WO2022263646A1

WO2022263646A1 - Compositions

Info

Publication number: WO2022263646A1
Application number: PCT/EP2022/066587
Authority: WO
Inventors: Stephen Mann
Original assignee: Sis (Science In Sport) Limited
Priority date: 2021-06-17
Filing date: 2022-06-17
Publication date: 2022-12-22
Also published as: GB202108656D0

Abstract

The present invention concerns compositions comprising carbohydrate, in defined ratios of glucose and fructose, that when consumed by a subject, the subject sufferers no, or minimal, gastrointestinal distress when the composition is consumed by the subject in an amount sufficient to provide about (120g) of carbohydrate per hour. The compositions are useful for improving the performance of a subject during exercise or during an event and are also useful for promoting recovery after exercise or an event.

Description

COMPOSITIONS

The present invention relates to nutritional compositions containing optimal amounts of carbohydrate that may be used by subjects to improve physical performance and improve post-exercise recovery.

It is well known that the ingestion of carbohydrate shortly before and during exercise can improve physical performance. Such supplementation has been found to be of particular importance in endurance sports such as cycling and long-distance running.

Sports scientists have made significant efforts to identify the best means of delivering carbohydrate such that optimal amounts of monosaccharide enter the blood stream and becomes available as an energy source to working muscles. It has been established that a number of factors can influence the usefulness of ingested carbohydrate. These factors include:

(a) the selection of glucose as a monosaccharide sugar, as a polysaccharide (e.g. maltodextrin) or a combination of the two;

(b) the inclusion of non-glucose sugars or polysaccharides;

(c) the ratio of (a): (b); and

(d) the concentration (and consequentially the volume a subject would need to consume) of carbohydrate in liquid products.

These factors can have significant effects on the efficacy of compositions intended to improve physical performance. One may assume that performance would be directly proportionate to the amount of carbohydrate that is consumed. However, the prior art teaches that there is a maximal amount of carbohydrate that can be consumed before gastrointestinal distress is caused which has the effect of reversing any hypothetical beneficial effects of increased carbohydrate consumption.

One area of development has focused on whether or not optimal performance is influenced by the concentration of sugars in a product. It has been observed that, on the one hand, the consumption of highly concentrated sugars can cause dehydration and cramps (particularly when consumed during exercise) and this may compromise performance whereas, on the other hand, the consumption of less concentrated sugars typically requires the consumption of relatively large volumes of liquid products and this can cause a feeling of bloating, nausea and sickness which in turn is detrimental to performance. A significant advance in the delivery of carbohydrates to subjects undertaking exercise was the development of SIS GO^® isotonic energy gels which effectively deliver a concentration of carbohydrate that is isotonic relative to blood plasma. Sugars delivered in this format are a more easily digestible supply of carbohydrate for energy during exercise.

Research has also focused on the influence of the relative amounts of different sugars in sports nutrition products. It has been established that solutions containing multiple- transportable monosaccharides during prolonged exercise may advantageously increase gastric emptying into the small intestine, increase intestinal fluid absorption, increase carbohydrate oxidation and improve endurance performance relative to single carbohydrate solutions. One area of sports science research has therefore focused on examining the usefulness of different carbohydrate compositions. O’Brien and colleagues (O’Brien et at. (2013) Medicine & Science in Sports & Exercise DOI: 10.1249/MSS.0b013e31828e12d4) investigated solutions comprising varying amounts of maltodextrin-glucose and fructose and established that glucose:fructose ratios of 1 :0.8 were optimal for improving performance. However, it remained the case that too much carbohydrate reversed the beneficial effects of an optimized ratio of glucose:fructose by causing gastrointestinal distress. Other research has examined the rate at which carbohydrate may be best consumed. Smith and colleagues (Smith et at. (2013) Medicine & Science in Sports & Exercise DOI: 10.1249/MSS.0b013e31827205d1 ) examined a range of carbohydrate solutions consumed at different rates and reported that fructose:glucose-maltodextrin ratios of 0.5:1 delivered at a rate of 78g/hrwas optimal for improving performance. Interestingly they reported that performance (in their case cycling performance) progressively decreased as carbohydrate ingestion rates increased above 78g/hr.

O’Brien’s research has led to product launches with glucose:fructose ratios of 1 :0.8. For instance, Flow Formulas (see www.flowformulas.com) produce an endurance drink comprising glucose:fructose in a ratio of 1 :0.8. Flowever, consistent with the findings of Smith et at. {supra), they specify that optimal performance will be achieved if their product is consumed at a rate of 78-102g/hr. It is recommended that only one of their products (comprising 90g carbohydrate) is consumed an hour. In fact, their website stresses that some training may be required to tolerate 90g of carbohydrate and provides recommendations for a subject to “train their gut” to tolerate up to 90g of carbohydrate.

Some recent research has examined the effects of carbohydrate on exercise induced muscle damage (as opposed to performance during exercise), Viribay and colleagues (Viribay et al. (2020) Nutrients 12, 1367 DOI: 10.3390/nu12051367) have reported that intake of 120g/hr of carbohydrate during endurance exercise may result in reduced muscle damage compared to current recommendations of up to 90g/hr. Flowever, their work did not address the gastrointestinal distress caused by high dose rates of carbohydrate during exercise and the associated reduction in performance.

It is an object of the present invention to provide compositions and dosing regimens that address the problems associated with the state of the art and provide solutions that enable subjects to consume efficacious amounts of carbohydrate that will improve both performance and promote post-exercise recovery. Furthermore, the applicant appreciates that active people desire products that are of relatively small volume that may be conveniently carried in sports bags or even on the person (for instance long distance runners and cyclists often carry gels on their person for consumption while running or riding). Such products are often described as “on the go” products. Most energy products on the market are not of a convenient “on the go” size because it is difficult to concentrate an effective amount of carbohydrate in a small volume. It is therefore a further object of the present invention to provide compositions and dose units of a convenient “on the go” size.

According to a first aspect of the invention there is provided a composition comprising carbohydrate wherein the carbohydrate primarily comprises glucose and fructose in a ratio (w/w) of about 1 :0.8; and wherein the composition is formulated such that a subject consuming the composition suffers no, or minimal, gastrointestinal distress when the composition is consumed by the subject in an amount sufficient to provide about 120g of carbohydrate per hour.

By “primarily” we mean that the carbohydrate component of the composition is at least 90% fructose and glucose (whether as monosaccharide or polysaccharide). Preferably the carbohydrate component of the composition is at least 95% fructose and glucose and more preferably the carbohydrate component of the composition is at least 97.5% fructose and glucose. In some embodiments the only carbohydrate in the composition is fructose and glucose (whether as monosaccharide or polysaccharide).

Compositions according to the invention should comprises glucose and fructose in a ratio (w/w) of about 1 :0.8. It will be appreciated that this ratio may be varied to a certain extent without significantly impacting on the efficacy of the composition for improving performance in a subject undertaking exercise and/or promoting post-exercise recovery. Accordingly, by “about 1 :0.8” we mean a glucose:fructose ratio of between 1 :0.6 and 1 :1. It is more preferred that by “about 1 :0.8” we mean a glucose: fructose ratio of between 1 :0.7 and 1 :0.9.

By “about 120g of carbohydrate per hour” we mean that a subject consumes a sufficient amount of a composition according to the invention to provide about 120g of carbohydrate per hour to the gastrointestinal tract. It will be appreciated that it is surprising that consumption of this amount of carbohydrate is beneficial when the state of the art is to recommend about 78g/hr or no more than 90g/hr. According to one embodiment of the invention by “about 120g of carbohydrate per hour” we mean greater than 90g/hr. In another embodiment of the invention by “about 120g of carbohydrate per hour” we mean 90 - 200g carbohydrate an hour, preferably we mean 100 - 150g carbohydrate an hour, more preferably we mean 110 - 130g carbohydrate an hour; and most preferably we mean 115 - 125g carbohydrate an hour.

By “gastrointestinal distress” we mean a subject develops at least one of the symptoms selected from nausea, regurgitation, cramps, stomach fullness, gas and an urge to defecate.

According to a second aspect of the invention there is provided a unit dose of a composition according to the first aspect of the invention suitable for use in delivering about 120g of carbohydrate per hour to a subject.

According to a third aspect of the invention there is provided a composition according to the first aspect of the invention or a unit dose of the composition according to the second aspect of the invention for use in improving performance and/or promoting post exercise recovery. By “improving performance” we mean either a) reducing the time taken to complete a set distance or b) extending the amount of time an individual is able to sustain exercise at a given workload or intensity. A person skilled in the art will appreciate that performance or work carried out by a subject may be assessed by measuring power output in watts. By way of example, compositions used according to the invention may typically improve performance by between 0.5 - 20% during endurance exercise (both cycling and running). In a preferred embodiment, compositions used according to the invention may improve performance by between 1 - 10% during endurance exercise (both cycling and running). In a more preferred embodiment, compositions used according to the invention may improve performance by between 2 - 5% during endurance exercise (both cycling and running). In another preferred embodiment a subject will benefit from use of the compositions if the subject is undertaking an activity that will involve both moderate and intense exercise (e.g. a long distance runner, cyclist or a person carrying out both (e.g. a triathlete) who undertakes a sprint finish at the end of an endurance race).

By “promoting post-exercise recovery” we mean the prevention or reduction of damage to muscles in the period following exercise or an event. Muscles require time to repair cells damaged during strenuous effort. Muscles also require time to metabolise nutrients, replenish glycogen stores and to synthesise new enzymes and energy-producing mitochondria. Evaluation of recovery from exercise is complex, as many systems are involved. However simple measures of wellbeing are reasonably good at monitoring recovery, and some of the most frequently used include: measurement of plasma norepinephrine levels; monitoring muscular strength and power before and after exercise sessions; evaluating muscle soreness after exercise (for example using a validated questionnaire to measure extent of DOMS - Delayed Onset Muscle Soreness); recording sleep disturbances (for example using devices which measure limb movement during sleep); evaluating stress and fatigue (for example using a POMS - Profile Of Mood States - or modified POMS questionnaire, validated for use in athletes); monitoring rates of perceived exertion during exercise (for example using a validated questionnaire system); monitoring heart rates during activity, and monitoring overall mood (for example using a modified POMS questionnaire). These variables have been demonstrated in studies to be reliable indicators of effective recovery.

According to a fourth aspect of the invention there is provided a method of improving performance in a subject undertaking exercise and/or promoting post-exercise recovery in a subject after exercise, the method comprising administering to a subject in need of such treatment a composition comprising carbohydrate wherein the carbohydrate primarily comprises glucose and fructose in a ratio

(w/w) of about 1 :0.8; and wherein the composition is consumed by the subject in an amount sufficient to provide about 120g of carbohydrate per hour.

The inventor recognised that sports nutrition products with carbohydrate components primarily comprising glucose and fructose in a ratio (w/w) of about 1 :0.8 are known and recommended for improving performance during endurance exercise. However, he also recognised that it was not recommended to consume such products at more than 90g/hr (and many sports authorities recommend no more than 60g/hr) because high doses of carbohydrate are widely reported to cause gastrointestinal distress. He decided to investigate the impact of different ratios of glucose:fructose and different dosing regimens (involving varying rates of carbohydrate consumption) on performance, recovery and gastrointestinal distress. To his surprise he found that compositions according to the invention, used according to treatment regimens according to the invention, were useful for improving performance and improving recovery after exercise and also did not cause gastrointestinal distress (which compromises performance). Preliminary work (data not presented) established that compositions according to the invention, when compared to products with glucose and fructose in a ratio of 2:1 , were effective in:

(A) enhancing total exogenous carbohydrate oxidation by 17%;

(B) enhancing mean power output during 10 maximal sprint efforts by 3%;

(C) increasing the percentage of ingested carbohydrate oxidised from 62% (2:1 ratio) to 74% (1 :0.8 ratio); and

(D) surprisingly reducing symptoms of stomach fullness and nausea when compared to the 2:1 ratio.

The inventor then tested the use of compositions comprising glucose and fructose in a ratio of 1 :0.8 at higher than conventional dosing rates. He was surprised to find that the abovementioned benefits, and particularly reduced gastrointestinal distress (D), could still be achieved when compositions according to the invention are administered such that a subject consumes up to 120g of carbohydrate per hour.

Carbohydrate Component

Carbohydrate components of compositions according to the invention primarily comprise (as defined above) glucose and fructose. The carbohydrate component may comprise at least 75%(w/w) of the carbohydrate component of the composition. Preferably the carbohydrate component comprises at least 85%(w/w) of glucose and fructose and more preferably the carbohydrate component comprises at least 90%(w/w) glucose and fructose. In preferred embodiments fructose and glucose comprise at least 90%(w/w), 95%(w/w) or 97.5%(w/w) of the carbohydrate component of the composition. In some embodiments the only carbohydrate in the composition is fructose and glucose (whether as monosaccharide or polysaccharide). Glucose Content

When referring to glucose herein we mean monosaccharide glucose (which may for instance be in the form of a powder, a syrup or be crystalline) and we also mean glucose present in an oligo or polysaccharide (for instance polymerised glucose in starch or maltodextrin).

The inventors have found that polysaccharides comprising glucose are useful in compositions according to the invention. Polysaccharides are complex carbohydrate polymers with properties which depend on the sugar units, type of glycosidic linkages and the degree of branching of the molecules.

It is preferred that a polysaccharide used in compositions according to the invention is a dextrin such as maltodextrin. Maltodextrins are modified starches produced by partial hydrolysis with intermediate length polymers of D-Glucose, primarily linked with a-1 ,4 and a-1 ,6 glycosidic bonds and having a Dextrose Equivalent < 20. Maltodextrins may be sourced from starches such as tapioca, potato, rice, maize and wheat. Preferred maltodextrins for use according to the invention are spray dried maize and waxy maize maltodextrins. It is preferred that maltodextrins used in the compositions have a degree of hydrolysis (DE) ranging from 7-9.

In another embodiment the polysaccharide may be a starch. The starch may be Waxy Starch or Pea Starch.

The inventor has also found that glucose as a monosaccharide may be included in compositions according to the invention.

In a preferred embodiment the composition comprises dextrose (glucose) in the form of a glucose syrup. Such syrups may be prepared by the hydrolysis of starch sourced from potato or wheat. It will be appreciated that the glucose content of a syrup may be varied by adjusting the amount of water in which the glucose is dissolved. Such to adjustments enable a formulator to control the glucose:fructose ratio by selecting a particular concentration of glucose syrup.

In another preferred embodiment the composition comprises dextrose (glucose) in the form of a powder.

In one embodiment, compositions according to the invention comprise at least one polysaccharide of glucose and also glucose as a monosaccharide. For instance, preferred compositions comprise glucose as a monosaccharide and also include glucose in the form of maltodextrin.

Fructose Content

Fructose is preferably included as a monosaccharide in compositions according to the invention.

In a preferred embodiment the composition comprises fructose in the form of a fructose syrup. It will be appreciated that the fructose content of a syrup may be varied by adjusting the amount of water in which the fructose is dissolved. Such adjustments enable a formulator to control the glucose:fructose ratio by selecting a particular concentration of fructose syrup.

In another preferred embodiment the composition comprises fructose in the form of a powder.

Sucrose

Glucose and fructose may be provided as polysaccharides comprising both glucose and fructose. Glucose and fructose may also be present in the form of the disaccharide sucrose. In some embodiments of the invention sucrose is included as an ingredient of the composition. It will be appreciated that a sucrose component will comprise glucose and fructose in a ratio of 1 :1. Accordingly a sufficient amount of other glucose including ingredients (e.g. glucose syrup, maltodextrin or starch) will need to be included with any sucrose to ensure that the ratio of glucose to fructose is about 1 :0.8.

Other Carbohydrate

It will be appreciated that compositions used according to the invention may comprises other carbohydrates. For instance, compositions may comprise some galactose. However, it will be appreciated that the carbohydrate component of the compositions should primarily be (as defined above) glucose and fructose and that glucose and fructose should be in a ratio of about 1 :0.8.

Pharmaceutical. Nutraceutical. Food and Drink formulations

The composition is preferably formulated such that it is suitable for human consumption. Such compositions may be in the form of a pharmaceutical product, nutraceutical product or a food or drink product. Preferred compositions are food or drink products and it is most preferred that the compositions are formulated for use as a sports nutrition product.

Compositions according to the invention comprise fructose and glucose and may also comprise other agents and excipients, as discussed below, to improve their commercial properties (e.g. to improve delivery, shelf-life and the like).

The compositions of the invention should be formulated for oral administration. As such, they can be formulated as powders, gels, chews, solutions, suspensions, syrups, tablets, capsules, lozenges and snack bars and drinks or beverages (e.g. liquid shots) by way of example. Such formulations can be prepared in accordance with methods well known to the art. For example, the composition may take the form of a powder and, in use, the powder may be dissolved in water to form a drink/solution for administration orally. By way of further example, the composition may be formulated as a gel for consumption before, or during an activity. By way of further example, the composition may be formulated as a chew or gummy barfor consumption before or during an activity.

One or more excipients selected from acid regulators, glazing agents, flavouring agents, colouring agents, preservatives and thickeners may be included in the compositions. Tonicity adjusting agents can be added to provide a solution of a particular osmotic strength, for example an isotonic solution. One or more pH-adjusting agents, such as buffering agents can also be used to adjust the pH to a particular value, and preferably maintain it at that value. Examples of buffering agents include sodium citrate/citric acid buffers and phosphate buffers.

Powder compositions may be packaged and a user my dilute the contents of the package to form a drink. Alternatively, a powder may be incorporated in a solid or semi solid dosage form, for example as a tablet, lozenge, capsule or granulate.

For tablet formation, the composition may be typically mixed with a diluent such as xylitol, sorbitol or mannitol; or modified cellulose or cellulose derivative such as powdered cellulose or microcrystalline cellulose or carboxymethyl cellulose. The tablets will also typically contain one or more excipients selected from granulating agents, binders, lubricants and disintegrating agents. Examples of disintegrants include starch and starch derivatives, and other swellable polymers, for example crosslinked polymeric disintegrants such as cross-linked carboxymethylcellulose, crosslinked polyvinylpyrrolidone and starch glycolates. Examples of lubricants include stearates such as magnesium stearate and stearic acid. Examples of binders and granulating agents include polyvinylpyrrolidone. Where the diluent is not naturally very sweet, a sweetener can be added, for example ammonium glycyrrhizinate or an artificial sweetener such as aspartame, or sodium saccharinate.

The compositions can also be formulated as powders, granules, gels or semisolids for incorporation into capsules. When used in the form of powders, the carbohydrate can be formulated together with any one or more of the excipients defined above in relation to tablets or can be presented in an undiluted form. For presentation in the form of a gel or semisolid, the carbohydrate can be dissolved or suspended in a viscous liquid or semisolid vehicle such as a polyethylene glycol, or a liquid carrier such as a glycol, e.g. propylene glycol, or glycerol or a vegetable or fish oil, for example an oil selected from olive oil, sunflower oil, safflower oil, evening primrose oil, soya oil, cod liver oil, herring oil, etc. These can then be filled into capsules of either the hard gelatine or soft gelatine type or made from hard or soft gelatine equivalents, soft gelatine or gelatine-equivalent capsules being preferred for viscous liquid or semisolid fillings. In one preferred embodiment, a composition according to the invention is provided in powder form optionally together with a preferred solid (e.g. powdered) excipient for incorporation into capsules, for example a hard gelatine capsule

The compositions according to the invention can be provided as unit dosage forms according to the second aspect of the invention. Such dose forms should comprise 5g - 200g carbohydrate per serving, preferably 10g - 120g per serving and more preferably in the range of 20g - 80g per serving. In preferred embodiments the composition or product comprises about 40g or 80g per serving of carbohydrate.

The composition of the invention can be included in a container, pack or dispenser together with instructions for administration.

Preferred Compositions for Human Consumption

Preferred compositions according to the invention are gels; powders for making drinks and chew bars.

Gel products

Aqueous gel products for consumption as a food supplement represent preferred compositions according to the invention. Such gels may be packaged such that the packaging may be torn open and the gel consumed during exercise. The gel products contain at least a source of carbohydrate (as discussed above) and a gelling agent. Gel products may additionally include one or more of electrolytes, antioxidants, preservatives, flavouring and sweeteners.

Gels should comprise a suitable agent or agents that form an edible gel with a consistency that makes it possible to easily squeeze the gel from packaging and also to be easily consumed.

A number of suitable gelling agents may be used that are known to the art. For instance, a gellan gum may be used (e.g. Kelcogel-F). In some embodiments the gel may comprise two gel agents. For instance, it may comprise a gellan gum and a xanthan gum.

In one embodiment gels are defined, and manufactured according to the methods disclosed, in WO 2007/083117 (e.g. as described on pages 19 - 22 of that specification) but wherein glucose/maltodextrin and fructose is included in a ratio of about 1 :08. It will be appreciated that gels according to the present invention may preferably be isotonic (relative to blood plasma) as disclosed in WO 2007/083117. Flowever, in some embodiments the gels may not be isotonic. A skilled person will appreciate that the tonicity of a product can be readily adapted (in view of the teaching of WO 2007/083117) according to need.

A preferred gel product for use according to the invention may comprise:

(1) water;

(2) fructose, and maltodextrin or glucose;

(3) one or more gelling agents;

(4) optionally flavouring; and

(5) optionally preservatives and/or antioxidants. It is preferred that gels according to the invention comprise at least 30% (w/w) water, preferably the gel comprises at least 40% (w/w) water. In some embodiments the gel comprises 35-75% (w/w) water and preferably 40-55% (w/w) water. For instance, the gel may comprise about 44%, 45%, 46%, 47%, 48% or 49% (w/w) water.

It is preferred that the carbohydrate component of a gel according to the invention (i.e. (2) above) comprises at least 35% (w/w) of the gel, preferably the carbohydrate component comprises at least 45% (w/w) of the gel. In some embodiments the carbohydrate component comprises 45-75% (w/w) of the gel and preferably 50-60% (w/w) of the gel. For instance, the gel may comprise about 51 %, 52%, 53%, 54% or 55% (w/w) carbohydrate.

It is preferred that the gelling agent is a gellan gum or a xanthan gum. In a preferred embodiment the gel comprises two gelling agents and it is preferred these gelling agents are a gellan gum and a xanthan gum. Gels according to the invention may comprise 0.05 - 2.5% (w/w) of total gelling agent and preferably 0.1-1 .0% (w/w) of total gelling agent. In one embodiment the gel may comprise about 0.2% total gelling agent. For instance, in most preferred embodiments a gel according to the invention comprises about 0.1%(w/w) gellan gum and about 0.1 %(w/w) xanthan gum

In one embodiment the gel product may comprise water; glucose or maltodextrin; fructose; a gellan gum and a Xanthan gum; a preservative and/or antioxidant; and flavouring.

Flavourings may be selected to prepare a gel of a chosen taste. For instance, preferred gels are apple flavoured; orange flavoured; lemon and lime flavoured; or strawberry and lime flavoured. Alternatively, blackcurrant or tropical flavourings may be used. Flavourings are preferably natural flavourings. Preservatives and/or antioxidants used in gels according to the invention may be selected from Potassium Sorbate, Sodium Benzoate, Sodium Citrate and citric acid.

Gels according to the invention may optionally include a salt (e.g. Sodium Chloride).

It will be appreciated that gels according to the invention may include further ingredients that may have advantageous effects in subjects undertaking exercise. By way of example, the gels may include nootropic substances. For instance, gels may further comprise at least one nootropic substance selected from L-Taurine, caffeine, L-Theanine or Citicoline. In a preferred embodiment a gel may include each of L- Taurine, caffeine, L-Theanine and Citicoline. It is preferred that gels according to the invention comprise no more than 5%(w/w) of nootropic substances and preferably comprise no more than 2.5%(w/w) of nootropic substances. In a preferred embodiment a gel according to the invention may comprise about 1.4% L-Taurine, about 0.2% caffeine, about 0.2% L-Theanine and about 0.3% Citicoline. The inclusion of nootropic substances enhances cognitive performance giving a “mental lift” to a subject which can also improve performance, especially in the latter phases of exercise. Accordingly in a preferred embodiment of the invention the composition is a gel which includes nootropic substances.

It will be appreciated that many of the above ingredients may be adjusted or substituted by a person skilled in the art of formulating gels for oral consumption.

Most preferred gels are described in Example 1.

A typical dose form of a gel for giving to a human subject may be 10-200ml of the abovementioned gels, preferably 20-150ml of gel, more preferably 30-120ml of gel, more preferably 40-80ml of gel and most preferably about 60ml of gel. The gel may comprise between comprise 5g - 200g of carbohydrate, preferably 10g - 120g carbohydrate and more preferably in the range of 20g - 80g carbohydrate. In preferred embodiments a gel comprises about 40g of carbohydrate.

In one embodiment, a gel according to the invention is a gel comprising about 60g carbohydrate (suitable for consuming up to two gels per hour). In another embodiment, a gel according to the invention is a gel comprising about 120g carbohydrate (suitable for consuming one gel per hour).

In a most preferred embodiment, a gel according to the invention is a 60ml gel comprising about 40g carbohydrate (suitable for consuming up to three gels per hour).

The inventor has found that gels are surprisingly useful when given to a subject during exercise. He has established that the abovementioned dose forms may be given such that a subject is dosed at about 120g/hr without any symptoms of gastrointestinal distress and at the same time improving performance and/or post-exercise recovery. Therefore, in a preferred embodiment of the invention, the composition is a gel for use during exercise. Preferred gels are isotonic relative to blood plasma. While the inventor does not wish to be bound by any hypothesis, he believes that isotonic gels according to the invention are particularly effective because they represent a small volume and are isotonic. Consumption of the small volume reduces distention of the stomach and helps to reduce gastrointestinal distress whilst the isotonicity of the gel improves delivery of 1 :08 (glucose:fructose) into a subject’s blood stream from where the carbohydrate may be transported to the muscles to have the maximum effect on performance.

Powder Products

Compositions according to the invention may also be provided in a powder form. Subjects may dilute the powder in water to form a solution for consumption.

Powder mixes may be used to fill sachets. A typical powder may comprise: (1) carbohydrate (primarily maltodextrin or glucose, and fructose); and

(2) flavouring.

It is preferred that a powder according to the invention comprises at least 75% (w/w) carbohydrate; preferably the carbohydrate component comprises at least 85% (w/w) of the powder; and more preferred that the carbohydrate component comprises at least 95% (w/w) of the powder. In some embodiments the carbohydrate component comprises 85-99.5% (w/w) of the powder and preferably 95-99% (w/w) of the powder. For instance, the powder may comprise about 95%, 96%, 97%, 98% or 99% (w/w) carbohydrate. In one embodiment the powder comprises 98.6% (w/w) carbohydrate.

In preferred embodiments the powder mix comprises only carbohydrate and flavouring. Such powder mixes preferably comprise fructose, maltodextrin and flavouring (e.g. orange flavouring).

Powders according to the invention may optionally further comprise further soluble excipients including: effervescent agents formed from carbonates, (e.g. bicarbonates such as sodium or ammonium bicarbonate); sweeteners (e.g. Stevia or sucralose), salts (e.g Sodium Chloride); and buffering agents, preservatives and/or antioxidants (e.g. Potassium Sorbate, Sodium Benzoate, Sodium Citrate and citric acid).

Powder compositions according to the invention may be split into quantities that make does units that may be easily consumed to achieve a dosing of 120g/hr when used by a subject. For instance, powders may be provided in quantities of about 40g, 60g, 80g or 120g. Powders are most preferably split into about 80g quantities (e.g. 82g) and sealed within sachets, pouches or tubs.

A dose unit of a powder composition according to the invention may comprise between 5g - 200g of carbohydrate, preferably 10g - 150g carbohydrate and more preferably in the range of 20g - 120g carbohydrate. A dose unit according to the invention may comprise 40g, 60g, 80g or 120g of a powder composition. In preferred embodiments a dose unit comprises about 80g of the powder.

In use the powder may be mixed with between 100 and 1 ,000mls of water and consumed before exercise is initiated or during exercise. More preferably the powder is mixed with between 250 and 750mls of water and then consumed. In some embodiments the powder is mixed with about 500mls of water and then consumed. In a preferred embodiment about 80g of a powder composition (e.g. 82g of the powder described in Table 3) is mixed with about 600mls of water to form a drink that is isotonic relative to blood plasma. While the inventor does not wish to be bound by any hypothesis, he believes that such isotonic drinks are particularly effective because their tonicity improves delivery of 1 :08 (glucose:fructose) into a subject’s blood stream from where the carbohydrate may be transported to the muscles to have the maximum effect on performance. Further the inventor has found that isotonic drinks are particularly effective for reducing or presenting gastrointestinal distress.

A most preferred powder product according to the invention is defined in Example 1 .

Chews or Gummies

Compositions according to the invention may also be provided as chews or gummies. Such chews or gummies may be provided as individual “sweets” or jellies or may be provided as a bar (from which individual chews or gummies may be bitten off).

A typical chew or gummy may comprise:

(1) maltodextrin or glucose, and fructose;

(2) a gelling agent (e.g. pectin);

(3) optionally a glazing agent (e.g. coconut oil, carnauba wax);

(4) optionally colour (e.g. a carotene or turmeric extract); (5) optionally flavouring; and

(6) optionally an acidity regulator

In one embodiment a chew or gummy may comprise: sucrose, glucose syrup, fructose syrup, pectin, corn starch, an acidity regulator (e.g. citric acid), a glazing agent (e.g. coconut oil, carnauba wax), colouring (turmeric extract) and a natural flavouring (e.g. orange or lemon).

A chew or gummy should preferably comprise at least 50% (w/w) carbohydrate. It is more preferred that a chew or gummy comprise at least 60% carbohydrate and even more preferred that a chew or gummy comprise at least 70% carbohydrate. In a preferred embodiment the chew or gummy comprises about 70-90% carbohydrate and preferably 75-85% carbohydrate.

In a most preferred embodiment of the invention the chew or gummy comprises sucrose, glucose syrup and fructose syrup. When this is the case a gluose:fructose ratio of 1 :0.8 may be achieved by adjusting the concentration of the syrups.

Multiple gummies or chews may be manufactured as a bar. The bar may be between 5g - 300g, preferably 10g - 200g and more preferably 20 - 100g. Each bar may be separated into individual gummies or chews which may for example by 5, 10, 15 or 20g each.

In one embodiment a bar may be about 60g and divisible into 6 x 10g chews. Such a bar will constitute a dose unit according to the invention.

In a preferred embodiment a bar may be about 30g and divisible into 3 x 10g chews and in this case 2 x 30g bars may be packaged together to form a dose unit. In a most preferred embodiment a bar may be about 30g and divisible into 3 x 10g chews and wherein each chew or gummy comprises about 75% carbohydrate. Accordingly, each 10g chew will provide about 7.5g of carbohydrate. Two of these 30g bars may be packaged together to form a dose unit according to the invention,

A most preferred chew bar according to the invention is defined in Example 1.

Dosing Regimens

Compositions according to the invention are useful when consumed by subjects undertaking a variety of exercises. They are particularly useful when taken during endurance exercises and are most effective when an event or exercise will take 2 hours or more (e.g. a triathlon, a long distance run or cycling event).

It will be appreciated that a dose of 120g/hr may be achieved by using one type of composition according to the invention although preferably a combination of products may be used.

By way of example, a fuelling strategy for a long distance runner or cyclist undertaking a 2 hour event could be to carry two 600ml bottles containing water with an 80g sachet powder dissolved in each bottle. This drink will help with hydration and should be sipped throughout the exercise, or taken at 20 minute intervals, with the aim of finishing the bottles by the end of the event. A chew bar dose unit (comprising 40g carbohydrate) may be consumed during the first hour of the exercise and a gel (comprising 40g carbohydrate) consumed in the second hour. Consumption of a gel also containing nootropics will provide a further boost during the second hour of the event. This regimen will result in the consumption of a total of 240g of carbohydrate at a rate of 120g/hr. The abovementioned regimen may be adapted for a three hour event. A subject could still carry two 600ml bottles containing water with an 80g sachet powder dissolved in each bottle. This drink will help with hydration and should be sipped throughout the exercise, or taken at 20 minute intervals, with the aim of finishing the bottles by the end of the event. Two chew bar dose units (comprising 40g carbohydrate each) and two gels (comprising 40g carbohydrate each) may be consumed during the three hour event. Consumption of a gel also containing nootropics may best provide a further boost if carried and then consumed in the third hour of the event. This regimen will result in the consumption of a total of about 360g of carbohydrate at a rate of 120g/hr.

The abovementioned regimen may be adapted for a four hour event. In this case a subject could carry three 600ml bottles containing water with an 80g sachet powder dissolved in each bottle. This drink will help with hydration and should be sipped throughout the exercise, or taken at 20 minute intervals, with the aim of finishing the bottles by the end of the event. Two chew bar dose units (comprising 40g carbohydrate each) and two gels (comprising 40g carbohydrate each) may be consumed during the four hour event. Consumption of a gel also containing nootropics may best provide a further boost if carried and then consumed in the fourth hour of the event. This regimen will result in the consumption of a total of about 360g of carbohydrate at a rate of 120g/hr.

It will be appreciated that the abovementioned regimens may be tailored for individual needs and in the light of the length, and difficulty of stages, of specific events. For instance, in some embodiments it may be desirable to consume a gel containing nootropics about 1 hour before the subject anticipates a “boost” may be required in an event. This could be with a sprint finish in mind or could be in advance of an anticipated difficult stage in the event (e.g. an uphill section of a cycling or running event). Dosing regimens represent an important aspect of the invention. Thus according to a fifth aspect of the invention there is provided a dosing regimen for improving performance in a subject without causing gastrointestinal distress in the subject comprising administering a dose unit according to the second aspect of the invention in sufficient quantities to deliver about 120g/hr of carbohydrate to the subject during an event or exercise.

Such dosing regimens are preferably employed when an event or exercise will last two hours or more.

EXAMPLE 1

The inventor developed gels, powder and chew bar compositions for use according to the invention.

2.1 Gels

Most preferred gel products for use according to the invention may comprise:

Table 1 :

The gel product of Table 1 may be manufactured by adding water to a mixing tank and heating to 25°C. Next gellan gum (Kelcogel-F) and sodium citrate is added to the vessel and the solution is then heated to 79°C with mixing. Once at temperature Sodium Benzoate, Potassium Sorbate, Citric acid, Xanthan gum and Sodium Chloride is added as a batch. Once these ingredients are mixed in, maltodextrin and fructose are added and the gel product mixed to homogeneity. Finally flavouring (e.g. orange) is added in the form of a liquid or powder and mixed in. The gel is then allowed to cool as it is applied to sachets.

Table 2: Gel with nootropics

The gel product of Table 2 was manufactured following the same process as described above except Taurine, caffeine, L-threonine and citicoline were added as a batch and mixed in after the maltodextrin and fructose. Finally the flavouring was added in the form of a liquid or powder. In one embodiment the flavouring may be an apple flavouring supplemented with malic acid.

Gels may be packaged into laminated foil sachets to ensure shelf life, using for example a gel packaging machine such as made by Universal Pack. Typical gel sizes range from about 40ml to about 100ml but preferably have a volume of about 60mls. Unit doses of gels may comprise approximately 40g of carbohydrate.

2.2 Powders

Powder mixes may be made to contain ingredients in the following quantities:

Table 3:

Preferred flavourings are orange; lemon and lime; or strawberry and lime.

Such powder mixes can be made by conventional dry-blending techniques, for example using a ribbon blender, IBC blender or similar, under suitable factory conditions controlling dust and humidity. Agents may be added to ensure free-flow of the resultant powder, e.g. anticaking agents. Packaging into suitable containers such as tubs or sachets should be done under conditions of strict dust control and controlled humidity.

The powders may be split into 40g, 80g or 120g dose units and sealed within sachets. Preferably a sachet comprises about 82 grammes of powder (i.e. about 80g carbohydrate) and the dose unit may be mixed with 500m Is or 600m Is of water and then consumed during exercise.

2.3 Chew or Gummies

Chew bars or Gummy/jelly bars may be made to contain ingredients in the following quantities:

Table 4:

It will be appreciated that the amount of sucrose (a disaccharide of glucose and fructose); the amount of corn starch; the concentration glucose in the glucose syrup and the amount used thereof; and the concentration of fructose in the fructose syrup and the amount used thereof; were all calculated such that the glucose:fructose ratio in the chew bar was 1 :0.8.

Preferred flavourings are orange and lemon.

The colouring may be a carotene or a Turmeric root extract. An appropriate process for making a chew bar involves heating water to 80°C and dissolving the pectin therein. The mix is then heated to 120°C and the syrups are then added. The mix is then cooled to 100-110°C and sucrose, colouring, citric acid and flavouring is added. This is mixed and the liquid dispensed into moulds for 30 g bars (which are shaped such that the bar is divisible into 3 x 10g chews) and the mixture allowed to cool until the bar has set to a jelly-like consistency. Finally, the starch and glazing agents are applied to the surface of the bar and the bars are then packaged. In this case a dose unit is provided by including 2 x 30g bars in the packaging. This provides 6 x 10g chews per serving.

EXAMPLE 2

The inventors proceeded to conduct trials whereby subjects were asked to consume the products described in Example 1 (i.e. compositions according to the invention).

2.1. METHODS Experimental overview

Cyclists completed two hours of submaximal exercise at an intensity corresponding to 95% lactate threshold on three separate occasions in which they consumed either a) Beta Fuel drink, b) Beta Fuel gels or c) Beta Fuel chew bars at a rate of 120 g/h. During exercise, expired gases, capillary blood, heart rate and subjective ratings of gastrointestinal symptoms and perceived exertion were collected at 30-minute intervals.

Measurement of exogenous carbohydrate oxidation

Plasma glucose isotope enrichment was measured as the tracer/tracee ratio (TTR) by gas chromatography-mass spectroscopy using a trimethyl silyl-O-methyloxime derivative, according to methods previously described (Pugh et al, 2020; https://doi.orq/10.1152/ajpendo.00452.2019) Assessment of gastrointestinal symptoms

Gastrointestinal symptoms (including nausea, regurgitation, cramps, stomach fullness, gas and urge to defecate) were measured using a 10-point visual analog scale (0 = no symptoms, and 10 = very severe symptoms). A score >4 was regarded as moderate symptoms which were beginning to effect exercise performance. Such methods have been previously described (Pugh et al, 2020; https://doi.orq/10.1152/aipendo.00452.2019).

Analysis of blood metabolites

Blood samples were obtained from a capillary fingertip blood sample (20 microliters), immediately placed in hemolyzing solution and analysed for glucose and lactate via an automated analyser (Biosen C-Line, EKF Diagnostics, UK).

Assessment of physiological responses to exercise

Heart rate was collected via a Bluetooth heart rate monitor (Polar F10, Polar, Finland) and ratings of perceived exertion were collected using a 15-point visual analog scale (6 = no exertion, and 20 = maximal exertion).

Assessment of exercise performance

Exercise performance was determined using an exercise capacity test whereby subjects cycle at 150% lactate threshold until exhaustion as previously described (Fell et al., 2021 ; doi: 10.1113/JP281127)

2.2 RESULTS

Physiological responses to exercise

Heart rate (152, 159 and 151 beats/min), and ratings of perceived exertion (11 , 12 and 11 ) were similar for drink, gel and chew bar trials, respectively. Exogenous carbohydrate oxidation

Mean rates of exogenous carbohydrate oxidation (90-120 min) were 1.42, 1.26 and 1.58 g/m in for drink, gel, and chew bar formats, respectively. Peak rates of exogenous carbohydrate oxidation were 1.44, 1.37 and 1.71 g/min for drink, gel and chew bar formats, respectively.

Blood metabolites

Blood glucose remained above 4 mmol/L during exercise during drink, gel and chew bar trials, whereas blood glucose dropped below 4 mmol/L during the water only trial, indicating the presence of hypoglycaemia. Blood lactate remained similar between all trials.

Gastrointestinal symptoms

During exercise, gastrointestinal symptoms were low (<4 on the scale of 0-10) across all product formats.

Exercise performance

When consuming carbohydrate at a rate of 120 g/h (using the drink format) exercise capacity was greater when compared with placebo (water only) (356 seconds vs. 95 seconds, respectively).

2.3 CONCLUSIONS

Consuming carbohydrate at a rate of 120 g/h, using drink, gel or chew bar formats, maintains blood glucose concentrations > 4 mmol/L when compared with water which led to the development of low blood glucose concentrations < 4 mmol/L. Furthermore, the consumption of carbohydrate at a rate of 120 g/h allows for peak exogenous carbohydrate oxidation rates between 1.3 and 1.7. When compared with placebo, consumption of carbohydrate at a rate of 120 g/h (using drink format) enhances exercise performance by 261 seconds. Despite this, gastrointestinal symptoms remained low across all product formats.

These data demonstrate that compositions according to the invention significantly improve performance and this improvement is achieved when carbohydrate is administered at 120g/hr. A skilled person may have considered an increased rate of delivery of carbohydrate to be desirable. However, the state of the art recommends administering carbohydrate at 78g/hr in order that gastrointestinal distress may be avoided. Surprisingly compositions according to the invention could be used to deliver carbohydrate at 120g/hr and without causing symptoms of gastrointestinal distress.

Claims

1. A composition comprising carbohydrate wherein the carbohydrate primarily comprises glucose and fructose in a ratio (w/w) of about 1 :0.8; and wherein the composition is formulated such that a subject consuming the composition suffers no, or minimal, gastrointestinal distress when the composition is consumed by the subject in an amount sufficient to provide about 120g of carbohydrate per hour.

2. The composition according to claim 1 comprising glucose as a monosaccharide.

3. The composition according to claim 1 comprising glucose in the form of a polysaccharide.

4. The composition according to claim 3 wherein the polysaccharide is maltodextrin.

5. The composition according to any one of claims 1 - 4 comprising glucose as a monosaccharide and a polysaccharide.

6. The composition according to any one of claims 1 - 5 comprising fructose as a monosaccharide.

7. The composition according to any one of claims 1- 6 wherein the composition is formulated as a sports nutrition product.

8. The composition according to claim 7 wherein the sports nutrition product is a gel, powder or chew/gummy bar.

9. The composition according to claim 8 wherein the sports nutrition product is a powder and, in use, is diluted to form a drink.

10. The composition according to claim 9 wherein the powder is diluted in sufficient water to make the drink isotonic relative to blood plasma.

11 . The composition according to claim 8 wherein the sports nutrition product is a gel and the gel is isotonic relative to blood plasma.

12. A unit dose of the composition according to any preceding claim comprising between 5g and 120g per serving of carbohydrate.

13. The unit dose according to claim 12 comprising between 7.5g and 80g per serving of carbohydrate.

14. The unit dose according to claim 12 in the form of a gel and comprising about 40g per serving of carbohydrate.

15. The unit dose according to claim 12 in the form of a chew or gummy bar and comprising about 40g per bar of carbohydrate.

16. The unit dose according to claim 12 in the form of a powder and comprising about 80g per serving of carbohydrate.

17. A composition according to any one of claims 1-11 or a unit dose of the composition according to any one of claims 12-16 for use in improving performance during exercise.

18. A dosing regimen for improving performance in a subject without causing, or minimising, gastrointestinal distress in the subject comprising administering a dose unit according to any one of claims 12-16 in sufficient quantities to deliver about 120g/hr of carbohydrate.