Nutritional composition for improvement of muscle functions and diurnal activity. RU patent 2506825.

FIELD: food industry.

SUBSTANCE: invention relates to a nutritional composition. The nutritional composition contains a combination of whey protein, leucine and at least an omega -3 polyunsaturated fatty acid chosen from the following group: eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid and docosapentaenoic acid. The composition glycaemic index is lower than 55.

EFFECT: composition is used for improvement of muscle function with mammals, for improvement of physical and diurnal activity as well as for improvement of anticancer therapy observation, for ensuring better prognosis from the point of view of life expectancy and life quality enhancement.

42 cl, 6 dwg, 8 tbl, 3 ex

The technical field to which the invention relates

The invention relates to a composition, including protein material containing leucine, and V-3 polyunsaturated fatty acids.

The invention also relates to the application of compositions suitable for improving muscle function at a mammal. The invention also relates to the composition is suitable for the improvement of the daily activity of a mammal.

The level of technology

The composition of the body, the functionality of muscles and daily activity are highly significant clinical parameters, because the function of muscles and daily activity make an important contribution to the quality of life of patients suffering from oncological disease. In addition, improved physical condition of the patient, reflected body composition and physical activity, can contribute to the cancer treatment. For example, the dosage chemotherapy can be carried out in accordance with the plan, not fit to reduced body weight patient.

Cachexia is one of the aspects of cancer causing the greatest weakening of, and is associated with increased severity of disease and mortality, declining quality of life, in violation of response to chemotherapy, increased susceptibility to the toxicity associated with chemotherapy, and high frequency of postoperative complications. Cachexia due to oncological disease can be identified as uncontrolled weight reduction with the reduction of not only the mass of adipose tissue, but also his lean body mass due to depletion of muscle. In addition to reducing the body weight, symptoms are exhaustion, weakness, swelling, violation of the immune response and worsening of motor and mental activity. It was shown that in patients with cachexia, high power consumption at rest is not consistent with the increase in consumption of nutrients, and in many cases food consumption is even reduced. So, about 45% of the cancer patients had loss of more than 10% of body weight compared with the level before diagnosis. The tumor may cause changes in the metabolism of protein, reminiscent of those observed in infections or damage. These changes are characterized by the collapse of total protein, increased oxidation of branched chain amino acids () in the muscles to support energy stores and synthesis amino acids. The degradation of protein organism-media especially stimulated by inflammatory mediators, generating media (for example, α, IL-6) (1), but also of the tumor by releasing factor, inducing proteolysis (PIF)(4). Further, the tumor has a high rate of own synthesis of protein, and has the ability to intracellular transport and catabolism .

Increased energy demand and inflammatory catabolic status leads to a significant reduction in body fat and to the deterioration of muscle mass. Thus, it is assumed that the nutritional support of cancer patients should be more focused on opposition to the destruction of total protein, rather than the increase in consumption of calories as such. To install a new, positive balance of the synthesis and protein degradation, the addition of protein should be accompanied by components, modifying and softening a catabolic signal. It has been described that a high level of amino acids is essential for increasing protein synthesis. It is known that branched chain amino acids and especially leucine control metabolism of protein in skeletal muscle by stimulating protein synthesis and for the suppression of protein degradation. Prospective trials enrichment amino acids, branched chain control calories and nitrogen through the full and parenteral nutrition in patients with sepsis really showed improvement in the level of pre-albumin and reduction in overall mortality in the group of patients with high value simplified scale of assessment of acute functional changes (LeGall-SAPS). It was noted that the application of rats- diet with the addition of 3% leucine led to a decrease in loss of lean body mass, the mass of the calf muscle and the content of myosin, compared with the control and diet. These data are corroborated by the observation that isoleucine increases protein synthesis in pregnant rats-, perhaps as a result of changes ubiquitin-proteasome system. In two clinical trials conducted a study of oral intake of additives with after surgical removal of the tumor, and noted the reduction of stay in the hospital, improvement of functional status within 3 months and increased body weight for 1 year. also used in the presence of tumour patients undergoing chemotherapy, received oral supplementation with for 1 year, which resulted in a decrease in common manifestations of the disease, nutritional status and quality of life. Other nutrients that may have anticancer effects are (0-3 polyunsaturated fatty acids (PUFA). Basically most clinical trials using V-3 PUFA noted the increase or maintenance of body weight (MT); while in two clinical trials no influence on the reduction of MT. In the latter, however, the period of use of the additive was only 2 weeks and/or included only a small number of patients. Other effects of the consumption of additives with the EPA or fish oil in cancer patients were overall increase in lean body mass, and increase total energy expenditure and physical activity, reducing the need for full injecting nutrition, and improved quality of life and even the expected improvement in survival.

WO 2004/026294 reveals nutrient compositions, including a mixture of amino acids in a free form and/or in the form of salt, rather than the intact protein to stimulate protein synthesis in the muscle or control body weight loss caused by the tumor, such as cancer cachexia. In addition, you may attend the intact protein. However, nutritional composition comprising at least 18 EN.% protein material, at least part of which is whey protein, at least 12% of mass leucine and V-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, acid and acid, is described in a single combination. Approximate nutrient compositions include Caseinate as a source of protein. In example 2 of WO 2004/026294 it is assumed that the consumption of three amino acids more effectively, than consumption of comparable numbers of intact protein in stimulation of the overall protein synthesis in the muscle.

The EP 1774973 A1 disclosed composition comprising protein material, the protein material provides at least 24 EN.% and at least 12% of mass leucine, on the basis of total protein material, for the treatment of insulin resistance. Not listed examples of compositions.

The essence of the invention

The objective of the invention is to provide compositions suitable for improving muscle function, preferably leading to the improvement of the daily activity of a mammal. In particular, the objective of this invention is to provide a nutrient composition for such purpose.

It was found that can be treated the subject with reduced muscle function or subject to a reduced risk of developing muscle function, with the help of a special composition, including protein material.

Accordingly, the present invention relates to a combination of whey protein, leucine, and at least one at least V-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, acid and acid, to improve muscle function at a mammal.

Preferably, the organoleptic properties of the composition is such that the composition as a whole is perceived as pleasant taste.

Preferably, the composition easily passes through the stomach.

Preferably, digestible components of the composition become easily accessible from consumption of the product.

Composition according to the invention in particular can be used to improve the function of skeletal muscle at a mammal. It is clear that improving the function of skeletal muscles could include improving one or both of improving muscle function mammal, dependent on muscle mass and improve muscle function, not dependent on muscle mass. To reduce muscle function depending on muscle mass, this may include the correction of maximum strength, maximum speed reduction or maximum speed of relaxation skeletal muscles. To reduce muscle function, not dependent on muscle mass, this may include a correction to the maximum power adjusted on muscle mass, maximum speed reduction, adjusted on muscle mass, or the maximum speed of relaxation, adjusted for muscle mass. In addition, it may improve the time needed to eliminate or relaxation.

In one incarnation of the composition according to the invention can be used for prophylaxis or treatment reduce muscle function, caused by or resulting from old age, disease, disorder, drugs, or injury, preferably, use of drugs, disease or disorder.

Decreased muscle function may, in particular, to emerge as a symptom caused by disease or defect, such as cancer, HIV infection, chronic obstructive pulmonary disease, renal failure, heart failure, and a pathological condition characterized by a high level of Pro-inflammatory cytokines in plasma and/or serum. Thus, the composition according to the invention can be applied, in particular for the treatment of mammal, suffering from a disease or disorder, selected from the group consisting of: cancer, HIV infection, chronic obstructive pulmonary disease, renal failure, heart failure, and a pathological condition characterized by high levels of proinflammatory cytokines in plasma and/or serum.

Preferably, disease or disorder is a form of cancer. In this context, reduced muscle function may be a loss of function depending on muscle mass, or loss of function that is not dependent on muscle mass.

Next, treatment with the use of medication, such as chemotherapy, can lead to decrease in muscle function. Thus, the invention also refers to a nutrient composition according to the invention, in which the medicine can be used in conditions of chemotherapy.

On the basis of experiments in which the arrangement in accordance with the invention was fed to mice-, as illustrated in the example below, the inventors have made the assumption that the composition according to the invention is effective for improving muscle functions of a mammal. In experiments it was shown that at least one of several physiological parameters associated with reduced muscle function turns out to be a positive influence.

In addition, it is assumed that the composition according to the present invention can be used to improve the forecast in terms of life expectancy and/or improve the quality of life. Factors that improve the quality of life, are, in particular, less fatigue, improvement of daily activity, increasing the reserves of the organism, improving the contrast between the activity in daylight and at night (night's sleep), improvement of General condition and reduction periods feelings of depression.

Protein material

Protein material is formed components that are made up of amino acids. The term «amino acids»as used here, includes amino acid residues (for example, in peptides). In particular, the term «protein material» includes free amino acids, salts of amino acids, ethers of amino acids, amino acid residues associated with molecules and peptides, including proteins. In addition, when reference is made to specific amino acids, for example, leucine, this means the inclusion of specific amino acid residues present in the form of salt, in bound form, and also in the form of free amino acids.

Peptide means a combination of two or more amino acids connected by one or more peptide bonds. When you enable the peptide amino acids are called amino acid residues. Peptides include oligopeptides and polypeptides, including proteins.

Polypeptide means the peptide chain, containing 14 or more amino acid residues. Oligopeptide means the peptide chain, containing from 2 to 13 amino acid residues.

Chiral amino acids present in the composition according to the invention, may be in an L-shape or in the D-form. Usually chiral amino acids are present in the composition according to the invention in an L-shape.

In one incarnation liquid composition in accordance with the invention, contains at least 7 g/100 ml protein material, preferably at least 8 g/100 ml, more preferably at least 9 g/100 ml, most preferably at least 10 g/100 ml

Protein material in the composition according to the invention provides at least 18 EN.%, preferably at least 20 EN.%, more preferably at least 22 EN.% from the whole composition. Protein material in the composition according to the invention usually provides 60 EN.% or less, preferably 40 EN.% or less, or more preferably 32 EN.% or less of the whole composition.

Protein material includes whey protein. Whey protein, among others, is considered preferable as it provides rapid release of amino acids in the blood after eating the food, for example, compared with casein. Thus, the authors suggest that the threshold concentration of amino acids, required for switching anabolic signal for the synthesis of protein in muscle can be easier to reach (for example, at lower dosage of protein material, or faster after eating).

Protein material can optionally contain the protein material from one or more other sources of protein, in particular, one of several sources of protein material selected from the group consisting of casein, Caseinate, soy and wheat, preferably casein. The specified source of protein or part of it can be modified, in particular, by hydrolysis of the (partial).

Serum indicates the origin of the globular protein, which can be distinguished from the serum. In particular, globular whey proteins can choose from a beta , alpha-lactalbumin and serum albumin, including their mixtures. Examples of mixtures containing serum proteins, are whey protein isolate and whey concentrate. Both sources contain predominantly intact serum proteins that are preferred in the context of this application.

In one incarnation protein material contains at least 10%mass, preferably at least 15 wt.% more preferably at least 20 mass%, most preferably at least 25% of mass serum, based on all the protein material. Usually whey fraction makes up 50% of mass or less, based on all the protein material, in particular, 40 wt.% or less, based on all the protein material, though - if necessary - can be achieved from more than 50 wt.% up to 100% of mass protein material by serum.

In particular, in the case of liquid composition, concentration denatured whey preferably not exceed 35% of mass on the basis of just protein material. It is preferable in terms of elimination of the risk of the gelatin during storage. Furthermore, the choice of serum compared with the free amino acids is preferred because the free amino acids have bad taste.

The presence of serum can provide a number of advantages. It is shown that serum is beneficial profile release from the point of view of speed of release of amino acids and trends to ensure the availability of amino acids for consumption by the body essentially the same time.

Profitable profile release of amino acids can be further strengthened by weak/partial hydrolysis at least part of whey protein, usually to the extent of 20% protein hydrolysis to free amino acids, preferably prior to the extent of 10% of protein hydrolysis to free amino acids.

For the specified reinforced the effect usually 50 wt.% whey protein or less (slightly) , in particular from 10 to 50%of mass.

If necessary, free amino acids or their part can be removed from the hydrolysate. Known suitable methods, for example, filtration, chromatography, or adsorption.

As a source of whey protein(s) preferably select fraction of serum containing less than 20% of mass kazeinovogo (GMF), more preferably less than 10% (mass).

Content of beta- preferably more than 40 wt.% more preferably from 46 to 80%of mass.

When used as an intact protein casein preferably contains a high concentration of beta-casein, in particular, more than 36 g/100 g casein, more specifically, from 38 to 70 g/100 g of casein.

In one incarnation at least part of the protein material is present in the form of free amino acids and their salts, or in the form of kongugata with other molecule than protein or peptide, the conjugate is able to split the free amino acid (or salt) and connection under the influence component of bile and/or secretion of the pancreas in the duodenum and/or ileum. In one embodiment, the number of free acid in this form, in particular, in salt form or in the free form is up to 15 wt.% of the total protein material, preferably 0,5-14%of mass.

The advantage of composition with a high content of peptide (>50 wt.%) is the taste, or other property composition, usually recognized the best in the consumption (oral). In addition, consumption of amino acids by the body can be more consistent.

In the private incarnation of the song contains leucine in the form of free acid, salt, dipeptide or conjugate with connection other than the amino acid, protein or peptide, where conjugate is capable of splitting the free amino acid (or salt), preferably in the intestine or stomach, or after absorption in enterocytes or liver.

Leucine is preferably at least 35%of mass, more preferably at least 40 wt.% on the basis of total protein leucine, present in the form of a peptide (oligopeptides, polypeptide, protein, preferably in the form of polypeptides and/or (intact) proteins.

Leucine is up to 100%of mass, preferably up to 80%of mass, on the basis of total protein leucine, present in the form of a peptide (oligopeptides, polypeptide, protein), preferably in the form of one or more of polypeptides and/or one or more (intact) proteins.

The content of leucine in the composition according to the invention is at least 12%of mass, at least 13%of mass, at least 16% of mass or at least 19% of mass on the basis of total protein material. Typically, the content of leucine is 50 wt.% or less In particular, it can be 30 mass.% or less, 25 wt.% or less, or 23% of mass or less, based on all the protein material. In one incarnation content leucine is from 12 to 23 wt.% on the basis of just protein material.

Preferably, the composition may contain glutamine and/or glutamic acid.

If there is glutamine, its content (defined as total glutamine and glutamic acid) is at least 15 wt.% on the basis of just protein material. In one incarnation content glutamine is from 15 to 28%of mass, preferably from 17 to 26%of mass, on the basis of total protein material.

Preferably, the composition may contain one or more of the group consisting of cystine, cysteine and equivalents cysteine, such as N-acetyl-cysteine, preferably, in the amount of at least 0.8%of mass, on the basis of just protein material. Typically, the content of cystine, cysteine and equivalents cysteine is 11% of mass or less. In particular, it is 8 wt.% or less, on the basis of just protein substances. In one incarnation content cystine, cysteine and equivalents cysteine is from 0.8 to 8 wt.% on the basis of just protein substances.

Homeostasis glutathione plays a role in maintaining the stability of the entire organism to oxidative stress. Heavy oxidative stress in the muscles may lead to a decrease in muscle function. In experiments on mice- inventors have found that the levels of glutathione in the liver were significantly reduced. The liver is the main provider of glutathione, and therefore the level of glutathione in the liver well reflects the level of glutathione in the body. Surprisingly, subsequent experiments conducted inventors have found that at least partial normalization of the level of glutathione in the liver cells occurs under the influence of glutamine and/or cysteine in the composition according to the invention. Especially good results were obtained when the song was attended by both amino acids. On the basis of these experiments, the inventors have made the assumption that the composition according to the invention, contains glutamine or cysteine, preferably in a concentration above, it is particularly effective for improving muscle functions of a mammal. In addition, it is assumed that the presence and glutamine, and cysteine in the composition according to the invention even more effectively and to improve muscle function mammal.

In one incarnation of the beneficial effects of glutamine and/or cysteine in respect of muscle function mammal is achieved through composition according to the invention, contains whey protein and casein.

In the arrangement in accordance with the invention of the mass ratio of leucine/(valine+isoleucine) is generally 1,0 or more, preferably 1,05 or more.

Throughout the product content of essential amino acids is usually at least 49%of mass, preferably from 49 up to 80%of mass, more preferably from 52 to 70% of mass from the total protein material produced by irreplaceable amino acids.

Lysine is usually between 7 to 15 g/100 g of protein material, preferably from 7.5 to 14 g/100 g of protein material.

Reducing the destruction of muscle protein using a composition according to the invention can also help to reduce losses of carnitine and/or lysine from muscles and contribute to levels of muscle carnitine and lysine. Thus, the composition according to the invention, includes carnitine, can contribute to the function of skeletal muscles. L-carnitine (beta-acetoxy-gamma-N,N,N-) is synthesized from the amino acids lysine and methionine, mainly in the liver and kidneys. Carnitine is needed for transport across the mitochondrial membrane fatty acids with medium and long chain, which are then subjected to beta-oxidation. In addition, it facilitates the removal of organic acids short-chain of mitochondria, thus freeing the mitochondrial coenzyme-And to participate in the beta-oxidation and the Krebs cycle. Thanks to these key functions, carnitine is concentrated in tissues using fatty acids as the primary dietary source of energy, such as skeletal and cardiac muscles.

Lack of carnitine is celebrated in some forms of cancer and is associated with increased fatigue. Three outdoor studies have indeed suggest that treatment carnitine reduces fatigue, measured on a scale fatigue. It turned out that one derivative carnitine, acid-soluble acyl-carnitine, especially decreased in cancer patients in comparison with healthy people. A significant decrease in total carnitine noted after three months of treatment, and it was assumed that carnitine deficiency is caused by chemotherapy. Another explanation of the development of carnitine deficiency can be that reducing the level of carnitine associated with the presence of cachexia. In conclusion, the lack of carnitine, as it seems, and chemotherapy induced, and progression of the disease (cachexia). These findings suggest that the use of additives with a composition according to the invention, includes carnitine, it is best to start immediately after diagnosis to prevent failure.

If carnitine is present, its content in the composition according to the invention is usually at least 5 mg / 100 kcal, preferably at least 10 mg / 100 kcal, at least 25 mg / 100 kcal, or at least 100 mg per 100 kcal. Typically, the content of carnitine is 2.5 g or less per 100 kcal, in particular 1,25 g or less per 100 kcal. In case of liquid product content carnitine preferably at least 10 mg/100 ml, at least 50 mg/100 ml, or at least 200 mg/100 ml Typically, the content of carnitine is 5 grams or less per 100 ml, in particular 2.5 g or less per 100 ml.

Taurine is the most abundant free amino acid in cardiac and skeletal muscles, and with a decrease in muscle mass it is derived from the muscles. Assume that taurine plays an important role in the movement of ions and processing of calcium in the muscles, and thus can affect the activity of the muscles. Deficit of taurine causes atrophy of cardiomyocytes, damage mitochondria and muscle fibers and heart-dysfunction - effects are likely associated with the functions of taurine. Reducing the destruction of muscle protein using a composition according to the invention also may help to reduce the loss of taurine from muscles and contribute to levels of taurine in the muscles, and therefore support muscle function.

If there is taurine, its content in the composition according to the invention is usually at least 5 mg / 100 kcal, preferably at least 10 mg / 100 kcal, at least 25 mg / 100 kcal, or at least 100 mg per 100 kcal. Typically, the content of taurine is 2.5 g or less per 100 kcal, in particular, 1,25 g or less per 100 kcal. In case of liquid product, content of taurine preferably at least 10 mg/100 ml, at least 50 mg/100 ml, or at least 200 mg/100 ml is Usually content of taurine is 5 grams or less per 100 ml, in particular, 2.5 g or less per 100 ml.

Lipid fraction

In the composition of the invention lipid fraction is usually provides at least 10 EN.%, preferably at least 20 EN.% or more preferably at least 25 EN.% from the whole composition. Lipid fraction of the composition according to the invention usually provides 50 EN.% or less, preferably 40 EN.% or less, or more preferably 35 EN.% or less of the whole composition.

The term «lipid fraction» means a fraction, containing one or more of lipids, including fatty acids, and derivatives of fatty acids (including three-, and monoglycerides and phospholipids) and -containing metabolites, such as cholesterol.

As stated above, the composition in accordance with the invention, contains at least one V-3 polyunsaturated fatty acids, selected from the group consisting of eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), acid (ETK) and acid (DICK).

In another embodiment composition in accordance with the invention, contains acid (YES). It is noted that the nutritional oils containing ATS, are dietary source of co-3 fatty acids, which allows you to more effectively improve the tissue concentration of EPA and duodenum than modern ALK-containing oil. Preferably, lipid fraction in the composition contains more than 0.5 wt.% KFOR, is more preferable than 0.6 wt.% KFOR, even more preferably more than 1.2 wt% KFOR, on the basis of the total lipids. The maximum number of more or less limited to a specific used source (type of fat of marine mammals), but the fat of marine mammals with the content of KFOR from 2 wt.% up to 5 wt.% (on the basis of the total lipids in oil) are commercially available. Preferably, the number of KFOR in the lipid fraction is in the range of 0.5 to 5 wt.%, on the basis of the total lipids. It is preferable that the number of KFOR was relatively high compared with the number of docosahexaenoic acid (DHA) and/or linolenic acids (LC). This ensures high efficiency and production attractive to the taste of the products in accordance with the invention of the mass ratio of KFOR and DHA at least 0,22, preferably at least 0,25, more preferably at least 0,30.

Composition according to the invention may be, in particular, the composition, in which at least 55% of mass the lipid fraction, preferably oils contain at least 4 wt.% one or both of eicosapentaenoic acid and docosahexaenoic acid.

In the arrangement in accordance with the invention of the lipid fraction contains less than 30 mass.% a saturated fatty acid, preferably less than 22% of mass on the basis of total lipid content.

The ratio of the V-3 to ω-6 polyunsaturated fatty acids can be chosen within a wide range, e.g. from 0.2 to 10, or from 0.4 to 3.0. In particular, the ratio of V-3 to ω-6 polyunsaturated fatty acids is less than 1.0, preferably 0,97 or less, preferably 0.95 or less. Attitude preferably more of 0.5 or higher, preferably 0.6 or higher. In particular, preferably ratio ranges from 0.5 up to 0,97, preferably from 0.6 to 0.95.

Carbohydrate fraction

In one embodiment, the composition in accordance with the invention, contains a fraction of indigestible carbohydrates, ensuring at least 20 EN.%, preferably at least 30 EN.%, or more preferably at least 38 EN.% from the whole composition.

Fraction of digestible carbohydrates in the composition according to the invention usually provides 70 EN.% or less, preferably 60 EN.% or less, preferably 48 EN.% from the whole composition.

The term «faction of indigestible carbohydrates» means a fraction, containing one or more digestible carbohydrates.

Digestible carbohydrates include , maltose and glucose. In particular, carbohydrate is considered if 90% of carbohydrates are digested quickly within 20 minutes in accordance with the method .

In particular, the composition of carbohydrate fractions can be selected to achieve a favourable consumption of carbohydrates, and respectively, of the necessary release of insulin after absorption. Respectively, favored the composition of the meeting one or more of the following criteria in regard to the content of carbohydrates.

In one incarnation less than 75% of mass carbohydrates are formed from the amount of sucrose content and maltodextrin.

In one incarnation of at least 40% of mass the total mass of carbohydrates derived from slowly digestible carbohydrates, i.e. in particular, carbohydrates, indigestible less rapidly than , maltose and glucose.

In one incarnation of the composition according to the invention, contains less than 60 wt.%, preferably from 20 to 50 wt.% the total mass of the carbohydrates from quickly digestible carbohydrates, in particular, of , maltose, glucose and other carbohydrates are digested at least as quickly.

In one embodiment more 20 wt.% the total mass of the carbohydrates are formed by at least one disaccharide, preferably from 22 to 60%of mass. In particular, in this incarnation, the disaccharide preferably selected from the group consisting of sucrose, trehalose, , lactose and other disaccharides (low-glycemic), preferably of trehalose and .

In one incarnation, there is at least one monosaccharide, other than glucose. Preferably specified monosaccharide is selected from the group consisting of galactose, mannose and ribose. Preferably, the total number specified monosaccharides(s) is from 0,5 up to 30 wt.% more preferably from 5 to 25 wt.% the total mass of carbohydrates.

In particular, the presence of ribose is profitable, preferably in combination with the (endogenous) folic acid to increase protein synthesis. It is implied that the combination of these two compounds provides increased production of guanosine-triphosphate at a mammal, which leads to increased protein synthesis by stimulating initiation factor 2 In, especially in patients with poor diet. Folic acid can be provided in one or more of the following forms: free folic acid, folinovaya acid, folic acid, folic acid, preferably in the reduced form, or as a derivative, conjugated with mono - or . If present, folic acid, its content is usually at least 95 mcg per 100 kcal carbohydrates, preferably from 110 up to 400 mg per 100 kcal carbohydrates, preferably from 125 to 300 mcg 100 kcal carbohydrates.

It is assumed that a profitable to improve muscle function in mammalian improve the daily activity, the improvement of physical activity provide better guidance in life expectancy, improving the observance of anticancer therapy or improve the quality of life is that the composition has a relatively low on the glycemic index. Contacting theory, it is assumed that the combination or the composition according to the invention, have a low glycemic index, benefits in respect of muscle protein synthesis, and/or muscle strength, as it contributed to the high sensitivity of muscle to insulin. High insulin sensitivity is considered to be favorable, because it improves the stimulating effect of insulin in muscle synthesis (stimulation of insulin starts switching anabolic signal in the muscles).

Accordingly, in a special incarnation of the composition is a nutritional composition with low glycemic index. In particular, it is considered preferable to the glycemic index composition was below 55, preferably below 45. Practically, the glycemic index is above zero, and usually at least 1, in particular, at least 5. Details of the definitions of the glycemic index composition shown in the examples below.

Specialist in a given field of technology may have the composition with a relatively low on the glycemic index on the basis of information disclosed here, and General knowledge. In particular, by increasing the percentage of carbohydrates, digested more slowly than glucose, or by increasing carbohydrate containing less glucose components on mass than glucose, glycemic index composition (unlike the usual conditions) decreases. Preferred examples of carbohydrates, digested more slowly than glucose, are isomaltulose, fructose, galactose, lactose and trehalose. Furthermore, the addition of fat and fiber may slow gastric emptying. Further, the fibers can form a physical barrier in the gut, slowing down the rate of absorption. Amino acids from protein can promote the release of insulin (especially leucine), and thus, increase the consumption of glucose by cells. All these mechanisms can contribute to the reduction of the glycemic index.

The faction is not digested carbohydrates

In one incarnation composition in accordance with the invention, contains a fraction not digested carbohydrates.

In the preferred composition carbohydrates are selected from the group galactooligosaccharides production and .

In particular, selected from the group galactooligosaccharides production short-chain, galactooligosaccharides production of long-chain, or any combination thereof.

In particular, selected from a group of short-chain, long-chain, or any combination thereof.

The preferred composition contains and .

Preferably, molar ratio to is in the range from 1:1 to 20:1, preferably from 5:1 to 12:1, and it is most preferable is approximately equal to 9:1.

means a circuit containing from 2 to 25 residues.

Oligosaccharide long-chain means circuit containing 10-25 residues. Oligosaccharide short-chain means circuit containing 2-9 residues, for example, 2-5 residues or 6-9 residues.

carbohydrates carbohydrates are remaining essentially no split in the small intestine of the person. In particular, carbohydrate is considered in the case when less than 10% of Sugars released within 20-120 minutes at a series of tests with a set of standard digestive enzymes in determining the method .

In the private incarnation, carbohydrate selected from the group with degree of polymerization (DP) from 2 to 50, with SP 2 to 60, oligomers containing more than 30 mass.% components of galacturonic acid and glucuronic acid with a molecular weight of 520 to 2200 Dalton, and any combination of these.

In the private embodiment of the present invention composition according to the invention may contain a mixture of neutral and acid oligosaccharides, as disclosed in the WO 2005/039597 (N.V. Nutricia)incorporated here by reference in its entirety. More specifically, sour oligosaccharides have a degree of polymerization (DP) from 2 to 5000, preferably from 2 to 1000, more preferably from 2 to 250, even more preferably from 2 to 50, it is most preferable from 2 to 10. If you apply a mixture of acid oligosaccharides with varying degrees of polymerization, the average JV mixture of acidic oligosaccharides preferably from 2 to 1000, more preferably from 3 to 250, even more preferably from 3 to 50. Sour Oligosaccharide can be homogeneous or heterogeneous carbohydrate. Sour oligosaccharides can be made from pectin, , alginate, chondroitin, hyaluronate acid, heparin, , bacterial carbohydrates, , fucoidan, or carrageenan, and preferably made of pectin or alginate. Sour oligosaccharide can be cooked on methods described in the WO 01/60378 incorporated here by reference. Sour oligosaccharide preferably made of highly pectin, which is characterized by a degree of methoxylation above 50%. As applied here, «the degree of methoxylation» (also referred to as the SE or «degree of esterification») is designed to determine the extent to which free groups of carboxylic acids contained in the chain acids are (for example, by methylation). Sour oligosaccharides preferably characterised by the degree of methoxylation above 20%, preferably above 50%, even more preferably above 70%. Preferably, sour oligosaccharides have the level of methylation above 20%, preferably above 50%, even more preferably above 70%. Sour oligosaccharides preferably applied in the amount from 10 mg to 100 g per day, preferably from 100 mg to 50 grams per day, even more preferably from 0.5 to 20 grams per day.

In accordance with another preferred embodiment of the invention, neutral oligosaccharide selected from the group consisting of , , not digested dextrins galactooligosaccharides production (including ), , , , , , and their mixtures. Most preferred, neutral oligosaccharide selected from the group consisting of , galactooligosaccharides production and .

Suitable oligosaccharides and methods of their production advanced described in the book Laere K.J.M. (Laere, K.J.M., Degradation of structurally different non-digestible oligosaccharides by intestinal bacteria: glycosylhydrolases of Bi. adolescentis. PhD-thesis (2000), Wageningen Agricultural University, Wageningen, The Netherlands), the full contents of which are hereby included by reference. TRANS- (CBT), for example, come under the trade mark Vivinal™ (Borculo Domo Ingredients, the Netherlands). dextrin, which can be done by means of pyrolysis corn starch, contains alpha(1 g 4), and C(1 g 6) links that are present in native starch, and also contains 1 g 2 and 1 g 3 communications and . Due to these structural properties, dextrin contains well defined, branched particles, which partially hydrolyzed by digestive enzymes person. Numerous other commercial sources not digested oligosaccharides easily accessible and well known to specialists in the field of technology. For example, comes Yakult Honsha Co., Tokyo, Japan. Soy oligosaccharide comes Calpis Corporation extends Ajinomoto U.S.A. hie., Teaneck, New York.

In another preferred embodiment of the composition according to the invention, contains sour oligosaccharide with SP 2 to 250 prepared with pectin, alginate, and their mixtures; and neutral oligosaccharide, selected from the group consisting , fructo-oligosaccharides, dextrins, , including , , , , , fructo-oligosaccharides, and their mixtures.

In another preferred embodiment of the composition according to the invention, contains two chemically different neutral oligosaccharide. It was established that the application of acidic oligosaccharides, United with two chemically different neutral , provides optimal synergy effect.

Preferably, the composition according to the invention, contains:

- sour oligosaccharides, as defined above;

- neutral oligosaccharide on the basis of galactose (in which more than 50% of monosaccharide units are units), preferably selected from the group consisting of and ; and

- neutral oligosaccharide on the basis of fructose and/or glucose (in which more than 50% of monosaccharide units are fructose and/or glucose, preferably, units), preferably inulin, and/or , it is most preferable to long chain (with an average JV between 10 and 60).

The mixture of acid and neutral oligosaccharides preferably applied in the amount from 10 mg to 100 g per day, preferably from 100 mg to 25 g a day, even more preferably from 0.5 to 20 grams per day.

Nutritional composition

Nutritional composition represents a song that contains natural components, preferably located in a food source, which can be sold without prescription in the form of supplements, functional foods or food ingredients, i.e. without a prescription or a veterinarian. Nutritional composition can also be a health food product, intended for dietary control of a disease or condition at a mammal under the supervision of a doctor or a veterinarian.

Composition according to the invention may be in the form of a liquid, for example, drink, in semi-solid form, such as yogurt or custard base, in the form of gel for example, jelly-like cakes, or in solid form, for example, chocolate bars and ice cream.

In one incarnation liquid composition made of concentrate, for example, from a liquid (for example, with a viscosity of less than approximately 80 MPa·s), semi-liquid concentrate (for example, more viscous than about 80 MPa·s and less about 400 MPa·s), gel or solid substance. With this preparation, you can use water to dilute the concentrate. In particular, such a preparation is carried out directly before applying compositions, for example, as for instant product.

One private embodiment of the invention is a nutrient composition containing protein material, lipid, and digestible carbohydrate, where:

a) the content of protein of the material provides 18 to 60 EN.%, in particular, from 18 to 50 EN.%, preferably from 20 to 40 EN.%, more preferably from 22 to 32 EN.% from the composition of the protein material contains serum;

b) the content of lipids provides 10 to 50 EN.%, preferably from 20 to 40 EN.%, more preferably between 25 and 35 EN.% from the entire composition;

The total energy value of liquid composition in accordance with the invention can be selected widely, for example, from 0.2 to 4 kcal/ml Usually it is at least a 0.3 kcal/ml, in particular, of at least 0.8 kcal/ml, more specifically, at least 1,2 kcal/ml Usually it is 3.0 kcal/ml or less, in particular, to 2.6 kcal/ml or less, more specifically, 2,4 kcal/ml or less. In the private incarnation, the lipid composition in accordance with the invention has the energy value in the range from 0.3 to 3.0 kcal/ml, preferably from 0.8 to 2.6 kcal/ml, preferably from 1.2 to 2.4 kcal/ml

In other private incarnation, the lipid composition in accordance with the invention has the energy value in the range from 0.2 to 1.0 kcal/ml, preferably from 0.4 to 0.9 kcal/ml

Factors that play a role in determining the necessary energy values are, on the one hand, simplicity is the achievement of high-value EN.% protein material, and on the other hand, rapid emptying of the stomach (increase anabolic response).

The total energy value of semi-liquid, gel or solid compositions in accordance with the invention can be selected in a wide range, e.g. from 1 to 15 kcal/. it is at least a 2.0 kcal/g, preferably, at least 2.8 kcal/g, even more preferably, at least 3.2 kcal/year Usually it is 12 kcal/g or less, preferably 10 kcal/g or less, or more preferably, 8,0 kcal/g or less. In the private incarnation semi-liquid, gel or solid composition according to the invention has the energy value in the range from 3.2 to 8.0 kcal/year

Additional components

In one incarnation of the composition may contain one or several additional components, such as at least one component selected from the group consisting of minerals, microelements and vitamins, preferably selected from the group consisting of sodium, potassium, chloride, fluoride iodide, calcium, phosphorus, magnesium, vitamin A, vitamin D3, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, folic acid, vitamin B12, Biotin, vitamin C, lipoic acid, zinc, iron, copper, manganese, molybdenum, selenium, and chromium.

Such components may be present in concentrations up to the recommended daily dose on a daily portion.

Zinc preferably present in the composition in a concentration of at least 2.8 mg / 100 kcal carbohydrates, preferably from 5.6 to 20 mg / 100 kcal carbohydrates, even more preferably 6-15 mg / 100 kcal carbohydrates.

Slow release of the drug for

In a preferred embodiment, the composition according to the invention further includes the drug for the slow release, effective for the release of amino acid in the duodenum and/or iliac intestine, where specified product contains at least one component selected from the group consisting of the amino acids in the form of free acid, amino acids in the form of salts and amino acids in the form of the conjugate with connection other than protein, where conjugate can be converted into free amino acid (or salt) and connection under the influence component of bile and/or pancreatic juice in the duodenum and/or jejunum.

Amino acid in the form with the slow-release preferably in liquid, semi-liquid or solid product.

A drug with a slow release may be prepared using conventional methods. Amino acid(s) can be covered with the material sensitive to pH, dissolves at pH characteristic of the duodenum/ileum (approximately pH 7), but not in the stomach (strongly acidic). Such membranes are well known in the art. Examples molecules are the molecules that make up certain peptides with amino acids, which don't split pepsin, or at least ineffective split under physiological conditions. Examples are choline, betaine, dimethylglycine and . Other suitable conjugating molecules include phospholipids, and glycerin.

Amino acids, preferably present in a preparation with a slow release, preferably chosen from leucine and other essential amino acids, in particular, methionine, lysine, tryptophan, phenylalanine and lysine, of which the most preferable is the lysine.

The preferred composition according to the invention applied according to the scheme of medical treatment. In particular, the composition can be used as adjuvant treatment for drugs, such as medicine, selected from the group consisting of anticancer agents, antiretroviral drugs, antigipertenziveh funds antitromboticheskih funds, antidepressants and antidiabetics funds. In particular, it is preferable to apply the product with Metformin or other anti-diabetic agent. These medicines in particular are considered to be stable in composition according to the invention and very effective. Specified medicine may be present in the composition according to the invention or used separately.

Next invention relates to a method of improving muscle function mammal, including the use of nutritional composition containing at least 18 EN.% protein material with the content of leucine at least 95% of mass on the basis of just protein material, the lipid fraction, containing at least one V-3-polyunsaturated fatty acids, selected from a group of eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), acid (ETK) and acid (KDP).

Composition according to the invention can be used under the supervision of a medical specialist, or apply yourself.

The composition can be used or enterally administered orally.

Mammal preferably a person.

The invention further illustrated in the following examples.

Description of drawings

Figure 1: Differences in A) the mass of the anterior tibial muscle and) mass fat in different groups

Con = click fed A control diet (AIN93), TV con = mouse- fed the control diet (AIN93), hpr = high protein, leu = leucine, fo = fish oil. Data are presented as mean + values SOS (standard error of the mean): * denotes difference from TB-con (p<0.02) (k=5,?=10%) (For more information about the statistics see Materials and methods).

Figure 2: the Function of skeletal muscle: the curve of the distribution of power (ex-vivo).

CON = click receiving the control diet, TB-CON = mouse- receiving the control diet, TB-SNC = mouse- treated with specific nutritional combination. Data are presented as mean + values SOS; data differ significantly from TB-CON at p<0.05 (k=2,?=10%).

A: the Maximum force reduction (total curves differ considerably from each other, p<0.01).

Century Maximum rate of reduction (total curves differ considerably from each other, p<0.01).

. speed relaxation (total curves differ considerably from each other, p<0.01).

D. CT90: the time required for a reduction from 10% to 90% of the maximum force (CON significantly different from TB-CON in the range 83-176 Hz; TB-SNC significantly different from TB-CON in the range 83-100 Hz).

Figure 3. The function of skeletal muscle load (ex vivo).

CON = click receiving the control diet, TB-CON = mouse- receiving the control diet, TB-SNC = mouse- receiving specific nutrient combination. Data are presented as mean + values SOS; data differ significantly from TB-CON at p<0.05, k=2,?=10%).

A: the Maximum force reductions (both curves differ significantly from TB-CON to repeat 70).

In: the Maximum force reduction, adjusted for muscle mass (CON significantly different from TB-CON for redo 30-50; TB-SNC does not differ significantly from TB-CON).

With: Maximum rate of reduction (both curves differ significantly from TB-CON to repeat 70).

D: Maximum rate of reduction, adjusted for muscle mass (CON significantly different from TB-CON for the first 30 repetitions (except repeat 5 (p=0.06)); TB-SNC significantly different from TB-CON for the first 10 repetitions).

Figure 4. Total daily activity.

A: the Total daily activity as % of daily activity for 2 nights for all groups. The essential relationship of time and the group (P<0.01).

In: the Total activity in the dark as % of daily activity for 2 nights for all groups.

With: the Total activity in the daytime as % of daily activity for 2 nights for all groups.

A: * P<0.05 compared with the TB-CON

D: Actogram representing the daily activity during the light period from 7 to 19 h (shaded Belm region) and in the dark age from 19 to 7 h (shaded in grey) on 1-19 day (vertical) for all groups separately.

Figure 5. The synthesis of muscle protein in patients with colorectal cancer.

Synthesis expressed as a fractional rate of the synthesis of patients suffering from colorectal cancer IV stage of receiving either a specific nutrient combination (SNC), control food Supplement. The factional synthesis rate was measured at baseline (baseline) and after taking the supplements.

Figure 6. Levels of plasma glucose in patients receiving specific nutrient combination (SNC) or control product.

Example 1

Materials and methods

The animals. Male mice CD2F1 at the age of 6-7 weeks (BALB/c x DBA/2, Harlan/Charles River, the Netherlands) were placed in individual cages in a room with controlled climate (the cycle of darkness: light 12:12 at a constant room temperature of 21±1 C). After acclimatization within one week mice were divided into three groups, mass: (1) control, gets the control diet; (2) mice-, fed the control diet, and (3) mice- treated with an experimental diet. Data shown is derived from a combination of several series of experiments with the same characteristics of animals and experimental procedures (if not specified otherwise)and differ only in the application of experimental diets. All procedures of the experiment were approved by the Ethics Committee on laboratory animals (Council of the Department of environmental protection, Bilthoven, Netherlands) and comply with the principles of good laboratory practice when working with animals.

Experimental diets (categories A and experiments). Experiments divided on: (A) the experiments are designed to analyze the effect of individual nutrients or combinations (adding a high amount of protein (hpr), leucine (leu), fish oil (fo)), to the basic ration (AIN93-M) and feed in the form of pellets; (C) the experiments are designed to analyze the effect of the complex of the nutrient combination like a song from Table 3, and includes all of the individual components analyzed in the experiment (A)and characterized by composition from AIN-93 to achieve a more humanised the diet of the Western type, provided in the form of a test-for technical reasons for the product.

The control diet AIN93-M of category A containing, per kg of food: 126 grams of protein (100% casein), 727 g of carbohydrate and 40 grams of fat (100% soy oil) (Research Diet Services, Wijk bij , the Netherlands). Experimental rations in this category down to the control diet through partial substitution of carbohydrates and/or soybean oil protein and leucine (151 g casein/kg and 16 g litzina/kg of food; TB+hpr+leu), high quantities of protein and fish oil (151 g casein and 22 grams of fish oil/kg of food; TB+hpr+fo), or high quantities of protein and fish oil (151 g casein/kg, 15 g litzina/kg and 22 grams of fish oil/kg of food; TB+hpr+leu+fo). 22 grams of fish oil containing 6,9 g EPA and 31 g DHA, provided the ratio of 2.2:1.

In the experiment category In the control diet was and compared with a control diet in experiments category A, and contained, kg feed 126 g of proteins (casein), 53 grams of fat (corn oil), and 699 grams of carbohydrates. experimental diet (hereinafter referred to as the Specific nutrient composition; SNC) contained kg feed: 210 grams of protein (189 g intact protein from which 68% casein and 32% serum and 21 grams free leucine), 53 grams of fat (20,1 g corn oil, 10.2 g canola oil, and 22.2 g fish oil), 561 g carbohydrates, 18 g and 2 g .

Tumor model. Cells With-26 adenocarcinoma click cultured in vitro in the environment RPMI 1640 with the addition of 5% fetal calf serum and 1% of penicillin-streptomycin. Tumor cells in condition and after washing suspended in a balanced salt solution without serum (HBSS) at concentration of 2.5 x 10 6 cells/ml Under General anesthesia (N 2/2 ), tumor cells (5 x 10 5 cells in 0.2 ml) administered subcutaneously administered to mice in the crotch area on the right side. Animals in the control group (C) have introduced imitating the solution of 0.2 ml HBSS.

Protocol of the experiment. After tumor cell inoculation or HBSS, evaluated the body weight, food consumption and tumor size (length and width) three times a week. Only in the experiment categories evaluated In the daily activity in the cells. In all experiments, the animals were anesthesia and weighed on the 20th day after tumor inoculation. Skeletal muscle (for example, the front muscle (TTA), the gastrocnemius muscle (mG), long extensor digitorum (mEDL) and muscle (mS), a tumor, a spleen, kidneys, liver, fat, thymus, heart and lungs were separated and weighed. The mass of the body base calculated by subtracting the tumor mass of body weight. In addition, the experiment categories analyzed In muscle function ex vivo.

Assessment of daily activity. Physical activity controlled permanently (24 hours) within the 20-day study period, starting from 2 days, with the use of sensors activity (dual technology sensor DUO 240, Visonic; adapted R. Visser, NIN, Amsterdam, the Netherlands), transforming the individual changes in the infrared mode, caused by the movements of animals, arbitrary indexes of activity. Sensors have been installed above the cells and were joined through the ports of entry and interface with a PC with software MED-IV PC for data collection (MED associates, St Albans, Vermont). Activity expressed in counts per hour for the entire 24-hour period, the dark period (active period) and light period (inactive period). Activity was calculated for each mouse individually and expressed relative to its total activity on a 2 day, for correction differences in the individual sensitivity of the sensors. Activity in the next two days to weaken variability on different days. To determine the mode of activity during the experiment, the hour-long activity and the activity in the dark/light expressed in percentage from the total daily activity and transformed in .

Statistics. All data were expressed as mean + values SOS (standard error of the mean). Statistical analysis was performed using SPSS 15.0 (SPSS Benelux, Gorinchem, the Netherlands). In the experiment And used different groups of animals, thus for all of the parameters was determined that the combination of data was if there was no interaction between the groups and experiments. Data on the composition of the body, tumor masses and authority on the 20th day was compared between the groups with the analysis of variations of variance (ANOVA) and the posterior minimum significant difference. A difference was considered significant if the value R below α/k; where a=10%, and k = the number of comparisons. For the experiment And the p-value must be lower than 0.02; for the experiment In a p-value should be lower than 0.05. Data on food consumption, body weight, daily activity, and muscle function, which controlled within 20 days after inoculation, analyzed the re-definition of ANOVA. For further differentiation of differences between groups were counting the difference, or Delta values from the first measurement in the whole range. These Delta values were compared between groups using ANOVA with minimum significant difference for pairwise comparisons between groups. For the function of skeletal muscles data of the first measurements on the 20th day did not match between the groups, so additional differentiation conducted point ANOVA analysis. Differences considered important in the bilateral p<0.05.

The influence of separate or combined components on the parameters of cachexia. Compared with control mice (Con), the mass of the body base and body weight were significantly lower in the control mice- (TV-con) on the 20th day after tumor inoculation (table 1A). For all the estimated parameters are not mentioned interaction between groups and experiment. The loss of weight of a body per-con mice occurred as a result of loss of fat mass (for example, fat and muscle mass (Figures 1A and 1B). No marked differences in food consumption between the groups on the full curves. When analyzing separately in the day, on the 20th day a group of Con significantly different from the per-con. Groups of mice- did not differ significantly from each other (table 1). Adding extra protein and leucine (TB+hpr+leu) or fish oil (TB+fo) did not change the body weight Compared with TV-con (table 1). However, adding fish oil to the additional protein (TB+hpr+fo) or fish oil to the additional protein and (TB+hpr+leu+fo) led to a significant increase in fat mass compared with TV-con (Figure 1). Dietary combination of all the components of the high amount of protein, leucine and fish oil (TB+hpr+leu+fo) led to a significant improvement in body weight and body base (table 1A), and muscle mass (TTA) and fat, compared with mice per-con (Figure 1). Additional effects of a combination of leucine and high protein content were established for muscle mass mTA in the presence of fish oil. Add each component gradually increased muscle mass (Figure 1A).

The influence of separate or combined nutrients the body composition and food consumption

Body mass, tumor and body base

Treatment

24,4±0,3

24,4±0,3

20,7±0,4

22,8±0,4

TB+hpr+leu

20,0±0,8

21,8±0,6

20,9±0,8

23,0±0,8

THEA-fo+hpr

22,2±0,8

34,2±0,7

TV+fo+hpr+leu

22,7±0,6

24,4 approximately 0.5

Consumption of food per day

Treatment

TV+hpf+leu

TB+fo+hpr

TB+fo+hpr+leu

Con = click fed A control diet (AIN93), TV con = mouse- fed the control diet (AIN93), hpr = high protein content, leu = leucine, fo = fish oil, CW = mass of the body base, BW = body weight and TW = mass of the tumor. Data are expressed as mean + values SOS: * = significant difference from TB-con (p<0.02, k=5,?=10%), for more information on statistics, see Materials and methods.

Parameters of cachexia in the result of application of a specific nutrient combination

The weight of the tumor and the foundations of the body during the autopsy (g-on the 20th day)

treatment

28,0±0,7

5,3 approximately 0.5

28,0±0,7

5,3 approximately 0.5

20,8 approximately 0.5

-0,7±0,4

18,7±0,4

-2,8±0,4

23,1±0,6

21.4 ħ 0,6

-0,7±0,7

The mass of bodies at autopsy) mg to 20 days)

treatment

, fat

44,5 ą 1.3

141 to + 4

9,2 about 1.1

6,7 approximately 0.5

33,4±0,9

108 + or-2

7.8 ħ 0,2

189 of + 20

38,1±0,9

118 to + / -3

8,3 approximately 0.5

The change in mass of the body over time

(Changes in body mass index (change in g: 0-20 compared to day 1 days)

treatment

5,5 ą1.0*

-0,1 approximately 0.5

with time

Consumption of food per day (g)

treatment

3,5 approximately 0.5

Con = click fed the control diet, TB-CON = mouse- fed the control diet, TB-SNC = mouse- treated with specific nutritional combination. BW = body weight; Delta-BW = BW-on the 20th day minus BW, 0 day, Delta-CW = CW on the 20th day minus CW 0 day, TW = mass of the tumor, the mTA = anterior tibial muscle, mG = calf muscle, mEDL=long extensor digitorum, mS = soleus. Data are expressed as mean + values SOS: * = significant difference from TB-CON (p<0.02, k=2,?=10%); # = statistically different from TB-CON for the full curve (p<0.05, k=2,?=10%). (For detailed information on statistics, see Materials and methods).

Muscle function ex-vivo (experiment category). Power-frequency (10-167 Hz, 250 MS) was measured ex vivo mEDL. Maximum strength, maximum speed reduction and maximum speed relaxation significantly differed in TB-CON compared to the CON and TB-SNC (Figures 2A, b and C). When these parameters were adjusted on muscle mass, General arrangement of curves remained. Significant differences, however, remained only between CON and TB-CON. For further study changes in muscle function, dependent on muscle mass, kept the time necessary to reduce (90). 90 32 defined as the time required for the development from 10% to 90% of the maximum force of contraction, at frequencies where is achieved .90 differed significantly between TB-SNC and TB-CON at lower frequencies where you can reach the full (83 and 100 Hz). These data suggest that at frequencies (83-100 Hz), suitable for effective physical activity (availability of ), in addition to the changes dependent on muscle mass, there are also changes, independent of the muscle mass that you can adjust the specific dietary intervention. Thus, tests with a load of 100 repeated pulses was performed using 83 Hz. Again, CON and TB-SNC differed significantly from TB-CON during the test load for maximum power reduction (Figure 3A) and maximum rate of reduction (Figure 3C). When the maximum corrected by a reduction in muscle mass (Figure 3B), the position of the curves remained, with the only significant difference between CON and TB-CON. The maximum rate of reduction in TB-SNC group, however, significantly different from TB-CON during the correction of the muscle mass in the first repetition load (<10 repetitions) (Figure 3D).

Physical activity (experiment category). Total daily activity showed a significant relationship between time and the group (P<0.01; RM-ANOVA) during the whole period (2-19 days). The level of activity of TB-CON mice was significantly lower than the control mice for 10-11 days (P<0.05), and from 16 day (P<0.01). Animals from the group of TB-SNC not differ significantly from the control animals in overall activity during the experiment, while their activity was significantly higher in the 18-19 day compared with the TB-CON mice (P<0.05) (Figure 4A). These differences in overall activity arose due to significant changes in their active period (i.e. dark period) (Figure 4). During the dark period TB-CON mice were significantly less active than control click on 16-17 and 18-19 day (0.01), that led to a drastic reduction of the total activity in mice TB-CON. Click TB-SNC were less active than control mice, during the dark period of the 18-19 day (P<0,05), but more active than the mouse TB-CON in these days (P<0,05).

In addition to reducing the level of daily activity of mice TB-CON, there was a substantial shift in the mode of daily activity, i.e. from the dark time to light, and in the control groups , and TB-SNC animals on 18-19 day (Figure 4C). To concentrate on the possible shift to the regime of daily activity, hours of activity per day (expressed as a percentage of the total (100%) of daily activity in specific day (figure 4D) (i.e. not belonging to 2 days and are not adjusted for the reduction of activity in groups ). At a basic level (2-3 day) all groups showed similar rhythms of day/night. The animals were active in the dark and had an inactive period in the light. Relative shift toward improving its activity during the light period was observed in TB-CON from the 16 days (as observed in less degree or was slow in TB-SNC group.

The discussion. In this study, a comparison of dietary intervention with individual and multiple components clearly supported the additional effect-pronged approach with specific nutrients on body composition in the mouse model carcinoma 26. In addition, specific nutrient combination also improves muscle function. Further, improved mode of activity, and the total daily activity, probably due to improvements in body composition and muscle function. These observations are important in clinical practice, since muscle function and daily activity contribute substantially to the quality of life of a cancer patient. Thus, these data are quite support the use of specific dietary support of cancer patients using a combination of many ingredients.

Data pay attention to the specific dietary needs of cancer patients to improve or prevent the signs of cachexia, and demonstrate the effects of different dietary interventions with selected ingredients or combination of nutrients in the mouse model 26 induced tumor cachexia. Observed no significant differences in food consumption between groups nor for the full curves, nor on analyses per day up to 10 days. These findings confirm previous observations that murine model 26 adenocarcinoma is not- model. However, the observation that in the experiment And food consumption in the group of Con significantly higher than that of TV mice on the 20th day, particularly specifies that if the tumor growth continues for several more days, the animals , probably, will develop anorexia. Differences in parameters between the control mice and mice- on the 20th day after tumor inoculation were comparable in amplitude to those described in other studies using mouse model 26 adenocarcinoma.

From individual components only fish oil raised a lot of fat. It was assumed that the mass of fat is important for the survival of the patient, while muscle mass unique contribution to the quality of life of the patient. Data on the muscle mass mTA showed that when analyzed concentration combination of all components, i.e. fish fat, high protein content and leucine need to have any material impact on muscle mass (Figure 1). These results are consistent with the hypothesis that in addition to enhancing the anabolic response, reduce protein catabolism through inflammation reduction to achieve a positive impact on a lot of muscle protein in a state of cachexia in cancer disease. Increasing evidence that an inflammatory response to the tumor makes a significant contribution to the development of cachexia. It is also assumed that the increase of catabolic processes compared with anabolic contributes to the inability to accumulation of lean body mass even when food intake is normal. Clinical data in the literature for different groups of patients suffering from cachexia, suggest that fish oil helps reduce catabolism and weight loss. Probably, fish oil are not only weakens the inflammatory response induced by the tumor, but also normalize insulin resistance is present in a state of cachexia. Increased survival noted in a mixed group of patients with advanced cancer at the use of V-3 fatty acids and vitamin E (Gogos, S.A., Ginopoulos, P., Salsa, Century, Apostolidou, E., Zoumbos, N. S., and Kalfarentzos, F. Cancer, 82: 395-402., 1998), which may also be caused by the immune modulation. Our data confirm the assumption that patients with cachexia fish oil can contribute to the conservation of body composition by reducing the inflammatory response. Consumption of high amount of protein with leucine (hpr+leu) did not result in substantial changes of the mass of the mTA. However, when added fish oil combination of high protein content and leucine (hpr+leu+fo) provided a significant addition of mass mTA. Thus, it is assumed that reduction of inflammatory condition using fish oil improves the sensitivity of animals to anabolic incentives, such as leucine and high quantity of protein, leading to improved conservation headlands muscle protein.

The results of in vivo studies suggest that and especially leucine regulate the metabolism of protein in muscle (Rooyackers, PU and Nair, .S. Annu Rev Nutr., 17: 457-485., 1997). This signal is connected with activation of mTOR pathway. It was reported that in healthy volunteers leucine provided the signal for the stimulation of muscle protein synthesis and perhaps reduced the destruction of muscle protein (Rennie, M.J., Bohe, J. Smith, K., Wackerhage, H., and Greenhaff, P.J Nutr., 136: 264S-268S., 2006). In healthy individuals this signal is probably a short-term due to the «phenomenon of full muscles»induced mechanisms of a normal dietary consumption and homeostatic control. On the contrary, long-term effects of additions marked in patients with metabolic or dietary deficiency, such as in patients with sepsis or oncological disease. It was noted that these groups of patients consumption leads to a positive impact on status, quality of life and overall survival. In addition, it was reported that protein synthesis can be promoted only in the presence of a large supply of a balance of essential amino acids (Rooyackers, PU and Nair, .S. Annu Rev Nutr., 17: 457-485., 1997). Together, these studies suggest that the combination of a high amount of protein and can provide improvement of the metabolism of protein, leading to increased muscle mass, which can contribute to the decrease in the manifestations of the disease and improve the quality of life. Our data suggest that consumption and leucine, and the high amount of protein contributes to the cumulative effect of maintaining muscle mass, achieved a total nutrient combination (Figure 1 and table 1).

To our surprise, a combination of additives with a high content of protein, leucine and fish oil provided additional effect against a broad spectrum of parameters characterizing cachexia. The group, which United all the nutritional components (click TB+hpr+leu+fo) was the only group showed a significant difference compared with the TV on all the analyzed parameters cachexia (for example, the mass of the body, the basics of body mass, muscle and fat (see Table 1)). Proposed additional effects of certain nutrients in the common combination is better illustrated by data on weight muscles (mTA Figure 1). These data clearly demonstrated the added effect of the approach with a variety of nutrients. We assume that the observable additional effects occur from possible differences in mechanistic purposes of these components, i.e. 1) stimulate anabolic signals by supplementing building blocks (amino acids) and by stimulation of mTOR (leucine), 2) reduce protein catabolism by reducing the inflammatory and hormonal responses (fish oil) and negative regulation of signaling pathway that leads to destruction protein (leucine), and possible interactions(s) between the two mechanisms. The second experiment confirmed the efficiency of nutrient combinations in relation to the preservation of body composition. In addition, in this experiment, a combination of ingredients has also improved parameters, which reflect physical activity, such as muscle function and mode of daily activity.

The mass of bodies (raw) of the kidneys, liver, intestines, thymus and heart is not changed or decreased with the development of cachexia. Nutritional support, leading to the increase of mass of the body base, does not compromise or partially stabilize the loss of mass of bodies. Further, none of the selected ingredients not raising the tumor mass. Full nutritional combination demonstrated reduction of tumors in the experiment Century

Fatigue, resulting from cancer cachexia, leads to a decrease in daily activity. Indeed, in the presence of tumors levels of daily activity of mice decreased over time, which is consistent with clinical reports about the cancer patients. It is unclear what mechanism induces a reduction in the activity of cancer patients. Decreased muscle mass and reduced muscle strength, can make a contribution in violation of the activity. In addition, the induced tumor inflammatory response may further reduce the daily activity. Physical activity is a major determinant of quality of life (Moses, A. W., Slater, C., Preston, So, Barber, M.D., and Fearon, K. C. Br J Cancer, 90: 996-1002, 2004). The full nutrient combination saves activity compared with mice TB-CON. This effect can be directly associated with improved preservation of physical activity (improvement of muscle mass and function). The impact of nutrient combination of other factors involved in physical activity, requires additional study.

Chevalier et al. reported that patients with advanced colon cancer, there is a decrease contrast between day and night activity (night) (Chevalier, V., Mormont, M.S., Cure, H, and Chollet, P. Oncol Rep, 10: 733-737, 2003.). It was assumed that the individual modes of activity are forward-looking in respect of survival, tumor response and quality of life of patients. The possibility of induced tumor violations of daily activity is confirmed by our data, indicating associated with tumor shift from the dark period of the day to light. Researched specific nutrient combination showed a clear tendency to reduce this effect. Normal sleep patients critically depends on the circadian release of melatonin from the pineal gland. It was noted that the DHA-enriched recipe normalize the secretion of melatonin from (V-3)-deficient rats (Zaouali-Ajina, M., Gharib, A., Durand, G., Gazzah, N., Claustrat, Century, Gharib, C., and Sarda, N. J Nutr, 129: 2074-2080, 1999); it may also explain the results obtained in our experiments.

Based on the results of this study clearly, we need to pay more attention to prevention of cachexia in order to preserve the quality of life of patients.

In conclusion, nourishing combination of high protein, leucine and fish oil improves the outcome of cachexia in mice inoculated cell line 26 adenocarcinoma. Not only increased the weight of the basics of body fat and muscle, but also improves muscle function and daily activity compared with mice- undergone a control diet. These data demonstrated that the addition of the individual ingredients are of limited value, and confirmed the need for a balanced combination of various ingredients to ensure-pronged approach to achieve the effect in difficult conditions of cancer cachexia.

Example 2: Examples of formulations.

Nutritional Supplement may in particular contain macro elements in the ranges specified in Table 3. A concrete example is shown in Table 4. In addition, there may be one or more micronutrients such as vitamins and minerals, etc) and/or one or more other additives food quality (for example, flavorings, preservatives, no- amino acids, such as carnitine).

Nutrient composition for fractional power (100 ml)

Protein material (equivalent) (g)

- whey protein

it leucine (g)

- including leucine in the form of free amino acids (g)

Carbohydrate (g)

- including unsaturated

- including omega-3 polyunsaturated fatty acids

- including EPA, DHA, Hetq, KDP

Soluble dietary fiber (g)

Nutrient composition for fractional power (100 ml)

Protein material (equivalent) (g)

- whey protein

it leucine (g)

- including leucine in the form of free amino acids (g)

Carbohydrate (g)

- including unsaturated

- including omega-3 polyunsaturated fatty acids

- including EPA, DHA, Hetq, KDP

Soluble dietary fiber (g)

Food for feeding through a tube may, in particular, contain macro elements in the ranges specified in Table 5. A concrete example is given in Table 6. In addition can be one or more micronutrients such as vitamins and minerals, etc) and/or one or more other additives food quality (for example, flavorings, preservatives).

Nutrient composition for feeding through a tube

Protein material (equivalent) (g)

- whey protein

it leucine (g)

- including leucine in the form of free amino acids (g)

Carbohydrate (g)

- including unsaturated

- including omega-3 polyunsaturated fatty acids

- including EPA, DHA, Hetq, KDP

Soluble dietary fiber (g)

The main ingredients of a specific composition according to the invention

Ingredients

Energy value

160 kcal /100 ml

Protein (27 EN.%)

10,1 g/100 ml, of which:

serum: 2.9 g/100 ml

-casein: 6,1 g/100 ml

- added leucine: 1.1 g/100 ml, which includes the following amino acids (on a mass basis of total protein):

L-leucine: 19,4%mass

L-glutamine/glutamic acid: 17,8%of mass

L-cysteine: 0,9%mass

Lysine: 7,5%of mass

Attitude Lei/(Shaft+Ile)=1,83

Carbohydrates (43 EN.%)

17,4 g/100 ml, of which:

- a mixture of sugars, including glucose, galactose, lactose, maltose, sucrose, and (12.7 g/100 ml)

- starch (4.3 g/100 ml)

Lipids (30 EN.%)

to 5.3 g/100 ml, of which:

-ALA (1.8 g/100 g of total lipids)

- EPA (11.9 g/100 g of total lipids)

- DHA (5.8 g/100 g of total lipids)

- WPC (1.4 g/100 g of total lipids)

- KFOR (1.8 g/100 g of total lipids)

- LUX (26,0 g/100 g of total lipids)

- AK (0.7 g/100 g of total lipids)

V-3/W-6=0,87

Dietary fiber

2 g/100 ml galactooligosaccharides production

L-carnitine

10.9 mg/100 ml

13.2 mg/100 ml

Viscosity

41 MPa·s

Example 3: Synthesis of muscle protein after the nutritional support of patients suffering from colorectal cancer.

Analyzed the ability of food for fractional consumption, containing specific nutrient combination described in Table 4, of the possible compositions, affect the rate of muscle protein synthesis, compared with the reference product, as described in Table 8.

The composition of additives

Specific nutrient combination (SNC) (100 ml)

Control (100 ml)

Carbohydrates

Carbohydrates

* SNC: 2.9 g of whey protein, 1.1 g litzina, balanced casein; in control only casein.

Design and methods

Subjects of research. Individuals involved in the study based on the criteria for inclusion/exclusion, described below. All individuals were able to spontaneous movement, could sit and stand on their own. Screening procedures were not carried out, because in the context of cancer treatment they have been done before the start of the study. In General, 24 subjects (12 per group) completed the study Protocol. Inclusion criteria were the following: (1) radiographic evidence of cancer, (2) age more than 40 years (men and women), (3) the ability to sign the Protocol of informed consent.

Overview of the study design. Conducted a randomized, controlled, double-blind study in parallel groups of patients with newly diagnosed metastatic colorectal cancer. With patients individually talked, and experimental procedures were explained, and received the signed Protocol of informed consent. After the adoption of the study subjects had food for 3 days before the experimental phase of the study for the standardization of food consumption. Food was prepared for use at home. In the evening before the study, patients should abstain from consumption of food and drinks (except water) from 22:00 hours and later. The experimental phase of the trial began the next morning and lasted about 10 hours. Twelve patients received food for fractional consumption, containing specific nutrient combination (SNC), and the other 12 patients consumed control additive (CS). Each subject was consuming 400 ml additives in two doses. Consumption of a second dose began twenty minutes later, after the consumption of the first dose power. Each dose consumed within 10 minutes. Subjects of arbitrarily distributed on the consumption of additives, separated by gender.

Experimental procedures. The morning of the research nurse placed two catheter 18-22 caliber in Vienna right and left arms, and one used for the sampling of blood, and the other for infusion indicator. After selection of the image of the blood to determine the level of background enrichment of amino acids and glucose fasting blood, conducted infuziu primary solution or «load» (2 mmol/kg) U-13C6-phenylalanine. Immediately after this was carried out continuous (of 0.07 mmol/kg/min infusion U-136-phenylalanine and supported during the experiment. Muscle biopsy spent 2 hours after the beginning of isotope infusion and again 5 hours later. Blood periodically taken from the catheter sampling on the forearm to determine the enrichment of amino acids (the relationship of matter to a substance in the plasma). Immediately after the second muscle biopsy gave one dose (200 ml), followed by the second dose (200 ml) after 20 minutes after the first use of the first dose. Each dose consumed within 10 minutes. Third muscle biopsy was performed after 300 minutes after the first use of the first dose supplements. Throughout the study, patients were lying in bed, except for visiting the bathroom. Muscle biopsy used to calculate the fraction of the speed of muscle protein synthesis (FSR). Plasma samples were analyzed for the enrichment of amino acids (the ratio of matter to designated substance in plasma), the concentration of glucose and amino acids.

Results. Base the synthesis of muscle protein was similar in the group of the SNC and the control group (in each n=12) of patients (see Figure 5). Consumption of 400 ml of a controlling power provided a fractional rate of synthesis similar to the basic rate of synthesis, while the consumption of a specific nutrient combinations in accordance with the invention (SNC) led to an increase in factional synthesis speed 1.4 from the base fractional synthesis speed.

Glucose concentrations decreased in patients treated with composition according to the invention (SNC) compared with patients who received the control additive (Figure 6). It was favourable, as the low glucose levels after consumption of food (in turn) lead to the improvement of the sensitivity of the muscle to anabolic signals (insulin).

Example 4. Definition of the glycemic index.

The definition. The glycemic index (GI) carbohydrate determines its ability to increase concentration of glucose after a meal. Products with a high value GUY provide higher blood glucose levels compared to products with a low GI. GI carbohydrate also predicts insulin response on this product.

GI carbohydrate count by assessing the glycemic response 2 hours after consumption 25 g of the product in comparison with the answer on 25 g standard glucose:

GUY is equivalent to «area under the curve response of blood glucose to the analyzed food product that contains 25 g of carbohydrate)), divided into «corresponding area after reception equivalent carbohydrate portions of glucose.

Methodology of determination of the glycemic index. When analyzing the GI available carbohydrate defined as: General carbohydrates minus carbohydrates (soluble and insoluble), which from a physiological point of view come from dietary fibers (for example, inulin, Foz, resistant starch 3 types).

Secured samples should be of a product is available in the trade for the consumer.

All the products are taken for analysis, tested in vivo, ie in 10 people who consumed amount of the product containing the equivalent of 25 g of available carbohydrates. These were healthy individuals, not suffered chronic diseases, diabetes, or abnormalities in glucose metabolism. BMI entities amounted to 18.5 to 27 kg/m 2 .

Control product supply: control food was powder, glucose, 25 g dissolved in 250 ml of water. Every individual analysis with the control food held at least twice.

Analyzed foods: analyzed food prepared in accordance with the manufacturer's instructions, introducing the food as it is commonly consumed. Analyzed food consumed once individually as a portion of providing 25 g of available carbohydrates, as defined above.

The subjects, according to the study Protocol: individuals tested in the morning on an empty stomach, after they not eaten 10-12 hours during the night. Selected two fasting blood sample (-5 and 0) with a difference in 5 minutes, after which the subjects consumed the analyzed or controlling food with equal speed within 15 minutes. Then selected samples of blood after 15, 30, 45, 60, 90 and 120 minutes after a meal. Analyzed and control products are consumed with 250 ml of drinking in a water. It remained constant for each analysis in the series.

24 hours prior to analysis GUY The day before each session, the subjects refrain from accepting alcohol and unusual level of physical activity and unusual level of reception of food. The subjects were administered in the evening foods rich in carbohydrates such as rice, pasta, bread, potatoes, and not too much fat. This food is not included beans or legumes products (to avoid the secondary effect of food on the following morning). It is important that they had dined, and do not abstain from food for 18 hours. The subjects were asked to maintain this state every time they would come to the session. After they ate dinner, entities do not consume food for 10 hours during the night before a test the next morning. During the period of abstinence from food they could only drink water.

Sampling of blood: the Blood was obtained by pricking a finger. Blood was collected without inhibitors of coagulation (heparin, EDTA). Analysis of glucose: defining the whole capillary blood or was measured using an automatic analyser glucose. In this case, used analyzers Hemocue glucose.

Data analysis: an Incremental area under the curve response of glucose (iAUC), not taking into account the size under the baseline, geometrically calculated as follows:

For the time t0, t1...tn concentration of glucose in the blood amounted G0, G1, ... Gn, respectively.

where Ax=AUC for the time interval x (i.e. between the tx-1 and tx).

For the first time interval (i.e. x=1): if G1>G0, A1=(G1 G0)x(t1-t0)/2; otherwise, A1=0

For other time intervals (i.e., x>1)

if Gx & GE G0 and Gx-1 & GE G0, Ax={[(Gx-G0)/2]+(Gx-1-G0)/2}x(tx-tx-1)

if Gx>G0 and Gx-1<G0, Ax=[(Gx-G0) 2 /(Gx Gx-1)]x(tx-tx-1)/2

if Gx<G0 and Gx-1>G0, Ax=[(Gx-1-G0) 2 /(Gx-1-Gx)]x(tx-tx-1)/2

if Gx≤G0 and Gx-with 1 < G0, Ax=0

Calculations GI among separate individuals the GI value is iAUC for each food product, expressed in percentage from the average value iAUC for two control products (glucose). GUY analyzed product is the average GUY±SOS from 10 individuals. From a dataset, you can exclude up to two values (for individuals whose GI differed from the mean by more than two standard deviation). SOS should be within 20% of the average.

A series of clinical trials 1: healthy volunteers.

Ten healthy volunteers with a value of BMI 18.5 to 27 kg/m was tested after a period of fasting for 10-12 hours. Each individual analyzed using a crossover design study, upon receipt of 25 g of carbohydrates from the standard drink with glucose (2 times), the standard fractional power (16 EN.% protein, 50 EN.% carbohydrates and 34 EN.% fat) or an experienced drink in accordance with the invention (the GI value for SNC counted in the form of incremental area under the curve response of blood glucose for each food product (iAUC) as a percent of the mean value iAUC controlling drinking from glucose.

Results. GI for standard fractional power amounted to 67±10, while the GUY for an experienced drink was 40 to + 4. Thus, GUY for Forticare was classified as low (<55), and to the standard of a fractional power as the average (55-70).

A series of clinical trials 2: oncological patients:

As described in Example 3, glucose concentrations decreased in patients treated with specific nutritional combination SNC, compared with patients who received the control additive (Example 3, Figure 5).

1. The combination of whey protein, leucine, and at least V-3 polyunsaturated fatty acid selected from the group: eicosapentaenoic acid, docosahexaenoic acid, acid and acid, to improve muscle function at a mammal, where the combination is included in the nutritional composition having glycemic index below 55.

2. The combination of claim 1 in which the muscular function is a function of the skeletal muscles.

3. The combination of claim 2, in which improve the function of the skeletal muscles includes the weakening of the loss of muscle function depending on muscle mass, specifically includes correction dependent on muscle mass, maximum strength, maximum speed reduction or maximum speed of relaxation skeletal muscles.

4. The combination of claim 2, in which improve the function of the skeletal muscles includes the weakening of the loss of muscle function, not dependent on muscle mass, in particular includes adjustment of the maximum force, adjusted on muscle mass, maximum speed reduction, adjusted on muscle mass, or the maximum speed of relaxation, adjusted for muscle mass.

5. The combination of claim 1 in which improvements in muscle function is directed to the prevention or treatment of muscle function, conditional or developing due to aging, disease, disorder, medication or injury, preferably of drugs, disease or disorder.

6. The combination of claim 5, in which disease or disorder is selected from the group consisting of oncological disease, HIV infection, chronic obstructive pulmonary disease, renal failure, heart failure, and a pathological condition characterized by high levels of proinflammatory cytokines in plasma and/or serum, preferably an oncological disease.

7. Combination of 6, where oncological disease the patient is undergoing chemotherapy is a cancer patients.

8. Combination in paragraph 7, where in the chemotherapy used the drug.

9. The combination of claim 1, which is a liquid that contains at least 7 g/100 ml protein material, preferably at least 8 g/100 ml, more preferably at least 9 g/100 ml, most preferably at least 10 g/100 ml

10. The combination of claim 9, protein material contains at least one protein source of protein, selected from the group consisting of casein, Caseinate, soy and wheat, preferably casein.

11. The combination of claim 9, in which the protein material contains at least 15 wt.%, preferably at least 25 wt.% whey proteins, calculated on the whole protein material.

12. The combination of claim 9, containing 12 to 23 wt.% leucine, in terms of whole protein material.

13. The combination of claim 9, containing from 16 to 28% by weight glutamine, preferably from 17 to 26% in terms of whole protein material.

14. The combination of claim 9, containing at least 0,7% Mas. one or more of the group consisting of cystine, cysteine and equivalents cysteine, preferably from 0.8 to 8 wt.% in terms of whole protein material.

15. The combination of claim 1, containing at least one substance, selected from a group of carnitine and taurine.

16. The combination of claim 1, containing at least 15 wt.% V-3 polyunsaturated fatty acid.

19. Combination of clause 17, in which the content carbohydrate is from 1 to 15 wt.% preferably from 2 to 12% more preferably from 3 to 10 wt.% in terms of dry substance.

20. The combination of claim 1, further comprising a protein material, lipid, and digestible carbohydrate, where: a) the content of protein of the material provides 18 to 60 EN.%, preferably from 20 to 40 EN.%, more preferably from 22 to 32 EN.% from the total composition of the protein material contains whey protein; (b) the content of lipid fraction provides 10 to EN 50.%, preferably from 20 to 40 EN.%, more preferably between 25 and 35 EN.% of all faculty; (c) the content of digestible carbohydrate provides 20 to 70 EN.%, preferably from 30 to 60 EN.%, more preferably from 38 to 48 EN.% of all faculty.

21. Nutritional composition to improve muscle function in mammalian containing a combination of claim 1, comprising: (a) at least 18 EN.% protein material, the protein material contains whey protein; (b) at least 12 wt.% leucine to mass of total protein material; and (c) the lipid fraction, containing at least the V-3 polyunsaturated fatty acids, selected from a group of eicosapentaenoic acid, docosahexaenoic acid, acid and acid.

22. Nutritional composition of item 21, in which muscle function is a function of the skeletal muscles.

23. Nutritional composition according to article 22, which improve the function of the skeletal muscles includes the weakening of the loss of muscle function depending on muscle mass, specifically includes correction dependent on muscle mass, maximum strength, maximum speed reduction or maximum speed of relaxation skeletal muscles.

24. Nutritional composition according to article 22, which improve the function of the skeletal muscles includes the weakening of the loss of muscle function, not dependent on muscle mass, in particular includes adjustment of the maximum force, adjusted on muscle mass, maximum speed reduction, adjusted on muscle mass, or the maximum speed of relaxation, adjusted for muscle mass.

25. Nutritional composition on any of .21-24, in which improvements in muscle function is directed to the prevention or treatment of muscle function, conditional or developing due to aging, disease, disorder, medication or injury, preferably of drugs, disease or disorder.

26. Nutritional composition according to section 25, in which disease or disorder is selected from the group consisting of oncological disease, HIV infection, chronic obstructive pulmonary disease, renal failure, heart failure, and a pathological condition characterized by high levels of proinflammatory cytokines in plasma and/or serum, preferably an oncological disease.

27. Nutritional composition of .26, where oncological disease the patient is undergoing chemotherapy is a cancer patients.

28. Nutritional composition according to item 27, where in the chemotherapy used the drug.

29. Nutritional composition of item 21, which is a liquid that contains at least 7 g/100 ml protein material, preferably at least 8 g/100 ml, more preferably at least 9 g/100 ml, most preferably at least 10 g/100 ml

30. Nutritional composition of item 21 or 29, in which the protein material additionally contains at least one protein source of protein, selected from the group consisting of casein, Caseinate, soy and wheat, preferably casein.

31. Nutritional composition of item 21 or 29, in which the protein material contains at least 15 wt.%, preferably at least 25 wt.% whey proteins, calculated on the whole protein material.

32. Nutritional composition of item 21 or 29 containing 12 to 23 wt.% leucine, in terms of whole protein material.

33. Nutritional composition of item 21 or 29 containing 16 to 28% by weight glutamine, preferably from 17 to 26% in terms of whole protein material.

34. Nutritional composition of item 21 or 29, containing at least 0,7% Mas. one or more of the group consisting of cystine, cysteine and equivalents cysteine, preferably from 0.8 to 8 wt.% in terms of whole protein material.

35. Nutritional composition of item 21 or 29, containing at least one substance, selected from a group of carnitine and taurine.

36. Nutritional composition of item 21 or 29, containing at least 15 wt.% V-3 polyunsaturated fatty acid to the mass of the lipid fraction.

37. Nutritional composition of item 21 or 29, additionally contains carbohydrate selected from the group galactooligosaccharides production and , preferably from a mixture of galactooligosaccharides production and with molar ratio galactooligosaccharides production to in the range from 1:1 to 20:1, preferably from 5:1 to 12:1, and it is most preferable, approximately equal to 9:1.

38. Nutritional composition of clause 37, in which carbohydrate selected from a group of with degree of polymerization (DP) from 2 to 50, with SP 2 to 60, oligomers containing more than 30% by weight components of galacturonic acid and glucuronic acid with a molecular weight of 520 to 2200 Yes, and any combination of these.

39. Nutritional composition of clause 37, in which the content carbohydrate is from 1 to 15 wt.% preferably from 2 to 12% more preferably from 3 to 10 wt.% in terms of dry substance.

40. Nutritional composition item 21, containing protein material, the lipid fraction and advanced digestible carbohydrate, in which: a) the content of protein of the material provides 18 to 60 EN.%, preferably from 20 to 40 EN.%, more preferably from 22 to 32 EN.% from the total composition of the protein material contains whey protein; (b) the content of lipid fraction provides 10 to 50 EN.%, preferably from 20 to 40 EN.%, more preferably between 25 and 35 EN.% of all faculty; (c) the content of digestible carbohydrate provides 20 to 70 EN.%, preferably from 30 to 60 EN.%, more preferably from 38 to 48 EN.% of all faculty.

41. Applying a combination of any one of claims 1 to 20 or nutritional composition on any of .21-40 to improve physical and improvement of daily activity.

42. Applying a combination of any one of claims 1 to 20 or nutritional composition on any of .21-40 to improve compliance cancer treatment, ensuring a better forecast from the point of view of increasing life expectancy and improving the quality of life.