PALATABLE HIGH FAT COMPOSITION The invention relates to a palatable orally-ingestible composition containing a high proportion of fat, which thus provides an easy way in which to provide energy in this form, and to methods of making such a composition. The compositions of the invention may contain a variety of different sources of fat. The invention may be used as a dietary supplement to provide a concentrated source of fat, or as a fat emulsion for special dietary use.

All publications, patents and patent applications cited herein are incorporated in full by reference.

Fat, like protein and carbohydrate, is a principal and essential component of the diet. At nine kilocalories per gram, fat is the most concentrated source of energy in the diet; protein and carbohydrates contribute only about four kilocalories per gram.

A proportion of dietary fat is vital to enable the body to function properly. For example, dietary fats are a source of fatty acids, including essential fatty acids that are necessary to assure the maintenance of good health. These fatty acids must be obtained from dietary sources (primarily vegetable oils), since the body cannot synthesize them itself. Fat is also responsible for transporting the fat-soluble vitamins A, D, E and K.

Fatty acids are classified by their structure as either saturated, monounsaturated or polyunsaturated. Saturated fats are mainly found in foods of animal origin, including the fats in whole milk, cream, cheese, butter, meat and poultry. Saturated fats also can be found in large amounts in some vegetable products, such as cocoa butter, coconut oil and palm oil.

Monounsaturated fats are found primarily in plants, but also are found in animals. Olive, peanut and canola oil are common examples of fats that are high in monounsaturated fatty acids. Polyunsaturated fats are found mostly in plants. Sunflower, corn, soybean, cotton seed and safflower oils are vegetable fats that contain a relatively high proportion of polyunsaturated fats.

High rates of fat oxidation can occur during aerobic exercise, and using fat to fuel exercise can spare muscle glycogen. Athletes, particularly endurance athletes, may need to consume 4,000- 6,000 kilocalories/day to maintain their energy balance, and daily fat consumption makes a significant contribution in meeting these energy needs. Fat can be the primary source of energy during low intensity (aerobic) activity, providing 50% of energy during aerobic exercise and 80% energy towards the end of long endurance events. This process occurs by way of a shift (from burning carbohydrate to burning fat) in the relative proportion of active metabolic pathways.

For use as nutritional supplements for endurance athletes, it would be particularly desirable to deliver as much fat as possible in a small volume. Endurance athletes must often carry their own food supplies, which means that the weight of their food must be as low as possible.

Presently, there is no efficient way to deliver large amounts of a specific type of fat orally in a palatable composition. As soon as fat compositions include more than around 20% of fat, the composition becomes unpalatable and any attempt to ingest the composition will result in nausea and may result in the immediate regurgitation of the composition. This means that fat compositions must generally be tube-fed.

Furthermore, certain individuals have a requirement for supplementary intake of fats. For example, post-operative patients have specific nutritional requirements for fat. Commonly, these requirements are met at present by providing lipid emulsions that contain long chain triglycerides (LCT emulsions) that are delivered parenterally. Parenteral delivery requires a degree of technical support (so increasing the burden on health services) and generally prevents such patients being treated at home. Certain pathological conditions, such as anaemia, also require a patient to intake supplemental dietary fat.

It would also be of great value if it were possible to vary exactly an individual's dietary intake of fat, so that the effects of particular fatty acids on that individual's metabolism could be assessed. There is of course great interest in the metabolic effect of ingesting too much fat, and in which types of fatty acid are beneficial or detrimental to health. However, there is also much interest in the effect that specific fatty acids have on the metabolism of obese individuals, or diseased individuals, such as those suffering from diabetes. It would be of great value to be able to alter the dietary intake of fats in such individuals and monitor the effects of various therapies on the disease state.

A useful summary of the clinical applications of fatty acid profiling and a summary of conditions that may be addressed by fatty acid supplements is provided by Lord and Bralley, 1999 (see http ://www. metametrix. com/articIes/artcLcaf. htm).

There are no products currently available that allow the delivery of specific types of fat in large amounts. A composition termed Calogen (SHS) is an emulsion consisting of long chain triglycerides (LCT) from highly refined peanut oil. This composition may be used as a dietary supplement to provide a concentrated source of fat in the form of long chain triglycerides.

However, this composition is limited to the delivery of peanut oil and does not allow the delivery of any kind of specific triglyceride.

A second composition, termed Microhpid@ (Mead Johnson Nutritionals), is a 50% fat emulsion for special dietary use in oral or tube-feeding formulas, that may be mixed into enteral formulas, beverages, and table food. This composition includes safflower oil (a rich source of polyunsaturated fats). Again, the technology used to produce Microlipid0 does not allow the generation of a composition that can be adjusted for different fat contents.

There is thus a great need for the development of a suitable methodology that would allow the design of high fat compositions that could deliver one or more specific types of fat as a nutritional supplement.

Summary of the invention According to the invention, there is provided a palatable ingestible composition for the oral delivery of fat, said composition comprising a) a triglyceride component in a proportion of at least about 20% w/w; b) an emulsifier component consisting of a partial glyceride; c) a flavouring agent; and d) an aqueous solvent.

The compositions of the invention are palatable, meaning that the invention does not suffer the drawbacks of currently available fat compositions. There is no product currently available that provides a composition with fat as the major energy source and which focuses on the composition of the fat. Furthermore, the compositions of the invention may be modified so as to incorporate any type of triglyceride.

The term"triglyceride"is used herein to refer to fats that may be used in the compositions of the invention. For example, saturated fatty acids are very hard to emulsify and are therefore difficult to incorporate into a composition in high proportions. The compositions of the invention may be designed so as to emulsify saturated fatty acids in high proportions (up to 50% and above).

The compositions of the invention incorporate high proportions of triglyceride. The proportion of triglyceride in the compositions according to the invention may be greater than 20% w/w, preferably, greater than 30%, more preferably, greater than 40%, even more preferably, 45%, most preferably, 50% or more. Suitable triglycerides may be composed of saturated fatty acids (for example, myristic acid, palmitic acid and stearic acid), monounsaturated fatty acids (for example, palmitoleic acid and oleic acid), polyunsaturated fatty acids (for example, linoleic

acid, linolenic acid, arachidonic acid and n-3 polyunsaturated acids), trans-unsaturated fatty acids, omega-3 fatty acids, trans fatty acids, or a mixture of one or more of these triglycerides.

The invention is of particular utility with respect to the use of high proportions of saturated fatty acids, such as palmitic and stearic acids, which are very difficult to emulsify and are thus very difficult to administer in high quantities. Until now, it has not been possible to incorporate such high amounts of saturated fatty acids into a palatable orally-ingestible composition. Such triglycerides cannot presently be delivered parenterally or orally.

In order to emulsify the triglyceride into a homogenous emulsion, an emulsifier component must be included in the composition of the invention. The emulsifier component should include a partial glyceride or combination of partial glycerides. This component has been found to be particularly effective in emulsifying triglycerides, particularly those composed of saturated fatty acids, in a high percentage proportion into aqueous solution.

The partial glyceride should be a monoglyceride or diglyceride or derivative thereof. A suitable source of partial glyceride is cocoa powder, which, in addition to protein and carbohydrate, contains a number of species of partial glyceride. A partial glyceride emulsifying agent known as HYMONO 8903K emulsifier (Quest International) has been found by the inventors to be particularly suitable for use in preparing compositions according to the invention.

The emulsifier component should be present in the compositions of the invention in an amount sufficient to emulsify the amount of triglyceride that is intended to be used in the composition.

Of course, the emulsifier component is more costly than the other components of the compositions of the invention, meaning that its use should ideally be restricted to the minimum amount that is necessary to emulsify the triglyceride. The proportion of emulsifier used will also vary dependent on the efficacy of the emulsifier used. The proportion of the emulsifier component should be between 0. 1% and 5% w/w. Preferably, a composition according to the invention contains between 0.5% and 1 % emulsifier, more preferably, around 0.5%.

The compositions of the invention should also contain a flavouring agent. The incorporation of a flavouring agent increases the palatability of the composition, so facilitating its ingestion and imparting a pleasant taste to the composition. In fact, the compositions of the invention taste rather pleasant, in contrast to high fat compositions that have been prepared previously, which induce nausea and even vomiting. In particular, it has been noted that cocoa powder has a potent activity as an emulsifier, and at the same time imparts a pleasant flavour. Cocoa powder is thus an example of a preferred flavouring agent according to the invention.

The choice of flavouring agent may differ depending on the individual or the organism for which the composition is intended. For example, if the composition is intended for veterinary use, the flavouring agent may not be a sweetener, but may impart a savoury taste (such as fish oil for cats, or meat flavour for dogs). For the uses of fatty acid supplements in dogs, see the following articles: Ackerman, 1995, Veterinary Medicine; 93 (12) : 1149-1155 ; Ackerman, 1997, Supplement to the Compendium on Continuing Education for the Practicing Veterinarian ; 19 (3): 93-96; Campbell,"Therapeutic indications for dietary lipids". In Kirk, <BR> <BR> RW (ed): Current Veterinary Therapy XI. WB Saunders Co. , Philadelphia PA; 1992; 36-39; DeGroot, 1998, Veterinary Forum; 42-48; Griffin et al., 1993, Current Veterinary <BR> <BR> Dermatology. Mosby-Year Book, Inc. , St. Louis, MO; 114-115; Mooney et al., 1998, American Journal of Veterinary Research; 59: 859-863; Scott et al., 1995"Small Animal Dermatology", WB Saunders Co. , Philadelphia PA; 214-217.

For humans, it is likely that sweeteners will generally be a component of the preferred flavouring agent, optionally in combination with cocoa powder, for example, to impart a chocolate flavour to the composition. Examples of sweeteners include Hermesetas granulated sweetener, saccharin and aspartame. Other examples will be clear to those of skill in the art.

The final ingredient of the compositions according to the invention is the solvent, which should be an aqueous solvent. Suitable aqueous solvents include water, an aqueous electrolyte solution or an aqueous-alcoholic solvent. Preferably, the solvent used is water.

The compositions of the invention may be used in a number of different ways. For example, the compositions may be used as dietary supplements to provide energy in the form of fat. Of course, this strategy is very different from the current goals of most food manufacturers, who, in view of the weight conscious public to whom they sell, aim to reduce the fat content of their products as much as possible.

In contrast, the compositions of the invention may be sold as nutritional supplements, particularly for individuals who participate in active or endurance sports, or those participating in expeditions, such as polar expeditions, or polar research. Some endurance athletes may need to consume 4,000-6, 000 kilocalories/day to maintain energy balance, particularly in long distance events such as ultra-marathons, long distance bicycle rides such as the Tour de France and adventure races. Daily fat consumption makes a significant contribution in meeting these energy needs. Furthermore, evidence has shown that increasing energy intake after exercise, while the athlete is resting, facilitates recovery and is likely to improve repeat performances that must be attempted within a short period of time. This is particularly important in

endurance events that continue over a number of days (Saris W. H. M. , Limits of human<BR> endurance: lessons from the Tour de France. In : Kinney J. M. , Tucker H. N. , eds. Physiology, Stress and Malnutrition. Philadelphia: Lippincott-Raven, 1997: 451-462; Joint position statement: nutrition and athletic performance. American College of Sports Medicine, American Dietetic Association, and Dieticians of Canada. Med. Sci. Sports Exerc. 2000; 32: 2130-2145).

The compositions of the invention allow such a significant fat intake without requiring the ingestion of a large amount of food. Ingesting small amounts of concentrated fat in this manner may also enhance the amount of triglyceride stored and increase the rate of its storage.

It is also possible that the compositions of the invention might be used to enhance the fat uptake of particular animal populations, such as domesticated livestock intended for human consumption. It may be that the flavour of the animal meat or its fatty acid composition may be altered beneficially, or that the weight or growth rate of the animal may be increased in order to reduce the cost of raising livestock. This aspect of the invention thus provides a method for enhancing the fat uptake of an animal comprising administering to the animal a palatable ingestible composition according to any one of the embodiments of the invention described above.

The compositions of the invention may also be used as a dietary source to deliver specific fatty acids to an individual. This may be useful to address specific deficiencies suffered by individuals. For instance, essential fatty acid deficiency has been suggested to underlie attention-deficit/hyperactivity disorder (Stevens et al., 1995, Am J Clin Nutr: 62: 761-8) and dyslexia; pre-term infants deprived of vital fatty acids during late pregnancy are likely to have failures of normal development, especially development of the visual system, if not provided with dietary supplements of omega-3 fatty acids (Innis, 1992, Lipids, 27 (11) : 879-887); higher palmitic and lower omega-3 fatty acids in serum are correlated with higher incidence of coronary heart disease in middle-aged men at high risk for cardiovascular disease (Simon et al., 1995, Stroke, 26: 778-82); changes in dietary fatty acid intake cause alterations in immune response, including anti-tumor activity (Erikson et al., 1995, J Nutr, 125: 1683S-1686S) and so on (see Lord and Bralley, 1999, loc cit). Use of the compositions of the invention as a dietary source may also maximize the nutritional value that the compositions may provide. This aspect of the invention thus provides a method for treating a disorder relating to a fatty acid deficiency in a patient, said method comprising administering to the patient a palatable ingestible composition according to any one of the embodiments of the invention described above.

The compositions of the invention may also be used as tools for human and animal research to increase specific fatty acids in the circulation and to test for the effect of this manipulation on physiology. In this manner, the effects of particular fatty acids on metabolism may be assessed, not only for healthy individuals, but also for individuals who are severely overweight or underweight. In this manner, the metabolic effect of ingesting too much or too little fat, or too much or too little of a specific type of fat may be assessed and the types of fatty acid that are beneficial or detrimental to health can be evaluated rationally. These effects may also be evaluated for diseased individuals, such as those suffering from diabetes, and the metabolic patterns found in diseased and healthy individuals can be compared. The compositions of the invention allow a researcher to be able to alter the dietary intake of fats in such individuals, as desired.

Furthermore, by applying specific fatty acids in conjunction with a candidate therapeutic or prophylactic agent for a disease or dysfunctional state, the effects of various therapies on fatty acid levels that are characteristic of the disease or dysfunctional state may be monitored.

It has been found that the compositions of the invention have an acceptable shelf-life, in that they can be stored refrigerated or at room temperature for a significant period of time and reconstituted by brief shaking before use. This is a further advantage of the compositions of the present invention, in that no specialized equipment or refrigeration is required to store the compositions. This means, for example, that the compositions may be sold to the public at normal grocer-type outlets and will not need to be prepared upon demand by dispensing chemists.

For long periods of storage, or on occasion, for convenience (for example, to reduce weight load in endurance events) compositions of the invention may also be freeze-dried. Granules of freeze-dried composition may then be reconstituted when required, for example, using warm water and stirring vigorously. Such freeze-dried or lyophilised compositions form a further aspect of the invention.

According to a still further aspect of the invention, there is provide a method of preparing a palatable ingestible composition according to any one of the embodiments of the invention described above, said method comprising the steps of: a) combining the triglyceride and emulsifier components and warming the mixture until the emulsifier component has melted into the oil ; b) adding the flavouring agent to the solution of triglyceride and emulsifier components; c) slowly mixing the solvent into the composition whilst stirring continuously;

d) blending the final composition together to form an emulsion.

Preferably, the method is performed in the order of steps recited above.

In step a), the triglyceride and emulsifier components are combined and the mixture is warmed, generally to around 65-70°C, when the emulsifier component will gradually melt into the oil. The temperature to which the mixture is raised will depend upon the type of triglyceride that is to be incorporated into the composition. For example, saturated fats are usually solid at room temperature, whilst monounsaturated fats are liquid and polyunsaturated fats are usually liquid at room temperature. The melting temperature may thus need to be increased above 70°C for compositions that incorporate a large amount of saturated triglyceride. The temperature should be kept well below boiling point.

The flavouring agent should then be mixed into the solution of triglyceride and emulsifier components.

The next step is the incorporation of the aqueous solvent into the composition. This should be done very slowly, with the solution being mixed continuously while the solvent is being incorporated. Finally, the resulting composition is blended together to form an emulsion. This may be performed using any of a number of techniques, as the skilled reader will be aware. In the case of a small-scale laboratory process, a hand-mixer may be used, homogenizing the composition for around two minutes.

Various aspects and embodiments of the present invention will now be described in more detail by way of example, with particular reference to compositions containing linoleic acid, palmitic acid or oleic acid. It will be appreciated that modification of detail may be made without departing from the scope of the invention.

Brief description of the Figures Figure 1 shows specific fatty acid composition during a test with olive oil in which small portions of the high fat emulsion are used to produce continuous absorption of the fat of interest (as triglycerides) accompanied by a slow infusion of heparin, a substance to activate the enzyme lipoprotein lipase ; Figure 2 shows specific fatty acid composition during safflower oil test; Figure 3 shows specific fatty acid composition during palm stearin test.

Examples Example 1: Preparation of fat-emulsion Material Different oils used: -Tesco'M olive oil, light and mild (73 g mono-unsaturated fatty acids, 14.3 g saturated fatty acids, 8.2 g polyunsaturated fatty acids) for enrichment in oleic acid in plasma Purified safflower oil (Anglia Oils Limited, King George Dock, Hull) for enrichment in linoleic acid in plasma -Palm stearin (Anglia Oils Limited, King George Dock, Hull) for enrichment in palmitic acid in plasma Quest International (HYMONO 8903K) emulsifier Cadbury's Cocoa powder (322 kcal, 23.1 g protein, 10.5 g carbohydrates, 20.8 g fat) Hermesetas granulated sweetener Bottled still water Accurate scale, Pan, Beakers, Hand mixer and plastic beaker, Bottles, Cooker Preparation For 200 ml : Weigh out: - 00 g of the appropriate oil in beaker -1 g of emulsifier (0.5 %) in weighing boat - 6 g of cocoa powder in weighing boat - 2 g of sweetener in weighing boat +/-150g of water in beaker Add emulsifier to oil Warm up oil plus emulsifier gently (@ 65-70 °C) by placing beaker in saucepan with boiling water or in microwave until emulsifier is melted Boil water in microwave

Add cocoa to hot oil Add sweetener to hot oil Add very slowly the appropriate amount of water to hot oil while mixing Mix everything with handmixer for at least 2 min.

Blend Example 2: Testing fat-emulsion for palatability and absorption in man The compositions of the invention have been tested for palatability and absorption in man.

Three different compositions have been used as research tools to increase specific fatty acids in the circulation in man.

This was achieved by feeding small portions of the high fat emulsion to produce continuous absorption of the fat (as triglycerides) of interest accompanied by a slow infusion of heparin, a substance to activate the enzyme lipoprotein lipase. This enzyme hydrolyses the absorbed triglycerides in the circulation into smaller components, non-esterified fatty acids (NEFA).

Figure 1 shows the increase in linoleic acid in plasma from eight volunteers when linoleic acid was the main fatty acid used in the composition.

Figure 2 shows the increase of mainly palmitic acid in plasma when palmitic acid was the main fatty acid used in the composition.

Figure 3 shows the increase in plasma oleic acid when oleic acid was the main fatty acid used in the composition.