NUTRITIONAL COMPOSITION, USE OF A NUTRITIONAL COMPOSITION AND PROCESS FOR THE MANUFACTURE OF A NUTRI

专利摘要:
nutritional composition, use of a nutritional composition, process for the manufacture of a nutritional composition, and product. the invention relates to the use of a lipid component specifically designed with an ideal fatty acid profile, an improved portion of the palmitic acid residues in the sn-2 position and present as lipid globules with a certain size for an early life diet to improve the development of a healthy body composition, in particular, obesity prevention, later in life.
公开号:BR112013031916B1
申请号:R112013031916-0
申请日:2012-06-18
公开日:2020-09-01
发明作者:Eline Marleen Van Der Beek；Marieke Abrahamse-Berkeveld；Annemarie Oosting；Martine Sandra Alles
申请人:N.V. Nutricia；
IPC主号:

专利说明:

FIELD OF THE INVENTION
[001] The present invention relates to the field of infant nutrition, and the effect of the lipid component of the early life diet on health and body composition later in life. HISTORY OF THE INVENTION
[002] Breastfeeding is the preferred method of feeding babies. Breastfed babies have a lower chance of becoming obese later in life, compared to infants fed standard formula, but little is known about the effects of ingredients in baby formulas on obesity later in life. Obesity is a major health problem in the western world. It is a medical condition in which the excess fat has accumulated to the point that it can have an adverse health effect, leading to shorter life expectancy, and is associated with many diseases, particularly heart disease and type 2 diabetes. Obesity is one of the main preventable causes of death in the world, with higher prevalence in adults and children, and the authorities see it as one of the most serious public health problems of the 21st century.
[003] The nutrition of babies with a lipid component that prevents obesity later in life is known. WO 2007/073192 refers to baby formulas comprising a low amount of linoleic acid and a low weight ratio of linoleic acid to alpha linolenic acid and LC-PUFA for the prevention of obesity later in life. WO 2007/073193 refers to baby formulas with specific linoleic acid to alpha-linolenic acid ratios, low in linoleic acid and comprising phospholipids, sphingolipids, cholesterol and / or choline plus uridine for later obesity prevention in life.
[004] The lipid component in baby formulas is typically present in the form of small lipid globules, which are obtained after a severe homogenization step. Small lipid globules are desirable because they result in a stable, non-cream-forming emulsion of lipid globules. The globules have a large surface area and, due to the low amount of polar lipids, such as phospholipids, in vegetable oils, the surface of the lipid globules is coated mainly with proteins, typically casein.
[005] WO 2010/0027258 and WO 2010/0027259 refer to formulas for babies with large lipid globules coated with phospholipids for the prevention of obesity later in life.
[006] Baby formulas predominantly comprise vegetable oils as a source of lipids and, in vegetable oils, unlike human or bovine milk, palmitic acid is mainly located at the sn-1 and sn-3 positions of the triglyceride molecule. Pancreatic lipases specifically hydrolyze palmitic acid, and the free released palmitic acid easily forms calcium-fatty acid complexes in the intestine, thereby reducing the bioavailability of calcium and palmitic acid and increasing stool hardness.
[007] Synthetic or structured lipids are known in the art, which comprise more residues of palmitic acid in the sn-2 position, and their presence in infant formulas increases palmitic acid absorption, calcium absorption and stool softness. An increase in bone mass is also reported. The reduction in obesity later in life was never revealed.
[008] WO 2005/051091 discloses a lipid preparation, to be included in baby formulas as a beneficial ingredient itself and to improve cognitive and vision development in particular, which is organized into a naturally occurring globular microstructure in human milk, which is based on vegetable lipids and a combination of glycerophospholipids phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI), and structured triglycerides such as Betapol® or InFat ™. The lipid preparation can additionally be enriched with omega-3 and omega-6 fatty acids, especially DHA and ARA.
[009] WO 2010/068105 discloses nutritional compositions for babies with a large lipid globule size.
[010] The present invention aims to provide infant nutrition with a lipid component that beneficially affects health and / or body composition later in life. SUMMARY OF THE INVENTION
[011] The inventors surprisingly found that the administration, early in life, of a diet comprising a lipid component with triglycerides with a greater portion of the residues of esterified palmitic acid in the sn-2 position of the glycerol backbone, affects growth and body composition later in life. When, in the beginning of life, a diet of the present invention comprising triglycerides with greater residues of esterified palmitic acid in the sn-2 position was administered, it was observed that, later in life, the body composition was altered, resulting in less accumulation of fat mass, less fat mass in relation to total body weight, greater lean body mass, greater body weight and greater muscle tissue compared to body composition after administering, in the beginning of life, a control diet with conventional vegetable triglycerides, even when the diet consumed later in life was the same in both groups. This lower accumulation of fat mass was observed, even when the accumulation of total body weight was greater. In particular, visceral adipose tissue in relation to subcutaneous adipose tissue has been reduced. This is surprising, since triglycerides with palmitic acid in the sn-2 position of the triglyceride backbone increase the absorption of fat, i.e. palmitic acid. Visceral obesity is more associated with health problems.
[012] The inventors recognized that when the lipid component is more adapted in its macromolecular architecture when it is organized into lipid globules, which are large, the programming effect on body composition and / or the health effects later in life, in particular, regarding obesity and insulin resistance and type 2 diabetes mellitus, are more advantageously improved. It was recognized that even greater improvement can be achieved by optimizing the composition of fatty acids. In particular, the inventors further recognized that the presence of triglycerides with higher esterified palmitic acid residues at the sn-2 position instead of the sn-1 or sn-3 positions in combination with an ideal fatty acid profile, preferably an acid profile fatty in relation to the weight ratio of linoleic acid to alpha-linolenic acid can result in an even greater improvement of the programming effect on body composition and / or health effects, in particular, regarding obesity and insulin resistance and type diabetes mellitus 2, later in life.
[013] This effect later in life is different from the direct effect on the diet. At the end of the dietary intervention on day 42, a similar fat mass relative to total body weight is observed compared to the control diet. Fat mass in young children has important roles in energy storage, isolation, storage of fat-soluble vitamins and hormonal development, such as the development of sensitivity to leptin and insulin and therefore it is not desired to reduce fat mass in babies and young children. Then, due to the lipids of the present invention consumed in childhood, differences in growth patterns arise, and the body is programmed differently, which results in a healthier body composition later in life, that is, adult life. The body is programmed to withstand a relatively obesogenic western-style diet.
[014] The present invention thus relates to nutritional compositions, in particular formulas for babies or growth milks for young children, comprising a lipid component with a structural design specifically adapted at multiple levels, level one being a composition of fatty acids improved with low n6 / n3 ideal, in particular, linoleic acid / alpha-linolenic acid ratios, level two being a greater number of palmitic acid residues located at the sn-2 position on the triglyceride backbone and the level three being a larger lipid globule size. The present invention, therefore, can be used for food compositions intended for babies and / or young children and is preferably intended to be consumed early in life to prevent obesity, visceral obesity, decrease or prevent insulin resistance, prevent type 2 diabetes, prevent metabolic syndrome, prevent cardio- or cerebrovascular diseases, increase lean body mass, increase muscle tissue, reduce relative fat mass, reduce fat mass accumulation, increase bone mass and / or increase bone mineral density later in life . DETAILED DESCRIPTION OF THE INVENTION
[015] The invention thus relates to a nutritional composition comprising carbohydrates, protein and lipids, in which the lipid is present in the form of lipid globules, in which i) the fatty acid composition of the lipid comprises linoleic acid and acid alpha-linolenic in a weight ratio of 2 to 10, ii) the fatty acid composition of the lipid comprises at least 10% by weight of palmitic acid based on total fatty acids, and at least 15% by weight of this palmitic acid is esterified to the sn-2 position of a triglyceride based on total palmitic acid, iii) the lipid globules have a modal volume diameter of 1.0 pm or above, and in which the nutritional composition is not human milk.
[016] The invention also relates to a nutritional composition as defined in this document, for use in one or more selected from obesity prevention, obesity risk reduction, obesity treatment, type 2 diabetes prevention, risk reduction of occurrence of insulin resistance and improvement of insulin sensitivity, prevention of metabolic syndrome and prevention of osteopenia and / or osteoporosis, reduced risk of occurrence of osteopenia and / or osteoporosis.
[017] The invention also relates to a nutritional composition as defined in this document, for use in improving body composition, improving body composition being selected from the group consisting of greater lean body mass, less fat mass in relation to weight total body mass, less visceral fat mass relative to total body weight, less visceral fat mass relative to total fat mass, less fat accumulation and greater muscle mass and greater bone mass and greater bone mineral density.
[018] The invention also relates to a method for one or more selected from obesity prevention, obesity risk reduction, obesity treatment, type 2 diabetes prevention, reduced risk of insulin resistance and improved insulin resistance insulin sensitivity, prevention or reduction of the risk of occurrence of metabolic syndrome, prevention or reduction of the risk of occurrence of osteopenia or osteoporosis, comprising the administration of a nutritional composition comprising carbohydrates, protein and lipids, in which the lipid is present in the form of lipid cells, where I) the fatty acid composition of the lipid comprises linoleic acid and alpha-linolenic acid in a weight ratio of 2 to 10, II) the fatty acid composition of the lipid comprises at least 10% by weight of acid palmitic based on total fatty acids, and at least 15% by weight of this palmitic acid is esterified to the sn-2 position of a triglyceride based on palmitic acid total, III) the lipid globules have a modal volume diameter of 1.0 pm or above, and in which the nutritional composition is not human milk.
[019] In other words, the invention relates to the use of a nutritional composition comprising carbohydrates, protein and lipids, in which the lipid is present in the form of lipid globules, in which i) the fatty acid composition of the lipid comprises acid linoleic and alpha-linolenic acid in a 2 to 10 weight ratio, ii) the fatty acid composition of the lipid comprises at least 10% by weight of palmitic acid based on total fatty acids, and at least 15% by weight of this palmitic acid is esterified to the sn-2 position of a triglyceride based on total palmitic acid, iii) the lipid globules have a modal volume diameter of 1.0 µm or above, and in which the nutritional composition is not human milk, for the manufacture of a nutritional composition for use in one or more selected from obesity prevention, reduction of obesity risk, obesity treatment, prevention of type 2 diabetes, reduction of the risk of occurrence of insulin and honey resistance insulin sensitivity, prevention of metabolic syndrome and prevention of osteoporosis or osteopenia.
[020] The invention also relates to a method for improving body composition, preferably a non-therapeutic method for improving body composition, the improvement of body composition being selected from the group consisting of more lean body mass, less fat mass in in relation to total body weight, lower visceral fat mass relative to total body weight, lower visceral fat mass relative to total fat mass, less fat accumulation, greater muscle mass, greater bone mass and greater bone mineral density, comprising the administration of a composition nutritional value comprising carbohydrates, protein and lipid, in which the lipid is present in the form of lipid globules, in which i) the fatty acid composition of the lipid comprises linoleic acid and alpha-linolenic acid in a weight ratio of 2 to 10, ii ) the fatty acid composition of the lipid comprises at least 10% by weight of palmitic acid based on total fatty acids, and at least 15% by weight this palmitic acid is esterified to the sn-2 position of a triglyceride based on total palmitic acid, iii) the lipid globules have a modal volume diameter of 1.0 pm or above, and in which the nutritional composition is not human milk .
[021] In other words, the invention relates to the use of a nutritional composition comprising carbohydrates, protein and lipids, in which the lipid is present in the form of lipid globules, in which i) the fatty acid composition of the lipid comprises acid linoleic and alpha-linolenic acid in a 2 to 10 weight ratio, ii) the fatty acid composition of the lipid comprises at least 10% by weight of palmitic acid based on total fatty acids, and at least 15% by weight of this palmitic acid is esterified to the sn-2 position of a triglyceride based on total palmitic acid, iii) the lipid globules have a modal volume diameter of 1.0 pm or above, and in which the nutritional composition is not human milk, for the manufacture of a nutritional composition for use in improving body composition, improving body composition being selected from the group consisting of higher lean body mass, lower fat mass in relation to total body weight, lower g mass visceral order relative to total body weight, less visceral fat mass relative to total fat mass, less fat accumulation, greater muscle mass, greater bone mass and greater bone mineral density.
[022] Obesity is considered a medical condition and, thus, the prevention of obesity, the reduction of the risk of obesity, and / or the treatment of obesity are seen as a method of treating the human body by therapy. This includes visceral obesity. Human individuals may suffer from visceral obesity, but not from general obesity. This situation is described as thin on the outside, fat on the inside, which is abbreviated in the technique as TOEI. A person suffering from visceral obesity is at a higher risk of becoming diabetic, although general obesity is not present. Thus, visceral obesity is considered a medical condition as well, and thus, the prevention of visceral obesity, the reduction of the risk of visceral obesity, and / or the treatment of visceral obesity are seen as a method of treating the human body by therapy . However, the improvement of body composition can be considered not to be therapeutic, which means that for all jurisdictions, this aspect can be properly called by the method, more particularly, a non-therapeutic method, to improve body composition as specified above.
[023] Type 2 diabetes mellitus, also called type 2 diabetes, is considered a medical condition and thus prevention of type 2 diabetes, reducing the risk of type 2 diabetes, and / or treating type 2 diabetes are seen as a method of the human body by therapy. Likewise, reducing insulin resistance, or preventing the occurrence of insulin resistance, or improving insulin sensitivity, is seen as medical treatment. LIPID COMPONENT
[024] The composition that is to be administered according to the present method or use comprises lipids. Lipids in the present invention are one or more selected from the group consisting of triglycerides, polar lipids (such as phospholipids, cholesterol, glycolipids, sphingomyelin), free fatty acids, mono- and diglycerides. Preferably, the composition comprises at least 70% by weight, more preferably, at least 80% by weight, more preferably, at least 85% by weight of triglycerides, even more preferably, at least 90% by weight of triglycerides, based on total lipids.
[025] The lipid preferably provides 30 to 60% of the total calories in the composition. More preferably, the present composition comprises lipid providing 35 to 55% of the total calories, even more preferably, the present composition comprises lipid providing 40 to 50% of the total calories. When in liquid form, for example, as a ready-to-eat liquid, the composition preferably comprises 2.1 to 6.5 q of lipids per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. Based on dry weight, the present composition preferably comprises 10 to 50% by weight, more preferably, 12.5 to 40% by weight of lipids, even more preferably 19 to 30% by weight of lipids. The lipid preferably comprises 80 to 100% by weight of triglycerides based on total lipids, more preferably 90 to 100% by weight.
[026] The lipid of the present invention preferably comprises vegetable lipids. The presence of vegetable lipids advantageously allows an ideal fatty acid profile, high in (poly) unsaturated fatty acids and / or more similar to human milk fat. The use of lipids from cow's milk alone, or other domestic mammals, does not provide an ideal fatty acid profile. This less ideal fatty acid profile, such as a large amount of saturated fatty acids, is known to result in greater obesity. Preferably, the present composition comprises at least one, preferably at least two lipid sources selected from the group consisting of linseed oil (linseed oil), rapeseed oil (such as rapeseed oil, low acid rapeseed oil erucic and canola oil), sage oil, perilla oil, purslane oil, alpine blackberry oil, yellow hawthorn oil, hemp oil, sunflower oil, high oleic sunflower oil, safflower oil, high safflower oil oleic, olive oil, blackcurrant seed oil, Echium oil, coconut oil, palm oil and palm kernel oil. Preferably, the present composition comprises at least one, preferably at least two lipid sources selected from the group consisting of linseed oil, canola oil, coconut oil, sunflower oil and high oleic sunflower oil. When in liquid form, for example, as a ready-to-eat liquid, the composition preferably comprises 2.1 to 6.5 g of vegetable lipids per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. Based on dry weight, the present composition comprises 10 to 50% by weight, more preferably, 12.5 to 40% by weight of vegetable lipids, even more preferably 19 to 30% by weight. Preferably, the composition comprises 40 to 100% by weight of vegetable lipids based on total lipids, more preferably, 50 to 100% by weight, more preferably, 70 to 100% by weight, even more preferably, 75 to 97% by weight . It is observed, therefore, that the present composition can also comprise non-vegetable lipids. Non-vegetable lipids can include lipids derived from milk fat and milk as a preferred source of phospholipids, fish, marine and / or microbial oils as a source of LC-PUFA. LIPID COMPONENT LEVEL ONE: FATTY ACID COMPOSITION
[027] In this document, LA refers to linoleic acid and / or acyl chain (18: 2 n6); ALA refers to alpha-linolenic acid and / or acyl chain (18: 3 n3); LC-PUFA refers to long-chain polyunsaturated fatty acids and / or acyl chains comprising at least 20 carbon atoms in the acyl grease chain and having 2 or more unsaturated bonds; DHA refers to docosahexaenoic acid and / or acyl chain (22: 6, n3); EPA refers to eicosapentaenoic acid and / or acyl chain (20: 5, n3); ARA refers to arachidonic acid and / or acyl chain (20: 4, n3); DPA refers to docosapentaenoic acid and / or acyl chain (22: 5, n3). PA refers to palmitic acid and / or acyl chains (C16: 0). Medium chain fatty acids (MCFA) refer to fatty acids and / or acyl chains with a chain length of 6, 8 or 10 carbon atoms.
[028] LA is preferably present in an amount sufficient to promote healthy growth and development, but in the least amount possible, to prevent the occurrence of obesity later in life. The composition, therefore, preferably comprises less than 15% by weight of LA, based on total fatty acids, preferably between 5 and 14.5% by weight, more preferably, between 6 and 10% by weight. Preferably, the composition comprises more than 5% by weight of LA based on fatty acids. Preferably, ALA is present in an amount sufficient to promote healthy baby growth and development. The present composition, therefore, preferably comprises at least 1.0% by weight of ALA based on total fatty acids. Preferably, the composition comprises at least 1.5% by weight of ALA based on total fatty acids, more preferably at least 2.0% by weight. Preferably, the composition comprises less than 10% by weight of ALA, more preferably, less than 5.0% by weight, based on total fatty acids. The LA / ALA weight ratio must be well balanced to prevent obesity, while at the same time, normal growth and development is guaranteed. Therefore, the present composition comprises an LA / ALA weight ratio of 2 to 10, more preferably 3 to 10, more preferably 3 to 7, more preferably 3 to 6, even more preferably 4 to 5.5, even more preferably from 4 to 5.
[029] Preferably, the composition comprises less than 10% by weight of short chain fatty acids based on total fatty acids, preferably less than 5% by weight, preferably less than 2% by weight. Short-chain fatty acids are fatty acids with a 2 to 5 acyl chain.
[030] Since MCFA contributes to less fat mass later in life when administered to a baby, the present composition preferably comprises at least 3% by weight of MCFA based on total fatty acids, more preferably, at least 10% by weight, even more preferably, 15% by weight. Since MCFA reduces fat deposition without preference for central fat mass, and since MCFA does not reduce the number of adipocytes, the present composition advantageously comprises less than 50% by weight of MCFA based on total fatty acids, more preferably, less than 30% by weight, even more preferably, less than 20% by weight.
[031] Preferably, the present composition comprises LC-PUFA, more preferably, LC-PUFA n-3, since LC-PUFA n-3 reduces obesity later in life, more preferably, central obesity. More preferably, the present composition comprises EPA, DPA and / or DHA, even more preferably, DHA. Since a low concentration of DHA, DPA and / or EPA is already effective, and normal growth and development are important, the content of LC-PUFA n-3 in the present composition, more preferably, DHA, preferably does not exceed 15 % by weight of the total fatty acid content, preferably, does not exceed 10% by weight, even more preferably, does not exceed 5% by weight. Preferably, the present composition comprises at least 0.15% by weight, preferably at least 0.35% by weight, more preferably, at least 0.75% by weight, of LC-PUFA n-3, more preferably, DHA , the total fatty acid content. In one embodiment, the present composition comprises at least 0.15% by weight of LC-PUFA n-3 based on total fatty acids selected from the group consisting of DHA, EPA, and DPA, more preferably, DHA.
[032] Since the group of n-6 fatty acids, especially arachidonic acid (ARA) and LA as its precursor, is opposed to the group of n-3 fatty acids, especially DHA and EPA and ALA as its precursors, The present composition comprises relatively low amounts of ARA. The content of LC-PUFA n-6, more preferably, ARA, does not exceed 5% by weight, more preferably, does not exceed 2% by weight, more preferably, does not exceed 0.75% by weight, even more preferably, does not exceed 0.5% by weight, based on total fatty acids. Since ARA is important in babies for ideal functional membranes, especially membranes of neurological tissues, the amount of LC-PUFA n-6, preferably ARA, is preferably at least 0.02% by weight, more preferably at least 0 , 05 wt%, more preferably at least 0.1 wt%, based on total fatty acids, more preferably at least 0.2 wt%. The presence of ARA is advantageous in a composition with low LA, since it remedies LA deficiency. The presence of preferably low amounts of ARA is beneficial in the nutrition to be administered to babies under the age of 6 months, one that, for these babies, baby formulas are generally the only source of nutrition. Preferably, the LC-PUFA n-6 / LC-PUFA n-3 weight ratio, more preferably the ARA / DHA weight ratio, is below 3, more preferably 2 or below, even more preferably 1 or below. A low LC-PUFA n-6 / LC-PUFA n-3 ratio, more preferably ARA / DHA, is especially preferred when the LA / ALA ratios are above 5, more preferably above 7, to counterbalance. In one embodiment, the present nutritional composition comprises LA and ALA in a ratio of LA / ALA above 5 and ARA and DHA in a ratio of ARA / DHA below 2. In one embodiment, the present nutritional composition comprises LA and ALA in an LA / ALA ratio of 5 or below 5, and ARA and DHA in an AA / DHA ratio of 2 or above 2. Arachidonic acid can also be abbreviated as AA. LIPID COMPONENT LEVEL TWO: PALMITIC ACID IN THE SN-2 POSITION OF THE TRIGLYCERID
[033] According to the present invention, the composition comprises triglycerides. Triglycerides comprise a glyceride molecule to which, through ester bonds, three residues of fatty acid are attached, which may be the same or different, and which are generally chosen from saturated and unsaturated fatty acids containing 6 to 26 carbon atoms, including, but not limited to, LA, ALA, oleic acid (C18: 1), PA and / or stearic acid (C18: 0). Such fatty acid triglycerides may differ in the fatty acid residues that are present and / or in the respective position (s) of the fatty acid residues (for example, in the position sn-1, -2, and / or -3). The triglycerides used in the present invention for the manufacture of a composition are chosen so that the amount of PA residues that are present in the triglycerides is 10% by weight or more, based on the total fatty acids present in the triglycerides, preferably more than 15% by weight. Preferably, the amount of PA residues that are present in the triglycerides is below 30% by weight, more preferably between 16 and 24%. The triglycerides used in the present invention for the manufacture of a composition are chosen so that of the total PA residues present in the triglycerides, at least 30%, preferably at least 35%, more preferably at least 40%, are in the sn position -2 or beta of triglyceride.
[034] The triglycerides of the present invention are commercially available - for example, from Loders Croklaan under the name Betapol ™ and / or can be prepared in a manner known per se, for example, as described in EP 0 698 078 and / or EP 0 758 846. Another suitable source is InFat ™ from Enzymotec. If these lipids are obtained by trans- or interesterification of plant triglycerides, these sources are, in the context of the present invention, called plant lipids. Preferably, the amount of triglycerides with the highest amount of palmitic acid residues at the sn-2 position of a triglyceride molecule that is comprised in the lipid fraction of the composition that is to be administered according to the present method or use, hereinafter also called composition final, it is between 10 and 100% by weight, preferably between 20 and 100% by weight, more preferably between 20 and 80% by weight, even more preferably between 50 and 80% by weight.
[035] A preferred source for triglycerides having palmitic acid in the sn-2 or beta position of the triglyceride is non-human animal fat, more preferably, non-human mammal milk fat, even more preferably, cow's milk fat. Preferably, fat from non-human mammal milk, in particular, cow's milk fat, is used in the form of anhydrous milk fat or butter oil. Preferably, the milk fat source is in a homogeneous fat phase, such as butter oil or anhydrous milk fat, and not in the form of oil in water emulsion, such as cream, since the lipid globules of the present invention can be prepared more easily during the manufacture of the nutritional composition of the present invention when in a homogeneous fat phase. Preferably, the amount of milk fat is between 10 and 100% by weight, based on total lipids, preferably between 10 and 80% by weight, based on total lipids, more preferably, between 20 and 80% by weight, more preferably, between 20 and 50% by weight, even more preferably, between 25 and 50% by weight, based on total lipids.
[036] Preferably, the amount of triglyceride with the highest amount of palmitic acid residues in the sn-2 position is such that the lipid fraction of the final nutritional composition comprises at least 10% by weight, more preferably, at least 15% by weight of palmitic acid residues, based on total fatty acid residues, and comprising at least 15% by weight of palmitic acid residues based on total palmitic acid residues at the sn-2 position of the triglyceride, more preferably at least 25% by weight, more preferably, at least 30% by weight, even more preferably, at least 35% by weight. Thus, preferably, at least 25% by weight, more preferably, at least 30% by weight, even more preferably, at least 35% by weight of palmitic acid are esterified to the sn-2 position of a triglyceride based on total palmitic acid . Preferably, the residues of palmitic acid in the final nutritional composition are below 30% by weight, based on total fatty acids comprised in the lipid fraction.
[037] Reduced obesity and / or better body composition later in life were seen when such a lipid component with higher amounts of palmitic acid located at the sn-2 position of the triglyceride molecules was consumed early in life. LIPID COMPONENT LEVEL THREE: LIPID BLOOD PROJECT LIPID BLOOD SIZE
[038] In accordance with the present invention, the lipid is present in the composition in the form of lipid globules. When in liquid form, these lipid globules are emulsified in the aqueous phase. Alternatively, the lipid globules are present in a powder, and the powder is suitable for reconstitution with water or another food-grade aqueous phase. Lipid globules comprise a nucleus and a surface. The core preferably comprises vegetable fat and preferably comprises at least 90% by weight of triglycerides, and, more preferably, essentially consists of triglycerides. Not all plant lipids that are present in the composition need necessarily be comprised in the nucleus of the lipid globules, but preferably a main part is preferably more than 50% by weight, more preferably more than 70% by weight, even more preferably, more than 85% by weight, even more preferably, more than 95% by weight, more preferably, more than 98% by weight of the plant lipids that are present in the composition are comprised in the lipid cell nucleus. In one embodiment, the core of the lipid globules comprises at least 40% by weight of triglycerides of plant origin, more preferably, at least 50% by weight, even more preferably, at least 70% by weight of triglycerides of plant origin, more preferably , the core of the lipid globules comprises at least 85% by weight, more preferably, at least 95% by weight of triglycerides of plant origin. The lipid globules of the present invention have a volume-weighted modal diameter above 1.0 pm, preferably above 3.0 pm, more preferably 4.0 pm or above, preferably between 1.0 and 10 pm, more preferably between 2 , 0 and 8.0 pm, even more preferably between 3.0 and 8.0 pm, more preferably between 4.0 pm and 8.0 pm. Preferably, in addition, the size distribution is such that at least 45% by volume, preferably at least 55% by volume, even more preferably at least 65% by volume, even more preferably at least 75% by volume. has a diameter between 2 and 12 pm. More preferably, at least 45% by volume, preferably at least 55% by volume, even more preferably at least 65% by volume, even more preferably, at least 75% by volume has a diameter between 2 and 10 pm. Even more preferably, at least 45% by volume, preferably at least 55% by volume, even more preferably at least 65% by volume, even more preferably, at least 75% by volume has a diameter between 4 and 10 pm. Preferably, less than 5% by volume has a diameter above 12 pm.
[039] Formulas for babies or standard growth milks have lipid globules with modal diameter below 0.5 pm. Large lipid globules have been found to have an improved effect on obesity later in life.
[040] The percentage of lipid cells is based on the volume of total lipids. The modal diameter refers to the diameter that is most present in the volume of total lipids, or the peak value in the graphical representation, having the diameter on the X axis, and the volume on the Y axis (%).
[041] The volume of the lipid cell and its size distribution can be appropriately determined using a particle size analyzer, such as the Mastersizer (Malvern Instruments, Malvern, United Kingdom), for example, by the method described in Michalski et al, 2001, Lait 81: 787-796. Phospholipip coating
[042] The present invention preferably comprises polar lipids. Polar lipids are amphipathic in nature and include glycerophospholipids, glycosphingolipids, sphingomyelin and / or cholesterol. More preferably, the composition comprises phospholipids (the sum of glycerophospholipids and sphingomyelin). Polar lipids in the present invention refer to the sum of glycerophospholipids, glycosphingolipids, sphingomyelin and cholesterol. Polar lipids, more preferably, phospholipids, are preferably present as a coating on the surface of the lipid globule. By "coating" it is understood that the outer surface layer of the lipid cell comprises polar lipids, while these polar lipids are practically absent in the nucleus of the lipid cell. The presence of polar lipids, in particular phospholipids, as a coating or outer layer of the lipid globule in the diet administered early in life has advantageously demonstrated to further decrease fat mass, decrease relative fat mass, that is, obesity, and / or increase lean body mass later in life. Thus, in one embodiment, the coating preferably comprises phospholipids and / or polar lipids. Not all of the polar phospholipids and / or lipids that are present in the composition need necessarily be comprised in the coating, but preferably, a major part is. Preferably, more than 50% by weight, more preferably, more than 70% by weight, even more preferably, more than 85% by weight, more preferably, more than 95% by weight of the polar phospholipids and / or lipids that are present in the composition are included in the coating of lipid globules.
[043] In one embodiment, in the nutritional composition according to the invention, lipid globules have a modal volume diameter of 1.0 pm or above, and are at least partially coated on the surface with phospholipids, the amount of phospholipids present in the nutritional composition being 0.5 to 20% by weight of phospholipids, based on total lipids. A combination of large lipid size and coating has an improved effect in preventing obesity later in life when compared to small lipid globules coated with phospholipids or large lipid globules not coated with phospholipids.
[044] The present composition preferably comprises glycerophospholipids. Glycerophospholipids are a class of lipids formed from fatty acids esterified in the hydroxyl groups in carbon-1 and carbon-2 of the backbone glycerol fraction, and a negatively charged phosphate group attached to the carbon-3 of glycerol through a ester bond, and optionally a choline group (in the case of phosphatidylcholine, PC), a serine group (in the case of phosphatidylserine, PS), an ethanolamine group (in the case of phosphatidylethanolamine, PE), an inositol group (in the case of phosphatidylinositol, PI) or a glycerol group (in the case of phosphatidylglycerol, PG) attached to the phosphate group. Lysophospholipids are a class of phospholipids with an acyl grease chain. Preferably, the present composition contains PC, PS, PI and / or PE, more preferably, at least PC.
[045] The present composition preferably comprises sphingomyelin. Sphingomyelins have a phosphorylcholine or phosphoryl ethanolamine molecule esterified to the 1-hydroxy group of a ceramide. They are classified as phospholipid, as well as sphingolipid, but they are not classified as glycerophospholipid, nor as a glycosphingolipid. Preferably, the present nutritional composition comprises 0.05 to 10% by weight of sphingomyelin based on total lipids, more preferably 0.1 to 5% by weight, even more preferably 0.2 to 2% by weight.
[046] The present composition preferably comprises glycosphingolipids. The term glycosphingolipids as in the present invention particularly refers to glycolipids with an amino alcohol sphingosine. The sphingosine backbone is linked by oxygen to a head group, such as the ethanolamine, serine or choline backbone. The backbone is also linked by amide to a fatty acyl group. Glycosphingolipids are ceramides with one or more sugar residues joined in a β-glycosidic bond in the 1- hydroxyl position. Preferably, the present composition contains gangliosides, more preferably, at least one ganglioside selected from the group consisting of GM3 and GD3.
[047] Sphingolipids are defined in the present invention as the sum of sphingomyelin and glycosphingolipids. Phospholipids are defined in the present invention as the sum of sphingomyelin and glycerophospholipids. Preferably, the phospholipids are derived from milk lipids. Preferably, the phospholipid: glycosphingolipid weight ratio is 2: 1 to 10: 1, more preferably, 2: 1 to 5: 1.
[048] Preferably, the present composition comprises phospholipids. Preferably, the present composition comprises 0.5 to 20% phospholipids based on total lipids, more preferably, 0.5 to 10% by weight, more preferably, 1 to 10% by weight, even more preferably 2 to 10% by weight, even more preferably, 3 to 8% by weight of phospholipids, based on total lipids. Preferably, the present composition comprises 0.1 to 10% by weight of glycosphingolipids based on total lipids, more preferably, 0.5 to 5% by weight, even more preferably, 2 to 4% by weight. Preferably, the present composition comprises 0.5 to 10% by weight (glycosphingolipids plus phospholipids) based on total lipids, more preferably, 1.0 to 10% by weight (glycosphingolipids plus phospholipids) based on total lipids.
[049] The present composition preferably comprises cholesterol. The present composition preferably comprises at least 0.005% by weight of cholesterol based on total lipids, more preferably, at least 0.02% by weight, more preferably, at least 0.05% by weight, even more preferably, at least 0 , 1% by weight. Preferably, the amount of cholesterol does not exceed 10% by weight based on total lipids, more preferably, it does not exceed 5% by weight, even more preferably, it does not exceed 1% by weight of total lipids.
[050] Preferably, the present composition comprises 0.6 to 25% polar lipids based on total lipids, wherein the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol, more preferably 0.6 to 12% by weight, more preferably, 1 to 10% by weight, even more preferably, 2 to 10% by weight, even more preferably, 3.0 to 10% by weight of polar lipids, based on total lipids, where the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol.
[051] Preferred sources for providing phospholipids, glycosphingolipids and / or cholesterol include egg lipids, milk fat, buttermilk fat and buttermilk fat (such as beta whey fat). A preferred source for phospholipids, particularly PC, is soy lecithin and / or sunflower lecithin. The present composition preferably comprises phospholipids derived from mammalian milk. Preferably, the present composition comprises phospholipids and glycosphingolipids derived from milk. Preferably, cholesterol is also obtained from milk. Preferably, the polar lipids, in particular, phospholipids, are derived from milk. Polar lipids, in particular, phospholipids, derived from milk include polar lipids, in particular, phospholipids, isolated from milk lipid, cream lipid, cream lipid, butter serum lipid (beta lipid), whey lipid, cheese lipid and / or buttermilk lipid. The buttermilk lipid is typically obtained during the manufacture of buttermilk. The butter whey lipid or beta whey lipid is typically obtained during the manufacture of anhydrous milk fat from butter. Preferably, phospholipids, glycosphingolipids and / or cholesterol are obtained from milk cream. The composition preferably comprises phospholipids, glycosphingolipids, and / or milk cholesterol from cows, mares, sheep, goats, buffaloes, mares and camels. It is more preferred to use a lipid extract isolated from cow's milk. The use of polar lipids from milk fat advantageously comprises polar lipids from milk fat globule membranes, which is more similar to the situation in human milk. Polar lipids, in particular phospholipids, derived from milk fat, advantageously decrease fat mass to a greater degree than polar lipids from other sources. Polar lipids, in particular, phospholipids, are located on the surface of the lipid globule, that is, as a coating or outer layer. It has been found that when polar lipids or phospholipids are present in the coating of the lipid globule, they are more effective than when they are dry mixed into the powdered product, i.e., present as ingredients as such. A suitable way of determining whether polar lipids are located on the surface of lipid globules is laser scanning microscopy. The concomitant use of polar lipids, in particular phospholipids, dairy products derived from domestic animals and triglycerides derived from vegetable lipids, therefore, allows the manufacture of lipid globules coated with a coating more similar to human milk, while at the same time provides an ideal fatty acid profile. Commercially available sources suitable for polar milk lipids include Corman's BAEF, SM2, SM3 and SM4 powder, Salibra of Glanbia, and Arla's LacProdan MFGM-10 or PL20. Preferably, the source of polar milk lipids comprises at least 4% by weight of phospholipids based on total lipids, more preferably, 7 to 75% by weight, more preferably, 20 to 70% by weight of phospholipids, based on lipids totals. Preferably, the weight ratio of phospholipids to protein is above 0.10, more preferably, above 0.20, even more preferably, above 0.3. Preferably, at least 25% by weight, more preferably, at least 40% by weight, more preferably, at least 75% by weight of the polar lipids, in particular phospholipids, are derived from polar milk lipids.
[052] Methods for obtaining lipid globules with a larger size and / or phospholipid coating are disclosed in WO 2010/0027258 and WO 2010/0027259.
[053] It is considered that, when the lipid component is designed according to the present invention, having an ideal fatty acid profile with a weight ratio of linoleic acid to alpha-linolenic acid of 2 to 10 and having a greater amount of palmitic acid located at the sn-2 position of the triglyceride molecule instead of the sn-1 or sn-3 position, and having the lipid component organized into larger lipid cells, a more improved effect in preventing obesity, preventing of insulin resistance, prevention of type 2 diabetes, prevention of metabolic syndrome, prevention of osteopenia and / or osteoporosis, or improvement of body composition later in life is observed. In particular, the presence of a greater amount of palmitic acid located at the sn-2 position of the triglyceride molecule instead of sn-1 or sn-3 improves, preferably synergistically, the anti-obesity or body composition effects of the lipids having an ideal fatty acid profile with a weight ratio of linoleic acid to alpha-linolenic acid of 2 to 10, and having the lipid component organized in larger lipid globules and / or coated with phospholipids. PROCESS
[054] The invention also relates to a process for the manufacture of a nutritional composition according to the invention, comprising the preparation of an aqueous phase comprising protein and digestible carbohydrates and the preparation of a fat phase comprising lipids, wherein the phospholipids are present in the aqueous and / or fat phase, in which the fatty acid composition of the lipid comprises linoleic acid and alpha-linolenic acid in a weight ratio of 2 to 10, in which the fatty acid composition of the lipid comprises at least minus 10% by weight of palmitic acid based on total fatty acids, and at least 15% by weight of palmitic acid is esterified to the sn-2 position of a triglyceride, based on total palmitic acid, the mixture of fat and phase aqueous and the homogenization of the fat and aqueous phase mixture in an oil-in-water emulsion with lipid globules at least partially coated on the surface with phospholipids, the amount of phospholipids present in the nutritional composition being 0.5 to 20% by weight of phospholipids based on total lipids.
[055] In addition, the invention relates to the product, preferably the nutritional composition obtained by the process according to the invention, for any of the uses or methods according to the invention. NUTRITIONAL COMPOSITION DIGERIBLE CARBOHYDRATES
[056] The composition comprises digestible carbohydrates. The digestible carbohydrate preferably provides 30 to 80% of the total calories in the composition. Preferably, the digestible carbohydrate provides 40 to 60% of the total calories. When in liquid form, for example, as a ready-to-eat liquid, the composition preferably comprises 3.0 to 30 g of digestible carbohydrates per 100 ml, more preferably 6.0 to 20, even more preferably 7.0 to 10.0 g per 100 ml. Based on dry weight, the present composition preferably comprises 20 to 80% by weight, more preferably 40 to 65% by weight of digestible carbohydrates.
[057] Preferred digestible carbohydrate sources include lactose, glucose, sucrose, fructose, galactose, maltose, starch and maltodextrin. Lactose is the main digestible carbohydrate present in human milk. Lactose advantageously has a low glycemic index. The present composition preferably comprises lactose. The present composition preferably comprises digestible carbohydrate in which at least 35% by weight, more preferably at least 50% by weight, more preferably at least 75% by weight, even more preferably, at least 90% by weight most preferably, at least 95 % by weight of the digestible carbohydrate is lactose. Based on dry weight, the present composition preferably comprises at least 25% by weight of lactose, preferably at least 40% by weight. NON-DIGERIBLE CARBOHYDRATES
[058] In one embodiment, the present composition comprises nondigestible oligosaccharides. Preferably, the present composition comprises nondigestible oligosaccharides with a degree of polymerization (DP) between 2 and 250, more preferably 3 and 60. The nondigestible oligosaccharides advantageously prevent the appearance of insulin resistance.
[059] Preferably, the present composition comprises fructo-oligosaccharides, galacto-oligosaccharides, and / or galacturonic acid oligosaccharides, more preferably, galacto-oligosaccharides, more preferably, transgalacto-oligosaccharides. In a preferred embodiment, the composition comprises a mixture of transgalacto-oligosaccharides and fructo-oligosaccharides. Suitable non-digestible oligosaccharides include, for example, Vivinal GOS (Frieslandcampina DOMO), Raftiline HP or Raftilose (Orafti).
[060] Preferably, the composition comprises 80 mg to 2 g of nondigestible oligosaccharides per 100 ml, more preferably 150 mg to 1.50 g, even more preferably 300 mg to 1 g per 100 ml. Based on dry weight, the composition comprises 0.25% by weight to 20% by weight, more preferably, 0.5% by weight to 10% by weight, even more preferably 1.5% by weight to 7.5% in weight. A smaller amount of nondigestible oligosaccharides will be less effective in preventing obesity, while a very high amount will result in side effects of bloating and abdominal discomfort. PROTEIN
[061] The present composition comprises proteins. The protein component preferably provides 5 to 15% of the total calories. Preferably, the present composition comprises a protein component which provides 6 to 12% of the total calories. More preferably, the protein is present in the composition below 9% based on calories, more preferably, the composition comprises between 7.2 and 8.0% protein based on the total calories, even more preferably, between 7.3 and 7.7% based on total calories. A low concentration of proteins advantageously guarantees a lower response to insulin, thus preventing the proliferation of adipocytes in babies. Human milk comprises less protein based on total calories than cow's milk. The concentration of proteins in a nutritional composition is determined by the sum of proteins, peptides and free amino acids. Based on dry weight, the composition preferably comprises less than 12% by weight of protein, more preferably between 9.6 to 12% by weight, even more preferably 10 to 11% by weight. Based on a ready-to-drink liquid product, the composition preferably comprises less than 1.5 g of protein per 100 ml, more preferably, between 1.2 and 1.5 g, even more preferably, between 1.25 and 1, 35 g.
[062] The source of the protein must be selected so that the minimum requirements for essential amino acid content are met, and satisfactory growth is guaranteed. Thus, protein sources based on cow's milk proteins, such as whey, casein and mixtures thereof, and soy, potato or pea based proteins are preferred. If whey proteins are used, the protein source is preferably based on acidic whey or sweet whey, isolated from whey protein or mixtures thereof, and may include oc-lactalbumin and β-lactoglobulin. More preferably, the protein source is based on acidic whey or sweet whey, from which caseino-glyco-macropeptide (CGMP) has been removed. Preferably, the composition comprises at least 3% by weight of casein based on dry weight. Preferably, the casein is intact and / or not hydrolyzed. For the present invention, the protein includes peptides and free amino acids. OTHERS
[063] The present composition is preferably particularly suitable for providing the dairy nutritional requirements to a human under the age of 36 months, particularly a baby under the age of 24 months, even more preferably, a baby under the age of 18 months. , more preferably, below 12 months of age. Thus, the nutritional composition is intended for food or is used to feed a human individual. The present composition comprises lipids, and digestible proteins and carbohydrates, wherein the lipid preferably provides 30 to 60% of the total calories, the protein preferably provides 5 to 20%, more preferably, 5 to 15% by weight of the total calories and the carbohydrate digestible preferably provides 25 to 75% of the total calories. Preferably, the present composition comprises a lipid providing 35 to 50% of total calories, protein providing 6 to 12% of total calories, and digestible carbohydrates providing 40 to 60% of total calories. In one embodiment, the protein provides 5 to 9% of the total calories. The amount of total calories is determined by the sum of calories derived from digestible protein, lipids and carbohydrates.
[064] The present composition is not breast milk. The present composition is not cow's milk (pure) or other mammal's milk (pure). The present composition preferably comprises vegetable lipids. The composition of the invention preferably comprises other ingredients, such as vitamins, minerals, according to international guidelines for baby formulas.
[065] In one embodiment, the nutritional composition according to the invention or the nutritional composition for use according to the invention is a formula for premature infants, formula for babies, accompanying formula or growth milk.
[066] To meet the baby's caloric requirements, the composition preferably comprises 50 to 200 kcal / 100 ml of liquid, more preferably 60 to 90 kcal / 100 ml of liquid, even more preferably 60 to 75 kcal / 100 ml of liquid. This caloric density guarantees an ideal relationship between water and calorie consumption. The osmolarity of the present composition is preferably between 150 and 420 mOsmol / 1, more preferably 260 to 320 mOsmol / 1. Low osmolarity aims to reduce gastrointestinal stress. Stress can induce the formation of adipocytes.
[067] Preferably, the composition is in a liquid form, with a viscosity below 35 mPa.s, more preferably below 6 mPa.s, as measured on a Brookfield viscometer at 20 ° C at a shear rate of 100 s-1. In one embodiment, the present composition is a powder. Suitably, the composition is in powder form, which can be reconstituted with water or another aqueous food-grade liquid, to form a liquid, or in a liquid concentrate form that must be diluted with water. It was found that the lipid cells maintained their sizes and coatings when reconstituted. When the composition is in a liquid form, the preferred volume administered daily is in the range of about 80 to 2500 ml, more preferably about 450 to 1000 ml per day. BABY
[068] Adipocytes proliferate during the first 36 months of life, as well as more limited at puberty. The amount of adipocytes is an important determinant in the degree of fat mass, adipose tissue and / or obesity later in life. Thus, the present composition is preferably administered to the human subject during the first years of life. In an embodiment of the use according to the present invention, the nutritional composition is intended for the feeding of a human individual aged between 0 and 36 months. It has been found that there is a predominance of adipocyte proliferation in the first 12 months of life with an ideal value in perinatal adipocyte proliferation. Thus, it is particularly preferred that the present composition is administered to a human subject in this lifetime. The present composition is therefore advantageously administered to a human from 0 to 24 months, more preferably, to a human from 0 to 18 months, even more preferably, to a human from 0 to 12 months, more preferably, to a human of 0 to 6 months old. The present invention particularly aims to prevent obesity later in life and is preferably not an obesity treatment. Thus, the present composition is preferably administered to an infant and / or small child who is not suffering from obesity or overweight. In an embodiment of the use according to the present invention, the nutritional composition is intended for the feeding of a non-obese human individual. Preferably, the composition should be used on babies having a weight appropriate for gestational age.
[069] Although adipocyte proliferation is more pronounced during the first 36 months of life and puberty, adipocytes are also formed to a lesser extent in the interval between 36 months and puberty. Then, in one embodiment, the present composition is preferably administered at an age of up to 5 years, more preferably, up to 10 years, more preferably, up to 13 years. OBESITY
[070] Obesity in the present invention refers to an excess of body fat mass. The fat mass is also known as adipose tissue or fat tissue. An adult human person suffers from obesity if more than 25% by weight (for men) or more than 30% by weight (for women) of body weight is fat mass. Obesity is often called adiposity.
[071] Appropriate ways to determine% body fat mass include underwater weighing, skinfold measurement, bioelectrical impedance analysis, computed tomography (CT / TAC Scan), magnetic resonance imaging (MRI / NMR), ultrasound and dual energy X-ray absorptiometry (DEXA). A preferred method is DEXA measurement. In the context of this invention, the body fat mass is determined by DEXA.
[072] The increased risk of health problems later in life, such as diabetes, in particular, type 2 diabetes, and metabolic syndrome, is related to the occurrence of visceral adiposity and not general obesity. The term 'visceral obesity' refers to a condition with greater visceral fat tissue. Adiposity is typically caused by (by accumulation of) excessive visceral adipose tissue. Visceral fat, also known as organ fat, intra-abdominal fat, peritoneal fat or central fat, is usually located within the peritoneal cavity, unlike subcutaneous fat, which is found under the skin and intramuscular fat, which is found interspersed with skeletal muscles. Visceral fat includes abdominal fat that surrounds vital organs and includes mesenteric fat, perirenal fat, retroperitoneal fat and preperitoneal fat (fat that surrounds the liver). A waist circumference of more than 102 cm in adult men or above 88 cm in adult women indicates the presence of visceral adiposity. Hip-to-waist ratios exceeding 0.9 in men and 0.85 in women indicate visceral adiposity. For children aged 3 to 19 years, appropriate cuts for age and sex dependent waist circumferences can be found in Taylor et al, 2000 Am J Clin Nutr 72: 490-495. An individual suffers from visceral adiposity when he meets one or more of the above criteria (referring to VAT thresholds, waist circumference or waist-to-hip ratio). APPLICATION
[073] The present composition is preferably administered orally to the baby. The present invention also aims to prevent the occurrence of obesity and / or to reduce the fat mass in the age above 36 months. In one embodiment, the present method is intended to prevent obesity, reduce the risk of obesity and / or to improve the body composition of a human individual when said human individual is over 36 months of age, preferably when said individual human being over 5 years old, particularly over 13 years old, more particularly over 18 years old. In one embodiment, the present method or present nutritional composition is intended for feeding a human individual aged 0 to 36 months and to prevent obesity, reduce the risk of obesity and / or improve body composition when said individual human being over 36 months of age, preferably to prevent obesity, reduce the risk of obesity and / or improve body composition at age over 5, particularly over 13, more particularly over 18. In one embodiment, preventing obesity, reducing the risk of obesity and / or improving body composition occurs later in life. Later in life is understood as an age that exceeds the age at which the diet is taken, preferably exceeding that age by at least one year. In one embodiment, the present method or present nutritional composition is intended to prevent visceral obesity and / or to reduce the visceral fat to subcutaneous fat ratio. The composition of the present invention, therefore, can advantageously be used to prevent obesity by reducing the risk of obesity later in life. Likewise, the composition can be used to prevent type 2 diabetes mellitus later in life, decrease or prevent insulin resistance and / or improve insulin sensitivity, prevent or reduce the risk of metabolic syndrome and prevent or reduce the risk osteopenia and / or osteoporosis, or reduce the risk of osteopenia and / or osteoporosis. Without wishing to be bound by theory, reduced visceral obesity later in life causes these effects. In addition, improving pancreatic development and liver function causes these effects.
[074] The inventors surprisingly found that when mice during infancy and childhood were fed a food composition according to the present invention, a different and significant effect on body composition later in life was observed compared to mice that , during the first and second infancy, were fed with a control food composition. Even after consuming a slightly Western-style obesogenic diet. The composition of the present invention, therefore, can advantageously be used to improve body composition later in life, in particular, greater lean body mass, less fat mass, less fat mass in relation to total body weight, less visceral fat mass in relation to total body weight, less visceral fat mass in relation to total fat mass, less fat accumulation, more muscle tissue. The composition of the present invention can also advantageously be used to increase bone mass and increase bone mineral density.
[075] Premature and / or small babies for gestational age often find growth recovery early in life. This is generally seen as a risk factor for adiposity later in life. Therefore, the composition of the present invention is advantageously used in premature babies or babies small for gestational age (SGA), in particular to feed a premature baby or a small baby for gestational age. A premature baby refers to a baby born before the standard period of pregnancy is completed, either before or at 37 weeks of the mother's pregnancy, that is, before or at 37 weeks from the beginning of the mother's last menstrual period. SGA babies are those whose birth weight lies below the 10th percentile for this gestational age. Premature babies and / or SGA include low birth weight babies (LBW babies), very low birth weight babies (VLBW babies) and extremely low birth weight babies (ELBW babies). LBW babies are defined as babies weighing less than 2500 g. VLBW babies are babies weighing less than 1500 g, and ELBW babies are babies weighing less than 1000 g.
[076] At a point in time corresponding to late adolescence or early adulthood in humans, the mice, which had previously consumed the food composition of the present invention before switching to the Western-style diet, had a significantly lower fat mass accumulated and a lower percentage of fat mass based on body weight and greater muscle tissue than mice that received a control composition during childhood. Total body weight and lean body mass were higher in mice fed the experimental diet early in life. In particular, visceral obesity has been reduced. This is advantageous since, in particular, visceral adipose tissue is more associated with health problems.
[077] In this document and in the claims, the verb "understand" and its conjugations is used in its non-limiting sense, to mean that items that follow the word are included, but items not specifically mentioned are not excluded. In addition, the reference to an element by the indefinite article "one" or "one" does not exclude the possibility that more than one element is present, unless the context clearly requires that there is only one element. The indefinite article "one" or "one", thus, generally means "at least one (a)". EXAMPLES EXAMPLE 1: EFFECTS OF STRUCTURED LIPIDS ON GROWTH AND BODY COMPOSITION LATER IN LIFE
[078] An experiment was carried out, in which the effects of an IMF with standard vegetable lipids were compared with IMF in which the lipid component comprises structured triglycerides with a greater amount of palmitic acid in the sn-2 position.
[079] Pregnant female C57 / BL6 mice and their offspring were exposed to the diet from day 2. The offspring started eating the diet themselves from day 15. They were completely fed on the diet from day 21. The experimental weaning diets continued until day 42. From day 42 to day 98, all puppies were fed the same diet based on the AIN-93G diet with an adjusted lipid fraction (containing 10% by weight of lipids, of the which 50% by weight are lard and 1% are cholesterol, based on total lipids), which is representative of a Western style diet.
[080] The experimental diets that were used for weaning were: 1) A rodent diet based on AIN-93G proteins, carbohydrates and fibers. In addition, the diet comprised 7% by weight of fat being a mixture of palm oil, coconut oil, rapeseed oil, sunflower oil, and high oleic acid sunflower oil. Typically, such vegetable oils comprise only 7.5% by weight of the total residues of palmitic fatty acid in the sn-2 position. 2) A rodent diet based on AIN-93G proteins, carbohydrates and fibers. In addition, the diet comprised 7% by weight of fat with 30% by weight based on total fats from a mixture of vegetable oil and 70% by weight based on the total fats of Betapol ™ 45 (Lipid Nutrition, Netherlands) in that about 45% of the total palmitic acid is esterified at the sn-2 position of the triglyceride. The amount of palmitic acid in Betapol ™ 45 was about 23% by weight based on total fatty acid residues.
[081] The triglyceride content in both diets was over 98% by weight, based on total lipids. The fatty acid composition of the diets is given in Table 1 and was very similar.
[082] On day 42, all mice switched to a "western style diet" comprising 10% by weight of lipids by day 98. The fatty acid composition of the western style diet is also shown in Table 1. Table 1 : Fatty acid composition of diets
*: about 35 to 45% by weight of palmitic acid residues at the sn-2 position of the triglycerides.
[083] The mice were weighed twice a week. Food intake was determined once a week throughout the experiment. To determine body composition (ie BMC, BMD, fat mass (FM) and fat free mass (FEM)) DEXA exams (dual energy X-ray absorptiometry) were performed under general anesthesia on days 42, 70 and 98 days after birth, respectively, by densitometry using a PIXImus digitizer (GE Lunar, Madison, WI, USA). At the age of 98 days, male mice were sacrificed, and fatty tissues and organs were weighed.
[084] Interestingly, mice from both diets showed a different growth pattern during the dietary intervention. Based on litter weight, and after day 21, the average body weight, the experimental group had lower (but not significant) weight compared to the control group between day 2 and day 31. From day 37 at day 42, the average body weight of puppies fed the experimental diet started to be higher than the control group. Table 2: Body weight, bone mineral content, bone mass density, fat mass and relative fat mass.

[085] The results are shown in table 2. On day 42, a direct effect of the structured lipid in the diet was observed in that body weight, the lean body mass and the fat mass were greater in the mice that consumed the lipid of the present invention.
[086] Interestingly, higher body weight and lean body mass compared to control mice were maintained later in life, even when the diet was similar. In addition, greater bone mineral content was observed later in life.
[087] Unexpectedly, the increase in fat mass and% fat was much smaller, and on day 98, a lower% fat mass was observed compared to control mice. Less fat mass accumulated during the period that the mice were on the Western-style diet, despite greater body weight. Thus, under the same dietary conditions, a healthier body composition later in life is achieved when it is preceded by greater growth (affecting lean body mass and fat mass) in late childhood, that is, the body receives beneficial imprinting. during childhood for healthier growth later in life. Low growth early in life is generally seen as a risk factor for later adiposity, but with the experimental diet, this surprisingly did not seem to be the case. Table 3: Adipose tissue and organ weights.


[088] Immediately after the final DEXA measurement on day PN 98, the dissection was performed. The organs and white adipose tissue (epididymal, perirenal, inguinal (subcutaneous) and retroperitoneal fat) were removed and weighed. The results are shown in Table 3. Muscle tissue was significantly higher in mice fed during childhood on the diet of the present invention than in control mice. EXAMPLE 2: IMPROVED EFFECT OF SN2 PALMITIC ACID, AND LIPID BLOOD BULB DESIGN ON GROWTH AND LATER BODY COMPOSITION IN LIFE
[089] An experiment was carried out, similar to example 1, in which the effects of diets with similar amounts of fat, but with different lipid components, in relation to the amount of palmitic acid in the sn-2 position of the triglyceride molecule and the design of lipid cells.
[090] C57 / BL6 pregnant female mice and their offspring were exposed to experimental diets from day 2. The offspring started eating the diet by themselves from day 15. They were completely fed on diets from day 21 The experimental diets continued until day 42. From day 42 to day 98, all puppies were fed the same diet based on the AIN-93G diet with an adjusted lipid fraction (containing 20% by weight of lipids (17% by weight of lard, 3% by weight of soy oil, 0.1% of cholesterol.) This diet represents a Western style diet.
[091] Experimental diets comprised 282 g of experimental baby formula (IMF). The rest of the diet was protein, carbohydrates and fiber from AIN-93G. All lipids present in the diet were derived from IMF. The total amount of lipids was 7% by weight based on the dry weight of the animal diet.
[092] The experimental MFI, which was present in the different diets, was prepared in a manner similar to that described in example IB of WO 2010/0027259. Diet 2 was prepared with high pressure homogenization.
[093] The detailed characteristics of the fat component of the different experimental MFIs used for the different animal diets are shown in Table 4. PA means palmitic acid.
[094] The amount of DHA was 0.2% by weight, and the amount of ARA was 0.36% by weight in all 6 experimental diets. In the Western style diet, the amount of LA was 11.9% by weight, the amount of ALA was 1.3% by weight, based on total fatty acids, and the LA / ALA ratio was 9.15.
[095] For diet 1, a mixture of palm oil, low erucic acid rapeseed oil, coconut oil, high oleic sunflower oil, sunflower oil, with a small amount of soy lecithin and a premix of LC-PUFA was used and additionally comprised buttermilk powder as a source of milk derived from phospholipids. The amount of vegetable fat in the final experimental IMF was about 95% by weight based on total fats.
[096] For diet 2, a mixture of anhydrous milk fat, coconut oil, low erucic acid rapeseed oil, sunflower oil, high oleic acid sunflower oil, with a small amount of soy lecithin and pre - mixture of LC-PUFA was used. The amount of vegetable fat was about 52% by weight based on total fats.
[097] Diet a 3 was similar to diet 2, but it also included buttermilk powder as a source of milk-derived phospholipids. A little less anhydrous milk fat was added to compensate for the milk fat present in the buttermilk powder. The amount of vegetable fat was about 51% by weight based on total fats. Table 4: Characteristics of the fat component of experimental diets
*:% by weight based on total fatty acids * *:% by weight based on total fats * ** "volumetric modal diameter in pm. * Percentage based on volume of lipid globules having a diameter between 2 and 12 pm
[098] The mice were weighed twice a week. Food intake was determined once a week throughout the experiment. To determine body composition (that is, bone mass content (BMC), bone mineral density (BMD), fat mass (FM) and fat-free mass / lean body mass (LBW)) DEXA exams (X-ray absorptiometry) dual energy) were performed under general anesthesia on day 42 and 70 days after birth, respectively, by densitometry using a PIXImus digitizer (GE Lunar, Madison, WI, USA).
[099] The results are shown in Table 5. Table 5: Effects of early life diets on weight development and body composition.

[0100] As shown in Table 5, a combination of a lipid with a greater amount of palmitic acid in the sn-2 position and a larger lipid globule coated with phospholipids while, at the same time, having an LA / ALA ratio low (diet 3) had a better effect on body composition later in life regarding higher lean body mass, lower fat mass, lower% body fat, higher bone mineral content and higher bone mineral density, compared to diet without a greater amount of palmitic acid in the sn-2 position (diet 1) or with a diet with small lipid globules not coated with phospholipids (diet 2). This effect was already present to some extent on day 42, that is, directly after having consumed the early life diets. But strikingly, the effects were even more pronounced on day 70, when the animals were fed the same western style diet for a while.
[0101] This is indicative of a greater effect on body composition and prevention of disorders, in particular, later in life, such as obesity, metabolic syndrome, type 2 diabetes and osteopenia when consuming a diet comprising lipids with an LA / ALA between 2 to 10, at least 10% by weight of palmitic acid, based on total fatty acids with at least 15% of the residues of palmitic acid in the sn-2 position, and with a lipid globule with a modal volume diameter above 1 pm further improved by the presence of 0.5% by weight to 20% by weight based on total phospholipid fats lining the lipid globules. EXAMPLE 3: IMF WITH STRUCTURED LIPIDS.
[0102] A baby formula for babies aged 0 to 6 months comprising, per 100 ml, 66 kcal, 1.3 g of protein (cow's milk protein, whey protein and casein in a weight ratio of 6 : 4), 7.3 g of digestible carbohydrates (mainly lactose), 3.5 g of lipids (mainly vegetable lipids), 0.54 g non-digestible oligosaccharides (trans galacto-oligosaccharides and long-chain fructo-oligosaccharides), salts minerals, trace elements, vitamins, cardinine, choline, myo-inositol and taurine as known in the art.
[0103] The composition of fatty acids is similar to that of diet 2 in example 1, except that, due to the presence of microbial oils, 0.2% by weight of LC-PUFA n3 (mainly DHA) and 0.35% by weight AA are present.
[0104] In addition, 0.6% by weight of buttermilk powder phospholipids was present (Corman SM2 source, Belgium) based on total lipids. The process was carried out like that of Diet 4 in example 1 of WO 2010/0027258, and the lipid globules had an average volume diameter above 1.0 pm and had a surface layer comprising phospholipids. EXAMPLE 4: FORMULA FOR BABIES
[0105] A baby formula comprising, per 100 ml, 66 kcal, 1.3 g of protein (protein derived from cow's milk, with whey protein and casein in a 6: 4 weight ratio), 7 , 3 g of digestible carbohydrates (mainly lactose), 3.4 g of lipids, of which 51% by weight of vegetable fat (low erucic acid rapeseed oil, sunflower oil, coconut oil, high acid sunflower oil oleic, soy lecithin) 48% by weight of milk fat (mainly anhydrous milk fat, and buttermilk powder), the remainder being fish oil, microbial oil as a source of LC-PUFA, 0.8 g of oligosaccharides nondigestible (trans galacto-oligosaccharides and long-chain fructo-oligosaccharides). Mineral salts, trace elements, vitamins, cardinine, choline, myo-inositol, and taurine as known in the art.
[0106] Buttermilk powder is present in an amount such that 1.5% by weight of phospholipids (derived from buttermilk powder), based on total lipids, was present. In addition, 0.1% by weight of soy-derived phospholipid is present based on total fats. The lipid globules had an average volume diameter of about 5 pm.
[0107] The fatty acid profile based on total fatty acids comprises 17.70% by weight of PA (of which 36%, based on total PA are in the sn-2 position), 13.96% in by weight of ARA, 0.2% 0 Ω ”9 9- 'UJo by weight of DPA.

权利要求:
Claims (20)
[0001]
1. NUTRITIONAL COMPOSITION, characterized by comprising carbohydrates, protein and lipids, in which the lipid is present in the form of lipid globules, in which i) the fatty acid composition of the lipid comprises linoleic acid and alpha-linolenic acid in a weight ratio from 2 to 10, ii) the fatty acid composition of the lipid comprises at least 10% by weight of palmitic acid based on total fatty acids, and at least 30% by weight of palmitic acid is esterified to the sn-2 position of a triglyceride based on total palmitic acid, iii) the lipid globules have a modal volume diameter of 1.0 pm or above, and in which the nutritional composition is not human milk.
[0002]
2. NUTRITIONAL COMPOSITION, according to claim 1, characterized in that it comprises less than 15% by weight of linoleic acid and more than 1% by weight of alpha-linolenic acid based on total fatty acids.
[0003]
NUTRITIONAL COMPOSITION, according to either of Claims 1 or 2, characterized in that it comprises at least 0.15% by weight of LC-PUFA n-3 based on total fatty acids selected from the group consisting of DHA, EPA, and DPA, more preferably, DHA.
[0004]
NUTRITIONAL COMPOSITION according to any one of claims 1 to 3, characterized in that at least 35% by weight of palmitic acid is esterified to the sn-2 position of a triglyceride based on total palmitic acid.
[0005]
5. NUTRITIONAL COMPOSITION, according to any one of claims 1 to 4, characterized in that the lipid globules are at least partially coated on the surface with phospholipids, the amount of phospholipids present in the nutritional composition, being 0.5 to 20% by weight of phospholipids, based on total lipids.
[0006]
6. NUTRITIONAL COMPOSITION, according to claim 5, characterized in that it comprises 0.5 to 20% by weight of phospholipids derived from mammalian milk, based on total lipids.
[0007]
NUTRITIONAL COMPOSITION, according to any one of claims 1 to 6, wherein the nucleus of lipid globules is characterized by comprising at least 40% by weight of triglycerides of plant origin.
[0008]
NUTRITIONAL COMPOSITION, according to any one of claims 1 to 7, characterized in that it comprises 10 to 50% by weight of lipids, based on the dry weight of the total composition.
[0009]
9. NUTRITIONAL COMPOSITION, according to any one of claims 1 to 8, characterized in that the lipids provide 30 to 60% of the total calories, the protein provides 5 to 20% of the total calories, and the digestible carbohydrates provide 25 to 75% of the calories totals.
[0010]
10. NUTRITIONAL COMPOSITION according to any one of claims 1 to 9, characterized in that it comprises at least 0.1% by weight of arachidonic acid based on the total weight of fatty acids and in which the amount of arachidonic acid does not exceed 2, 0% by weight based on the total weight of fatty acids.
[0011]
11. NUTRITIONAL COMPOSITION, according to any one of claims 1 to 10, characterized in that the proteins provide 5 to 9% of the total calories.
[0012]
12. NUTRITIONAL COMPOSITION, according to any one of claims 1 to 11, characterized in that it additionally comprises non-digestible oligosaccharides.
[0013]
13. NUTRITIONAL COMPOSITION, according to any one of claims 1 to 12, characterized in that the composition is a powder.
[0014]
14. USE OF A NUTRITIONAL COMPOSITION, according to any one of claims 1 to 13, characterized by being for the manufacture of a nutritional composition for one or more uses selected from obesity prevention and obesity risk reduction.
[0015]
15. USE OF A NUTRITIONAL COMPOSITION, according to any one of claims 1 to 13, characterized in that it is for the manufacture of a nutritional composition for use in improving body composition, the improvement of body composition being selected from the group consisting of the largest body mass, lower fat mass in relation to total body weight.
[0016]
16. USE, according to either of claims 14 or 15, characterized in that the nutritional composition is intended for the feeding of a human individual aged between 0 and 36 months.
[0017]
17. USE, according to claim 16, characterized in that it is for preventing obesity, reducing the risk of obesity and / or improving the body composition in a human individual, when said human individual is over 36 months of age, preferably when said human individual is over the age of 5 years.
[0018]
18. USE, according to any one of claims 14 to 17, characterized in that the nutritional composition is intended for the feeding of a non-obese human individual.
[0019]
19. USE, according to any of claims 14 to 18, characterized in that the nutritional composition is a formula for premature infants, formula for babies, accompanying formula or growth milk.
[0020]
20. PROCESS FOR THE MANUFACTURE OF A NUTRITIONAL COMPOSITION, as defined in claims 1 to 13, characterized in that it comprises the preparation of an aqueous phase comprising protein and digestible carbohydrates and the preparation of a fat phase comprising lipids, in which phospholipids are present in the aqueous and / or fat phase, in which the fatty acid composition of the lipid comprises linoleic acid and alpha-linolenic acid in a weight ratio of 2 to 10, in which the fatty acid composition of the lipid comprises at least 10% in weight of palmitic acid based on total fatty acids, and at least 30% by weight of palmitic acid is esterified to the sn-2 position of a triglyceride, based on total palmitic acid, the mixture of fat and aqueous phase and homogenization of the mixture of fat and aqueous phase in an oil-in-water emulsion with lipid globules at least partially coated on the surface with phospholipids, the amount of phospholipids present in the composition being from 0.5 to 20% by weight of phospholipids based on total lipids.

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法律状态:
2018-01-23| B07D| Technical examination (opinion) related to article 229 of industrial property law|

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2018-03-27| B15K| Others concerning applications: alteration of classification|Ipc: A61K 31/202 (2006.01), A23L 33/115 (2016.01), A23L |

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2018-04-03| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

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2019-03-26| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa)|Free format text: NOTIFICACAO DE DEVOLUCAO DO PEDIDO POR NAO SE ENQUADRAR NO ART. 229-C DA LPI. |

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2019-12-10| B06U| Preliminary requirement: requests with searches performed by other patent offices: suspension of the patent application procedure|

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2020-05-12| B09A| Decision: intention to grant|

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2020-09-01| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 18/06/2012, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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PCT/NL2011/050437|WO2012173467A1|2011-06-16|2011-06-16|Metabolic imprinting effects of specifically designed lipid component|

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NLPCT/NL2011/050437|2011-06-16|

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PCT/NL2012/050428|WO2012173486A1|2011-06-16|2012-06-18|Metabolic imprinting effects of specifically designed lipid component|

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