ES2773670T3 - Nutritional compositions with large diameter lipid globules with a coating comprising polar lipids - Google Patents

Abstract

Nutritional composition comprising a) from 10 to 50% by weight of vegetable lipids on the dry weight of the composition, and b) lipid globules i. with a volume weighted modal diameter greater than 1.0 µm, preferably between 1.0 and 10 µm, and / or ii. with a diameter of 2 to 12 μm in an amount of at least 45, more preferably at least 55% by volume on total lipids and where the composition comprises from 0.3 to 25% by weight of polar lipids on total lipids, where the polar lipids are the sum of phospholipids, glucosphingolipids and cholesterol, and where the volume and size distribution of the lipid globules is determined by the method described in Michalski et al. al, 2001, Lait 81: 787-796, using a Mastersizer, Malvern Instruments, Malvern, UK, as a particle size analyzer, and where the lipid globules are coated with a layer of polar lipids, and where the composition comprises a weight ratio of linoleic acid to alpha-linolenic acid between 2 and 15, for use in preventing obesity and / or reducing the risk of obesity, where the nutritional composition is to feed a human subject aged between 0 and 36 months and to prevent obesity later in life and / or reduce the risk of obesity later in life, when said human subject is over 18 years of age.

Description

DESCRIPTION

Nutritional compositions with large diameter lipid globules with a coating comprising polar lipids

FIELD OF THE INVENTION

[0001] The invention is related to the field of infant milk formulas and growth milks for the prevention of obesity later in life.

BACKGROUND

[0002] Breastfeeding is the preferred method of feeding babies. However, there are circumstances that make breastfeeding impossible or less desirable. In those cases, infant formulas are a good alternative. The composition of modern infant formulas is tailored in such a way that it meets many of the special nutritional needs of the rapidly growing and developing baby.

[0003] Still, it appears that improvements can be made in the constitution of infant milk formulas. Breastfed babies are less likely to become obese later in life than formula-fed babies, but little is known about the effects of ingredients in infant formulas on obesity later in life . Until now, most of the research has been devoted to the role of protein concentration or fatty acid composition. Obesity is a major health problem in the Western world. It is a medical condition in which excess accumulates in such a way that it can have an adverse effect on health, reducing life expectancy and is associated with many diseases, particularly heart disease and type 2 diabetes. Obesity is one of the leading preventable causes of death worldwide, with an increasing prevalence in adults and children, and is considered by the authorities to be one of the most serious public health problems of the 21st century.

[0004] The present invention is related to such future healthy body composition.

[0005] Patent WO 2007/073194 refers to infant formulas comprising phospholipids, sphingolipids and cholesterols for the prevention of obesity. WO 2007/073193 refers to infant formulas with a specific ratio of linoleic acid to alpha-linolenic acid, low content of linoleic acid and comprising phospholipids, sphingolipids, cholesterol and / or choline plus uridine for the prevention of obesity later in life. Patent EP1800675 refers to a composition with polyunsaturated fatty acids, proteins and manganese and / or molybdenum to improve the composition of the membrane for the treatment of a wide variety of disorders.

[0006] Michalski et al, 2005, J Dairy Sci 88: 1927-1940 reveals the size distribution of lipid globules in human milk and infant formula. Patent WO 2005/051091 refers to a combination of lipids that, when dispersed or emulsified in an essentially aqueous medium with other ingredients of infant formula, forms a substantially homogeneous dispersion or emulsion that has a microstructure containing lipid globules that is essentially mimetic. of the corresponding globular microstructure of natural HMFs. Patent SU 1084006 discloses foods for children and disabled people with a lipid globule size of 4 pM in diameter, similar to human milk.

SUMMARY OF THE INVENTION

[0007] The inventors have surprisingly discovered that lipid globule size in infant formulas affects body composition later in life. Specific selection of lipid globule size in infant formulas results in a decrease in fat mass and / or a decrease in obesity later in life. Specific selection for lipid globule size in infant formulas also resulted in increased lean body mass later in life. When an infant formula of the present invention comprising lipids with a lipid globule size greater than that present in conventional infant formulas was administered early in life, it was observed that later in life the body composition changed, resulting in less fat mass and less fat mass relative to total body weight and an increase in lean body mass compared to body composition when giving conventional infant formula. In particular, visceral obesity, which is more associated with health problems, was reduced. In particular, adipocyte hypertrophy was reduced. Obesity caused by hypertrophy of adipocytes is believed to be indicative of the onset of obesity later in life and is more associated with health problems such as insulin resistance than obesity caused by adipocyte hyperplasia.

[0008] The considerable difference between the investigated formulas was the size of the lipid globules, while the fatty acid profile was similar in the formulas.

[0009] The formulas investigated furthermore allowed good growth and similar development early in life and, more particularly, had no effect on fat mass early in life. Therefore, there was no a direct effect, that is, a preventive effect of obesity, of diet. This is advantageous, as fat mass plays an important role in energy storage, isolation, fat-soluble vitamin storage, and hormonal development, such as the development of leptin and leptin sensitivity for infants and young children. insulin and therefore it is desirable to decrease fat mass in infants and young children.

[0010] An even improved effect on fat mass, and fat mass relative to total body mass later in life, was observed when large lipid globules were covered by an outer layer of polar lipids. This improvement could not be explained by the presence of the polar lipids themselves, since the mere addition of polar lipids without coating of the lipid globules did not show these enhanced effects.

[0011] Standard infant milk formulas have vegetable fat as a lipid component. The lipid is homogenized to create a stable emulsion and the lipid globules are small, with a volume-weighted modal diameter of approximately 0.3 - 0.6 | _im. Less than 55% by volume of total lipids, typically less than 35% by volume, has a size between 2 and 12 | _im. Lipid globules are largely covered with milk proteins, particularly casein.

[0012] The present invention relates to infant formulas or growth milks for young children comprising vegetable fats with a lipid globule size greater than that of standard infant formulas. The present composition comprises lipid globules with a lipid volume-weighted modal diameter above 1.0 µm, preferably between 1.0 and 10 µm, and / or with at least 45, more preferably at least 55% in volume with a diameter of 2 to 12 | _im over total lipids. This can be achieved by homogenizing the lipid component comprising vegetable fat at lower pressures, preferably in the presence of polar lipids, to coat the enlarged lipid globules and make them more stable. The oil-in-water emulsion thus obtained has been found to be stable for at least 48 h. In particular, when the formulas are dried to powder and subsequently reconstituted with water to obtain a ready-to-drink formula shortly before use, no disadvantageous effects with respect to stability are observed.

[0013] Surprisingly, it has now been discovered that lipid globule size administered early in life is one of the determining factors affecting body composition, in particular fat mass, more in particular visceral fat mass and lean body mass, later in life. This effect on fat mass was even more pronounced when large lipid globules were coated with polar lipids such as phospholipids. Since no acute effects of the diet on body composition were advantageously observed, it is concluded that the diet programmed the body or left an imprint on it in such a way that it resulted in the development of an improved body composition later in life after further growth under similar conditions.

[0014] Therefore, the present invention can be used for food compositions intended for infants and / or young children in order to prevent obesity, visceral obesity, increase lean body mass and / or decrease fat mass later in the life.

DETAILED DESCRIPTION

[0015] The present invention therefore relates to a nutritional composition comprising

a) from 10 to 50% by weight of vegetable lipids on the dry weight of the composition, and

b) lipid globules

i) with a volume-weighted modal diameter greater than 1.0 | _im, preferably between 1.0 and 10 | _im, and / or

ii) with a diameter of 2 to 12 µm in an amount of at least 45, more preferably at least 55% by volume on the total lipids.

and where the composition comprises from 0.3 to 25% by weight of polar lipids over total lipids, where the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol,

and where the volume and size distribution of lipid globules is determined by the method described in Michalski et al, 2001, Lait 81: 787-796, using a Mastersizer, Malvern Instruments, Malvern, United Kingdom, as a size analyzer of particle, and wherein the lipid globules are coated with a layer of polar lipids, and wherein the composition comprises a weight ratio of linoleic acid to alpha-linolenic acid of between 2 and 15,

for use in the prevention of obesity and / or to reduce the risk of obesity, wherein the nutritional composition is to feed a human subject between the ages of 0 and 36 months and to prevent obesity later in life and / or reduce the risk of obesity later in life, when said human subject is older than 18 years.

[0016] For the sake of clarity, it is noted that lipid globules as defined in b) comprise plant lipids as defined in a) or, in other words, that a) and b) overlap.

Furthermore, the invention relates to a nutritional composition comprising

a) 10 to 50% by weight of plant lipids on the dry weight of the composition, and

b) lipid globules

i) with a volume-weighted modal diameter greater than 1.0 | _im, preferably between 1.0 and 10 | _im, and / or

ii) with a diameter of 2 to 12 | _im in an amount of at least 45% by volume, more preferably at least 55% by volume on the total lipids, and

c) from 0.6 to 25% by weight of polar lipids over total lipids, where the polar lipids include phospholipids, glycosphingolipids and cholesterol, and where the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol over total lipids ,

and where the volume and size distribution of the lipid globules is determined by the method described in Michalski et al, 2001, Lait 81: 787-796, using a Mastersizer, Malvern Instruments, Malvern, United Kingdom, as a size analyzer of particle, and wherein the lipid globules are coated with a layer of polar lipids, and wherein the composition comprises a weight ratio of linoleic acid to alpha-linolenic acid of between 2 and 15.

Obesity

[0018] The present composition is preferably administered to a human subject with an age less than 36 months, preferably less than 18 months, more preferably less than 12 months, even more preferably less than 6 months. Preferably, the human subject is not obese and / or is not overweight.

[0019] Obesity in the present invention refers to an excess of body fat mass. Fat mass is also known as adipose tissue or fatty tissue. An adult human person is obese if more than 25% by weight (for men) or more than 30% by weight (for women) of body weight is fat mass. Obesity is sometimes known as adiposity.

[0020] Suitable ways to determine% body fat mass are hydrostatic weighing, skinfold measurement, bioelectrical impedance analysis, computed tomography (CT / CT), magnetic resonance imaging (MRI / MRI), ultrasound and dual energy x-ray absorptiometry (DEXA). A preferred method is DEXA measurement. In the context of this invention, body fat mass is determined by DEXA.

[0021] The increased risk of health problems later in life, such as diabetes and cardiovascular disease, is related to the appearance of visceral adiposity and not to general obesity. The term "visceral obesity" refers to a condition with increased visceral adipose tissue. Visceral adiposity is usually caused by (accumulation of) excessive visceral fatty tissue. Visceral fat, also known as organ fat, intra-abdominal fat, peritoneal fat, or central fat, is normally found within the peritoneal cavity, as opposed to subcutaneous fat found under the skin and intramuscular fat found sandwiched in skeletal muscles. Visceral fat includes abdominal fat that surrounds vital organs and includes mesenteric fat, perirenal fat, retroperitoneal fat, and preperitoneal fat (fat that surrounds the liver). A waist circumference greater than 102 cm in adult men or greater than 88 cm in adult women indicates the presence of visceral adiposity. A hip-waist ratio greater than 0.9 in men and 0.85 in women indicates visceral adiposity. For children 3 to 19 years, appropriate limits for age- and gender-dependent waist circumferences can be found in Taylor et al, 2000 Am J Clin Nutr 72: 490-495. A subject has visceral adiposity when he meets one or more of the above criteria (with respect to VAT, waist circumference thresholds, or waist-to-hip ratio).

Lipid component

[0022] The present composition comprises lipids. Lipids preferably provide 30 to 60% of the total calories in the composition. More preferably, the present composition comprises lipids that provide 35 to 55% of the total calories, even more preferably the present composition comprises lipids that provide 40 to 50% of the total calories. When in liquid form, for example as a ready-to-drink liquid, the composition preferably comprises 2.1 to 6.5 g of lipids per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. Based on the dry weight, the present composition preferably comprises 10 to 50% by weight, more preferably 12.5 to 40% by weight of lipids, even more preferably 19 to 30% by weight of lipids.

[0023] Lipids include polar lipids (such as phospholipids, glycolipids, sphingomyelin, and cholesterol), monoglycerides, diglycerides, triglycerides, and free fatty acids. Preferably, the composition comprises at least 75% by weight, more preferably at least 85% by weight of triglycerides on total lipids.

[0024] The lipids of the present invention comprise plant lipids. The presence of vegetable lipids advantageously allows an optimal fatty acid profile, high in (poly) unsaturated fatty acids and / or more reminiscent of the fat of human milk. The use of lipids from cow's milk alone, or from other domestic mammals, does not provide an optimal fatty acid profile. This less optimal fatty acid profile, like a large amount of saturated fatty acids, is known to increase obesity. Preferably, the present composition comprises at least one, preferably at least two lipid sources selected from the group consisting of linseed oil (flax seed oil), rapeseed oil (such as rapeseed oil, rapeseed oil). Low erucic acid rapeseed and canola oil), sage oil, perilla oil, purslane oil, lingonberry oil, sea buckthorn oil, hemp oil, sunflower oil, high oleic sunflower oil, oil safflower, high oleic safflower oil, olive oil, blackcurrant seed oil, viborera oil, coconut oil, palm oil and palm kernel oil. Preferably, the present composition comprises at least one, preferably at least two lipid sources selected from the group consisting of linseed oil, canola oil, coconut oil, sunflower oil, and high oleic sunflower oil. Commercially available plant lipids are typically offered in the form of a continuous oil phase. When in liquid form, for example as a ready-to-drink liquid, the composition preferably comprises 2.1 to 6.5 g of plant lipids per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. On the dry weight, the present composition preferably comprises 10 to 50% by weight, more preferably 12.5 to 40% by weight of vegetable lipids, even more preferably 19 to 30% by weight. Preferably, the composition comprises 50 to 100% by weight of plant lipids on total lipids, more preferably 70 to 100% by weight, even more preferably 75 to 97% by weight. It is therefore noted that the present composition may also comprise non-plant lipids. Suitable and preferred non-plant lipids are further specified below.

Lipid blood cell size

[0025] According to the present invention, lipids are present in the composition in the form of lipid globules, emulsified in the aqueous phase. The lipid globules of the present invention have

1. a volume-weighted modal diameter greater than 1.0 | _im, preferably greater than 3.0 | _im, more preferably 4.0 | _im or greater, preferably between 1.0 and 10 | _im, more preferably between 2, 0 and 8.0 | _im, even more preferably between 3.0 and 8.0 | _im, most preferably between 4.0 and 8.0 | _im and / or 2. a size distribution such that at least 45% by volume, preferably at least 55% by volume, even more preferably at least 65% by volume, even more preferably at least 75% by volume has a diameter between 2 and 12 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 has 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 has a diameter between 4 and 10 µm.

[0026] The percentage of lipid globules is based on the total lipid volume. Modal diameter refers to the diameter that is most present as a function of total lipid volume, or the maximum value in a graphical representation, with the diameter on the X axis and the volume (%) on the Y axis. The globule volume Lipid and its size distribution can be suitably determined using a particle size analyzer such as a Mastersizer (Malvern Instruments, Malvern, UK), for example, by the method described in Michalski et al, 2001, Lait 81: 787-796 .

Polar lipids

[0027] The present invention comprises polar lipids. Polar lipids are amphipathic in nature and include glycerophospholipids, glycosphingolipids, sphingomyelin, and cholesterol. In particular, the composition comprises phospholipids (the sum of glycerophospholipids and sphingomyelin). The polar lipids of the present invention refer to the sum of glycerophospholipids, glycosphingolipids, sphingomyelin and cholesterol. Polar lipids are present as a coating or outer layer of the lipid globule. It has been found that the presence of polar lipids as the coating or outer layer of the lipid globule advantageously decreases fat mass and relative fat mass, ie obesity. The presence of polar lipids helps to keep the lipid globules emulsified in the aqueous composition. This is especially important when the size of the lipid globule is large. Thus, according to the present invention, the lipid globules are coated with a layer of phospholipids or polar lipids. Therefore, lipid globules comprise a core and a coating. The core comprises vegetable fat and preferably comprises at least 90% by weight of triglycerides and more preferably consists essentially of triglycerides. The coating comprises phospholipids and / or polar lipids. Not all phospholipids and / or polar lipids that are present in the composition have to be necessarily included in the coating, but preferably a large part of them is. Preferably more than 50% by weight, more preferably more than 70% by weight, even more preferably more than 85% by weight, most preferably more than 95% by weight of the phospholipids and / or polar lipids that are present in the composition are comprised of the lipid globule coating. Not all the plant lipids that are present in the composition have to necessarily be comprised in the core of the lipid globules, but preferably a large part of them is, preferably more than 50% by weight, more preferably more than 70% by weight , even more preferably more than 85% by weight, even more preferably more than 95% by weight, most preferably more than 98% by weight of the plant lipids that are present in the composition are comprised in the core of the lipid globules.

[0028] The present composition preferably comprises glycerophospholipids. Glycerophospholipids are a class of lipids formed from fatty acids esterified at the hydroxyl groups at carbon 1 and carbon 2 of the remainder of the glycerol backbone and a negatively charged phosphate group attached to carbon 3 of glycerol through a ester bond, and optionally a choline group (in case of phosphatidylcholine, PC), a serine group (in case of phosphatidylserine, PS), an ethanolamine group (in case of phosphatidylethanolamine, PE), an inositol group (in case of phosphatidylinositol, PI) or a glycerol group (in the case of phosphatidylglycerol, PG) attached to the phosphate group. Lysophospholipids are a class of phospholipids with a fatty acyl chain. Preferably the present composition contains PC, PS, PI and / or PE, more preferably at least PC. Preferably, the glycerophospholipids comprise negatively charged phospholipids, in particular PS and / or PI. Negatively charged glycerophospholipids advantageously improve the stability of the oil-in-water emulsion.

[0029] The present composition comprises glycosphingolipids. The term "glycosphingolipids" as used in the present invention particularly refers to glycolipids with an amino alcohol, sphingosine. The backbone of sphingosine is O-linked to a charged main group such as the main chain of ethanolamine, serine, or choline. The main chain is also linked by an amide bond to a fatty acyl group. Glycosphingolipids are ceramides with one or more sugar residues attached in a p-glucosidic bond at the 1-hydroxyl position. Preferably, the present composition contains gangliosides, more preferably at least one ganglioside selected from the group consisting of GM3 and GD3.

[0030] The present composition preferably comprises sphingomyelin. Sphingomyelins have a phosphorylcholine or phosphorylethanolamine molecule esterified at the 1-hydroxy group of a ceramide. They are classified as phospholipids and sphingolipids, but they are not classified as glycerophospholipids or glycosphingolipids.

[0031] Sphingolipids are defined in the present invention as the sum of sphingomyelin and glycosphingolipids. Phospholipids are defined in the present invention as the sum of sphingomyelin and glycerophospholipids. Preferably, the phospholipids are derived from milk lipids. Preferably, the weight ratio of phospholipids: glycosphingolipids is 2: 1 to 10: 1, more preferably 2: 1 to 5: 1.

[0032] The present composition comprises phospholipids. Preferably, the present composition comprises 0.2 to 20% by weight of phospholipids on total lipids, more preferably 0.5 to 20% by weight of phospholipids on total lipids, more preferably 0.5 to 10% in weight, more preferably 1 to 10% by weight, even more preferably 3 to 8% by weight. Preferably, the present composition comprises 0.1 to 10% by weight of glucosphingolipids on total lipids, more preferably 0.5 to 5% by weight, even more preferably 2 to 4% by weight. Preferably, the present composition comprises 0.3 to 20% by weight (glycosphingolipids plus phospholipids) on total lipids, more preferably 0.5 to 20% by weight (glycosphingolipids plus phospholipids) on total lipids, more preferably 1 10% by weight.

[0033] The present composition comprises cholesterol. The present composition preferably comprises at least 0.005% by weight of cholesterol on total lipids, more preferably at least 0.02% by weight, more preferably at least 0.05% by weight, even more preferably at least 0.1% by weight. Preferably, the amount of cholesterol does not exceed 10% by weight of total lipids, more preferably it does not exceed 5% by weight, even more preferably it does not exceed 1% by weight of total lipids.

[0034] The present composition comprises from 0.3 to 25% by weight of polar lipids over total lipids, wherein the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol, more preferably 0.6 to 25% by weight of polar lipids over total lipids, more preferably 0.6 to 12% by weight, more preferably 1 to 10% by weight, even more preferably 3 to 10% by weight.

[0035] Preferred sources for providing phospholipids, glucosphingolipids and / or cholesterol are egg lipids, milk fat, buttermilk fat, and buttermilk fat (such as beta whey fat). A preferred source of phospholipids, particularly PC, is soy lecithin and / or sunflower lecithin. The present composition preferably comprises phospholipids derived from milk. Preferably, the present composition comprises phospholipids and glycosphingolipids derived from milk. Preferably, cholesterol is also obtained from milk. Preferably, the polar lipids are derived from milk. Polar lipids derived from milk include polar lipids isolated from milk lipids, cream lipids, buttermilk lipids (beta whey lipids), whey lipids, cheese lipids and / or whey lipids. Whey lipids are typically obtained during the manufacture of buttermilk. Buttermilk lipid or beta whey lipid is typically obtained during the manufacture of anhydrous milkfat from butter. Preferably, the phospholipids, glycosphingolipids and / or cholesterol are obtained from the cream of the milk. The composition preferably comprises phospholipids, glycosphingolipids and / or cholesterol from the milk of cows, mares, sheep, goats, buffaloes, equids and camels. Most preferred is to use a lipid extract isolated from cow's milk. Polar lipids derived from fat milk advantageously decrease fat mass to a greater extent than polar lipids from other sources. Preferably, the polar lipids are located on the surface of the lipid globule, that is, as a coating or outer layer. A suitable way to determine if polar lipids are found on the surface of lipid globules is laser scanning microscopy as described in Example 1. Concomitant use of polar lipids derived from pet milk and lipid derived triglycerides Therefore, it makes it possible to manufacture lipid globules with an architecture more similar to human milk, while at the same time providing an optimal fatty acid profile. Suitable commercially available sources for polar milk lipids are BAEF, SM2, SM3 and SM4 powder from Corman, Salibra from Glanbia and LacProdan MFGM-10 or PL20 from Arla. Preferably, the milk polar lipid source comprises at least 4% by weight of phospholipids on total lipids, more preferably 7 to 75% by weight, more preferably 20 to 70% by weight of phospholipids on total lipids .

[0036] Preferably, the weight ratio of phospholipids to protein is greater than 0.10, more preferably greater than 0.20, even more preferably greater than 0.3. Preferably at least 25% by weight, more preferably at least 40% by weight, most preferably at least 75% by weight of the polar lipids is derived from polar lipids in milk.

Fatty acid composition

[0037] In this document, LA refers to an acyl and / or linoleic acid chain (18: 2 n6); ALA refers to a chain of acyl and / or α-linolenic acid (18: 3 n3); LC-PUFA refers to long chain acyl and / or polyunsaturated fatty acid chains comprising at least 20 carbon atoms in the fatty acyl chain and with 2 or more unsaturated bonds; DHA refers to an acyl chain and / or docosahexaenoic acid (22: 6, n3); EPA refers to an acyl chain and / or eicosapentaenoic acid (20: 5 n3); ARA refers to an acyl and / or arachidonic acid chain (20: 4 n6); DPA refers to an acyl and / or docosapentaenoic acid chain (22: 5 n3). Medium chain fatty acids (MCFA) refer to acyl and / or fatty acid chains with a chain length of 6, 8 or 10 carbon atoms.

[0038] LA is preferably present in an amount sufficient to promote healthy growth and development, but in an amount that is as low as possible to prevent the onset of obesity later in life. Therefore, the composition preferably comprises less than 15% by weight of LA on total fatty acids, preferably between 5 and 14.5% by weight, more preferably between 6 and 10% by weight. Preferably, the composition comprises more than 5% by weight of LA on the fatty acids. Preferably, ALA is present in an amount sufficient to support healthy growth and development of the baby. Therefore, the present composition preferably comprises at least 1.0% by weight of ALA on the total fatty acids. Preferably, the composition comprises at least 1.5% by weight of ALA on total fatty acids, more preferably at least 2.0% by weight. Preferably, the composition comprises less than 10% by weight of ALA, more preferably less than 5.0% by weight of total fatty acids. The LA / ALA weight ratio must be well balanced to prevent obesity while ensuring normal growth and development. Therefore, the present composition comprises a LA / ALA weight ratio between 2 and 15, more preferably between 2 and 7, more preferably between 4 and 7, more preferably between 3 and 6, even more preferably between 4 and 5, 5, even more preferably between 4 and 5.

[0039] Since MCFAs contribute to reduced fat mass later in life when administered to an infant, the present composition preferably comprises at least 3% by weight of MCFA on total fatty acids, more preferably at least 10% by weight, even more preferably 15% by weight. Since MCFAs reduce body fat deposition without a preference for central fat mass, and since MFCAs do not decrease the number of adipocytes, the present composition advantageously comprises less than 50% by weight of MCFA on total fatty acids, plus preferably less than 40% by weight, even more preferably less than 25% by weight.

[0040] Preferably, the present composition comprises LC-PUFA n-3, since LC-PUFA n-3 reduce obesity later in life, more preferably central obesity. More preferably, the present composition comprises EPA, DPA and / or Ha, even more preferably DHA. Since a low concentration of DHA, DPA and / or EPA is already effective and normal growth and development are important, the LC-PUFA n-3 content of the present composition preferably does not exceed 15% by weight of the total content of fatty acids, preferably it does not exceed 10% by weight, even more preferably it does not exceed 5% by weight. Preferably, the present composition comprises at least 0.2% by weight, preferably at least 0.5% by weight, more preferably at least 0.75 % by weight, of LC-PUFA n-3 with respect to the total content of fatty acids.

As the group of fatty acids n-6, especially arachidonic acid (AA) and LA as its precursor, counteracts the group of fatty acids n-3, especially DHA and EPA and ALA as their precursors, the The present composition comprises relatively low amounts of AA. The content of LC-PUFA n-6 preferably does not exceed 5% by weight, more preferably does not exceed 2.0% by weight, more preferably does not exceed 0.75% by weight, even more preferably does not exceed 0, 5% by weight, on total fatty acids. Since AA is important in infants to obtain optimal functional membranes, especially neurological tissue membranes, the amount of LC-PUFA n-6 is preferably at least 0.02% by weight, more preferably at least 0.05% by weight, more preferably at least 0.1% by weight on the total fatty acids, more preferably at least 0.2% by weight. The presence of AA is advantageous in a low LA composition, since it makes up for the LA deficiency. The presence of preferably small amounts of AA is beneficial in foods to be administered to infants under 6 months of age, as infant formulas are generally the only food source for these infants.

[0042] Preferably, in addition to the plant lipid, a lipid selected from fish oil (preferably tuna oil) and oil from single-celled organisms (such as algae, microbial oil and fungal oil) is present. These oil sources are suitable as LC-PUFA sources. Preferably, as a source of LC-PUFA n-3, oil from single-celled organisms, including algae oil and microbial oil, is used as these oil sources have a low EPA / DHA ratio, which results in a greater anti-obesity effect. . More preferably, fish oil (even more preferably tuna oil) is used as a source of LC-PUFA n-3, as it has a higher EPA concentration, which is advantageous since EPA is an eicosanoid precursor. which have an additional effect against obesity. Thus, in one embodiment, the present composition further comprises at least one lipid selected from the group consisting of fish oil, marine oil, algae oil, mushroom oil, and microbial oil.

Process for obtaining lipid globules

[0043] The present composition comprises lipid globules. The size of the lipid globule can be manipulated by adjusting the process steps by which the present composition is manufactured. A suitable and preferred way to obtain larger lipid globule sizes is to adapt the homogenization process. In standard infant milk formula, the lipid fraction (which generally comprises vegetable fat, a small amount of polar lipids and fat soluble vitamins) is mixed into the aqueous fraction (which generally comprises water, skim milk, whey, digestible carbohydrates such as lactose , water-soluble vitamins and minerals and optionally indigestible carbohydrates) by homogenization. If no homogenization were carried out, the lipid part would very quickly become creamy, that is, it would separate from the aqueous part and would collect on top. Homogenization is the process of dividing the fat phase into smaller sizes so that it no longer quickly separates from the aqueous phase, but remains in a stable emulsion. This is achieved by passing the milk under high pressure through small holes. However, the present inventors have found that homogenization at a pressure lower than that commonly applied in the preparation of infant formula resulted in larger lipid globules of the present invention, while maintaining a sufficiently stable emulsion.

[0044] The process comprises the following steps:

1 Mix of ingredients

[0045] The ingredients of the composition are mixed, eg preferably homogeneously mixed. Basically, a lipid phase, which comprises plant lipids, and an aqueous phase are added. The ingredients of the aqueous phase may comprise water, skim milk (powder), whey (powder), low-fat milk, lactose, water-soluble vitamins and minerals. Preferably, the aqueous phase comprises proteins, digestible carbohydrates and polar lipids, more preferably phospholipids. Preferably, the aqueous phase comprises non-digestible oligosaccharides. Preferably, the aqueous phase is established at a pH between 6.0 and 8.0, more preferably pH 6.5 to 7.5. Preferably, the polar lipids, in particular the phospholipids, are derived from milk. The presence of polar lipids advantageously results in more stable lipid globules. This is especially important in the case of larger lipid cells. Advantageously, the presence of polar lipids present in the aqueous mixture prior to homogenization results in the coating of the lipid globules, which consist essentially of triglycerides, with a layer of polar lipids.

[0046] Preferably, the lipid phase comprises from 50 to 100% by weight of plant lipids on the total weight of the lipid phase. Instead of in the aqueous phase, the polar lipids, more preferably the phospholipids, can also be present in the lipid phase or in both phases. Alternatively, the polar lipids can be added separately to an aqueous and lipid phase. Preferably, the weight ratio of phospholipid to total lipid is 0.2 to 20% by weight, more preferably 0.5 to 10% by weight, even more preferably 3 to 8% by weight 0.2.

[0047] The aqueous and lipid phase are preferably heated before adding them to each other, preferably at a temperature of 40 ° C to 80 ° C, more preferably 55 ° C to 70 ° C, even more preferably 55 ° C to 60 ° C. The mixture is also kept at this temperature and is mixed evenly. A suitable way to make a homogeneous mix is to use an Ultra-Turrax T50 for approximately 30-60 s at 5000-10000 rpm. Subsequently, demineralized water can be added to this mixture, to obtain the desired% dry matter. A desired% dry matter is, for example, 15%. Alternatively, the lipid phase is injected into the aqueous phase immediately prior to homogenization. It is preferred that the injection be performed immediately before homogenization and at low pressure to obtain stable large lipid globules.

[0048] Minerals, vitamins, and stabilizer gums can be added at various points in the process depending on your sensitivity to heat. Mixing can be done, for example, with a high-shear mixer. In the process of the present invention, skimmed milk (casein) is preferably not present in this step and is added to the composition after homogenization of the fat fraction in the aqueous fraction (comprising compounds such as whey, whey protein , lactose).

2 Pasteurization

[0049] Preferably, the mixture is then pasteurized. Pasteurization involves a rapid heating step under controlled conditions that microorganisms cannot survive. A temperature of 60 to 80 ° C, more preferably 65 to 75 ° C, maintained for at least 15 s, generally adequately reduces the vegetative cells of the microorganisms. Various pasteurization methods are known that are commercially feasible. Alternatively, this step can also be performed prior to mixing as in step 1 and / or can be replaced by the 60 ° C heating step of step 1.

3 Homogenization

[0050] Subsequently, the optionally pasteurized mixture is homogenized. Homogenization is a process that increases the uniformity and stability of the emulsion by reducing the size of the lipid globules in the formula. This step of the process can be performed with a variety of mixing equipment, which apply high shear to the product. This type of mixing breaks the lipid globules into smaller globules. The mixture obtained is preferably homogenized in two steps at high temperature and pressure, for example 60 ° C at 30 to 100 and 5 to 50 bars respectively, with a total pressure of 35 to 150 bars. Alternatively, the mixture obtained is preferably homogenized in two steps at a lower temperature, between 15 and 40 ° C, preferably about 20 ° C at 5 to 50 and 5 to 50 bars respectively, with a total pressure of 5 to 100 bars. In one embodiment, the mixture obtained is homogenized at 30-100 bar in the first step. In another embodiment, the mixture obtained is homogenized at 5-50 bar in the first step.

[0051] This is notably lower than standard pressures, which are typically 250 to 50 bars, respectively, thus a total pressure of 300 bars.

[0052] What pressure to apply will depend on the specific homogenizer used. A suitable way is to use a pressure of 100 bar in the first step and 50 bar in the second step in a H 2006 Niro Suavi NS homogenizer at a temperature of 60 ° C. A suitable way is to use a pressure of 5 bar in the first step and 20 bar in the second step in a Niro Suavi NS 2006 H homogenizer at a temperature of 20 ° C. Subsequently, optionally, other ingredients other than lipids can be added.

4 Sterilization

[0053] Subsequently, the emulsion obtained in step 3 is preferably sterilized. Preferably, sterilization takes place online at ultra high temperature (UHT) and / or in appropriate containers to obtain a formula in the form of a sterile liquid. A suitable way for UHT treatment is a treatment at 120-130 ° C for at least 20 s. Alternatively, the emulsion obtained in step 3 is concentrated by evaporation, subsequently sterilized at ultra-high temperature and subsequently spray-dried to obtain a spray-dried powder with which appropriate containers are filled.

[0054] Alternatively, this sterilization step is performed before the homogenization step. Preferably, the composition obtained by the above process is subsequently spray dried.

[0055] The difference in the coating of the lipid globules can be further derived from the zeta potential. The Zeta potential (Z potential) measures the difference in millivolts (mV) in electrokinetic potential between the tightly bound layer around the surface and the distant zone of electroneutrality and is a measure of the magnitude of the repulsion or attraction between the particles of a dispersion. Its value is also related to the stability of colloidal dispersions. A high absolute zeta potential will confer stability, that is, the solution or dispersion will resist aggregation.

Digestible carbohydrate component

[0056] The composition preferably comprises digestible carbohydrates. The digestible carbohydrate preferably provides 30 to 80% of the total calories of the composition. Preferably, the digestible carbohydrate provides 40 to 60% of the total calories. When in liquid form, for example as a ready-to-drink liquid, the composition preferably comprises 3.0 to 30 g of digestible carbohydrates per 100 ml, more preferably 6.0 to 20, even more preferably 7.0 to 10.0 g per 100 ml. On a dry weight basis, the present composition preferably comprises 20 to 80% by weight, more preferably 40 to 65% by weight of digestible carbohydrates.

[0057] Preferred sources of digestible carbohydrates are lactose, glucose, sucrose, fructose, galactose, maltose, starch, and maltodextrin. Lactose is the main digestible carbohydrate present in human milk. The present composition preferably comprises lactose. The present composition preferably comprises digestible carbohydrates, wherein at least 35% by weight, more preferably at least 50% by weight, more preferably at least 75% by weight, even more preferably at least 90% by weight, most preferably at least 95% by weight of the digestible carbohydrate is lactose. On dry weight, the present composition preferably comprises at least 25% by weight of lactose, preferably at least 40% by weight.

Indigestible oligosaccharides

[0058] Preferably, the present composition comprises non-digestible oligosaccharides with a degree of polymerization (GP) between 2 and 250, more preferably 3 and 60. The non-digestible oligosaccharides advantageously prevent the appearance of insulin resistance, which will also have as result in a reduction in obesity and / or fat mass later in life. Furthermore, the presence of indigestible oligosaccharides advantageously results in a low gut microbiota in Firmicutes and high in Bacteroidetes, which results in a reduction in obesity. Therefore, the nondigestible oligosaccharides are supposed to potentiate the anti-obesity effects of the larger lipid globules of the composition according to the present invention.

The nondigestible oligosaccharide is preferably selected from the group consisting of fructo-oligosaccharides (such as inulin), galacto-oligosaccharides (such as transgalacto-oligosaccharides or beta-galacto-oligosaccharides), glucooligosaccharides (such as gentio-, nigero- and cyclodextrin- oligosaccharides), arabino-oligosaccharides, mananooligosaccharides, xyl-oligosaccharides, fuco-oligosaccharides, arabinogalacto-oligosaccharides, glucomano-oligosaccharides, galactoman-oligosaccharides, sialic acid comprising oligosaccharides and oligosaccharides of uronic acid. Preferably, the composition comprises gum arabic in combination with a non-digestible oligosaccharide.

[0060] Preferably, the present composition comprises fructo-oligosaccharides, galacto-oligosaccharides and / or galacturonic acid oligosaccharides, more preferably galacto-oligosaccharides, most preferably transgalacto-oligosaccharides. In a preferred embodiment, the composition comprises a mixture of transgalacto-oligosaccharides and fructo-oligosaccharides. Preferably, the present composition comprises galactooligosaccharides with a GP of 2-10 and / or fructo-oligosaccharides with a GP of 2-60. The galacto-oligosaccharide is preferably selected from the group consisting of transgalacto-oligosaccharides, lacto-N-tetraose (LNT), lacto-N-neotetraose (neo-LNT), fucosyl-lactose, fucosylated LNT and fucosylated neo-LNT. In a particularly preferred embodiment, the present method comprises the administration of transgalacto-oligosaccharides ([galactose] ⁿ -glucose; where n is an integer between 1 and 60, that is, 2, 3, 4, 5, 6 , ...., 59, 60; preferably n is selected from 2, 3, 4, 5, 6, 7, 8, 9 or 10). Transgalacto-oligosaccharides (TOS) are sold, for example, under the trademark Vivinal ™ (Borculo Domo Ingredients, The Netherlands). Preferably, the saccharides of the transgalacto-oligosaccharides are linked by p bonds.

[0061] The fructo-oligosaccharide is a non-digestible oligosaccharide comprising a chain of fructose units linked by p-bonds with a GP or an average GP of 2 to 250, more preferably 10 to 100. The fructo-oligosaccharide includes inulin, levan and / or a mixed type of polyfructan. An especially preferred fructo-oligosaccharide is inulin. Fructo-oligosaccharide suitable for use in the compositions is also already commercially available, for example Raftiline®HP (Orafti).

[0062] The uronic acid oligosaccharides are preferably obtained from the degradation of pectin. The uronic acid oligosaccharides are preferably galacturonic acid oligosaccharides. Therefore, the present composition preferably comprises a pectin degradation product with a GP between 2 and 100. Preferably, the pectin degradation product is prepared from apple pectin, beet pectin and / or citrus pectin. Preferably the composition comprises transgalacto-oligosaccharide, fructooligosaccharide, and a pectin degradation product. The weight ratio of transgalacto-oligosaccharide degradation product: fructo-oligosaccharide: pectin is preferably (20 to 2): 1: (1 to 3), more preferably (12 to 7): 1: (1 to 2 ).

[0063] Preferably, the composition comprises 80 mg to 2 g of nondigestible oligosaccharides per 100 ml, more preferably 150 mg to 1.50 g, even more preferably 300 mg to 1 g per 100 ml. On the dry weight, the composition preferably comprises from 0.25% by weight to 20% by weight, more preferably from 0.5% by weight to 10% by weight, even more preferably from 1.5% by weight to 7 , 5% by weight. A smaller amount of indigestible oligosaccharides will be less effective in preventing obesity, while too high an amount will result in side effects of bloating and abdominal discomfort.

Protein component

[0064] The present composition preferably comprises proteins. The protein component preferably provides 5 to 15% of the total calories. Preferably, the present composition comprises a protein component that provides 6 to 12% of the total calories. More preferably, the protein is present in the composition below 9% of the calories, more preferably the composition comprises between 7.2 and 8.0% protein of the total calories, even more preferably between 7.3 and 7, 7% of total calories. A low protein concentration advantageously ensures a lower insulin response, thus avoiding the proliferation of adipocytes in babies. Human milk contains less protein based on total calories than cow's milk. The concentration of proteins in a nutritional composition is determined by the sum of proteins, peptides and free amino acids. On dry weight, the composition preferably comprises less than 12% by weight of protein, more preferably between 9.6 and 12% by weight, even more preferably 10 to 11% by weight. Based on a ready-to-drink liquid product, the composition preferably comprises less than 1.5 g of protein per 100 ml, more preferably between 1.2 and 1.5 g, even more preferably between 1.25 and 1.35 g .

[0065] The source of the protein should be selected in such a way that the minimum requirements for the content of essential amino acids are met and satisfactory growth is guaranteed. Therefore, protein sources based on cow's milk proteins such as whey, casein and mixtures of these 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 or sweet whey, whey protein isolate or mixtures thereof and may include α-lactalbumin and p-lactoglobulin. More preferably, the protein source is based on acid whey or sweet whey from which casein glycomacropeptide (CGMP) has been removed. The removal of CGMP from the sweet whey protein advantageously reduces the threonine content of the sweet whey protein. A reduced threonine content is also advantageously achieved by using acid whey. Optionally, the protein source can be supplemented with free amino acids, such as methionine, histidine, tyrosine, arginine, and / or tryptophan to improve the amino acid profile. Preferably, α-lactalbumin enriched whey protein is used to optimize the amino acid profile. The use of protein sources with an optimized amino acid profile closer to that of human breast milk allows all essential amino acids to be provided at a reduced protein concentration, below 9% based on calories, preferably between 7 , 2 and 8.0% based on calories and still ensure satisfactory growth. If using sweet whey from which CGMP has been removed as a protein source, it is preferably supplemented with free arginine in an amount of 0.1 to 3% by weight and / or free histidine in an amount of 0.1 to 1, 5% by weight on the total protein.

[0066] Preferably, the composition comprises at least 3% by weight of casein on the dry weight. Preferably, the casein is intact and / or not hydrolyzed.

Nutritional composition

[0067] The present composition is preferably is particularly suitable for providing daily nutritional requirements to a human being with an age less than 36 months, particularly a child with an age less than 24 months, even more preferably a child with an age below to 18 months, most preferably less than 12 months of age. Therefore, the nutritional composition is for feeding or is used for feeding a human subject. The present composition comprises a lipid, and preferably a protein and preferably a digestible carbohydrate component, wherein the lipid component preferably provides 30 to 60% of the total calories, the protein component preferably provides 5 to 20%, plus preferably 5 to 15% by weight of the total calories and the digestible carbohydrate component preferably provides 25 to 75% of the total calories. Preferably, the present composition comprises a lipid component that provides 35 to 50% of the total calories, a protein component provides 6 to 12% of the total calories, and a digestible carbohydrate component provides 40 to 60% of the calories. totals. The amount of total calories is determined by the sum of calories derived from proteins, lipids and digestible carbohydrates.

[0068] The present composition is not human breast milk. The present composition comprises plant lipids. The compositions of the invention preferably comprise other fractions, such as vitamins or minerals in accordance with international directives for infant formulas.

[0069] In one embodiment, the composition is a powder suitable for preparing a liquid composition after reconstitution with an aqueous solution, preferably with water. Preferably the composition is a powder to be reconstituted with water. Surprisingly, it has been found that the size and the coating with the polar lipids of the lipid globules remained the same after the drying step and subsequent reconstitution. The presence of larger lipid globules may have a slightly negative effect on the long-term stability of the liquid composition. However, the separation of the lipid and aqueous layers was not observed within 48 h, which is much longer than the time elapsed between reconstitution of the powder in a ready-to-drink liquid and its consumption, which will be less than 24 hours. h and typically within 1 h. The composition which is in powder form therefore has a further advantage in the present invention with large lipid globules.

[0070] To meet the caloric needs of the baby, the composition preferably comprises 50 to 200 kcal / 100 ml of liquid, more preferably 60 to 90 kcal / 100 ml of liquid, even more preferably 60 to 75 kcal / 100 ml of liquid. This caloric density ensures an optimal ratio between water consumption and calories. The osmolarity of the present composition is preferably between 150 and 420 mOsmol / l, more preferably 260 to 320 mOsmol / l. The low osmolarity aims to reduce gastrointestinal stress. Stress can induce the formation of adipocytes.

[0071] Preferably, the composition is in liquid form, with a viscosity of less than 35 mPa.s, more preferably less than 6 mPa.s, measured in a Brookfield viscometer at 20 ° C at a shear rate of 100 s-1 . Suitably, the composition is in the form of a powder, which can be reconstituted with water to form a liquid, or as a liquid concentrate, which must be diluted with water. When the composition is in liquid form, the preferred volume administered daily is in the range of about 80 to 2500 ml, more preferably about 450 to 1000 ml per day.

Baby

[0072] Adipocytes proliferate during the first 36 months of life and are more limited at puberty. The number of adipocytes is an important determinant in the degree of fat mass, adipose tissue and / or obesity in the future. Therefore, the present composition is preferably administered to the human subject during the first 3 years of life. In use according to the present invention, the nutritional composition is for feeding a human subject between 0 and 36 months of age. It has been found that there is a predominance of adipocyte proliferation in the first 12 months of life with optimal perinatal adipocyte proliferation. Therefore, it is particularly preferred that the present composition is administered to a human subject in this period of life. Therefore, the present composition is advantageously administered to a human 0-24 months, more preferably a human 0-18 months, most preferably a human 0-12 months. The present invention is particularly aimed at preventing obesity in the future and is not a treatment for obesity. Therefore, the present composition is preferably administered to an infant and / or young child who is not overweight or obese. In one embodiment of the use according to the present invention, the nutritional composition is for feeding a non-obese human subject. Preferably, the composition should be used in infants who have an appropriate weight for gestational age.

[0073] Preferably, the composition is to be used in babies who have been born prematurely or who are small for gestational age. These babies experience progressive growth after birth, which is an additional risk of developing obesity and / or too much fat in the future. Preferably, the composition is to be used in babies who are large for gestational age. These babies are at higher risk of developing obesity and / or too much fat in the future. Preferably, the composition should be used in babies born to mothers suffering from obesity and / or diabetes. Such babies are at a higher risk of developing obesity and / or too much fat in the future.

Application

[0074] The present composition is preferably administered orally to the baby. The present invention also aims to prevent the onset of obesity and / or reduce fat mass at the age greater than 36 months. The present nutritional composition is for feeding a human subject between 0 and 36 months old and for preventing obesity and / or reducing the risk of obesity when said human subject is older than 18 years. In one embodiment, the present nutritional composition is for preventing visceral obesity.

[0075] The inventors have surprisingly discovered that when mice were fed during infancy and childhood a food composition comprising enlarged lipid globules, a different and significant effect on body composition was observed later in life compared with mice that had been fed during infancy and childhood a food composition that had a similar fatty acid composition, but a smaller lipid globule size. On day 42, which is a time point corresponding to childhood in a human environment, no difference in growth (weight) was observed between the two groups, but from day 42 both groups were fed a Western-style diet it was high in fat. Surprisingly, on day 126, which is a time point corresponding to adulthood in In humans, mice that had previously consumed the food composition of the present invention before resorting to the Western-style diet had significantly lower fat mass and lower relative fat mass than mice that had received a control composition. In other experiments it was shown that the presence of a polar lipid coating or outer layer around these lipid globules in the diet further decreased fat mass and relative fat mass compared to large lipid globules without this coating. It has also been surprisingly found that, compared to the control diet, the administration of a diet comprising large lipid globules during infancy resulted in a specific decrease in visceral fat mass later in life, that is, reduced the visceral obesity later in life. This is advantageous, since visceral obesity in particular is more associated with health problems. Furthermore, it was observed that the hypertrophy of adipocytes was reduced. Obesity caused by hypertrophy of adipocytes is believed to be indicative of obesity later in life and is more associated with health problems such as insulin resistance than obesity caused by adipocyte hyperplasia. This is a further indication that diet does not have an acute effect in treating or preventing obesity (which is unwanted in infants) but rather a programming effect to prevent the onset of obesity later in life.

[0076] In this document and in its claims, the verb "understand" and its conjugations are used in their non-limiting sense to mean that the elements that follow the word are included, but the elements not specifically mentioned are not excluded. Furthermore, the 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 "un" or "una" generally means "at least one".

EXAMPLES

Example 1 : Process to prepare an infant milk formula ( IMF) with a larger lipid globule size

Example 1 A:

[0077] An infant formula was prepared comprising, per kg of powder, 4800 kcal, 248 g of lipids, 540 g of digestible carbohydrates, 55 g of non-digestible oligosaccharides and 103 g of protein. The composition was prepared using BAEF powder (Corman, Goé, Belgium), a mixture of vegetable oil, demineralized whey powder, lactose, indigestible oligosaccharides (galacto-oligosaccharides and long-chain fructo-oligosaccharides in a weight ratio of 9 / one). Vitamins, minerals, trace elements were also used as known in the art.

[0078] The amount of BAEF was such that 7.24% by weight of phospholipids (from BAEF) based on total lipids were present in the composition. Based on small amounts of phospholipids in the oil mixture, the total amount of phospholipids was 7.39% by weight on total lipids. BAEF powder also delivered a small amount of cholesterol (approximately 0.08% by weight on the total lipids of the infant formula) and glycosphingolipids (approximately 1.65% of the glycosphingolipids on the total lipids of the infant formula). The BAEF powder was mixed with galacto-oligosaccharides, lactose, vitamin premixes and mineral premixes in water, at room temperature, by shaking. Potassium hydroxide was used to set the pH to 6.8-7.0. The dry weight matter of the mixture was about 27%. The mixture was heated to 60 ° C. The vegetable oil mixture was also heated to 60 ° C and added to the aqueous phase and mixed with an Ultra-Turrax T50 for about 30-60 sec at 5000-10000 rpm. Subsequently demineralized water was added to achieve a dry matter content of approximately 15%.

Subsequently, the oil and water mixture was homogenized at a pressure of 100 bars in a first step and 50 bars in a second step in a H 2006 Niro Suavi NS homogenizer. The temperature was 60 ° C. Subsequently, demineralized whey powder was added to reach a final dry matter content of 18%. The product was treated by UHT at 125 ° C for 30 s. The product was dried to a powder by spray drying. The maltodextrin together with the long chain inulin was dry mixed with the powder. The size of the lipid globules was measured with a Mastersizer 20000 (Malvern Instruments, Malvern, UK). The volumetric modal diameter was 7.3 | _im. A second, much smaller peak was present at 0.52 | _im. The volume% of lipid globules with a size between 2 and 12 μm was 71% based on the total lipid volume. The largest lipid globules of the present invention were verified by confocal laser scanning microscopy to be coated with phospholipids, before spray drying and after reconstitution of the water spray dried powder. In both cases, the lipid globules were covered with a layer of phospholipids. As fluorescent probes, Annexin V Alexa Fluor 488 ( in vitro molecular probes ) were used to label phospholipids, and Nile Red (Sigma-Aldrich) were used to label triglycerides. After marking the milk samples, Vectrahield mounting medium (Vector laboratories inc., Burliname, USA) was added to reduce particle movement and photo bleaching. Observations were made using a Zeiss laser scanning microscope with excitation wavelengths of 488/543/633 nm and emission filters set at bandpass 505-530 and bandpass 560-615. Also the size of the lipid globules was the same before drying and after reconstitution of the spray dried powder with water.

[0080] As a control, lipid globules from a standard infant formula (Nutrilon 1) did not show phospholipid labeling as seen with confocal laser scanning microscopy. Instead, the beads were covered with protein, as determined by Fast Green FCF fluorescent protein staining. The volumetric modal diameter of the lipid globules in this standard infant milk formula was measured at 0.5 | _im. A second, much smaller peak was present at 8.1 | _im. The volume% of lipid globules with a size between 2 and 12 µm was 34% based on the total lipid volume.

[0081] Human milk was also analyzed and this showed a volumetric modal diameter of lipid globules of 5.3 | _im. The volume% of lipid globules with a size between 2 and 12 μm was 98% of the total lipid volume. The lipid globules were covered with a layer of phospholipids.

[0082] The zeta potentials and volume weighted mean diameters were also measured. The results are shown in Table 1.

Example 1B:

[0083] Infant formula was prepared in a similar manner to Example 1A. The oil blend was prepared using vegetable oils, oil soluble vitamins, and antioxidants. Both the aqueous phase and the oil blend were heated to 65 ° C before mixing. The oil blend was added to the aqueous phase and mixed with an Ultra-Turrax T50 for about 30-60 sec at 5000-1000 rpm. The dry weight of this mixture was approximately 26%. The product was treated with UHT for 30 s at 125 ° C and subsequently cooled to 20 ° C.

[0084] For diet 2 and 3 and 4, this mixture was homogenized in two steps at a pressure of 5 and 20 bars, respectively, in a Niro Suavi NS 2006 H homogenizer. For diet 1, the homogenization pressure was 200 and 50 bar, respectively, in a Niro Suavi NS 2006 H homogenizer. The products were dried to powder by spray drying. Long chain inulin was dry mixed with the powder. For diet 1 and 2, no added polar lipids were found. The amount of vegetable glycerophospholipids was 0.2% by weight on total fats for diets 1 and 2. Diets 1 and 2 did not contain sphingolipids and cholesterol. Powdered buttermilk was used for diets 3 and 4. Diet 3 comprised 1.83% by weight of glycerophospholipids over total fat, of which approximately 90% was derived from powdered buttermilk and approximately 10% was already present in the standard IMF derived from vegetable oils, and furthermore comprised sphingolipids derived from milk, of which the majority (approximately 0.47% by weight on total fat) was sphingomyelin; the rest were glycosphingolipids, of which the majority (more than 60%) was GD3 with a concentration of approximately 0.13% on total fat. Diet 3 comprised approximately 0.05% by weight milk derived cholesterol on total fat. Diet 4 comprised half the amount of milk-derived polar lipids over total fat in diet 3.

[0085] In diet 3, the powdered buttermilk comprising these polar lipids was dry mixed after homogenization, sterilization, and the spray drying step to avoid coating of the lipid globules. In diet 4, the polar butter lipids were present in the aqueous phase during the homogenization step to coat the lipid globules.

[0086] The size of the lipid globules was measured with a Mastersizer 20000 (Malvern Instruments, Malvern, UK) and is shown in Table 2. The coating of the lipid globules with polar lipids in diet 4 and the absence of coating in diet 1, 2 and 3 it was confirmed by the confocal laser scanning microscopy method as described above.

T l 2: r rí i l l l li í i if r n l h

[0087] After 5 months of storage at room temperature, the size of the lipid globules of diet 1 had not changed, with a volumetric modal diameter of 0.5. Furthermore, the volumetric modal diameter of diets 2, 3 and 4 was quite stable, 4.8 | _im, 7.9 | _im, and 6.6 | _im respectively.

Example 2: effect of lipid globule size programming on adult body composition

[0088] The offspring of dams C57 / BL6 were weaned from day 15 onwards. The experimental weaning diets continued until day 42. From day 42 to day 126, all pups were fed the same diet based on the AIN-93G diet with an adjusted lipid fraction (containing 10% by weight of lipids, of which 50% by weight was butter and 1% was cholesterol, based on total lipids), which is representative of a Western-style diet.

[0089] The experimental diets that were used for weaning were:

1) a control diet based on an infant milk formula (IMF). This diet comprised 282 g of standard IMF (Nutrilon 1) per kg, with the lipid globule size as mentioned in Example 1A. The rest of the diet was AIN-93G protein, carbohydrates, and fiber. All lipids present in the diet were derived from MFI.

2) a diet based on the IMF of the present invention. This diet differed from diet 1 in that it comprised 282 g of the IMF of Example 1A, that is, it comprised larger lipid globules than the control. All lipids present in the diet were derived from MFI.

[0090] On day 42, all mice were switched to a "western-style diet" comprising 10% by weight of lipids until day 126. The composition of the diets is given in Table 3. The fatty acid composition of the two experimental diets and the "cafeteria" one is shown in Table 4. The fatty acid profile of the two experimental diets was very similar.

T l: m i i n i x rim n l r k

[0091] Mice were weighed twice a week. Food intake was determined once a week throughout the experiment. To determine body composition (i.e., fat mass (MG) and lean mass (MM)) DEXA (dual energy X-ray absorptiometry) scans were performed under general anesthesia at 6, 10, and 14 weeks of age, 42, 70, 98, and 126 days after birth, respectively, by densitometry using a PIXImus imager (GE Lunar, Madison, WI, USA). At the age of 126 days, Male mice were sacrificed and the organs were dissected and weighed (viz. fatty tissues, liver, tibialis muscle). The blood was analyzed to obtain the parameters of leptin, resistin and insulin (fasting).

Table 4: Com osition of fats of the experimental diets.

Results:

[0092] No effect on growth (body weight) and food intake was observed during the experimental period between the groups. Furthermore, the development of fat mass (determined by DEXA) was not significantly different on day 42 (end of the diet intervention period).

[0093] A subsequent treatment with a western-style diet between day 42 and day 126 of all groups resulted in clear differences in body composition at the end of the experiment (day 126), see Table 5. Fat mass and Relative fat mass developed later in life were reduced in pups that had received the diet with the largest lipid globules during infancy and childhood, compared to pups that had received the control diet. Overall body weight was comparable between the two groups. The experimental group had a higher lean body mass.

Table 5: Weight cor oral cor oral mass t ra relative ground mass.

[0094] The liver in the control group had a mean weight of 157 g (ie 0.07) and in the experimental diet 1.44 g (ie 0.15). This is indicative of a reduction in fatty liver in the experimental group. The tibial muscle was 95.3 g (mean, with s.e. 2.1) in the control group and 96.7 g (s.e. 3.2) in the experimental group. This corresponds to the effects on lean body mass. The effects on fatty tissues are shown in Table 6. In the experimental group, the animals showed a higher amount of brown adipose tissue (BAT), but lower amounts of white adipose tissue (WAT), such as retroperitoneal fat (rp). , inguinal (i) and epididymal (e). The presence of brown adipose tissue is advantageous for babies for isolation purposes. White adipose tissue is present in both adults and babies and is used to store energy. Lower visceral fat mass (i.e. eWAT and rpWAT) is also advantageous, as it will decrease the risk of insulin insensitivity or insulin resistance.

Table 6: Adi bear dye mass in mice on day 126.

[0095] Fasting insulin levels were lower in the experimental group (1200 units) than in the control group (1470 units). This is indicative of a reduced signal from adipocytes. Leptin levels decreased in the experimental group (6000 units) compared to the control group (9500). Resistance also decreased in the experimental group (1350) compared to the control group (1550). This is indicative of a normal appetite and a reduced tendency to adiposity, that is, increased fat mass, respectively.

[0096] These results demonstrate that fat mass, relative fat mass and / or obesity in adulthood clearly decrease with an early diet with increased lipid globule size. It is concluded that foods that comprise lipid globules with altered lipid architecture program and / or leave an imprint on the body early in life in such a way that later in life a healthier body composition develops, with less fat mass , relative fat mass and / or an increase in lean body mass.

Example 3: programming effect of lipid globule size on body composition of adults

[0097] The same experimental animal model and setup was used as in Example 2, except that the experiment was terminated on day 98 instead of day 128.

[0098] The experimental diets that were used for weaning were:

1) a control diet based on infant formula (IMF). This diet comprised 282 g of standard IMF per kg of IMF 1 from Example 1B, ie, small lipid globules, and no added polar lipids. The remainder of the diet consisted of carbohydrates, fiber, and AIN-93G protein. All lipids present in the diet were derived from MFI.

2) an IMF-based diet which is not according to the present invention. This diet differed from diet 1 in that it comprised 282 g of IMF 2 of example 1B, that is, it comprised larger lipid globules than the control and had no added polar lipids. All lipids present in the diet were derived from MFI. 3) an iMf based diet which is not according to the present invention with added phospholipids. This diet differed from diet 2 in that it comprised 282 g of IMF 3 of Example 1B, that is, it comprised lipid globules larger than the control and added polar lipids, not located in the outer surface layer of the lipid globule. All lipids present in the diet were derived from MFI.

4) an IMF-based diet of the present invention. This diet differed from diet 3 in that it comprised 282 g of IMF 4 of Example 1B, that is, it comprised larger lipid globules than the milk-derived polar lipid coated control. All lipids present in the diet were derived from MFI.

[0099] The composition of the diets is similar to that of Table 3 of Example 2. The fatty acid composition of the two experimental and cafeteria diets is similar to that of Table 4 of Example 2, with a linoleic acid (LA) calculated as 14 % in diets 1 and 2 and 13.2 % in diets 3 and 4 based on total fatty acids, with an alpha linolenic acid (ALA) of 2.6 in diets 1 and 2 and 2.5% in diets 3 and 4 on total fatty acids and with LA / ALA of 5.4 in diets 1 and 2 and 5.3, in diets 3 and 4 respectively. The amount of DHA was 0.2% by weight in the 4 diets, and the amount of ARA was 0.35% by weight in the diets 1 and 2 and 0.36% by weight in the diets 3 and 4.

Results:

[0100] No effect on growth (body weight) and food intake was observed during the experimental period between the groups. Furthermore, the development of body weight and fat mass (determined with DEXA) was not significantly different on day 42 (end of the diet intervention period).

[0101] A subsequent treatment with a western-style diet between day 42 and day 98 of all groups resulted in clear differences in body composition at the end of the experiment (day 98), see Table 7. Fat mass and Relative fat mass developed later in life was reduced in mice that had received the diet with the largest lipid globules during their infancy and childhood, compared to mice that had received the control diet.

[0102] From the above results it can be deduced that the increase in the size of the lipid globule produces a decrease in the fat mass and the relative fat mass (compare diet 1 with diet 2). The decrease in fat mass and relative fat mass is even greater when lipid globules are coated with polar lipids derived from milk lipids (compare diet 4 with diet 1 or 2). This enhanced effect is considered not only due to the polar lipids themselves, but can also be attributed to the coating of the lipid globules, since with diet 3 the effects are much less pronounced than with diet 4.

T l: M i i n r n l í.

[0103] The effect on fat tissues is shown in Table 8. Larger lipid globules especially produced a decrease in visceral fat (perirenal fat and epididymal fat) compared to subcutaneous fat (compare diet 1 with diet two).

[0104] White adipose tissue is present in both adults and infants and is used to store energy. A lower visceral fat mass (i.e. eWAT and rpWAT) is advantageous, as it will decrease the risk of insulin insensitivity or insulin resistance.

[0105] In adipose tissues (eWAT and iWAT) of mice fed diet 1 and diet 4, cell size was determined on day 98. Adipocytes were isolated and mean diameter was determined by analysis of image from microscopic photographs. The volume was calculated as V = (n / 6) (3a2 X2) X, where X and a2 are the mean and variance of the diameter. The mean volume of adipocytes in eWAT, representative of visceral fat, of mice fed diet 1 was 5.1 106 | _im3 (eg, 0.56 106) and of mice fed diet 4 was 4 .3 106 | _im3 (eg, 0.52 106) The mean volume of adipocytes in iWAT, representative of subcutaneous fat, was lower. In mice fed diet 1 it was 2.0 106 | _im3 (eg 0.16 106) and that of mice fed diet 4 was 1.7106 | _im3 (eg 0.1.4 106 ). The number of cells was slightly higher in the mice fed diet 4. No differences were observed in% lipid content and lipid density of adipose fat mass.

[0106] These results demonstrate that fat mass, relative fat mass and / or obesity in adulthood clearly decrease with an early diet with increased lipid globule size. These effects are even more pronounced when large lipid globules are covered with polar lipids. Additionally, the larger lipid globules produced a specific effect in reducing visceral obesity. It is concluded that foods comprising lipid globules with altered lipid architecture programs the body and / or leaves an imprint on it early in life in such a way that later in life, during growth in similar circumstances, a healthier body composition, with less fat mass and / or relative fat mass.

Example 4: Infant formula with larger lipid globules.

[0107] An infant formula comprising, per kg of powder, 4810 kcal, 255 g of lipids, 533 g of digestible carbohydrates, 58 g of non-digestible oligosaccharides (galacto-oligosaccharides and long-chain fructo-oligosaccharides in a weight ratio of 9/1), 96 g of protein and vitamins, minerals, trace elements as known in the art.

[0108] The lipid composition is such that 0.57% by weight of the lipids is composed of phospholipids. The composition comprises approximately 0.17% by weight of glycosphingolipids on total lipids. The composition comprises approximately 0.006% by weight of cholesterol on total lipids. As a source of phospholipids, glycosphingolipids and cholesterol SM-2 powder are used (Corman, Goé, Belgium). About 97-98% of the lipids are plant lipids, the rest are dairy fats, fish oil, and microbial oil. The amount of lC-PUFA is approximately 0.64% by weight based on total fatty acids. The LA / ALA ratio is 5.2.

[0109] Homogenization was carried out in a similar manner to Example 1. The volumetric modal diameter was greater than 1 | _im. The% by volume of lipid globules with a size between 2 and 12 μm was greater than 45% on the total volume of lipids.

Claims (9)

1. Nutritional composition comprising a) 10 to 50% by weight of plant lipids on the dry weight of the composition, and b) lipid globules i. with a volume weighted modal diameter greater than 1.0 | _im, preferably between 1.0 and 10 | _im, and / or ii. with a diameter of 2 to 12 | _im in an amount of at least 45, more preferably at least 55% by volume on the total lipids and where the composition comprises from 0.3 to 25% by weight of polar lipids over total lipids, where the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol, and where the volume and size distribution of the lipid globules is determined by the method described in Michalski et al. al, 2001, Lait 81: 787-796, using a Mastersizer, Malvern Instruments, Malvern, UK, as a particle size analyzer, and where the lipid globules are coated with a layer of polar lipids, and where the composition comprises a weight ratio of linoleic acid to alpha-linolenic acid between 2 and 15, for use in preventing obesity and / or reducing the risk of obesity, where the nutritional composition is for feeding a human subject aged between 0 and 36 months and to prevent obesity later in life and / or reduce the risk of obesity later in life, when said human subject is over 18 years of age. 2. Nutritional composition for use according to claim 1, wherein said lipid globules have a volume weighted modal diameter greater than 3.0 | _im. 3. Nutritional composition for use according to any of claims 1-2, wherein at least 65% by volume of the lipid globules over the total lipids has a diameter between 2 and 12 µm. 4. Nutritional composition for use according to any of claims 1-3, wherein the nutritional composition is for feeding a non-obese human subject. 5. Nutritional composition for use according to any of claims 1-4, for use in the prevention of visceral obesity. 6. Nutritional composition comprising a) 10 to 50% by weight of plant lipids on the dry weight of the composition, and b) lipid globules i) with a volume-weighted modal diameter greater than 1.0 | _im, preferably between 1.0 and 10 | _im, and / or ii) with a diameter of 2 to 12 | _im in an amount of at least 45% by volume, more preferably at least 55% by volume on the total lipids, and c) from 0.6 to 25% by weight of polar lipids over total lipids, where the polar lipids include phospholipids, glycosphingolipids and cholesterol, and where the polar lipids are the sum of phospholipids, glycosphingolipids and cholesterol over total lipids , and wherein the volume and size distribution of the lipid globules is determined by the method described in Michalski et al, 2001, Lait 81: 787-796, using a Mastersizer, Malvern Instruments, Malvern, United Kingdom, as a size analyzer of particles, and wherein the lipid globules are coated with a layer of polar lipids, and wherein the composition comprises a weight ratio of linoleic acid to alpha-linolenic acid of between 2 and 15. Composition according to claim 6, in which the lipids have a fatty acid profile with a weight ratio of linoleic acid to alpha-linolenic acid of between 4 and 7. Composition according to any of claims 6-7, further comprising at least one lipid selected from the group consisting of fish oil, marine oil, algae oil, mushroom oil and microbial oil. 9. Nutritional composition according to any of claims 6-8, or nutritional composition for use according to any one of claims 1-5, wherein the nutritional composition is a powder suitable for obtaining a liquid composition after reconstitution with an aqueous solution, preferably with water.