds or biologically active or inert compounds can be included in the dietary supplement of the invention. Such other nutritional compounds include any one or more of phytonutrients, dioscorea complex, plant extracts, herbal extracts, plant parts, herbal components, vitamins or minerals. These nutritional nds can be added to the y supplement of the invention, or they can be provided tely to a mammal being administered said dietary supplement.

There are many plant and herbal extracts with suspected or trated nutritional value which can promote good health and can be incorporated in or administered along with the dietary supplement of the invention. Such plant and herbal extracts can be obtained according to well known procedures for the extraction of substances, compounds or agents from plants or herbs.

Many different types of vitamins and ls can be included in the dietary supplement of the invention. While a few vitamins and minerals of synthetic origin do possess nutritional value, particular embodiments of the dietary supplement herein n nutritionally effective amounts of non-toxic vitamins and minerals obtained predominantly from l sources.

The term “nutritionally effective ” as used herein refers to that amount which will provide a beneficial ional effect or response in a mammal. For example, as nutritional response to vitamin- and mineral-containing dietary supplements varies from mammal to mammal, it should be understood that nutritionally effective amounts of said vitamins and minerals will vary, respectively. Thus, while one mammal may require a particular profile of vitamins and ls present in defined amounts, r mammal may require the same particular e of vitamins and minerals present in different defined s.

Other compounds, agents and nutrients can also be included in the dietary supplement of the invention, such as, for example, cellulose, calcium ate, kola nut, kola nut extract, country mallow, Atlantic kelp, cayenne pepper, silica, stearic acid, amino acids, glycine, lysine, glutamic acid, arginine, m carbonate, orchic substances, boron citrate, chromium picolinate, essential fibers, essential oils, essential botanicals, essential enteric ecology and flora growth promoters, essential fatty acids, live tic flora, proteins and enzymes.

The dietary supplement of the invention has been prepared and administered to mammals in powdered, titutable powder, liquid—solid suspension, liquid, capsule, tablet, caplet, lotion and cream dosage forms. It should be readily obvious to one of ordinary skill in the science of formulations that the present dietary supplement can also be formulated appropriately for irrigation, ophthalmic, otic, rectal, sublingual, transdermal, buccal, vaginal, or dermal administration. Thus, other dosage forms such as chewable candy bar, concentrate, drops, elixir, emulsion, film, gel, granule, chewing gum, jelly, oil, paste, pastille, , shampoo, rinse, soap, sponge, suppository, swab, syrup, chewable n form, or chewable tablet can be used.

Due to varying diets among people, the dietary supplement of the invention can be administered in a wide range of dosages and formulated in a wide range of dosage unit strengths. For e, for those people who are missing from their diet nine of the eleven essential saccharides, a dietary ment containing those nine saccharides in nutritionally effective s can be formulated. As well, for those people whose bioabsorption of ial saccharides is extremely efficient, a dietary supplement formulation containing reduced amounts of essential saccharides can be prepared.

It should be noted that the dosage of the dietary supplement can also vary according to a particular ailment or disorder that a mammal is suffering from when taking the supplement. For example, a person suffering from chronic fatigue syndrome, or f1bromyalgia, will lly require a dose different than an alcoholic who is trying to discontinue alcohol consumption in order to obtain a nutritional benefit. An appropriate dose of the dietary supplement can be readily determined by monitoring patient response, i.e., general health, to particular doses of the supplement. As well, when another agent such as a utrient, plant extract, herbal extract and/or dioscorea complex is being administered to a mammal along with the present glyconutritional dietary supplement, the appropriate doses of the ment and each of the agents can be readily ined in a like fashion by monitoring patient response, i.e. general health, to particular doses of each.

It is contemplated by the invention that the dietary supplement can be administered simultaneously or sequentially in one or a combination of dosage forms. While it is possible and even likely that the t dietary supplement will provide an ate overall health benefit, such benefit may take days, weeks or months to materialize. Nonetheless, the present glyconutritional dietary supplement will provide a beneficial nutritional response in a mammal ing it.

The present invention describes the beneficial effects of plant polysaccharides on cognitive performance and mood in middle—aged adults. The method of the present invention uses a ized, double—blind, placebo—controlled design to study the acute effects of a unique combination of plant ccharides on tasks of , high cognitive demand serial subtraction tasks l Threes and Serial Sevens), and a Rapid Visual Information Processing (RVIP) task in adults aged 45—60 years. The results from this study show beneficial effects of acute consumption of plant polysaccharide on memory performance and tasks of high ive demand. Importantly, these enhancement effects were independent of blood glucose responses. l, the findings of the present invention suggest that polysaccharides enhance memory.

The dietary supplement of the present invention comprises a ionally effective amount of isolated and purified acetylated mannose and a nutritionally effective amount of at least five isolated and purified saccharides selected from: ose, glucose, mannose, xylose, N— acetylneuraminic acid, fucose, N—acetylgalactosamine, N—acetylglucosamine, arabinose, glucuronic acid, galacturonic acid, iduronic acid and arabinogalactan. In one aspect of the present, invention the at least five isolated and purified saccharides are essential rides and further comprise glucosamine and rhamnose.

The acetylated mannose and the at least five isolated and purified saccharides are provided in monomeric, oligomeric and/or polymeric forms and may be available in the powdered form, dissolved in a liquid or is encapsulated.

It will be understood by the skilled artisan that the acetylated mannose and the saccharides may be obtained from a variety of natural sources. Non-limiting examples for the source of the acetylated mannose is the group consisting of aloe vera and acetylated polymannose, and the saccharides may be obtained from the group consisting of gum tragacanth, guar gum, grain flour, rice flour, sugar cane, beet sugar, , milk, agar, algin, locust bean gum, psyllium, karaya gum, seed gums, Larch tree extract, gum ghatti, starch, cellulose, degraded cellulose, se, high se corn syrup, pectin, , acacia, gum arabic, alginic acid, carrageenan, dextran, xanthan gum, chondroitin e, sucrose, maltose, glucan, lentinan, mannan, levan, hemi- cellulose, inulin, fructan, and lactose.

In addition to improving cognitive performance and mood, the present inventors hypothesise that the dietary supplement may be used for the modification of behavior in alcohol dependent mammals comprising nutritionally effective amounts of the natural and/or synthetic monomeric, oligomeric and/or polymeric forms of acetylated mannose, gum ghatti, gum tragacanth, glucosamine, corn starch and arabinogalactan. The dietary supplement may reduce the craving for alcohol in an alcohol ent mammal being administered the supplement. In another particular embodiment, the dietary ment may improve the l well being of the alcohol dependent mammal by reducing at least one of depression and anger or increasing at least one of cognition, energy and positive outlook.

The dietary supplement sed herein may reduce the undesired side—effects in mammals receiving biologically effective agents that cause said side—effects, said dietary supplement comprising nutritionally ive amounts of the natural and/or synthetic monomeric, oligomeric and/or polymeric forms of acetylated mannose, gum ghatti, gum tragacanth, amine, corn starch and arabinogalactan. The dietary supplement may reduce the undesired side—effects of central nervous system drugs.

The s conducted in the present invention employed a randomized, double—blind, placebo controlled, parallel groups design. Participants were ly assigned to receive the plant polysaccharide e or, alternatively, a sucrose or starch placebo.

Volunteers for the study were recruited through word of mouth, television and print media from local olitan communities in Adelaide and Melbourne. The sample ted of healthy middle—aged men and women aged between 45 and 60 yrs. Inclusion criteria included proficiency in English, no history of major heart surgery, es, or taking medications for rain injury or neurological or psychiatric conditions that, could affect cognitive performance.

The study presented herein excluded volunteers having a history of one or more stress disorders, post tic stress disorder (PTSD), phobias, psychological traumas, alcohol abuse, and adverse reactions to one or more central nervous system (CNS) drugs. However, it will be understood that the dietary supplement described hereinabove is expected to have beneficial effects on cognition and mood of subjects suffering from the one or more exclusion conditions of this study.

There were 93 individuals enrolled in the study: 19 duals withdrew prior to their first visit due to work commitments, inability to keep the appointment visit time, and concurrent life/family s; and 1 individual who no longer wanted to complete the activities withdrew consent ay through the assessment. There were 73 eers that completed the acute intervention study.

Prior to participation, volunteers provided written informed consent and completed the background health questionnaire to determine age, height, and weight in order to calculate body mass index (kg/m2), years of education, number of hours of work per week, self-rated , (rated on a scale from 1: poor to 5 = excellent), number of dietary supplements used, number of medications used, number of hours of exercise per week, number of cigarettes smoked per day and alcohol consumption (number of standard drinks ed in a typical day). Descriptive statistics of the three treatment groups are presented in Table 1. In addition, participants also completed the Profile of Mood state questionnaire (POMS) and Short-form health survey (SF- 36) to determine background mood and well—being. The study was approved by the University of South Australia and Swinburne University of Technology Human Research Ethics tees.

Procedure: Each participant attended the ch facility on a single day for a period of 3.5 hours during which they completed 2 testing sessions, 1 baseline test and l post-treatment test.

All testing took place between 08:00 — 12:00 and 13:00—18:00. On testing days, ipants abstained from consuming any stimulants (i.e., tea, coffee, other caffeine containing products) for 2 hours before their visit. All volunteers were fasted for 2 hours before their visit. Each study day comprised of a practice module, a eatment baseline g session on the mood and cognitive measures, this was immediately followed by a eatment blood glucose measurement, and administration of treatment.

Participants were allocated, using a random number generator randomization code, to one of three treatment conditions: sucrose (icing sugar), placebo (rice flour) and plant saccharides (Ambrotose ex). Given the different densities of the three supplement conditions, each treatment was weighed and measured with scoop s to provide equated 4 g doses. The supplement was delivered to each participant on a tablespoon with 100 ml of water. Each participant was cted by the ors to carefully consume the powder, without breathing in or out over it, by g it in their mouth and g it down with the water provided within minutes. Additional water was provided on request. Participants were then instructed to rest for minutes to allow for absorption. Following the 30 minute absorption time, a finger-capillary blood glucose measurement was taken. The post treatment g session then commenced with alternate forms of the RAVLT and Cognitive demand battery. Following tion of the testing session, a final blood glucose measurement was taken. shows the running order for the study day.

Table 1: Baseline health and demographic means for each of the three treatment .

Background Variable Treatment Condition Polysaccharides Sucrose Placebo N= 23 N= 24 N= 26 Gender M=8,F=15 M=9,F=17 M=9,F=15 Age in years 53(4.41) 52 (4.35) 53 (4.49) BMI (kg/m2) 27 (4.48) 29(8.00) 26 (3.82) Years of Education 16 (4.70) 15(3.32) 15(3.99) Self rated health 4.0 (.90) 4.9 (.62) 4.1 (.56) Hrs ofwork/week 23.5 (15.81) 21.4(19.04) 19.5 (18.24) Hrs of exercise/week 4.5 (4.01) 4.3 (3.77) 4.4 (3.49) No# supplements 1.91(1.37) 2.66 (2.28) 2.86(1.88) No# medications 1.61(1. 19) 1.38 (.76) 1.62(.51) No# of Alcohollc drlnks/week .7 (6.18) 5-5 (6.11) 5.2(4.56) No# of glasses ofwater /day 3.7 (2.38) 3.8 (2.12) 4.1 (4.14) Measures: Learning and Memory and ive Measures Learning and Memory: The Rey ry-Verbal Learning Test (RAVLT) [1] was used to assess immediate recall, delayed recall, learning and recognition memory. The examiner reads aloud 15 nouns (list A) over five trials and after each trial, participants are asked to recall, in any order, as many of the 15 words as possible. Scores for the 5 trials are summed to produce a measure of immediate recall, the difference between trial 5 and 1 is used as a measure of learning. After a sixth trial consisting of 15 different words (list B) participants are again required to recall the words that were presented in list A (trial 7), and then again after an interval of 60 minutes (trial 8). The scores from trials 7 and 8 are used to produce a measure of d recall, the difference between the words recalled in trials 8 and 7 is used as a e of forgetting, the difference between trial 7 and trial 5 is used as a score of interference. After trial 8, participants are presented with a sheet of 50 words ning the words from lists A and B among 20 distracter words. Participants are asked to recognize the words from lists A and B and indicate the list they came from. Each word correctly identified is awarded one point producing a measure of recognition.

Cognitive Demand Battery: The computerized battery comprises of 6 repetitions of a 10 min assessment that measures the speed, accuracy and mental fatigue of mance during continuous, cognitively demanding tasks. Each 10 min cycle of this battery comprises two serial subtraction tasks (Serial Threes - 2 min, and Serial Sevens - 2 min), a Rapid Visual Information Processing Task (RVIP- 5 min) and Visual ue mental fatigue scale (1 min). Tasks within this battery have been shown to be sensitive to the effects of other nutritional interventions, such a Panax ginseng and cocoa [2, 3].The dual tasks are bed below. a) Serial Threes subtraction task (2 min): Participants are required to count backwards in threes from a random starting number between 800 and 999 presented on the er screen.

Participants are instructed to enter their answer as quickly and as accurately as possible by using the linear number keys at the top of the computer keyboard. The starting number is cleared from the screen once participants enter their first se. Each subsequent three digit response by participants is presented on the screen as sks. Participants press the enter key to signal the end of each response and clear the three asterisks from the screen. The task is scored for the number of correct and incorrect responses, average reaction time, and proportion of correct responses made given average reaction time (accuracy vs speed). b) Serial Sevens subtraction task (2 min): This task is identical to the serial threes task except that participants are asked to subtract sevens.

C) Rapid visual Information Processing Task (RVIP — 5 min): Participants are required to r a continuous series of digits for target strings of three consecutive odd or three consecutive even digits. The digits are presented on the screen at a rate of 100 per minute. The participant responds by pressing the space bar as y as possible when they detect a target string of digits. The task is scored for number of target strings correctly detected, percentage of correct answers, number of false alarms, average reaction time for correct detections and proportion of correct responses made given average reaction time acy vs speed). d) ‘Mental-fatigue’ visual analogue scale (1 min): ipants rate their subjective feelings of mental e on a 100 mm visual analogue scale with anchors of ‘not at all’ and ‘very much Mood and Well—being Measures: Background general mood and well—being were assessed with the Profile of Mood States (POMS) and Sf—36 health survey to determine any ound differences between the groups. Subjective mood states on the testing day that may be effected by treatment conditions were assessed with l paper-pencil State-trait anxiety questionnaire, and 1 visual analogue scale that measures three mood states, alertness, calmness and contentedness. (i) The POMS [4] is a self-report questionnaire that contains 65 items pertaining to six mood states: tension-anxiety, sion-dejection, anger-hostility, vigour-activity, fatigue-inertia, and confusion—bewilderment. Participants are asked to rate these on a 5-point scale (0: not at all to 4: extremely) indicating how they have felt during the past week including today. (ii) The SF—36 health survey [5] provides a measure of functional physical and logical health across seven general health and well-being concepts: 1) limitations in physical ties because of health problems; 2) limitations in social activities e of al or nal ms; 3) limitations in usual role activities because of physical health problems; 4) general mental health (psychological distress and well-being); 5) limitations in usual role activities because of emotional problems; 6) vitality (energy and fatigue); and 7) general health perceptions. (iii) The State-trait anxiety questionnaire [6] contains 20 items that record the presence (e.g. ‘1 am tense’) and absence (e.g. ‘I feel at ease’) of anxiety symptoms. Participants are asked to rate each item according to how they are generally feeling on a four-point scale ranging from ‘not at WO 48887 all’ or t never’ to ‘Very much so” or ‘almost always’. These are combined to provide a sum score between 20 and 80 (a lower score representing lower anxiety). (iv) The Bond-Lader visual analogue scale (VAS) [7] consists of 16 x 100 mm visual analogue scales. Participants indicate their current subjective state of mood for the 16 pairs of linked antonyms (e.g., attentive-dreamy, trouble-tranquil, happy-sad, alert-drowsy) by using the computer mouse to click on the line at a position that reflects their levels of mood. The resultant scores are combined to provide measures of self—rated alertness, calmness and contentedness.

Blood Glucose ement: Blood glucose samples were measured using an automated er (Accu—check, optimal blood glucose monitor and testing strips). Blood samples were collected using self administered single use—capillary, disposable blood sampling lancet tips.

Alcohol soaked cleansing swabs were used for pre—sampling sterilisation. The blood glucose reading were assessed and recorded at three testing points: pre—treatment, reatment and post cognitive testing.

Statistical Analysis: The primary outcomes were memory performance, mood and performance on the Cognitive Demand Battery (CDB) and the subjective ratings of mental e. All data were analyzed using SPSS 17 statistical package as “change from pre dose baseline ’, using Analysis of Variance ). To test for chance ne differences which may have skewed change—from—baseline scores, prior to the primary statistical analysis, one—way ANOVA’s with Bonferroni correction, were run all on all baseline demographics, general mood and well—being measures, and all pre—dose ne measures to determine any potential covariates in outcomes.

Baseline health and wellbeing: There were no icant differences between groups on background demographic measures, Table 1. There was a significant difference between groups on the POMS scale of anxiety (F (3, 68) = 3.25, p = .044), seen in Table 2. Post hoc comparisons revealed that no group was significantly different from another, however the ion of means suggested that the placebo group was less s than those in the polysaccharide and e groups (p = .06 and .08 respectively).

Therefore the anxiety sub-scale from the POMS was used as covariate in is for any differences between the groups on the baseline and post treatment measures of memory, cognitive demand tasks and subjective mood ratings.

There were no significant differences between groups on measures of memory or subjective mood ratings at baseline. There was a marginally insignificant difference between groups on the percentage correct and number correct on the rapid Visual information processing task from the demand battery ( p = .052 and p =.053 respectively). Whilst insignificant, those in the polysaccharide group exhibited a higher mean performance than those in the placebo condition (p = .08) but not the sucrose group (p = .14). Therefore, in analysis of post treatment change from baseline scores on the RVIP task, baseline performance was used as a covariate.

Table 2: Means and Standard ions for baseline mood and eing measures.

Treatment Condition Polysaccharides Sucrose Placebo N= 23 N= 24 N= 26 Profile ofMood States (POMS) Anxiety** .26) 5.76(6.04) 2.39 (3.99) n 7.26 (5.79) 6.92 (4.77) 6.56( 3.23) Depression 6.34 (8.1) 5.76 (5.88) 4.04 (5.55) Vigor 17.17 ( 6.76) 17.38 (6.13) 18.17 (6.02) Confusion 6.21 (4.90) 5.46 (4.31) 4.82 (3.68) Fatigue 6.65 (5.14) 6.42 (5.54) 6.08 (4.88) Total Mood Disturbance 15.04 (29.31) 12.96 (26.56) 5.08 (19.28) SF-36 Physical Functioning 27.72 (2.71) 27.61 (2.15) 27.17(3.29) Role — physical 7.36(1.09) 7.03(1.48) 6.95 (1.52) Social Functioning 8.95(1.73) 9.03(1.34) 8.86(1.68) Role-Emotional .02) 5.34 (1.12) 5.73 (.54) General health 18.31 (2.67) 18.15 (2.16) 17.95(2.49) Vitality 16.27 (4.48) 16.80 (3.29) 17.00 (3.72) Health transition 3.04 (.48) 2.76 (.65) 2.60 (.89) Mental health 24.27 (3.83) 25.20 (3.22) 24.30 (4.47) Bodily pain 8.82 (2.84) 10.32 (1.83) 9.04 (3.00) ** F (2, 71) = 3.25,p = .045.

Effects of acute supplementation: Memory: The post—dose ‘change—from—baseline’ scores are presented in Table 3. There was a significant difference between groups in change from baseline performance on tasks of recognition memory (F (3,68) = 5.89, p = .004), list A (F (3,68) = 3.17, p = .044) and List B (F (3,68) = 5.17, p =.009) respectively. Post hoc analysis showed that those in the polysaccharide group recognized icantly more words overall than those in the sucrose group (p = .004) only, post treatment. ically, those in the polysaccharide condition recognized significantly more words from List B than those in the sucrose group (p = 0. 007).

There was a trend for those in the ccharide ion to recognise more words from list A compared to sucrose (p: .083), but not placebo.

Cognitive demand: Serial 3s: There was a significant main effect of time on the number of t answers (F (5, 340) = 2.16, p = .05), and trend towards a main effect of treatment (F (2, 68) = 2.70, p = .07), with the direction of means indicating a higher number correct responses in the polysaccharide group compared to those in the sucrose group (p = .07) but not placebo.

There was no significant time by treatment interaction (F (10, 340) = .94, p = .48).

There was a significant main effect of time on the proportion of t answers given e reaction time (F (5, 340) = 3.94, p = .002), and a trend towards a main effect of treatment (F (2, 70) = 2.96, p = .058), with the direction of means indicating a higher proportion of correct responses given average reaction time in the polysaccharide group compared to those in the sucrose group (p = .058) but not placebo. There was no significant time by treatment interaction (F (10, 340) = 0.898, p = 0.54).

There were no statistically icant effects ated with either time, treatment, or time by treatment interactions on the number of incorrect responses made or average reaction.

Serial 7s: There was a significant main effect of time on the number of correct answers made (F(5, 340) = 2.52, p = .02), but no significant main effect of treatment (F (2, 68) = .547, p = .58). There was a significant time by treatment interaction (F (10, 340) = 2.53, p = .006).

Pairwise comparisons showed a significant difference between groups at 20 min with those in polysaccharide group making significantly more correct responses than the placebo group (p = .02) and those in the e group making significantly more correct ses than the placebo group (p = .04).

There was no significant main effect of time on the proportion of correct answers given average reaction time (F (5, 340) = 1.66, p = 0.14), nor a main effect of treatment (F (2,68) =0.93, p = 0.39). There was a significant time by treatment interaction (F (10, 340) = 1.91, p = 0.04).

Pairwise comparisons showed a significant difference between groups at 20 min with those in polysaccharide group making significantly more correct responses than the placebo group (p = .03), but not sucrose.

There were no statistically significant effects associated with either time, treatment, or time by treatment ctions on the number of incorrect responses made or average reaction.

RVIP: There were no statistically cant effects ated with either time, ent or time by treatment interactions on the total number of ses, number of correct or incorrect responses made.

Mental Fatigue: There was a main effect of time on subjective ratings of mental fatigue (F (5, 340) = 75.44, p , with increasing fatigue across time, shown in There was no significant main effect of treatment (F (2, 68) = 2.04, p = .13) or time by treatment interaction (F (10, 340) = 1.39, p = .18). Pairwise comparisons showed a cant difference between groups at 10 min (F (2, 70) = 4.27, p = .018), with those in the polysaccharide group reporting a significant reduction in feelings of fatigue approximately 40 minutes post consumption, compared to those in the sucrose group (p = .01) Mood: There were no statistically significant effects associated with either treatment on tive levels of anxiety measured by the State-trait questionnaire, or on the Bond—lader scales of alertness, contentedness, and calmness as change from baseline .

Blood e measurement: There was a significant main effect of time (F (2, 140) = 37.28, p <.001) and significant interaction of time and treatment condition (F (4,140) = 8.39, p = <.001).

There was no significant main effect of treatment condition (F(2, 70) = 2.41, p = .09). Pairwise comparisons show that at 30 minutes post ingestion of supplement, those who consumed the polysaccharide supplement had significant lower blood glucose se than those who had consumed placebo (p = .038) and sucrose ( p<.001). Specifically, there was no rise in blood glucose response following polysaccharide intake compared to the blood glucose response or those individuals who consumed sucrose and placebo, as shown in Table 3: Means and Standard deviations for RAVLT post—dose change from baseline scores.

Measure Treatment Condition F(3,68) Polysaccharides Sucrose Placebo N= 23 N= 24 N= 26 RA VLT Trial 1 -0.78 (1.78) —0.26 (2.23) —0.54(1.81) 0.429 Trial 2 —0.60 (2.08) —0.57 (2.13) —0.95 (2.47) 0.017 Trial 3 0.21 (1.95) —0.42 (1.83) —0.58 (1.55) 1.35 Trial4 -0.04 (2.05) —0.42 (1.72) —0.08 (2.20) 0.263 Trial 5 0.08 (1.59) —0.19(1.72) 0.58 (1.74) 0.918 Sum Immediate Recall —1.13(5.54) —1.88 (5.83) —1.58 (6.00) 0.103 Trial 6 (List B) -0.08 (2.02) —0.84 (2.16) —0.25 (2.11) 0.821 Trial 7 —0.82 (2.90) —1.53 (2.37) —1.08 (3.29) 0.369 Trial 8 —1.91 (3.02) —3.23 (2.80) —2.29 (3.23) 1.18 Sum delayed recall —2.73 (5.21) —4.76 (4.18) —3.37(5.56) Recog A —0.26 (3.29) —2.38 (2.46) —2.37 (4.11) 3.28* Recog B —0.26 (3.10) —3.38 (3.55) —1.45 (3.61) 4.99* Sum ition —0.52 (5.24) —5.76 (4.91) —3.83 (6.07) 5.89* erence —0.91 (2.77) —1.34 (2.18) —1.66 (2.88) 0.417 (trial 7 - trial 5) Learning 0.86 (2.20) 0.07 (2.78) 1.12 (2.43) 1.20 (trial 5- triall) Forgetting -1.08 (2.82) —1.69 (3.06) —1.20 (3.42) 0.254 (trial 8 - trial7 ) *p= <.05 The t study describes the acute effects of saccharides (Ambrotose® Complex) on cognition and mood in —aged adults. The study presented herein is used to determine whether rides have positive acute effects on memory, cognition, well—being, and mood and whether any effects may be explained through glycaemic effects, for example the provision of glucose as a lic substrate. The methodology used provided a novel design to examine the s of treatment (saccharides, sucrose, and placebo) n subjects across highly effortful and mentally fatiguing conditions.

The results presented hereinabove show a significant effect of plant polysaccharide consumption on recognition memory performance compared to sucrose consumption. Specifically, despite sing subjective ratings of mental fatigue, recognition of words previously learned was significantly higher for those who consumed plant—polysaccharides compared to e. This positive effect on recognition memory performance ts that those who received plant— polysaccharides were aided in encoding the information ted and could retrieve that information, when presented with the words as a cue, more readily.

With regard to performance on tasks in the cognitive demand battery, there was a trend s a treatment effect of polysaccharides on the number and proportion of Serial Three ctions made (p = .07 and .058 respectively). However, the only significant time and treatment interaction was obtained for Serial Seven ctions. Specifically, there was a significant interaction between treatment conditions and the number of correct responses made.

Importantly, pairwise comparisons showed a significantly greater number of correct responses being performed at the 2nd cycle of the battery (approximately 1 hour post consumption) for those in the polysaccharide condition compared to those in the placebo condition.

Performance on Serial Sevens subtraction tasks is rated as significantly more demanding than Serial Threes (Kennedy and y, 2000), and relies more heavily on working memory and executive resources. The current results suggest that consumption of plant polysaccharides maintains working memory performance despite conditions of mental fatigue. Interestingly, the trends towards improved performance on Serial Threes following intake of plantpolysaccharides , may indicate potential working memory and attention effects, as performance on both serial three and serial seven tasks have attention components.

In relation to mood, there was no icant interaction between ent condition and changes in subjective ratings of feelings of anxiety, alertness, contentedness or calmness. 2012/034752 antly, the recognition memory and working memory effects were observed following plant—polysaccharide intake, independent of blood glucose response. The absence of a raised blood glucose following intake of plant-polysaccharides indicates that the memory effects were not directly related to the modulation of blood e levels.

In sion, this is a first of kind study of the acute ts for cognitive function associated with plant—polysaccharide consumption in healthy middle—aged adults, independent of blood e response. These findings t that the consumption of 4 g of plant polysaccharides may be beneficial for recognition memory performance and cognitive tasks reflecting working memory and ive function during highly demanding and mentally fatiguing conditions. The results of the present invention may have implications for individuals who require a memory ‘boost’ to cope with the demands that a busy, taxing lifestyle places upon cognitive ces.

It is contemplated that any embodiment discussed in this specification can be ented with respect to any method, kit, reagent, or composition of the invention, and vice versa. Furthermore, compositions of the ion can be used to e methods of the invention.

It will be understood that particular embodiments described herein are shown by way of illustration and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims.

All publications and patent applications ned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more, 3’ CCat least one,” and “one or more than one.’ 3 The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a tion that refers to only alternatives and “and/or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.

As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as des” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open—ended and do not e additional, unrecited elements or method steps.

The term “or ations thereof” as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof” is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this e, expressly included are ations that contain repeats of one or more item or term, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The d n will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise nt from the context.

All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present sure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the ce of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

Claims (17)

What is claimed 1. is:

1. Use of a dietary supplement in the manufacture of a formulation for therapeutically improving mood, reducing stress, anxiety or mental fatigue, or any combination thereof in a healthy human subject; wherein a nutritionally effective amount of the dietary supplement is to be administered to the y human subject in an amount sufficient to therapeutically improve mood, reduce stress, anxiety, mental fatigue, or any combination thereon, and wherein the healthy human subject has been previously identified by the use of one or more tests being in need of improvement in mood, reduction of stress, anxiety, or mental fatigue, or any combination thereof; wherein the dietary supplement comprises a nutritionally ive amount of isolated and purified acetylated e, and a nutritionally effective amount of at least five isolated and purified saccharides selected from the group consisting of: galactose, glucose, mannose, xylose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, ylglucosamine, arabinose, glucoronic acid, galacturonic acide, iduronic acid and ogalactan.

2. The use of claim 1, wherein the dietary ment is to be orally administered.

3. The use of claim 1, wherein the dietary supplement is a , is ved in a liquid, is encapsulated, or any combinations f.

4. The use of claim 1, further comprising: one or more previously obtained test s to assess the mood, stress and anxiety level, or any combinations thereof in the healthy human subject prior to the administration of the dietary supplement to determine a baseline or pre-test level for the healthy human subject; one or more previously obtained test results to assess the mood, stress and anxiety level, or any combinations thereof in the healthy human subject at one or more specified time-points after the administration of the y supplement to determine a post-test level for the healthy human subject; and comparison of the baseline and the est levels to determine continuation, ation, or modification of the administration of the dietary supplement in the healthy human subject.

5. The use of claim 1, further comprising the use of previously obtained test results measuring blood e levels prior to and after administration of the dietary supplement.

6. The use of claim 1, wherein the dietary supplement does not cause an elevated blood glucose level in the subject.

7. The use of claim 1, wherein the dietary ment is to be administered simultaneously or sequentially in one or a combination of dosage forms.

8. The use of claim 1, wherein the dietary supplement is to be administered simultaneously or sequentially with one or more vitamins, other nutritional supplements, or any ations thereof.

9. Use of a dietary supplement in the manufacture of a formulation for therapeutically improving mood, reducing stress, anxiety, mental e, or any ations thereof in a y human subject without elevation of blood glucose levels; wherein a nutritionally effective amount of the dietary supplement is to be administered to the healthy human subject in an amount sufficient to therapeutically improve mood, reduce stress, anxiety, mental fatigue, or any combination thereof; and wherein the healthy human subject has been previously identified by the use of one or more tests as being in need of improvement in mood, reduction of stress, anxiety, mental-fatigue, or any combination thereof; wherein the dietary ment comprises a nutritionally effective amount of isolated and ed acetylated mannose, and a nutritionally effective amount of at least five isolated and purified saccharides selected from the group consisting of: galactose, glucose, mannose, xylose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine, arabinose, glucoronic acid, uronic acide, ic acid and arabinogalactan.

10. The use of claim 9, n the dietary ment is to be orally administered.

11. The use of claim 9, wherein the dietary supplement is a powder, is dissolved in a liquid, is encapsulated, or any combinations thereof.

12. The use of claim 9, further comprising the use of previously obtained measurement of blood glucose levels prior to and after administration of the dietary supplement.

13. The use of claim 9, further comprising a termination of the stration of the dietary supplement in case of an abnormally elevated blood glucose levels.

14. The use of claim 9, further comprising: one or more previously ed test results to assess the mood, stress and anxiety level, or any ations thereof in the healthy human subject prior to the administration of the dietary supplement to determine a baseline or pre-test level for the healthy human subject; one or more previously obtained test results to assess the mood, stress and anxiety level, or any ations thereof in the healthy human subject at one or more specified time-points after the administration of the dietary ment to determine a post-test level for the healthy human subject; and comparison of the baseline and the post-test levels to determine continuation, termination, or cation of the administration of the dietary supplement in the healthy human subject.

15. The use of claim 9, wherein the dietary supplement is to be administered simultaneously or tially in one or a combination of dosage forms.

16. The use of claim 9, wherein the dietary supplement is to be administered simultaneously or sequentially with one or more vitamins, other ional supplements, or any combinations thereof.

17. The use of any one of claim 9-16, wherein the at least five isolated and purified saccharides further comprise glucosamine and rhamnose.