Title: Gender specific synthetic nutritional compositions and nutritional systems comprising them.

Technical field: The invention relates to gender specific synthetic nutritional compositions, to nutritional systems comprising them and, to their use to provide optimised nutrition and/or one or more health benefit to an infant.

Background of the invention

Even though breastfeeding is optimal for infants, existence of certain conditions may not be in the best interests of the infant and it may contraindicate breastfeeding (AAP, 2012; Lawrence, 2013). In such cases, where the sole source of nutrition is not available to the infant, alternative strategies to feed them have to be devised. Feeding infants with Synthetic nutritional compositions e.g. Infant formula is one such strategy.

The compositions of the aforementioned synthetic nutritional compositions aim to replicate those of human milk. However, replicating HM is not a simple task. HM not only contain numerous components, its composition is extremely dynamic and these dynamic changes remain largely unexplored and uncharacterized. Whilst it is known that components and/or their quantities may vary depending on a variety of factors including the stage of lactation, circadian rhythms and even gender, it is not known which of the numerous components vary or how they vary e.g. by stage of lactation and/or gender.

Surprisingly it has now been found that 1 to 2 months, and up to 1 month, more particularly up to 2 weeks and 2 weeks to 1 month, postpartum, there is a difference in the alpha-lactalbumin concentration range found in HM produced by mother's to girls in comparison to mother's to boys . This finding stems from a cross-sectional study of HM wherein, H M samples from mothers to either boys or girls were collected at various stages postpartum and analysed. Further, it was also surprisingly found that up to 1 month, more particularly up to 2 weeks and 2 weeks to 1 month, postpartum, the mean alpha-lactalbumin concentration of HM produced by mothers to boys was statistically higher than that produced for mothers to girls and, that up to 1 to 2 months, the mean alpha-lactalbumin concentration of HM produced by mothers to boys was statistically lower than that produced for mothers to girls.

Because these gender differences in the concentration of alpha-lactalbumin in HM have never been previously identified, it is not reflected in the compositions of synthetic nutritional compositions available today. Further, because these gender differences were not known. There was no incentive for gender specific synthetic nutritional compositions comprising total protein within a range identified for a particular gender to be developed.

Alpha-lactalbumin is a protein and, optimum intake of proteins helps to ensure optimum growth and development in infants. Further optimum intake of alpha-lactalbumin has been linked to a host of health benefits e.g. optimized immune functions, better gut maturation, optimum growth and development physically and cognitively, and a lower risk of obesity and

cardiovascular disease. Further still, alpha-lactalbumin is known to have a strong

gastroprotective activity and may be effective in preventing gastrointestinal infections.

Additionaily, products of the digestion of alpha-lactalbumin, or intermediates thereof, e.g. peptide fragments, are known to have antibacterial and prebiotic activity, immunostimulatory effect, and a positive effect on mineral absorption.

Optimum growth and development and/or health benefits may be immediate and/or long term. Long term health benefits may only be evident in months or years e.g. 6 months, 9 months, 12 months, 5 years, 10 years, or 20 years. Accordingly, there remains a need for gender specific synthetic nutritional compositions, and nutritional systems comprising them, having compositions within which the identified gender differences, with respect to concentration of alpha-lactalbumin, found in H M 1 to 2 months, and up to 1 month, more particularly up to 2 weeks and 2 weeks to 1 month, postpartum are more accurately reflected and thereby optimised. Summary of the invention

The invention is set out in the claims. The inventors have found that the concentration range of alpha-lactalbumin in HM varies 1 to 2 months, and up to 1 month, more particularly up to 2 weeks and 2 weeks to 1 month, postpartum depending on the gender of the mother's infant. In light of this finding the inventors have developed gender specific nutritional compositions and nutritional systems comprising them, that reflect these identified gender differences. Prior to aforementioned findings the skilled person has not incentive to develop such gender specific synthetic nutritional compositions or to include them in nutritional systems.

The concentration of alpha-lactalbumin in the gender specific synthetic nutritional compositions of the invention, and nutritional systems comprising them, more accurately reflect the concentration of alpha-lactalbumin found in HM produced for infants of the same gender and age. In light of this and, because H M is considered optimal with respect to infant nutrition, they can provide an optimized amount of total alpha-lactalbumin to an infant of 1 to 2 months of age, and up to 1 month of age, more particularly up to 2 weeks of age and 2 weeks to 1 month of age.

The gender specific synthetic nutritional compositions can be prepared from a gender neutral synthetic nutritional composition by measuring out an appropriate amount of said gender neutral synthetic nutritional composition and mixing it with an additive and/or diluent.

Since optimised alpha-lactalbumin intake helps to ensure optimum growth and development in infants, the gender specific synthetic nutritional compositions, and nutritional systems of the invention, can also be used to treat, prevent or mitigate sub optimal growth and development e.g. obesity in an infant. The gender specific synthetic nutritional composition is selected from the group consisting of: infant formula, and a composition for infants that is intended to be added or diluted to human milk e.g. HM fortifier.

In addition to that set out above, the inventors have also found that the mean concentration of alpha-lactalbumin in HM does not differ (higher or lower) by gender after 2 months postpartum. In light of this, in addition to comprising the gender specific synthetic nutritional compositions of the invention, the nutritional systems disclosed herein may optionally also comprise synthetic nutritional compositions for infants more than 2 months of age wherein, the concentration of alpha-lactalbumin does not differ by gender for infants of the same age. Accordingly, the nutritional systems of the invention may also provide optimized nutrition and/or one or more health benefits for an infant up to 12months old, up to 9 months old, up to 8months old, up to 6 month old.

Drawings

FIG.l is a graphical representation of the mean concentration of alpha-lactalbumin in HM by gender at up to 2 weeks (5-11 days), 2 weeks to 1 month (12-30 days), 1 to 2 months (31 to 60 days) , 2 to 4 months (61 to 120 days), and 4 to 8 months (121 to 240 days) postpartum. Detailed Description

As stated herein, the inventors performed a cross sectional study evaluating the nutrient composition of HM collected from mothers at various stages of lactation (up to 2 weeks (5-11 days), 2 weeks to 1 month (12-30 days), 1 to 2 months (31 to 60 days), 2 to 4 months (61 to 120 days), and 4 to 8 months (121 to 240 days) postpartum). The study indicated different min and max ranges for the concentration of alpha-lactalbumin by gender. Surprisingly, the results of this study indicated that 1 to 2 months, and up to 1 month, more particularly up to 2 weeks and 2 weeks to 1 month, postpartum, there is a difference in the mean concentration of alpha- lactalbumin in HM depending on the gender of the mother's infant. Further details of the study, analysis techniques and results are given in example 1. Based on the findings of the study, the inventors have designed gender specific synthetic nutritional compositions for infants 1 to 2 months, up to 1 month, up to 2 weeks, and 2 weeks to 1 month of age wherein, the concentration of alpha-lactalbumin is adapted based on that found in HM produced for an infant of the same gender and age.

The term "gender specific synthetic nutritional composition" as used herein refers to any synthetic nutritional composition, intended to be consumed by an infant that is specifically adapted to the nutritional needs of either a female or male enfant. Appropriate types of gender specific synthetic nutritional compositions are dependent on age. Non limiting examples of gender specific synthetic nutritional compositions for infants from birth to 4 months include; infant formulae, and a composition for infants that is intended to be added or diluted with HM e.g. HM fortifier. Non limiting examples of gender specific synthetic nutritional compositions for infants from 4 months to 12 months include infant formulae, a composition for infants that is intended to be added or diluted with HM e.g. HM fortifier, or food stuffs intended for consumption by infants either alone or in combination with H M e.g. complementary foods.

The term "infant" as used herein refers to a human infant of 12 months of age or less.

In a first aspect of the invention there is provided a gender specific synthetic nutritional composition for an infant 1 to 2 months, up to 1 month of age, up to 2 weeks of age or 2 weeks to 1 month of age wherein, the concentration of alpha-lactalbumin is adapted based on that found in HM produced for an infant of the same gender and age. The gender specific synthetic nutritional composition can be a male specific synthetic nutritional composition or a female specific synthetic nutritional composition.

In an embodiment the gender specific synthetic nutritional composition is a female specific synthetic nutritional composition for an infant of 1 to 2 months of age and comprises alpha- lactalbumin in a concentration of 2067.9mg to 4630.3mg, 2854.6mg to 4630.3mg,1975.35mg to 4008.75mg, 2483.7mg to 3500.4mg, or 2992.05mg, per L.

The total protein content of the gender specific synthetic nutritional compositions of the invention is expressed in mg/L. This may refer to the total protein content of a reconstituted gender specific synthetic nutritional composition. In an embodiment the gender specific synthetic nutritional composition is a male specific synthetic nutritional composition for an infant of 1 to 2 months of age and comprises alpha- lactalbumin in a concentration of 1802.2mg to 4630.3mg, 1802.2mg to 2854mg, 2022.27mg to 3412.03mg, 2369.71mg to 3064.59mg, or 2717.15mg, per L.

In an embodiment the gender specific synthetic nutritional composition is a female specific synthetic nutritional composition for an infant of up to 1 months of age and comprises alpha- lactalbumin in a concentration of 1386mg to 4511.6mg, 1386mg to 3261mg, 2034.24mg to 4333.56mg, 2609.07mg to 3758.73mg, or 3183.90mg to 3091.36mg, per L.

In an embodiment the gender specific synthetic nutritional composition is a male specific synthetic nutritional composition for an infant of up to 1 month of age and comprises alpha- lactalbumin in a concentration of 1771.5mg to 4701. llg, 2252.96mg to 4426.6mg, 2796.37mg to 3883.19mg, 3261.84mg to 4701. llmg, or 3250.67mg to 3339.78mg, per L. In an embodiment the gender specific synthetic nutritional composition is a male specific synthetic nutritional composition for an infant of up to 2 weeks of age and comprises alpha- lactalbumin in a concentration of 1771.5mg to 4701. llmg, 2252.96mg to 4426.6mg, 2796.37mg to 3883.19mg, 3261.84, to 4701.11, or 3339.78mg, per L.

In an embodiment the gender specific synthetic nutritional composition is a female specific synthetic nutritional composition for an infant of up to 2 weeks of age and comprises alpha- lactalbumin in a concentration of 1386mg to 4511.6mg, 1386mg to 3261mg, 2034.24mg to 4333.56mg, 2609.07mg to 3758.73mg, or 3183.90mg, per L.

In an embodiment the gender specific synthetic nutritional composition is a male specific synthetic nutritional composition for an infant of 2 weeks to 1 month of age and comprises alpha-lactalbumin in a concentration of 2435. lmg to 4467. lmg, 2435.19mg to 4084.95mg, 2833.53mg to 3667.81mg, 3171.015 to 4467. lmg, or 3250.67mg per L. In an embodiment the gender specific synthetic nutritional composition is a female specific synthetic nutritional composition for an infant of 2 weeks to 1 month of age and comprises alpha-lactalbumin in a concentration of 2135mg to 3949.4mg, 2135mg to 3171mg, 2294.54mg to 3888.18mg, 2692.95mg to 3489.77mg, or 3091.36mg per L.

The alpha-lactalbumin concentration can be measured by methods well known in the art. In particular the concentration of alpha-lactalbumin can be measured by Kjeldahl nitrogen analysis as described in Lynch & Barbano (1999) J AOAC International, vol 82, pl389, or colorimetric methods such as Bradford or BCA assay as described in Bradford (1976) Anal. Biochem. 72: 248; Smith et al. (1985) Anal. Biochem. 150: 76).

Any source of alpha-lactalbumin known to be employed in the types of synthetic nutritional compositions disclosed herein, may be comprised within in the gender specific synthetic nutritional compositions of the invention.

Non limiting examples of sources of alpha-lactalbumin include human alpha-lactalbumin, bovine alpha-lactalbumin, buffalo alpha-lactalbumin, and combinations thereof.

The alpha-lactalbumins may be intact, hydrolysed, partially hydrolysed, or any combination thereof.

The gender specific synthetic nutritional compositions of the invention can also comprise any other ingredients or excipients known to be employed in synthetic nutritional compositions. Non limiting examples of such ingredients include: other proteins, carbohydrates, oligosaccharides, lipids, prebiotics or probiotics, essential fatty acids, nucleotides, nucleosides, vitamins, minerals, and other micronutrients.

Non limiting examples of other proteins include casein, whey protein, soy protein, rice protein, corn protein, oat protein, barley protein, rye protein, pea protein, egg protein, sunflower seed protein, potato protein, fish protein, meat protein, and combinations thereof. Non limiting examples of carbohydrates include lactose, saccharose, maltodexirin, starch, and combinations thereof.

Non limiting examples of lipids include: palm olein, high oleic sunflower oil, high oleic safflower oil, canola oil, fish oil, coconut oil, bovine milk fat, and combinations thereof.

Non limiting examples of essential fatty acids include: linoleic acid (LA), a-linolenic acid (ALA) and polyunsaturated fatty acids (PUFAs). The nutritional compositions of the invention may further contain gangliosides monosialoganglioside-3 (GM3) and disialogangliosides 3 (GD3), phospholipids such as sphingomyelin, phospholipids phosphatidylcholine,

phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and combinations thereof.

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.

Further examples of oligosaccharide are 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.

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 animalis, 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, Saccharomyces boulardii or mixtures thereof, preferably selected from the group consisting of Bifidobacterium longum NCC3001 (ATCC BAA-999), Bifidobacterium longum NCC2705 (CNCM I- 2618), Bifidobacterium longum NCC490 (CNCM 1-2170), Bifidobacterium lactis NCC2818 (CNCM 1-3446), Bifidobacterium breve strain A, Lactobacillus paracasei NCC2461 (CNCM 1-2116), Lactobacillus johnsonii NCC533 (CNCM 1-1225), Lactobacillus rhamnosus GG (ATCC53103), Lactobacillus rhamnosus NCC4007 (CGMCC 1.3724), Enterococcus faecium SF 68 (NCC2768; NCIMB10415), and combinations thereof. Non limiting examples of Nucleotides include: cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP), guanosine monophosphate (GMP), and combinations thereof.

Non limiting examples of vitamins and minerals include: vitamin A, vitamin Bl, vitamin B2, vitamin B6, vitamin Bi2, vitamin E. vitamin K. vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine, L- carnitine, and combinations thereof. Minerals are usually added in salt form. Other suitable and desirable ingredients of synthetic nutritional compositions, that may be employed in the gender specific nutritional compositions of the invention, are described in guidelines issued by the Codex Alimentarius with respect to the type of synthetic nutritional composition in question e.g. Infant formula, H M fortifier, follow on formula, or food stuffs intended for consumption by infants e.g. complementary foods.

The gender specific compositions of the invention may be prepared by methods well known in the art for preparing that type of synthetic nutritional composition e.g. infant formulae, follow on formulae, a composition for infants that is intended to be added or diluted with HM e.g. HM fortifier, or food stuffs intended for consumption by infants either alone or in combination with H M e.g. complementary foods.

An exemplary method for preparing a gender specific powdered infant formula is as follows. A protein source, including alpha-lactalbumin, carbohydrate source, and fat source may be blended together in appropriate proportions. Emulsifiers maybe included in the blend . Vitamins and minerals may be added at this point but are usually added later to avoid thermal

degradation . Any lipophilic vitamins, emulsifiers and the like may be dissolved into the fat source prior to blend ing. Water, preferably water which has been subjected to reverse osmosis, may then be mixed in to form a liq uid mixture.

The liquid mixture may then be thermally treated to reduce bacterial loads. For example, the liquid mixture may be rapidly heated to a temperature in the range of about 80°C to about 1 10°C for about 5 seconds to about 5 minutes. Th is may be carried out by steam injection or by heat exchanger; for example a plate heat exchanger.

The liquid mixture may then be cooled to about 60°C to about 85°C; for example by flash cooling. The liquid mixture may then be homogen ised; for example in two stages at about 7 MPa to about 40 MPa in the first stage and about 2 MPa to about 14 MPa in the second stage. The homogenised mixture may then be further cooled to add any heat sensitive components such as vitamins and minerals. The pH and solids content of the homogen ised mixture is conveniently standardised at this point.

The homogen ised mixture can be transferred to a suitable d rying apparatus such as a spray drier or freeze d rier and converted to powder. The powder should have a moisture content of less than about 3% by weight.

If it is desired probiotic(s) can be added, they may be cultured accord ing to any suitable method and prepared for add ition to the infant formula by freeze-d rying or spray-d rying for example. Alternatively, bacterial preparations can be bought from specialist suppliers such as Christian Hansen and Morinaga already prepared in a suitable form for add ition to food products such as infant formula. Such bacterial preparations may be added to the gender specific powdered infant formula by dry mixing.

The gender specific compositions of the invention may also be prepared from a gender neutral synthetic nutritional composition in a method comprising; measuring out an appropriate amount of said gender neutral synthetic nutritional composition and mixing it with an additive and/or diluent e.g. water so as to arrive at a gender specific nutritional composition in accordance with the invention.

The additive may be a gender specific additive comprising protein in a particular concentration so that when mixed with the gender neutral synthetic nutritional composition, and optionally a diluent, the resulting mixture is a gender specific synthetic nutritional composition of the invention.

The gender neutral synthetic nutritional composition can be prepared by methods well known in the art. For example, as laid out above for infant formula. One or more of the gender specific synthetic nutritional compositions of the invention can be included in a nutritional system.

The term "nutritional system" as used herein refers to a collection of more than one synthetic nutritional composition advertised or sold as part of the same product range e.g. a collection of infant formulas sold under the same brand and adapted to the nutritional needs of infants of differing genders and/or ages. The synthetic nutritional compositions making up the nutritional system may be packaged individually e.g. in capsules or boxes. Said packages can be sold individually, grouped together e.g. wrapped by plastic film or combined in a box, or in a combination of these two ways.

The nutritional system may comprise only gender specific synthetic nutritional compositions, or it may comprise a mix of gender specific and gender neutral synthetic nutritional compositions.

The term "gender neutral" as used herein is synonymous with unisex. In a further aspect of the present invention there is provided a nutritional system comprising at least one of the gender specific synthetic nutritional compositions of the invention.

In an embodiment the nutritional system comprises at least one gender specific synthetic nutritional composition for a male infant and at least one gender specific nutritional composition for a female infant wherein, said male and female gender specific synthetic nutritional compositions are for infants of the same age selected from the group consisting of: 1 to 2 months of age, up to 1 month of age, up to 2 weeks of age, or 2 weeks to 1 month of age.

The herein referenced study indicated that the mean concentration of alpha-lactalbumin comprised in HM produced for male infants up to 1 month of age, more particularly up to 2 weeks of age or 2 weeks to 1 month of age, was higher than that produced for female infants of the same age. Conversely, the study indicated that mean concentration of alpha-lactalbumin comprised in HM produced for male infants of 1 to 2 months of age was equal to or less than that produced for female infants of the same age.

In an embodiment the gender specific synthetic nutritional compositions, comprised within the nutritional system, are for infants of up to 1 month of age, up to 2 weeks of age, or 2 weeks to 1 month of age and the concentration of alpha-lactalbumin in said male gender specific synthetic nutritional composition is higher than that of said female gender specific synthetic nutritional composition.

The concentration of alpha-lactalbumin in the male gender synthetic nutritional compositions may be higher by any amount.

In an embodiment the nutritional system comprises male and female gender specific synthetic nutritional compositions for infants up to 1 month of age wherein, the ratio of the alpha- lactalbumin concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is 1:3.4 to 1:1.0002, 1:3.4 to 1:1.04, or 1:1.27 to 1:1.04, and/or the male gender specific nutritional composition comprises 3315. lmg to O.OOlmg, 3315.1 to 155.88mg, 2332.1 to 159.31, 517.7mg to 189.5mg, 385.5mg to 300. lmg, or 3315. lmg to 0.84mg, per L more alpha-lactalbumin than the female gender specific nutritional composition.

In an embodiment the nutritional system comprises male and female gender specific synthetic nutritional compositions for infants up to 2 weeks of age wherein, the ratio of the alpha- lactalbumin concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is 1:3.4 to 1:1.0002, 1:3.4 to 1:1.04, or 1:1.27 to 1:1.04, and/or the male gender specific nutritional composition comprises 3315. lmg to 0.001mg,3315.1mg to 155.88mg, 385.5 mg to 189.5mg, or 3315. lmg to 0.84mg, per L more alpha-lactalbumin than the female gender specific nutritional composition. In an embodiment the nutritional system comprises male and female gender specific synthetic nutritional compositions for infants 2 weeks to 1 month of age wherein, the ratio of the alpha- lactalbumin concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is 1:2.09 to 1:1.000005, 1:2.09 to 1:1.05, orl:14 to 1:1.13, and/or the male gender specific nutritional composition comprises 2332mg to O.OOlmg, 2332mg to 159.31mg, 517.7mg to 300. lmg, or 2332mg to 015mg per L more alpha- lactalbumin than the female gender specific nutritional composition.

In another embodiment the gender specific synthetic nutritional compositions, comprised within the nutritional system, are for infants of 1 to 2 months of age and the concentration of alpha-lactalbumin in said male gender specific synthetic nutritional composition is lower than that of said female gender specific synthetic nutritional composition.

The concentration of alpha-lactalbumin in the male gender synthetic nutritional compositions may be lower by any amount.

In another embodiment the nutritional system comprises male and female gender specific synthetic nutritional compositions for infants 1 to 2 months of age wherein, the ratio of the alpha- lactalbumin concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is 1:0.9998 to 1.087, or 1:0.90 to 1:0.87, and/or the female gender specific nutritional composition comprises O.OOlmg to

274.9mg, 0.6 to 274.9mg, or 265.7mg to 274.9mg, per L more alpha-lactalbumin than the male gender specific nutritional composition.

In addition to that disclosed hereinabove, the referenced study further indicated that after 2 months postpartum there is no difference in the mean concentration of alpha-lactalbumin in HM depending on the gender of the mother's infant.

In another embodiment the nutritional system further comprises gender specific synthetic nutritional compositions for infants of more than 1 month of age and/or more than 2 months of age wherein, the concentration of alpha-lactalbumin does not differ by gender for infants of the same age.

In another embodiment the nutritional system further comprises gender neutral specific synthetic nutritional compositions for infants more than 1 month or 2 months of age.

Non limiting examples of ages, or ranges thereof, more than 1 month of age, include: 2 months, 3 months, 2-4mths, 3-6mths, 4-6mths, 4-8mths 6-12mths, 7-12mths. The nutritional system may further comprise nutritional compositions for children older than 12months.

A gender specific synthetic nutritional composition and/or nutrition system according to the invention is particularly suitable for use in a method of preparing single servings of infant formula using capsules, each capsule of which contains a unit dose of a synthetic nutritional composition in concentrated form, and which is equipped with opening means contained within the capsule to permit draining of the reconstituted synthetic nutritional composition directly from the capsule into a receiving vessel such as a baby bottle. Such a method is described in WO2006/077259. The different synthetic nutritional compositions, including gender specific and gender neutral synthetic nutritional compositions, which may be comprised within a nutrition system, may be packed into individual capsules and presented to the consumer in multipacks containing a sufficient number of capsules to meet the requirements of an infant of a particular age or age range, for one week for example. Suitable capsule constructions are disclosed in

WO2003/059778.

The capsules can contain the synthetic nutritional compositions, (gender specific and gender neutral) in the form of powders or concentrated liquids in both cases for reconstitution by an appropriate amount of water. Both the composition and the quantity of infant formula in the capsules may vary according to the gender and/or age of the infant. If necessary, different sizes of capsules may be provided for the preparation of infant formulas for infants of different genders and/or ages.

The gender specific synthetic nutritional compositions, or nutritional systems comprising them, better reflect the differences in the concentration of alpha-lactalbumin found in HM depending on the gender of the mother's infant at one or more stages of lactation. As stated herein, optimum alpha- intake helps to ensure optimum growth and development in infants, and has been linked to a host of immediate and long term health benefits.

In another aspect of the present invention there is provided a gender specific synthetic nutritional composition and/or nutritional system as disclosed herein for use to treat, prevent or mitigate sub optimal growth and development e.g. obesity, of an infant .

A gender specific synthetic nutritional composition may provide an optimum amount of total alpha-lactalbumin to an infant of 1 to 2 months of age, up to 1 month of age, up to 2 weeks of age, and/or 2 weeks to 1 month of age.

The nutritional system may provide an optimum amount of total alpha-lactalbumin and to an infant up to 12 months of age, up to 9 months of age, up to 8 months of age, up to 6 months of age, up to 1 month of age. In another aspect of the present invention there is provided a method for providing an optimum amount of alpha-lactalbumin to an infant of 1 to 2 months, up to 1 month of age, up to 2 weeks of age, or 2 weeks to 1 month of age comprising: a) Optionally preparing a gender specific synthetic nutritional compositions according to the invention from a gender neutral synthetic nutritional composition;

b) Feed ing a gender specific synthetic n utritional compositions according to the invention to an infant 1 to 2 months of age, up to 1 month of age, up to 2weeks of age or 2 weeks to 1 month of age..

As stated herein. The gender specific synthetic nutritional compositions may be prepared from gender neutral synthetic nutritional compositions. Accordingly, in another aspect of the present invention there is provided a kit for providing an optimized amount of total a lpha-lactalbumin and to an infant of 1 to 2 months of age, up to 1 month of age, up to 2 weeks or 2 weeks to 1 month of age, the kit comprising: a) A gender neutral synthetic n utritional composition

b) A label ind icating dosage requirements for an infant so as to arrive at a gender specific nutritional composition in accordance with the invention.

The dosage requirements may be with respect to the quantity of the gender neutral synthetic nutritional employed and/or consumption freq uency e.g. 4 times per day.

Subjects included in the survey referenced herein were recruited from 4 provinces across China. Accordingly, the gender specific synthetic nutritional compositions and/or n utritional systems disclosed herein can be particularly relevant for Ch inese infants, and or infants born in populations having common genetic origins and/or eth nic origins and/or common d ietary habits thereto e.g. Asian, Indian, and/or Mongoloid populations. It should be appreciated that all features of the present invention disclosed herein can be freely combined and that variations and modifications may be made without departing from the scope of the invention as defined in the claims. Furthermore, where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred to in this specification.

There now follows a series of non-limiting examples that serve to illustrate the invention.

Examples

Example 1

The concentration of alpha-lactalbumin in HM samples collected from mothers to either male or females was analysed at various stages postpartum. The HM samples were collected as part of a cross sectional survey of H M. The study criteria is set out below:

Study population

• Number of subjects

Total 540 healthy subjects were enrolled, allowing a drop-out rate of 10 percent. They were comprised of: - 480 Lactating mothers in 3 cities (Beijing, Suzhou and Guangzhou)

- 30 mothers per city for each of the 5 time points (5 toll days, 12 to 30 days, 1 to 2 months, 2 to 4 months, and 4 to 8 months)

Inclusion/Exclusion criteria

• Inclusion: Healthy Chinese lactating mothers without history of acute and chronic diseases; exclusively breast feeding mothers during 4 months after delivery were enrolled.

• Exclusion: Chinese lactating mothers having history of psychopathic tendencies and having no dietary memory.

The concentrations of alpha-lactalbumin in the HM samples, collected as part of the above detailed study, were analysed using a LabChip GX II gel electrophoresis system from Perkin Elmer according to the manufacturer's protocols. It's a microfluidic chip-based gel electrophoresis system that separates and quantifies proteins similar to polyacrylamide gel electrophoresis (PAGE) with the advantage of automated high-throughput 96-well plate capacity. Purified human alpha-lactalbumin was used to generate a calibration curves for precise quantification of this protein in human milk.

The results of the compositional analysis of the HM survey, with respect to concentration of alpha-lactalbumin, are shown in table I. Concentration of alpha-lactalbumin mg/L

Female Male

Stage Min Mean SD Max Min Mean SD Max

5 to 11 1386.0 3183.9 574.83 4511.6 1771.5 3339.78 543.41 4701.1 days

12 to 2135.0 3091.36 398.41 3949.4 2435.1 3250.67 417.14 4467.1 30 days

1 to 2 2067.9 2992.05 508.35 4630.3 1802.2 2717.15 347.44 4630.3 months

2 to 4 1776.6 2505.35 316.65 3076.1 1672.3 2531.51 415.61 3580.7 months

4 to 8 1559.7 2347.20 450.10 3441.0 908.7 2290.17 487.65 3441.0 months

Table I

The results of the compositional analysis were then subject to a statistical analysis employing the following statistical model:

Concentration = sex + timeframe + timeframe + sex : timeframe - city + ε p referring to the residual error and sex:timeframe referring to the interaction between these 2 variables.

The following table shows the estimates for gender differences per timeframe along with the corresponding Pvalues.

The results of the Statistical analysis (statistical inference) are show in in table II.

1 to 2 Alpha- 247.2599 59.5259 434.99031 0.00996048 months lactalbumin

2 to 4 Alpha- -26.1588 -213.0850 160.76743 0.78339949 months lactalbumin

4 to 8 Alpha- 28.6020 -159.6406 216.84468 0.76535028 months lactalbumin

Table II

A P-value inferior to 0.1 for a particular timeframe suggests that there is a statistically significant difference in the concentration of alpha-lactalbumin in HM produced for males and females infants at that specific timeframe. As can be seen from the results in table II, a statistically significant difference in the concentration of alpha-lactalbumin between HM produced for male and female infants was identified at 1 to 2 months postpartum, up to 1 month postpartum, more specifically 5 to 11 days postpartum, and 12 to 30 days postpartum. No statistically significant difference was identified in the concentration of alpha-lactalbumin between HM produced for male and female infants older than 2 months postpartum Viz. 2 to 4 months and 4 to 8 months.

Example 2

Examples of gender specific infant formulas are given in table III

2 weeks to 1 month of

Up to 2 weeks of age 1 to 2 months of age age

F M F M F M

Ingredients Per Litre Per Litre Per Litre

Energy

670 670 670 670 670 670 (kcal)

12.1 13.8 10.01 10.8 12.1 13.8 including including including including including including

Alpha- Alpha- Alpha- Alpha- Alpha- Alpha-

Protein (g) lactalbumi lactalbumi lactalbumi lactalbumi lactalbumi lactalbumi n in a n in a n in a n in a n in a n in a concentrati concentrati concentrati concentrati concentrati concentrati on of 3.18g on of 3.34g on of 3.09g on of 3.25g on of 2.99g on of 2.72g Fat (g) 35.7 35.7 35.7 35.7 35.7 35.7

Linoleic acid

5.3 5.3 5.3 5.3 5.3 5.3 (g)

a-Linolen ic

675 675 675 675 675 675 acid (mg)

Lactose (g) 74.7 74.7 74.7 74.7 74.7 74.7

Prebiotic

(100% GOS) 4.3 4.3 4.3 4.3 4.3 4.3 (g)

Minera ls (g) 2.5 2.5 2.5 2.5 2.5 2.5

Na (mg) 150 150 150 150 150 150

K (mg) 590 590 590 590 590 590

CI (mg) 430 430 430 430 430 430

Ca (mg) 410 410 410 410 410 410

P (mg) 210 210 210 210 210 210

Mg (mg) 50 50 50 50 50 50

Mn (Mg) 50 50 50 50 50 50

Se (Mg) 13 13 13 13 13 13

Vita min A

700 700 700 700 700 700 (ng RE)

Vita min D

10 10 10 10 10 10 (Hg)

Vita min E

5.4 5.4 5.4 5.4 5.4 5.4 (mg TE)

Vita min Kl

54 54 54 54 54 54 ( g)

Vita min C

67 67 67 67 67 67 (mg)

Vita min B l

0.47 0.47 0.47 0.47 0.47 0.47 (mg)

Vita min B2

1 1 1 1 1 1 (mg)

N iacin (mg) 6.7 6.7 6.7 6.7 6.7 6.7

Vita min B6

0.5 0.5 0.5 0.5 0.5 0.5 (mg)

Lactoferrin

1 1 1 1 1 1 (bovine) g

Folic acid

60 60 60 60 60 60

Pantothen ic

3 3 3 3 3 3 acid (mg) Vita min B 12

2 2 2 2 2 2 (Hg)

Biotin ^g) 15 15 15 15 15 15

Choline

67 67 67 67 67 67 (mg)

Fe (mg) 8 8 8 8 8 8

Kng) 100 100 100 100 100 100

Cu (mg) 0.4 0.4 0.4 0.4 0.4 0.4

Zn (mg) 5 5 5 5 5 5

Table III

Example 3

An example of a nutritiona l system in accordance with the invention is given in table IV.

Table IV