AN INFANT FORMULA COMPOSITION IN LIQUID FORM
Field of the Invention
This invention relates to infant formula compositions containing lutein and
zeaxanthin and the use of such compositions as a source of nutrition for infants.
Background of the Invention
Lutein and zeaxanthin are naturally occurring xanthophyils (plant pigments
that are a sub-class of carotenoids) found in commonly consumed foods such as
spinach, kale, corn and oranges. Humans cannot synthesize lutein or zeaxanthin,
therefore, the only source of lutein and zeaxanthin in the human body is from the
diet. Unlike beta-carotene, lutein and zeaxanthin cannot be converted into vitamin A.
Lutein and zeaxanthin have similar chemical structures and can only be distinguished
from one another using specialized analytical methods. The compounds can be
referred to collectively as "lutein + zeaxanthin" to reflect that the compounds were not
separated during chemical analysis.
Lutein and zeaxanthin are the only common dietary carotenoids found in the
retina of the human eye. The mechanism of selective accumulation of lutein and
zeaxanthin in the eye is currently poorly understood. However, the fact that lutein
and zeaxanthin are accumulated in the human eye indicates that they may perform a
biological function. Lutein and zeaxanthin may protect the retina from damage by
acting as antioxidants or filtering out damaging wavelengths of blue light. In addition,
lutein and zeaxanthin may improve visual acuity by filtering out blue light that is not
fully focused by the lens (Hammond, et al, Arch Biochem Biophys (2001), 385, p. 41-
46). These properties may be especially important for the young infant because
infant visual acuity develops slowly during the first months of life (McCulloch, Opthal
Physiol Opt (1998), 18. p. 140-146) and their eyes do not filter out harmful light as
well as adults (Gaillard, et al. IOVS (2000), 41. p. 1454-1459).

Although the compounds lutein and zeaxanthin are well-known, very little
information is available about lutein and zeaxanthin in relation to the diet of human
infants. Several studies have measured the amount of lutein and/or zeaxanthin in
cord blood (Kiely et al., Eur J Clin Nutr (1999), 53, p. 711-715; Oostenbrug et al.,
BrJ Nutr (1998), 80, p. 67-73; Oostenbrug et al., Eur J Clin Nutr (1998), 52,
p. 754-759; Yeum et al., J Am Coll Nutr (1998), 17, p. 442-447). However, these
findings relate to lutein and zeaxanthin derived from the mother's blood and not from
the infant's own dietary sources. One review included preliminary data on plasma
lutein levels in nine breastfed infants (Jewell et al., Proc Nutr Soc (2001), 60,
p. 171-178) and an abstract by the same authors (Jewell, et al, Proc Nutr Soc (2001),
60, OCB) followed up plasma lutein and zeaxanthin in a group of preterm infants for
up to five weeks. These investigations found that there is a high correlation between
lutein and zeaxanthin concentrations in the plasma of mothers and their breast fed
infants. However, the authors did not compare plasma levels of lutein or zeaxanthin
in formula-fed versus breastfed infants. Another paper compared plasma levels of
some carotenoids in breast-fed versus formula fed infants, but plasma levels of lutein
or zeaxanthin were not reported (Sommerburg et al., Eur. J. Pedialr. (2000) 159:
86-90).
A poster entitled "Contribution of Beta Carotene (PC) from pC Enriched
Formulae to Individual and Total Serum Carotenoids in Term Infants" presented at
the Society for Pediatric Research meeting at Seattle. Washington, USA, in May of
1994, compared plasma concentrations of carotenoids in full term formula-fed versus
breast-fed infants. The findings demonstrated that in formula-fed infants, serum
carotenoid levels (including lutein levels) are lower in comparison to breast-fed
infants.
Chemical analyses of lutein and zeaxanthin in post-mortem infant eyes have
been reported in three studies, although none of these studies has differentiated
between breastfed and formula-fed infants. Handelman et al., (IOVS (1988), 29,
p. 850-855) reported retina lutein and zeaxanthin levels for two infants while Bone,
et al, reported lutein and zeaxanthin levels for five infants in one study (Bone et al.,
Exp. Eye Res. (1997) 64, 211-218) and four infants in another (Bone et al., IOVS

(1988), 29, p. 843-849). In general, infants had lower total retina concentrations of
lutein and zeaxanthin than children or adults, but the ratio of lutein to zeaxanthin was
much higher in infants compared to adults. Thus, infants are distinct from older
children and adults with respect to lutein and zeaxanthin in the eye.
Several studies have measured the combined lutein + zeaxanthin content of
human milk samples. See, e.g., Canfield et al., Eur. J. Nutr., 40:30-38 (2001);
Schweigert et al., Int. J. Vitam. Nutr. Res.. 70(3) p. 79-83 (2000); Canfield et al., Am.
J. Clin. Nutr.. 67:276-283 (1998); Canfield et al., Anal. Chem. 69, p. 1873-1881
(1997); Giuliano et al., Methods In Immunology, Vol. 213 p. 381-399 (1992); and
Patton et al.. LIPIDS, Vol. 25. No. 3. p. 159-165 (1990). One study has separately
reported lutein versus zeaxanthin levels in human milk (Khachik et al. Anal. Chem.
(1997), 69, 1873-1881). Thus, human breast milk contains lutein and zeaxanthin.
However, lutein and zeaxanthin are not currently added to any infant formula.
Formulations containing carotenoids, such as lutein and zeaxanthin, among
other ingredients, are known. U.S. Patent No. 6,261,598 discloses carotenoid
formulations containing B-carotene, lycopene and lutein and the use thereof in
human foods.
WO 200137781 discloses aqueous dispersions of nutrients selected from (a)
an isoflavone. (b) lycopene, (c) lutein and (d) a co-enzyme for use in beverages and
cosmetics.
EP774251 discloses the use of the 3R-3'R stereoisomer of zeaxanthin in the
manufacture of medicaments as nutritional supplements for the treatment or
prophylaxis of macular degeneration in humans.
EP1155620 discloses nutritional compositions for dietary supplements
) comprising a mineral portion, at least 40% fish oil and a vitamin portion including a
selection of vitamins and derivatives thereof selected from beta carotene, B-complex
vitamins, Vitamin C, Vitamin D. Vitamin E, folic acid and biotin.

However, the use of lutein and zeaxanthin in infant formula compositions has
heretofore not been described. Accordingly, there is a need for such a formulation.
Summary of the Invention
The present invention is related to an infant formula composition comprising
lutein and zeaxanthin. The invention is further directed to a method for feeding an
infant comprising administering to the infant a composition comprising lutein and
zeaxanthin.
Detailed Description of the Invention
The lutein and zeaxanthin components useful in the present formula may be
in the form of free xanthophylls, xanthopyll esters or other chemical forms of lutein or
zeaxanthinand may be prepared by any one or more of various methods recognized
by those skilled in the art. For example, lutein and zeaxanthin may be obtained by
extraction from marigolds or other xanthophylls-rich sources, chemical synthesis,
fermentation or other biotechnology-derived and enriched xanthophyll sources. A
suitable form of lutein and zeaxanthin useful in the present invention is available
commercially as "Lutein 5% TG" from Roche Vitamins, Inc., (Parsippany, NJ).
The infant formula composition of the present invention may comprise lutein
and zeaxanthin in an amount of about 6 to about 230 mcg/Liter. Preferably the
present infant formula compositions contain about 15 to about 44 mcg/Liter, more
preferably about 20 to about 30 mcg, liter and most preferably, about 25 meg/Liter of
lutein and zeaxanthin. The amounts of lutein and zeaxanthin disclosed herein refer
to the combined amount of the compounds lutein and zeaxanthin and not these
compounds individually. Therefore, as long as the formulations contain the total
amount of lutein and zeaxanthin set forth herein, the amounts of the individual
components is not critical.
The use of lutein and zeaxanthin in the present amounts closely resembles
the amounts of such compounds found in human breast milk on a worldwide basis.

As reported at the 2000 International Society for Research on Human Milk and
Lactation Meeting, one study analyzed the total lutein and zeaxanthin content of
human milk samples from 450 women from nine countries. The lowest individual
concentration of lutein and zeaxanthin observed was 6 mcg/Liter and the highest
concentration was 230 mcg/Liter
The following table sets forth the average concentration of lutein and
zeaxanthin in milk samples from each of the nine countries.

The infant formula compositions of the present invention may be prepared by
utilizing conventional bovine milk and protein based formulas such as S-26 or soy
protein based formulas such as Nursoy available from Wyeth Nutrition.
The infant formula compositions of the invention may also contain vitamins
and minerals considered to be essential in the daily diet. These vitamins and
minerals should be present in the infant formula compositions in nutritionally
significant amounts. Examples of suitable vitamins and minerals include vitamin A,
vitamin B complex, vitamin C, vitamin D, vitamin E, vitamin K, calcium, magnesium,
sodium, potassium, phosphorous, copper, zinc, iodine, selenium, iron, niacin, folic
acid, pantothenic acid, biotin, choline, inositol and manganese.

The infant formula compositions may further comprise one or more lipid
sources as will be recognized by those skilled in the art. Furthermore, the present
compositions may contain additional materials shown to have beneficial effects, such
as nucleotides, immunoglobulins, and polyunsaturated fatty acids.
The present invention will now be described with references to the following
examples.
Example 1
An exemplary infant formula composition according to the present invention is
as follows:

The fat blend of the formula is as follows:
The formula of Example 1 was prepared by blending 4500mg of lutein and
zeaxanthin (Lutein 5% TG available from Roche Vitamins) with the fat soluble
vitamins of the formulation. This blend was then added to the fat blend to obtain a
final concentration of lutein and zeaxanthin of 225mg per kg of finished formula
powder. The remainder of the ingredients were blended and the final mix was dried
to obtain a powder.
The present invention may be embodied in other specific forms without
departure from the present as essential attributes thereof and, accordingly, reference
should be made to the approval and claims rather than to the foregoing specification
as indicating the scope of the invention.

WE CLAIM :-
1. An infant formula composition in liquid form comprising lutein and
zeaxanthin in an amount of 6 to 230 mcg/L.
2. An infant formula composition as in Claim 1 comprising lutein and
zeaxanthin in an amount of 15 to 44 mcg/L.
3. An infant formula composition as in Claim 2 comprising lutein and
zeaxanthin in an amount of 20 to 30 mcg/L.
4. An infant formula composition as in Claim 3 comprising 25 mcg/L of luteii
and zeaxanthin.
5. An infant formula composition in the form of a dry powder, wherein said
composition may be reconstituted by adding water to produce a composition of Claim 1.
6. An infant formula composition as in Claim 1, further comprising at least
one of Vitamin A, Vitamin D, Vitamin E and Vitamin B complex.
7. An infant formula composition as in Claim 1, further comprising at least
one of calcium, magnesium, sodium, potassium, phosphorous, copper, zinc, iodine,
selenium and iron.
8. A method of feeding an infant comprising administering to said infant a
nutritionally sufficient amount of the formula of Claim 1.
9. An infant formula composition in liquid form substantially as herein
described particularly with reference to the examples.

Infant formula compositions are provided which comprise lutein and zeaxanthin.