WO2008108651A1 - Infant foods with optimized amino acid composition - Google Patents

Infant foods with optimized amino acid composition Download PDF

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Publication number
WO2008108651A1
WO2008108651A1 PCT/NL2008/050133 NL2008050133W WO2008108651A1 WO 2008108651 A1 WO2008108651 A1 WO 2008108651A1 NL 2008050133 W NL2008050133 W NL 2008050133W WO 2008108651 A1 WO2008108651 A1 WO 2008108651A1
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WIPO (PCT)
Prior art keywords
infant food
ratio
food
infant
acid
Prior art date
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PCT/NL2008/050133
Other languages
French (fr)
Inventor
Cornelis Glas
Anne Schaafsma
Original Assignee
Friesland Brands B.V.
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Publication date
Application filed by Friesland Brands B.V. filed Critical Friesland Brands B.V.
Priority to EP08723884A priority Critical patent/EP2134186A1/en
Publication of WO2008108651A1 publication Critical patent/WO2008108651A1/en

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Classifications

    • 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 OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/15—Reconstituted or recombined milk products containing neither non-milk fat nor non-milk proteins
    • A23C9/1512—Reconstituted or recombined milk products containing neither non-milk fat nor non-milk proteins containing isolated milk or whey proteins, caseinates or cheese; Enrichment of milk products with milk proteins in isolated or concentrated form, e.g. ultrafiltration retentate
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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 invention relates to food compositions, such as infant food and dietary supplements for children.
  • the invention relates to infant foods which have a favorable effect on brain development, and the development and/or use of the cognitive skills of a child. It is known from research into the relation between food in an early stage of life, body growth and learning development at a later age that early unhealthy or suboptimal dietary habits can cause problems in the development of the brains. As a result, there is a risk of a learning ability deviating from the norm and a lower IQ. If the dietary habits still improve after a bad start, then a growth spurt occurs, where the (length) retardation is for the most part made up for. However, the cognitive developmental delay often remains.
  • omega-3 and omega-6 fatty acids which are said to be proven to be important for the retina function and the brain function.
  • the product is available in a liquid variant, especially for children who find it difficult to swallow pills.
  • omega-3 and omega-6 fatty acids such as docosahexaenoic acid (DHA) and arachidonic acid (AA).
  • the invention contemplates providing a food or supplement which contributes to an optimal development and/or use of the cognitive skills during the first years of life of a child, i.e. from birth to about 7 years.
  • the child preferably has no congenital metabolic disorder, such as for instance phenylketonuria (PKU).
  • PKU phenylketonuria
  • the term 'cognitive skills' comprises a range of passive and active mental activities directed to taking in, processing, assessing, applying and (re)producing information, such as listening, reading, remembering, speaking, writing, seeing, understanding, judging and deciding.
  • the invention therefore relates to a method for selecting an infant food which has a favorable effect on the development and/or use of the cognitive skills of a child, comprising determining the age of the child and correlating the age with an infant food optimal for that age, where an age of 1 year at most is correlated with an infant food with a tryptophan : tyrosine ratio based on weight (T/T ratio) of > 0.3 and where an age from 1 year is correlated with an infant food with a T/T ratio of ⁇ 0.3.
  • This selection method makes it possible to choose food which, depending on the age of a child, supports the development and use of cognitive skills as well as possible. Infant foods with different T/T ratios are known per se from the prior art.
  • US 6,506,422 for instance relates to a food based on casein glycomacropeptide (cGMP) intended for infants and children who suffer from phenylketonuria (PKU). It discloses a food for infants and children of up to 2 years with a T/T ratio of 0.386, and an infant food intended for children from 2 years with a T/T ratio of 0.25.
  • cGMP casein glycomacropeptide
  • PKU phenylketonuria
  • US 6,506,422 does not link the T/T ratio to the development of cognitive skills.
  • it does not teach that the T/T ratio as it is found in mother's milk should already be reduced at a very young age (around an age of 12 months) in order to stimulate the cognitive development of the child as well as possible.
  • WO2004/112507 discloses an infant or "follow-on" formula comprising at least one long-chain polyunsaturated fatty acid (LC-PUFA) and at least one probiotic, and the use thereof for stimulating the immune system and a healthy mental development of infants and young children. It teaches that the amino acid composition is preferably similar to that of mother's milk.
  • LC-PUFA long-chain polyunsaturated fatty acid
  • the T/T ratio of an example formula is 0.53.
  • WO2004/112507 attributes the effects on the mental development to the fatty acids, and nothing teaches or suggests the importance of the T/T ratio for the mental development.
  • the present invention provides a method for supporting and/or optimizing the development and/or use of the cognitive skills of a child, comprising selecting an infant food according to above -described selection method, followed by preparing the selected infant food and administering the prepared infant food to the child. For instance, for an infant aged 1 year at most, an infant food with a
  • an infant food can be selected with a T/T ratio of > 0.45, preferably ⁇ 0.45 and ⁇ 0.8. In the following period of 7 up to 12 months, for instance, a food can be chosen with a T/T ratio lower than 0.45.
  • the invention further provides a method for selecting an infant food which as a favorable effect on the development and/or use of the cognitive skills of a child, comprising determining the age of the child and correlating the age with an infant food optimal for that age, where an age from 1 year is correlated with an infant food with a T/T ratio of ⁇ 0.3.
  • the T/T ratio of the infant food after the first year of life is preferably between about 0.1 and 0.3.
  • Trp and Tyr are both part of the group of amino acids which are essential for children, and the importance of the presence of essential amino acids in infant food is known.
  • the aim is to approximate the composition of mother's milk.
  • the amino acid composition of an infant food is based on the amino acid composition of an infant food based on the amino acid composition of the nutritive protein fraction of mother's milk.
  • Human milk is relatively rich in Trp, mainly as a result of the Trp-containing proteins ⁇ -lactalbumin, immunoglobulin A and lactoferrin. However, the latter two are not or hardly used.
  • the Trp/Tyr ratio in most known infant foods approximates that of mother's milk, i.e. 0.4 or more. It is known that Trp, a precursor for the neurotransmitters serotonin and melatonin, makes an important contribution to a healthy sleep pattern. See for instance Heine et al, (Amino
  • Trp in mother's milk follows a circadian rhythm, with a peak at 3:00 am. This was found to be correlated with a peak at 6.00 pm for metabolite 6-sulphatoxymelatonin in the urine of infants who were exclusively fed with mother's milk (Cubero et al Neuro Endocrinol Lett. 2005 Dec;26(6):657-61). This finding has resulted in a set of two infant formulas for regulating the day /night rhythm, consisting of a 'day formula' with a Trp content of maximally 1.7 g/100 g of protein and a 'night formula' with minimally 3.5 g/100 g of protein (WO2006/034955).
  • Trp transporter mechanism for the "large neutral amino acids" as they are known in the field abbreviated as "LNAA”.
  • LNAA low neutral amino acids
  • Trp transport through the blood-brain barrier is competitively influenced by the concentration of these LNAA.
  • the Trp/LNAA ratio in plasma is therefore very important for the availability of Trp, and accordingly serotonin synthesis, in the brains.
  • the Trp/LNAA ratio in mother's milk is about 0.056 while this is 0.041 in cow's milk.
  • Alpha lactalbumin contains a relatively high content of Trp compared to leucine, isoleucine, valine, phenylalanine, tyrosine and methionine.
  • Trp/LNAA ratio In order to achieve the desired Trp/LNAA ratio in infant food, it has generally been accepted to enrich cow's milk -based infant food with cow's milk alpha lactalbumin or the hydrolysate thereof. See for instance Heine et al. (1996, Acta Paediatr. 85:1024-8); WO98/14204 and WO03/055322.
  • Dutch patent NL1025900 in the name of applicant indicates that it can also have an advantage to include, in addition to alpha lactalbumin, extra proline in the food.
  • EP0951842 teaches a preferred Trp/LNAA ratio in infant food of 4.8- 10: 100, in combination with relatively high levels of folic acid, vitamin B6 and vitamin B 12.
  • Tyr is known to be a precursor of the neurotransmitters dopamine, noradrenaline and adrenaline. Receptors for these neurotransmitters are present in areas of the nervous system involved in regulating movement, mood, attention and functions of the intestines.
  • US2006/0030625 describes a dietary supplement for the treatment of a neurotransmitter deficiency, comprising a neurotransmitter precursor such as DOPA, tyrosine and 5- hydroxytryptophan, in combination with a cofactor activating the synthesis of a neurotransmitter.
  • Trp supply
  • LNAA large, neutral amino acids
  • an infant food is prepared with the desired T/T ratio.
  • the term 'infant food' comprises both protein-containing dietary supplements and complete formulas providing the complete nutrition of an infant or child, such as a formula for infants or prematurely born infants. It may also be a so-called "follow -on" milk, which can be used after about the first 6 months, such as for instance for the preparation of porridge.
  • An infant food according to the invention typically relates to a complete formula comprising a protein source, a carbohydrate source, a lipid source and the conventional minerals and vitamins.
  • An infant food according to the invention may be based on a known infant food based on (hydrolyzed) cow's milk proteins, such as casein, whey proteins or mixtures thereof, but also based on vegetable proteins, such as proteins from cereals and legumes.
  • Trp and Tyr may also be present in the form of intact proteins, protein fragments (e.g. hydrolysates) and/or free L-amino acids or salts thereof. If free amino acids are used, it is important to remove any pollutions which may cause a toxic reaction.
  • Tyr and/or Trp is present in the form of a protein or protein hydrolysate.
  • proteins or protein hydrolysates may be selected by their T/T ratio.
  • one or more milk proteins and/or hydrolysates thereof are used.
  • Table 1 below provides an overview of the Trp and Tyr contents of suitable milk protein sources for the preparation of a product with a high T/T ratio (at least 0.3) and/or for the preparation of a product with a low T/T ratio (less than 0.3).
  • a skilled person can combine two or more protein sources to achieve the desired T/T ratio.
  • Suitable milk protein sources include demineralized whey protein powder such as Deminal ⁇ O (Friesland Foods Domo, The Netherlands), protein obtained from whey coming from cheese preparation with rennet and after desalination, whey protein from acid whey, coming from acid casein preparation, whey protein hydrolysate, alpha lactalbumin, glycomacropeptide (cGMP), casein, beta casein, alpha s-casein and casein hydrolysate.
  • Deminal ⁇ O Franceland Foods Domo, The Netherlands
  • protein obtained from whey coming from cheese preparation with rennet and after desalination whey protein from acid whey, coming from acid casein preparation, whey protein hydrolysate, alpha lactalbumin, glycomacropeptide (cGMP), casein, beta casein, alpha s-casein and casein hydrolysate.
  • cGMP glycomacropeptide
  • mother's milk has a ratio of 0.53.
  • a whey protein derivate is used which is obtained from the permeate after microfiltration of skimmed milk.
  • a derivate has a T/T ratio from about 0.57 to about 0.73.
  • casein and whey protein coming from sweet, desalinated whey is used.
  • the relative proportion of casein/whey protein is adjusted, optionally in combination with addition of extra amino acids, for instance in the form of free L-Trp and/or L-Pro (see Example 1).
  • casein as a protein source
  • casein hydrolysates for the preparation of an infant food for infants and children with cow's milk allergy, or an increased risk of developing this, the use of casein as a protein source is preferred, in particular (extensive) casein hydrolysates.
  • the T/T ratio can be increased by supplementing with (free) Trp.
  • a selected infant food contains no more than 7 grams of the amino acid threonine (Thr) and/or at least 3.5 grams of phenyl alanine (Phe) per 100 grams of protein.
  • a carbohydrate source any type of carbohydrate or mixture of two or more different carbohydrates, which are typically used in infant food formulas, can be used. Suitable carbohydrate sources are disaccharides such as lactose and saccharose, monosaccharides, such as glucose, and maltodextrins, starch and carbohydrate sources with a prebiotic effect. Carbohydrates with a high glycemic index, such as glucose and maltodextrin, can increase the Trp/LNAA ratio in the blood.
  • the lipid source in an infant food according to the invention with a specific T/T ratio may be any lipid or combination of lipids which is suitable for use in infant food.
  • suitable lipid sources are tri, di and monoglycerides, phospholipids, sphingolipids, fatty acids and esters or salts thereof.
  • the lipids may have an animal, vegetable, microbial or synthetic origin.
  • GLA gamma-linolenic acid
  • DHGLA di-homo-gamma-linolenic acid
  • AA arachidonic acid
  • SA stearidonic acid
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • DPA docosapentaenoic acid
  • CLA conjugated linoleic acid
  • CLA is important in the protection against eczema and respiratory diseases in children. This is particularly the case for the cis-9, trans-11 and trans-10, cis-12 isomers of CLA.
  • AA can be added to the composition with a view to an optimal tolerance induction against protein allergy.
  • a selected infant food contains at least docosahexaenoic acid (DHA), linolenic acid (LA) and/or alpha linolenic acid (ALA).
  • DHA docosahexaenoic acid
  • LA linolenic acid
  • ALA alpha linolenic acid
  • the DHA content is 0.1-1.0% based on the total fat content.
  • the LA/ALA ratio is preferably between 4:1 and 20:1, more preferably between 5:1 and 10:1.
  • the infant food may contain one or more conventional micro ingredients such as vitamins, antioxidants, minerals, free amino acids (such as proline, glutamate), nucleotides, taurine, carnitine, choline and polyamines.
  • antioxidants examples include BHT, ascorbyl palmitate, vitamin E, alpha and beta carotene, lutein, zeaxanthin, lycopene and phospholipids.
  • BHT ascorbyl palmitate
  • vitamin E alpha and beta carotene
  • lutein zeaxanthin
  • lycopene phospholipids.
  • micro nutrients which can be important to brain development and/or brain function
  • higher doses can be used.
  • Such ingredients are, for instance, DHA, choline and taurine.
  • the selected infant food contains, for instance, at least 0.04 g of choline per 100 g of dry matter.
  • Choline may be present in different forms, for instance in the form of choline salt (such as choline chloride) and/or choline -containing lipids (such as phosphatidyl choline or a lipid mixture known by the name lecithin).
  • the selected infant food may contain at least 0.03 g of taurine per 100 g of dry matter.
  • the infant food comprises both choline and taurine, still more preferably in combination with DHA and/or precursors thereof, such as ALA and EPA.
  • an infant food may be selected to which one or more probiotic bacterial strains are added.
  • Probiotics generally have a favorable effect on the digestibility of the infant food.
  • some probiotics can stimulate the tolerance to milk proteins.
  • an infant food contains a strain chosen from the group consisting of Bifidobacterium strains and lactic acid-forming strains, such as the lactic acid-forming Lactobacillus and Streptococcus groups.
  • a probiotic is present in an amount of minimally 10exp6 to 10exp7 colony -forming units per strain per gram of product.
  • the selected infant food comprises a prebiotic, preferably chosen from fructo and/or galacto-oligosaccharides, with short or long chains, inulin, fucose -containing oligosaccharides, beta glycans, carob flour, gums, pectins, sialyloligosaccharides, sialyllactose, galactans with short or long chains, and nucleotides.
  • a prebiotic preferably chosen from fructo and/or galacto-oligosaccharides, with short or long chains, inulin, fucose -containing oligosaccharides, beta glycans, carob flour, gums, pectins, sialyloligosaccharides, sialyllactose, galactans with short or long chains, and nucleotides.
  • fucose-containing oligosaccharides as they are present in mother's milk. According to a surprising finding of the inventors,
  • fuco-oligosaccharides have immune-modulating and tolerance -increasing properties, particularly in children who are hereditarily predisposed to develop an allergy to milk proteins. They can also increase resistance and/or tolerance in case of infections by pathogens.
  • the infant food to be selected contains, for instance, up to 8 grams of fuco-oligosaccharides per 100 g of dry matter.
  • the selected infant food may have a liquid or powder form, the latter needing to be reconstituted with a liquid, typically water, before use.
  • a liquid typically water
  • suitable packages for such products Liquid products may, for instance, be packaged in bottles, cans or cartons from laminated cardboard. Powdery products may be packaged in sachets, vacuum packages or cans.
  • a further aspect of the present invention relates to a container comprising a product combination of at least one first infant food for use during the first year of life with a T/T ratio of ⁇ 0.3 and a second infant food for use after the first year of life with a T/T ratio of ⁇ 0.3.
  • a set or kit of different products also referred to as "kit-of-parts”
  • kit-of-parts is, for instance, a "family-sized package” with foods for infants and/or children within one family who belong to different age groups.
  • the container contains the product combination of a) a powdery infant formula with a T/T ratio of 0.45-0.60 and b) a powdery toddler formula with a T/T ratio of 0.27- 0.29.
  • the container contains at least three different infant foods, each with a different T/T ratio and adjusted to a different age group. It comprises, for instance, an infant food with a T/T ratio between 0.45 and 0.8 for a baby of 0-6 months, an infant food with a T/T ratio between 0.3 and 0.45 for use during 6-12 months and an infant food with a T/T ratio lower than 0.3 for use from 1 year.
  • the Thr content is no more than 7 grams per 100 grams of protein, and/or the Phe content is at least 3.5 grams per 100 grams of protein.
  • Foods were prepared for infants in the age groups 0- ⁇ 6 months, 6-12 months and >12 months.
  • the ratio of casein (coming from skimmed milk) was reduced relative to whey protein coming from sweet desalinated whey as the age advanced. Only the formula for the age group of 0-6 months was also enriched with the amino acid tryptophan.
  • the casein (48 parts alpha + 36 parts beta + 16 parts kappa + gamma) contained a TRP content of 1.7 grams per 100 grams of protein and a TYR content of 6.3 grams per 100 grams of protein.
  • the whey protein coming from the sweet desalinated whey contained per 100 grams of protein: 1.7 grams of TRP and 2.4 grams of TYR.
  • compositions per age group are shown, as well as the T/T ratios which were supplied per age group.
  • Foods were prepared for infants in the age groups of 0- ⁇ 6 months, 6- 12 months and > 12 months.
  • the ratio of casein was kept constant relative to different types of "whey protein derivates". All foods were enriched with 5% fuco-oligosaccharides, while, in the food intended for the group of 0-6 months, extra tryptophan was included.
  • the casein had a TRP content of 1.7 grams per 100 grams of protein and a TYR content of 6.3 grams per 100 grams of protein.
  • the whey protein derivates and their contents of TRP and TYR are indicated in the table below. The table also indicates the compositions and T/T ratios of the foods supplied per age group.
  • the T/T ratio for the first year of life is similar to that of mother's milk.

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Abstract

The invention relates to food compositions, such as infant food and dietary supplements for children. In particular, it relates to infant foods which have a favorable effect on the cognitive skills of a child. The invention provides a method for selecting an infant food which contributes to the development and/or use of the cognitive skills of a child, comprising determining the age of the child and selecting a food optimal for that age, wherein, for an age of 1 year at most, an infant food with a tryptophan : tyrosine ratio based on weight (T/T ratio) of ≥ 0.3 is selected and wherein, for an age from 1 year, an infant food with a T/T ratio < 0.3 is selected.

Description

Title: Infant foods with optimized amino acid composition
The invention relates to food compositions, such as infant food and dietary supplements for children. In particular, the invention relates to infant foods which have a favorable effect on brain development, and the development and/or use of the cognitive skills of a child. It is known from research into the relation between food in an early stage of life, body growth and learning development at a later age that early unhealthy or suboptimal dietary habits can cause problems in the development of the brains. As a result, there is a risk of a learning ability deviating from the norm and a lower IQ. If the dietary habits still improve after a bad start, then a growth spurt occurs, where the (length) retardation is for the most part made up for. However, the cognitive developmental delay often remains.
The development of (infant) foods and supplements which contribute to a good learning ability has recently received a lot of attention. It meets the wish of many parents to offer their children an optimal start in life as early as possible. Thus, dietary supplements have been developed to support the eye function and the brain function. These often contain omega-3 and omega-6 fatty acids which are said to be proven to be important for the retina function and the brain function. The product is available in a liquid variant, especially for children who find it difficult to swallow pills. There is also infant food with added omega-3 and omega-6 fatty acids, such as docosahexaenoic acid (DHA) and arachidonic acid (AA). Recently, a low -fat margarine was introduced with the fatty acid DHA therein, which was said to contribute to a healthy development of the brains. It is an object of the present invention to provide a food or supplement which can make a favorable contribution to the development of the brains, and the development and/or use of the cognitive skills of the child. In particular, the invention contemplates providing a food or supplement which contributes to an optimal development and/or use of the cognitive skills during the first years of life of a child, i.e. from birth to about 7 years. The child preferably has no congenital metabolic disorder, such as for instance phenylketonuria (PKU). The term 'cognitive skills' comprises a range of passive and active mental activities directed to taking in, processing, assessing, applying and (re)producing information, such as listening, reading, remembering, speaking, writing, seeing, understanding, judging and deciding.
One or more of above-mentioned objects can be achieved on the basis of the insight of the present inventors that, depending on the age of the child, the ratio of the alpha amino acids L -tryptophan (Trp) to L-tyrosine (Tyr) in the food is important for a good cognition. More in particular, it is an object to use, in the first stage of life, a food with a Trp/Tyr ratio which is optimal for the structuring of the brains, the wellbeing and the sleep pattern of the child, to then timely (in this case from the first year of life) switch to a second stage in which further development and use of the brains is favored by use of a food with a lower Trp/Tyr ratio optimal for these purposes.
The invention therefore relates to a method for selecting an infant food which has a favorable effect on the development and/or use of the cognitive skills of a child, comprising determining the age of the child and correlating the age with an infant food optimal for that age, where an age of 1 year at most is correlated with an infant food with a tryptophan : tyrosine ratio based on weight (T/T ratio) of > 0.3 and where an age from 1 year is correlated with an infant food with a T/T ratio of < 0.3. This selection method makes it possible to choose food which, depending on the age of a child, supports the development and use of cognitive skills as well as possible. Infant foods with different T/T ratios are known per se from the prior art. US 6,506,422 for instance relates to a food based on casein glycomacropeptide (cGMP) intended for infants and children who suffer from phenylketonuria (PKU). It discloses a food for infants and children of up to 2 years with a T/T ratio of 0.386, and an infant food intended for children from 2 years with a T/T ratio of 0.25. However, US 6,506,422 does not link the T/T ratio to the development of cognitive skills. In addition, it does not teach that the T/T ratio as it is found in mother's milk should already be reduced at a very young age (around an age of 12 months) in order to stimulate the cognitive development of the child as well as possible. WO2004/112507 discloses an infant or "follow-on" formula comprising at least one long-chain polyunsaturated fatty acid (LC-PUFA) and at least one probiotic, and the use thereof for stimulating the immune system and a healthy mental development of infants and young children. It teaches that the amino acid composition is preferably similar to that of mother's milk.
The T/T ratio of an example formula is 0.53. WO2004/112507 attributes the effects on the mental development to the fatty acids, and nothing teaches or suggests the importance of the T/T ratio for the mental development.
Further, the present invention provides a method for supporting and/or optimizing the development and/or use of the cognitive skills of a child, comprising selecting an infant food according to above -described selection method, followed by preparing the selected infant food and administering the prepared infant food to the child. For instance, for an infant aged 1 year at most, an infant food with a
T/T ratio > 0.3 and < 1.0 is selected.
More in particular, for an infant aged 0 to 6 months, an infant food can be selected with a T/T ratio of > 0.45, preferably ≥ 0.45 and < 0.8. In the following period of 7 up to 12 months, for instance, a food can be chosen with a T/T ratio lower than 0.45. The invention further provides a method for selecting an infant food which as a favorable effect on the development and/or use of the cognitive skills of a child, comprising determining the age of the child and correlating the age with an infant food optimal for that age, where an age from 1 year is correlated with an infant food with a T/T ratio of < 0.3. The T/T ratio of the infant food after the first year of life is preferably between about 0.1 and 0.3.
Trp and Tyr are both part of the group of amino acids which are essential for children, and the importance of the presence of essential amino acids in infant food is known. Typically, the aim is to approximate the composition of mother's milk. See for instance EP 0418593, in which the amino acid composition of an infant food is based on the amino acid composition of an infant food based on the amino acid composition of the nutritive protein fraction of mother's milk. Human milk is relatively rich in Trp, mainly as a result of the Trp-containing proteins α-lactalbumin, immunoglobulin A and lactoferrin. However, the latter two are not or hardly used. The Trp/Tyr ratio in most known infant foods approximates that of mother's milk, i.e. 0.4 or more. It is known that Trp, a precursor for the neurotransmitters serotonin and melatonin, makes an important contribution to a healthy sleep pattern. See for instance Heine et al, (Amino
Acids (1995) 9:191-205).
It has recently been demonstrated that the content of Trp in mother's milk follows a circadian rhythm, with a peak at 3:00 am. This was found to be correlated with a peak at 6.00 pm for metabolite 6-sulphatoxymelatonin in the urine of infants who were exclusively fed with mother's milk (Cubero et al Neuro Endocrinol Lett. 2005 Dec;26(6):657-61). This finding has resulted in a set of two infant formulas for regulating the day /night rhythm, consisting of a 'day formula' with a Trp content of maximally 1.7 g/100 g of protein and a 'night formula' with minimally 3.5 g/100 g of protein (WO2006/034955). The intracellular transport of Trp is mediated by a general transporter mechanism for the "large neutral amino acids", as they are known in the field, abbreviated as "LNAA". These are leucine, isoleucine, valine, phenylalanine, tyrosine and methionine. Trp transport through the blood-brain barrier is competitively influenced by the concentration of these LNAA. The Trp/LNAA ratio in plasma is therefore very important for the availability of Trp, and accordingly serotonin synthesis, in the brains. The Trp/LNAA ratio in mother's milk is about 0.056 while this is 0.041 in cow's milk. Alpha lactalbumin contains a relatively high content of Trp compared to leucine, isoleucine, valine, phenylalanine, tyrosine and methionine. In order to achieve the desired Trp/LNAA ratio in infant food, it has generally been accepted to enrich cow's milk -based infant food with cow's milk alpha lactalbumin or the hydrolysate thereof. See for instance Heine et al. (1996, Acta Paediatr. 85:1024-8); WO98/14204 and WO03/055322. Dutch patent NL1025900 in the name of applicant indicates that it can also have an advantage to include, in addition to alpha lactalbumin, extra proline in the food. WO2006/034955 further argues the advantage of including extra nucleotides. EP0951842 teaches a preferred Trp/LNAA ratio in infant food of 4.8- 10: 100, in combination with relatively high levels of folic acid, vitamin B6 and vitamin B 12.
Tyr is known to be a precursor of the neurotransmitters dopamine, noradrenaline and adrenaline. Receptors for these neurotransmitters are present in areas of the nervous system involved in regulating movement, mood, attention and functions of the intestines. US2006/0030625 describes a dietary supplement for the treatment of a neurotransmitter deficiency, comprising a neurotransmitter precursor such as DOPA, tyrosine and 5- hydroxytryptophan, in combination with a cofactor activating the synthesis of a neurotransmitter. It appears from the above that favorable effects of Trp (suppletion) in infant food have already been described, and that the ratio of Trp relative to other large, neutral amino acids (LNAA) is relevant to the final uptake of Trp in the brains. However, nothing in the prior art teaches or suggests that a correct adjustment of the Trp/Tyr ratio depending on the age of the child is relevant to an optimal development and/or use of cognitive skills. More in particular, it has not been described before that, after a first stage with a dietary accent on the sleep/wake rhythm, growth and rest of the infant, reducing the T/T ratio in the food should be started in time to support the development and use of cognition.
For use of a method according to the invention, an infant food is prepared with the desired T/T ratio. The term 'infant food' comprises both protein-containing dietary supplements and complete formulas providing the complete nutrition of an infant or child, such as a formula for infants or prematurely born infants. It may also be a so-called "follow -on" milk, which can be used after about the first 6 months, such as for instance for the preparation of porridge.
An infant food according to the invention typically relates to a complete formula comprising a protein source, a carbohydrate source, a lipid source and the conventional minerals and vitamins. An infant food according to the invention may be based on a known infant food based on (hydrolyzed) cow's milk proteins, such as casein, whey proteins or mixtures thereof, but also based on vegetable proteins, such as proteins from cereals and legumes.
Trp and Tyr may also be present in the form of intact proteins, protein fragments (e.g. hydrolysates) and/or free L-amino acids or salts thereof. If free amino acids are used, it is important to remove any pollutions which may cause a toxic reaction. Preferably, Tyr and/or Trp is present in the form of a protein or protein hydrolysate. For instance, proteins or protein hydrolysates may be selected by their T/T ratio. Preferably, one or more milk proteins and/or hydrolysates thereof are used. Table 1 below provides an overview of the Trp and Tyr contents of suitable milk protein sources for the preparation of a product with a high T/T ratio (at least 0.3) and/or for the preparation of a product with a low T/T ratio (less than 0.3). On the basis of the amino acid composition, a skilled person can combine two or more protein sources to achieve the desired T/T ratio. Suitable milk protein sources include demineralized whey protein powder such as DeminalδO (Friesland Foods Domo, The Netherlands), protein obtained from whey coming from cheese preparation with rennet and after desalination, whey protein from acid whey, coming from acid casein preparation, whey protein hydrolysate, alpha lactalbumin, glycomacropeptide (cGMP), casein, beta casein, alpha s-casein and casein hydrolysate.
Table 1: Trp and Tyr contents and T/T ratios in milk protein sources
Figure imgf000008_0001
Figure imgf000009_0001
According to the EEC Directive, mother's milk has a ratio of 0.53.
In a specific embodiment, a whey protein derivate is used which is obtained from the permeate after microfiltration of skimmed milk. Such a derivate has a T/T ratio from about 0.57 to about 0.73.
In another embodiment, for the food, a mixture of casein and whey protein coming from sweet, desalinated whey is used. Depending on the desired T/T ratio, the relative proportion of casein/whey protein is adjusted, optionally in combination with addition of extra amino acids, for instance in the form of free L-Trp and/or L-Pro (see Example 1).
For the preparation of an infant food for infants and children with cow's milk allergy, or an increased risk of developing this, the use of casein as a protein source is preferred, in particular (extensive) casein hydrolysates. The T/T ratio can be increased by supplementing with (free) Trp.
In one embodiment, a selected infant food contains no more than 7 grams of the amino acid threonine (Thr) and/or at least 3.5 grams of phenyl alanine (Phe) per 100 grams of protein. As a carbohydrate source, any type of carbohydrate or mixture of two or more different carbohydrates, which are typically used in infant food formulas, can be used. Suitable carbohydrate sources are disaccharides such as lactose and saccharose, monosaccharides, such as glucose, and maltodextrins, starch and carbohydrate sources with a prebiotic effect. Carbohydrates with a high glycemic index, such as glucose and maltodextrin, can increase the Trp/LNAA ratio in the blood.
The lipid source in an infant food according to the invention with a specific T/T ratio may be any lipid or combination of lipids which is suitable for use in infant food. Examples of suitable lipid sources are tri, di and monoglycerides, phospholipids, sphingolipids, fatty acids and esters or salts thereof. The lipids may have an animal, vegetable, microbial or synthetic origin. Of particular interest are polyunsaturated fatty acids such as gamma-linolenic acid (GLA), di-homo-gamma-linolenic acid (DHGLA), arachidonic acid (AA), stearidonic acid (SA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and conjugated linoleic acid (CLA). CLA is important in the protection against eczema and respiratory diseases in children. This is particularly the case for the cis-9, trans-11 and trans-10, cis-12 isomers of CLA. AA can be added to the composition with a view to an optimal tolerance induction against protein allergy. Preferably, a selected infant food contains at least docosahexaenoic acid (DHA), linolenic acid (LA) and/or alpha linolenic acid (ALA). In one embodiment, the DHA content is 0.1-1.0% based on the total fat content. With respect to LA and ALA, the LA/ALA ratio is preferably between 4:1 and 20:1, more preferably between 5:1 and 10:1. Further, the infant food may contain one or more conventional micro ingredients such as vitamins, antioxidants, minerals, free amino acids (such as proline, glutamate), nucleotides, taurine, carnitine, choline and polyamines. Examples of suitable antioxidants are BHT, ascorbyl palmitate, vitamin E, alpha and beta carotene, lutein, zeaxanthin, lycopene and phospholipids. With regard to the doses of such micro ingredients, existing directions can be followed, which are known to a skilled person.
However, for micro nutrients which can be important to brain development and/or brain function, higher doses can be used. Such ingredients are, for instance, DHA, choline and taurine.
The selected infant food contains, for instance, at least 0.04 g of choline per 100 g of dry matter. Choline may be present in different forms, for instance in the form of choline salt (such as choline chloride) and/or choline -containing lipids (such as phosphatidyl choline or a lipid mixture known by the name lecithin). Further, the selected infant food may contain at least 0.03 g of taurine per 100 g of dry matter. Preferably, the infant food comprises both choline and taurine, still more preferably in combination with DHA and/or precursors thereof, such as ALA and EPA.
Further, it may be advantageous to select an infant food to which one or more probiotic bacterial strains are added. Probiotics generally have a favorable effect on the digestibility of the infant food. Also, some probiotics can stimulate the tolerance to milk proteins. Preferably, an infant food contains a strain chosen from the group consisting of Bifidobacterium strains and lactic acid-forming strains, such as the lactic acid-forming Lactobacillus and Streptococcus groups. Typically, a probiotic is present in an amount of minimally 10exp6 to 10exp7 colony -forming units per strain per gram of product.
In one embodiment, the selected infant food comprises a prebiotic, preferably chosen from fructo and/or galacto-oligosaccharides, with short or long chains, inulin, fucose -containing oligosaccharides, beta glycans, carob flour, gums, pectins, sialyloligosaccharides, sialyllactose, galactans with short or long chains, and nucleotides. In particular, there is a preference for fucose-containing oligosaccharides, as they are present in mother's milk. According to a surprising finding of the inventors, they have a supporting effect on brain development and brain functions. Further, fuco-oligosaccharides have immune-modulating and tolerance -increasing properties, particularly in children who are hereditarily predisposed to develop an allergy to milk proteins. They can also increase resistance and/or tolerance in case of infections by pathogens. The infant food to be selected contains, for instance, up to 8 grams of fuco-oligosaccharides per 100 g of dry matter.
The selected infant food may have a liquid or powder form, the latter needing to be reconstituted with a liquid, typically water, before use. A skilled person knows the suitable packages for such products. Liquid products may, for instance, be packaged in bottles, cans or cartons from laminated cardboard. Powdery products may be packaged in sachets, vacuum packages or cans.
A further aspect of the present invention relates to a container comprising a product combination of at least one first infant food for use during the first year of life with a T/T ratio of ≥ 0.3 and a second infant food for use after the first year of life with a T/T ratio of < 0.3. Such a set or kit of different products (also referred to as "kit-of-parts") is, for instance, a "family-sized package" with foods for infants and/or children within one family who belong to different age groups. For instance, the container contains the product combination of a) a powdery infant formula with a T/T ratio of 0.45-0.60 and b) a powdery toddler formula with a T/T ratio of 0.27- 0.29. In another embodiment, the container contains at least three different infant foods, each with a different T/T ratio and adjusted to a different age group. It comprises, for instance, an infant food with a T/T ratio between 0.45 and 0.8 for a baby of 0-6 months, an infant food with a T/T ratio between 0.3 and 0.45 for use during 6-12 months and an infant food with a T/T ratio lower than 0.3 for use from 1 year.
With respect to the composition of the set of infant foods in such a container, the same possibilities and preferences hold as described above with regard to the infant food to be selected. Preferably, the Thr content is no more than 7 grams per 100 grams of protein, and/or the Phe content is at least 3.5 grams per 100 grams of protein.
The invention is illustrated hereinbelow on the basis of a number of examples.
Example 1
Foods were prepared for infants in the age groups 0-<6 months, 6-12 months and >12 months. In the foods, the ratio of casein (coming from skimmed milk) was reduced relative to whey protein coming from sweet desalinated whey as the age advanced. Only the formula for the age group of 0-6 months was also enriched with the amino acid tryptophan. The casein (48 parts alpha + 36 parts beta + 16 parts kappa + gamma) contained a TRP content of 1.7 grams per 100 grams of protein and a TYR content of 6.3 grams per 100 grams of protein. The whey protein coming from the sweet desalinated whey contained per 100 grams of protein: 1.7 grams of TRP and 2.4 grams of TYR.
In the following table, the compositions per age group are shown, as well as the T/T ratios which were supplied per age group.
Figure imgf000013_0001
Figure imgf000014_0001
Example 2
Foods were prepared for infants in the age groups of 0-<6 months, 6- 12 months and > 12 months. In the foods, the ratio of casein was kept constant relative to different types of "whey protein derivates". All foods were enriched with 5% fuco-oligosaccharides, while, in the food intended for the group of 0-6 months, extra tryptophan was included. The casein had a TRP content of 1.7 grams per 100 grams of protein and a TYR content of 6.3 grams per 100 grams of protein. The whey protein derivates and their contents of TRP and TYR are indicated in the table below. The table also indicates the compositions and T/T ratios of the foods supplied per age group.
Figure imgf000015_0001
Figure imgf000016_0001
Example 3
Prepared were foods based on casein hydrolysate, intended for long- term preventive use in children with an allergic family anamnesis. The foods for the benefit of these children intended for the first year of life and afterwards were composed as indicated in the table below.
Figure imgf000016_0002
Figure imgf000017_0001
- the T/T ratio for the first year of life is similar to that of mother's milk.
- the T/T ratio for the period after 1 year optimally takes into account the desired cognitive development.

Claims

1. A method for selecting an infant food which contributes to the development and/or use of the cognitive skills of a child, comprising determining the age of the child and selecting a food optimal for that age, wherein, for an age of 1 year at most, an infant food with a tryptophan : tyrosine ratio based on weight (T/T ratio) of ≥ 0.3 is selected and/or wherein, for an age from 1 year, an infant food with a T/T ratio of < 0.3 is selected.
2. A method for supporting and/or optimizing the development and/or use of the cognitive skills of a child, comprising selecting an infant food according to the method of claim 1, preparing the selected infant food and administering the selected infant food to the child.
3. A method according to claim 1 or 2, wherein, for an infant aged 1 year at most, an infant food with a T/T ratio ≥ 0.3 and < 0.1 is selected.
4. A method according to any one of claims 1-3, wherein, for an infant aged 0 to 6 months, an infant food with a T/T ratio of ≥ 0.45, preferably > 0.45 and < 0.8, is selected.
5. A method according to any one of the preceding claims, wherein, for a child at the age from 1 year, an infant food with a T/T ratio of ≥ 0.1 and < 0.3 is selected.
6. A method according to any one of the preceding claims, wherein a food is selected in which Trp and/or Tyr are present in the form of proteins, preferably milk proteins, or hydrolysates thereof, and/or as free alpha amino acid.
7. A method according to claim 6, wherein Trp and/or Tyr are present in the form of a protein source chosen from the group consisting of demineralized whey protein powder, protein obtained from whey coming from cheese preparation with rennet and after desalination, whey protein from acid whey, coming from the acid casein preparation, whey protein hydrolysate, alpha lactalbumin, glycomacropeptide (cGMP), casein, beta casein, alpha s-casein and casein hydrolysate.
8. A method according to any one of the preceding claims, wherein a food is selected which contains one or more components chosen from the group consisting of (poly) unsaturated fatty acids, free fatty acids, free amino acids, nucleotides, choline, taurine, phospholipids, sphingolipids, probiotics and prebiotics.
9. A method according to claim 8, wherein the selected infant food contains at least 0.04 g of choline per 100 g of dry matter, for instance in the form of choline salt and/or choline -containing lipids.
10. A method according to claim 8 or 9, wherein the selected infant food contains at least 0.03 g of taurine per 100 g of dry matter.
11. A method according to any one of claims 8-10, wherein the selected infant food contains gamma-linolenic acid (GLA), di-homo-gamma-linolenic acid (DHGLA), arachidonic acid (AA), stearidonic acid (SA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and/or conjugated linoleic acid (CLA), more preferably at least DHA.
12. A method according to any one of claims 8-11, wherein the selected infant food contains one or more probiotic bacterial strains, preferably chosen from the group of Bifidobacterium strains and lactic acid-forming strains.
13. A method according to any one of claims 8-12, wherein the selected infant food comprises a prebiotic, preferably chosen from fructo and/or galacto-oligosaccharides, with short or long chains, inulin, fucose -containing oligosaccharides, beta glycans, carob flour, gums, pectins, sialyloligosaccharides, sialyllactose, galactans with short or long chains, and nucleotides.
14. A container comprising a product combination of at least a first infant food for use during the first year of life with a tryptophan : tyrosine ratio based on weight (T/T ratio) of > 0.3; and a second infant food for use after the first year of life, with a T/T ratio < 0.3.
15. A container according to claim 14, comprising an infant food with a T/T ratio between 0.45 and 0.8 for use during 0-6 months, an infant food with a T/T ratio between 0.3 and 0.45 for use during 6-12 months and an infant food with a T/T ratio lower than 0.3 for use from 1 year.
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