Infant formula milk powder having special lipid structure for reducing pediatric blood pressure

Abstract

The present invention relates to an infant formula milk powder for controlling and reducing blood pressure in children, comprising large lipid globules and / or lipid globules with a phospholipid coating.

Description

Technical Field

[0001] The present invention relates to infant nutrition products, in particular to infant formula milk powder, for use in reducing blood pressure in children. Background Art

[0002] Infant formula or follow-on formula is usually used when breastfeeding is insufficient or unsuccessful, or when breastfeeding is not an option, usually for medical reasons. Commercial infant formula is usually used to provide a supplemental source of nutrition or the sole source of nutrition in the early stages of life. These formulas contain a range of nutrients to meet the nutritional needs of growing infants and typically include fats, carbohydrates, proteins, vitamins, minerals and other nutrients that contribute to optimal infant growth and development.

[0003] Nutritional experiences during the first few months of life may influence their susceptibility to chronic diseases in adulthood. Early nutritional experiences during early development can lead to programming of regulatory mechanisms: a phenomenon known as metabolic imprinting.

[0004] Hypertension is one of the leading health risk factors in the world. Blood pressure in adulthood has been shown to be predicted by childhood blood pressure, which continues from childhood to adolescence and adulthood. Elevated blood pressure in childhood has been shown to be associated with risk of hypertension in adulthood (Yang et al., 2020, J Hypertens 38:2346-2355). Observational studies have demonstrated that higher maternal pre-pregnancy BMI, maternal hypertension, relatively lower birth weight, shorter gestational age (preterm birth), limited breastfeeding period, and more rapid BMI increase in early life contribute to higher childhood blood pressure at 6 years of age.

[0005] Human milk lipids have a unique physical structure consisting of large lipid globules with a volume-based mode diameter of about 4 μm on average, with a triglyceride core coated with a three-layer membrane (milk fat globule membrane (MFGM)). Due to industrial processing procedures to achieve a stable and reproducible final product, the volume-based mode diameter of lipid droplets in standard infant formula milk powder is about 0.3-0.5 μm, and is not surrounded by MFGM but by proteins (e.g., casein). Standard commercially available formula milk powders also contain mainly vegetable oils and have small lipid droplets and proteins adhered to the surface. Infant formula milk powders with lipid globules with a structure more similar to lipid globules in human milk have been described. In WO 2012 / 173467, a specially designed lipid component with an optimal fatty acid profile (i.e., an enhanced portion of palmitic acid residues present in the form of lipid globules of a certain size and / or coating) is disclosed for use in a diet in early life to improve the development of healthy body composition, particularly to prevent obesity in later life.

[0006] In the prior art in the field of infant nutrition related to blood pressure in childhood, it is clear that dietary supplementation of infant formula with long-chain polyunsaturated fatty acids (LCPUFA) is associated with lower blood pressure in later childhood at 6 years of age (Forsyth et al., BMJ [British Medical Journal] 2003 Vol. 326, bmj.com 2003; 326:953). In addition, supplementation of infant formula with a milk fat globule membrane (MFGM) component resulted in a lipid profile closer to that of breastfed infants at 12 months of age (intervention 0-6 months; Timby et al., Pediatr Res [Journal of Pediatric Research] 2014, 76(4):394-400). This may be related to lipid status later in life, but this particular clinical trial did not provide any information beyond 12 months of age. WO2013 / 153071 discloses a nutritional composition comprising MFGM and milk fat, particularly for use in blood pressure and other related cardiovascular and metabolic diseases, although no effect on blood pressure in childhood is mentioned and the composition does not contain large lipid globules. WO2013 / 191542 relates to an infant formula comprising milk fat, phospholipid-coated large lipid globules and MFGM as a source of phospholipids. Although metabolic syndrome and cardiovascular disease are also mentioned, the focus is on the effects on obesity and body composition. The effects of the composition on blood pressure in childhood are not mentioned. WO 2013 / 36122 also describes the use of phospholipid-coated large lipid globules and MFGM for reducing total blood cholesterol levels later in life, including related conditions such as hypertension.

[0007] Primary pediatric or childhood hypertension is associated with target organ damage, particularly to the heart. Therefore, identifying potential preventive measures to prevent elevated blood pressure in childhood and / or primary childhood hypertension is of vital importance. Summary of the invention

[0008] After the healthy full-term infant experimental formula milk powder of the first four months after birth was carried out nutritional intervention, the inventor measured blood pressure in the follow-up at the age of 5. The experimental infant formula milk powder comprises a lipid component in the form of a large lipid globule coated with phospholipids. The control group received a control infant formula milk powder without a lipid component in the form of a large lipid globule coated with phospholipids, but the lipid component is in the form of a standard small lipid globule coated with protein. Both formula milk powders are used in up to 17 weeks (4 months) after birth. The control milk formula milk powder and the experimental milk formula milk powder are similar in terms of calorie content, and are also similar in terms of total fat, carbohydrates and protein content.

[0009] This is the first investigation of the long-term programmatic effects on childhood health outcomes using a nutritional composition comprising large lipid globules coated with phospholipids. The inventors discovered a beneficial effect of the composition on the (nutritional) program of infant metabolism, leading to lower blood pressure in childhood.

[0010] Specifically, the inventors were surprised to find that diastolic and arterial blood pressures were lower in the group receiving the experimental formula compared to the control group at age 5. Blood pressure remained significantly lower after correction for current childhood BMI.

[0011] These findings suggest that administration of infant formulae with similar calorie content and macronutrient content may have different and beneficial effects on blood pressure in early childhood, with additional benefits independent of the beneficial effects reported when LCPUFAs are added to the formulae. This is due to differences in the configuration of the lipid components with large lipid globules coated with phospholipids. DETAILED DESCRIPTION

[0012] Therefore, a first aspect of the present invention relates to a method for promoting a reduction in childhood blood pressure and / or reducing the risk of elevated blood pressure in children less than 13 years of age, the method comprising administering to an infant a nutritional composition selected from infant formula and follow-on formula, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm and wherein the lipid globules have a coating comprising a phospholipid.

[0013] The present invention may also be formulated as a nutritional composition selected from infant formula and follow-on formula for use in reducing the risk of childhood elevated blood pressure in children less than 13 years of age, wherein the nutritional composition comprises lipid, protein and digestible carbohydrates, and wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising a phospholipid.

[0014] In some jurisdictions, administration of a nutritional composition to an infant is considered non-therapeutic. In those cases, the present invention may be described as being carried out by administering a nutritional composition as defined above. For clarity, the method may also be defined as a non-therapeutic method for reducing blood pressure in childhood and / or reducing the risk of elevated blood pressure in childhood as defined above. By definition, the term "non-therapeutic" excludes any therapeutic effect.

[0015] In some jurisdictions, administration of a nutritional composition to an infant is itself considered therapeutic. In this context, the invention may also be formulated as the use of a lipid globule in the manufacture of a nutritional composition for reducing the risk of childhood hypertension in children less than 13 years of age, the nutritional composition being selected from infant formula and follow-on formula, wherein the nutritional composition comprises lipid, protein and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising a phospholipid.

[0016] Preferably, in the method, use or composition for use according to the invention, blood pressure is reduced in childhood and / or the risk of elevated blood pressure in childhood is reduced when compared to a similar child consuming an infant formula or follow-on formula not comprising lipid globules having a mode diameter based on volume of at least 1.0 μm and not having a diameter of 2 to 12 μm in an amount of at least 45% by volume of total lipids and not comprising a coating comprising phospholipids on the surface, more particularly blood pressure is reduced in childhood and / or the risk of elevated blood pressure in childhood is reduced when compared to a similar child consuming a standard infant formula comprising a follow-on formula comprising lipid globules having a mode diameter based on volume of about 0.5 μm and not having a coating comprising phospholipids.

[0017] A second aspect of the present invention relates to a method for preventing pediatric hypertension in children less than 13 years of age, the method comprising administering to an infant a nutritional composition selected from infant formula and follow-on formula, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume-weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm and wherein the lipid globules have a coating comprising phospholipids.

[0018] The present invention may also be formulated as a nutritional composition selected from infant formula and follow-on formula for use in the prevention of pediatric hypertension in children less than 13 years of age, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume-weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising a phospholipid.

[0019] The present invention may also be formulated as the use of lipid globules in the manufacture of a nutritional composition selected from infant formula and follow-on formula for the prevention of pediatric hypertension in children less than 13 years of age, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume-weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising a phospholipid.

[0020] In the context of the present invention, the nutritional composition is not human milk. Also in the context of the present invention, the nutritional composition is not bovine milk, in particular non-homogenized bovine milk.

[0021] In the context of the present invention, the nutritional composition is selected from an infant formula or a follow-on formula, both formulas preferably comprising 3 to 7 g lipid / 100 kcal, 1.25 to 5 g protein / 100 kcal and 6 to 18 g digestible carbohydrates / 100 kcal.

[0022] Lipid globule size

[0023] According to the present invention, the nutritional composition comprises lipid globules. When in liquid form, these lipid globules are emulsified in an 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, preferably providing a ready-to-drink formula milk powder. The lipid globules comprise a core and a surface. The core preferably comprises vegetable fat, and preferably comprises at least 90wt% triglycerides, and more preferably the core is substantially composed of triglycerides. Not all of the plant lipids present in the composition must be included in the core of the lipid globules, but preferably most of the plant lipids present in the composition, preferably more than 50wt%, more preferably more than 70wt%, even more preferably more than 85wt%, even more preferably more than 95wt%, most preferably more than 98wt% are included in the lipid globules core. In a preferred embodiment, the core of the lipid globules comprises at least 40wt% plant-derived triglycerides, more preferably at least 50wt%, even more preferably at least 70wt% plant-derived triglycerides, even more preferably the core of the lipid globules comprises at least 85wt%, more preferably at least 95wt% plant-derived triglycerides. The lipid globules in the nutritional composition preferably have a volume-weighted mode diameter greater than 1.0 μm, preferably higher than 3.0 μm, more preferably higher than 4.0 μm, preferably between 1.0 and 10 μm, more preferably between 2.0 and 8.0 μm, even more preferably between 3.0 and 8.0 μm, most preferably between 4.0 and 8.0 μm. In addition, the size distribution is preferably performed in the following way: 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 of the lipid globules have a diameter between 2 and 12 μm. 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 of the lipid globules have a diameter between 2 and 10 μm. 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 of the lipid globules have a diameter between 4 and 10 μm. Preferably less than 5% by volume have a diameter greater than 12 um.

[0024] Standard infant formula milk powder or follow-up formula milk powder typically have based on volume less than 0.5 μ m, typically at the lipid globules of the mode diameter between 0.3-0.5 μ m.Compared with infant formula milk powder with relatively small size lipid globules, it has been found that relatively large lipid globules have an unexpected reduction effect on childhood blood pressure.The volume percentage of lipid globules is based on total lipid volume.The mode diameter relates to the maximum diameter based on total lipid volume, or the peak value in the diagram, which represents diameter on the X-axis and represents volume (%) on the Y-axis.

[0025] The volume of lipid globules and their size distribution can be suitably determined using a particle size analyzer such as the Mastersizer 2000 (Malvern Instruments, Malvern, UK), for example by the method described by Michalski et al., 2001, Lait 81:787-796.

[0026] Coating with phospholipids

[0027] According to the present invention, the nutritional composition comprises phospholipids. Phospholipids belong to polar lipids. Polar lipids are amphiphilic in nature and include glycerophospholipids, glycosphingolipids, sphingomyelins and optionally cholesterol. Phospholipids refer to the sum of glycerophospholipids and sphingomyelins. Phospholipids exist in the form of a coating on the surface of lipid globules. By "coating" it is meant that the outer surface layer of the lipid globules comprises phospholipids, which are hardly present in the lipid globules core. Not all phospholipids present in the composition necessarily need to be included in the coating, but preferably the main part needs to be. Preferably more than 30wt%, more preferably more than 50wt%, more preferably more than 70wt%, even more preferably more than 85wt%, most preferably more than 95wt% of the phospholipids present in the composition are included in the coating of the lipid globules. The nutritional composition preferably comprises at least 0.5wt% phospholipids based on total lipids. Preferably the phospholipids comprise at least 5 wt% sphingomyelin based on total phospholipids, more preferably at least 7.5 wt%, even more preferably 10 wt% sphingomyelin, and most preferably at least 15 wt% sphingomyelin based on total phospholipids.

[0028] In the nutritional composition, the lipid globules preferably have a volume weighted mode diameter of 1.0 μm or more and are at least partially coated on the surface with phospholipids. Preferably, the amount of phospholipids present in the nutritional composition ranges from 0.5 to 20 wt% phospholipids based on total lipids. The combination of large lipid globule size and phospholipid coating shows an unexpected lowering effect on blood pressure in children when compared to lipid globules that are small and not coated with phospholipids.

[0029] According to the present invention, the nutritional composition preferably comprises glycerophospholipids. Glycerophospholipids are a class of lipids formed by esterification of fatty acids having the following characteristics, which are esterified via ester bonds at the hydroxyl groups on carbon-1 and carbon-2 of the main chain glycerol part and at the negatively charged phosphate group attached to the carbon-3 of glycerol, 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 phospholipid group. Lysophospholipids are a class of phospholipids with one fatty acyl chain. Preferably, the composition of the present invention contains PC, PS, PI and / or PE, more preferably at least PC.

[0030] Preferably, the nutritional composition comprises sphingomyelin. Sphingomyelin has a phosphocholine or phosphoethanolamine molecule esterified to the 1-hydroxyl group of ceramide. They are classified as phospholipids and sphingolipids, but not as glycerophospholipids or glycosphingolipids. Preferably, the nutritional composition comprises 0.05 to 10 wt% sphingomyelin based on total lipids, more preferably 0.1 to 5 wt%, even more preferably 0.2 to 2 wt%.

[0031] According to the present invention, the nutritional composition preferably comprises glycosphingolipids. As in the present invention, the term glycosphingolipids specifically refers to glycolipids having the amino alcohol sphingosine. The sphingosine backbone is O-connected to a charged head group (e.g., an ethanolamine, serine, or choline backbone). The backbone is also an amide group connected to a fatty acyl group. Glycosphingolipids are ceramides having one or more sugar residues that are linked to a β-glycosidic bond at the 1-hydroxyl position. Preferably, the nutritional composition comprises gangliosides, more preferably at least one ganglioside selected from the group consisting of GM3 and GD3.

[0032] In the present invention, sphingolipids are defined as the sum of sphingomyelin and glycosphingolipids. Preferably, the phospholipids are derived from milk lipids. Preferably, the weight ratio of phospholipids:glycosphingolipids is 2:1 to 10:1, more preferably 2:1 to 5:1.

[0033] Preferably the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids, more preferably 0.5 to 10 wt%, more preferably 1 to 10 wt%, even more preferably 2 to 10 wt%, even more preferably 3 to 8 wt% phospholipids based on total lipids. Preferably the nutritional composition comprises 0.1 to 10 wt% glycosphingolipids based on total lipids, more preferably 0.5 to 5 wt%, even more preferably 2 to 4 wt%. Preferably the nutritional composition comprises 0.5 to 10 wt% (glycosphingolipids plus phospholipids) based on total lipids, more preferably 1.0 to 10 wt% (glycosphingolipids plus phospholipids) based on total lipids. In one embodiment, the nutritional composition comprises phospholipids, wherein the phospholipids comprise glycolipids, and / or are derived from or form part of milk fat globule membrane (MFGM), preferably bovine milk MFGM.

[0034] According to the present invention, the nutritional composition preferably comprises cholesterol. The nutritional composition preferably comprises at least 0.005wt% cholesterol based on total lipids, more preferably at least 0.01wt%, more preferably at least 0.02wt%, more preferably at least 0.05wt%, even more preferably at least 0.1wt%. Preferably, the amount of the cholesterol is no more than 10wt% based on total lipids, more preferably no more than 5wt%, even more preferably no more than 1wt% of total lipids.

[0035] According to the present invention, the nutritional composition preferably comprises 0.6 to 25 wt% polar lipids based on total lipids, wherein the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol, more preferably 0.6 to 12 wt%, more preferably 1 to 10 wt%, even more preferably 2 to 10 wt%, even more preferably 3.0 to 10 wt% polar lipids based on total lipids, wherein the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol.

[0036] Preferred sources for providing phospholipids, glycosphingolipids and / or cholesterol are egg lipids, milk fat, buttermilk fat and case serum fat, such as β-serum fat. Preferred sources of phospholipids (particularly PC) are soy lecithin and / or sunflower lecithin. According to the present invention, the nutritional composition preferably comprises phospholipids derived from mammalian milk. Preferably, the nutritional composition comprises phospholipids and glycosphingolipids derived from milk. Preferably, cholesterol is also obtained from milk. Preferably, the polar lipids (particularly phospholipids) are derived from milk. The polar lipids (particularly phospholipids) derived from milk include polar lipids (particularly phospholipids) separated from milk lipids, cream lipids, cream serum lipids, case serum lipids, β-serum lipids, whey lipids, cheese lipids and / or buttermilk lipids. The buttermilk lipids are typically obtained during the manufacture of buttermilk. The case serum lipids or β-serum lipids are typically obtained during the manufacture of anhydrous milk fat by butter. Preferably, the phospholipids, glycosphingolipids and / or cholesterol are obtained from milk cream. The nutritional composition preferably comprises phospholipids, glycosphingolipids and / or cholesterol derived from cow's milk, mare milk, sheep milk, goat milk, buffalo milk, horse milk and camel milk. Most preferably, a lipid extract separated from cow's milk is used. The use of polar lipids derived from milk fat advantageously comprises the polar lipids derived from milk fat globule membranes, which are more similar to the situation in human milk. Compared to polar lipids from other sources, polar lipids derived from whole milk, particularly phospholipids, are advantageously more effective in reducing blood pressure in childhood. The polar lipids, particularly phospholipids, are located on the surface of lipid globules, i.e., as a coating or outer layer. It is generally believed that when the phospholipids are present in the coating of lipid globules, they are more effective than being dry blended into a powdered product (i.e., existing as an ingredient itself). A suitable method for determining whether the polar lipids, particularly phospholipids, are located on the surface of lipid globules is a laser scanning microscope. Suitable commercially available sources of milk polar lipids including phospholipids are BAEF, SM2, SM3 and SM4 powders from Corman, Salibra from Glanbia and LacProdan MFGM-10 or PL20 from Arla. Preferably, the source of milk polar lipids comprises at least 4 wt% phospholipids based on total lipids, more preferably 7 to 75 wt%, most preferably 20 to 70 wt% phospholipids based on total lipids. Preferably, the weight ratio of phospholipids to protein is higher than 0.10, more preferably higher than 0.20, even more preferably higher than 0.3. Preferably at least 25 wt%, more preferably at least 40 wt%, most preferably at least 75 wt% of the polar lipids, in particular phospholipids, are derived from milk polar lipids.

[0037] Methods for obtaining lipid globules of increased size and having a phospholipid coating are disclosed in WO 2010 / 0027258, WO 2010 / 0027259 and WO 2013 / 135738.

[0038] Infant formula and follow-on formula

[0039] The nutritional composition is selected from infant formula and follow-up formula. This means that the nutritional composition of the present invention is not human milk. Alternatively, the term "formula" means that it relates to an artificially manufactured composition, or in other words, it is synthetic. Therefore, in one embodiment, the nutritional composition is selected from artificial infant formula and artificial follow-up formula, or synthetic infant formula and synthetic follow-up formula. In this context, infant formula refers to an artificially manufactured nutritional composition, which is intended for infants aged 0 to about 4 to 6 months and is intended to be used as a substitute for human milk. Typically infant formula is suitable for use as a sole source of nutrition. Such formula is also referred to as starting formula. Formula for infants starting from 4 to 6 months to 12 months is intended to be supplementary feeding on other foods when infants start weaning. Such formula is also referred to as follow-up formula. Infant formula and follow-up formula meet strict regulations, such as EU Commission Directive 2016 / 127.

[0040] The nutritional composition preferably comprises 3 to 7 g lipid / 100 kcal, more preferably 4 to 6 g lipid / 100 kcal, most preferably 4.5 to 5.5 g lipid / 100 kcal, 1.25 to 5 g lipid / 100 kcal, more preferably 1.35 to 4 g protein / 100 kcal, more preferably 1.5 to 3 g protein / 100 kcal, more preferably 1.25 to 2.5 g protein / 100 kcal, more preferably 1.25 to 2.25 g / 100 kcal, even more preferably 1.25 to 2.1 g protein / 100 kcal, and 6 to 18 g digestible carbohydrates / 100 kcal, more preferably 8 to 16 g digestible carbohydrates / 100 kcal, most preferably 10 to 15 g digestible carbohydrates / 100 kcal.

[0041] Lipids

[0042] Herein, LA refers to linoleic acid (18:2n6); ALA refers to alpha-linolenic acid (18:3n3); PUFA refers to polyunsaturated fatty acids; MUFA refers to monounsaturated fatty acids; LC-PUFA refers to long-chain unsaturated fatty acids, which contain at least 20 carbon atoms and have 2 or more unsaturated bonds; DHA refers to docosahexaenoic acid (22:6, n3); EPA refers to eicosapentaenoic acid (20:5n3); ARA refers to arachidonic acid (20:4n6); DPA refers to docosapentaenoic acid (22:5n3). PA refers to palmitic acid (C16:0). Medium-chain fatty acids (MCFA) refer to fatty acids having 8 or 10 or 12 carbon atoms. In the context of the present invention, it is understood that a reference to a fatty acid means that it can be attached to a glycerol backbone.

[0043] The lipids in the nutritional composition preferably comprise plant lipids. The lipids present in the nutritional composition preferably comprise PUFAs, more preferably LC-PUFAs. The nutritional composition preferably comprises 5 to 35 wt% PUFAs based on total fatty acids, more preferably 10 to 30 wt% PUFAs, most preferably 15 to 20 wt% PUFAs. In a preferred embodiment, the lipids in the nutritional composition comprise at least 10 wt% polyunsaturated fatty acids based on total fatty acids. It is also preferred that the nutritional composition comprises monounsaturated fatty acids (MUFAs), preferably 10 to 80 wt% MUFAs based on total fatty acids, more preferably 20 to 70 wt% MUFAs, most preferably 35 to 55 wt% MUFAs. In the context of the present invention, the weight percentage of fatty acids based on total fatty acids is calculated as all fatty acids are free fatty acids, therefore, it is not considered whether the fatty acids are attached to the glycerol backbone.

[0044] LA is preferably present in a sufficiently balanced amount to ensure healthy growth. Therefore, the nutritional composition preferably comprises less than 20wt% LA, more preferably 5 to 16wt%, most preferably 10 to 14.5wt% based on total fatty acids. Preferably, the nutritional composition comprises at least 5wt% LA based on total fatty acids. Per 100kcal, the nutritional composition preferably comprises 350-1400mg LA. Preferably, ALA is present in a sufficiently balanced amount to ensure healthy growth. Therefore, the nutritional composition preferably comprises at least 1.0wt% ALA based on total fatty acids. More preferably, the nutritional composition comprises at least 1.5wt% ALA based on total fatty acids, most preferably at least 2.0wt%. Preferably, the nutritional composition comprises less than 12.5wt% ALA, more preferably less than 10.0wt%, most preferably less than 5.0wt%. Preferably, the nutritional composition comprises a LA / ALA weight ratio of 2 to 20, more preferably 3 to 16, more preferably 4 to 14, most preferably 5 to 12.

[0045] Preferably, the nutritional composition comprises less than 10wt% short-chain fatty acids based on total fatty acids, more preferably less than 8wt%, even more preferably less than 6wt%, most preferably less than 5wt%. Preferably, the nutritional composition comprises at least 0.5wt% short-chain fatty acids based on total fatty acids, more preferably at least 0.6wt%, preferably at least 0.9wt%, more preferably at least 1.2wt%, more preferably at least 2.0wt%. Short-chain fatty acids are fatty acids with acyl chains of 2 to 6 carbon atoms. Preferably, the nutritional composition comprises less than 10wt% butyric acid (acyl chains of 4 carbon atoms) based on total fatty acids, more preferably less than 8wt%, more preferably less than 6wt%, more preferably less than 5wt%, most preferably less than 4wt%. Preferably, the nutritional composition comprises at least 0.5wt% butyric acid based on total fatty acids, preferably at least 0.6wt%, preferably at least 0.9wt%, more preferably at least 1.2wt%. The nutritional composition preferably comprises at least 3 wt% medium chain fatty acids (MCFA) based on total fatty acids, more preferably at least 10 wt%, even more preferably at least 15 wt%. The composition of the present invention advantageously comprises less than 50 wt% MCFA based on total fatty acids, more preferably less than 30 wt%, even more preferably less than 20 wt%.

[0046] According to the present invention, the nutritional composition preferably comprises LC-PUFA, more preferably n-3LC-PUFA. More preferably, the nutritional composition comprises EPA, DPA and / or DHA, even more preferably DHA. The content of n-3LC-PUFA (more preferably DHA) in the nutritional composition is preferably not more than 15wt% of the total fatty acid content, preferably not more than 10wt%, even more preferably not more than 5wt%. Preferably, the nutritional composition comprises at least 0.15wt%, preferably at least 0.35wt%, more preferably at least 0.75wt% of the total fatty acid content of n-3LC-PUFA, more preferably DHA. In one embodiment, the composition of the present invention comprises at least 0.15wt% n-3LC-PUFA based on total fatty acids, and the total fatty acids are selected from the group consisting of DHA, EPA and DPA, more preferably DHA.

[0047] As a group of n-6 fatty acids, especially arachidonic acid (ARA) and LA as its precursors, offset with a group of n-3 fatty acids, especially DHA, EPA and ALA as its precursors, the nutritional composition comprises a relatively low amount of ARA. The n-6 LC-PUFA (more preferably ARA) content preferably does not exceed 5wt% based on total fatty acids, more preferably does not exceed 2.0wt%, more preferably does not exceed 0.75wt%, even more preferably does not exceed 0.5wt%. ARA may also be absent.

[0048] Palmitic acid at the sn-2 position of triglycerides

[0049] The lipids in the nutritional composition preferably comprise triglycerides. Triglycerides comprise a glyceride molecule to which three fatty acid residues are attached via ester bonds, which three fatty acid residues may be the same or different and are generally selected from saturated and unsaturated fatty acids containing 6 to 26 carbon atoms, including but not limited to LA, ALA, oleic acid (C18:1), palmitic acid (PA; C16:0) and / or stearic acid (SA; C18:0). The fatty acid residues of such fatty acid triglycerides may be different, and the fatty acid residues are present and / or at one or more corresponding positions of the fatty acid residues, such as at the sn-1, -2 and / or -3 positions. The triglycerides used in the nutritional composition are preferably selected so that the amount of PA residues present in the triglyceride is 10 wt% or more, preferably more than 15 wt%, based on the total fatty acids present in the triglyceride. Thus, in one embodiment of the nutritional composition, the lipid comprises a triglyceride comprising at least 10 wt% palmitic acid based on total fatty acids, and wherein at least 15 wt% of the palmitic acid is present in the sn-2 position of the triglyceride, based on the weight of the total palmitic acid. Preferably, the amount of PA residues present in the triglyceride is less than 30 wt%, more preferably in the range of 16 to 24 wt%, based on the total fatty acids. The triglyceride used in the nutritional composition is preferably selected such that the total PA residues present in the triglyceride are at least 15 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, even more preferably at least 35 wt%, and most preferably at least 40 wt% of the PA is located in the sn-2 or β position of the triglyceride.

[0050] Triglycerides suitable for the nutritional composition are commercially available (e.g. under the name Betapol from Loders Croklaan). TM ) 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 TM In case these lipids are obtained by transesterification or interesterification of vegetable triglycerides, these sources are regarded as vegetable lipids in the context of the present invention.

[0051] The preferred source of triglycerides with palmitic acid at the sn-2 or beta position of the triglyceride is non-human animal fat, more preferably non-human mammal milk fat, even more preferably bovine milk fat. Preferably non-human mammal milk fat (especially bovine milk fat) is preferably used in the form of anhydrous milk fat or ghee. Since the lipid globules of the nutritional composition of the present invention can be prepared more easily when they are in a homogenous fat phase, it is preferred that the source of the milk fat is in a homogenous fat phase, such as ghee or anhydrous milk fat, and is not present in the form of an oil-in-water emulsion (such as cream). Therefore, in a preferred embodiment of the nutritional composition of the present invention, the lipid comprises milk fat, preferably bovine milk fat in an amount of 10 to 100 wt% based on total lipids, preferably 10 to 80 wt% based on total lipids, more preferably 10 to 70 wt%, more preferably 20 to 80 wt%, more preferably 20 to 70 wt%, more preferably 30 to 70 wt%, more preferably 15 to 60 wt%, more preferably 20 to 60 wt%, even more preferably 25 to 55 wt% based on total lipids.

[0052] When such lipid compositions having increased amounts of palmitic acid located at the sn-2 position of the triglyceride molecule were administered, an unexpected lowering effect on blood pressure in children was observed.

[0053] In a preferred embodiment, the present invention relates to a nutritional composition selected from infant formula and follow-on formula for use in reducing the risk of childhood hypertension in children under 13 years of age, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids, and the lipids comprise triglycerides (the triglycerides comprising at least 10 wt% palmitic acid based on total fatty acids), and wherein at least 15 wt% of the palmitic acid based on total palmitic acid is present in the sn-2 position of the triglycerides. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0054] In another preferred embodiment, the present invention relates to a nutritional composition selected from infant formula and follow-on formula for use in reducing the risk of childhood hypertension in children under 13 years of age, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, and wherein the lipids contain at least 10 wt% mammalian milk fat, in particular bovine milk fat, based on total lipids, wherein the nutritional composition comprises lipid globules having a volume-weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0055] In another preferred embodiment, the present invention relates to a nutritional composition selected from infant formula and follow-on formula for use in preventing pediatric hypertension in children less than 13 years of age, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids, and the lipids comprise triglycerides (the triglycerides comprising at least 10 wt% palmitic acid based on total fatty acids), and wherein at least 15 wt% of the palmitic acid based on total palmitic acid is present in the sn-2 position of the triglycerides. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0056] In another preferred embodiment, the present invention relates to a nutritional composition selected from infant formula and follow-on formula for use in the prevention of pediatric hypertension in children under 13 years of age, wherein the nutritional composition comprises lipids, proteins and digestible carbohydrates, and wherein the lipids contain at least 10 wt% mammalian milk fat, in particular bovine milk fat, based on total lipids, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0057] The invention may also be described as the use of lipid globules in the manufacture of a nutritional composition selected from infant formula and follow-on formula for reducing the risk of childhood hypertension in children under 13 years of age, wherein the nutritional composition comprises lipid, protein and digestible carbohydrate, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids, and the lipids comprise triglycerides (the triglycerides comprising at least 10 wt% palmitic acid based on total fatty acids), and wherein at least 15 wt% of the palmitic acid based on total palmitic acid is present in the sn-2 position of the triglycerides. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0058] The invention may also be described as the use of lipid globules in the manufacture of a nutritional composition selected from infant formula and follow-on formula for reducing the risk of childhood hypertension in children under 13 years of age, wherein the nutritional composition comprises lipid, protein and digestible carbohydrates, and wherein the lipid contains at least 10 wt% mammalian milk fat, in particular bovine milk fat, based on total lipids, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0059] The present invention may also be described as the use of lipid globules in the manufacture of a nutritional composition selected from infant formula and follow-on formula for use in the prevention of pediatric hypertension in children less than 13 years of age, wherein the nutritional composition comprises lipid, protein and digestible carbohydrate, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids, and the lipids comprise triglycerides (the triglycerides comprising at least 10 wt% palmitic acid based on total fatty acids), and wherein at least 15 wt% of the palmitic acid based on total palmitic acid is present in the sn-2 position of the triglycerides. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0060] The invention may also be described as the use of lipid globules in the manufacture of a nutritional composition selected from infant formula and follow-on formula for use in the prevention of pediatric hypertension in children less than 13 years of age, wherein the nutritional composition comprises lipid, protein and digestible carbohydrates, and wherein the lipid contains at least 10 wt% mammalian milk fat, in particular bovine milk fat, based on total lipids, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids. Preferably, the nutritional composition comprises 0.5 to 20 wt% phospholipids based on total lipids.

[0061] Preferably, blood pressure is reduced in childhood and / or the risk of elevated blood pressure in childhood is reduced when compared to similar children consuming an infant formula or follow-on formula not comprising lipid globules having a mode diameter based on volume of at least 1.0 μm and having a diameter of 2 to 12 μm in an amount of at least 45 volume % based on total lipids and not comprising a coating (comprising phospholipids) on the surface and comprising less than 10 wt % mammalian milk fat based on total lipids, more particularly, preferably blood pressure is reduced in childhood and / or the risk of elevated blood pressure in childhood is reduced when compared to similar children consuming a standard infant formula comprising a follow-on formula having lipid globules having a mode diameter based on volume of about 0.5 μm and not having a coating comprising phospholipids and comprising at least about 97 wt % vegetable lipids based on total lipids.

[0062] protein

[0063] The nutritional composition preferably comprises protein, preferably in the amount specified above. The source of the protein is preferably selected in the following manner: meet the minimum requirements of the essential amino acid content and ensure satisfactory growth. Therefore, protein sources based on bovine milk protein (such as whey protein, casein and mixtures thereof) and proteins based on soy, potato or pea are preferred. In the case of using whey protein, the protein source is preferably based on acid whey or sweet whey, whey protein isolate or a mixture thereof and can include alpha-lactalbumin and beta-lactoglobulin. More preferably, the protein source is based on acid whey or sweet whey, and casein-sugar-macropeptide (CGMP) has been removed therefrom. Preferably, the composition comprises at least 3wt% casein based on dry weight. Preferably, the casein is complete and / or non-hydrolyzed. For the present invention, protein includes peptides and free amino acids.

[0064] Digestible carbohydrates

[0065] The nutritional composition preferably comprises digestible carbohydrates, preferably in the amount specified above. Preferred digestible carbohydrate sources are 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 nutritional composition preferably comprises lactose. The nutritional composition preferably comprises digestible carbohydrates, wherein at least 35wt%, more preferably at least 50wt%, more preferably at least 75wt%, even more preferably at least 90wt%, most preferably at least 95wt% of the digestible carbohydrates are lactose. Based on dry weight, the composition of the present invention preferably comprises at least 25wt% lactose, preferably at least 40wt%.

[0066] Indigestible Carbohydrates

[0067] In a preferred embodiment, the nutritional composition comprises non-digestible oligosaccharides.Preferably, the nutritional composition comprises non-digestible oligosaccharides having a degree of polymerization (DP) of 2-250, more preferably 3-60.

[0068] Preferably the composition of the present invention comprises oligofructose, inulin and / or galacto-oligosaccharide, more preferably galacto-oligosaccharide, most preferably trans-galacto-oligosaccharide. In a preferred embodiment, the composition comprises a mixture of trans-galacto-oligosaccharide and oligofructose or inulin. Suitable non-digestible oligosaccharides are for example Vivinal GOS (FrieslandCampina DOMO), Raftilin HP or Raftilose (Orafti).

[0069] Preferably, the nutritional composition comprises 80 mg to 2 g of non-digestible 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 nutritional composition preferably comprises 0.25 wt% to 20 wt%, more preferably 0.5 wt% to 10 wt%, even more preferably 1.5 wt% to 7.5 wt% non-digestible oligosaccharides.

[0070] application

[0071] In the method or use according to the present invention, the nutritional composition is applied to an infant or for an infant. In the context of the present invention, the infant is at most 12 months old. Preferably, the nutritional composition is applied to or for a full-term infant. A full-term infant means an infant born at a gestational age of 37 to 42 weeks. Preferably, the nutritional composition is applied to or for a healthy infant. Preferably, the nutritional composition is used at least within the first 2 months after birth, preferably at least within the first 3 months after the birth of the infant, and more preferably at least within the first 4 months after the birth of the infant. Preferably, the nutritional composition is applied to an infant less than 12 months old, preferably less than 6 months old, more preferably less than 4 months old. In a preferred embodiment, the nutritional composition is applied to an infant of 0 to 6 months old, preferably 0 to 4 months old.

[0072] The present invention provides a nutritional composition for use in reducing the risk of elevated blood pressure in children. Children in childhood refer to children under the age of 13. Reducing the risk of elevated blood pressure in children is suitable for children under the age of 13, preferably children under the age of 10, preferably children under the age of 8, preferably children under the age of 6, preferably children in the first 5 years after birth, preferably 5 years old, and wherein the child is preferably at least 1 year old.

[0073] The present invention provides a nutritional composition for use in preventing pediatric hypertension in a subject. A child with pediatric hypertension refers to a child with hypertension who is less than 13 years old. Prevention of pediatric hypertension is applicable to children who are less than 13 years old, preferably less than 10 years old, preferably less than 8 years old, preferably less than 6 years old, preferably in the first 5 years after birth, preferably 5 years old, and wherein the child is preferably at least 1 year old.

[0074] Preferably, the blood pressure is diastolic pressure or arterial pressure, or diastolic pressure and arterial pressure.

[0075] In one embodiment according to the invention, a reduction in blood pressure in infants is facilitated, and / or a reduction in or risk of higher blood pressure in infants and children is achieved.

[0076] Examples

[0077] Example 1: Experimental and control formula milk powder

[0078] Diet 1: Control formula

[0079] An infant formula milk powder, each 100 ml of ready-to-drink formula milk powder has 66 kcal, 1.3 g protein (whey protein and casein ratio of 6 / 4 w / w), 7.3 g digestible carbohydrates (mainly lactose), 3.4 g fat, 0.8 g short-chain oligosaccharide (from 9 / 1 w / w) GOS) and long-chain oligofructose (from ), minerals, vitamins, trace elements and other micronutrients as known in the art and in accordance with the instructions for infant formula. The formula is provided in powder form with instructions for reconstitution with water. About 13.6 g of the powder is reconstituted to 100 ml of ready-to-drink infant formula.

[0080] The fat component contained mainly vegetable fats (palm oil, low-erucic acid rapeseed oil, coconut oil, high-oleic acid sunflower oil and a blend of sunflower oils), a small amount of soy lecithin (0.13 wt %) and about 1.5 wt % LC-PUFA premix (fish oil and microbial oil).

[0081] The lipid globules have a mode diameter of about 0.5 μm based on volume, and the volume % of lipid globules having a mode diameter between 2 and 12 μm is less than 10.

[0082] Diet 2: Experimental Infant Formula

[0083] An infant formula similar to Diet 1 with the following differences:

[0084] The fat component consists of about 51 wt% vegetable fat (low erucic acid rapeseed oil, coconut oil, high oleic acid sunflower oil and a blend of sunflower oil), about 44 wt% anhydrous bovine milk fat, 1.5 wt% LC-PUFA containing oils (fish oil and microbial oil), 0.13 wt% soy lecithin, and about 3.6 wt% milk fat from buttermilk rich in milk lecithin or milk fat globule membrane (milk lecithin is about 1.5 wt% based on total lipids).

[0085] The lipid globules have a mode diameter of about 5.6 μm based on volume, and the volume % of lipid globules having a mode diameter between 2 and 12 μm is greater than 45. The phospholipids are present in a coating on the lipid globules.

[0086] The fatty acid composition of diet 1 and 2 is very similar in saturated, monounsaturated and polyunsaturated acid, and n3 and n6 PUFA content.The amount of the palmitic acid of diet 1 and diet 2 is 18.4wt% and 17.7wt% (based on total fatty acids) respectively.For diet 2, the palmitic acid residue of about 36wt% is located at the sn-2 position, and for diet 1, the amount of palmitic acid is about 13wt%.The amount of C4:0 (butyric acid) is 0.10wt% in diet 1 and is 1.39wt% in diet 2, and the amount of C6:0 (hexanoic acid) is 0.24wt% in diet 1 and is 0.98wt% in diet 2.This wt% is based on the total fatty acids in this infant formula milk powder.

[0087] Example 2: Study plan and study population

[0088] After one or both parents / one or more legal guardians signed informed consent, eligible formula-fed infants were randomized to receive either the experimental product or the control product for a double-blind period of up to 17 weeks (depending on their age at the start of the study). Parents whose infants participated in the study up to 17 weeks of age (4 months) and who did not withdraw consent were asked to participate in a follow-up study at 3-5 years of age.

[0089] The subjects were in a sitting position after resting for 5 minutes, and systolic and diastolic blood pressure were measured at the right brachial artery using a sphygmomanometer, and the mean blood pressure was recorded as the average of four measurements. All measurements were performed by trained research staff using calibrated equipment and according to standard protocols.

[0090] Arterial blood pressure (ABP) was defined based on systolic blood pressure (SBP) and diastolic blood pressure (DBP) as follows: ABP = (1 / 3*SBP) + (2 / 3*DBP). Blood pressure results were defined as normal (<90th percentile), elevated (values ​​≥90th to <95th percentile), or hypertensive (≥95th percentile) based on age-standardized, sex-standardized, and height-standardized SBP or DBP values ​​according to the AAP clinical practice guidelines. To evaluate blood pressure results and after confirming the assumption of normality, analysis of covariance (ANCOVA) was used with treatment group as a fixed effect and sex, maternal education, maternal pre-pregnancy BMI, continent (Europe, Asia) as covariates (results not shown) and 5-year-old child's BMI as a covariate (see Table 1).

[0091] Use the All statistical analyses were performed using SAS (SAS Enterprise Guide 4.3 or higher) (SAS Institute Inc., Cary, NC).

[0092] Blood pressure measurement results

[0093] The results of blood pressure measurements are listed in Table 1 .

[0094] Table 1: Estimated mean blood pressure results at 5 years

[0095]

[0096] The estimated mean diastolic and arterial blood pressures in the experimental group were both statistically significantly lower than those in the control group, and the systolic blood pressure was lower in the experimental group compared with the control group, although not statistically significant.

[0097] Children with elevated blood pressure or hypertension were found at follow-up at age 5. The numbers of infants with normal blood pressure, elevated blood pressure, and hypertension are reported in Table 2.

[0098] Table 2: Blood pressure results at 5 years old

[0099]

[0100] *Height was not recorded for one child in each group, which means that for these children, the blood pressure category (normal, elevated, hypertensive) could not be determined.

[0101] Compared with the control group, children in the experimental group had a lower probability of elevated blood pressure after adjustment for covariates including current childhood BMI at 5 years of age.

Claims

1. A nutritional composition selected from infant formula and follow-on formula comprising lipid, protein and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids, for use in reducing the risk of childhood hypertension in children under the age of 13 years.

2. The nutritional composition according to claim 1, wherein the risk of elevated blood pressure in childhood is reduced when compared to similar children consuming infant formula and follow-on formula comprising lipid globules having a mode diameter based on volume of about 0.5 μm and not having a coating comprising phospholipids.

3. Nutritional composition for use according to any one of the preceding claims, wherein the hypertension is diastolic blood pressure or arterial pressure, or diastolic blood pressure and arterial pressure.

4. A nutritional composition selected from infant formula and follow-on formula comprising lipid, protein and digestible carbohydrates, wherein the nutritional composition comprises lipid globules having a volume weighted mode diameter of at least 1.0 μm and / or wherein at least 45 vol.% of the lipid globules have a diameter of 2 to 12 μm, and wherein the lipid globules have a coating comprising phospholipids, for use in the prevention of pediatric hypertension in children under the age of 13 years.

5. Nutritional composition for use according to any of the preceding claims, wherein the nutritional composition is administered to infants between 0 and 6 months of age, preferably between 0 and 4 months of age.

6. A nutritional composition for use according to claim 5, wherein the infant is a full-term infant.

7. A nutritional composition for use according to claim 5 or 6, wherein the infant is a healthy infant.

8. A nutritional composition for use according to any one of the preceding claims, comprising at least 0.5 wt% phospholipids based on total lipids.

9. Nutritional composition for use according to any one of the preceding claims, wherein the phospholipids comprise at least 5 wt% sphingomyelin based on total phospholipids.

10. Nutritional composition for use according to any one of the preceding claims, wherein the phospholipids are derived from milk lipids.

11. A nutritional composition for use according to any one of the preceding claims, wherein the lipid comprises a triglyceride comprising at least 10 wt% palmitic acid based on total fatty acids, and wherein at least 15 wt% palmitic acid based on total palmitic acid is present in the sn-2 position of the triglyceride.

12. Nutritional composition for use according to any one of the preceding claims, wherein the lipid comprises at least 10 wt% milk fat, preferably bovine milk fat, based on total lipids.

13. A nutritional composition for use according to any one of the preceding claims, wherein the formula is a powder suitable for reconstitution with water to provide a ready-to-drink formula.

Images