Particulate nutritional composition with large lipid globules

Abstract

The present invention relates to particulate nutritional compositions such as an infant formula, a follow-on formula or a young child formula that comprises lipid globules having a volume weighted mode diameter of at least 1.0 µm, preferably wherein at least 40 vol.% of the lipid globules has a diameter between 2 µm and 12 µm, wherein the particulate nutritional composition has a particle size distribution leading to improved properties.

Description

[0001] PARTICULATE NUTRITIONAL COMPOSITION WITH LARGE LIPID GLOBULES

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to particulate nutritional compositions such as an infant formula, a follow- on formula or a young child formula that comprises lipid globules having a volume weighted mode diameter of at least 1 .0 pm, preferably wherein at least 40 vol.%, based on lipid volume, of the lipid globules has a diameter between 2 pm and 12 pm, wherein the particulate nutritional composition has a particle size distribution leading to improved properties.

[0004] BACKGROUND OF THE INVENTION

[0005] Infant or follow-on formulae are commonly used when breastfeeding is inadequate or unsuccessful for medical reasons, or because of a choice not to breastfeed. Commercial infant formulae are commonly used to provide supplemental or sole source of nutrition in early life. These formulae comprise a range of nutrients to meet the nutritional needs of the growing infant, and typically include fat, carbohydrate, protein, vitamins, minerals, and other nutrients helpful for optimal infant growth and development.

[0006] Nutritional compositions for infants and young children are often sold as powders to be reconstituted with water or in some instances as ready to drink or concentrated liquid compositions. Those compositions are intended to cover most or all the nutritional needs of the infants or young children.

[0007] Human milk lipids have a distinct physical structure composed of large lipid globules with an average volume-weighted mode diameter of about 4 pm existing of a triglyceride core coated by a tri-layer of membranes, the milk fat globule membrane (MFGM). The volume-weighted mode diameter of lipid droplets in standard infant formula is about 0.3 to 0.5 pm due to the industrial processing procedures to achieve stable and reproducible end products and is not surrounded by MFGM but mostly by proteins such as casein. Standard commercially available formulae also mostly contain vegetable oils and have small lipid droplets with proteins adhering to the surface.

[0008] Infant formula with lipid globules with an architecture more similar to the lipid globules in human milk and a process to prepare those have been described in for example WO2013 / 135739 and WO2016 / 146496. More in particular, the lipid globules in the nutritional compositions disclosed in these documents have a volume weighted mode diameter of more than 1 .0 pm and / or a substantial part of the lipid globules have a diameter between 2 pm and 12 pm. The process by which these nutritional compositions are prepared in WO2016 / 146496 involves the steps of: a) providing an aqueous phase with a dry matter content of 5 to 75 wt.% (based on total weight of the aqueous phase), which comprises at least one protein component, b) providing a liquid lipid phase, which comprises at least one lipid, and c) carrying out a first homogenization step by homogenizing the lipid phase with the aqueous phase in a ratio of 3 to 50 % (w / w) so as to obtain a first lipid and protein component-containing composition comprising lipid globules, wherein at least 10 vol.% of the lipid globules have a diameter of >12 pm and / or wherein the lipid globules have a volume-weighted mode diameter from 5 to 25 pm, d) carrying out a second homogenization step by homogenizing the first lipid and protein component-containing composition obtained in step c) with an atomizer, wherein the particle size of the lipid globules obtained in step c) is reduced so as to obtain a second lipid and protein component-containing composition comprising lipid globules, wherein less than 10 vol.% of the lipid globules have a diameter of >12 pm and / or wherein the lipid globules have a volume- weighted mode diameter from 2.5 to 7 pm.

[0009] EP3043660B1 relates to a process using a rotary atomizer for preparing a spray-dried composition with large, phospholipid coated lipid globules.

[0010] NZ519401A relates to a process for producing a spray dried powder of baby food, whole-milk or skimmilk. This document defines a “grain score”, which is a self-defined score as a measure for the amount of white spots left on the sides of a beaker after reconstituting the powder, by stirring it and leaving it for 5 minutes. The composition of these white spots is not disclosed in this document.

[0011] SUMMARY OF THE INVENTION

[0012] It has now been found that the particulate nutritional compositions as described in the above disclosures can be further improved. The dissolution properties thereof in water were established to be suboptimal, in particular, if cold water was used and / or if the consumer did not shake the bottle properly. Also, it was established that there was room to improve the free fat content of the compositions, the wettability and the particle density of the particulate nutritional composition.

[0013] Quite unexpectedly, the particulate nutritional compositions of the present invention with lipid globules with an architecture more similar to the lipid globules in human milk, viz. which contain the same large lipid globules as in the disclosures referred to above, but in which the powder particle size distribution is adjusted provides for compositions that are easier to dissolve in water, and that additionally have a lower free fat content and a higher particle density.

[0014] In a study on properties of particulate nutritional compositions containing large lipid globules with a volume weighted mode diameter of at least 1.0 pm and / or wherein a substantial part of the lipid globules have a diameter of between 2 pm and 12 pm, it was unexpectedly found that dissolution is improved when the powder particle diameters are increased, namely to provide for a Dio of at least 75 pm, and one or more of a D20 of at least 135 pm and a D50 of at least 235 pm, D10, D20 and D50 being based on volume.

[0015] As a larger particle size distribution results in a smaller surface area of the powder particles, one would expect a reduced solubility. However, the larger particle sizes of the powder particles were surprisingly leading to improved solubility, even when a bottle is not shaken. Accordingly, the present invention provides a particulate nutritional composition comprising lipid and protein, and optionally carbohydrates, wherein the lipid in the particles is in the form of lipid globules and wherein the lipid globules have a mode diameter, based on volume, of at least 1.0 pm and / or at least 40 vol.% of the lipid globules have a diameter between 2 and 12 pm; and wherein the particles have: i) a Dio of at least 75 pm, and ii) one or more of a D20 of at least 135 pm and a D50 of at least 235 pm, the D10, D20 and D50 being based on volume.

[0016] The invention also pertains to the use of the particulate nutritional composition to prepare a reconstituted nutritional composition by adding a food grade aqueous liquid to the particulate nutritional composition.

[0017] The present invention in addition provides a process to prepare such particulate nutritional compositions, and solutions containing the reconstituted particulate nutritional composition. Said process comprising the steps of a. Providing an aqueous phase with a dry matter content of 10-60 wt.% based on total weight of the aqueous phase which comprises at least one protein component; b. Providing a lipid phase which comprises at least one lipid; c. Mixing the lipid phase with the aqueous phase to provide an oil in water emulsion; d. Spray-drying the oil in water emulsion in a spray-drier to provide particles and fine particles; e. Recirculating the fine particles obtained in step d. to and / or in the spray-drier; f. Optionally further drying the particles obtained in step d.; g. Optionally (dry) blending further particles with the particles obtained in step d. or step f..

[0018] Though recirculation of fines into the atomization zone as such is known in the field of spray drying, it leading to a product having particles with specific particle size properties and more in particular leading to a product having improved dissolution properties, reduced free fat and increased particle density were totally unexpected.

[0019] Better dissolution of a particulate nutritional composition in water herein includes two elements, first that it is possible to use relatively cold water for preparing a bottle with reconstituted powder and second that thorough shaking is not required to get full dissolution and a uniform reconstituted liquid without lumps or remaining powder.

[0020] A reduction in free fat content in the particulate nutritional composition is desirable as free fat is subject to oxidation and could lead to a composition becoming rancid and this would negatively influence shelf life. An increased particle density is desirable because having particles with an increased mass makes that particles tend to float less on liquid when reconstituted. Floating will delay or hinder the reconstitution in an aqueous liquid.

[0021] The invention further pertains to a particulate nutritional composition, as described herein above, for use in the prevention of the development of obesity later in life, improving the immune system, preventing infections, improving the recovery from infections, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem.

[0022] The invention also pertains to a non-therapeutic method for the promotion of metabolic health, the promotion of the development of good body composition, the promotion of balanced growth, the promotion of lean growth, the promotion of cognitive development, improving brain health and / or providing beneficial prebiotic effect, said method comprising administration to a subject of the particulate nutritional composition as described herein above.

[0023] DETAILED DESCRIPTION OF THE INVENTION

[0024] As used herein, the following terms have the following meanings.

[0025] The term “particulate nutritional composition” as used herein refers to a nutritional composition comprising particles, a synonym is a “powdered nutritional composition’.

[0026] The term “infant” as used herein refers to a child under the age of 12 months.

[0027] “Infant formula” or “follow-on formula” or “young child formula” means that it concerns a composition that is artificially made or in other words that it is a synthetic composition (i.e., the synthetic composition is not breast milk). Hence the nutritional composition is preferably an artificial infant formula or an artificial follow-on formula or an artificial young child formula or a synthetic infant formula or a synthetic follow- on formula or a synthetic young child formula.

[0028] Infant formula refers to nutritional compositions, artificially made, intended for infants of 0 months to about 4 months to 6 months of age and are intended as a substitute for human milk. Typically, infant formulae are suitable to be used as sole source of nutrition. Such infant formulae are also known as starter formula. Follow-on formulae are for infants starting with at 4 months to 6 months of life to 12 months of life and are intended to be supplementary feedings for infants that start weaning on other foods. Infant formulae and follow-on formulae are subject to strict regulations, for example for the EU regulations no. 609 / 2013 and no. 2016 / 127.

[0029] The term “young child” as used herein refers to a child aged between one and three years, also called a toddler. Young child formula refers to nutritional compositions, artificially made, intended for infants of 12 months to 36 months, which are intended to be supplementary feedings for infants. In the context of the present invention, young child formula can also be named growing-up milk.

[0030] “Base powders” for an infant formula, follow on formula, or young child formula are particulate nutritional compositions to which in a further blending step one or more further ingredients are added to make a complete formula meeting the regulations referred to above. In preferred embodiments the base powder contains at least a lipid and protein ingredient, in more preferred embodiments the base powder contains at least a lipid, a protein and a carbohydrate ingredient. Ingredients that are blended with the base powder are in preferred embodiments one or more non-digestible oligosaccharides, LCPUFA;s probiotics, vitamins and minerals. Most preferred this blending step is a dry blending step and the one or more of non-digestible oligosaccharides, LCPUFA’s, probiotics, vitamins and minerals are blended in their powder form.

[0031] As used herein in the context of powder particle size distributions, the percentile D10 is a particle diameter, below which 10 vol.% of the sample volume exists. D20 is a particle diameter, below which 20 vol.% of the sample volume exists. Similarly, D50 is the particle diameter, below which 50 vol.% of the sample volume exists. In the same way, one can determine the particle diameter for percentile DY, below which Y% of the sample volume is below. When size distribution is linked to particles or fine particles, it refers to the size distribution of powder particles, unless the context clarifies that the size distribution of the lipid globules within the nutritional composition was intended.

[0032] The volume-based size distribution of the lipid globules and the particles in the particulate nutritional composition, including D10, D20, D50 and D90, can suitably be determined using a laser diffraction particle size analyzer such as a Mastersizer 2000 (Malvern Instruments, Malvern, UK) or Mastersizer 3000 (Malvern Panalytical, Malvern, UK). In the Examples, a suitable method is described both for the lipid globule size distribution, as for the powder particle size distribution.

[0033] Delta D90-D10 as used herein is the difference between the D90 and the D10 value and is an indication of the spread of the particle size distribution.

[0034] Fine particles (sometimes also referred to as fines) are defined as particles with a D20 based on volume of lower than 75 pm, more preferably lower than 60 pm, even more preferably lower than 50 pm. In another preferred embodiment, fine particles have a D10 based on volume of below 50 pm, more preferably below 40 pm, even more preferably 30 pm or less. In yet another preferred embodiment fine particles have a D90 based on volume of below 200 pm, more preferably below 175 pm, even more preferably below 150 pm.

[0035] The degree to which a particulate nutritional composition is “dissolvable” depends on various properties which can be classified as wettability, sinkability, dispersibility, and solubility. Wettability or wetting time is a measure of the time (seconds) it takes to wet a dry powder and is determined following the standard method ISO-17758-2014 with two adjustments, namely that water with a temperature of 40 deg C was employed and that 13 grams of powder was used per 250 ml of water. A short wetting time means that powder dispersion / dissolution typically proceeds faster.

[0036] In the context of the present invention, the free fat content was determined by the method described by Sorensen et al. (Analytical Methods for Dry Milk Products, 4thEdition, 1978). The method from Sorensen et al. was adapted as follows; 5 g of particulate nutritional composition was mixed with 50 ml petroleum ether and agitated for 15 minutes. The mixture was filtered, and the petroleum ether phase (filtrate) was collected. The extraction was repeated: the remaining solid was mixed with 50 additional ml of petroleum ether and agitated for 15 minutes. The mixture was filtered, and the petroleum ether phase was collected and merged with the first filtrate. The petroleum ether was evaporated. The solid residue was dried at 102 °C for 90 minutes. The free fat content (%) was calculated as follows:

[0037] , , weight of the solid residue free fat content (%) = - - - — — - - - x 100 weight of the sample

[0038] Particle density is the mass density of the individual particles that make up the nutritional particulate composition. Particle density is distinct from bulk density which is the mass density of a defined volume of particles and that is also influenced by voids between the particles. Particle density in the context of this invention is calculated by dividing the mass of a sample by its true volume. The true volume is measured by gas pycnometry using a UltraPyc 1200E (Quantachrome Instruments, USA) applying the pressure-volume-relation for gas as described by the Boyle’s law.

[0039] In this document and in its claims, the verb "to comprise" and its conjugations is used in its non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. In addition, reference to an element by the indefinite article "a" or "an" does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there be one and only one of the elements. The indefinite article "a" or "an" thus usually means "at least one".

[0040] Formula

[0041] The nutritional composition is preferably in the form of a medical nutritional product, an infant formula, a follow-on formula, or a young child formula. This means that the composition is not human milk. It also means that the nutritional composition is not native cow’s milk or native milk from another mammal. The nutritional composition is preferably an infant formula or a follow-on formula. More preferably the nutritional composition is an infant formula.

[0042] In some embodiments the nutritional composition is preferably a base powder for any of the above products to which some ingredients are still to be added in a (dry) blending step. The nutritional composition comprises protein, and lipid, and optionally digestible carbohydrates, wherein the lipid preferably provides 30 to 60% of the total calories, the protein provides 5% to 20% of the total calories and when added, the digestible carbohydrates provide 25% to 75% of the total calories.

[0043] The nutritional composition is preferably an infant formula or follow-on formula and preferably comprises 3 g to 7 g lipid / 100 kcal, more preferably 4 g to 6 g lipid / 100 kcal, even more preferably 4.5 g to 5.5 g lipid / 100 kcal, preferably comprises 1.7 g to 3.5 g protein / 100 kcal, more preferably 1.8 g to 2.1 g protein / 100 kcal, even more preferably 1 .8 g to 2.0 g protein / 100 kcal and preferably comprises 5 g to 20 g digestible carbohydrate / 100 kcal, more preferably 6 g to 16 g digestible carbohydrate / 100 kcal, even more preferably 10 g to 15 g digestible carbohydrate / 100 kcal.

[0044] Preferably the nutritional composition is an infant formula or follow-on formula, and preferably has an energy density of 60 kcal / 100 ml to 75 kcal / 100 ml, more preferably 60 kcal / 100 ml to 70 kcal / 100 ml, when in a ready-to-drink form. This caloric density ensures an optimal balance between hydration and caloric intake.

[0045] The particulate nutritional composition preferably has a dry matter content of at least 90 wt.%, more preferably 92.5-100 wt.%, even more preferably 95-99.9 wt.%.

[0046] Preferably, the particulate nutritional composition comprises 80-99.5 wt.% of base powder particles, more preferably 85-99 wt.% of base powder particles. Further particles that may be preferably added are components that can be added in a dry blending step, such as digestible carbohydrates, non- digestible oligosaccharides, LCPUFA’s, probiotics, minerals and vitamins.

[0047] The weight ratio between the base powder particles and the further particles in the particulate nutritional composition is preferably at least 10:1 , more preferably 25:1-1500:1 , and most preferably 50:1-1000:1 .

[0048] Preferably the particle size distribution of the particles have a D10 of 75 pm to 150 pm, more preferably 85 pm to 140 pm, even more preferably 95 pm to 130 pm. Preferably, the particle size distribution of the particles have a D10 of at least 85 pm, even more preferably at least 95 pm.

[0049] Preferably the particle size distribution of the particles have a D20 of 135 pm to 200 pm, more preferably 145 pm to 190 pm, even more preferably 150 pm to 180 pm. In an embodiment the particles preferably have a D20 of at least 135 pm, more preferably a D20 of at least 145 pm, even more preferably at least 150 pm.

[0050] Preferably the particle size distribution of the particles have a D50 of 235 pm to 340 pm, more preferably 240 pm to 320 pm, even more preferably 245 pm to 300 pm. In an embodiment the particles preferably have a D50 of at least 235 pm, more preferably at least 245 pm, even more preferably at least 255 pm. In an embodiment, the particle size distribution of the particles have a D90 of less than 650 pm, more preferably less than 600 pm, even more preferably less than 550 pm. In an embodiment the particles have a D90 of at least 400 pm, more preferably at least 410 pm, even more preferably at least 420 pm.

[0051] Preferably, the particle size distribution of the particles have a delta D90-D10, based on volume, of less than 500 pm, more preferably less than 475 pm, even more preferably less than 450 pm. The delta D90- D10 is preferably more than 300 pm, more preferably more than 350 pm.

[0052] In a preferred embodiment the nutritional composition has a free fat content of less than 10%, more preferably less than 8%, and even more preferably less than 6%.

[0053] In a preferred embodiment the nutritional composition has a particle density of at least 1.000 g / cm3, more preferably at least 1 .050 g / cm3, and even more preferably at least 1 .150 g / cm3. The particle density is preferably less than 2.000 g / cm3

[0054] In a preferred embodiment the wettability of the nutritional composition is less than 100 sec, preferably less than 75 sec, more preferably less than 50 sec, most preferably less than less than 40 seconds.

[0055] Process

[0056] The process of the invention for producing the particulate or reconstituted nutritional composition, as described herein above, comprises the steps of a. Providing an aqueous phase with a dry matter content of 10-60 wt.% based on total weight of the aqueous phase which comprises at least one protein component; b. Providing a lipid phase which comprises at least one lipid; c. Mixing the lipid phase with the aqueous phase to provide an oil in water emulsion; d. Spray-drying the oil in water emulsion in a spray-drier to provide particles and fine particles; e. Recirculating the fine particles obtained in step d. to and / or in the spray-drier; f. Optionally further drying the particles obtained in step d.; g. Optionally (dry) blending further particles with the particles obtained in step d. or step f.

[0057] For the avoidance of doubt, the particles and fine particles in step d. refer to (fine) powder particles of the nutritional composition to be produced and not to the lipid globules.

[0058] In a preferred embodiment the spray-drier comprises: i. an atomization zone comprising at least one inlet for fine particles, and one or more inlets for the oil-in-water emulsion connected to one or more atomizers; ii. a downstream drying zone comprising at least one outlet for the particles; and

[0059] Hi. an outlet, preferably at least one outlet, for air and fine particles; and wherein the fine particles are collected after exiting their outlet and are recirculated to the at least one inlet for fine particles of the atomization zone. Preferably the collection of fine particles is done by separating the air from the fine particles in a cyclone, more preferably in at least one cyclone.

[0060] In a particularly preferred embodiment, step c. and step d. of the process are as follows: c. Mixing the lipid phase and the aqueous phase to provide an oil in water emulsion, wherein at least 10 vol.% of the lipid globules in the oil in water emulsion have a diameter of >12 pm and / or wherein the lipid globules in the oil in water emulsion have a volume-weighted mode diameter from 5 to 25 pm, preferably 7 to 15 pm; d. Spray-drying the oil in water emulsion in a spray-drier to provide particles and fine particles, wherein the size of the lipid globules is reduced so as to obtain particles comprising lipid globules, wherein less than 10 vol.% of the lipid globules have a diameter of >12 pm and / or wherein the lipid globules have a volume-weighted mode diameter from 2.5 to 7 pm, preferably 3 to 6 pm.

[0061] Further details about performing steps c. and d. in this manner can be found in WO2016146496.

[0062] Preferably, the process comprises dry blending of further particles with the particles obtained in step d. or step f, more preferably with the particles obtained in step f. These further particles preferably comprise one or more of digestible carbohydrates, non-digestible oligosaccharides, LCPUFA’s, probiotics, minerals and vitamins.

[0063] Preferably, in step a. an aqueous phase is provided with a dry matter content of 10 wt.% to 60 wt.% (based on total weight of the aqueous phase), which comprises at least one protein component, and optionally carbohydrate, even more preferably 20 to 50 wt.%

[0064] Preferably, in step c. the lipid phase is mixed with the aqueous phase in a ratio of 5 wt.% to 50 wt.% using a mixer to provide an oil in water emulsion. Preferably, the mixer in step c. is an inline mixer, rotor stator mixer, or a static mixer; more preferably an inline mixer.

[0065] The oil in water emulsion preferably has a dry matter content of 30 to 70 wt.%, more preferably it is higher than 40 wt.%.

[0066] The atomizers employed in step d. of the process can be any atomizer known in the art, preferably a rotary atomizer or a pneumatic atomizer is employed, such as a 2 fluid nozzle.

[0067] In a preferred embodiment, a gas is injected during the process, more preferably into the aqueous phase of step a. and / or into the oil in water emulsion provided in step c.

[0068] Lipid globule size The lipid is present in the particles of the nutritional composition in the form of lipid globules. The lipid globules comprise a core and a surface.

[0069] The lipid globules in the nutritional composition preferably have mode diameter, based on volume, of at least 1 .0 pm, more preferably at least 2.0 pm, even more preferably at least 3.0 pm, and most preferably at least 4.0 pm. Preferably, the lipid globules have a mode diameter, based on volume, between 1 .0 and 10 pm, more preferably between 2.0 and 8.0 pm, even more preferably between 3.0 and 7.0 pm, and most preferably between 4.0 pm and 6.0 pm.

[0070] Alternatively, or preferably in addition, the size distribution of the lipid globules is preferably in such a way that at least 45 volume % (vol.%), more preferably at least 55 vol.%, even more preferably at least 65 vol.%, and most preferably at least 75 vol.% of the lipid globules have a diameter between 2 and 12 pm. In a more preferred embodiment, at least 45 vol.%, preferably at least 55 vol.%, more preferably at least 65 vol.%, and most preferably at least 75 vol.% of the lipid globules have a diameter between 2 and 10 pm. In an even more preferred embodiment, at least 45 vol.%, more preferably at least 55 vol.%, yet even more preferably at least 65 vol.%, and most preferably at least 75 vol.% of the lipid globules have a diameter between 4 and 10 pm. Preferably less than 5 vol.% of the lipid globules have a diameter above 12 pm.

[0071] The percentage of lipid globules is based on volume of total lipid. The mode diameter relates to the diameter which is the most present based on volume of total lipid, or the peak value in a graphic representation, having on the X-axis the diameter and on the Y-axis the volume (%).

[0072] The volume of the lipid globules and its size distribution can suitably be determined using a particle size analyzer such as a Mastersizer 2000 (Malvern Instruments, Malvern, UK), for example by the method described in Michalski et al, 2001 , Lait 81 : 787-796.

[0073] Phospholipid

[0074] The lipid in the nutritional composition preferably comprises 0.5 to 20 wt.% phospholipids based on total lipid and the lipid globules preferably have a coating on the surface comprising said phospholipids. Preferably, the nutritional composition comprises 0.6 to 10 wt.%, more preferably 0.7 to 8 wt.%, even more preferably 0.8 to 6 wt.%, and most preferably 1 to 5 wt.% phospholipids based on total lipid.

[0075] Phospholipids are amphipathic of nature and include glycerophospholipids and sphingomyelin. By ‘coating’ is meant that the outer surface layer of the lipid globules comprises phospholipid, whereas phospholipid is virtually absent in the core of the lipid globule. A suitable way to determine whether phospholipid is located on the surface of lipid globules is confocal laser scanning microscopy or transmission electron microscopy; see for instance Gallier et al. (A novel infant milk formula concept: Mimicking the human milk fat globule structure, Colloids and Surfaces B: Biointerfaces, 136 (2015), 329- The nutritional composition preferably comprises glycerophospholipids. Examples of glycerophospholipids are phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylglycerol (PG). Preferably the nutritional composition comprises one or more of PC, PS, PI and PE, more preferably the nutritional composition comprises at least PC.

[0076] The nutritional composition preferably comprises sphingomyelin. Sphingomyelins have a phosphorylcholine or phosphorylethanolamine molecule esterified to the 1 -hydroxy group of a ceramide. They are classified as phospholipid as well as sphingolipid, but are not classified as a glycerophospholipid nor as a glycosphingolipid. Preferably the nutritional composition comprises 0.05 to 10 wt.% sphingomyelin based on total lipid, more preferably 0.1 to 5 wt.%, even more preferably 0.2 to 2 wt.%. Preferably the nutritional composition comprises at least 5 wt.%, more preferably 5 to 40 wt.% sphingomyelin based on total phospholipid, more preferably 10 to 35 wt.%, even more preferably 15 to 35 wt.% sphingomyelin, based on total phospholipid.

[0077] The nutritional composition preferably comprises glycosphingolipids. The term glycosphingolipids in the present context particularly refers to glycolipids with an amino alcohol sphingosine. The sphingosine backbone is O-linked to a charged head-group such as ethanolamine, serine or choline backbone. The backbone is also amide linked to a fatty acyl group. Glycosphingolipids are ceramides with one or more sugar residues joined in a beta-glycosidic linkage at the 1-hydroxyl position, and include gangliosides. Preferably the nutritional composition contains gangliosides, more preferably at least one ganglioside selected from the group consisting of GM3 and GD3. Preferably the nutritional composition comprises 0.1 to 10 wt.% glycosphingolipids based on total lipid, more preferably 0.5 to 5 wt.%, even more preferably 2 to 4 wt.% glycosphingolipids, based on total lipid.

[0078] The nutritional composition preferably comprises cholesterol. The nutritional composition preferably comprises at least 0.005 wt.% cholesterol based on total lipid, more preferably at least 0.02 wt.%, even more preferably at least 0.05 wt.%, and most preferably at least 0.1 wt.% cholesterol based on total lipid. Preferably the amount of cholesterol does not exceed 10 wt.% based on total lipid, more preferably does not exceed 5 wt.%, most preferably does not exceed 1 wt.% of cholesterol based on total lipid in the nutritional composition.

[0079] Preferred sources for providing the phospholipid, glycosphingolipid and / or cholesterol are egg lipids, milk fat, buttermilk fat and butter serum fat (such as beta serum fat). Another preferred source for phospholipid, particularly PC, is soy lecithin and / or sunflower lecithin.

[0080] The nutritional composition preferably comprises phospholipid derived from mammalian milk. Preferably the nutritional composition comprises phospholipid and glycosphingolipid derived from mammalian milk. Preferably also cholesterol is derived from mammalian milk. The nutritional composition preferably comprises phospholipid, glycosphingolipid and / or cholesterol derived from mammalian milk of cows, mares, sheep, goats, buffalos, horses and camels. More preferably the nutritional composition comprises phospholipid, glycosphingolipid and / or cholesterol derived from cow’s milk.

[0081] Phospholipid derived from mammalian milk includes preferably phospholipid that is derived from milk lipid, cream lipid, cream serum lipid, butter serum lipid (beta serum lipid), whey lipid, cheese lipid and / or buttermilk lipid. Buttermilk lipid is typically obtained during the manufacture of buttermilk. Butter serum lipid or beta serum lipid is typically obtained during the manufacture of anhydrous milk fat from butter. More preferably the phospholipid, glycosphingolipid and / or cholesterol is derived from whey, e.g., a whey protein concentrate. Suitable commercially available sources for phospholipid from milk are BAEF, SM2, SM3 and SM4 powder of Corman, Salibra of Glanbia, Vivinal MFGM of FrieslandCampina and LacProdan MFGM-10 or PL20 from Aria.

[0082] The use of phospholipid from mammalian milk fat advantageously comprises the use of milk fat globule membranes, which are more reminiscent to the situation in human milk. The concomitant use of phospholipid derived from mammalian milk and triglycerides derived from vegetable lipids therefore enables the manufacture of coated lipid globules with a coating more similar to human milk, while at the same time providing an optimal fatty acid profile.

[0083] Preferably the phospholipid is derived from mammalian milk, more preferably derived from or forms part of milk fat globule membrane (MFGM). Preferably the phospholipid is derived from cow’s milk, more preferably derived from or forms part of cow’s MFGM.

[0084] Preferably the nutritional composition comprises phospholipid and glycosphingolipid and more preferably the weight ratio of phospholipid : glycosphingolipid is from 2:1 to 12:1 , more preferably from 2:1 to 10:1 and even more preferably 2:1 to 5:1.

[0085] Lipid

[0086] The nutritional composition comprises lipid. The term “lipid” as used herein refers to one or more selected from the group consisting of triglycerides, polar lipids (such as phospholipids, cholesterol, glycolipids, sphingomyelin), free fatty acids, monoglycerides and diglycerides.

[0087] The lipid provides preferably 30 to 60% of the total calories of the nutritional composition. More preferably the nutritional composition comprises lipid providing 35 to 55% of the total calories, even more preferably the nutritional composition comprises lipids providing 40 to 50% of the total calories. The lipids are preferably present in an amount of 4 to 6 g per 100 kcal. When in liquid form, e.g., as a ready-to-feed liquid, the nutritional composition preferably comprises 2.1 to 6.5 g lipids per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. Based on dry weight, the nutritional composition preferably comprises 10 to 50 wt.%, more preferably 12.5 to 40 wt.% lipids, even more preferably 19 to 30 wt.% lipids. The lipid preferably comprises vegetable lipids. The presence of vegetable lipids advantageously enables an optimal fatty acid profile, high in polyunsaturated fatty acids and / or more reminiscent to human milk fat. Lipids from mammalian milk alone, e.g., cow’s milk, do not provide an optimal fatty acid profile. The amount of essential fatty acids is too low in mammalian milk.

[0088] Preferably the nutritional composition comprises at least one, preferably at least two vegetable lipid sources selected from the group consisting of linseed oil (flaxseed oil), rape seed oil (such as colza oil, low erucic acid rape seed oil and canola oil), sunflower oil, high oleic sunflower oil, safflower oil, high oleic safflower oil, olive oil, coconut oil, palm oil and palm kernel oil.

[0089] In one preferred embodiment, the nutritional composition comprises 5 to 98 wt.% vegetable lipids based on total lipids, more preferably 10 to 95 wt.%, more preferably 20 to 80 wt.%, even more preferably 25 to 75 wt.%, most preferably 40 to 60 wt.% of vegetable lipids based on total lipids. Preferably, the nutritional composition also comprises non-vegetable lipids. Preferably, said non-vegetable lipids are one or more non-vegetable lipids selected from mammalian milk fat, mammalian milk derived lipid as a preferred source of phospholipid, and fish, marine and / or microbial oils as source of LC-PUFA.

[0090] Faty acid composition

[0091] SFA relates to saturated fatty acids and / or acyl chains, MUFA relates to mono-unsaturated fatty acid and / or acyl chains, PUFA refers to polyunsaturated fatty acids and / or acyl chains with 2 or more unsaturated bonds; LC-PUFA refers to long chain polyunsaturated fatty acids and / or acyl chains comprising at least 20 carbon atoms in the fatty acyl chain and with 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 n6); DPA refers to docosapentaenoic acid and / or acyl chain (22:5 n3). n3 or omega 3 PUFA refers to polyunsaturated fatty acids and / or acyl chains with 2 or more unsaturated bonds and with an unsaturated bond at the third carbon atom from the methyl end of the fatty acyl chain, n6 or omega 6 PUFA refers to polyunsaturated fatty acids and / or acyl chains with 2 or more unsaturated bonds and with an unsaturated bond at the sixth carbon atom from the methyl end of the fatty acyl chain.

[0092] The nutritional composition preferably comprises LA, which refers to linoleic acid and / or acyl chain (18:2 n6). LA is an n6 PUFA and the precursor of n6 LC-PUFA and is an essential fatty acid as it cannot be synthesized by the human body. LA preferably is present in a sufficient amount to promote a healthy growth and development, yet in an amount as low as possible to prevent negative, competitive, effects on the formation of n3 PUFA and a too high n6 / n3 ratio. The nutritional composition therefore preferably comprises less than 25 wt.%, more preferably less than 20 wt.%, more preferably less than 15 wt.% LA based on total fatty acids. The nutritional composition preferably comprises at least 5 wt.% LA based on fatty acids, preferably at least 7.5 wt.%, more preferably at least 10 wt.% based on total fatty acids. The nutritional composition preferably comprises ALA, which refers to alpha-linolenic acid and / or acyl chain (18:3 n3). ALA is a n3 PUFA and the precursor of n3 LC-PUFA and is an essential fatty acid as it cannot be synthesized by the human body. Preferably ALA is present in a sufficient amount to promote a healthy growth and development of the infant. The nutritional composition therefore preferably comprises at least 0.5 wt.%, more preferably at least 1.0 wt.%, more preferably the nutritional composition comprises at least 1.5 wt.%, even more preferably at least 2.0 wt.% ALA based on total fatty acids. Preferably the nutritional composition comprises less than 10 wt.% ALA, more preferably less than 5.0 wt.% ALA based on total fatty acids.

[0093] The weight ratio LA / ALA preferably is well balanced to ensure an optimal n6 / n3 PUFA, n6 / n3 LC PUFA and DHA / ARA ratio in the cellular membranes. Therefore, the nutritional composition preferably comprises a weight ratio of LA / ALA from 2 to 20, more preferably from 3 to 15, more preferably from 5 to 12, more preferably from 5 to 10. Preferably the n6 PUFA / n3 PUFA weight ratio is from 3 to 20, more preferably from 3 to 15, more preferably from 5 to 12, more preferably from 5 to 10.

[0094] Preferably, the nutritional composition comprises n3 LC-PUFA, such as EPA, DPA and / or DHA, more preferably DHA. As the conversion of ALA to DHA may be less efficient in infants, preferably both ALA and DHA are present in the nutritional composition. Preferably the nutritional composition comprises at least 0.05 wt.%, preferably at least 0.1 wt.%, more preferably at least 0.2 wt.%, of DHA based on total fatty acids. Preferably the nutritional composition comprises not more than 2.0, preferably not more than 1 .0 wt.%, of DHA based on total fatty acids.

[0095] The nutritional composition preferably comprises ARA. Preferably the nutritional composition comprises at least 0.05 wt.%, preferably at least 0.1 wt.%, more preferably at least 0.2 wt.%, of ARA based on total fatty acids. As the group of n6 fatty acids, especially ARA counteracts the group of n3 fatty acids, especially DHA, the nutritional composition preferably comprises relatively low amounts of ARA. Preferably the nutritional composition comprises not more than 2.0 wt.%, preferably not more than 1 .0 wt.%, of ARA based on total fatty acids. Preferably the weight ratio between DHA and ARA is between % to 4 / 1 , more preferably between % to 2 / 1 , more preferably between 0.6 and 1 .5.

[0096] Protein

[0097] The nutritional composition comprises protein. The protein preferably provides 5 to 15% of the total calories, more preferably 6 to 12% of the total calories. Preferably protein is present in the nutritional composition below 3.5 gram per 100 kcal, more preferably between 1.8 and 2.1 g protein per 100 kcal, and most preferably between 1.85 and 2.0 g protein per 100 kcal. The protein concentration in a nutritional composition is determined by the sum of protein, peptides and free amino acids. Based on dry weight, the nutritional composition preferably comprises less than 12 wt.% protein, more preferably between 9.6 and 12 wt.%, most preferably between 10 and 11 wt.% protein. Based on a ready-to-drink liquid product the nutritional composition preferably comprises less than 1.5 g protein per 100 ml, more preferably between 1 .2 and 1 .5 g, even more preferably between 1 .25 and 1 .35 g protein per 100 ml. The source of the protein is preferably selected in such a way that the minimum requirements for essential amino acid content are met and satisfactory growth is ensured. Hence protein sources based on cows' milk proteins such as whey, casein and mixtures thereof and proteins based on soy, potato or pea are preferred. In case whey proteins are used, the protein source is preferably based on acid whey, sweet whey, whey protein isolate or mixtures thereof. Preferably the nutritional composition comprises at least 3 wt.% casein based on dry weight. Preferably the protein in the nutritional composition is intact and / or non-hydrolyzed.

[0098] Digestible carbohydrates

[0099] The nutritional composition preferably comprises digestible carbohydrates. The digestible carbohydrates preferably provide 30 to 80% of the total calories of the nutritional composition. Preferably the digestible carbohydrates provide 40 to 60% of the total calories. Based on calories the nutritional composition preferably comprises of 5 to 20 g of digestible carbohydrates per 100 kcal, more preferably 7.5 to 15 g. When in liquid form, e.g. as a ready-to-feed liquid, the nutritional composition preferably comprises 3 to 30 g digestible carbohydrate per 100 ml, more preferably 6 to 20 g, even more preferably 7 to 10 g per 100 ml. Based on dry weight, the nutritional composition preferably comprises 20 to 80 wt.%, more preferably 40 to 65 wt.% digestible carbohydrates.

[0100] 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 carbohydrate, wherein at least 35 wt.%, more preferably at least 50 wt.%, more preferably at least 75 wt.%, and most preferably at least 95 wt.% of the digestible carbohydrate is lactose. Based on dry weight the nutritional composition preferably comprises at least 25 wt.% lactose, preferably at least 40 wt.%.

[0101] Human milk oligosaccharides

[0102] The nutritional composition preferably comprises human milk oligosaccharides (HMO). The term “human milk oligosaccharides” or “HMO” as used herein refers to non-digestible oligosaccharides which are present in human breast milk. Human breast milk comprises two types of carbohydrates: lactose and HMO. HMO are the third most abundant component of human breast milk, after lactose and lipids. Human breast milk contains three major HMO types: fucosylated HMO, sialylated HMO and N- acetylated HMO.

[0103] Suitable HMO for the preparation of the nutritional composition are commercially available, for example from Kyowa Hakko Bio, Japan; Friesland Campina, The Netherlands; Glycom DSM, Denmark and Chr. Hansen, Denmark. Otherwise, it is well within the reach of the skilled person to obtain HMO by isolation from suitable sources or by chemical synthesis using methods known in the art. Preferably, the wt. ratio of HMO to mammalian milk derived phospholipids in the nutritional composition is between 1 :10 to 30:1 , more preferably between 1 :5 to 20:1 , and most preferably between 1 :1 to 10:1 .

[0104] When the nutritional composition is a ready-to-drink liquid nutritional composition, the composition preferably comprises 20-400 mg HMO per 100 ml, more preferably 30-300 mg HMO per 100 ml and most preferably 40-250 mg HMO per 100 ml HMO.

[0105] When the nutritional composition is a particulate nutritional composition, the composition preferably comprises 300-4000 mg HMO per 100 g dry weight, more preferably 450-2000 mg HMO per 100 g dry weight.

[0106] When expressed in amounts based on calories, preferably the nutritional composition comprises 30- 600 mg HMO per 100 kcal, more preferably 45-450 mg HMO per 100 kcal and most preferably 60-375 mg HMO per 100 kcal.

[0107] The HMO in the nutritional composition is preferably selected from 2’-fucosyllactose (2’FL), 3- fucosyllactose (3-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), para-lacto-N-neohexaose (para-LNnH), sialic acid, 3' sialyllactose (3’SL), 6' sialyllactose (6’SL), difucosyllactose (DFL), lacto-N- fucopentaose, lacto-N-fucohexaose, lacto-N-difucohexaose, sialyl-lacto-N-tetraose (LSTa), sialyl-lacto- N-tetraose b (LSTb), sialyl-lacto-N-tetraose c (LSTc), disialyllacto-N-tetraose (DSLNT), lacto-N- neodifucohexaose (LNnDFH I), fucosyllacto-N-hexaose, fucosyllacto-N-neohexaose, difucosyllacto-N- hexaose I, difuco-lacto-N-neohexaose, difucosyllacto-N-neohexaose I, difucosyllacto-N-neohexaose II, fucosyl-para-Lacto-N-hexaose, and tri-fuco-para-Lacto-N-hexaose I and combinations thereof.

[0108] The HMO preferably comprises at least 2 types of HMO, more preferably at least 3 types of HMO, even more preferably at least 4 types of HMO, and most preferably at least 5 types of HMO. Preferably, these types of HMO are selected from 2’-fucosyllactose (2’FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), para-lacto-N-neohexaose (para-LNnH), sialic acid, 3' sialyllactose (3’SL), 6' sialyllactose (6’SL), difucosyllactose (DFL), lacto-N-fucopentaose, lacto-N-fucohexaose, lacto- N-difucohexaose, sialyl-lacto-N-tetraose (LSTa), sialyl-lacto-N-tetraose b (LSTb), sialyl-lacto-N-tetraose c (LSTc), disialyllacto-N-tetraose (DSLNT), lacto-N-neodifucohexaose (LNnDFH I), fucosyllacto-N- hexaose, fucosyllacto-N-neohexaose, difucosyllacto-N-hexaose I, difuco-lacto-N-neohexaose, difucosyllacto-N-neohexaose I, difucosyllacto-N-neohexaose II, fucosyl-para-Lacto-N-hexaose, and tri- fuco-para-Lacto-N-hexaose I and combinations thereof.

[0109] In a preferred embodiment, the HMO is selected from 2’FL, 3-FL, DFL, LNT, LNnT, 3’SL, 6’SL, and combinations thereof. More preferably the HMO is selected from 2’FL, 3-FL, LNT, 3’SL, 6’SL and combinations thereof. In a particularly preferred embodiment, the nutritional composition comprises 5 types of HMO, said 5 types of HMO being 2’FL, 3-FL, LNT, 3’SL, and 6’SL. More preferably, the HMO comprises 40-60 wt.% 2’FL, 10-20 wt.% 3-FL, 20-30 wt.% LNT, 2-7 wt.% 3’SL, and 4-8 wt.% 6’SL based on total HMO weight.

[0110] In alternative preferred embodiment, the HMO comprise at least 40 wt.%, more preferably 45-100 wt.%, and most preferably 50-90 wt.% of 2’FL based on total HMO weight.

[0111] In yet another alternative preferred embodiment, the HMO comprises a combination of 2’FL and LNnT, more preferably the HMO consists of the combination of 2’FL and LNnT. Preferably, the HMO comprises 60-90 wt.% 2’FL and 10-40 wt.% LNnT based on total HMO weight, more preferably the HMO comprises 65-85 wt.% 2’FL and 15-35 wt.% LNnT and most preferably the HMO comprises 70-80 wt.% 2’FL and 20-30 wt.% LNnT.

[0112] GOS and FOS

[0113] The nutritional composition preferably comprises galacto-oligosaccharides (GOS) and / or fructooligosaccharides (FOS), more preferably the nutritional composition comprises GOS and FOS. GOS and FOS are both non-digestible oligosaccharides which act as a prebiotic.

[0114] The GOS are preferably transgalacto-oligosaccharides. A suitable GOS is commercially available, for example VivinalOGOS (FrieslandCampina DOMO). Preferably the GOS are short chain galactooligosaccharides (scGOS) with an average degree of polymerization (DP) in the range of 1 to 10, more preferably in the range of 3 to 7.

[0115] A suitable FOS is commercially available, for example RaftilinOHP or Raftilose® (Orafti). Preferably the FOS are long chain fructo-oligosaccharides (IcFOS) with an average DP in the range of 10-100, more preferably in the range of 20 to 60.

[0116] Preferably, the weight ratio of GOS to FOS ranges from 100:1 to 1 :10, more preferably from 20:1 to 1 :1 , even more preferably from 7:1 to 10:1 , and most preferably the weight ratio is 9:1. Preferably these weight ratio’s apply to scGOS and IcFOS.

[0117] Preferably, the weight ratio of GOS and / or FOS combined to HMO ranges from 20:1 to 1 :10, more preferably from 15:1 to 1 :5 and most preferably from 10:1 to 1 :1 .

[0118] Preferably, the nutritional composition comprises 80 mg to 2 g of GOS and / or FOS per 100 ml, more preferably 150 mg to 1 .5 g, most preferably 300 mg to 1 g of GOS / FOS per 100 ml.

[0119] Based on dry weight, the nutritional composition preferably comprises 0.25-20 wt.%, more preferably 0.5-10 wt.%, and most preferably 1 .5-7.5 wt.% of GOS and / or FOS. Probiotics

[0120] The nutritional composition preferably comprises probiotic bacteria. The term “probiotic bacteria” as used herein refers to live beneficial bacteria that provide health benefits when consumed, generally by improving or restoring the gut microbiota. The term “gut microbiota” as used herein refers to all microorganisms, including bacteria, archaea, virus, and fungi, that are found in the digestive tract of a human subject.

[0121] The probiotic bacteria are preferably selected from Lactobacillus, Bifidobacterium and combinations thereof, more preferably the probiotic bacteria comprise Bifidobacterium, even more preferably the probiotic bacteria are Bifidobacterium, yet even more preferably the probiotic bacteria are Bifidobacterium breve and most preferably the probiotic bacteria are the strain B. breve M-16V (Mori nag a).

[0122] The probiotic bacteria are preferably provided in therapeutically effective amounts. The nutritional composition preferably contains between 104and 1 O10colony forming units (cfu) probiotic bacteria per gram dry weight of the present composition, more preferably between 105and 109, and most preferably between 106and 108CFU probiotic bacteria per gram dry weight.

[0123] When the nutritional composition is a liquid nutritional composition, preferably a ready-to-drink liquid nutritional composition, the liquid nutritional composition preferably comprises 106and 1 O10colony forming units (cfu) probiotic bacteria per 100 ml, more preferably between 107and 109CFU per 100 ml.

[0124] Application of the nutritional composition

[0125] The particulate nutritional composition of the present invention, as described herein above, and their reconstituted ready to drink liquids are suitable for achieving beneficial effects in subjects, preferably human subjects, more preferably, infants, toddlers, and children.

[0126] In the next embodiments ‘particulate nutritional composition, as described herein above’ refers to the particulate nutritional composition according to the first aspect of the invention and all preferred embodiments equally apply to this third and fourth aspect of the invention.

[0127] Accordingly, in a preferred embodiment, the present invention provides a particulate nutritional composition, as described herein above, for use in the promotion of metabolic health, the promotion of the development of good body composition, prevention of the development of obesity later in life, the promotion of balanced growth, the promotion of lean growth, the promotion of cognitive development, improving brain health, improving gut health, providing beneficial prebiotic effect, increasing immune cell function and immune health, preventing infections or improving the recovery from infections, stimulating intestinal barrier functions I epithelial cell modulators and so to improve gut health and reducing the risk of gut health problems and / or improving a recovery of a gut health problem. A third aspect of the invention pertains to particulate nutritional composition, as described herein above, for use in the prevention of the development of obesity later in life, improving the immune system, preventing infections, improving the recovery from infections, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem.

[0128] The invention also covers a method for the prevention of the development of obesity later in life, improving the immune system, preventing infections, improving the recovery from infections, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem, said method comprising administration to a subject of the particulate nutritional composition, as described herein above.

[0129] The invention may also be worded as the use of lipid globules in the manufacture of a particulate nutritional composition, as described herein above, for the prevention of the development of obesity later in life, improving the immune system, preventing infections, improving the recovery from infections, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem.

[0130] Worded differently, the invention also pertains to the use of the particulate nutritional composition, as described herein above, for the prevention of the development of obesity later in life, improving the immune system, preventing infections, improving the recovery from infections, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem..

[0131] Gut health includes improving the microbiota in the gut so as to treat and / or prevent gut dysbiosis, to decrease the abundance of opportunistic pathogens, and / or to increase the abundance of beneficial bacteria in the gut.

[0132] Preferably, the particulate nutritional composition, as described herein above, is for use in the prevention of the development of obesity later in life, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem. More preferably, the particulate nutritional composition, as described herein above, is for use in the prevention of the development of obesity later in life and / or improving gut health.

[0133] A fourth aspect of the invention pertains to a non-therapeutic method for the promotion of metabolic health, the promotion of the development of good body composition, the promotion of balanced growth, the promotion of lean growth, the promotion of cognitive development, improving brain health and / or providing beneficial prebiotic effect, said method comprising administration to a subject of the particulate nutritional composition as described herein above.

[0134] Preferably, the non-therapeutic method is for the promotion of balanced growth, the promotion of cognitive development, improving brain health and / or providing beneficial prebiotic effect. More preferably, the non-therapeutic method is for the promotion of balanced growth and / or the promotion of cognitive development.

[0135] To support that the nutritional composition are effective for the uses as described above, reference is made to the following documents:

[0136] • Gallier S. et al., Natural and processed milk and oil body emulsions: Bioavailability, bioaccessibility and functionality. Food Structure 13, 2017,13-23.

[0137] • Breij L. et al., An infant formula with large, milk phospholipid-coated lipid droplets containing a mixture of dairy and vegetable lipids supports adequate growth and is well tolerated in healthy, term infants. Am J Clin Nutr, 2019;109(3): 586-596; and

[0138] • the following pre-published patent applications:

[0139] WO2010027258, WO2010027259, W02011115490, WO2011115491 , WO2012173485, WO2012173486, WO2013191542, WO2015065193, WO2016163881 , WO2017064304, W02018104512 and WO2024156893.

[0140] Use

[0141] A further aspect of the invention relates to the use of the particulate nutritional composition, as described herein before, for preparing reconstituted liquid formula, more preferably liquid ready-to-drink formula. The invention also covers the reconstituted liquid composition obtained in such preparation.

[0142] Examples

[0143] In the Examples the following methods were employed:

[0144] Powder particle size distribution

[0145] The powder particle size distribution (PSD) was analyzed using laser diffraction (Malvern Mastersizer 3000) equipped with a dry dispersion unit (Aero S) operated at 1 bar dispersion pressure. Optical properties for evaluation of data were 1 ,53 I 0,1 and using non-spherical particle type. From the PSD, three parameters: dio, d2o, dso (all by volume) are shown.

[0146] Lipid globule size distribution

[0147] The volume of the lipid globule and its size distribution was determined using a particle size analyzer (Malvern Mastersizer 2000) by the method described in Michalski et al, 2001 , Lait 81 : 787-796.

[0148] Free fat content

[0149] The free fat content of example 1 was analysed as described by Sorensen et al. (Analytical Methods for Dry Milk Products, 4thEdition, 1978). The method from Sorensen et al. was adapted as follows; 5 g of particulate nutritional composition was mixed with 50 ml petroleum ether and agitated for 15 minutes. The mixture was filtered and the petroleum ether phase (filtrate) was collected. The extraction was repeated: the remaining solid was mixed with 50 additional ml of petroleum ether and agitated for 15 minutes. The mixture was filtered and the petroleum ether phase was collected and merged with the first filtrate. The petroleum ether was evaporated. The solid residue was dried at 102 °C for 90 minutes. The free fat content (%) was calculated as follows:

[0150] , , weight of the solid residue free fat content (%) = - - - — — - - - x 100 weight of the sample

[0151] Particle density

[0152] The particle density was calculated by dividing the sample weight divided by its true volume. The true volume is measured by gas pycnometry using a UltraPyc 1200E (Quantachrome Instruments, USA) applying the pressure-volume-relation for gas as described by the Boyle’s law.

[0153] Wettability

[0154] Wettability or wetting time was measured according to the standard method ISO-17758-2014 with two adjustments, namely that water with a temperature of 40 °C was employed and that 13 grams of powder was used per 250 ml of water.

[0155] Example 1

[0156] A powdered infant formula was prepared comprising per kg final product about 5030 kcal, about 294 g lipid (35 wt.% palm oil, 25 wt.% coconut oil, 21 wt.% sunflower oil, 19 wt.% rapeseed oil), about 452 g digestible carbohydrates, about 66 g non-digestible oligosaccharides and about 121 g protein (60 wt.% whey, 40 wt.% casein). Also, vitamins, minerals, trace elements as known in the art were used. The composition was prepared using a milk phospholipid (MFGM) source, whey protein, skimmed milk powder, lactose, an oil blend (fat) and non-digestible oligosaccharides.

[0157] An aqueous phase, comprising protein, digestible carbohydrates, milk phospholipid source and the other ingredients, except the fat and fat-soluble vitamins, was prepared by combining the components under mild mixing. The dry matter content of the aqueous phase was 24%. The aqueous phase was pasteurized 360 seconds at 80 °C, after which it was heat treated for 2.6 seconds at 126 °C using direct steam infusion, followed by concentrating the aqueous phase to 46% using a multistage falling film evaporator. The concentrated water phase was reheated to 78 °C using tubular heat exchangers.

[0158] A lipid phase was prepared by adding together the lipid and fat-soluble vitamins. The lipid phase was heated to 80°C and added to the water phase forming a pre-emulsion. The total dry matter content of the lipids and aqueous phase mixture was 55 wt. %. The pre-emulsion was fed into a rotor-stator machine (Ystral, in-line dispersing machine). After this emulsification step, the emulsion was spray dried in a Multi Stage Dryer (GEA, NIRO-MSD) by using pneumatic atomizers (2-fluid) at 5 bar air pressure and an inlet temperature of 195 °C for the drying gas. The fines were separated from the outlet air via cyclones and redirected into the drying chamber in the atomizing zone. Powder samples were collected after the production process and were characterized. The powder particle size distribution, the fat globule size distribution, the free fat content, particle density and wettability were determined. The values are shown in Tables 1 and 2. Example 2

[0159] A powdered infant formula was prepared using the same process as in example 1 , comprising per kg final product about 4830 kcal, about 261 g lipid (50 wt.% anhydrous milkfat, 25 wt.% sunflower oil, 17 wt.% rapeseed oil, 8 wt.% coconut oil), about 507 g digestible carbohydrates, about 66 g non-digestible oligosaccharides and about 98 g protein (60 wt.% whey, 40 wt.% casein). The composition was prepared using a milk phospholipid (MFGM) source, whey protein, skimmed milk powder, lactose, an oil blend (fat) and non-digestible oligosaccharides. Also vitamins, minerals, trace elements as known in the art were used.

[0160] Example 3

[0161] A powdered infant formula was prepared using the same process as in example 1 , comprising per kg final product about 4720 kcal, about 224 g lipid (48 wt.% anhydrous milkfat, 27 wt.% sunflower oil, 17 wt.% rapeseed oil, 8 wt.% coconut oil), about 565 g digestible carbohydrates, about 63 g non-digestible oligosaccharides and about 96 g protein (50 wt.% whey, 50 wt.% casein). The composition was prepared using a milk phospholipid (MFGM) source, whey protein, skimmed milk powder, lactose, an oil blend (fat) and non-digestible oligosaccharides. Also, vitamins, minerals, trace elements as known in the art were used.

[0162] In Example 3, some fines separated from the outlet air cyclones were subjected to a powder particle size distribution analysis. The fine powder particles were established to have a dio, d2o and dso of 30 pm, 45 pm and 97 pm, respectively.

[0163] Table 1 . Lipid globule particle size distribution of reconstituted powders

[0164] Table 2. Powder particle size, free fat percentage, particle density and wettability

[0165] Example 4 - Dissolution tests

[0166] In consumer tests, baby bottles were prepared using the powder from Example 1 or a comparative powder. Both powders had the same nutritional composition as Example 1 . The comparative powder was prepared according to the process described in WO2016146496, in this process no recirculation of the fines was applied.

[0167] The powders differed in their powder characteristics in terms of powder particle size, free fat, particle density (Table 3). Powder was scooped into a baby bottle containing lukewarm water in a typical ratio for infant formula. The powder from example 1 was almost instantaneously dissolved after gently swirling, where with the comparative powder undissolved lumps were observed. The comparative powder could only be dissolved after vigorously shaking. Table 3. Powder particle size, free fat percentage, particle density

Claims

CLAIMS1 . A particulate nutritional composition comprising lipid and protein, and optionally carbohydrates, wherein the lipid in the particles is in the form of lipid globules and wherein the lipid globules have a mode diameter based on volume of at least 1 .0 pm and / or at least 40 vol.% of the lipid globules have a diameter between 2 and 12 pm; and wherein the particles have: i. a Dio of at least 75 pm, and ii. one or more of a D20 of at least 135 pm and a D50 of at least 235 pm, the D10, D20 and D50 being based on volume.

2. The composition of claim 1 comprising at least 0.5 wt.% of phospholipids based on total lipid wherein preferably the lipid globules have a coating comprising the phospholipids.

3. The composition of claim 1 or 2, wherein the D10 is at least 85 pm.

4. The composition of any one of the preceding claims, wherein, the D20 is at least 145 pm.

5. The composition of any one of the preceding claims, wherein the D50 is at least 245 pm.

6. Composition of any one of the preceding claims having a free fat content of less than 10%.

7. Composition of any one of the preceding claims, wherein the particle density is higher than 1 .000 g / cm3.

8. Composition of any one of the preceding claims, wherein the wettability is less than 100 sec.

9. Composition of any one of the preceding claims containing digestible carbohydrates, and preferably additionally one or more of non-digestible oligosaccharides, vitamins, minerals and probiotics.

10. Composition of any one of the preceding claims reconstituted in a food grade aqueous solution to provide a ready to drink solution.

11. Composition of any one of the preceding claims that is an infant milk formula, a follow on formula, a young child formula, or a medical nutritional product.

12. Process for producing the particulate or reconstituted nutritional composition according to any one of the preceding claims, comprising the steps of a. Providing an aqueous phase with a dry matter content of 10-60 wt.% based on total weight of the aqueous phase which comprises at least one protein component;b. Providing a lipid phase which comprises at least one lipid; c. Mixing the lipid phase with the aqueous phase to provide an oil in water emulsion; d. Spray-drying the oil in water emulsion in a spray-drier to provide particles and fine particles; e. Recirculating the fine particles obtained in step d. to and / or in the spray-drier; f. Optionally further drying the particles obtained in step d.; g. Optionally (dry) blending further particles with the particles obtained in step d. or step f..

13. Process according to claim 12, wherein the spray-drier comprises: i. an atomization zone comprising at least one inlet for fine particles, and one or more inlets for the oil-in-water emulsion connected to one or more atomizers; ii. a downstream drying zone comprising at least one outlet for the particles; andHi. at least one outlet for air and fine particles; and wherein the fine particles are collected after exiting their outlet and are recirculated to the at least one inlet for fine particles of the atomization zone.

14. Process according to claim 12 or 13, wherein the collection of fine particles is done by separating the air from the fine particles in a cyclone, preferably in one or more cyclones.

15. Particulate nutritional composition of any one of claims 1 to 11 for use in the prevention of the development of obesity later in life, improving the immune system, preventing infections, improving the recovery from infections, improving gut health, reducing the risk of gut health problems and / or improving a recovery of a gut health problem.

16. Non-therapeutic method for the promotion of metabolic health, the promotion of the development of good body composition, the promotion of balanced growth, the promotion of lean growth, the promotion of cognitive development, improving brain health and / or providing beneficial prebiotic effect, said method comprising administration to a subject of the particulate nutritional composition of any one of claim 1 to 11.

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