Low calorie infant nutrition

Abstract

Disclosed is a synthetic nutritional composition comprising a protein fraction, a fat fraction, and a carbohydrate fraction, where the nutritional composition is a liquid or powder that can be reconstituted with water to an oil-in-water emulsion, where the nutritional composition has an energy content per 100 ml of less than 55 kcal / 100 ml.

Description

[0001] This invention relates to a synthetic nutritional composition. Specifically, the invention relates to a synthetic nutritional composition comprising protein fractions, fat fractions, and carbohydrate fractions, wherein the nutritional composition is a liquid or powder that can be reconstituted with water into an oil-in-water emulsion, wherein the nutritional composition has an energy content of less than 55 kcal / 100 ml, and relates to an age-tailored nutritional system for infants from birth to 6 months of age, the age-tailored nutritional system comprising such a composition.

[0002] Furthermore, the present invention relates to the use of such compositions in the prevention of obesity and / or improvement of body composition. Additionally, the present invention relates to a method of feeding human subjects, the method comprising the step of administering a nutritional composition according to the invention. The present invention also relates to a method for manufacturing a nutritional composition according to the invention. Background Technology

[0003] Breastfeeding is the best way to ensure a baby's healthy growth and development in the first few months of life. The WHO recommends breastfeeding exclusively for the first six months of life, followed by the introduction of safe and appropriate complementary foods to supplement continued breastfeeding until two years of age or longer. However, when a mother is unable or chooses not to breastfeed for any reason, a safe breastfeeding alternative is needed. Breast milk substitutes produced according to strict international ingredient and safety standards are legally recognized, such as those stipulated in the Codex Alimentarius, European Commission Directive 2006 / 141 / EC, the US FDA, or Chinese standard GB 10765-2021 (National Food Safety - Infant Formula).

[0004] While the Sustainable Development Goals (SDGs) were ambitious when adopted by the UN General Assembly in 2015, they are still considered a major achievement among comprehensive goals. These 17 goals together form a comprehensive roadmap to a better world, supplemented by 169 specific, measurable targets covering everything from water to education, from food to health, and are achievable by 2030. However, a key omission appears to be the complete lack of mention of obesity, despite the fact that more than 1.9 billion adults worldwide are overweight or obese. It is noteworthy that obesity impacts major health and development issues. Research indicates that obesity is a relevant and necessary component of the global development agenda and must be prioritized to successfully achieve targets related to mortality from noncommunicable diseases (J. Ralston et al., Current Obesity Reports (2021) 10:54–60 https: / / doi.org / 10.1007 / s13679-020-00420-y).

[0005] Human obesity is often attributed to Western lifestyles, high-fat diets, and reduced physical activity. While these factors certainly contribute to adult obesity, compelling data suggests this explanation is overly simplistic. Recent research has demonstrated that maternal / fetal malnutrition or overnutrition predisposes offspring to overeating and increases the risk of later-life obesity. The Behavioral Susceptibility Theory (BST) proposes that individuals who inherit a stronger appetite or lower sensitivity to satiety are more likely to overeat due to food-related factors. The BST suggests that appetite is influenced by metabolic, genetic, environmental, and social factors, which may collectively lead to an energy imbalance, resulting in weight gain. Other data support the prevailing view that all infants have full appetite control at birth and that responsive feeding promotes healthy infant development. Rapid weight gain in the first two years of life may be caused by non-responsive feeding (C. Llewellyn and J. Wardle, Physiology & Behavior 152 (2015) 494–501; http: / / dx.doi.org / 10.1016 / j.physbeh.2015.07.006).

[0006] It has long been known that the composition of human milk changes from colostrum to late lactation, and that there are differences in a single feeding and between circadian rhythms.

[0007] The formula feeding recommendations do not include drinking water recommendations for infants aged 0-12 months, especially 0-6 months. In the first year of life, and especially in the first 6 months, all food consumed by infants is in the form of milk or infant formula with a predetermined nutrient level per 100 ml.

[0008] When infants consume infant formula as their sole source of food and fluids, they receive a fixed amount of nutrients along with a certain amount of fluids, and vice versa. The inventors unexpectedly discovered that if infants stop drinking formula after receiving sufficient nutrients for normal growth and development, their water requirements exceed those obtained through formula. When infants need more water, they drink more formula, thus receiving more nutrients than necessary for normal growth and development (i.e., overfeeding), leading to increased weight gain in infancy and initiating obesity programming. The first six months of life are a critical window for this obesity programming, particularly the development of appetite and satiety hormones, which will continue to influence food intake regulation later in life (De Fluiter et al., European Journal of Nutrition

[2021] 60:3717–3725).

[0009] There is a continued need to develop infant formula that replicates the nutritional characteristics of human milk as closely as possible.

[0010] Therefore, it is desirable to prevent rapid weight gain and / or overfeeding during infancy.

[0011] By reducing the energy and / or nutrient content per 100 ml of infant formula, especially during the first 1, 2, 3, and 4 months of life, all these problems will be partially or completely eliminated or overcome.

[0012] This would violate existing infant formula regulations, such as the minimum and maximum nutrient levels per 100 kcal specified in the Codex Alimentarius, which stipulates an average daily intake of 750 ml for infants from birth to six months of age (Codex Alimentarius - Standard for infant formula and formulas for special medical purposes intended for infants [Codex Alimentarius - Standard for infant formula and formulas for special medical purposes intended for infants] CXS 72-1981; originally CAC / RS 72-1972. Adopted as a global standard in 1981. Revised in 1983, 1985, 1987, 2011, 2015, 2016, 2020. Fully revised in 2007). The inventors unexpectedly discovered that, in both tropical and non-tropical regions, regardless of birth month, formula-fed infants fed according to standard instructions experience dehydration during the first 3 to 6 months of life. Based on this finding, total daily water intake should be reconsidered, especially in the first few months of life, such as the first 3 to 6 months, preferably the first 3 months. Furthermore, these findings can be used to reconsider the need to update existing formula feeding recommendations.

[0013] Therefore, the present invention provides an infant nutrition product and an age-customized nutrition system comprising such a product for different age groups. The invention further provides uses of such a product or age-customized nutrition system of the type mentioned in the first paragraph, the features of which are described in the claims.

[0014] Nutritional information for infant formula is well-known. Typically, such formulas are phased according to the child's age; Stage 1 formula or starter formula is for children aged 0 to 6 months, Stage 2 formula or follow-on formula is for children aged 6 to 12 months, and Stage 3 formula or toddler formula or growing-up milk is for children aged 1 to 2 years. Other age-specific nutrition systems for infants are known from WO 2009 / 068549, which relates to the use of a protein source comprising whey and casein to provide an age-specific nutrition system for infants. This system comprises two infant formulas, each suitable for a different age group and each containing the same protein source. The whey:casein ratio of each formula is selected within the range of 100:0 to 40:60 and reduced according to the infant's age, and the protein content of each formula is selected within the range of 1.5 to 3.0 g protein / 100 kcal and reduced according to the infant's age. The method of feeding an infant during the first six months of life is also disclosed, comprising feeding the infant at least partially during the first one to eight weeks of life a first infant formula having a protein source comprising whey and optionally casein and having a whey:casein ratio between 100:0 and 60:40 and a protein content between 1.8 and 3.0 g protein / 100 kcal; and feeding the infant at least partially during the remaining period of the first six months of life a second infant formula. Summary of the Invention

[0015] In a first aspect, the present invention relates to a synthetic nutritional composition comprising a protein fraction, a fat fraction, and a carbohydrate fraction, wherein the nutritional composition is a liquid or powder that can be reconstituted with water into an oil-in-water emulsion, and wherein the energy content of the nutritional composition is less than 55 kcal / 100 ml, preferably less than 53 kcal, particularly preferably less than 52 kcal, more preferably less than 50 kcal, even more preferably less than 48 kcal, and most preferably less than 46 kcal.

[0016] On the other hand, the present invention relates to an age-customized nutrition system for infants from birth to 6 months of age, the age-customized nutrition system comprising two or more formulation products, wherein the first formulation product is a nutritional composition according to the invention, and wherein the first formulation product is used for at least part of the infant’s feeding during the first 3 months, preferably at least part of the first 2 months, and the second formulation product is used for at least part of the infant’s feeding during the remaining 6 months, and wherein the energy content of the second nutritional formulation product is higher than that of the first nutritional product, preferably wherein the energy content of the second nutritional formulation product is 58 kcal / 100 ml or higher.

[0017] In another aspect, the present invention relates to the compositions or age-customized nutrition systems of the present invention for use in preventing obesity and / or reducing the risk of obesity later in life. In another aspect, the present invention relates to the compositions or age-customized nutrition systems of the present invention for use in improving body composition, wherein the improvement in body composition is selected from one or more of the group consisting of: an increase in lean body mass relative to total body mass and a decrease in fat mass relative to total body mass. The improvement in body composition can be therapeutic or non-therapeutic. In another aspect, the present invention relates to the compositions or age-customized nutrition systems of the present invention as anti-obesity compositions. In yet another aspect, the present invention relates to the use of the compositions or age-customized nutrition systems of the present invention in improving body composition, wherein the improvement in body composition is selected from one or more of the group consisting of: an increase in lean body mass relative to total body mass and a decrease in fat mass relative to total body mass.

[0018] Furthermore, the present invention relates to a method of feeding a human subject, the method comprising the step of administering a nutritional composition according to the invention, or comprising the step of administering an age-customized nutritional system according to the invention to the subject, preferably wherein the age of the human subject is between 0 and 12 months, more preferably wherein the age of the subject is between 0 and 6 months.

[0019] In another aspect, the present invention relates to a method for manufacturing a nutritional composition according to the invention, the method comprising the following steps:

[0020] i. Prepare an aqueous phase containing proteins and digestible carbohydrates and a fatty phase containing lipids, wherein the fatty acid composition of the lipids comprises linoleic acid and α-linolenic acid in a weight ratio of 2 to 10.

[0021] ii. Mix the fatty phase and the aqueous phase, and homogenize the mixture of the fatty phase and the aqueous phase to form an oil-in-water emulsion.

[0022] iii. Optionally, the oil-in-water emulsion of ii. is dried into a powder. Attached Figure Description

[0023] Figure 1 This diagram illustrates the different pathways through which water is lost from an infant's body, such as respiratory water loss (via the lungs, RespWL), sweat water loss (SWL), transepidermal water loss (TEWL), renal water loss (urine, RWL), and fecal water loss (FWL). Daily water loss is the sum of these: RespWL, SWL, TEWL, RWL, and FWL.

[0024] exist Figures 2A to 2D This study compared the daily water loss (in mL) of infants born in different months and cities throughout the year with their planned infant formula intake (mL / day). Data from Chicago (USA) was used in... Figures 2A to 2D The figures show the recommended daily water intake (gray bars) (i.e., the amount in ml of infant formula based on the manufacturer's instructions) and water requirements, as determined based on the extended HumMod model. Figure 2A A) Data for babies born in January, February, and March is shown; B) Data for babies born in April, May, and June is shown; C) Data for babies born in July, August, and September is shown; and D) Data for babies born in October, November, and December is shown.

[0025] Similar data from Sydney (Australia) Figures 3A to 3D The data shown in the figure are as follows: A) shows data for birth months of January, February, and March; B) shows data for birth months of April, May, and June; C) shows data for birth months of July, August, and September; and D) shows data for birth months of October, November, and December.

[0026] Thessaloniki data in Figures 4A to 4D The data shown in the figure are as follows: A) shows data for birth months of January, February, and March; B) shows data for birth months of April, May, and June; C) shows data for birth months of July, August, and September; and D) shows data for birth months of October, November, and December.

[0027] definition

[0028] As used herein, the term "reconstituted beverage" refers to a drinkable product prepared according to the manufacturer's instructions by dissolving a powder in a liquid (such as dissolving infant formula in water). The drinkable product is preferably drinkable by an infant using a bottle with a nipple. Such bottles with nipples are well-known and readily available commercially. The drinkable product preferably has a viscosity of less than 800 cP (at 25°C and 1 atmosphere), such as between 1 cP and 500 cP, preferably between 1 cP and 400 cP, and more preferably between 1 cP and 200 cP.

[0029] As used herein, "formulated product" means a product that provides a reconstituted drinkable product when reconstituted with a liquid, preferably with water, more preferably with boiling water (preferably cooled to below 37°C). Once consumed, the reconstituted beverage should not be too hot to avoid burning the subject's tongue or mouth. Therefore, the temperature of the liquid should normally be 37°C or below.

[0030] Formulated products are typically powders, but in some cases may be easily soluble tablets or cubes. Alternatively, formulated products may be liquids that may need to be diluted or “ready to drink.” Examples of formulated products include those that optionally provide complete nutrition to subjects after reconstitution into a reconstituted beverage, such as IFT products, subsequent formula (FOF), and young child formula (YCF-Jr) products. Formulated products have a recommended daily dose (i.e., amount) of formula per subject; the recommended number of feeding times per subject per day; and a recommended ratio between the expected amount of formula and the expected amount of liquid. These recommendations may vary depending on the type and brand of the formula and are provided by the manufacturer.

[0031] As used herein, the term "infant formula," also known as "infant formula product," refers to a nutritional composition intended for use in infants aged 0 to 6 months. "Infant formula" refers to a breast milk substitute specifically manufactured to meet the nutritional needs of an infant during the first few months of life until the introduction of appropriate complementary feeding. The product is processed and packaged to prevent contamination under all normal handling, storage, and distribution conditions. Energy, carbohydrate, fat, and protein contents are exemplified elsewhere herein. The compositions of this invention compensate for the risk of excessive energy intake in the first few months of life by having lower energy levels compared to standard dietary recommendations (e.g., as defined in the European Commission directive cited above or in the Codex Alimentarius Standard for Infant Formula and Formulas for Special Medical Purposes Intended for Infants - STAN 72-1981).

[0032] Infant formula encompasses starter formula. Generally, starter formula is used as a breast milk substitute for infants from birth to 6 months, while follower formula or subsequent formula is used for infants from 6 to 12 months. Toddler formula is specifically designed for children aged 1-3 years.

[0033] The term "infant" refers to a child under 12 months of age.

[0034] The term "toddler" refers to a child aged between one and three years old.

[0035] The term "starter formula" refers to a food designed for specific nutritional purposes in infants during the first six months of life.

[0036] The term "nutritional composition" refers to a composition that nourishes a subject. This nutritional composition is typically taken orally and usually includes a lipid or fat source, a carbohydrate source, and a protein source.

[0037] The term "synthetic composition" refers to a composition artificially prepared that contains at least one compound produced in vitro by chemical and / or biological and / or physical means (e.g., by chemical reaction, enzymatic reaction, or by fractionation process). An example of such a fractionation process is the separation of milk into different fractions (e.g., fat and protein fractions). For the avoidance of doubt, the synthetic composition is not prepared in vivo by a human or animal.

[0038] As used herein, the term "reconstituted beverage" refers to a drinkable product prepared according to the manufacturer's instructions by dissolving powder in a liquid (such as dissolving infant formula in water).

[0039] The term "prebiotic" refers to a prebiotic that beneficially affects the host's indigestible carbohydrates by selectively stimulating the growth and / or activity of healthy bacteria (such as Bifidobacteria) in the human colon (Gibson et al.; Nutrition Research Reviews (2004), 17, 259–275).

[0040] The term "probiotics" refers to microbial cell preparations or microbial cell components that have a beneficial effect on the health or well-being of the host. (Salminen et al., Trends in Food Science & Technology, Vol. 10, No. 3, March 1999, pp. 107-110).

[0041] Renal solute load (RSL) refers to all endogenous or dietary solutes that need to be excreted through the kidneys. Potential renal solute load (PRSL) refers to dietary solutes that, if not transferred to new tissue synthesis and not lost through non-renal pathways, need to be excreted in the urine.

[0042] PRSL = N / 28 + Na + Cl + K + P a

[0043] Where N is nitrogen, Na is sodium, Cl is chlorine, K is potassium, and P a This refers to available phosphorus, and the unit is millimoles (or milliosmols), excluding N, which is total N in mg. The term N / 28 indicates nitrogenous solute (mmol), which is based on the assumption that the modal number of N atoms per molecule is 2, i.e., N is expressed in mmol of urea. P a Equals total P, except in soy-based diets, where P a It accounts for approximately two-thirds of the total P.

[0044] As used in this article, FA refers to fatty acids; SFA refers to saturated fatty acids, and LC SFA refers to long-chain saturated fatty acids. Long-chain saturated fatty acids are saturated fatty acids with 12 or more carbon atoms.

[0045] The energy content of the compositions of the present invention was calculated using the Atwater Universal Coefficient System. This system uses a single coefficient for each energy-producing substrate (protein, fat, carbohydrate). The energy value of protein is 17 kJ / g (4.0 kcal / g), the energy value of fat is 37 kJ / g (9.0 kcal / g), and the energy value of digestible carbohydrates is 17 kJ / g (4.0 kcal / g). Indigestible carbohydrates (such as GOS, FOS, inulin) have an energy value of 8 kJ / g (2.0 kcal / g).

[0046] It must also be noted that, as used in the specification and appended claims, the singular forms “a / an” and “the” include a plural of objects unless the context clearly indicates otherwise. For example, a component referred to in the singular is intended to comprise multiple components.

[0047] It will be understood that, unless otherwise defined, any reference to weight, weight ratio, etc. in this disclosure refers to dry matter, and in particular the dry matter of the composition.

[0048] Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0049] As used herein, the term “comprising” is synonymous with “including” or “containing”, is open-ended, and does not exclude other undescribed elements, components, or method steps; while the term “consisting of” is a closed term that does not include any other elements, steps, or components not expressly described.

[0050] Throughout this application, where publications are cited, the disclosures of those publications are incorporated herein by reference in their entirety to more fully describe the level of technology to which this invention pertains.

[0051] Overweight and obesity are defined as abnormal or excessive fat accumulation that poses a health risk. A body mass index (BMI) over 25 is considered overweight, and over 30 is considered obese. BMI is expressed in kg / m². 2 It is expressed and calculated by dividing a person’s weight (in kilograms) by the square of their height (in meters).

[0052] Unless explicitly stated in the examples or otherwise, all numerical values ​​indicating amounts of material or reaction and / or conditions of use in the specification shall be understood to be modified by the word “about” when describing the broadest scope of the invention. Generally, it is preferred to practice within the stated numerical limits. Furthermore, unless explicitly stated otherwise: percentages, “parts”, and ratio values ​​are by weight; descriptions of groups or classes of materials suitable or preferably used for a given purpose in relation to the invention mean that a mixture of any two or more components of that group or class can be equally suitable or preferred; descriptions of components in chemical terms refer to components when added to any combination specified in the specification and do not necessarily exclude chemical interactions between components of the mixture once mixed; the first definition of acronyms or other abbreviations applies to all subsequent uses of the same abbreviation herein, and necessary modifications are applied to normal grammatical variations of the initially defined abbreviation; and unless explicitly stated otherwise, the measurement of a property is determined by the same technique as the same property previously or subsequently referenced. Detailed Implementation

[0053] In a first aspect, the present invention relates to a synthetic nutritional composition comprising a protein fraction, a fat fraction, and a carbohydrate fraction, wherein the nutritional composition is a liquid or powder that can be reconstituted with water into an oil-in-water emulsion, and wherein the energy content of the nutritional composition is less than 55 kcal / 100 ml, preferably less than 53 kcal, particularly preferably less than 52 kcal, more preferably less than 50 kcal, even more preferably less than 48 kcal, and most preferably less than 46 kcal.

[0054] In one embodiment, the energy content of the nutritional composition of the present invention per 100 g of powder is less than 467 kcal, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal.

[0055] It will be understood that energy content (e.g., in kcal / 100 ml) or other content levels refer to the levels in ready-to-drink products. Such ready-to-drink products can be obtained by reconstituted powdered synthetic nutritional products with water according to the manufacturer's instructions.

[0056] In one embodiment, the nutritional composition of the present invention is a nutritional composition for full-term infants, preferably not small-for-gestational-age infants. In another embodiment, the nutritional composition of the present invention is for infants weighing 3 kg or more.

[0057] In one embodiment, the energy content of the nutritional composition of the present invention is less than 55 kcal / 100 ml, and the energy content / 100 g powder is less than 467 kcal, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal. Preferably, the energy content of the nutritional composition is less than 53 kcal / 100 ml, and the energy content / 100 g powder is less than 467 kcal, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal. Particularly preferably, the energy content of the nutritional composition is less than 52 kcal / 100 ml, and the energy content is less than 467 kcal / 100 g of powder, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal. In another embodiment, the energy content of the nutritional composition is less than 50 kcal / 100 ml, and the energy content is less than 467 kcal / 100 g of powder, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal. In yet another, even more preferred embodiment, the energy content of the nutritional composition is less than 48 kcal / 100 ml, and the energy content / 100 g powder is less than 467 kcal, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal.

[0058] In another embodiment, the energy content of the nutritional composition is less than 46 kcal / 100 ml, and the energy content of the powder is less than 467 kcal, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal.

[0059] The potential renal solute load (PRSL) of the compositions of the present invention should not be too high, as this will lead to dehydration in infants. Too low a PRSL may lead to water intoxication. In one embodiment, the PRSL of the compositions of the present invention is between 60 and 120 mOsm / 100 ml, preferably between 80 and 110 mOsm / 100 ml. Preferably, the PRSL of the compositions of the present invention is between 60 and 120 mOsm / 100 ml, and the contribution of protein to the PRSL is between 40% and 70%, preferably between 45% and 65%. The contribution of protein to the PRSL is the proportion of protein in the total PRSL.

[0060] The reduced energy level of the compositions of the present invention can be achieved by reducing the fat content per 100 ml of existing infant formula, or alternatively by reducing the fat and protein content. Preferably, the monovalent ion level per 100 ml is the same as that in standard infant formula. More preferably, the monovalent ion level and carbohydrate content per 100 ml are the same as those in standard infant formula.

[0061] The compositions of the present invention can be prepared using methods known in the field of infant formula preparation.

[0062] The drinkable product is preferably designed for infants to drink from vials with nipples. Such vials are well-known and readily available commercially. The drinkable product preferably has a viscosity of less than 800 cP (at 25°C and 1 atmosphere), such as between 1 cP and 500 cP, preferably between 1 cP and 400 cP, and more preferably between 1 cP and 200 cP. Water has a viscosity of 1.0016 mPa⋅s at 20°C.

[0063] In short, the nutritional composition according to the present invention can be prepared by a method comprising the following steps:

[0064] i. Prepare an aqueous phase containing proteins and digestible carbohydrates and a fatty phase containing lipids, wherein the fatty acid composition of the lipids comprises linoleic acid and α-linolenic acid in a weight ratio of 2 to 10.

[0065] ii. Mix the fatty phase and the aqueous phase, and homogenize the mixture of the fatty phase and the aqueous phase to form an oil-in-water emulsion.

[0066] iii. Optionally, the oil-in-water emulsion of ii. is dried into a powder.

[0067] Methods for preparing infant formula are known in the art, for example from US 20040101596 A1 or EP 0969728 A1. An exemplary method for preparing age-customized powdered infant formula is as follows: A protein source, a carbohydrate source, and a fat source can be blended together in appropriate proportions. An emulsifier can be included in the blend. Vitamins and minerals can be added at this point, but are usually added later to avoid thermal degradation. Prior to blending, any lipophilic vitamins, emulsifiers, etc., can be dissolved in the fat source. Water, preferably water subjected to reverse osmosis, can then be mixed in to form a liquid mixture. The liquid mixture can then be heat-treated to reduce bacterial load. For example, the liquid mixture can be rapidly heated to a temperature in the range of about 72°C to about 110°C for about 5 seconds to about 5 minutes. This can be done using a heat exchanger (e.g., a plate heat exchanger), optionally in combination with steam injection. The liquid mixture can then be cooled to about 60°C to about 85°C; for example, by flash cooling. The liquid mixture can then be homogenized; for example, in two stages, in the first stage at about 7 MPa to about 40 MPa, and in the second stage at about 2 MPa to about 14 MPa. The homogenized mixture can then be further cooled to add any heat-sensitive components, such as vitamins and minerals. At this point, the pH and solids content of the homogenized mixture can be conveniently normalized. The homogenized mixture can be transferred to a suitable drying device (such as a spray dryer or freeze dryer) and converted into a powder. The powder should have a moisture content of less than about 3% by weight.

[0068] If desired, one or more probiotics can be added. These can be cultured using any suitable method and prepared for use in infant formula, for example, by freeze-drying or spray-drying. Alternatively, bacterial preparations already formulated for use in food products such as infant formula can be purchased from specialized suppliers such as Christian Hansen and Morinaga. Such bacterial preparations can be added to age-specific powdered infant formula via dry mixing. Similarly, prebiotics and human milk oligosaccharides (HMOs) can be added to formula via dry mixing. Prebiotics and HMOs can be purchased from specialized suppliers such as FrieslandCampina.

[0069] Examples of prebiotics include, but are not limited to, galactooligosaccharides (GOS), inulin, and fructooligosaccharides (FOS), or combinations thereof. Examples of HMOs include, but are not limited to, 2'FL, 3FL, LNT, LNnT, 3'GL, 6'GL, 3SL, 6SL, and combinations thereof. 2'-Fucose-based lactose (2'FL) is a preferred HMO.

[0070] In one embodiment, the protein content in the composition of the present invention is between 1.6 and 3.0 g protein / 100 kcal; in another embodiment, it is between 1.8 and 3.0, preferably between 2.0 and 2.9, and more preferably between 2.0 and 2.5.

[0071] In one embodiment, the protein fraction comprises goat or bovine milk protein, and the amount of goat or bovine milk protein in the protein fraction of the composition of the present invention is greater than 80 wt% (as determined relative to the total amount of protein in the composition), preferably greater than 90 wt%. In another embodiment, the amount of bovine milk protein in the protein fraction of the composition of the present invention is greater than 80 wt% (as determined relative to the total amount of protein in the composition), preferably greater than 90 wt%. In yet another embodiment, the amount of goat protein in the protein fraction of the composition of the present invention is greater than 80 wt% (as determined relative to the total amount of protein in the composition), preferably greater than 90 wt%.

[0072] The protein fraction can be milk protein, such as casein or whey, or alternatively, plant protein, such as soy protein or rice protein. Preferably, it is ruminant milk protein, more preferably derived from cow's milk, sheep's milk, or goat's milk, or a combination thereof, and most preferably from cow's milk. WPC and SPC are well-known milk fractions containing whey protein. Both WPC and SPC are the result of separating skim milk into fractions rich in casein and rich in whey protein; by curdling (i.e., cheese making), acidification, or microfiltration. In yet another embodiment, the protein fraction comprises a mixture of whey and casein in a ratio between 100:0 and 20:80, preferably a whey to casein ratio between 70:30 and 20:80, and more preferably a whey to casein ratio between 70:30 and 50:50.

[0073] Whey protein concentrate (WPC) is a product obtained by ultrafiltration and, optionally, reverse osmosis (to further concentrate the product (removing water)) of acidic whey or caseous whey, and optionally combined with demineralization. Through ultrafiltration, most of the water, lactose, and ash are removed from the product, thereby concentrating the whey protein.

[0074] Serum protein concentrate (SPC) is also a concentrated protein product, differing from whey protein concentrate (WPC) in the source of the whey fraction. Unlike acidic whey or caseous whey, the protein in SPC originates from the microfiltration of skim milk. This microfiltration produces a concentrated casein retentate fraction and a serum fraction containing a majority of whey protein as a permeate fraction. Typically, such permeate fractions are then subjected to ultrafiltration and / or reverse osmosis to remove lactose, ash, and water. If necessary, the resulting product can be demineralized.

[0075] In another embodiment, the protein fraction of the composition of the present invention contains partially hydrolyzed proteins. This improves the digestibility of the composition. In one embodiment, the protein fraction comprises at least 10 wt% partially hydrolyzed protein, as determined relative to the total amount of protein. Hydrolyzed proteins suitable for the compositions of the present invention can be obtained using methods known in the art, such as via chemical or enzymatic hydrolysis, for example, as disclosed in WO 2006130204 or EP 0922392. As used herein, the hydrolyzed proteins have a molar mass of 5000 Daltons or less.

[0076] The fat fraction (also called lipid fraction) in the synthetic composition of the present invention may comprise different oils, such as vegetable oils, fish oils, ruminant milk fat, or combinations thereof. Preferably, the composition comprises ruminant milk fat, more preferably a combination of vegetable oils and ruminant milk fat. Even more preferably, this combination of lipids is supplemented with fish oil. Fat consists of glycerol ester residues linked to carboxylic acids via ester bonds. Therefore, a fat molecule comprises glycerol ester residues and three fatty acid acyl groups. The acyl group linked to the first carbon atom of the glycerol ester is also called the sn1-linked acyl group, just as the acyl group linked to the second carbon atom of the glycerol ester is called the sn2-linked acyl group and the acyl group linked to the third carbon atom of the glycerol ester is called the sn3-linked acyl group.

[0077] An acyl group contains a carbonyl group (C double bond oxygen atom) attached to an alkyl group R; (RC=O). In organic chemistry, the acyl group (IUPAC name: alkanoyl) is usually derived from carboxylic acids and has the formula RCO-, where R represents an alkyl group attached to a carbon atom of the C=O group via a single bond. As used herein, the alkanoyl group is referred to by the name of the corresponding anion (as the conjugate base of the acid). For example, the C4 acyl group (CH3-CH2-CH2-C(O)-) is called a butyrate ester or C4:0, where "4" indicates the total number of carbon atoms in the group and "0" indicates the number of unsaturated carbon-carbon bonds. Similarly, C16:0 refers to palmitic acid (CH3(CH2)-). 14 COOH), while palmitate refers to CH3(CH2). 14 CO.

[0078] The lipid fraction in the compositions of the present invention may comprise a mixture of different oils, such as a mixture of vegetable oils and milk fats. Optionally, long-chain polyunsaturated fatty acids (LC-PUFAs) (such as those selected from the group consisting of DHA, ARA, and EPA in one embodiment) may be added to the lipid fraction; preferably, the composition comprises DHA, ARA, and EPA. Such LC-PUFAs are found in fish oil. It should be understood that fish oil may be replaced by polyunsaturated fatty acids (PUFAs) from any other source that provides docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and optionally arachidonic acid (ARA).

[0079] In one embodiment, the content of fat in the composition of the present invention is between 3.5 and 6.0 g fat / 100 kcal, preferably between 3.6 and 5.5, and more preferably between 3.7 and 5.0.

[0080] The lipid fraction in the synthetic composition of the present invention preferably comprises at least 0.2 wt% butyrate, preferably at least 0.5 wt%, more preferably at least 1.0 wt%, particularly preferably at least 1.5 wt%, and most preferably at least 1.8 wt%, as determined relative to the total amount of fatty acids in the lipid fraction; furthermore, the amount of sn-1,3-linked butyrate (C4:0) accounts for more than 70%, preferably more than 80%, and more preferably more than 90% of the total butyrate.

[0081] In another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 0.5 wt% butyrate, and further, the amount of butyrate linked to sn-1,3 accounts for more than 70%, preferably more than 80%, and more preferably more than 90% of the total butyrate. Preferably, in another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 1.0 wt% butyrate, and further, the amount of butyrate linked to sn-1,3 accounts for more than 70%, preferably more than 80%, and more preferably more than 90% of the total butyrate. More preferably, in another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 1.5 wt% butyrate, and further, the amount of butyrate linked to sn-1,3 accounts for more than 70%, preferably more than 80%, and more preferably more than 90% of the total butyrate. Even more preferably, in another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 1.8 wt% butyrate, and further, the amount of butyrate linked to sn-1,3 accounts for more than 70%, preferably more than 80%, and more preferably more than 90% of the total butyrate.

[0082] In one embodiment, the fat fraction of the composition of the present invention comprises milk fat, and the amount of milk fat is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, even more preferably at least 40 wt%, and most preferably at least 50 wt%, as determined relative to the total amount of fat in the composition of the present invention.

[0083] In another embodiment, the amount of vegetable oil is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, and most preferably at least 40 wt%, as determined relative to the total amount of fat in the synthetic composition of the present invention.

[0084] In one embodiment, the amount of milk fat is at least 10 wt%, as determined relative to the total amount of fat in the composition of the present invention; and the amount of vegetable oil is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, and most preferably at least 40 wt%, as determined relative to the total amount of fat in the synthetic composition of the present invention.

[0085] In one embodiment, the amount of milk fat is at least 30 wt%, as determined relative to the total amount of fat in the composition of the present invention; and the amount of vegetable oil is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, and most preferably at least 40 wt%, as determined relative to the total amount of fat in the synthetic composition of the present invention.

[0086] In one embodiment, the amount of milk fat is at least 40 wt%, as determined relative to the total amount of fat in the composition of the present invention; and the amount of vegetable oil is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, and most preferably at least 40 wt%, as determined relative to the total amount of fat in the synthetic composition of the present invention.

[0087] In yet another embodiment, the amount of milk fat is at least 50 wt%, as determined relative to the total amount of fat in the composition of the present invention; and the amount of vegetable oil is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, and most preferably at least 40 wt%, as determined relative to the total amount of fat in the synthetic composition of the present invention.

[0088] A mixture of milk fat and vegetable oil is preferred because it can be more similar to human milk fat in terms of fatty acid composition and the distribution of these fatty acids on triacylglycerol (TAG) molecules. Therefore, in one embodiment, the fat fraction comprises milk fat and vegetable oil, preferably wherein the amount of milk fat is at least 10 wt%, as determined relative to the total fat content. Vegetable oils for human consumption are well known in the art and include one or more of sunflower oil, palm oil, and rapeseed oil.

[0089] Suitable milk fat for the compositions used in this invention is mammalian milk fat. Preferably, it is milk fat derived from ruminants, more preferably from the group consisting of: cow's milk fat, sheep's milk fat, goat's milk fat, camel's milk fat, and horse's milk fat; even more preferably from cow's milk fat or goat's milk fat; most preferably cow's milk fat, particularly preferably cow's milk fat. Milk fat can be obtained from various milk fractions, such as whole milk, cream, butter, anhydrous milk fat, etc. As used herein, the term "ruminant milk fat" refers to a milk fat source derived from the milk of ruminants, preferably cow's milk fat. In principle, the milk fat source can be any available ruminant milk fat source, such as whole milk, cream, anhydrous milk fat (AMF), or a milk fat fraction produced by dry fractionation, critical CO2 extraction, or other fractionation methods known in the art. However, whole milk and / or cream have been found particularly suitable as milk fat sources.

[0090] Preferably, the ruminant milk fat is bovine milk fat, and the fat is selected from the group consisting of whole milk, cream, and anhydrous milk fat (AMF). More preferably, the cow is a dairy cow. In one embodiment, the milk fat is bovine whole milk or cream. In one embodiment, the ruminant milk fat is bovine whole milk; in another embodiment, the ruminant milk fat is milk fat; and in yet another embodiment, the ruminant milk fat is bovine AMF.

[0091] The carbohydrate fraction of the compositions of the present invention refers to the amount of digestible carbohydrates (such as lactose, sucrose, maltodextrin, glucose, and maltose). Preferred digestible carbohydrates are lactose, maltodextrin, and glucose. Dietary fiber (such as GOS, FOS, inulin, and HMO) is an indigestible carbohydrate. In one embodiment, the carbohydrate content of the compositions of the present invention, expressed as g carbohydrate / 100 kcal, is between 9.0 and 15.0; preferably between 10 and 14, more preferably between 11 and 13.

[0092] In a preferred embodiment, the nutritional composition of the present invention is an infant formula for infants aged 0 to 4 months, preferably 0 to 3 months, and more preferably 0 to 2 months.

[0093] In another embodiment, the composition of the present invention is a synthetic composition.

[0094] In another embodiment, the synthetic nutritional product is a complete nutritional product, preferably an infant formula product, such as newborn food or infant formula. Preferably, the product is an infant formula product.

[0095] The compositions of the present invention may further comprise vitamins and minerals. The level and type of vitamins and minerals added depend on the type of product and are known to those skilled in the art. Thus, in one embodiment, the compositions of the present invention further comprise one or more of minerals, vitamins, probiotics, and / or prebiotics, preferably wherein the composition comprises galactooligosaccharides (GOS) and human milk oligosaccharides. More preferably wherein the composition comprises 2'FL (2' fucose-based lactose), and even more preferably 2'FL and 3'GL (3' galacose-based lactose).

[0096] In one embodiment, the energy content of the composition of the present invention is at least 40 kcal / 100 ml and / or at least 340 kcal / 100 g powder. Alternatively, it is at least 42 kcal / 100 ml and / or at least 356 kcal / 100 g powder, preferably at least 44 kcal / 100 ml and / or at least 373 kcal / 100 g powder.

[0097] On the other hand, the present invention relates to an age-customized nutrition system for infants from birth to 6 months of age, the age-customized nutrition system comprising two or more formulation products, wherein the first formulation product is a nutritional composition according to the invention, and wherein the first formulation product is used for at least part of the feeding of the infant during the first 3 months, preferably the first 2 months, and the second formulation product is used for at least part of the feeding of the infant during the remaining 6 months, and wherein the energy content of the second nutritional formulation is higher than that of the first nutritional product, preferably wherein the energy content of the second nutritional formulation is 58 kcal / 100 ml or higher, more preferably wherein the energy content of the second nutritional formulation is 60 kcal / 100 ml or higher, such as 61 kcal / 100 ml or higher.

[0098] The compositions or age-customized nutrition systems of the present invention can be used to prevent obesity and / or reduce the risk of obesity later in life (e.g., at age 3 or 10). Preferably, later in life refers to age 20 or 40. Satiety programming is expected to have a lasting effect on the subject throughout their life, and therefore is expected to prevent and / or reduce the risk of obesity in adulthood.

[0099] Since obesity is associated with abnormal or excessive fat accumulation in the body, a lower risk of obesity later in life helps improve body composition. Therefore, in one embodiment, the compositions or age-tailored nutrition systems of the present invention can be used to improve body composition, the improvement being selected from the group consisting of: increased lean body mass relative to total body mass and decreased fat mass relative to total body mass. The present invention also relates to the use of the compositions and / or nutrition systems of the present invention in the manufacture of medicaments for improving body composition, and / or for the prevention of obesity and / or reduction of the risk of obesity later in life.

[0100] In another aspect, the present invention relates to a method of feeding a human subject, the method comprising the step of administering a nutritional composition according to the invention, or comprising the step of administering an age-customized nutritional system according to the invention to the subject, preferably wherein the age of the human subject is between 0 and 12 months, more preferably wherein the age of the subject is between 0 and 6 months.

[0101] It should also be understood that the present invention is not limited to the specific embodiments and methods described herein, as specific components and / or conditions can certainly vary. Furthermore, the terminology used herein is for the purpose of describing specific embodiments of the invention only and is not intended to be limiting in any way.

[0102] The invention is described below with reference to the following non-limiting examples.

[0103] Example

[0104] Physiological model

[0105] The inventors have noted that regulations concerning infant nutrition are guided by nutrient amounts per 100 kcal and per 100 ml, as well as daily kcal amounts, rather than by daily fluid volumes (e.g., daily water volumes in ml). This differs from the nutrient amounts per 100 ml in human breast milk, as nutrient levels per 100 ml in breast milk vary with temperature. For example, the fat content in breast milk from Bedouin women decreases by 42% from winter to summer. Similarly, the lactose content increases by 12%, as shown in Table 1.

[0106] Table 1. Milk, water, lactose, and fat content in women with bedouin

[0107] (Source: Yagil et al., Journal of Arid Environments, 1986, 11, pp. 243-247)

[0108]

[0109] *p = 0.01; **p = 0.005; ***p = 0.001.

[0110] A similar trend was observed in cow's milk. (Yagil et al., Journal of Arid Environments, 1986, 11, pp. 243-247).

[0111] Even in mild weather conditions, bottle-fed infants frequently fail to achieve adequate water intake levels, as demonstrated by the 2013 Nutri-Bébé cross-sectional survey (Chouraqui et al. 2018; Public Health Nutrition: 21(3), 502–514). In this paper, total water intake (TWI) was assessed in approximately 1200 non-breastfed children aged 0.5–35 months during the winter of 2013. It was compared to the adequate intake (AI) set by the EFSA. In infants, 90% had a water:energy ratio below the AI, and similarly, approximately 75% of toddlers did. Studies have shown a significant difference between actual water intake and recommended water intake in young children (Chouraqui, J., Thornton, S., Seconda, L., and Kavouras, S. (2022). Total water intake and its contributors ininfants and young children. British Journal of Nutrition, 128(3), 531-541. doi:10.1017 / S0007114521003469).

[0112] WHO guidelines for infants aged 6-12 months: Non-breastfed infants and toddlers require at least 400-600 mL / day of additional fluids in temperate climates (excluding an estimated 200-700 mL / day of water from milk and other foods), and 800-1200 mL / day of additional fluids in hot climates. Pure, clean (and boiled if necessary) water should be provided several times a day to ensure the infant's thirst is relieved. (WHO 2005 - Guiding principles for feeding non-breastfed children 6-24 months of age) https: / / apps.who.int / at iris / bitstream / handle / 10665 / 43281 / 9241593431.pdf)

[0113] Therefore, it can be concluded that feeding formula to infants when they only need to quench their thirst carries the risk of overfeeding.

[0114] As Azad et al. demonstrated, similar effects exist in bottled breast milk. They concluded that breastfeeding was negatively correlated with rate of weight gain and BMI. These associations were dose-dependent, partially weakened when breast milk was bottle-fed, and significantly weakened after the neonatal period with the introduction of formula. (MB Azad et al. Infant Feeding and Weight Gain: Separating Breast Milk From Breastfeeding and Formula From Food. Pediatrics, Oct 2018; 142(4): e20181092. 10.1542 / peds.2018-1092). Unbound by any particular theory, the inventors believe this is an effect triggered by the infant's thirst-driven intake. To confirm this, an infant physiological model was created to calculate the water requirement (also known as water loss) of infants aged 0–12 months, as such a model did not previously exist. It is based on the HumMod (hummod.org) model: extending the HumMod model, which covers humans aged 1 year and older, to cover infants aged 0-12 months. Temperature (°C), relative humidity (%), atmospheric pressure (mbar), infant age (weeks), and infant weight (kg) are used as input parameters to calculate respiratory water loss (via lungs, RespWL), sweat water loss (SWL), transepidermal water loss (TEWL), renal water loss (urine, RWL), and fecal water loss (FWL). Daily water loss is the sum of RespWL, SWL, TEWL, RWL, and FWL. See also Figure 1 .

[0115] The daily calorie intake for infants of different ages is based on regulations and remains similar to that of existing infant formula. The amount of monovalent ions per 100 mL also remains similar to that of existing infant formula.

[0116] The model assumes that the infant is fed only infant formula and that infant formula is the only source of fluids the infant receives, which is consistent with nutritional recommendations for infants aged 0-6 months.

[0117] Using this model, the fluid loss of infants in different cities (in mL / day) was calculated. For each of these cities, outdoor temperature was used as input to the simulation. Outdoor temperature data was optionally combined with indoor temperature information and used as additional input parameters. Outdoor temperature data was obtained from openweathermap.org, which provides historical temperature data for +37,000 cities. The average daily outdoor temperature for each city was calculated based on 6 years of historical data.

[0118] Because temperature is affected by seasonality, such as hot summers and cold winters, simulations were performed assuming the infant was born in different months of the year. This was compared to an intake of 830 mL of infant formula per day as indicated on the formula's label.

[0119] This comparison reveals a systematic overconsumption of IFT products to meet an infant's water needs (i.e., total water loss) during the first few months of life, particularly the first 0-6 months, preferably the first 0-4 months, and more preferably the first 3 months (e.g., 0-3 months), regardless of birth month. Surprisingly, this overconsumption occurs in all climatic regions. This is illustrated in Figures 2 through 4. The infant's water needs appear to be independent of room temperature.

[0120] Data from Chicago (USA) Figures 2A to 2D The figures show the recommended daily water intake (gray bars) (i.e., the amount in ml of infant formula based on the manufacturer's instructions) and water requirements, as determined based on the extended HumMod model. Figure 2A Figure A shows data for infants born in January, February, and March; Figure B shows data for infants born in April, May, and June; Figure C shows data for infants born in July, August, and September; and Figure D shows data for infants born in October, November, and December. Chicago has a Dfa climate (hot, humid continental climate) according to the Köppen system. These figures clearly show that birth month has little effect on differences in water requirements. Particularly in the first four months of life, water requirements are significantly higher than the amount of infant formula provided according to the manufacturer's instructions. This leads to thirst in infants, thus requiring more formula. This is considered to be due to thirst-driven formula intake, resulting in infants receiving more nutrients than needed.

[0121] Similar results were obtained for Sydney (Australia) (humid subtropical climate, classified as CFA according to the Köppen climate classification) and Thessaloniki (Greece), as follows: Figures 3A to 3D and Figures 4A to 4D As shown.

[0122] Simulations reveal that in addition to the fluids they receive daily through infant formula, babies need approximately 200 ml of water. To compensate for this fluid requirement, babies will drink more formula, thus obtaining more nutrients and calories than they need.

[0123] The simulation also revealed that this result was independent of outdoor temperature (whether it was as hot as a Sydney summer or as cold as a Chicago winter).

[0124] Examples of illustrative compositions according to the present invention

[0125] This example illustrates the macronutrient levels of a standard Stage 1 infant formula and three compositions according to the invention.

[0126] For the calculations in this example, assume that...

[0127] Dissolve 13.0 g of the reference product powder in 90 ml of water;

[0128] - A suggested daily intake of 830 ml of ready-to-drink product;

[0129] - This invention's product can be consumed daily in a dose of 1056 ml.

[0130] The reference product is an average composition of three commercially available stage 1 infant formula foods. Examples 1, 2, and 3 are compositions according to the present invention (Table 2).

[0131] Table 2 shows the nutrients in the compositions according to the present invention.

[0132]

[0133]

[0134]

Claims

1. A synthetic nutritional composition comprising protein fraction, fat fraction and carbohydrate fraction, wherein the nutritional composition is a liquid or powder that can be reconstituted with water into an oil-in-water emulsion, wherein the energy content of the nutritional composition is less than 55 kcal / 100 ml, preferably less than 53 kcal, particularly preferably less than 52 kcal, more preferably less than 50 kcal, even more preferably less than 48 kcal, and most preferably less than 46 kcal.

2. The nutritional composition of claim 1, wherein the composition... a. For infants weighing 3.0 kg or more; and / or b. Has a carbohydrate content of 6.2 or higher per 100 mL.

3. The nutritional composition according to claims 1 and 2, wherein the energy content per 100 g powder is less than 467 kcal, preferably less than 450 kcal, particularly preferably less than 442 kcal, more preferably less than 424 kcal, even more preferably less than 408 kcal, and most preferably less than 390 kcal.

4. The nutritional composition as claimed in any of the preceding claims, wherein the energy content is at least 40 kcal / 100 ml and / or at least 340 kcal / 100 g powder.

5. The nutritional composition as claimed in any of the preceding claims, wherein the protein content is between 1.6 and 3.0 g protein / 100 kcal; or wherein the protein content is greater than 1 g / 100 mL; or wherein the protein content is between 1.6 and 3.0 g protein / 100 kcal, and wherein the protein content is greater than 1 g / 100 mL.

6. The nutritional composition as claimed in any of the preceding claims, wherein the fat content is between 3.5 and 6.0 g fat / 100 kcal.

7. The nutritional composition as claimed in any of the preceding claims, wherein the carbohydrate content is between 9.0 and 15.0 g carbohydrate / 100 kcal.

8. The nutritional composition as claimed in any of the preceding claims, wherein the protein fraction comprises a mixture of whey and casein in a ratio between 100:0 and 20:80, preferably in a whey to casein ratio between 70:30 and 20:

80.

9. The nutritional composition as claimed in any of the preceding claims, wherein the nutritional composition is an infant formula for infants aged 0 to 4 months.

10. The nutritional composition as claimed in any of the preceding claims, wherein the fat fraction comprises milk fat and vegetable oil, preferably wherein the amount of milk fat is at least 10 wt%, as determined relative to the total fat content.

11. The nutritional composition as claimed in any of the preceding claims, wherein the composition further comprises one or more of minerals, vitamins, probiotics and / or prebiotics, preferably wherein the composition comprises galactooligosaccharides (GOS) and human milk oligosaccharides.

12. An age-customized nutrition system for infants from birth to 6 months of age, the age-customized nutrition system comprising two or more formula products, wherein the first formula product is a nutritional composition as described in any one of claims 1 to 10, and wherein the first formula product is used for at least part of the feeding of the infant during the first 3 months, preferably the first 2 months, and the second formula product is used for at least part of the feeding of the infant during the remaining 6 months, and wherein the energy content of the second nutritional formula product is higher than that of the first nutritional product, preferably wherein the energy content of the second nutritional formula product is 58 kcal / 100 ml or higher.

13. The composition of any one of claims 1 to 10 or the age-customized nutrition system of claim 11, for use in preventing obesity and / or reducing the risk of obesity later in life.

14. The composition of any one of claims 1 to 10 or the age-customized nutrition system of claim 11, for use in improving body composition, wherein the improvement in body composition is selected from one or more of the group consisting of: an increase in lean body mass relative to total body mass and a decrease in fat mass relative to total body mass.

15. A method of feeding a human subject, the method comprising the step of administering a nutritional composition as described in any one of claims 1 to 10, or comprising the step of administering to the subject an age-customized nutritional system as described in claim 11, preferably wherein the age of the human subject is between 0 and 12 months, more preferably wherein the age of the subject is between 0 and 6 months.

16. A method for manufacturing a nutritional composition as described in any one of claims 1 to 10, the method comprising the following steps: i. Prepare an aqueous phase containing proteins and digestible carbohydrates and a fatty phase containing lipids, wherein the fatty acid composition of the lipids comprises linoleic acid and α-linolenic acid in a weight ratio of 2 to 10. ii. Mix the fatty phase and the aqueous phase, and homogenize the mixture of the fatty phase and the aqueous phase to form an oil-in-water emulsion. iii. Optionally, the oil-in-water emulsion of ii. is dried into a powder.

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