Background of the invention [0002] Breast-feeding is often declared as a good feeding practice in mammalians including humans. It is believed to provide the kind. ot essential continuity in the food supply that helps overcome the sudden stress experienced at birth and that supports the discontinuous development of the newborn during the first weeks of extra- uterine life. The nine months of intra-uterine development of the human foetus share some analogy with the period of convalescence of hospital patients: confined sterile environment and glucose-based parenteral feeding. In principle, all essential dietary ingredients (vitamins & minerals) are transferred from the mother's blood to differentiating and growing foetal tissues. Vitamin F (essential fatty acids) is no exception to this rule. Among these vitamins are those of plant origin (EFAs) and those of animal origin (LCPs) that the mother synthesises prior + n M f a rs

[00031 At birth, mother substitutes some glucose for fats in milk in addition to adding some protecting nutritional agents (immunoglobulins, decoy carbohydrates, etc) for the protection of the gastro intestinal tract of the baby that is suddenly exposed to environmental invasions. Except for this change in the source of energy that occurs at birth and which is important for the intestinal absorption of fat soluble vitamins, the newborn finds in its mother milk the same dietary panel of essential nutrients that he relied on during the nine month of gestation. Among the animal-derived nutrients present in human milk are CHL and LCPs that fulfil baby's needs until his own lipid metabolic pathways are being switched on to a level that could eventually cope with the requirements of the still-developing tissues and later tissue homeostasis.

[0004] Experiments carried out with mammalians as well as epidemiological human studies have clearly established a relationship between a shortage in animal- derived nutrients at birth and behavioural deficiencies and/or abnormalities (growth, motricity, emotivity, learning performance, IQ, visual acuity, etc) at later stages of development. Re-balancing the diet when the first signs of impairment are observed has been shown to normalise the chemical composition of the tissues, however damage to behaviour, visual and nervous system function are not easily reversed.

[0005] If breast-feeding is abandoned as a feeding practice for more appropriate socially accepted methods, infant formula manufacturers should critically evaluate the content of vitamin F in their product. The relative constancy of the breast milk composition has made some recommendations feasible and such have been endorsed by scientific communities (ESPPGAN, 1991 ; BNF, 1993) and official expert panels (FAO/WHO, 1994). Another expert

panel (LSRO, 1998) did recommend that the question of requiring the addition of specific LCPs to infant formulas be reassessed in five years.

[0006] The FAO/WHO report on Fats and Oils in Human Nutrition (1994)'specified recommended amounts of animal- derived fatty acids in preterm and term infant formulas (table 1).

Table 1: FAO/WHO recommendation for LCPs in preterm and mg/kg BWmg/100 ml formula LCPs Pre-Term Term Pre-Term Term LA 700 600 467 400 a-LnA 50 50 33. 5 33. 5 AA 60 40 40 27 DHA 40 20 27 13. 5 BW : bodyweight, Pre-term & term infants: 150 ml formula/kg BW/day.

(0007] When compared to the average composition of mature human milk (table 2), the WHO/FAO recommendation for term infant formula lie well in line with the amount of LCPs found in breast milk, but the latter is more diverse in those fatty acids.

Table 2: Composition of mature human milk LAY ZA AA a-LnA EPA DPA CHN CHL DHLA DHA Human Milk 350 13.65 11.70 26.32 1.30 12.65 14.5 18.0 (mg1100m1) 25. 35 13. 95 LA: linoleic acid, y-LA: gamma-linolenic acid, DHLA : dihomo-y-linolenic acid, AA : arachidonic acid, a-LnA : alpha-linolenic acid, EPA: eicosapentaenoic acid, DPA:

docosapentaenoic acid, DHA: docosahexaenoic acid, CHN: choline, CHL. : cholesterol.

[0008] AA is crucial to the growth of cell organs and tissues whilst DHA. is particularly important to the proper development of the brain and the retina.

[0009] Of major interest is the presence of A6- desaturase products (y-LA and DHLA) in human milk which may well be crucial to the early establishment of a favourable thromboxane/prostacyclin ratio in the newborn with beneficial effects on blood pressure, clotting ability, kidney and immune system functions.

Aims of the invention [0010] The present invention aims to provide a manufactured lipid emulsion and food composition comprising it, having an improved balanced dietary source of vitamin F, in order to improve the general health of humans, especially of infants.

[OOll] A further aim of the present invention is to provide such a manufactured lipid emulsion having a formula suitable for feeding infants and which may mimic breast feeding.

[0012] A further aim of the invention is to provide such compositions having a balanced dietary source of vitamin F suitable for feeding infants, which is easily obtained from naturally occurring sources at low costs.

Summary of the invention [0013] The present invention is related to a manufactured lipid nano-emulsion having an improved balanced dietary source of vitamin F (especially having a formula suitable for feeding (supplementing) infants, comprising (on a dry basis, fig. 1) between about 10 and

about 20% by weight of phospholipids, including about 1 to about 2% by weight of choline, about 1,5 to about 2,5% by weight of cholesterol, about 35 to about 45% by weight of essential fatty acids and between 35 and 45% by weight of non-essential fatty acids, the total of the emulsion being 100% by weight, which are preferably pre-emulsified animal (preferably egg yolk) phospholipid micelles having an advantageous diameter lower than 0,22 pm, said nano- emulsion being obtained from naturally occurring sources which mimic breast milk micelles (breast milk lipid pattern), but do not correspond to said breast milk product. The emulsion according to the invention does not comprise specific elements present in human breast milk such as antibodies obtained from the mother.

[0014] Said manufactured product is an encapsulation of essential oils in animal (preferably egg) phospholipid micelles, which provides a means to closely mimic the characteristics of emulsified state of human milk and is suitable to adjust fatty acid composition of i. e. cow milk to existing officially recognised standards (tables 1 and 2).

[0015] The manufactured lipid nano-emulsion (particle size < 200 nm) having improved balanced dietary sources of vitamin F are characterised by their extreme level of dispersion which, on the one hand, allows to eliminate bacterial contamination prior to sterilisation and hence to avoid heat-derived pyrogen contamination and, on the other hand, is extremely bio-available through its easy digestion in the gastro-intestinal tract of human of all ages. When distributed in disposable one dose-vials, the manufactured lipid emulsion is also extremely stable against oxidation and contamination since it is essentially kept in sterile sealed containers under nitrogen and it is open at the time of consumption.

[00163 This emulsion (Baby Vitamin F) ensures the new-born of a plentiful supply of prostaglandins with beneficial effects on blood pressure, clotting ability, kidney function and immune system function.

[0017] Among other things, it gives the baby a healthy cardiovascular start into its new world.

[0018] Preferably, the manufactured lipid emulsion according to the invention is a mixture of conditionally essential fatty acids comprising in one gram (on a dry basis, fig. 1) a similar amount of phospholipids (about 145 mg including 14,5 mg of choline, about 18 mg of cholesterol, about 415 mg of essential fatty acids as those found in 100 ml of breast milk (table 2), together with 12, 5% (392 mg) of non-essential fatty acids.

[0019] Such manufactured lipid emulsion could be made available in liquid form (i. e., in small individual vials to be incorporated into the infant bottles prior to consumption) or in powder forms (i. e., spray dried on maltodextrin based carriers).

[0020] Such manufactured lipid emulsion could be mixed with a safe source of other non-essential fats (for instance butter oil or interesterified vegetable oils), which transforms it into an ideal nutritive lipid source suitable for infants. The latter can eventually be spray- dried on a carrier (preferably an element selected from the group consisting of electrodialysed whey and non-fat milk) and eventually containing other additives (vitamines, minerals, ribonucleotides, prostaglandines, immunoglobulines, etc) in order to obtain an ideally balanced infant formula or food composition.

[0021] Preferably, the essential fatty acids are long chain polyunsaturated fatty acids which are linolenic acid (LA), gamma-linolenic acid (y-LA), dihomo-y-linolenic

acid (DHLA), arachidonic acid (AA), alpha-linolenic acid (a-LnA), eicosapentaenoic acid (EPA), docosatentaenoic acid (DPA) and docosahexaenoic acid (DHA).

[0022] Preferably, the lipid emulsion according to the invention comprises as essential fatty acids 30 to 40% linoleic acid, 1 to 2% y-linolenic + dihomo-y-linolenic acid, 0.75 to 1.5% arachidonic acid, 2.0 to 3.0% a- linolenic acid, 0.1 to 0.2% eicosapentaenoic acid, 1.0 to 1.5% docosapentaenoic acid + docosahexaenoic acid.

[0023] Preferably, the arachidonic acid (AA) is obtained from egg yolk phospholipids, the docosahexaenoic acid (DHA) and the eicosapentaenoic acid (EPA) are obtained from marine (fish) oils and the gamma-linolenic acid is obtained from plant (borage) oils.

[0024] Other characteristics of the specific infant formula according to the invention are described in details hereafter.

Short description of the drawings [0025] Fig. 1 represents the lipid emulsion according to the invention (Baby Vitamin FTM).

Detailed description of the invention Infant formula of the product according to the invention (Baby Vitamin F Tm) [0026] Baby Vitamin FTM exclusively contains naturally occurring sources of essential-and conditionally essential fatty acids, and does not rely on single cell oils (SCO) (table 3).

Table 3: Source of fatty acids in Baby Vitamin F Fatty acid Chemical name Abbreviation Source Linoleic C18 : 2o6 LA Sunflower, soja a-linolenic C18: 3m3 a-LnA y-linolenic C18: 3m6 y-LA Plant oil Dihomo-y-linolenic C20: 3 DHLA primrose) Arachidonic C20 : 4m6 AA Animal phospholipids (egg, mammalian) Eicosapentaenoic C20: 5o) 3 EPA Marine oil (fish, Docosapentaenoic C22: 5m3 DPA mammalian) Docosahexaenoic C22: 6a) 3 DHA

[0027] The encapsulation of essential oils in 4%- animal (preferably egg) phospholipid micelles (145 mg phospholipids for 3. 8 g total fat in 100 ml formula) provides a means to closely mimic the characteristic emulsified state of human milk and/or to adjust fatty acid composition of infant formulas to existing officially recognised standards. The product according to the invention (Baby Vitamin FTM) is advantageously an all-in- one emulsion containing animal (preferably egg yolk) phospholipid-derived AA in association with a mixture of highly emulsified LCPs (Fig. 1).

[0028] The product according to the invention is a mixture of the'conditionally-essential'fatty acids found in mature human milk (415 mg per 100 ml). One gram of the product according to the invention provides a similar amount of phospholipids, cholesterol, essential fatty acids

as that found in breast milk, together with non-essential fatty acids. When present in enriched infant formula, they behave as a similarly dispersed source of long chain polyunsaturated fatty acids associated with the right level of cholesterol and choline.

[0029] Advantageously, it provides similar amount of choline (CHN: 14.5 mg/100 ml) and cholesterol (CHL : 18.0 mg/100 ml) as those naturally occurring in human milk, provides increased resistance to oxidation and improves digestibility and uptake. The unique natural arrangement of high-value dietary ingredients in animal (preferably egg) phospholipid finely dispersed micelles makes them homeostatic with the gastro intestinal tract of the baby and quantitatively available through digestion.

Furthermore, animal phospholipids do not present specific antigenic sites, while free or associated with other nutrients such as amino acids and oils.

[0030] Egg yolk phospholipids (EYPLs) have recently been registered as a Novel Food in the European Community (EC 258/97). They differ from phospholipids of plant origin in that they are extremely rich in phosphatidylcholine (PC) and bear substantial amount of naturally-occurring arachidonic acid (AA).

[0031] Phospholipids occur naturally in all natural tissues of vegetable and animal origin. Animal cell membranes differ from their plant ancestors in that they contain long chain polyunsaturated fatty acids (LCPs) and cholesterol (CHL). LCPs appear to be specifically attached to membrane phospholipids. There seems to have been an evolutionary pressure towards the simultaneous appearance of LCPs and CHL in cell membranes of both marine and terrestrial animals in a close to balance ratio. This universal rule contrasts with the rather peculiar distribution of @3-LCPs in long chain triglycerides (LCTs)

found in some cold sea plankton, fish and mammals, and of 6-LCPs in long chain triglycerides (LCTs) found in some land-based fungi, and which appears to be an evolutionary adaptation of primary organisms to a rather hostile environment.

[0032] Membrane fluidity and deformability are important parameters to the enzymic activities of the cell surface and the right balance of LCPs and CHL is probably the single most important factor influencing the rheological properties of the cell membrane. LCPs in membranes are also involved in cell signalling through their conversion to eicosanoids, mainly from arachidonic acid (AA, C20: 4m6), dihomo-y-linolenic acid (DHLA, C20: 3co6) and eicosapentaenoic acid (EPA, C20: 5o) 3). In normal people, the concentration of arachidonic acid in tissue lipids remains almost constant whatever the type of diet they live on. There seems to be some definite requirements for tissue AA-derived eicosanolds production. On the other hand, the presence of DHLA and EPA in cell membrane seems to be related to their dietary level which, in turn, is seen as a potential good indicator for cellular health, tissue homeostasis and global feel good factor. Indeed, DHLA and EPA-derived eicosanoids have been characterised as regulatory metabolites that are complementary to those more potent, though essential, derived from AA.

[0033] LCPs and CHL can be synthesised by the human body but there seems to be critical timing in life (pregnant women, newborn, stressful active people, ageing people, hospital patients, etc) where a balanced source of these animal-derived ingredients is beneficial. Animal phospholipid-based micelles, seem to be a very appropriate food vector for these'conditionally-essential'vitamins.

[0034] The advantages of animal (egg) phospholipids as cell membrane refreshing nutrient are described hereafter: -Phospholipids from animal origin are the single ubiquitous source of LCP. The by-functional biological species is essential to the integrity of all cell membranes in living organisms, -their relative concentration of G) 6 and co3 LCPs can be adjusted by simple dietary means to comply with changing human requirements at various stages of life development, -they naturally bear LCPs at the sn-2 position of the glycerol carrier which become quantitatively (>95%) available upon digestion for tissue incorporation, -they are homeostatic with the GI tract environment.

They transform to lysophospholipids upon digestion, enhancing their emulsifying properties and their capacity to encapsulate and help resorption of other water-and lipid-soluble nutrients, -they contain a high proportion of PC that contribute to maintaining an optimum level of serum free choline in between meals (fasting) through a slow release of the vitamin without providing offensive fishy body odour characteristic of free choline supplementation, -they act as a technological aid in combining with essential oils from plant and marine origin to form highly dispersed emulsions resistant to fatty acid peroxidation, -they contribute to the synthesis of smaller phospholipid-rich chylomicrons and, in turn, higher level of HDL that patrol within the body and clean cell membranes from oxidised cholesterol and phospholipids, egg yolk phospholipids are declared Novel Foods in the European Community (EC 258/97) under the generic designation egg phospholipids'.

REFERENCES BNF, British Nutrition Foundation (1993)-Unsaturated fatty acids. Nutritional and physiological significance.

The Report of the British Nutrition Foundation's Task Force. London, Chapman & Hall.

COMA (1995) Report on Health and Social Subjects No. 46, Nutritional Aspects of Cardiovascular Diseases, ISBN 0 11 321875 3, HMSO, London.

ESPPGAN, European Society for Pediatric Gastroenterology and Nutrition/Committee on Nutrition (1991)-Committee Report. Comment on the content and composition of lipids in infant formulas. Acta. Paediatr. Scand. 80,887-896.

FAO/WHO, Food and Agriculture Organisation/World Health Organisation (1994)-Expert consultation on fats and oils in human nutrition. Food and Nutrition Paper No. 57, Ch. 7,49-55.

LSRO (1998) taken from Nutraceuticals World July/August 1999, Infant Formula Requirements Released, pp. 62-68.

'Columbus@, the natural original egg-A model for healthy animal-derived food (1998) Leatherhead Food RA Food Industry Journal, 1,289-300.

Lecithin and choline-A clinical monograph (1997) Central Soya Company Inc., Fort Wayne, Indiana.

Dietary 3 and zu fatty acids-Biological effects and nutritional essentiality (1989) Life Sciences, Vol. 171, Series A, Plenum Press, ISBN 0-306-43231-5.

Fats that Heal, Fats that Kill (1997) 5th ed., Alive Books, Burnaby, Canada, ISBN 0-920470-40-8.

Availability of seed oils from finnish berries (1999) University of Turku, Finland, Tema-Team 6555-99, ISBN 952-91-1003-0