WO2011063809A1

WO2011063809A1 - Diet product comprising alginate

Info

Publication number: WO2011063809A1
Application number: PCT/DK2010/000153
Authority: WO
Inventors: Finn Larsen; Morten Møller Georg JENSEN; Arne Vernon Astrup; Mette Kristensen; Thomas Meinert Larsen; Anita Belza Sparre
Original assignee: S-Biotek Holding Aps
Priority date: 2009-11-24
Filing date: 2010-11-24
Publication date: 2011-06-03

Abstract

The present invention relates to the use of an alginate for the preparation of a liquid diet product for treating or preventing obesity, wherein the diet product is administered in a dosage of at least 350 mL alginate solution in an aqueous dissolved form, wherein the alginate forms a gel at a pH of 3 or less; the invention also relates to a liquid diet product for treating or preventing obesity comprising an alginate in an aqueous dissolved form at a pH value not causing the alginate to form a gel, wherein a subject suffering from or at risk of suffering from obesity is administered a unit dose of the diet product of at least 350 mL

Description

Diet product comprising alginate

The present invention relates to the use of alginate for the preparation of an aqueous dietary product for the treatment or prevention of unwanted overweight and obesity. The dietary product may be used for the regulation of the feeling of satiety and subsequently the food intake in humans or animals. The invention also relates to a liquid dietary product for the treatment or prevention of unwanted overweight and obesity comprising an alginate in an aqueous dissolved form at a pH value not causing the alginate to form a gel.

Background of the invention

Even with good dietary advice experience shows that it is not easy to make people to consume more soluble dietary fibres even though it has shown to be beneficial to health, especially in subjects suffering from diabetes and/or obesity.

Dietary fibres are commonly used in the regulation of food intake. Dietary fibres are grouped into 2 types: soluble and insoluble fibres. The insoluble dietary fibres are present in coarse bread and starchy vegetables. Examples of insoluble fibres comprise cellulose, hemicellu- lose, lignin and pectin. The soluble fibres are present in fruit and vegetables. Examples of soluble fibres comprise guar, dextran, alginate, starch, amylose, amylopectin, xanthan, pullulan, carrageenan and gel- Ian.

US 2004/0228903 discloses a liquid edible composition having a pH of more than 5 and containing pectin or alginate together with a calcium salt. The calcium salt may be present in an amount exceeding its maximum solubility in the edible liquid, however it will dissolve in the stomach under the influence of the pH reduction and/or the rise in temperature. Typical calcium salts are CaC0₃ and CaHP0₄. The increasing calcium concentration will stimulate the gelation of pectin and/or alginate as calcium ions and the polysaccharides form a rigid matrix. The alginate or pectin used has a viscosity below 50 cP at a shear rate of 100 s^"1. The alginate suggested in US 2004/0228903 contains from 100 to 100,000 residues of mannuronic or guluronic acid corresponding to a molecular weight range from about 18,000 to 20,000 and up to more than 10 x 10⁶ depending on the amount of sodium in the molecule; the ratio between mannuronic and guluronic acid is not specified. The liquid composition of US 2004/0228903 is suited for use as a soft drink re- placer, which may be used in the prevention or treatment of overweight. As a soft drink replacer the unit dosage of the liquid composition of US 2004/0228903 may be between 25 and 2000 mL in volume, for example between 100 and 400 mL; the volume of this unit dosage appears to correspond to the 'unit dosage' of a typical soft drink. The viscosity of the liquid composition of US 2004/0228903 is below 50 mPas at a shear rate of 100 s^"1; in order to obtain this value addition of thinners, such as polyols, may be required.

WO 2005/020717 and WO 2005/020719 relate to food products for use in a weigth control plan which in addition to alginate and insolu- ble calcium salt, also comprise protein. The food products may be a liquid or a spoonable edible product. The alginate employed in 2005/020717 and WO 2005/020719 must have a guluronic acid content of at least 60% and preferably has a molecular weight of at least 0.5 x 10⁵. The food products of WO 2005/020717 and WO 2005/020719 are meal replacers intended to replace a conventional meal as part of a weight loss plan, and these product may be liquid, spoonable or solid, e.g. in the form of a cereal bar. 2005/020717 defines a spoonable product in terms of rheological parameters; for example, the Bingham viscosity is less than 500 mPas at shear rates between 100 and 300 s^"1. As meal replacers the products of WO 2005/020717 and WO 2005/020719 must contain protein, e.g. from 1 to 25% by weight. The serving size of the product of WO 2005/020717 corresponds to the serving size of a single portion, and for a liquid food product the volume may be between 100 and 500 mL, for example 200 to 350 mL. However, no effect of the volume of the serving size is demonstrated.

The compositions of US 2004/0228903, WO 2005/020717 and WO 2005/020719 are intended for use as a soft drink or a meal replacer, respectively. Providing a dietary product in such a form to replace e.g. a meal may be disadvantageous as the subject in need of weight loss may lack motivation to go through a long lasting diet using such products. Furthermore, a meal replacer may only be expected to have an effect in the treatment of overweight in light of the meal it replaces. However, taking into account the lifestyle causing obesity, then it may be advan- tageous also to consider food and snacks consumed between meals.

The rigid matrix, putatively causing the effect on satiety in the products of WO 2005/020717, WO 2005/020719 and US 2004/0228903, is formed when calcium ions are complexed with homogeneous blocks of guluronic acid in alginate or pectin to form an "egg box" structure. Con- trol of the calcium concentration throughout the gelling process is crucial for a uniform gel to evolve. If the initial concentration of calcium is too high the polysaccharide will precipitate rather than forming a gel. The conditions in the stomach may be difficult to control due to interpersonal differences and the presence of or lack of food in the stomach. Further- more, the rigid matrix formed from alginate and calcium ions may also be slowly degraded so that an adverse effect on nutrient uptake from the guts can be expected.

Calcium-induced gelation implies that a high amount of calcium salt must be present in the product before consumption. In the products a cco rd i n g to U S 2004/ 0228903 , W O 2005/ 0207 1 7 a n d W O 2005/020719, the calcium salt is present as an insoluble salt. Since a drink is generally desired to have a low viscosity to obtain consumer acceptance the insoluble calcium salt is likely to precipitate during storage. Apart from the inconvenience of shaking the drink before consumption a non homogeneous product further has the disadvantage that the consumer may not obtain the calcium salt in a proper dose for an optimal gelation to take place.

US 5,324,526 discloses an alginate-containing food product, e.g. a beverage, aimed at utilising the beneficial effects of alginate as a dietary fibre, such as for the prevention of overweight and obesity and diabetes, e.g. by reducing the activity of insulin to synthesise fats from glucose. The alginate is used as a dietary fibre and is produced by degradation of commercially available alginate by a certain pressure and temperature scheme. The scheme can be selected to produce an alginate within the molecular weight range of 10,000 to 900,000, as is relevant for the product of US 5,324,526. The alginate containing food or beverage of US 5,324,526 has an alginate content of 1 to 50% by weight; a most preferred range is 5 to 10% by weight. Alginates with the desired ability to reduce glucose in blood in rats and at the same time stabilise the amount of insulin have an average molecular weight of 50,000. If the alginate is shorter, i.e. around a molecular weight of 10,000 the alginate shows no tendency to reduce the blood glucose. For an alginate of a molecular weight of 100,000 the tendency to reduce blood glucose is similarly reduced compared to the alginate having a molecular weight of 50,000. Probably due to the production method, the viscosity of the alginates is low. Thus, a typical alginate of an average weight of 60,000 has at 30°C in an aqueous concentration of 5.2-5.3% a viscosity of 13 cP.

The effects of the alg inate conta ini ng food prod uct of US

5,324,526 were only tested with rats. The results of such experiments can not necessarily be extrapolated for human beings. Furthermore, any effect on satiety or general well-being in a human subject from this product cannot be derived from experiments with rats. In particular, the dosages given to the rats may not be scaleable to provide any meaningful information on the required dosage for any effect in humans, nor of the optimal formulation of the dose.

US 2002/0068110 describes a dietary food formula comprising a mixture of agar, carrageenans, alginate, chlorella, spirulina, and water; alginate may be present in a concentration of 1 to 450 g/L, and the remaining fibres in a similar amount. The volume of the unit dosage is 100 ml_ plus the volume added from the dietary fibres.

WO 2008/098579 relates to a dietary product comprising an alginate in an aqueous dissolved or swelled form at a pH value causing the alginate not to gel. The dietary product of WO 2008/098579 avoids several of the disadvantages of the prior art, e.g. the alginate does not require an increased calcium concentration in order to stimulate the gelation of the alginate. According to WO 2008/098579 the viscosity of a 4% solution of an appropriate alginate should be above 100 mPas, although examples of dietary products disclosed in WO 2008/098579 contained 1% or less of alginate. The composition of the alginate employed in WO 2008/098579 in respect of mannuronic acid to guluronic acid (M/G-ratio) is deemed of minor importance, though an M/G-ratio above 1.0 was found to be useful. The concentration of alginate suggested in WO 2008/098579 is given as a range from 0.2 to 20 g per kg (weight of the diet product), i.e. 0.02 to 2%, with a preferred range from 0.15 to 1%. In specific examples doses of up to 2.5 g alginate were administered in up to 0.4 L volume, thus corresponding to the volume of a con- ventional soft drink.

It is well-known that the size of the human stomach is not correlated with the body height and body weight of an individual as demonstrated by Cox (1945, Cal West Med, 63(3) : 267-268). The present inventors therefore believe that there may be a hitherto unknown effect of the volume of a satiety inducing dietary product.

The object of the present invention is to provide a dietary product benefiting from the effects on satiety of dietary fibres. The invention aims to provide a dietary product, which can help a subject in adjusting his or her diet not to contain excessive amounts of energy. In particular, the invention aims to provide a simple product not requiring to be formulated as a meal replacer but utilising the effect on satiety to reduce the total energy intake of a subject and thereby prevent or reduce overweight. Summary of the invention

A first aspect of the invention relates to the use of an alginate for the preparation of an aqueous dietary product for the treatment and/or prevention of overweight and obesity. The dietary product has a pH value not causing the alginate to form a gel and the dietary product is administered at a dosage of at least 350 mL.

The present inventors have surprisingly found that satiety inducing factors are strongly correlated with the volume of a dietary prod- uct containing soluble dietary fibres. Thus, it has been found that the effect of a liquid dietary product administered at a volume of 330 mL was not significant when compared to the administration of 330 mL of placebo, whereas when the dietary product was administered at an increased volume the feeling of satiety was increased significantly which subsequently should lead to a reduction in prospective food intake.

In another aspect the invention relates to an aqueous dietary product for treatment or prevention of overweight and obesity comprising an alginate in an aqueous dissolved form at a pH value not causing the alginate to form a gel, wherein a subject suffering from or at risk of suffering from obesity or overweight is administered a unit dosage of the dietary product of at least 350 mL. The subject being administered the unit dosage is generally an adult. If an adolescent or a child is treated the dosage may be adjusted to the age of the person being treated.

The present inventors have found that ingestion, e.g. prior to the intake of a meal, a dosage of at least 350 mL of a liquid dietary product comprising an alginate which forms a gel when exposed to the gastric juice/gastric acid provides an efficient modulating effect on the appetite, e.g. the appetite is reduced at the time of the meal intake. In other embodiments the unit dosage volume may also be increased so that the volume may be at least 400 mL, 450 mL, 500 mL, 550 mL, 600 mL etc. In another aspect, the present invention relates to the aqueous product mentioned above and the use thereof for increasing the perceived satiety. In still another aspect of the invention, it relates to the aqueous product mentioned above and the use thereof for decreas- ing the prospective food intake.

Any alginate may be used in the present invention provided it forms a gel at a pH of 3 or less. In contrast, when the alginate is present at a higher pH it does not form a gel, e.g. when used according to the invention it is in an aqueous dissolved form at a pH value not causing the alginate to form a gel. Thus, the alginate is soluble in water and may be activated by acid causing the dietary product of low viscosity to form a thick gel in the stomach due to the low pH value present there. With "activation" is meant that the alginate changes from a low-viscosity form to a form of higher viscosity. The activation of the alginate by acid is of importance as it causes the fibres to have effect, e.g. an effect on regulation of satiety, by causing distension of the stomach. Furthermore, it is likely that the gel formed has an active function in detaining fats, thereby inhibiting their uptake in the stomach or bowels. By these means some food constituents, including fats, can pass undigested.

An alginate of any molecular weight may be used for the preparation of a liquid dietary product according to the invention. However, in order to obtain a sufficiently low viscosity of the dietary product the molecular weight of the alginate should not be above 150,000. Likewise, in order to provide a sufficient effect on satiety the molecular weight of the alginate should be at least 10,000.

In one embodiment the alginate has a ratio of mannuronic acid to guluronic acid (M/G) of less than 1, suitably as less than 0.8. Thus, it has been found that an alginate with a larger amount of guluronic acid compared to mannuronic acid has improved gelling properties upon lowering the pH. Preferably the amount of guluronic acid is above 60% and the amount of mannuronic acid is below 40%.

A suitable alginate is XPU - LVG500 506/08 obtainable from Cargill (Minneapolis, MN, USA). Also preferred is Protanal LFR 5/60 ob- tainable from FMC. Protanal LFR 5/60 has a content of guluronic acid of 65-75% and a content of mannuronic acid of 25-35%. A further suitable alginate product is Manugel LBA obtainable for FMC Biopolymer.

The dietary product prepared using the alginate may be described in terms of the viscosity of the dietary product. It is preferred that the dietary product has a low viscosity to provide user acceptance. For example, in one embodiment the alginate provides a viscosity in the dietary product of no more than 50 mPas. The viscosity of the dietary product may readily be measured using any conventional equipment, for example using a rheometer of the Bohlin product range of Malvern In- struments Ltd. (Malvern, Worcestershire, UK) such as a Bohlin CVOR rheometer.

When the alginate used in the present invention is exposed to a pH below 3, e.g. as found in gastric juice it forms a gel. The formation of the gel may be observed with a corresponding increase in viscosity. Thus, when exposed to acidic conditions at a pH below 3, the viscosity of a solution, i.e. a dietary product, with the alginate increases. In a certain embodiment of the invention the viscosity of the dietary product is increased 100 times or more when the pH is lowered to 3 or less. The gel formed upon lowering the pH will generally be of non-Newtonian rheol- ogy. For example, the gel may be characterised as being of pseudo- plastic rheology meaning that the observed viscosity of the gel is decreased when the gel is exposed to an increasing shear rate. The viscosity of the gel will typically be recorded at ambient temperature at shear rates between 0.1 s^"1 and 90 s^"1, e.g. the viscosity of the gel may be measured at 20 s^"1 and the recorded viscosity may be compared to the viscosity measured before formation of the gel.

The dietary product may also be described in terms of its water retention capacity upon formation of a gel. Formation of a gel will result in the binding of water molecules in the gel, and in one embodiment the dietary product upon formation of a gel has a water retention capacity (WRC) of at least 400 g of water per litre of dietary product. It is believed that this WRC may be indicative of the satiety inducing effect of the gel, i.e. of the dietary product. In particular, the higher the WRC for an alginate the better the effect of the dietary product. The WRC of a dietary product may be determined by the formation of a gel by lowering the pH and determining the mass of the gel and the mass of the free water, and from these parameters then be able to calculate how much water is retained in the gel. For example, the WRC may be measured by centrifugation of the gel and recording the weight of the gel and the weight of the supernatant; appropriate conditions may be centrifugation for 10 min at 3500 rpm (e.g. in a Rotina 48R centrifuge from Hettich Zentrifuge). In order to select an alginate for use in the preparation of a dietary product, the WRC may also be expressed specifically for the algi- nate as WRC per mass of alginate. This value may then be used to determine the necessary concentration of the alginate in the dietary product to obtain a WRC of 400 g/L.

The gel formation caused by the alginate in the dietary product may also be reversible. Thus, in one embodiment the formation of the gel by lowering the pH to 3 or less may be reversed by increasing the pH to above 3, suitably above pH 5. The present inventors believe that a reversible formation of a gel is advantageous for a dietary product which increases satiety. Upon oral intake the dietary product will be exposed to the low pH found in the stomach which will trigger the formation of a bulking gel, which subsequently will increase the feeling of satiety. However, when the gel leaves the stomach it will be exposed to increasing pH in the duodenum (pH 6-8) which will reverse the gel formation. Thus, the effect of the gel will be limited to the stomach and any adverse ef- fects such as constipation due to the bulking agent may not occur.

The dietary product of the present invention may contain further biopolymers. Examples of such biopolymers include pectin, cellulose, xanthan, curdlan, pullulan, hyaluronic acid, gelatin, chitin, inulin, carra- geenan, xanthan gym, dextran, etc. In a certain embodiment of the present invention the alginate is used in combination with pectin.

Pectins are a common type of carbohydrate gelling agent, generally obtained from dilute acid extracts of citrus or apple pulp. They are an important constituent of the cell walls and soft tissue of vegetables and fruits, where they contribute to the mechanical properties of the cell wall and influence cell adhesion. Pectins are for example found in root crops such as carrots and beetroot, as well as in tubers, such as potatoes and are commercially extracted from citrus peels, apple pomace and sugar beet pulp. Pectin is composed of long, regular sequences of 1, 4-linked-D-galacturonate residues which in nature may be partially me- thyl-esterified. A typical pectin molecule comprises 200 to 1000 galactu- ronic acid units connected in a linear chain having alternating rhamnose units inserted into the main uronide chain. The ester content varies with the source of the raw material and may also be varied during extraction. Pectins are divided into two main categories: high methoxylated pectins (hereafter referred to as HM pectin) , which are characterized by a degree of methoxylation above 50%, more particularly between 50% and 80%, and low methoxylated pectin (hereafter referred to as LM pectin) having a degree of methoxylation below 50%, more particularly between 30% and 50%. As used herein, "degree of methoxylation" is intended to mean the extent to which free carboxylic acid groups contained in the polygalacturonic acid chain are present as the methyl ester. Both HM and LM pectins form gels. However, these gels form via totally different mechanisms (Voragen et al, In Food polysaccharides and their applica- tions, pp 287-339. Marcel Dekker, Inc. New York, 1995). LM pectin forms a gel in the presence of calcium, thus, it is "calcium-reactive." The calcium-LM pectin gel network is built by formation of what is commonly referred to as an "egg-box" junction zone in which Ca²⁺ causes the cross-linking of two stretches of polygalacturonic acid chains. Calcium- LM pectin gel formation is influenced by several factors, including DM, ionic strength, pH, and molecular weight. Furthermore, the calcium-LM pectin gelation is more efficient at a neutral pH of about 7.0 than at an acidic pH of about 3.5. Lastly, the addition of monovalent counter ion (NaCI) enhances the gelation, i.e., less calcium is required for gel forma- tion. HM pectin forms a gel in the presence of high concentrations of co- solutes, such as sucrose, at low pH. HM pectins are generally not reactive with calcium ions and therefore cannot form a calcium gel. However, certain HM pectins have been reported to be calcium sensitive and capable of calcium gel formation. In addition, HM pectins can be made cal- cium-reactive by a block wise de-esterification process while still having a DM of >50%. See, Christensen et al. U.S. Pat. no. 6,083,540. Pectins are typically utilized in the food industry and classified by the FDA as "GRAS" (Generally Regarded As Safe). They have also long been used as colloidal and anti-diarrhea agents. Recently, pectins have been utilized in the areas of medical device and drug delivery (Thakur et al . , Critical Reviews in Food Science & Nutrition 37, 47-73, 1997). In the case of drug delivery, pectin has found its presence in many experimental formulations for oral drug delivery to the colon because pectin is readily degraded by bacteria present in this region of the intestines. In an aspect of the present invention, dietary product according to the present invention comprises 0.05-5.0 wt% HM pectins , which are preferably characterized by a degree of methoxylation of above 50%, preferably within the range of 50-90%, still more preferably within the range of 55-85% most preferably within the range of 60-80%.

According to WO 2008/022857 it was found that the molecular weight of the pectin does not affect the gel strength of the gel formed upon ingestion, but does affect the viscosity of the liquid composition itself. More in particular, it was found that low molecular weight HM pec- tins form similarly strong interactions with alginate as do high molecular weight HM pectins. Thus, the addition of low molecular weight HM pectin will reduce the viscosity of the product and improve the mouth feel thereof, without a concomitant decrease in strength of the gel particles formed in the stomach as compared with the use of high molecular weight HM pectins. Therefore, according to a preferred embodiment, dietary products are provided, wherein the average molecular weight of the HM pectin is within the range of 50-500 kDa, more preferably within the range of 75-250 kDa, still more preferably 90-200 kDa.

In the above aspect of the invention HM pectins are used in combination with alginates, since they are capable of forming a sufficiently rigid matrix at a pH found in the stomach of a normal human, typically a pH of below 3.5. The liquid dietary product of the invention typically contains 0.08 - 2.5 wt. %, preferably 0.1 - 1.0 wt. %, more preferably 0.2 - 0.8 wt . % of HM pectin based on the total weight of the composition.

The dietary product prepared by using an alginate may also comprise a calcium salt, such as an insoluble calcium salt providing Ca²⁺ ions at less than about 200 ppm when the pH is changed to below 3. However, it is preferred that the dietary product does not contain added calcium, e.g. in the form of insoluble calcium salts.

The dietary product prepared by using an alginate is not particularly limited to the concentration of the alginate, as long as the dietary product prepared is capable of forming a gel when exposed to a pH of 3 or less, and optionally fulfil the requirements of other embodiments as described above. However, in one embodiment the amount of alginate as an aqueous dissolved form ranges from 10 g/L to 50 g/L in the dietary product. Alternatively, the product may range from 20 g/L to 40 g/L. A preferred concentration of alginate is about 30 g/L.

The liquid dietary product of the invention may also be formulated as a meal replacement further comprising protein, fat, digestible carbohydrates and/or other nutrients, such as vitamins and the like. However, it is preferred that the dietary product does not contain substantial amounts of a protein source. In other embodiments the liquid diet product does not contain substantial amounts of a source of fat and/or a source of digestible carbohydrate fibres.

In a certain aspect of the invention the dietary product of the invention is formulated as a dry powder for mixing with an aqueous liquid, such as water, prior to administering the dose. The dry powder con- taining the alginate may be added to the aqueous liquid during mixing to obtain a dietary product. Typically, a single dosage of the present dietary product may be prepared by mixing the blend of aqueous liquid and dry powder containing alginate using a blender, such as a hand blender. Generally, a mixing time of less than 30 seconds is sufficient for obtain- ing a product in which the particles of the dry powder will not sediment during the subsequent ingestion of the dietary product.

Although fibres from administration of alginate supplement are found to have an effect on the stomach the fibres per se in the dietary product is believed to have limited effect with respect to loss of weight. Instead the effect is believed to arise from an increased feeling of satiety (reduced appetite) in the subject to whom the dietary product is administered, so that the subject after having been administered the dietary product will tend to ingest less food (e.g. reduce the spontaneous energy intake). Hence, the alginate, when used for the preparation of a dietary product according to the invention, is suited as a diet supplement which can reduce the amount of intake during ingestion of a meal. Thus, in order for the dietary product to have the desired effect a preferred administration is prior to taking in a meal, e.g. as a "preload". In one embodiment, the dietary product is administered no more than 2 hours prior to a subject's intake of a meal. The administration of the dietary product may also occur sooner than 2 hours prior to a meal intake, such as not more than 1 hour prior to a subject's intake of a meal, e.g. not more than 30 minutes prior to a subject's intake of a meal. Administration of the dietary product may be relevant before any meal of the day for the subject, although it may be advantageous to administer the dietary product prior to the meal of the day when the subject typically has the largest energy intake during the day. Ideally the dietary product should be taken before any major meal intake, i.e. ideally three times per day before the three major meals (breakfast, lunch and dinner). However, the effect of the dietary product on satiety may also prevent the subject in consuming food or snacks between meals, which is considered advantageous for a weight loss plan for a subject.

The dietary product may be administered daily for a period with a duration of several days or weeks, for example as a course of a diet. For example, according to one embodiment the dietary product is administered one or more times per day, the interval between administrations being at least 2 hours. Multiple administrations during a day may be especially advantageous in order for a subject to obtain a weight loss. In a preferred embodiment, the dietary product is administered prior to all meals ingested by a subject during a day. In other embodiments, the dietary product is administered before two meals, such as the two meals normally containing the highest energy intake for the subject during a day. A single dosage of the dietary product may be consumed in 30 minutes or less, such as within 15 minutes or less, preferably within 5 minutes or less.

In general, all parameters described above for the different embodiments are relevant to both the aspect relating to the use of an alginate for the preparation of a liquid dietary product as well as to the as- pect relating to the liquid dietary product of the invention. However, it is preferred that the liquid dietary product of the invention is in the form of a ready-to-drink product although other forms are also contemplated. It is also preferred that the liquid diet product is in unit dosage form.

In yet another aspect the invention relates to a kit for the preparation of a liquid dietary product for the treament and/or prevention of obesity. Typically, the kit comprises a unit dosage of alginate of at least 4 g and instructions for use of the kit, e.g. comprising details as outlined above. The alginate may be in a dried form for dissolving in an appropriate volume, i.e. at least 350 ml_, or the unit dosage may contain the alginate in a concentrated stock solution for dilution into the appropriate volume.

In yet another aspect the invention relates to a method for regulating, e.g. decreasing, appetite in a subject. This method may e.g. be used in a diet with the intention to cause a weight loss to the subject; for example a subject may desire to loose weight for cosmetic reasons or alternatively the subject may be pathologically obese and be in need of weight loss for medical reasons. A diet dosage regimen will typically have a duration of several days or weeks depending on the aim of the subject undergoing the diet. For example, the subject may intend to loose a certain amount of body mass. The method for regulating appetite may thus comprise the daily intake, such as one to four times a day, preferably prior to a meal, of the diet product of the invention in order to help the subject to followe the diet. The daily intake may be continued for the duration of the diet.

Brief description of the figures

Figure 1 shows the subjective feeling of appetite after intake of a sodium alginate supplement or a placebo based on the results of a Visual Analogue Scale (VAS) questionnaire.

Figure 2 shows the results presented in Figure 1 as incremental Area Under Curve (iAUC). Figure 3 shows the results of the VAS questionnaire summed into an appetite score.

Figure 4 shows the energy uptake during an ad libitum meal fol- lowing intake of low and high dosages of alginate supplement and corresponding placebo supplements, respectively.

Figure 5 shows self-reported estimates of well-being during a study of alginate test supplements or placebo.

Figure 6 shows changes in systolic blood pressure during treatment with low dosage of alginate or placebo. Figure 7 shows changes in diastolic blood pressure during treatment with high dosage of alginate or placebo.

Figure 8 shows the concentration of paracetamol in the blood after treatment with alginate supplement or placebo in low dosage.

Figure 9 shows the concentration of paracetamol in the blood after treatment with alginate supplement or placebo in high dosage.

Detailed description of the invention The present inventors have found that when an alginate is used in the preparation of a liquid dietary product the volume of the dietary product significantly influences the effect of the dietary product; the invention thus relates to the use of an alginate for the preparation of a liquid dietary product and a liquid dietary product comprising an alginate. The invention will now be described in more detail referring to specific embodiments. In order to more fully explain the invention, definitions of the terms employed in this document are given below.

By conducting studies the present inventors have provided evidence that ingestion of an alginate, e.g. in the form of a sodium algi- nate, in the prescribed volume of at least 400 mL volume, results in an increased feeling of satiety beyond the reduction of appetite which would be expected as a consequence of ingesting the alginate in a smaller volume. For example, the studies conducted by the present inventors did not show a significant effect on the appetite in a subject when administered with a preload of 10 g of alginate in 330 mL volume. Furthermore, it has been found that the volume of the dietary product required to cause an effect on satiety does not correlate with the body weight of an adult subject. It is believed by the present inventors that a volume of at least 350 mL containing an alginate capable of forming a gel upon exposure to the acidic conditions in the stomach provides distention of the stomach upon ingestion thereby inducing release of hormones such as cholecystokinin and a concomitant feeling of satiety. Thus, in specific embodiments the volume of the diet product is about 400 mL, 450 mL, 500 mL, 550 mL, or 600 mL. In a preferred embodiment the volume of the dietary product is about 500 mL. Likewise, it has been found that the amount alginate in the dietary product required to cause an effect on satiety does not correlate with the body weight of the subject, but that it is important that the alginate causes formation of a gel upon exposure to the acidic conditions in the stomach.

The term "subject" as referred to in connection with the present invention refers to any human or mammal. Preferably, the subject is in need of loss of weight, e.g. for cosmetic reasons or due to pathological obesity. The dietary product can be meant for cosmetic use, in which it is used in relation to a desire of loss of weight in order to improve appearance. The dietary product can also be used on pathologically obese individuals at risk of increased morbidity and mortality. Typically, a subject having a body mass index (BMI) of less than 30 kg/m², such as be- tween 25 and 30 kg/m², may desire to loose weight for cosmetic reasons whereas a su bject with a BMI a bove 30 kg/m² may be considered pathologically obese. However, these ranges are not to be considered too rigid. For example, a physically active subject may have a high BMI, e.g. above 30, without being considered pathologically overweight or even obese.

Alginates commonly originate from seaweeds or bacteria and are polyuronides made up of a sequence of two hexuronic acids: β-D- mannuronic acid and a-L-guluronic acid. Usually, the two sugars are not distributed at random along the chain, but sometimes form blocks of up to twenty units. The proportion of these blocks depends on the source of the alginate, e.g. the originating species of seaweed, and the method of production. Less important factors are the degree of maturity, age and where the material was harvested. The ratio of mannuronic to guluronic acid (M/G) in an alginate can vary from 0.4 to 1.6. However, the present invention is, not particular dependent on the M/G ratio since the gelling of the alginate in the absence of calcium may be caused by hydration of the polymer. In the absence of substantial amounts of calcium it is preferred that the M/G-ratio is less than 1. For example, the M/G-ratio may be less than 0.9; less than 0.8; less than 0.7; less than 0.6 or less than 0.5.

Any alginate may be used in the present invention. However, alginate is, according to the invention, primarily used as a salt of an alkaline or alkaline earth metal, eg. sodium, lithium, potassium, calcium etc. Sodium alginate is commonly preferred due to ease of solubility and inclusion hereof on the list of additives approved by the European Union (e.g. alginate is E401). Hence, sodium alginate is approved as an additive to foods. It is widely used in foods when a thickening of the food in question is desired. Usually, in contrast to this invention, this involves an activated sodium alginate, i.e. a dissolved, but inactivated, sodium alginate is used, which reacts upon a lowering of the pH value as happens in the stomach. Sodium alginate can be obtained in pharmaceutical and food approved varieties. Sodium alginate originates in seaweed, especially brown seaweed from the Norwegian Sea or the Atlantic Ocean.

Alginates are available commercially, and appropriate alginates are currently marketed by companies such as FMC BioPolymer (Philadelphia, PA, USA), e.g. under the trademark Protanal; Cargill (Minneapolis, MN, USA), e.g. under the trademarks Satialgine, Algogel, Cecalgum; and CP Kelco ApS (Lille Skensved, Denmark).

In the context of the present invention, the term "to form a gel" refers to the change in viscosity of an alginate solution when exposed to acidic conditions, e.g. when in contact with gastric juice of about pH 2. The formation of a gel may also be referred to as "activation" of the alginate. In a preferred embodiment of the present invention the viscos- ity of the dietary product containing the alginate in a dissolved form is increased 100 times or more upon formation of the gel. In other embodiments, the increase may be at least 150 times, at least 200 times, at least 250 times or at least 300 times. The viscosity of the gel may appropriately be recorded at a shear rate of 20 s^"1 for comparing to the viscosity of the alginate in solution, i.e. the dietary product. The methods for determining viscosities of the alginate solution and the formed gel are described in detail in Example 1 below.

Correspondingly, it is also believed that the viscosity of the formed gel should be at least 5 Pas when the viscosity is measured at a shear rate of 20 s^"1 (see Example 1 for a description of appropriate methods of analysis) for the diet product to have a desired effect on the feeling of satiety. Other appropriate minimum viscosities for the gel are 8, 9, 10, 11, 12, 13, 14, 15 Pas etc., likewise recorded at a shear rate of 20 s^"1.

The water retention capacity (WRC) of the dietary product, as defined above, should be at least 400 g of water per liter of dietary product, although in specific embodiments the WRC is at least 450 g/L, at least 500 g/L, at least 550 g/L, at least 600 g/L, at least 650 g/L or at least 700 g/L. The WRC provides an indication of the amount of gel formed in the stomach upon ingestion, and this value may be seen in relation to the volume of dietary product ingested. Thus, it is believed that ingestion of at least 400 mL of a dietary product with a WRC of at least 400 g/L, e.g. at least 650 g/L, will cause distension of the stomach and subsequently inducing satiety in the subject ingesting the dietary product. Distention of the stomach caused by ingestion of the dietary product is in turn believed to cause release of amongst other mediators, chole- cystokinin, thus mediating a feeling of satiety in the subject.

In case the alginate is selected from its specific WRC, i.e. the WRC per mass of alginate, the alginate would typically have a specific WRC of at least 15 g water per g dry weight of alginate, such as at least 20 g/g or at least 25 g/g. The specific WRC for the alginate may then be used to calculate the necessary concentration of alginate in the diet product in order to obtain the necessary WRC for the diet product. For example, an alginate with a specific W C of 20 g/g at a concentration of 30 g/L will provide a WRC of 600 g/L.

The acid induced gel formation of alginate is preferably reversible by exposing the gel to a pH of above 3, such as a pH above 5. The reversibility may be examined by first causing formation of a gel by adding acid and afterwards by addition of alkaline, such as NaOH, e.g. in 1 M concentration. When addition of alkaline is initiated the viscosity of the sample is monitored, and the pH may also be monitored. The reversibility may be expressed in terms of amount of alkaline required to reverse the gel, and the time required to reversal may likewise be monitored. The time required for reversal of the gel will typically be dependent on the concentration of the alginate in the dietary product. It is preferred that the gel formation may be reversed in less than 15 minutes, for example less than 10 minutes or less than 5 minutes.

The viscosity of a solution of alginate may depend on inter alia the size of the alginate molecules as expressed by the molecular weight. For example, very large molecules may provide a high viscosity in an aqueous solution. The alginate used in the present invention is preferably of a molecular weight of 150,000 or less, or more preferred 120,000 or less. However, to obtain a gel of sufficient resilience when exposed to the gastric juice i.e. gastric acid the molecular weight of the alginate should be at least 10,000, such as above 30,000, more preferably it is at least 60,000. Appropriate viscosity measurements are outlined in Example 1 below; this example also demonstrates how the resilience of the gel may be characterised.

Some alginates require calcium to form a gel, and the dietary product of the invention may contain a minor amount of an insoluble calcium salt to support the gelation when exposed to the gastric juice. Useful insoluble calcium salt are calcium salts which are insoluble at the pH of the dietary product but which become soluble at a more acidic pH, such as that of gastric juice, resulting in a release of the calcium. Examples of useful insoluble calcium salts are those formed by the combination of the calcium cation with the carbonate anion or the phosphate anion. Specific examples of insoluble calcium salts include CaHP0₄ and CaC0₃.

In the embodiment comprising an insoluble calcium salt, the amount of insoluble calcium salt in the dietary product usually provides less than 200 ppm calcium ions when the pH is changed to less than 3, such as around pH of 2. In a preferred embodiment the amount of insoluble calcium salt in the dietary product provides less than 50 ppm dissolved calcium ions when the pH is changed to less than 3, such as around pH 2. In a preferred embodiment, however, the dietary product of the invention does not contain added calcium, such as an added in- soluble calcium salt. Insignificant amounts of calcium salts may be present in the tap water used for preparation of the diet product.

However, preferably insoluble calcium salts should not be present in the dietary product in substantial amounts. In embodiments of the invention in which insoluble calcium salts are present, though, the amount thereof is suitably less than 1% by weight based on the weight of the alginate. Preferably the amount of calcium salts is less than 0.1% by weight based on the weight of the alginate. It can be speculated that the presence of calcium ions, especially above 200 ppm, during gelation may provide an excessive gel formation leading to a too high viscosity in the stomach of the subject and furthermore may prevent reversible gel formation.

Sodium alginate can be formulated in any aqueous solution, including pure water, almost without any addition to its own taste. In liquids such as soft drinks, squash or juice the taste of sodium alginate per se can be masked to an extent where it essentially cannot be tasted or felt.

The dietary product according to this invention can have any pH value not causing activation of the sodium alginate. The pH value, at which sodium alginate gels, is dependent upon origin and pre-treatment. The pH value is, in an aspect of the related invention, above 4, suitably 5 or above.

Besides alginate, the dietary product of the present invention furthermore, can contain a mono- or disaccharide, e.g. saccharose, glucose or invert sugar, as a mono- or disaccharide which improves the solubility of alginate. The concentration of mono- or disaccharide is usually chosen depending on the concentration of alginate. According to an aspect of the invention the concentration of mono- or disaccharide is in the range of 0.1 to 60 g per kg of diet product, suitably 10 to 40 g per kg.

The dietary product may also comprise other components and as such constitute a meal replacement. In the context of the present invention a "meal replacement" is a dietary product intended to replace a normal meal. Thus, a meal replacement will comprise nutrients in addi- tion to the alginate. For example, a meal replacement product may contain protein, fat, digestible carbohydrate fibres and/or other nutrients, such as vitamins and the like in order to ensure that the diet of the subject contains a balanced composition of energy. However, in a certain embodiment of the invention the dietary product does not contain added protein, and in yet other embodiments the dietary product does not contain a source of fat and/or a source of digestible carbohydrate fibres. In these embodiments the dietary product may be referred to as a "supplement" meaning that the dietary product is to be ingested in addition to normal meals, and that the dietary product is not intended to replace a meal.

When used as a supplement, the dietary product may reduce the spontaneous energy intake of the subject in a subsequently ingested meal. In this context, the term "spontanous energy intake" refers to the amount of energy ingested by the subject when the subject is only re- stricted by its appetite. Thus, when the dietary product is administered prior to a meal of a subject the appetite of the subject may be reduced and the subject will eat less. According to the invention it is preferred that the dietary product is administered no more than 2 hours prior to a subject^' s meal intake. However, in order to regulate the appetite, e.g. decrease the appetite, the dietary product may be ingested at least 10 minutes prior to a meal intake. Typically, ingestion will take place 10 to 30 minutes prior to a meal intake in order to obtain a sufficient gelfor- mation in the stomach. It is well known that individuals often ingest meals too fast as the brain takes approximately 10 to 30 minutes to reg- ister the filling of the stomach. By the stepwise filling of the stomach (dietary product followed by a meal) it can be speculated that the brain will register the fullness of the stomach and thereby the subject will intake less food and probably fewer calories.

The liquid dietary product of the present invention can be produced in various forms, e.g. as a liquid pharmaceutical formulation, or as a beverage, such as a soft drink or a soup. In either case the dietary product may be formulated as a meal replacement product or as a dietary supplement. The dietary product can also be incorporated into products which are on the market already. This enables the opportunity of exploiting the distribution system which is already in place i.e. producers of soft drinks, who have equipment for production and distribution all over or in parts of the world with the only change to add alginate to the product. By this means, a soft drink with a slimming effect is achieved because the intake of soluble fibres in combination with the acid content of the stomach produces a gel.

In another aspect, the invention relates to a kit for the preparation of a liquid dietary product for the treatment and/or prevention of overweight and/or obesity. The kit will preferably contain a unit dosage of alginate, such as in a capsule, a vial, a plastic bag a sachet etc., of e.g. at least 4 g and instructions for use of the kit. The kit may also contain several unit dosages, for example one or more unit dosages of alginate for each day of a planned diet. The unit dosages may also contain more than 4 g of alginate, such as for example 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45 or 50 g of alginate. Each unit dosage may also comprise other components, such as an insoluble calcium salt and/or a mono- or disaccharide as outlined above, sweetening agents, flavour components, colouring agents, etc. The kit may also contain one or more unit dosages comprising in addition to the alginate components to constitute a meal replacement. It is not of fundamental importance how the alginate in the unit dosage is formulated and distributed, and the alginate may be in a dry form, e.g. as a powder or granulate, or the alginate may be in a concentrated solution for mixing with an appropriate volume of liquid to form the liquid dietary prod- uct.

The instructions contained in the kit will explain to the user, e.g. the subject, how to mix and dissolve the alginate in an appropriate volume, e.g. at least 350 mL, preferably about 400 mL or about 500 mL. Preferably, the liquid is water, although the user may also be instructed how to select an aqueous liquid of appropriate acidity for dissolving the alginate. The instructions may also contain information to the user on the optimal time for administration of the product relative to the time of a meal intake, and the instructions may inform the user on an appropri- ate dosage regimen in terms of an optimal number of dosages to ingest during a day.

Especially diabetics may experience a significant improvement in the regulation of the blood sugar level with the use of liquid dietary product of the invention and at the same time a loss of weight will en- hance an improvement of health in the long term. Thus, the present invention also relates to a method for regulating the blood sugar and/or insulin in a patient in need thereof, said method comprising the step of administering in an amount of 350 mL or above a composition containing alginate in a dissolved form at a pH value not causing the alginate to gel.

Examples

The purpose of the below-mentioned experiments was to select an appropriate alginate for use in the preparation of a dietary product and investigate the effect of a drinkable supplement based on sodium alginate fibres. Characterisation of alginates is thus described in Example 1 and in Example 2 a series of test meals was designed to measure the effect of the liquid diet product of the invention, and the effect of a an alginate solution in 500 mL volume was compared to an alginate solution in 330 mL volume. Example 3 shows compositions of exemplary liquid diet products according to the invention. Example 1

Selection of an alginate

Methods

Three different alginates were provided by Cargill, Inc. (Minneapolis, MN, USA) and characterised for use in a diet product. The alginates are referred to as Satialgine S20, XPU-LVE500 and XPU-LVG500.

Solutions of the alginates of concentrations of 5, 7.5, 10, 12, 15, 20, 25, 30 and 35 g/L were prepared by initially weighing alginate powders on an analytical balance (Sartorius Analytic A2005, Sartorius, Ger- many) and then dissolving the alginates in 100 mL aliquots of water (milli-Q water) in glass beakers using magnetic stirring at 500 rpm. After 5 min the beakers were transferred to a waterbath at 39°C and the fibres allowed to dissolve for a further 90 to 120 min.

Aliquots of 50 mL volume were withdrawn from each solution and transferred to plastic beakers where 2 mL aliquots of 500 mM HCI were added at 10 s intervals under magnetic stirring (600 to 800 rpm) until a pH of 1.20 was reached. The pH was monitored using a Metrohm Swiss model 691 pH-meter.

Viscosity was measured using a Bohlin C-Vor rheometer (Mal- vern Instruments Ltd. ). The fibre solution (at pH 5.50 to 6.00) or the gel mass (pH 1.20) was carefully transferred to a steel cup (DG 47/27 double gap, 10 mL or v25, 10 mL, respectively) and left standing for 5 min to equilibrate the sample before recording the viscosity at a constant temperature of 20°C. The measurements were conducted at different shear rates between 0.1 and 90 s^"1 with 15 registrations over a time span of 5 min.

Analysis of oscillatory shear rheology was performed to describe the ability of the viscous gels to resist mechanical stress and thereby characterise the fragility of the network of the gel mass. Oscillatory shear rheology was analysed on the rheometer at a constant shear frequency of 1 Hz; the stress amplitude was varied over 25 steps where the mechanical stress was controlled and gradually increased from 1 to 500 Pa. Stress was applied for 12 s at a time for each step and the am- plitude was registered, and the elastic modulus (G') and the viscous modulus (G") were calculated.

The water retention capacities (WRC) of the gelled alginate samples were analysed by centrifuging at 3500 rpm for 10 min in a Rot- ina 48R centrifuge from Hettich Zentrifuge, Germany and subsequently measuring the weight of the supernatant and the gel. The WRC was expressed in mass of water retained per liter of alginate solution prior to gelation and also in specific values per dry mass of alginate.

Reversibility of the gel formation was examined by transferring the gelled samples to 100 mL disposable plastic beakers with magnetic stirring at 600 to 800 rpm and adding 500 p L aliquots of 1 M NaOH every 30 s. The pH was monitored using the Metrohm Swiss model 691 pH-meter. Addition of NaOH was continued until the sample became liquid again. The amount of NaOH added was noted as well as the time for reversion as recorded using a stop watch.

Analysis of gel weight, WRC and reversibility was repeated three times and viscosity measurements twice.

Results

It was found that the alginates XPU-LVE500 and XPU-LVG500 provided viscosities below 50 mPas at all concentrations up to 30 g/L; at 35 g/L the viscosity of XPU-LVG500 was recorded as 75 mPas. In contrast, the viscosity of the Satialgine S20 solutions increased above 50 mPas already at 15 g/L.

Gel viscosities increased with increasing alginate concentration for all three alginate types. The XPU-LVG500 alginate provided a viscosity at a shear rate of 20 s^"1 of about 5 Pas at a concentration of 15 g/L, and at 25 g/L and above the viscosity was above 10 Pas. In contrast, the XPU-LVE500 alginate did not provide a gel with a viscosity above 5 Pas at any tested concentration, whereas the Satialgine S20 did not provide a gel viscosity above 10 Pas at the tested concentrations.

Table 1 shows the transition points where the viscous modulus (G") for each of the three alginates surpassed the respective elastic modulus (G'), i.e. where G'=G". This point illustrates the value of shear stress where the gel changes from an elastic gel to a gel of a more liquid character. A low value indicates a fragile gel whereas a higher value generally indicates a more resilient gel. Table 1 Transition points (G'=G") recorded in oscillatory shear rheology

Concentration Satialgine S20 XPU-LVE500 XPU-LVG500

(g/L) (Pa) (Pa) (Pa)

25 281 57.4 204

30 204 108 530

35 149 78.8 386

At lower concentrations the Satialgine S20 alginate generally had higher values for the transition points than the other alginates. However, at higher concentrations, e.g. at 30 g/L and above the XPU-LVG500 alginate provided a more resilient gel. Provision of a resilient gel upon acidification is seen as advantageous for a diet product.

The XPU-LVG500 alginate was found to provide a higher WRC than the other alginates at all concentrations analysed. However, it was found that the specific WRC values varied with the concentration of algi- nate in the solution for all three alginates. Solutions of XPU-LVG500 consistently provided a WRC upon gel formation above 20 g/g at all concentrations, and a concentration of only 10 g/L of XPU-LVG500 was required to provide a WRC above 400 g per L alginate solution.

Gel formation for all three alginates was found to be reversible by addition of sodium hydroxide. The amount of sodium hydroxide required for reversal for the alginates XPU-LVG500 and Satialgine S20 did not differ significantly, whereas XPU-LVE500 required less sodium hydroxide. Following reversal of gel formation a higher final pH was recorded for Satialgine S20 than the other two. Gel reversal for XPU-LVE500 generally occurred faster than for XPU-LVG500 and Satialgine S20, but at concentrations above 25 g/L the reversal for XPU-LVG500 was significantly faster than for Satialgine S20; at concentrations above 20 g/L gel formation for XPU-LVG500 was reversed in about 10 min for all concentrations.

On this basis it was estimated that the alginate XPU-LVG500 at a concentration of 30 g/L provided an optimal balance of viscosity before and after gel formation, resilience of the gel, water retention capacity and reversal time for gel formation. It was therefore decided to conduct experiments with XPU-LVG500 at 30 g/L as a diet product as described in Example 2. However, this selection should not be regarded as limiting for the invention, and it is contemplated that other alginates may also be used within the scope of the invention or that combinations of different alginates may likewise be employed.

Example 2

A. Experimental design

A study with 19 healthy males and females in the age of 20 to 45 years was conducted. The subjects were normal to moderately obese (BMI 21-28 kg/m²).

The experiment was based on a total of four meal experiments. A meal experiment consisted of a standard breakfast meal of 2 MJ and an ad libitum lunch meal. Before each meal a test supplement was ad- ministered to the subjects with a pre-load time of half an hour.

The test subjects were randomised into four different treatments by randomised block design. Each treatment being either a specific dosage of alginate or a placebo. Table 2 presents the type, concentration and dosage of the respective fibre under examination. The so- dium alginate treatment was tested in a low dosage of 330 ml_ and a high dosage of 500 ml_ together with corresponding placebo test supplements.

The test subjects only performed limited physical activity which was reproduced with each experiment. In addition, the test subjects were restricted from hard exercise within 24 hours prior to each meal experiment. On the evening of the day prior to a meal experiment a standardised evening meal of 4 MJ from Department of Human Nutrition, University of Copenhagen was given. Intake of water, lavatory visits and other activity was noted on the first meal experiment and reproduced on later experiments.

Table 2

Test supplement Dose Total amount of alginate (g)

Placebo 330 ml_ 0

+ 3% alginate XPU-LVG500 330 mL 9.9

+ 3% alginate XPU-LVG500 500 mL 15

Placebo 500 mL 0

In the beginning of each meal experiment the blood pressure of each test subject was measured. A Venflon catheter was put in place to take blood samples during the meal experiment. The subjective feeling of hunger for each test subject was registered on a Visual Analogue Scale (VAS) every half an hour. The VAS test contained four parameters in order to determine an appetite score defined as:

Appetite score = (Satiety + stuffedness + ( 100 - prospective intake) + (100 - hunger))/4

Thus, each test subject reported their subjective feelings for each parameter to calculate the score; the score was expressed in the unit millimeters.

The test supplement was based on sodium alginate fibres (XPU- LVG500) extracted from brown seaweed in a concentration of 3% (equivalent to 15 g of fibre per Vz L of test supplement). Characterisation of the alginate is described above in Example 1.

B. Effect of alginate supplement on appetite

In the experiment the subjective feeling of appetite was measured using a VAS questionnaire as explained above, and the results of the VAS questionnaire are presented in Figure 1 as a function of time (in min). The questions regarded hunger, satiety, stuffedness and prospective intake, and Figure la-d show the values obtained for a unit dosage of 330 mL, respectively, and correspondingly Figure le-h show the respective values for a unit dosage of 500 mL.

From the results it is apparent that test subjects experienced a significant increase in satiety and reduced prospective intake when treated with a high dosage of sodium alginate compared with placebo treatment. The corresponding treatment with low dosage of sodium alginate did not show a significant difference in appetite between alginate based supplement and the placebo treatment.

Figure 2 plots the results of Figure 1 as incremental Area under Curve (iAUC); the iAUC is calculated as the area under the curve from 0 min to 270 min for each test supplement, i.e. placebo of 330 and 500 mL and alginate of 330 and 500 mL, respectively. Figure 2a shows the iAUC for the 330 mL unit dosages, and Figure 2b shows the iAUC for 500 mL unit dosages. Comparing the rating of appetite as iAUC it is also shown that treatment with high dosage of alginate-based supplement increases the feeling of satiety with approximately 40% (P<0.01) and reduces prospective intake with approximately 50% (P<0.01). Further- more, a tendency to decreased hu nger with approxi mately 30% (P=0.07) was found. Treatment with low dosage of alginate-based supplement did not show significant difference from the placebo based treatment, however, a non statistical trend in favour of alginate supplement was observed (P>0.1).

The results of the VAS questionnaire is summed into an appetite score calculated as described above for each of the four test supplements. The appetite scores are presented in Figure 3 as a function of time from 0 to 270 min; Figure 3a shows the appetite scores for the 330 mL unit dosages, and Figure 3b shows the score for 500 mL unit dosages. The experiments showed an increased appetite score of approximately 20% and 60% for low and high alginate-based supplement treatment, respectively, compared with the corresponding placebo treatments. An increased appetite score indicates increased satiety and feeling of fullness together with reduced hunger at prospective intake. C. Ad libitum energy intake

In the experiment outlined above under A. Experimental design, the spontaneous energy intake during the ad libitum lunch meals was found to be significantly lower with alginate-based treatment at low dosage compared with placebo treatment. Table 3 and Figure 4 present the results of the measurements with Figure 4a showing results for unit dosages of 330 mL and Figure 4b showing results for unit dosages of 500 mL. The difference was analysed using variance analysis (AIMOVA) in a mixed linear model adjusted for significant effect of covariates. The energy uptake was found to be nearly 10% lower when treated with a low dosage of test supplement compared to placebo treatment. A lower spontaneous energy intake of 5% was also observed for the high dosage of alginate-based supplement. From the results it is also found that the high dosage of alginate reduces the energy uptake the most in absolute figures.

Table 3

Alginate Placebo P-value

Energy intake (kJ) at low 3237 ± 184 3513 ± 183 ^*P<0.05 dosage (330 mL)

Energy intake (kJ) at high 3121 ± 200 3280 ± 197 P>0.05 dosage (500 mL)

^{^}ANOVA: effect of treatment (p<0.05)

D. Side-effects from intake of test supplement

Side-effects were registered during the experiment outlined above under A. Experimental design. Table 4 presents the number of single accounts of self-reported side-effects during intake of alginate-based supplement and placebo supplement. The reported number of side-effects did not differ significantly between alginate containing test supplement and placebo (P>0.1). Table 4

Side-effect Alginate Placebo Alginate Placebo

(330 mL) (300 mL) (500 mL) (500 mL)

Heatburn 1 1 3 2 uctus 2 3 4 2

Distended 5 3 8 7

Nausea 8 3 8 7

Stomach 0 1 1 0 ache

Rumbling in 7 9 11 10 the stomach

Wind 8 8 8 8

Diarrhea 0 1 0 2

Constipation 0 0 0 0

Total 31 29 41 36

Figure 5 presents the test subjects' self-reported estimates of well-being with Figure 5a showing the results for unit dosages of 330 mL and Figure 5b showing results for unit dosages of 500 mL. Neither side- effects nor measure of well-being indicate any significant difference between treatment with sodium alginate supplement or placebo supplement (P>0.1). E. Hemodynamic measurements

The systolic and diastolic blood pressure of the subjects of the experiment outlined above under A. Experimental design were measured regularly throughout the experiment. Figure 6 and 7 present the results of the measurements for systolic and diastolic blood pressure, respectively, expressed as changes in baseline corrected blood pressure compared to the value at t=0. The a-panels show the values for the 330 mL-unit dosages and the b-panels for the 500 mL-unit dosages. No apparent differences were seen with respect to the systolic blood pressure when comparing the treatments of alginate supplement of high and low dosage with the corresponding placebo supplemental drinks.

The diastolic blood pressure was significantly lowered during the course of the meal experiment when treating with a high dosage of alginate supplement. The low dosage did not show the same tendency. Treatment with high dosage of alginate supplement resulted in a significant reduction of the diastolic blood pressure of -2% compared with placebo results.

F. Stomach clearance rate

Paracetamol was used as marker for the rate of emptying the stomach. Since paracetamol is not absorbed from the stomach but will only reach the blood stream after being absorbed from the duodenum the level of paracetamol in the blood provides an indication of the clearance rate of the stomach. Paracetamol was administered together with the breakfast meal in a total dosage of 1500 mg in 3 tablets of 500 mg each. The concentration of paracetamol in the blood was used as a measure for the rate of emptying the stomach.

Figure 8 and 9 present the levels of paracetamol in the blood of the subjects for the 330 mL-unit dosages and the 500 mL-unit dosages, respectively. The values are displayed as a function of time from 0 to 270 min in the a-panels, and in the b-panels the integrated results of the a-panels are shown as iAUC-plots. The blood levels of paracetamol after administration of alginate supplement or placebo in 330 mL dosages did not differ significantly, and thus no effect was found on the rate of emptying the stomach. However, after administration of the alginate supplement in the 500 mL dosage the blood level of paracetamol was significantly lower than for the administration of placebo, and a reduced rate of emptying the stomach was thus observed when treating with a high dosage of alginate compared to the corresponding placebo treat- ment.

Example 3

Exemplary dietary products A stock solution was prepared by dissolving 30 g XPU-LVG500 per 1 L of water. While stirring the stock solution the components indicated below for each drink were added.

Orange drink:

Stock solution

Aspartam, 1% aq.

Orange flavour¹

Beta-caroten, 0.1% in plant

Carmin colour, 8.2% aq.

Lemon drink

Stock solution 500 mL

Aspartam, 1% aq. 30 g

Lemon emulsion 0.8 g

Green colour² 0.08 g

Passion fruit drink

Stock solution

Aspartam, 1% aq.

Passion fruit flavour³

Beta-caroten, 0, 1% in plant

Carmin colour, 8.2% aq.

Cola drink

Stock solution

Aspartam, 1% aq.

Cola flavour⁴

Brown colour⁵

Natural flavour preparation in ethanol.

2Quinolin yellow (E104) 2.0% and Green S (E 142) 0.17%.

3Natural passion fruit flavours in propylene glycol (E 1520) and triacetin (E 422). Natural cola flavours in propylene glycol (E 1520)Ammoniated caramel (E 150d), 80% aq.

Claims

35 P A T E N T C L A I M S

1. Use of an alginate for the preparation of an aqueous dietary product for treatment or prevention of overweight and obesity, wherein the dietary product has a pH value not causing the alginate to form a gel and the dietary product is administered at a unit volume dosage of at least 350 ml_.

2. A aqueous dietary product for treatment or prevention of overweight and obesity comprising an alginate in an aqueous dissolved form at a pH value not causing the alginate to form a gel, wherein a sub- ject suffering from or at risk of suffering from obesity or overweight is administered a unit dosage of the dietary product of at least 350 ml_.

3. The use according to claim 1 or the aqueous dietary product according to claim 2, wherein the alginate has a ratio of mannuronic acid to guluronic acid (M/G) of less than 1.

4. The use according to claim 1 or 2 or the aqueous dietary product according to claim 2 or 3, wherein the alginate provides a viscosity to the dietary product of no more than 50 mPas.

5. The use according to any one of claims 1 or 3 to 4 or the aqueous dietary product according to any one of claims 2 to 4, wherein the dietary product upon formation of the gel has a water retention capacity (WRC) of at least 400 g of water per litre of dietary product.

6. The use according to any one of claims 1 or 3 to 5 or the aqueous dietary product according to any one of claims 2 to 5, wherein the formation of the gel by lowering the pH to 3 or less may be reversed by increasing the pH to above 3.

7. The use according to any of claims 1 or 3 to 6 or the aqueous dietary product according to any of claims 2 to 6, wherein the viscosity of the dietary product is increased 100 times or more when the pH is reduced to 3 or less.

8. The use according to any of claims 1 or 3 to 7 or the aqueous dietary product according to any of claims 2 to 7, wherein the dietary product does not contain added calcium.

9. The use according to any of claims 1 or 3 to 8 or the aqueous dietary product according to any of claims 2 to 8, wherein the amount of 36

alginate in aqueous dissolved form ranges from 10 g/L to 50 g/L, preferably 20 g/L to 40 g/L.

10. The use according to any of claims 1 or 3 to 9 or the aqueous dietary product according to any of claims 2 to 9, wherein the die- tary product is administered no more than 2 hours prior to a subject taking a meal, such as no more than 1 hour prior to a subject taking a meal, e.g. no more than 30 minutes prior to the subject taking a meal.

11. The use according to any of claims 1 or 3 to 10 or the aqueous dietary product according to any of claims 2 to 10, wherein the die- tary product is administered one or more times per day, the distance in time between administrations being at least 2 hours.

12. The use according to any of claims 1 or 3 to 11 or the aqueous dietary product according to any of claims 2 to 11, wherein the dietary product is administered at a unit volume dosage of at least 400 mL.

13. The use according to any of claims 1 or 3 to 12 or the aqueous dietary product according to any of claims 2 to 12, wherein aqueous dietary product is prepared by mixing a dry powder containing an alginate and an aqueous liquid.