WO2017167418A1 - Compositions nutritionnelles et leur utilisation - Google Patents

Compositions nutritionnelles et leur utilisation Download PDF

Info

Publication number
WO2017167418A1
WO2017167418A1 PCT/EP2016/080792 EP2016080792W WO2017167418A1 WO 2017167418 A1 WO2017167418 A1 WO 2017167418A1 EP 2016080792 W EP2016080792 W EP 2016080792W WO 2017167418 A1 WO2017167418 A1 WO 2017167418A1
Authority
WO
WIPO (PCT)
Prior art keywords
nutritional composition
brain
composition
mcfa
cognitive
Prior art date
Application number
PCT/EP2016/080792
Other languages
English (en)
Inventor
Frederic Destaillats
Jonas HAUSER
Original Assignee
Nestec S.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nestec S.A. filed Critical Nestec S.A.
Priority to BR112018067926A priority Critical patent/BR112018067926A2/pt
Priority to AU2016401061A priority patent/AU2016401061A1/en
Priority to EP16823175.1A priority patent/EP3435787A1/fr
Priority to RU2018138024A priority patent/RU2018138024A/ru
Priority to US16/089,124 priority patent/US20190104759A1/en
Priority to MX2018011335A priority patent/MX2018011335A/es
Priority to CN201680083179.9A priority patent/CN108777997A/zh
Publication of WO2017167418A1 publication Critical patent/WO2017167418A1/fr
Priority to PH12018550151A priority patent/PH12018550151A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1528—Fatty acids; Mono- or diglycerides; Petroleum jelly; Paraffine; Phospholipids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
    • A23C9/206—Colostrum; Human milk
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention concerns a nutritional composition, for example a synthetic nutritional composition, for use to promote and/or support a health status characterized by optimal brain and cognitive functions' development and/or prevention of neurocognitive deficits.
  • This composition is for use in mammals, preferably in humans, more preferably in infants.
  • Brain structure in particular the amount and/or spatial distribution of myelinated matter throughout the brain, for cognitive functioning and intelligence is well documented.
  • Brain structure in particular the amount and/or spatial distribution of myelin throughout the brain, affects brain connectivity e.g. via what pathway and how quickly and efficiently, messages in the form of neural impulses are communicated within the brain and in particular between different brain regions. This interbrain communication can play a role in cognitive functioning and learning, and may serve to physiological limit/enhance intellectual, cognitive and/or learning potential and to regulate cognitive functioning.
  • the present invention relates to a nutritional composition, for example a synthetic nutritional composition, for infants, in particular for infants born preterm or with low- birth weight (LBW) or who experienced intra-uterine growth retardation (IUGR), such as a pre-term formula or a human milk fortifier.
  • the composition comprises medium chain fatty acid (MCFA) derivatives.
  • MCFA medium chain fatty acids
  • MCFA Medium chain fatty acids
  • Such fatty acid derivatives had been previously identified as being fundamental components of brain myelin and white matter and their availability as being key during early phase of brain maturation.
  • the nutritional composition for example the synthetic nutritional composition, of the present invention, promotes and/or supports a health status characterized by optimal brain and cognitive functions' development and/or prevention of neurocognitive deficits.
  • the present invention provides a nutritional composition, for example the synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize brain and/or cognitive functions' development.
  • MCFA medium chain fatty acids
  • the present invention provides the use of one or more MCFA derivative for the manufacture of a nutritional composition, for example the synthetic nutritional composition, for promoting and/or supporting and /or optimizing brain and/or cognitive functions' development.
  • the present invention provides for a method for promoting and/or supporting and/or optimizing brain and/or cognitive functions' development in an human subject in need thereof comprising administering to such subject a nutritional composition, for example the synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative.
  • a nutritional composition for example the synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative.
  • MCFA medium chain fatty acids
  • the present invention provides for the use of a nutritional composition, for example a synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize brain and/or cognitive functions' development.
  • a nutritional composition for example a synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize brain and/or cognitive functions' development.
  • MCFA medium chain fatty acids
  • Figure 1 is a schematic representation of fatty acid metabolism wherein variations in specific fatty acids derivatives in RCB-PE compartment (in particular palmitic acid (16:0), vaccenic acid (n-7, 18:1), gondoic acid (n-9, 20:1), erucic acid (n-9, 22:1) and mead acid (n- 9, 20:3)) observed in premature infants on consumption of a human milk fortifier according to the present invention are highlighted.
  • variations in specific fatty acids derivatives in RCB-PE compartment in particular palmitic acid (16:0), vaccenic acid (n-7, 18:1), gondoic acid (n-9, 20:1), erucic acid (n-9, 22:1) and mead acid (n- 9, 20:3)
  • Figure 2 Shows the impact of DHA on MBP, NF, and/or MBP/NF at day 18 and/or day 30.
  • Figure 3 Shows the impact of sialic acid on A2B5, MBP, MAG, NF, MBP/NF, and/or MAG/NF at day 6, day 18 and/or day 30.
  • Figure 4 Shows the impact of stearic acid on MAG and MBP mRNA expression and on MBP and Betalll Co-expression.
  • Figure 5 Shows the impact of DHA on MAG and MBP mRNA expression and on
  • promote and/or “promoting” indicates a factor or a number of factors causing a certain process to occur.
  • support and/or “supporting” indicates a factor or a number of factors sustaining a certain process once it has started to occur.
  • brain and cognitive functions' development within the context of the present invention in meant to identify a normal development for brain and/or mental processes, structures, skills and abilities selected, for example, in the group consisting of: de novo myelination; brain structure, in particular the amount and spatial distribution of myelinated matter throughout the brain, and/or in specific brain regions; brain connectivity; intellectual potential; cognitive potential; learning potential; cognitive functioning; cognition; cognitive skills and abilities; and/or learning.
  • de novo myelination refers to development myelination and in particular the process by which naked axons in the brain of a subject are myelinated during growth and development. It is a process that starts, in particular in specific brain regions, in utero and continues postnatally, and that is most prolific in the first 5 years of a human subject's life, in particular the first 2 & 3 years of a human's life, in particular the first years of human's life.
  • the term “cognition” as used herein refers to the intellectual processes by which one individual becomes aware of, perceives, or comprehends ideas; thus, the ability to think and understand. Cognition includes all aspects of information processing, perception, attention, thinking, reasoning, understanding and remembering as well as psychomotor, language, memory, concentration, executive functions and problem-solving abilities.
  • cognitive skills or “cognitive abilities” as used herein refer to cognitive and/or mental ability or capacity of a subject.
  • the term may refer to one or more of; information processing, perception, attention, thinking, reasoning, understanding and remembering, psychomotor including gross motor and fine motor potential, visual including visual reception, language including expressive and receptive language, memory and recall, concentration, executive function including problem-solving, decision-making and inhibition.
  • brain structure refers to the structure of grey and white matter within the brain and specific brain regions, and in particular to myelinated white matter within the brain and specific brain regions as determined by de novo myelination i.e. by the de novo structural deposition of myelin. More particularly the term refers to the amount and/or spatial distribution of myelinated matter throughout the brain, and/or in specific brain regions, and even more particularly the amount and/or temporal spatial distribution of myelinated matter throughout the brain and/or in specific brain regions.
  • intellectual potential refers to the possible intellectual ability or capacity attainable by a subject as determined by physiological factors.
  • intellectual potential may refer to fluid intelligence.
  • fluid intelligence refers to a subject's neural potential and/or a subject's novel or abstract problem solving capability as determined by physiological factors. This is distinct from crystallized intelligence which is determined, at least in part by learned or acculturated knowledge.
  • cognitive potential refers to the possible cognitive and/or mental ability or capacity possibly attainable by a subject as determined by physiologica l factors.
  • the term may refer to one or more of; information processing potential, perception potential, attention potential, thinking potential, reasoning potential, understanding and remembering potential, psychomotor potential including gross motor and fine motor potential, visual potential including visual reception potential, auditory potential, language potential including expressive and receptive language potential, memory and recall potential, concentration potential, executive function potential including problem-solving, decision-making and inhibition potential.
  • learning potential refers to the possible ability or capacity a subject has to learn e.g. how easily and/or quickly a subject may be able to acquire knowledge or skills through experience, study or being taught, as determined by physiological factors. As well as the possible ability a subject has to adapt in response to environmental factors, as determined by physiological factors.
  • Training refers to the acquisition of knowledge or skills through experience, study, or by being taught.
  • compositions of the invention may have a short term or long term effect on cognitive functioning, including the development of cognitive functions, and/or learning, and on preventing or minimising any neuro cognitive deficits, impairment or delay.
  • Said short term effect may only be apparent in days, weeks, or months.
  • Said long term effect may only be apparent in years e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60. 70, 80, 90 years.
  • cognitive potential is selected from the group consisting of vision potential, auditory potential, motor function and psychomotor potential (including coordination and execution of movement potential), and/or executive functioning potential including problem solving potential, social processing, behaviour interaction potential, and social-emotional functioning potential.
  • compositions of the invention may have a short term or long term effect e.g. enhancement effect, on vision, motor function and psychomotor function, and/or executive functioning including problem solving, social processing, behaviour interaction, and/or language.
  • Said short term effect may only be apparent in days, weeks, or months.
  • Said long term effect may only be apparent in years e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60. 70, 80, 90 years.
  • subject refers to a mammal, in particular a cat, dog or human, more particularly the term refers to a human, even more particularly a human infant or child and even more particularly still a human infant or child fed infant formula and/or growing up milk.
  • infant refers to a human infant of up to 12 months of age and includes preterm and very preterm born infants, infants having a low birth weight i.e. a new born having a body weight below 2500g (5.5 pounds) either because of preterm birth or restricted fetal growth, and infants born small for gestational age (SGA) i.e. babies with birth weights below the 10th percentile for babies of the same gestational age.
  • SGA gestational age
  • child refers to a human of 1 to 18 years of age, more specifically a human of 1 to 10 years of age, even more specifically a human of 1 to 5 years of age, and even more specifically a human of 1 to 2 years of age.
  • formula fed infant or child refers to an infant or child fed either infant formula and/or growing up milk.
  • breastfed subject refers to a subject, In particular an infant or child, fed human breastmilk, in particular from a nutritionally replete mother.
  • preterm or premature means an infant or young child that was not born at term. Generally it refers to an infant born prior to the completion of 37 weeks of gestation.
  • Term born infant indicates an infant born after 37 weeks gestation.
  • Low birth weight indicates a newborn's body weight below 2500g (5.5 pounds), either as a result of preterm birth (i.e. before 37 weeks of gestation) and/or due to restricted foetal growth.
  • low birth weight it should be understood as any body weight under 2500g at birth. It therefore encompasses:
  • VLBW very low birth weight
  • SGA Small-for-gestational-age
  • Postnatal period is the period beginning immediately after the birth of a child and extending for about six weeks.
  • the expression "nutritional composition” means a composition which nourishes a subject.
  • This nutritional composition is usually to be taken enterally, orally, parenterally or intravenously, and it usually includes a lipid or fat source and optionally a protein source and /or optionally a carbohydrate source and/or optionally minerals and vitamins.
  • the nutritional composition is for oral use.
  • hypoallergenic nutritional composition means a nutritional composition which is unlikely to cause allergic reactions.
  • synthetic composition means a mixture obtained by chemical and/or biological means, which can be chemically identical to the mixture naturally occurring in mammalian milks.
  • synthetic nutritional composition identifies nutritional composition as above defined which are obtained by chemical and/or biological means, which can be chemically identical to a the mixture which also naturally occurr, for example in mammalian milks.
  • synthetic nutritional compositions as herein defined are comprised within the scope of the present invention and all the embodiments described in the present application apply as well to such synthetic nutritional composition.
  • said synthetic nutritional composition is selected from the group consisting of; growing up milk, infant formula or a composition for infants that is intended to be added or diluted with human breast milk (hereinafter "HM") e.g. HM fortifier, or a food stuff intended for consumption by an infant and/or child either alone or in combination with HM e.g. complementary foods.
  • HM human breast milk
  • infant formula means a foodstuff intended for particular nutritional use by infants during the first four to six months of life and satisfying by itself the nutritional requirements of this category of person (Article 1.2 of the European Commission Directive 91/321/EEC of May 14, 1991 on infant formulae and follow-on formulae).
  • starter infant formula means a foodstuff intended for particular nutritional use by infants during the first four months of life.
  • pre-term formula or “preterm formula” means an infant formula intended for a preterm infant or for an infant with low-birth weight (LBW) or who experienced intra-uterine growth retardation (IUGR) or for infants small for gestational age (SGA).
  • LW low-birth weight
  • IUGR intra-uterine growth retardation
  • SGA gestational age
  • fortifier or “human milk fortifier” (HMF) refers to liquid or solid nutritional compositions suitable for mixing with breast milk or infant formula, for example a preterm infant formula.
  • milk fortifier it is meant any composition used to fortify or supplement either human breast milk, infant formula, growing-up milk or human breast milk fortified with other nutrients.
  • fortifier refers to a composition which comprises one or more nutrients having a nutritional benefit for infants, both preterm infants, with low-birth weight (LBW) or infants who experienced intra-uterine growth retardation (IUGR) or infants small for gestational age (SGA), and term infants.
  • LW low-birth weight
  • IUGR intra-uterine growth retardation
  • SGA gestational age
  • weaning period means the period during which the mother's milk is substituted by other food in the diet of an infant.
  • fatty acid indicates a carboxylic acid with a long aliphatic chain, which is either saturated or unsaturated and refers to a compound of formula (XI I)
  • R 22 is a C3 to C43 branched or unbranched acyclic alkyl, or acyclic alkenyl group.
  • R 22 is a C3 to C43 branched or unbranched acyclic alkyl, or acyclic alkenyl group, and even more particularly a C3 to C 28 branched or unbranched acyclic alkyl, or acyclic alkenyl group.
  • Mixture of such compounds are a lso comprised within the scope of the invention and/or the term.
  • MCFA medium chain fatty acid
  • R 22 is C 7 or Cg branched or unbranched acyclic a lkyl, or acyclic alkenyl group .
  • Non limiting examples of such MCFA are: capric acid (8:0) and caprylic acid (10:0). Mixture of such compounds are also comprised within the scope of the invention and/or the term.
  • long chain fatty acid LCFA
  • R 22 is Cn branched or unbranched acyclic alkyl, or acyclic alkenyl group or longer, in particular C13 to C23.
  • Long chain fatty acids may be saturated, mono unsaturated (M UFA) or polyunsaturated (PUFA).
  • Non limiting examples of such LCFA are: lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), lignoceric acid (24:0), vaccenic acid (n-7, 18:1), gondoic acid (n-9, 20:1), erucic acid (n-9, 22:1), mead acid (n-9, 20:3), alpha-linolenic acid (ALA) (n-3, 18:3), Eicosapentaenoic acid (EPA) (n-3, 20:5), Docosapentaenoic acid (DPA n-3) (n-3, 22:5), Docosahexaenoic (DHA) (n-3, 22:6), Linoleic acid (LA) (n-6, 18:2), Dihomo-gamma-linolenic acid (DGLA) (n-6, 20:
  • LCFA belonging to the n-6 and n-3 series constitute the so called "essential fatty acids” whose biosynthesis can't be initiated by metabolic mechanisms in the absence of linoleic and alpha-linoleic acid substrate introduced with the diet.
  • SCFA short chain fatty acid
  • de novo biosynthesis of fatty acids derivatives within the context of the present invention refers to the ability of mammals, in particular humans, to synthetize fatty acids derivatives by metabolic processes starting from available carbon-containing substrates (such as for example amino acids, carbohydrates, fatty acids).
  • fatty acid derivative refers to a compound comprising a fatty acid, other than a phospholipid, and in particular to a free fatty acid, and/or a monoacylglycerol (hereinafter MAG), and/or a diacylglycerol (hereinafter DAG), and/or a triacylgylcerol (hereinafter TAG) and/or a cholesterol ester. More particularly the term refers to a MAG, DAG, TAG and/or a cholesterol ester. Even more particularly the term refers to a TAG. Mixture of such compounds are also comprised within the scope of the invention and/or the term.
  • MAG monoacylglycerol
  • DAG diacylglycerol
  • TAG triacylgylcerol
  • a cholesterol ester More particularly the term refers to a MAG, DAG, TAG and/or a cholesterol ester. Even more particularly the term refers to a TAG. Mixture of such compounds are also comprised within
  • MAG refers to a glycerol molecule in which one of the OH groups has formed an ester bond with a fatty acid.
  • MAG refers to a compound of formula (X)
  • R 18 R 19 or R 20 are H and wherein one of R 18 R 19 or R 20 is a C4 to C44 saturated or unsaturated acyl group.
  • DAG refers to glycerol molecule in which two of the OH groups have formed an ester bond with two fatty acids.
  • DAG refers to a compound of formula (X)
  • R 18 R 19 or R 20 are H and wherein two of R 18 R 19 or R 20 are C4 to C44 saturated or unsaturated acyl groups.
  • the two C4 to C44 saturated or unsaturated acyl groups may be the same or different.
  • TAG refers to glycerol molecule in which three of the OH groups have formed an ester bond with three fatty acids.
  • TAG refers to a compound of formula (X)
  • R 18 R 19 or R 20 are C4 to C44 saturated or unsaturated acyl groups.
  • the three C4 to C44 saturated or unsaturated acyl groups may all be the same, all different, or two may be the same and one different.
  • cholesterol refers to a compound of formula (XI)
  • R 21 is a C2 to C43 branched or unbranched acyclic alky, or acyclic alkenyl group.
  • R 12 is a C3 to C43 branched or unbranched acyclic alkyl, or acyclic alkenyl group and,
  • R 13 is a C3 to C43 branched or unbranched acyclic alkyl, or acyclic alkenyl group.
  • R 12 and R 13 are, independently of each other, C7 to C27 branched or unbranched acyclic alkyl, or acyclic alkenyl groups which together with their adjacent carbonyl group correspond to C8 to C28 saturated or unsaturated fatty acid residues, and even more particularly R 12 and R 13 are, independently of each other, C13 to C23 branched or unbranched acyclic alkyl, or acyclic alkenyl groups which together with their adjacent carbonyl group correspond to C14 to C24 saturated or unsaturated fatty acid residues. Mixture of such compounds are also comprised within the scope of the invention and/or the term.
  • prebiotic means non-digestible carbohydrates that beneficially affect the host by selectively stimulating the growth and/or the activity of healthy bacteria such as bifidobacteria in the colon of humans (Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125:1401-12).
  • vitamin refers to any vitamin.
  • Non limiting examples of vitamins include: vitamin A, vitamin Bl, vitamin B2, vitamin B6, vitamin K, vitamin C, vitamin D, niacin, biotin, pantothenic acid, folic acid, vitamin B12, and combinations thereof.
  • folic acid is to be intended as identifying all the folic acid present in the nutritional compositions, for example synthetic nutritional compositions, of the invention either as such or in the form of one physiologically acceptable salt thereof (folate) and mixtures thereof.
  • composition of the present invention can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise depending on the needs.
  • Nutritional compositions according to the present invention for example synthetic nutritional compositions, provide MCFA in the form of TAGs.
  • nutritional compositions according to the present invention for example synthetic nutritional compositions, promote and/or support and /or optimizing brain and/or cognitive functions' development via promotion and/or support and/or optimization of de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acid derivatives.
  • nutritional compositions according to the present invention promote and/or support and /or optimizing brain and/or cognitive functions' development via promotion and/or support and/or optimization of de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acid derivatives and/or via promotion and/or support and/or optimization of brain de novo myelination.
  • the present invention provides for the use of a nutritional composition, for example a synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acids.
  • MCFA medium chain fatty acids
  • the present invention provides for the use of a nutritional composition, for example a synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize brain de novo myelination.
  • a nutritional composition for example a synthetic nutritional composition, comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize brain de novo myelination.
  • MCFA medium chain fatty acids
  • a nutritional compositions according to the present invention for example a synthetic nutritional composition, is provided to promote and/or support and /or optimizing brain and/or cognitive functions' development via promotion and/or support and/or optimization of de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acid derivatives and/or via promotion and/or support and/or optimization of brain de novo myelination.
  • a nutritional compositions according to the present invention for example a synthetic nutritional composition, is provided to promote and/or support and /or optimizing brain and/or cognitive functions' development via promotion and/or support and/or optimization of de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acid derivatives and/or via promotion and/or support and/or optimization of brain de novo myelination, in an infant who was born preterm or with low-birth weight (LBW) or who experienced intrauterine growth retardation (IUGR).
  • LW low-birth weight
  • IUGR intrauterine growth retardation
  • nutritional compositions according to the present invention promote and/or support and /or optimizing brain and/or cognitive functions' development in an infant who was born preterm or with low-birth weight (LBW) or who experienced intra-uterine growth retardation (IUGR).
  • LW low-birth weight
  • IUGR intra-uterine growth retardation
  • the nutritional composition according to the present invention for example synthetic nutritional compositions, promote and/or support and /or optimizing brain and/or cognitive functions' development and prevent of neurocognitive deficits.
  • composition of the invention may be any type of composition suitable and intended for direct administration to a subject, for example an infant who was born preterm or with low-birth weight (LBW) or who experienced intra-uterine growth retardation (IUGR).
  • LW low-birth weight
  • IUGR intra-uterine growth retardation
  • composition will be a synthetic nutritional composition.
  • nutritional compositions according to the present invention is a pre-term formula.
  • the pre-term formula according to the present invention comprises MCFA in an amount of up to 40% by weight of the total content of lipid.
  • the preterm formula comprises at least 20% MCT by weight of the total lipid content, such as at least 25%, preferably at least 30%, such as at least 35%, even more preferably 40% by weight of the total lipid content.
  • the preterm formula according to the present invention comprises MCFA derivatives in amount ranging from 0.1 to 25%w/w, for example in an amount ranging from 0.5 to 20%w/w, for example in an amount ranging from 1 to 15%w/w of dry powder.
  • the liquid preterm formula according to the present invention comprises MCFA derivatives in amount ranging from 0.01 to 4 g/lOOmL of liquid formula, for example in an amount ranging from 0.05 to 3 g/lOOmL, for example in an amount ranging from 0.1 to 3.5 g /100mL.
  • the preterm formula according to the present invention comprises MCFA derivatives in amount ranging from 0.01 to 5 g/lOOKcal of formula, for example in an amount ranging from 0.05 to 4 g/lOOKcal, for example in an amount ranging from 0.1 to 3 g /lOOKcal.
  • the preterm formula according to the present invention comprises fatty acid derivatives in amount ranging from 10 to 40% w/w, MCFA derivatives in amount ranging from 0.1 to 25%w/w, 5 to 50%w/w protein and 10 to 80%w/w carbohydrates.
  • the nutritional compositions according to the present invention is a human milk fortifier.
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 2 to 40%w/w, for example in an amount ranging from 5 to 30%w/w, for example in an amount ranging from 5 to 20%w/w for example in an amount ranging from 7 to 18%w/w.
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 0.08 to 1.6 g/lOOmL of HMF reconstituted in human breast milk, for example in an amount ranging from 0.2 to 1.2 g/lOOmL, for example in an amount ranging from 0.25 to 0.75 g /lOOmL.
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 2 to 10 g/lOOKcal of HMF, for example in an amount ranging from 1.2 to 7.5 g/lOOKcal, for example in an amount ranging from 1.75 to 4.5 g
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 0.05 to 2.5 g/lOOKcal of HMF reconstituted in human breast milk, for example in an amount ranging from 0.2 to 2.0 g/lOOKcal, for example in an amount ranging from 0.5 to 1.5 g /lOOKcal.
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 40 to 80%w/w of total fatty acid derivatives, for example in an amount ranging from 50 to 75%w/w, for example in an amount ranging from 55 to 70%w/w.
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 5 to 40 %w/w of total fatty acid derivatives/lOOmL of HMF reconstituted in human breast milk, for example in an amount ranging from 10 to 20 %w/w of total fatty acid derivatives/lOOmL of HMF reconstituted in human breast milk.
  • the human milk fortifier according to the present invention comprises MCFA derivatives in amount ranging from 5 to 40 %w/w of total fatty acid derivatives/lOOKcal of HMF reconstituted in human breast milk, for example in an amount ranging from 10 to 20 %w/w of total fatty acid derivatives/lOOKcal of HMF reconstituted in human breast milk.
  • the human milk fortifier according to the present invention comprises 5 to 40%w/w fatty acid derivatives, wherein 40 to 80%w/w are constituted by MCFA derivatives.
  • the human milk fortifier according to the present invention comprises 5 to 30%w/w fatty acid derivatives, wherein 50 to 75%w/w are constituted by MCFA derivatives, 20 to 50%w/w protein and 15 to 40%w/w carbohydrates.
  • the nutritional composition for example the synthetic nutritional composition, can besides from comprising MCFA derivatives comprise other nutrients, such as e.g. lipids (including fatty acid derivatives), proteins, carbohydrates, vitamins, minerals, probiotics, or prebiotics.
  • MCFA derivatives comprise other nutrients, such as e.g. lipids (including fatty acid derivatives), proteins, carbohydrates, vitamins, minerals, probiotics, or prebiotics.
  • lipid refers to one or more lipids and may be any free fatty acid or ester of fatty acids that are suitable for being fed to an infant.
  • Lipid includes for example monoglycerides, diglycerides, triglycerides, phospholipids, cholesterol, free fatty acids, derivatives of fatty acids and combinations thereof.
  • the lipids used to prepare the fortifier can be naturally liquid or solid at room temperature. In some particular embodiments at least a part of the lipids used to prepare the fortifier are naturally liquid at room temperature.
  • the nutritional composition for example the HMF according to the invention, comprises lipid in an amount above 25% of the caloric content. In another embodiment, the nutritional composition, for example the HMF according to the invention, comprises lipid in an amount above 75% of the caloric content.
  • lipids are present in the nutritional composition, for example the HMF, in an amount of at least 30% of the caloric content, such as at least 35% of the caloric content.
  • the lipids are selected from the group of monoglycerides, diglycerides, triglycerides, phospholipids, cholesterol, free fatty acids, derivatives of fatty acids and combinations thereof.
  • the lipids are selected from the group of arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, linoleic acid, a-linolenic acid, milk fat, structured lipids phospholipid, and combinations thereof.
  • Structured lipids may be monoglycerides, diglycerides, triglycerides, cholesterol, palmitic acid esterified in the sn-2 position or interesterified palm stearin.
  • Lipids may be derived from various sources.
  • the lipid source may be any lipid or fat source which is suitable for use in nutritional compositions, to be fed to infants, for example some vegetable or animal fats or oils.
  • the lipid is provided from oils or fats.
  • Preferred lipid sources include coconut oil, soy oil, corn oil, olive oil, safflower oil, sunflower oil, palm oil, palm kernel oil, low erucic rapeseed oil (canola oil), marine oil, cottonseed oil, soy lecithin's, palm oil, milk fat, structured lipids, egg-derived oils, fungal oils, algal oils and combinations thereof.
  • Particularly preferred oils are canola oils, soy lecithin, palm olein, and sunflower oil.
  • the lipid comprises one or more polyunsaturated fatty acid, preferably long chained polyunsaturated fatty acids.
  • the polyunsaturated fatty acids, and in particular the long chain ones are important for the cell membrane function and the development of the brain and visual system in infants. Further, the long chain polyunsaturated fatty acids are important in the formation of bioactive eicosanoids. Brain grey matter and the retina are complex neural functions related to energy supply and the composition of dietary fatty acids.
  • the composition comprises arachidonic acid, docosahexaenoic acid, or a combination thereof as the lipid component.
  • the arachidonic acid and docosahexaenoic acid may be alone or in combination with other lipids, such as linoleic acid and/or a-linolenic acid.
  • the content of arachidonic acid in the nutritional composition according to the invention is at least 0.005%w/w, such as at least 0,0075%, for example at least 0.01% w/w.
  • the content of arachidonic acid in the nutritional composition of the invention ranges between 0.001%w/w to l%w/w , for example from 0.01%w/w to 0.5%w/w.
  • the content of arachidonic acid in the HMF according to the present invention is at least 0.2% by weight of the total lipid content, such as at least 0,30%, in particular at least 0,38%, even more preferably at least 0.65%, such as 0,70% by weight of total lipid content.
  • the HMF comprises arachidonic acid in an amount of up to 2.5% by weight on the total lipid content, such as at in the range of 0.2 to 2.0%, preferably from 0.3 to 1.5%, such as from 0.35 to 1.2%, even more preferably from 0.4 to 0.9% by weight of the total lipid content.
  • the content of docosahexaenoic acid in the nutritional composition of the invention for example a preterm formula, ranges between 0.001%w/w to l%w/w , for example from 0.01%w/w to 0.5%w/w.
  • the content of docosahexaenoic acid in the nutritional composition according to the invention is at least 0.05%w/w, such as at least 0.075%w/w, for example at least 0.1% w/w.
  • the content of docosahexaenoic acid in the HMF according to the present invention is ranging from 0.05% to 5% w/w, such as from 0.075% to 3%w/w, for example from 0.1% to 2% w/w.
  • the content of docosahexaenoic acid in the HMF according to the present invention is preferably at least 0.05% by weight of the total lipid content, such as at least 0,1%, for example at least 0.15%, such as 0,5% by weight of total lipid content.
  • the composition comprises docosahexaenoic acid in an amount of up to 3.0% by weight on the total lipid content, such as from 0.0.5% to 2.5%, preferably from 0,1 to 2.0%, such as from 0.15 to 1.50%by weight of the total lipid content.
  • the nutritional composition according to the present invention comprises fatty acid derivatives comprising ARA and DHA
  • said ingredients may for example be comprised in the composition of the invention in amounts resulting in a weight ratio of DHA:ARA in the range of 4:1 to 1:4, for example 3:1 to 1:3, for example 2:1 to 1:2, for example 1.5:1 to 1:1.5, in particular 1.1:1 to 1:1.1.
  • DHA and ARA Docosahexaenoic (DHA) and arachidonic acid (ARA) are both known to provide beneficial effects in infants, such as enhancing brain and vision development. DHA and ARA are therefore necessary for infants, both preterm and term infants, but in particular for a preterm infant. Further, DHA and ARA have shown beneficial effects on measures of cognitive development during the first year of life, and on immune phenotypes.
  • suitable sources of ARA and DHA include marine oil, egg-derived oils, fungal oil, algal oil, and combinations thereof.
  • the nutritional composition according to the invention for example a synthetic nutritional composition, comprises linoleic acid, a- linolenic acid or a combination thereof as lipid.
  • the nutritional composition of the invention for example a human milk fortifier, comprises linoleic acid in an amount ranging from 0.1%w/w to 5%w/w of dry composition.
  • the nutritional composition of the invention for example a preterm powder formula, comprises linoleic acid in an amount ranging from 0.5 to 10%w/w of dry composition.
  • the nutritional composition of the invention for example a preterm liquid formula, comprises linoleic acid in an amount ranging from 0.05 to 5g/100mL of formula.
  • the nutritional composition of the invention for example a human milk fortifier, comprises ⁇ -linolenic acid in an amount ranging from 0.1%w/w to 3%w/w of dry composition.
  • the nutritional composition of the invention for example a preterm powder formula, comprises ⁇ -linolenic acid in an amount ranging from 0.01 to 5%w/w of dry composition.
  • the nutritional composition of the invention for example a preterm liquid formula, comprises ⁇ -linolenic acid in an amount ranging from 0.01 to 2g/100mL of formula.
  • the lipid may also be eicosapentaenoic acid (20:5n-3).
  • the nutritional composition of the invention for example a human milk fortifier, comprises eicosapentaenoic acid in an amount ranging from 0.01%w/w to 5%w/w of dry composition.
  • the nutritional composition of the invention for example a preterm powder formula, comprises eicosapentaenoic acid in an amount ranging from 0.01 to 5%w/w of dry composition.
  • the nutritional composition of the invention for example a preterm liquid formula, comprises eicosapentaenoic acid in an amount ranging from 0.05 to 20mg/100mL of formula.
  • the lipid comprises one or more of phospholipids.
  • the content of phospholipid in the composition according to the present invention is preferably from 0.5 to 20% by weight of the total lipid content, such as from 0.8 to 15%, even more preferably from 1.0 to 10%, such as from 1.5 to 8% by weight of the total content of lipid.
  • phospholipids may be phosphatidylcholine, phosphatidylserine, phosphatidylinositol and/or sphingomyelin, in particular sphingomyelin.
  • composition according to the present invention does not comprise any phospholipids.
  • compositions of the invention can also comprise any other ingredients or excipients known to be employed in the type of composition in question e.g. infant formula, preterm formula and/or human milk fortifiers.
  • Non limiting examples of such ingredients include: proteins, amino acids, carbohydrates, oligosaccharides, lipids, prebiotics or probiotics, nucleotides, nucleosides, other vitamins, minerals and other micronutrients.
  • Vitamins include: proteins, amino acids, carbohydrates, oligosaccharides, lipids, prebiotics or probiotics, nucleotides, nucleosides, other vitamins, minerals and other micronutrients.
  • composition according to the present invention may further comprise one or more vitamin.
  • the presence and amounts of specific minerals and other vitamins will vary depending on the intended population.
  • vitamins may be folic acid, vitamin B12 and vitamin B6, in particular folic acid and vitamin B12, in particular folic acid.
  • the composition comprises one or more vitamin which is lipid-soluble, for example one or more of vitamin A, vitamin D, vitamin E and vitamin K.
  • Vitamin D is important for supporting a large number of physiological processes such as neuromuscular function and bone mineralisation.
  • the preferred amount of vitamin D given to an infant in the first months of life is 800-1000 IU per day, i.e. 20-25 ⁇ g per day.
  • a nutritional composition for example a synthetic nutritional composition, to supply energy to an infant which also contributes to the recommended intakes of vitamin D.
  • An infant is normally fed 5-8 times a day, and the amount of vitamin per serving should therefore not exceed 5.0 ⁇ g vitamin D, preferably the amount per serving should be 3-4 ⁇ g vitamin D.
  • the amount of vitamin D in the nutritional composition is thus preferably from 75 to 125 ⁇ g per 100 g of the total composition, such as from 80 to 120 ⁇ g per 100 g of the total composition, even more preferably from 85 to 110 ⁇ g per 100 g of the total composition.
  • the composition comprises from 0.5 to 10.0 ⁇ g vitamin D per 100 kcal of the composition, such as from 1.0 to 8.0 ⁇ g vitamin D per 100 kcal, preferably from 2.0 to 7.0 ⁇ g vitamin D per 100 kcal, even more preferably from 3.5 to 5.5 ⁇ g vitamin D per kcal of the composition.
  • Vitamin K is important to help blood to clot.
  • the human breast milk contains low amounts of vitamin K and the infants immature intestinal tract may not produce enough vitamin K to meet the infants own needs.
  • he amount of vitamin K in the nutritional composition according to the present invention is preferably from 50 to 400 ⁇ g per 100 g of the total composition, such as from 100 to 300 ⁇ g per 100 g of the total composition, preferably 200 ⁇ g per 100 g of the total composition.
  • the nutritional composition comprises from 1 to 30 ⁇ g vitamin K per 100 kcal, such as form 5 to 20 ⁇ g vitamin K per 100 kcal, preferably from 7 to 15 ⁇ g vitamin K per 100 kcal, even more preferably from 8 to 12 ⁇ g vitamin K per 100 kcal.
  • Vitamin A prevents infections, while vitamin E protects the body from harmful substances and serves as an antioxidant.
  • the daily intake of vitamin A in an infant is preferably from 400 to 1000 ⁇ g/kg/day.
  • the nutritional composition of the invention for example a human milk fortifier, comprises from 1 to 30 mg vitamin A per 100 g of the total composition, such as from 5 to 20 mg per 100 g of the total composition, preferably from 8 to 15 mg per 100 g of the total composition.
  • the composition comprises from 0.1 to 3.0 mg vitamin A per 100 kcal, such as from 0.2 to 2.0 mg vitamin A per 100 kcal, preferably from 0.3 to 1.2 mg vitamin A per 100 kcal, even more preferably from 0.4 to 0.8 mg vitamin A per 100 kcal.
  • the daily intake of vitamin E in an infant is preferably 2.2 to 11 mg per day.
  • the nutritional composition of the invention in particular a human milk fortifier, comprises from 50 to 200 mg vitamin E per 100 g of the total composition, such as from 75 to 150 mg vitamin E per 100 g of the total composition, preferably from 85 to 115 mg vitamin E per 100 g of the total composition.
  • the composition comprises from 1 to 10.0 mg vitamin E per 100 kcal, such as from 2 to 8.0 mg vitamin E per 100 kcal, preferably from 3 to 7 mg vitamin E per 100 kcal, even more preferably from 4 to 6 mg vitamin E per 100 kcal.
  • the composition further comprises one or more mineral.
  • Examples of minerals are sodium, potassium, chloride, calcium, phosphate, magnesium, iron, zinc, copper, selenium, manganese, fluoride, iodine, chromium, or molybdenum.
  • the minerals are usually added in salt form.
  • the minerals may be added alone or in combination.
  • minerals may be iron, zinc, calcium, phosphorus, copper, and magnesium, in particular iron.
  • the mineral is calcium.
  • composition further comprises a protein source.
  • the composition may comprise one or more protein.
  • protein sources based on whey, casein and mixtures thereof may be used as well as protein sources based on soy.
  • the protein source may be based on acid whey or sweet whey or mixtures thereof and may include alpha-lactalbumin and beta-lactoglobulin in any desired proportions.
  • the proteins can be at least partially hydrolyzed in order to enhancement of oral tolerance to allergens, especially food allergens. In that case the composition is a hypoallergenic composition.
  • the nutritional composition according to the invention may be cow's milk whey based infant formula.
  • the formula may also be a hypoallergenic (HA) formula in which the cow milk proteins are (partially or extensively) hydrolysed.
  • the formula may also be based on soy milk or a non-allergenic formula, for example one based on free amino acids.
  • the nutritional composition for example a human milk fortifier, comprises up to 55% protein of the caloric content, for example up to 50%.
  • the composition comprises up to 45% protein, such as up to 40% protein, or up to 35% protein, based on the caloric content.
  • the composition is free of protein. By “free” is hereby meant that the composition may comprise traceable amounts of protein, such as less than 1% protein.
  • protein refers to both proteins derived from a source of protein, to peptides and to free amino acids in general. There can be one or several proteins.
  • protein if present, is made of whey proteins. In another embodiment of the invention, the protein, if present, comprises lactoferrin.
  • the protein(s) in the protein source may be intact or hydrolysed or a combination of intact and hydrolysed proteins.
  • intact means in the context of the present invention proteins where the molecular structure of the protein(s) is not altered according to conventionally meaning of intact proteins.
  • intact is meant the main part of the proteins are intact, i.e. the molecular structure is not altered, for example at least 80% of the proteins are not altered, such as at least 85% of the proteins are not altered, preferably at least 90% of the proteins are not altered, even more preferably at least 95% of the proteins are not altered, such as at least 98% of the proteins are not altered. In a particular embodiment, 100% of the proteins are not altered.
  • hydrolysed means in the context of the present invention a protein which has been hydrolysed or broken down into its component peptides or amino acids.
  • the proteins may either be fully or partially hydrolysed.
  • at least 70% of the proteins are hydrolysed, preferably at least 80% of the proteins are hydrolysed, such as at least 85% of the proteins are hydrolysed, even more preferably at least 90% of the proteins are hydrolysed, such as at least 95% of the proteins are hydrolysed, particularly at least 98% of the proteins are hydrolysed.
  • 100% of the proteins are hydrolysed.
  • Hydrolysation of proteins may be achieved by many means, for example by prolonged boiling in a strong acid or a strong base or by using an enzyme such as the pancreatic protease enzyme to stimulate the naturally occurring hydrolytic process.
  • the protein(s) according to the present invention may also be derived from free amino acids, or a combination of free amino acids and a source of protein, such as whey, lactoferrin and casein.
  • the whey protein may be a whey protein isolate, acid whey, sweet whey or sweet whey from which the caseino-glycomacropeptide has been removed (modified sweet whey).
  • the whey protein is modified sweet whey.
  • Carbohydrates The composition according to the present invention can also contain a carbohydrate source, preferably as prebiotics, or in addition to prebiotics. Any carbohydrate source conventionally found in infant formulae such as lactose, saccharose, maltodextrin, starch and mixtures thereof may be used although the preferred source of carbohydrates is lactose.
  • a carbohydrate source conventionally found in infant formulae such as lactose, saccharose, maltodextrin, starch and mixtures thereof may be used although the preferred source of carbohydrates is lactose.
  • the composition may comprise one or more carbohydrate.
  • the nutritional composition for example a human milk fortifier, comprises up to 40% carbohydrate of the caloric content.
  • the composition comprises up to 35% carbohydrate, such as up to 300% carbohydrate, based on the caloric content.
  • the composition is free of carbohydrate. By “free” it is hereby meant that the composition may comprise traceable amounts of carbohydrates, such as less than 1% carbohydrate.
  • Non limiting examples of carbohydrates include lactose, saccharose, maltodexirin, starch, and combinations thereof.
  • the nutritional composition according to the present invention may optionally comprise other compounds which may have a beneficial effect such as probiotics (like probiotic bacteria) in the amounts customarily found in nutritional compositions to be fed to infants.
  • probiotics like probiotic bacteria
  • Lactobacillus are the most common microbes employed as probiotics. However, other probiotic strains than Lactobacillus may be used in the present nutritional composition, for example the synthetic nutritional composition, for example Bifidobacterium and certain yeasts and bacilli.
  • the probiotic microorganisms most commonly used are principally bacteria and yeasts of the following genera: Lactobacillus spp., Streptococcus spp., Enterococcus spp., Bifidobacterium spp. and Saccharomyces spp.
  • the probiotic is a probiotic bacterial strain.
  • Probiotic bacteria are bacteria which have a beneficial effect on the intestinal system of humans and other animals.
  • it is particularly Bifidobacteria and/or Lactobacilli.
  • a probiotic is a microbial cell preparation or components of microbial cells with a beneficial effect on the health or well-being of the host.
  • Non limiting examples of probiotics include: Bifidobacterium, Lactobacillus, Lactococcus, Enterococcus, Streptococcus, Kluyveromyces, Saccharoymces, Candida, in particular selected from the group consisting of Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium a ni ma lis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus salivarius, Lactobacillus lactis, Lactobacillus rhamnosus, Lactobacillus johnsonii, Lactobacillus plantarum, Lactobacillus salivarius, Lactococcus lactis, Enterococcus faecium, Saccharomyces cerevisiae
  • the composition further comprises one or more probiotic.
  • the nutritional composition according to the present invention comprises one or more prebiotic.
  • the synthetic nutritional composition according to the present invention comprises one or more prebiotic. None limiting examples of prebiotics include: oligosaccharides optionally containing fructose, galactose, mannose; dietary fibers, in particular soluble fibers, soy fibers; inulin; and combinations thereof.
  • Preferred prebiotics are fructo-oligosaccharides (FOS), galacto- oligosaccharides (GOS), isomalto-oligosaccharides (IMO), xylo-oligosaccharides (XOS), arabino-xylo oligosaccharides (AXOS), mannan-oligosaccharides (MOS), oligosaccharides of soy, glycosylsucrose (GS), lactosucrose (LS), lactulose (LA), palatinose-oligosaccharides (PAO), malto-oligosaccharides, gums and/or hydrolysates thereof, pectins and/or hydrolysates thereof, and combinations of the foregoing.
  • FOS fructo-oligosaccharides
  • GOS galacto- oligosaccharides
  • IMO isomalto-oligosaccharides
  • XOS xylo-oligosaccharides
  • oligosaccharide is described in Wrodnigg, T. M.; Stutz, A.E. (1999) Angew. Chem. Int. Ed. 38:827-828 and in WO 2012/069416 which is incorporated herein by reference.
  • the nutritional composition according to present invention may comprise emulsifiers and/or stabilizers such as lecithin, citric esters of mono- and diglycerides, monoglycerides, diglycerides and the like. This is especially the case if the composition is provided as a combination of oils and an aqueous liquid, e.g. as an emulsion.
  • the nutritional composition of the present invention may also optionally comprise other substances which may have a beneficial effect such as nucleotides, nucleosides, and the like in the amount customarily found in nutritional compositions to be fed to infants.
  • optional ingredients may be ones normally known for use on food and nutritional products, in particular infant formulas or infant formula fortifiers, provided that such optional materials are compatible with the essential components described herein, are safe and effective for their intended se, and do not otherwise unduly impair product performance.
  • Non-limiting examples of such optional ingredients include preservatives, anti-oxidants, buffers, colorants, flavours, thickening agents, stabilizers, and other excipients or processing aids.
  • composition according to the present invention may be prepared in any suitable manner.
  • a composition may be prepared by blending together the ingredients, such as lipid, protein and/or carbohydrate in appropriate proportions.
  • emulsifiers may be included in the blend at this stage.
  • the vitamins and minerals may be added at this stage but are usually added later to avoid thermal degradation.
  • Any lipophilic vitamins, such as vitamin A, D, E and K, and emulsifiers may be dissolved into the fat source prior to blending.
  • Water preferably water which has been subjected to reverse osmosis, may then be mixed in to a liquid mixture.
  • the mixture may then be thermally treated to reduce bacterial loads.
  • Any heat sensitive components such as vitamins and minerals may be added after heat treatment.
  • Synthetic Nutritional composition comprising one or more medium chain fatty acid (MCFA) derivative for use in promoting and/or supporting and/or optimizing brain and/or cognitive functions' development in a subject.
  • MCFA medium chain fatty acid
  • Synthetic nutritional composition for use according to anyone of embodiments a) to f) which is a human milk fortifier.
  • Synthetic nutritional composition for use according to embodiment g) which comprises 5 to 40%w/w fatty acid derivatives, wherein 40 to 80%w/w are constituted by MCFA derivatives.
  • Synthetic nutritional composition for use according to embodiment g) or h) which comprises 5 to 30%w/w fatty acid derivatives, wherein 50 to 75%w/w are constituted by MCFA derivatives, 20 to 50%w/w protein and 15 to 40%w/w carbohydrates.
  • Synthetic nutritional composition for use according embodiment j) which comprises MCFA derivatives in amount ranging from ranging from 0.1 to 25%w/w.
  • Synthetic nutritional composition for use according to embodiment j) or k) which comprises fatty acid derivatives in amount ranging from 10 to 40% w/w, MCFA derivatives in amount ranging from 0.1 to 25%w/w, 5 to 50%w/w protein and 10 to 80%w/w carbohydrates.
  • Synthetic nutritional composition according to any of the preceding embodiment, which is a synthetic nutritional composition.
  • MCFA derivatives for the manufacture of a synthetic nutritional composition, for example a synthetic nutritional composition as described in embodiment g) to i) or j) to I), for promoting and/or supporting and/or optimizing brain and/or cognitive functions' development in a subject.
  • Method for promoting and/or supporting and/or optimizing brain and/or cognitive functions' development in an subject in need thereof comprising administering to such subject a synthetic nutritional composition, for example a synthetic nutritional composition as described in embodiment g) to i) or j) to I), comprising one or more medium chain fatty acids (MCFA) derivative.
  • MCFA medium chain fatty acids
  • Synthetic nutritional composition for use according to anyone of the preceding embodiments wherein the brain and/or cognitive functions' development which is promoted and/or supported and/or optimized is selected in the group consisting of: de novo myelination; brain structure, in particular the amount and spatial distribution of myelinated matter throughout the brain, and/or in specific brain regions; brain connectivity; intellectual potential; cognition; cognitive potential; learning potential; cognitive functioning; cognitive skills and abilities; cognitive functioning; and learning.
  • n) Use according to embodiment n) wherein the brain and/or cognitive functions' development which is promoted and/or supported and/or optimized is selected in the group consisting of: de novo myelination; brain structure, in particular the amount and spatial distribution of myelinated matter throughout the brain, and/or in specific brain regions; brain connectivity; intellectual potential; cognition; cognitive potential; learning potential; cognitive functioning; cognitive skills and abilities; cognitive functioning; and learning.
  • a nutritional composition for example a synthetic nutritional composition as described in embodiment g) to i) or j) to I), comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acids.
  • a nutritional composition for example a synthetic nutritional composition as described in embodiment g) to i) or j) to l) context comprising one or more medium chain fatty acids (MCFA) derivative to promote and/or support and /or optimize brain de novo myelination.
  • a nutritional compositions according to the present invention for example a synthetic nutritional composition as described in embodiment g) to i) or j) to l) heap is provided to promote and/or support and /or optimizing brain and/or cognitive functions' development via promotion and/or support and/or optimization of de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acid derivatives and/or via promotion and/or support and/or optimization of brain de novo myelination.
  • a nutritional compositions according to the present invention for example a synthetic nutritional composition as described in embodiment g) to i) or j) to I
  • a nutritional compositions according to the present invention is provided to promote and/or support and /or optimizing brain and/or cognitive functions' development via promotion and/or support and/or optimization of de novo biosynthesis of long chain saturated and/or long chain monounsaturated fatty acid derivatives and/or via promotion and/or support and/or optimization of brain de novo myelination, in an infant who was born preterm or with low-birth weight (LBW) or who experienced intra-uterine growth retardation (IUGR).
  • LLBW low-birth weight
  • IUGR intra-uterine growth retardation
  • Example 1 The impact of the fortification of human milk with a lipid composition comprising according to the invention was tested in premature infants using a lipid free human milk fortifier as a control.
  • the human milk fortifier containing lipids is abbreviated as nHM F and the control human milk fortifier which do not contain added lipids as cHMF.
  • the new fortifier provided 1.4g partially hydrolyzed whey protein, 0.7g lipids (as medium chain triglycerides and docosahexaenoic acid), 1.5g carbohydrate (as maltodextrin), with a blend of micronutrients.
  • the control fortifier (cHMF) was commercially marketed at the start of the trial (FM85 Human Milk Supplement, Nestle, Switzerland), and provided l.Og extensively hydrolyzed whey protein, no lipids, 3.3g carbohydrate (as lactose and maltodextrin), with a blend of micronutrients.
  • the nHMF contained higher concentrations of vitamins A, D, E, K, B6, B12, thiamin, niacin, pantothenic acid, magnesium, iron, zinc, manganese, copper, selenium, sodium, potassium, chloride, choline, inositol, taurine, and ca rnitine compared to cH M F, but both fortifiers contained identical levels of calcium and phosphorus.
  • the estimated composition of preterm HM (20) fortified with each fortifier is presented in Table 1 herebelow.
  • Linoleic acid (LA, mg) - 958.00
  • Blood (0.7 mL) was collected in EDTA-containing vaccutainers from the infant within Dl and again on D21 of life. The blood was immediately centrifuged for 10 min at 1300 x g, and plasma and RBC were stored in microtubes at -80°C until analysis.
  • Plasma lipids were extracted from plasma according to Folch et al. "A simple method for the isolation and purification of total lipids and from animal tissues", J. Biol. Chem. 1957, 226:497-509. he lipid classes were separated by thin-layer chromatography (TLC) and sample migration was performed with hexane/diethyl ether/acetic acid (80/20/1; v/v/v). After drying the lipid classes were visualized by spraying the TLC plate with 1,2- dichlorofluorescein and detected under UV-light. The lipid fractions (PL and TAG) were identified by comparison with standards and were scraped-off to be collected in glass tubes.
  • TLC thin-layer chromatography
  • Standard trimyristoleine and diheptadecanoyl-sn-glycero-3-phosphoethanolamine were added to the TAG and PL extracts, respectively.
  • Fatty acids in plasma TAG and PL were transesterified according to the method of Morrison and Smith, "Preparation of fatty acid methyl esters and dimethylacetals from lipids with boronfluoride- methanol" Journal of Lipid Research, vol.5, 1964 .
  • RBC phospholipid classes separation and Fatty acid methyl esters (FAM E) preparation Lipids were extracted from the RBC according to the method of Peuchant et al., "One- step extraction of human erythrocyte lipids allowing rapid determination of fatty acid composition", Analytical Biochemistry, v:181 i:2 p:341-4, .1989C and PE were sepa rated from RBC lipid extract by TLC and sample migration was performed with chloroform /methanol/acetic acid/water (50/37.5/3.5/2; vol/vol/vol) as migration solvent. PC and PE were visualized by spraying the TLC with 1,2-dichlorofluorescein and detected under UV- light.
  • FAM E Fatty acid methyl esters
  • the lipid fractions from PC and PE were identified by comparison with standards and were scraped-off and collected in glass tubes. Standard diheptadecanoyl-sn-glycero- 3-phosphoethanolamine and -phosphatidylcholine were added to the PE and PC extracts, respectively. FAM E were obtained as described for plasma TAG and PL fractions.
  • FAM E were ana lyzed by gas-liquid chromatograpy (GLC) on a BPX 70 capillary colum n (60 m long, 0.25 ⁇ film, 0.25 mm i.d., SGE, hydrogen as carrier gas, split ratio of 1:80).
  • the GLC system consisted of a gas chromatograph Focus GS (Thermofinnigan, Courtaboeuf, France) equipped with a flame-ionization detector maintained at 250°C. The injector temperature was 250°C. The column temperature was increased from 150°C to 200°C (1.3°C/min), maintained at 200°C for 20 min, increased from 200°C to 235°C (10°C/min), and held at 235°C for 20 min.
  • Fatty acid relative concentration was analysed at visit 5 (log-transformation) using a (mixed-effect) ANCOVA model adjusts for gestational age at day 1, weight at day 1, fatty acid concentration at day 1, gender, center and treatment group (with center considered as random effect).
  • the fatty acid composition of circulating lipids and in particular plasma triacylglycerols (plasma TAG), plasma phospholipids (plasma PL), red blood cells phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) were ana lyzed.
  • Phosphatidylethanolamine fatty acid composition from RCB-PE compartment a recognized marker in human of the fatty acid metabolism and accumulation in tissues and especially brain [see I nnis S, "n-3 fatty acids requirements in the newborn", LI PIDS, Vol. 27, no.11 (1992) and Sauerwald U.
  • ANCOVA model for the log of the sum of monounsaturated fatty acids (M UFA) concentration at day 21 (visit 5) in plasma phospholipids (plasma PL), plasma triacylglycerols (plasma TAG), red blood cells phosphatidylcholine (RBC-PC) a nd red blood cells phosphatidylethanolamine (RBC-PE) with gestational age at day 1, weight at day 1, log of the S AGM I concentration at visit 1, gender and treatment group as cova riates, center considered as a random effect - Estimates, standard errors, 95% confidence intervals for treatment effect are displayed. Two-sided p-value is given for the treatment effect (ITT analysis set) ESTIMATE STD. ERROR 2.50% 97.50% P-VALUE
  • Neurons / Oligodendrocytes were cultured as previously described by Charles et al., 2000. Pregnant female rats of 17 days gestation were killed by cervica l dislocation (Rats Wistar) and the foetuses removed from the uterus. The Forebrains were removed and placed in ice-cold medium of Leibovitz (L15) containing 2% of Penicillin-Streptomycin (PS) and 1% of bovine serum albumin (BSA). Forebrains were dissociated by trypsinisation for 20 min at 37 ⁇ C (Trypsin EDTA IX).
  • PS Penicillin-Streptomycin
  • BSA bovine serum albumin
  • DM EM Dulbecco's modified Eagle's medium
  • FCS foetal calf serum
  • the supernatant was discarded and the cells of pellet were re- suspended in a culture medium consisting of Neurobasal supplemented with 2% of B27, 2 mM of L-glutamine (L Glu), 2% of PS solution, 1 % of FCS and 10 ng/ml of platelet-derived growth factor (PDGF-AA). Viable cells were counted in a Neubauer cytometer using the trypan blue exclusion test. The cells were seeded at a density of 20000 cells/well in 96 well-plates pre-coated with poly-L-lysine and laminin.
  • a culture medium consisting of Neurobasal supplemented with 2% of B27, 2 mM of L-glutamine (L Glu), 2% of PS solution, 1 % of FCS and 10 ng/ml of platelet-derived growth factor (PDGF-AA). Viable cells were counted in a Neubauer cytometer using the trypan blue exclusion test. The cells were seeded at a
  • estradiol The day following seeding (day 1 of culture), cells were incubated with a test com pound (selected from those listed in table 3), or estradiol. Control cells were not incubated with a test compound or estradiol. Estradiol was used as positive control. Estradiol is known to induce OPC (Oligo dendrocytes precursors cells) proliferation. The positive effect of estradiol on OL differentiation has also been demonstrated, as has its effect on the early myelination process. The positive effect of estradiol on neurite outgrowth was also published (for review see Alevaro et al., 2010).
  • the plates were maintained at 37°C in a humidified incubator, in an atmosphere of air (95%)-C02 (5%). Half of the medium was replaced every other day with fresh medium and test compound or control compound. The test or control compounds were maintained at the defined concentration for the duration of the experiments. Compounds were tested on 1 culture (6 wells per conditions). Cells were then used on day 12, 18 or 30 of culture to measure one of either proliferation of OPC, differentiation of OPC into OL and early myelination process (myelin wrapping), or maturation of OL (myelin maturation) and mature myelination process (myelin wrapping).
  • the total number of OPC (number of A2B5 positive cells) was quantified (to evaluate the proliferation), the axonal network was measured (total axonal length (NF)) to assess the effect of the compound on the neuronal network (the quality of the myelination is directly linked to the quality of the axonal network).
  • Differentiation of OPC into OL and myelination process (myelin wrappinfi) - Measurement of number and area of MAG positive cells, overlap MAG/NF wrappiri , and total axonal lenfith (NF)
  • cells were fixed by a cold mixture of absolute ethanol (95%) and pure acetic acid (5%) for 5 min. The cells were then permeabilized and non-specific sites were blocked with a solution of phosphate buffered saline (PBS) containing 0.1% of saponin and 1% FCS for 15 min at room temperature.
  • PBS phosphate buffered saline
  • the total number of OL was quantified (number and area of MAG positive cells) (to evaluate the differentiation process), as well as the wrapping of OPC around axons (overlap MAG/NF wrapping) (myelination process).
  • the axonal network was measured (total axonal length (NF) to assess the effect of the compounds on the neuronal network.
  • the total number of OL was assessed (number and area of MBP positive cells) (to evaluate the OL maturation) as well as the wrapping of myelin around axon (overlap M BP/NF(wrapping)).
  • the axonal network was measured (Total axonal length (N F)) to assess the effect of the compounds on the neuronal network.
  • Results were expressed in terms of cumulated mea n length in ⁇ of neurite network, or myelin sheath labeled for a given marker (MAG or M BP) per field.
  • the overlapping area between NF and MAG or MBP was measured to evaluate the wrapping.
  • PLATE 1 (A2B5 / NF)
  • SA Stearic acid
  • SA Stearic acid
  • SA Stearic acid
  • Feeder layer preparation Dissociation of neonatal cortices and maintenance of mixed glial cultures
  • Tissue were subsequently triturated using a sterile flame-polished glass Pasteur pipette, then 4 mL of mixed glial culture media per brain was added. Cells were centrifuged at 1200 rpm ( ⁇ 300 g) for 5 min, then cells were resuspended in warm mixed glial culture media and plated into PLL-coated flask.
  • Hippocampal neurons were isolated from embryonic (E18) pups of Sprague Dawley rats. Briefly, following animal sacrifice, brains were isolated, meninges removed from the medial aspect of the cerebral hemispheres, then hippocampi dissected out and kept at 4°C until process completion.
  • mixed glia culture medium containing microglia and OPCs cells were collected and pre-plated on P100 petri dish (not treated for culture) for 30 minutes in order to purify OPCs cells; microglia cells start immediately to adhere to petri while OPCs cells remained in the surnatant medium.
  • Pen/Strep (0.33% from stock) 33 units/mL Penicillin and 33 ⁇ g/mL Streptomycin
  • Bovine insulin from 1 mg/mL stock

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pediatric Medicine (AREA)
  • Biophysics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention concerne une composition nutritionnelle visant à maintenir ou favoriser un état de santé caractérisé par un développement optimal du cerveau et des fonctions cognitives et/ou à prévenir les déficits neurocognitifs. Cette composition est destinée à être utilisée chez les mammifères, de préférence chez l'être humain et, par exemple, chez les nourrissons.
PCT/EP2016/080792 2016-03-30 2016-12-13 Compositions nutritionnelles et leur utilisation WO2017167418A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
BR112018067926A BR112018067926A2 (pt) 2016-03-30 2016-12-13 composições nutricionais e seus usos
AU2016401061A AU2016401061A1 (en) 2016-03-30 2016-12-13 Nutritional compositions and their use
EP16823175.1A EP3435787A1 (fr) 2016-03-30 2016-12-13 Compositions nutritionnelles et leur utilisation
RU2018138024A RU2018138024A (ru) 2016-03-30 2016-12-13 Питательные композиции и их применение
US16/089,124 US20190104759A1 (en) 2016-03-30 2016-12-13 Nutritional compositions and their use
MX2018011335A MX2018011335A (es) 2016-03-30 2016-12-13 Composiciones nutritivas y su uso.
CN201680083179.9A CN108777997A (zh) 2016-03-30 2016-12-13 营养组合物及其用途
PH12018550151A PH12018550151A1 (en) 2016-03-30 2018-09-05 Nutritional compositions and their use

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201662315187P 2016-03-30 2016-03-30
US201662315280P 2016-03-30 2016-03-30
US62/315,280 2016-03-30
US62/315,187 2016-03-30
US201662328047P 2016-04-27 2016-04-27
US62/328,047 2016-04-27
EP16169351.0 2016-05-12
EP16169351 2016-05-12

Publications (1)

Publication Number Publication Date
WO2017167418A1 true WO2017167418A1 (fr) 2017-10-05

Family

ID=55967160

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2016/080792 WO2017167418A1 (fr) 2016-03-30 2016-12-13 Compositions nutritionnelles et leur utilisation

Country Status (5)

Country Link
EP (1) EP3435787A1 (fr)
CN (1) CN108777997A (fr)
AU (1) AU2016401061A1 (fr)
BR (1) BR112018067926A2 (fr)
WO (1) WO2017167418A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020089291A1 (fr) * 2018-10-30 2020-05-07 Société des Produits Nestlé S.A. Compositions nutritionnelles, leur utilisation dans la réduction de stress métabolique et procédé de réduction de stress métabolique
WO2022200526A1 (fr) * 2021-03-24 2022-09-29 Ammeva Gmbh Lait maternel déshydraté destiné à être utilisé comme complément alimentaire, aliment à usage médical particulier et aliment complet pour nourrissons

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5886037A (en) * 1996-11-20 1999-03-23 N.V. Nutricia Nutritional composition for the treatment of hypertriglyceridaemia and hyperchylomicronaemia
EP2436275A1 (fr) * 2007-06-26 2012-04-04 N.V. Nutricia Composition de lipides pour améliorer la fonction cérébrale
WO2012069416A1 (fr) 2010-11-23 2012-05-31 Nestec S.A. Mélange d'oligosaccharides et produit alimentaire, notamment préparation pour nourrissons, comprenant ledit mélange
WO2014166790A1 (fr) * 2013-04-10 2014-10-16 Nestec S.A. Lait infantile à teneur faible en acides gras à chaîne moyenne et à teneur relativement élevée en acides gras insaturés, et son utilisation pour favoriser le bon établissement des fonctions cognitives chez les nourrissons
US20140322425A1 (en) * 2005-03-09 2014-10-30 Abbott Laboratories Concentrated human milk fortifier liquid
WO2016050754A1 (fr) * 2014-09-30 2016-04-07 Nestec S.A. Composition nutritionnelle à faible teneur en acides gras à chaîne moyenne dans des proportions spécifiques, et ses utilisations

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007108690A1 (fr) * 2006-03-23 2007-09-27 N.V. Nutricia Formule pour prématurés
SE536599C3 (sv) * 2012-04-10 2017-01-10 Hero Ag Näringssammansättning med lågt kalori- och lågt proteininnehåll
RU2648375C2 (ru) * 2013-04-10 2018-03-26 Нестек С.А. Детская смесь с низким содержанием жирных кислот со средней длиной цепи в определенных пропорциях и ее применение при стимуляции и/или обеспечении сбалансированного роста грудных детей

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5886037A (en) * 1996-11-20 1999-03-23 N.V. Nutricia Nutritional composition for the treatment of hypertriglyceridaemia and hyperchylomicronaemia
US20140322425A1 (en) * 2005-03-09 2014-10-30 Abbott Laboratories Concentrated human milk fortifier liquid
EP2436275A1 (fr) * 2007-06-26 2012-04-04 N.V. Nutricia Composition de lipides pour améliorer la fonction cérébrale
WO2012069416A1 (fr) 2010-11-23 2012-05-31 Nestec S.A. Mélange d'oligosaccharides et produit alimentaire, notamment préparation pour nourrissons, comprenant ledit mélange
WO2014166790A1 (fr) * 2013-04-10 2014-10-16 Nestec S.A. Lait infantile à teneur faible en acides gras à chaîne moyenne et à teneur relativement élevée en acides gras insaturés, et son utilisation pour favoriser le bon établissement des fonctions cognitives chez les nourrissons
WO2016050754A1 (fr) * 2014-09-30 2016-04-07 Nestec S.A. Composition nutritionnelle à faible teneur en acides gras à chaîne moyenne dans des proportions spécifiques, et ses utilisations

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
CARNIELLI V P ET AL: "Medium-chain triacylglycerols in formulas for preterm infants: Effect on plasma lipids, circulating concentrations of medium-chain fatty acids, and essential fatty acids", THE AMERICAN JOURNAL OF CLINICAL NUTRITION, AMERICAN SOCIETY FOR NUTRITION, US, vol. 64, no. 2, 1 August 1996 (1996-08-01), pages 152 - 158, XP009171933, ISSN: 0002-9165 *
DEONI SEAN C L ET AL: "Breastfeeding and early white matter development: A cross-sectional study", NEUROIMAGE, vol. 82, 15 November 2013 (2013-11-15), pages 77 - 86, XP028705588, ISSN: 1053-8119, DOI: 10.1016/J.NEUROIMAGE.2013.05.090 *
DEONI: "Breastfeeding and early white matter development: a cross sectional study", NEUROLMAGE, vol. 82, 2013, pages 77 - 86
FOLCH ET AL.: "A simple method for the isolation and purification of total lipids and from animal tissues", J. BIOL. CHEM., vol. 226, 1957, pages 497 - 509
GIBSON GR; ROBERFROID MB.: "Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics", J NUTR., vol. 125, 1995, pages 1401 - 12
INNIS S: "n-3 fatty acids requirements in the newborn", LIPIDS, vol. 27, no. 11, 1992
J. PEDIATR., vol. 155, 2009, pages 344 - 9
MORRISON; SMITH: "Preparation of fatty acid methyl esters and dimethylacetals from lipids with boronfluoride-methanol", JOURNAL OF LIPID RESEARCH, vol. 5, 1964
PEUCHANT ET AL.: "One-step extraction of human erythrocyte lipids allowing rapid determination of fatty acid composition", ANALYTICAL BIOCHEMISTRY, vol. 181 I, no. 2, pages 341 - 4
RAMIREZ M ET AL: "Plasma and red blood cell fatty acid composition in smallfor gestational age term infants fed human milk or formula", CLINICAL NUTRITION, CHURCHILL LIVINGSTONE, LONDON, GB, vol. 17, no. 4, 1 August 1998 (1998-08-01), pages 177 - 183, XP004680260, ISSN: 0261-5614, DOI: 10.1016/S0261-5614(98)80054-X *
SAUERWALD U. ET AL., EFFECT OF DIFFERENT LEVELS OF DHA SUPPLY ON FATTY ACID STATUS AND LA AND ALA CONVERSION ON PRETERM INFANTS, vol. 4, no. 3, March 2012 (2012-03-01)
SVENNERHOLML.: "Myelination and Demyelination", 1978, article "Lipid and fatty acid composition of human cerebral myelin during development"
WRODNIGG, T. M.; STUTZ, A.E., ANGEW. CHEM. INT. ED., vol. 38, 1999, pages 827 - 828

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020089291A1 (fr) * 2018-10-30 2020-05-07 Société des Produits Nestlé S.A. Compositions nutritionnelles, leur utilisation dans la réduction de stress métabolique et procédé de réduction de stress métabolique
WO2022200526A1 (fr) * 2021-03-24 2022-09-29 Ammeva Gmbh Lait maternel déshydraté destiné à être utilisé comme complément alimentaire, aliment à usage médical particulier et aliment complet pour nourrissons

Also Published As

Publication number Publication date
AU2016401061A1 (en) 2018-08-16
CN108777997A (zh) 2018-11-09
BR112018067926A2 (pt) 2019-01-02
EP3435787A1 (fr) 2019-02-06

Similar Documents

Publication Publication Date Title
US20220378078A1 (en) Compositions and their use
US11026444B2 (en) Composition comprising human milk oligosaccharides (HMO) for use in the improvement of short term memory and other cognitive benefits
US20210268005A1 (en) Composition comprising human milk oligosaccharides for use in improving, enhancing, promoting or modulating a gabaergic function in the central nervous system
WO2017167415A1 (fr) Compositions comprenant des acides gras et leur utilisation
EP3436032A1 (fr) Compositions comprenant des minéraux et leur utilisation
EP4233905A2 (fr) Compositions nutritionnelles et préparations pour nourrissons pour favoriser la myélinisation dans le cerveau
US20180360091A1 (en) Nutritional compositions and infant formulas to promote myelination in the brain
WO2017167417A1 (fr) Compositions comprenant de la choline et leur utilisation
WO2017167416A1 (fr) Compositions comprenant un phospholipide et leur utilisation
WO2017167418A1 (fr) Compositions nutritionnelles et leur utilisation
EP4205560A1 (fr) Compositions nutritionnelles et préparations pour nourrissons permettant de favoriser la myélinisation dans le cerveau
EP4233908A2 (fr) Compositions nutritionnelles et préparations pour nourrissons permettant de favoriser la myélinisation dans le cerveau
US20180360093A1 (en) Nutritional compositions and infant formulas to promote myelination in the brain
US20190104759A1 (en) Nutritional compositions and their use
RU2810236C2 (ru) Композиция, содержащая олигосахариды грудного молока, для применения в улучшении, усилении, стимуляции или модулировании гамкергической функции в центральной нервной системе
RU2819351C2 (ru) Композиция, содержащая олигосахариды грудного молока, для применения в улучшении, усилении, стимулировании или модулировании серотонинергической функции в центральной нервной системе
RU2791622C2 (ru) Композиция, содержащая олигосахариды грудного молока (огм), для применения в улучшении кратковременной памяти и получении других когнитивных преимуществ
US20220000164A1 (en) Nutritional compositions, their use in reducing metabolic stress and method of reducing metabolic stress

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref document number: 2016401061

Country of ref document: AU

Date of ref document: 20161213

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: MX/A/2018/011335

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112018067926

Country of ref document: BR

WWE Wipo information: entry into national phase

Ref document number: 2016823175

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2016823175

Country of ref document: EP

Effective date: 20181030

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16823175

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 112018067926

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20180905