Nutritional Composition for Improving the Mammalian Immune System

Abstract

The invention relates to a nutritional composition comprising (a) at least 18 en % of proteinaceous matter; (b) at least 12 wt % of leucine, based on total proteinaceous matter; (c) a lipid fraction comprising at least a ω-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid and docosapentaenoic acid; (d) an immune modulator; for improving the immune function in a mammal, preferably a human.

1 . Nutritional composition comprising
 (a) at least 18 en % of proteinaceous matter;   (b) at least 12 wt % of leucine, based on total proteinaceous matter;   (c) a lipid fraction comprising at least a ω-3 polyunsaturated fatty acid being eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid or docosapentaenoic acid;   (d) an immune modulator;   
       for use in the improvement of the immune function in a mammal suffering from cancer. 
     
     
         2 . Nutritional composition according to  claim 1 , wherein improving the immune function comprises at least one of the following effects:
 improving a Th1-mediated immune response;   increasing the activity or number of natural killer (NK) cells;   increasing pathogen-specific or tumour-specific IgA, IgG or IgM antibody production;   increasing IgA, IgG or IgM concentrations to normal range values in the blood of mammals with sub-normal levels of said antibodies;   increasing the total number of white blood cells in mammals with treatment- or disease-induced decreased number of white blood cells;   increasing the number or activity of phagocytic cells in mammals with treatment- or disease-induced decreased number of phagocytic cells;   improving cell-mediated cytotoxic responses against pathogens, pathogen-infected cells or tumour cells;   improving the barrier function of mucosal epithelia by increasing sIgA excretion, increasing intestinal mucus production, decreasing epithelial permeability or decreasing microbial translocation across the epithelia with the exception of non-infectious uptake of microbes by local immune cells;   improving the composition of the intestinal microbiota by increasing the number or activity of beneficial bacteria such as bifidobacteria or lactobacilli, by improving the colonization resistance of the intestinal microbiota, by decreasing the number of potential pathogenic organisms in the intestinal microbiota, or by decreasing the pH of the intestinal content; or   mounting effective immune responses against cancer cells, either as a primary treatment or as an adjuvant treatment to eradicate residual cancer cells.   
     
     
         4 . Nutritional composition according to  claim 1 , wherein improving the immune function in said mammal comprises treatment of neutropenia. 
     
     
         5 . Nutritional composition according to  claim 1 , wherein said mammal suffers from a reduced immune function due to or resulting from cancer, the reduced immune function manifesting itself as a symptom being infections, inflammations, vascular complications, bad wound healing, mucositis or stomatitis. 
     
     
         6 . Nutritional composition according to  claim 1 , wherein the composition for use in the improvement of the immune function is for a treatment of a reduced immune function, due to or resulting from trauma, wherein the trauma being surgery, drug treatment, chemotherapy or radiotherapy. 
     
     
         7 . Nutritional composition according to  claim 1 , for enhancing the effectiveness of an immunotherapy in mammals receiving an anti-cancer immunotherapy or planning to start anti-cancer immunotherapy within a period of two months. 
     
     
         8 . Nutritional composition according to  claim 1 , wherein the immune modulator being immune system modulating indigestible carbohydrates, lactoferrin, glycine, immune system modulating drugs, or immune system modulating bacteria or fragments thereof. 
     
     
         9 . Nutritional composition according to  claim 8 , wherein the immune modulator is an indigestible carbohydrate selected from the group of galactomannans having a degree of polymerisation (DP) between 2 and 50, xylans having a DP of 2 to 60, oligomers having more than 30 wt % of galacturonic acid or glucuronic acid moieties having a molecular weight of 520-2200 Dalton, galactooligosaccharides, fructooligosaccharides, and any combination thereof;
 or wherein the immune modulator is an immune system modulating drug selected from the group of
 Growth factors suitable for preventing or treating neutropenia (granulocytopenia) or treatment-related dysfunction of the immune system in cancer patients, in particular 1) granulocyte-colony stimulating factor and derivatives thereof, such as Filgrastim, Neupogen, Pegfilgrastim and Neulasta, 2) granulocyte macrophage-colony stimulating factor, such as Sargramostim, Leukine and Molgramostim, and 3) stem cell factor, such as Ancestim and StemGem; or wherein the immune modulator is selected from the group of 
 Antibiotics suitable for preventing or treating infections in cancer patients with neutropenia or anti-cancer treatments that render them susceptible to infections; or wherein the immune modulator is selected from the group of of immune system modulating probiotic bacteria, immune system modulating bacterial fragments, immune system modulating CpG oligonucleotides and immune system modulating heat-shock proteins. 
   
     
     
         10 . A liquid nutritional composition according to  claim 1 , comprising at least 7 g/100 ml of proteinaceous matter. 
     
     
         11 . Nutritional composition according to  claim 1 , wherein the proteinaceous matter comprises at least 15 wt % of whey protein. 
     
     
         12 . Nutritional composition according to  claim 1 , comprising 12 to 23 wt % of leucine, based on total proteinaceous matter. 
     
     
         13 . Nutritional composition according to  claim 1 , comprising 4 to 20 wt % of glutamine, based on total proteinaceous matter. 
     
     
         14 . Nutritional composition according to  claim 1 , comprising at least 0.7 wt % of cystine, cysteine or cysteine equivalents, based on total proteinaceous matter. 
     
     
         15 . Nutritional composition according to  claim 1 , comprising at least 15 wt % of an ω-3 polyunsaturated fatty acid, based on total lipid content. 
     
     
         16 . Nutritional composition according to  claim 1 , wherein the lipid fraction further comprises at least one ω-6 polyunsaturated fatty acid, and wherein the molar ratio of ω-3 polyunsaturated fatty acids to ω-6 polyunsaturated fatty acids is less than 1.0. 
     
     
         17 . Nutritional composition according to  claim 1 , comprising proteinaceous matter, a lipid, and a digestible carbohydrate, wherein
 a) the proteinaceous matter content provides 18 to 50 en % of the total composition;   b) the lipid content provides 10 to 50 en % of the total composition;   c) the digestible carbohydrate content provides 20 to 70 en % of the total composition.   
     
     
         18 . Nutritional composition comprising
 (a) at least 18 en % of proteinaceous matter, wherein the proteinaceous matter comprises 10-50 wt. % whey protein based on total proteinaceous matter;   (b) at least 12 wt % of leucine, based on total proteinaceous matter;   (c) at least 15 wt. % ω-3 polyunsaturated fatty acid being eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid or docosapentaenoic acid, based on total lipid content;   (d) an immune modulator being galactooligosaccharides or fructooligosaccharides;   
       wherein the total indigestible carbohydrate content amounts to 1-15 wt. % based on total dry matter. 
     
     
         19 . The method of  claim 4  wherein the neutropenia is chemotherapy-induced neutropenia. 
     
     
         20 . The liquid nutritional composition of  claim 1 , comprising at least 8 g/100 ml of proteinaceous matter. 
     
     
         21 . The liquid nutritional composition of  claim 1 , comprising at least 9 g/100 ml of proteinaceous matter. 
     
     
         22 . The liquid nutritional composition of  claim 1 , comprising at least 10 g/100 ml of proteinaceous matter. 
     
     
         23 . Nutritional composition according to  claim 1 , comprising 5 to 10 wt % glutamine, based on total proteinaceous matter. 
     
     
         24 . Nutritional composition according to  claim 1 , comprising 0.8 to 8 wt % of cystine, cysteine or cysteine equivalents, based on total proteinaceous matter. 
     
     
         25 . Nutritional composition according to  claim 1 , wherein the lipid fraction further comprises at least one ω-6 polyunsaturated fatty acid, and wherein the molar ratio of ω-3 polyunsaturated fatty acids to ω-6 polyunsaturated fatty acids is from 0.5 to 0.97. 
     
     
         26 . Nutritional composition according to  claim 1 , wherein the lipid fraction further comprises at least one ω-6 polyunsaturated fatty acid, and wherein the molar ratio of ω-3 polyunsaturated fatty acids to ω-6 polyunsaturated fatty acids is from 0.6 to 0.95.