NZ705719B2 - 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 ion The present invention relates in general to the field of dietary supplements, and more ularly, to a dietary supplement sing plant polysaccharides that has a beneficial effect on cognitive performance and mood in middle—aged adults.

Background Art Without limiting the scope of the invention, its background is described in connection with health effects of plant polysaccharides including dietary supplements thereof.

US. Patent No. 7,157,431 issued to Mcanalley et a1. (2007) discloses compositions of plant carbohydrates 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 ive compositions as dietary supplements. The dietary composition herein can include phytonutrients, Vitamins, minerals, herbal extracts, and other non-toxic nutrients. The utritional 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 describes the beneficial health effects of dietary supplements containing plant polysaccharides. More specifically, the t ion 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, mental-fatigue, modifying behavior, or any combinations thereof in a human subject comprising the steps of: identifying the human subject in need of improvement of cognition, mood, learning, memory, reduction of stress, y, mental-fatigue, ing or, or any ations thereof and administering a nutritionally effective amount of a dietary supplement in an amount sufficient to improve cognition, mood, learning, memory, reduce , anxiety, mental-fatigue, modifying behavior, or any combinations thereof. In one aspect of the instant invention, the dietary ment 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 f in the human subject prior to the administration of the dietary supplement to determine a baseline or pre—test level for the human subject, (ii) performing one or more tests to assess the cognition, memory, mood, stress and anxiety level, or any ations thereof in the human subject at one or more specified time-points after the administration of the dietary ment to determine a post-test level for the human subject, and (iii) comparing the baseline and the post- test levels to determine continuation, termination, or modification of the administration of the dietary supplement in the human subject.

In another aspect, the human subject may suffer from one or more heart conditions, diabetes, head/brain injury, neurological conditions, egenerative conditions, psychiatric conditions, or any combinations thereof In yet r aspect, the stress or the anxiety arises from one or more stress disorders, Post Traumatic Stress Disorder (PTSD), s, psychological traumas, or any combinations thereof In another aspect, the dietary supplement ates one or more adverse effects induced by central nervous 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 y supplement. In another aspect, the dietary ment 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 administered simultaneously or sequentially with one or more drugs, ns, other nutritional supplements, or any combinations thereof.

The dietary supplement described in the method hereinabove comprises: (i) a nutritionally effective amount of isolated and purified ated mannose and (ii) a nutritionally effective amount of at least five isolated and purified rides ed from: galactose, glucose, mannose, xylose, N—acetylneuraminic acid, fucose, N—acetylgalactosamine, N— acetylglucosamine, arabinose, onic acid, galacturonic acid, iduronic acid and arabinogalactan. 2012/034752 A method for improving cognition, mood, ng, memory, reducing 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, learning, memory, reduction of stress, anxiety, mental-fatigue, modifying or, or any combinations f and administering a nutritionally effective amount of a dietary supplement in an amount sufficient to improve cognition, mood, learning, memory, reduce stress, anxiety, -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 encapsulated, or any combinations thereof. In yet r aspect, the method ses the step of measuring blood glucose levels prior to and after administration of the dietary supplement and the step of terminating the administration of the y supplement in case of an abnormally elevated blood glucose levels.

The method, as described hereinabove, further comprises additional steps, these e: (i) ming 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 pre-test level for the human subject, (ii) performing one or more tests to assess the cognition, memory, mood, stress and anxiety level, or any combinations thereof in the human subject at one or more specified oints 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 determine continuation, termination, or modification of the administration of the dietary supplement in the human t. In one aspect, the human subject may suffer from one or more heart ions, diabetes, head/brain injury, neurological conditions, neurodegenerative ions, psychiatric conditions, or any combinations thereof. In another aspect, the stress or the anxiety arises from one or more stress disorders, Post tic Stress Disorder (PTSD), s, psychological traumas, 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 supplements, or any ations thereof. The dietary supplement comprises: (i) a nutritionally effective amount of isolated and purified acetylated mannose and a nutritionally effective amount of at least five isolated and purified saccharides ed from: galactose, e, mannose, xylose, ylneuraminic acid, fucose, N— acetylgalactosamine, N-acetylglucosamine, arabinose, glucuronic acid, galacturonic acid, iduronic acid and arabinogalactan. In a related aspect the at least five isolated and purified saccharides r se glucosamine and rhamnose.

In yet another ment, the present invention discloses a method for improving cognition, mood, learning, memory, reducing stress, y, mental-fatigue, modifying or, or any combinations f in a human subject without elevation of blood glucose levels comprising the steps of: identifying the human subject in need of improvement of cognition, mood, learning, , reduction of stress, anxiety, -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 ations 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 isolated and ed saccharides selected from: galactose, glucose, mannose, xylose, N—acetylneuraminic acid, fucose, N-acetylgalactosamine, N—acetylglucosamine, arabinose, glucuronic acid, galacturonic acid, iduronic acid and arabinogalactan.

Description of the Drawings For a more complete tanding of the features and advantages of the present invention, 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 g the participants subjective ratings of mental fatigue post treatment; and is a plot showing the effects of polysaccharides, placebo and sucrose on blood glucose levels.

Description of the Invention While the making and using of various 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 ion, 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 singular entity, but include the general class of which a specific e may be used for illustration. The ology herein is used to be specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims.

As used herein, the term “carbohydrate” is used interchangeably with the terms “saccharide”, “polysaccharide”, “oligosaccharide” and “sugar” the definitions of which are well known in the art of carbohydrate chemistry. gh the compositions of the invention are intended to e 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, rhamnose, e and galactose. Therefore, by controlling the amount of particular gums in a given dietary supplement, one can control the amount of the tive saccharides in said dietary supplement.

Although the t invention es 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 ts, herbal extracts, plant parts, herbal components, vitamins or minerals. These nutritional compounds can be added to the dietary supplement of the invention, or they can be provided separately 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 minerals can be included in the dietary ment 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 natural sources.

The term “nutritionally effective amount” as used herein refers to that amount which will provide a beneficial nutritional effect or se 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 ive amounts of said vitamins and minerals will vary, respectively. Thus, while one mammal may require a particular profile of vitamins and minerals present in defined amounts, r mammal may require the same particular profile of ns and minerals present in different defined amounts.

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

The dietary supplement of the invention has been prepared and administered to mammals in ed, reconstitutable 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, , 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, pellet, shampoo, rinse, soap, , suppository, swab, syrup, chewable gelatin form, or chewable tablet can be used.

Due to varying diets among , the dietary supplement of the invention can be stered in a wide range of dosages and ated in a wide range of dosage unit ths. For example, for those people who are missing from their diet nine of the eleven essential saccharides, a dietary supplement containing those nine rides in ionally effective amounts can be formulated. As well, for those people whose bioabsorption of essential 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 t or disorder that a mammal is suffering from when taking the supplement. For example, a person suffering from chronic fatigue syndrome, or yalgia, will generally 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 y supplement can be readily determined by ring patient response, i.e., general health, to particular doses of the supplement. As well, when another agent such as a phytonutrient, 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 supplement and each of the agents can be readily determined in a like fashion by monitoring t 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 present dietary supplement will provide an immediate overall health benefit, such benefit may take days, weeks or months to materialize. Nonetheless, the present glyconutritional dietary supplement will provide a cial ional response in a mammal consuming it.

The present invention describes the beneficial effects of plant polysaccharides on cognitive performance and mood in —aged adults. The method of the present invention uses a randomized, double—blind, placebo—controlled design to study the acute s of a unique combination of plant polysaccharides on tasks of memory, high cognitive demand serial subtraction tasks (Serial Threes and Serial Sevens), and a Rapid Visual ation 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 cognitive demand. Importantly, these enhancement effects were independent of blood glucose responses.

Overall, the findings of the present ion suggest that polysaccharides enhance memory.

The dietary supplement of the t invention comprises a nutritionally effective amount of isolated and purified ated mannose and a nutritionally effective amount of at least five isolated and ed saccharides selected from: galactose, glucose, mannose, xylose, N— acetylneuraminic acid, fucose, N—acetylgalactosamine, N—acetylglucosamine, arabinose, onic acid, galacturonic acid, iduronic acid and arabinogalactan. In one aspect of the t, ion the at least five isolated and purified saccharides are essential saccharides and further comprise glucosamine and rhamnose.

The acetylated mannose and the at least five isolated and purified rides are provided in monomeric, oligomeric and/or polymeric forms and may be available in the powdered form, dissolved in a liquid or is encapsulated. 2012/034752 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 ting 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, potato, milk, agar, algin, locust bean gum, um, karaya gum, seed gums, Larch tree extract, gum ghatti, starch, cellulose, degraded cellulose, fructose, high fructose corn syrup, pectin, chitin, acacia, gum arabic, alginic acid, carrageenan, dextran, xanthan gum, chondroitin sulfate, sucrose, e, glucan, lentinan, mannan, levan, hemi- cellulose, inulin, fructan, and lactose.

In on 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 dependent mammal being administered the supplement. In r particular embodiment, the y supplement may e the overall well being of the l 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 disclosed herein may reduce the red side—effects in mammals receiving biologically effective agents that cause said side—effects, said dietary supplement comprising nutritionally effective s of the natural and/or synthetic monomeric, oligomeric and/or polymeric forms of acetylated mannose, gum ghatti, gum anth, glucosamine, corn starch and arabinogalactan. The dietary supplement may reduce the undesired side—effects of central nervous system drugs.

The studies conducted in the t invention employed a randomized, —blind, placebo controlled, parallel groups design. Participants were randomly assigned to receive the plant polysaccharide mixture or, alternatively, a sucrose or starch placebo.

Volunteers for the study were ted through word of mouth, television and print media from local metropolitan 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 head/brain injury or neurological or psychiatric conditions that, could affect ive performance.

The study presented herein excluded volunteers having a history of one or more stress disorders, post traumatic 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 ed to have cial effects on cognition and mood of subjects suffering from the one or more exclusion ions of this study.

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

Prior to participation, volunteers provided n informed consent and ted 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 health, (rated on a scale from 1: poor to 5 = excellent), number of dietary supplements used, number of tions used, number of hours of exercise per week, number of cigarettes smoked per day and alcohol consumption (number of standard drinks consumed in a typical day). Descriptive statistics of the three treatment groups are ted 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 Committees.

Procedure: Each participant attended the research facility on a single day for a period of 3.5 hours during which they completed 2 g 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, participants abstained from ing 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 pre—treatment baseline testing session on the mood and cognitive measures, this was immediately followed by a pre—treatment 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 tose ®Complex). Given the different ies of the three supplement conditions, each treatment was weighed and measured with scoop amounts to provide equated 4 g doses. The supplement was delivered to each participant on a tablespoon with 100 ml of water. Each participant was instructed by the inventors to carefully consume the powder, without breathing in or out over it, by putting 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 s to allow for absorption. Following the 30 minute absorption time, a finger-capillary blood glucose measurement was taken. The post treatment testing session then commenced with alternate forms of the RAVLT and Cognitive demand y. ing completion 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 groups.

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 ) 27 (4.48) 29(8.00) 26 (3.82) Years of ion 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) 56) No# of glasses ofwater /day 3.7 (2.38) 3.8 (2.12) 4.1 (4.14) 2012/034752 Measures: Learning and Memory and Cognitive Measures Learning and Memory: The Rey Auditory-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 ted 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 delayed recall, the difference between the words recalled in trials 8 and 7 is used as a measure 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 containing 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 tly 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 es the speed, accuracy and mental fatigue of performance 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 analogue mental fatigue scale (1 min). Tasks within this y have been shown to be sensitive to the s of other nutritional interventions, such a Panax ginseng and cocoa [2, 3].The individual tasks are described below. a) Serial Threes subtraction task (2 min): Participants are required to count rds in threes from a random starting number between 800 and 999 presented on the computer 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 rd. The starting number is cleared from the screen once participants enter their first response. Each subsequent three digit response by ipants is presented on the screen as asterisks. 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 on time, and tion of correct responses made given average on time acy vs speed). b) Serial Sevens subtraction task (2 min): This task is identical to the serial threes task except that ipants are asked to subtract sevens.

C) Rapid visual ation Processing Task (RVIP — 5 min): Participants are required to monitor 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 quickly as possible when they detect a target string of digits. The task is scored for number of target s 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 (accuracy vs speed). d) ‘Mental-fatigue’ visual ue scale (1 min): Participants rate their subjective feelings of mental fatigue 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 background differences between the groups. Subjective mood states on the g day that may be ed 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 ns 65 items pertaining to six mood : tension-anxiety, depression-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 e of functional physical and psychological health across seven general health and well-being concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) tions in usual role ties 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] ns 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 oint scale ranging from ‘not at all’ or ‘almost never’ to ‘Very much so” or ‘almost always’. These are combined to e 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 ue . 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, ss and contentedness.

Blood Glucose Measurement: Blood glucose samples were measured using an automated analyzer (Accu—check, optimal blood glucose r and testing ). 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, post—treatment and post ive testing.

Statistical Analysis: The primary outcomes were memory performance, mood and mance on the Cognitive Demand Battery (CDB) and the subjective ratings of mental fatigue. All data were analyzed using SPSS 17 statistical package as “change from pre dose baseline ’, using Analysis of Variance (ANOVA). To test for chance baseline differences which may have skewed —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 baseline measures to determine any potential covariates in es.

Baseline health and wellbeing: There were no significant 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 direction of means ted that the placebo group was less anxious than those in the ccharide and sucrose groups (p = .06 and .08 respectively).

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

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 ation 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 e 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 Deviations for baseline mood and well—being measures.

Treatment Condition Polysaccharides Sucrose Placebo N= 23 N= 24 N= 26 Profile ofMood States (POMS) Anxiety** 5.73(5.26) 5.76(6.04) 2.39 (3.99) Tension 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 bance 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) l health 18.31 (2.67) 18.15 (2.16) 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 significantly more words overall than those in the sucrose group (p = .004) only, post treatment. Specifically, those in the polysaccharide ion recognized significantly more words from List B than those in the sucrose group (p = 0. 007).

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

Cognitive demand: Serial 3s: There was a significant main effect of time on the number of correct answers (F (5, 340) = 2.16, p = .05), and trend towards a main effect of ent (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 ent interaction (F (10, 340) = .94, p = .48).

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

There were no statistically significant effects associated 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 icant 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 sucrose group making significantly more correct responses than the o 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 interactions on the number of incorrect responses made or average reaction.

RVIP: There were no statistically significant effects associated with either time, treatment or time by treatment interactions on the total number of responses, 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 sing fatigue across time, shown in There was no significant main effect of treatment (F (2, 68) = 2.04, p = .13) or time by ent ction (F (10, 340) = 1.39, p = .18). Pairwise comparisons showed a significant difference between groups at 10 min (F (2, 70) = 4.27, p = .018), with those in the ccharide group reporting a significant ion 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 subjective levels of anxiety measured by the State-trait questionnaire, or on the Bond—lader scales of alertness, contentedness, and calmness as change from baseline scores.

Blood glucose 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 isons show that at 30 minutes post ingestion of ment, those who consumed the polysaccharide supplement had cant lower blood glucose response than those who had consumed placebo (p = .038) and sucrose ( p<.001). Specifically, there was no rise in blood glucose se 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. e 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) 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 Recognition —0.52 (5.24) —5.76 (4.91) —3.83 (6.07) 5.89* Interference —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 present study describes the acute s of plant—saccharides (Ambrotose® Complex) on cognition and mood in middle—aged . The study presented herein is used to determine whether saccharides 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 metabolic substrate. The ology used provided a novel design to examine the effects of treatment (saccharides, sucrose, and o) between 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 ption. Specifically, despite increasing subjective ratings of mental fatigue, recognition of words previously learned was significantly higher for those who consumed polysaccharides compared to sucrose. This positive effect on recognition memory performance suggests 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 ive demand battery, there was a trend towards a ent effect of polysaccharides on the number and proportion of Serial Three subtractions made (p = .07 and .058 respectively). However, the only significant time and treatment interaction was obtained for Serial Seven subtractions. 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 y (approximately 1 hour post consumption) for those in the polysaccharide condition compared to those in the placebo condition.

Performance on Serial Sevens ction tasks is rated as significantly more demanding than Serial Threes (Kennedy and Scholey, 2000), and relies more y on working memory and executive resources. The current results t that consumption of plant polysaccharides maintains working memory performance despite conditions of mental e. 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 on to mood, there was no significant ction between treatment condition and changes in subjective ratings of gs of anxiety, alertness, contentedness or calmness.

Importantly, 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 polysaccharides indicates that the memory effects were not directly related to the modulation of blood glucose levels.

In conclusion, this is a first of kind study of the acute benefits for cognitive function associated with plant—polysaccharide consumption in healthy middle—aged adults, independent of blood glucose response. These findings suggest that the consumption of 4 g of plant ccharides may be beneficial for recognition memory performance and cognitive tasks reflecting working memory and executive function during highly demanding and ly fatiguing conditions. The results of the present invention may have ations for individuals who require a memory ‘boost’ to cope with the demands that a busy, taxing yle places upon cognitive resources.

It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method, kit, reagent, or composition of the invention, and vice versa. Furthermore, compositions of the ion can be used to achieve 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 ations mentioned 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 g 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 atives only or the alternatives are mutually exclusive, gh the sure ts a definition that refers to only alternatives and “and/or.” hout this ation, the term ” 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 ts.

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 “includes” and “include”) or “containing” (and any form of containing, such as “contains” and in”) are inclusive or open—ended and do not exclude additional, unrecited elements or method steps.

The term “or combinations 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 t, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless ise apparent 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 bed in terms of preferred embodiments, it will be nt 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 sequence of steps of the method described herein without departing from the t, 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 t 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 ing 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 t 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 effective amount of isolated and purified ated e, and a nutritionally effective amount of at least five isolated and purified saccharides selected from the group consisting of: galactose, glucose, mannose, , N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine, arabinose, glucoronic acid, galacturonic acide, iduronic acid and arabinogalactan.

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

3. The use of claim 1, n the dietary supplement is a , is dissolved in a liquid, is encapsulated, or any combinations thereof.

4. The use of claim 1, further comprising: one or more previously obtained test results to assess the mood, stress and anxiety level, or any combinations thereof in the healthy human t prior to the administration of the dietary supplement to determine a baseline or st level for the y human subject; one or more previously obtained test s 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 dietary supplement to determine a post-test level for the healthy human subject; and comparison of the baseline and the post-test levels to ine continuation, termination, or modification of the administration of the dietary ment in the healthy human t.

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

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 supplement is to be stered 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 combinations thereof.

9. Use of a dietary supplement in the manufacture of a formulation for therapeutically improving mood, reducing stress, y, mental fatigue, or any combinations thereof in a healthy 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 ement in mood, reduction of stress, anxiety, mental-fatigue, or any combination thereof; wherein the dietary supplement comprises a nutritionally effective amount of isolated and purified ated mannose, and a nutritionally ive amount of at least five isolated and purified saccharides selected from the group consisting of: galactose, e, mannose, xylose, N-acetylneuraminic acid, fucose, ylgalactosamine, N-acetylglucosamine, arabinose, onic acid, galacturonic acide, iduronic acid and arabinogalactan.

10. The use of claim 9, wherein the dietary supplement is to be orally administered.

11. The use of claim 9, wherein the y 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 obtained test results to assess the mood, stress and anxiety level, or any combinations f in the healthy human t 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 s to assess the mood, stress and anxiety level, or any combinations f in the healthy human subject at one or more specified time-points after the administration of the dietary supplement 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 modification of the administration of the dietary supplement in the healthy human subject.

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

16. The use of claim 9, n the dietary supplement is to be administered aneously or sequentially with one or more vitamins, other nutritional ments, 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. 0 HR 00 MIN BASELINE ASSESSMENT: MOOD, MEMORY AND ION BLOOD GLUCOSE 1 HR 30 MIN FINGER PRICK-1 TREATMENT 30 MIN ABSORPTION TIME BLOOD GLUCOSE 2 HRS 00 MIN FINGER PRICK - 2 POST TREATMENT ASSESSMENT: MOOD, MEMORY AND COGNITION BLOOD GLUCOSE 3 HRS 30 MIN FINGER PRICK - 3 SUBSTITUTE SHEET (RULE 26) 10.00 SCORE FIGURE DEPICTS MEAN 00.00 CHANGE FROM BASELINE PRE-TREATMENT NE SCORE (LOWER SCORES INDICATE LOWER RATINGS -10.00 OF MENTAL FATIGUE POST FROM TREATMENT), WITH INCREASING SCORES CHANGE INDICATING INCREASING -20.00 -A- tx1-SACCHARIDES METAL FATIGUE OVER TIME -E|- tx 2-PLACEBO tx 3-SUCROSE -30.00 1 2 3 4 5 6 TIME IN 10 MIN CYCLES POST TREATMENT SUBSTITUTE SHEET (RULE 26) CHANGES IN BLOOD GLUCOSE LEVELS OVER TIME 6.40 ACUTE SUPPLEMENT CONDITION -A- tx 1-SACCHARIDES mmol/I 6.20 —EI— tx 2-PLACEBO —e— tx 3-SUCROSE LEVEL 6.00 E 5.80 5.60 BLOOD 5.00 BASELINE 30 MIN POST 1 HR 45 MIN POST SUPPLEMENT SUPPLEMENT TIME SUBSTITUTE SHEET (RULE 26)