# Patent

## Title
Compositions for improved oxidative status in companion animals

## Abstract

A food composition that is useful for increasing antioxidant levels in the body is provided having increased levels of sulfur-containing amino acids, such as methionine, cysteine, or mixtures thereof. Methods of using these compositions for increasing antioxidant levels in the body in mammals, especially in companion animals, are also provided.

## Background
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 10/884,733, filed Jul. 2, 2004, which claims the benefit of U.S. Provisional Application 60/485,194, filed Jul. 7, 2003, and which claims the benefit of U.S. Provisional Application No. 60/608,925, filed Jul. 3, 2003, which is a conversion of Ser. No. 10/613,604, filed Jul. 3, 2003, from a utility application to a provisional application, which applications are hereby incorporated by reference in their entirety.


FIELD
The present invention relates to companion-animal diet compositions and, more particularly, to companion-animal diet compositions and methods for increasing blood antioxidant levels and/or oxygen radical absorptive capacity in companion animals.
BACKGROUND
Oxidative stress can result from either or both of an excess of free radicals and a decrease in antioxidant levels in the body. Many diseases and conditions are thought to be associated with increased oxidative stress. Nevertheless, effective dietary approaches for reducing oxidative stress have not been available.
SUMMARY
Accordingly, the inventors herein have succeeded in discovering that feeding a diet composition comprising a sulfur-containing antioxidant, in particular, a sulfur-containing amino acid, decreases oxidative stress by increasing blood antioxidant levels.
Thus, in various embodiments, the present invention includes a method for increasing blood antioxidant levels in a companion animal. The companion animal can be a young companion animal such as a kitten or a puppy or an adult companion animal such as a cat or a dog. The terms “cat” and “feline” are used interchangeably herein. The method can comprise feeding to the companion animal, in particular, a feline an effective amount of a diet comprising at least one sulfur-containing antioxidant. The sulfur-containing antioxidant can be, in particular, a sulfur-containing amino acid. In various embodiments, the sulfur-containing antioxidant can be a sulfur-containing antioxidant other than lipoic acid. In various embodiments, the feline can be a young feline.
The present invention can also include, in various embodiments, a diet composition suitable for feeding to young companion animals. The diet composition can comprise a sulfur-containing antioxidant and, in particular, a sulfur-containing amino acid, in an amount effective in increasing blood antioxidant levels. The sulfur-containing antioxidant can be a sulfur-containing antioxidant other than lipoic acid.
In various embodiments, the companion animal can be a feline and the feline can be a young feline. In various embodiments, the companion animal can be a dog and, in particular, a puppy.
The sulfur-containing antioxidant can, in various embodiments, include sulfur-containing amino acids including cysteine, methionine, taurine, glutathione, s-adenosyl methionine, n-acetyl cysteine, cystathionine, cysteic acid, cysteine sulfinic acid, cystine, methionine sulfone, methionine sulfoxide, betaine, methyl hydroxy analog of methionine and mixtures thereof or a methyl ester of said sulfur-containing amino acid such as, for example, methionine methyl ester. In particular, for compositions and methods involving cats, the sulfur-containing antioxidant can be methionine at a concentration of, for example, from about 0.8 wt. % to about 1.5 wt. %; cysteine at a concentration of, for example, from about 0.2 wt. % to about 0.7 wt. %; of a mixture of cysteine and methionine at a total concentration of, for example, from about 1.0 wt. % to about 2.2 wt. %. For compositions and methods involving dogs, the sulfur-containing antioxidant can be methionine at a concentration of, for example, from about 0.3 wt. % to about 0.6 wt. %; cysteine at a concentration of, for example, from about 0.15 wt. % to about 0.4 wt. %; of a mixture of cysteine and methionine at a total concentration of, for example, from about 0.45 wt. % to about 1 wt. %.
In various embodiments, an increase in antioxidant levels can be indicated by the measurement of by an increase in blood taurine concentrations, an increase in blood oxygen radical absorptive capacity, an increase in blood vitamin E concentrations or combinations thereof. The increase in antioxidant levels can produce improved cognitive function, decreased brain aging, decreased DNA damage, decreased oxidative stress from exercise, improved immune function, improved management of diabetes, improved management of cardiovascular disease, improved management of gastrointestinal disease, increased growth performance in young animal, increased longevity in adult felines or combinations thereof.


DETAILED DESCRIPTION
The present invention provides compositions and methods for increasing blood antioxidant levels in a companion animal and, in particular, a feline. The compositions and methods can involve a diet comprising at least one sulfur-containing antioxidant and, in particular, a sulfur-containing amino acid at a concentration effective in increasing blood antioxidant levels and/or oxygen radical absorptive capacity in the companion animal.
In various embodiments, the compositions and methods can be used with companion animals such as cats or dogs of any age. Young companion animals such as kittens or puppies can be animals up to about one year of age; adult animals can be cats of an age from about one to about seven years and dogs of an age from about one to about five-seven years, depending upon the breed; and senior animals can be cats or dogs of an age greater than about seven years. In various embodiments, the compositions and methods of the present invention can be used in young companion animals such as kittens or puppies from birth up to about one year of age.
A dietary antioxidant, or precursor thereof, can be defined as “a substance in foods that significantly decreases the adverse effects of reactive species, such as reactive oxygen and nitrogen species, on normal physiological function in humans”. (Dietary Reference Intakes of Vitamin C, Vitamin E, Selenium, and Carotenoids, Food and Nutrition Board Institute of Medicine, National Academy Press, Washington, D.C., April, 2000, p. 42, said reference being incorporated in its entirety by reference).
Numerous antioxidants can be found in nature and many of such antioxidants are sulfur-containing antioxidants. For example, while not intending to be bound by any theoretical mechanism of action, the sulfur-containing amino acid, methionine, is believed to possess free-radical scavenging activity by virtue of its containing a sulfur which is oxidizable, as well as its having chelating ability. Methionine can also serve as precursor of other antioxidant compounds such as, for example, cysteine. As another example, the sulfur-containing amino acid, cysteine, also contains an oxidizable sulfur and this amino acid can serve as a precursor of the antioxidant glutathione. In a further example of a sulfur-containing antioxidant, the sulfonic amino acid, taurine, is believed to act as an antioxidant by reacting with excess hypochlorite produced in the process of phagocytosis to form N-chlorotaurine. Specific, non-limiting examples of sulfur containing antioxidants include sulfur-containing amino acids including cysteine, methionine, taurine, glutathione, s-adenosyl methionine, n-acetyl cysteine, cystathionine, cysteic acid, cysteine sulfinic acid, cystine, methionine sulfone, methionine sulfoxide, betaine, methyl hydroxy analog of methionine, sulfur containing amino acids in addition to those listed above, methyl esters of amino acids such as methionine methyl ester, and the like including other sulfur-containing substance exhibiting the properties described above.
The sulfur-containing antioxidants or sulfur-containing amino acids of the present invention can be naturally occurring or synthetic substances. In various embodiments, the sulfur-containing antioxidants include antioxidants other than lipoic acid.
Total sulfur-containing antioxidants can be supplied to dogs and cats as sulfur-containing amino acids such as, for example, methionine, cysteine and cystine, betaine, and methyl hydroxy analog of methionine. These amino acids and other amino acids can be provided in the pure form as d- and l-isomers, or can be provided by ingredients rich in sulfur-containing amino acids such as poultry by-product meal, soybean meal, corn gluten meal, and the like. Table 1 provided indicates acceptable levels of methionine, cysteine, and Total Sulfur-containing Amino Acids (TSAA), i.e. the total of the concentrations of methionine and cysteine.









TABLE 1






Canine
Feline



















Met
0.3-0.6%
0.8-1.5%



Cys
0.15-0.4% 
0.2-0.7%



TSAA
0.45-1%  
  1-2.2%









The present invention provides a food composition having increased levels of sulfur-containing antioxidants such as the amino acid methionine, for use in mammals, especially companion animals, and particularly for use in dogs or cats. The addition of sulfur-containing amino acids to a feline or canine food can increase the levels of antioxidants in the body, and can provide enhanced growth in young animals, improved longevity in adult animals, and assist in managing age-related problems in older animals.
The term “wt %” as employed throughout the specification and claims refers to wt % calculated on a dry matter basis.
The above compositions and methods are particularly useful wherein the oxidative status of the companion animal can benefit from increased levels of antioxidants, such as young animals in the growth stage, mature animals in need of antioxidants as a preventative for development of disease states related to oxidative stress, and in aging animals already demonstrating health issues related to oxidative stress, such as decreased cognitive abilities.
The base food composition containing these additional sulfur-containing amino acids may be any nutritionally complete diet typically employed with companion animals, and will be suitable for the animal's dietary needs. Additional nutrients where appropriate, including nutraceutical compounds that provide health benefits, may be added.
Canned or dry food may be employed. Wet cat or dog food generally has a moisture content greater than about 65%. Semi-moist cat or dog food typically has a moisture content between about 20% and about 65% and may include humectants, potassium sorbate, and other ingredients to prevent microbial growth (bacteria and mold). Dry cat or dog food (kibble) generally has a moisture content below about 10% and its processing typically includes extruding, drying and/or baking in heat.
Levels of sulfur-containing amino acids may be measured by suitable means known in the art. The maximum levels of total sulfur-containing amino acids, levels of methionine, and levels of cysteine may be added to the feed up to the toxic levels of said amino acids. Toxic levels of the sulfur-containing amino acids may be defined as levels of the amino acids that result in an overall imbalance of the levels of the other amino acids present. Toxic levels of the sulfur-containing amino acids for dogs and cats are further known in the art. As an example, methionine levels in cat foods are not allowed to exceed 1.5 wt % by the American Association of Feed Controllers.
Sulfur-containing amino acids, such as methionine, cysteine, and mixtures thereof, provided in the present food composition are from about 0.15 to about 2.2 wt %. Suitable representative minimum sulfur-containing amino acids concentrations include about 0.15, about 0.2, about 0.3, about 0.45, about 0.8, about 1, about 1.2, and about 1.4 wt %. Suitable representative maximum sulfur-containing amino acids concentrations include about 0.5, about 0.7, about 1, about 1.5, and about 2.2 wt %. Preferred for the present invention are sulfur-containing amino acid concentrations of from about 0.15 to about 1.5 wt %. Additionally preferred for the practice of the present invention are sulfur-containing amino acid concentrations of from about 0.3 to about 1 wt %. Particularly preferred for the practice of the present invention are sulfur-containing amino acid concentrations of from about 0.3 to about 0.6 wt %.
Methionine can be present in the diet compositions of the present invention at a concentration of at least about 0.15%, at least about 0.3 wt. %, at least about 0.4 wt. %, at least about 0.6 wt. %, at least about 0.8 wt. %, at least about 0.9% wt. %, at least about 1 wt %, at least about 1.1 wt. % up to about 1.5% or greater. Cysteine can be present in the diet compositions of the present invention at concentrations of at least about 0.15 wt. %, at least about 0.2 wt. %, at least about 0.3 wt. %, at least about 0.4 wt. %, at least about 0.5% wt. % up to about 0.7% or greater. The combination of methionine and cysteine can also be present at a total concentration of sulfur amino acids of at least about at least about 0.3 wt. %, at least about 0.45 wt. %, at least about 0.6 wt. %, at least about 0.8 wt. %, at least about 1.0 wt. %, at least about 1.2 wt. %, at least about 1.4 wt. %, at least about 1.5 wt. %, at least about 1.6 wt. %, up to about 2.2 wt. %.
When the term “food” is used, this can refer not only to a food product which typically provides most, if not all, the nutrient value for a companion animal, but may also refer to such items as a snack, treat, supplement, and the like.
The food composition may be provided to any mammal, particularly a companion animal, such as a dog or cat, which is in need of improved levels of antioxidants, thus resulting in improved growth rate, or in assistance with health issues that may result from aging.
The benefit provided by the present composition which includes increased levels of methionine, cysteine, or mixtures thereof, has been observed as provided in the data below in growing kitten as an increase in the rate of weight gain.
Example 1
This example illustrates the effect of a food composition having increased amounts of methionine on growth performance in kittens.
Dietary methionine was increased above NRC (1986) and AAFCO (2001) estimates for growing kittens. The results indicate that methionine levels of 1.2 to 1.5 wt % in canned cat foods improve oxygen radical absorption capacity and vitamin E concentrations in the blood of growing kittens, thus improving antioxidant status in growing kittens.
Dietary methionine was fed to growing kittens at three levels (0.77, 1.14, and 1.50%) to determine the effect of methionine on growth performance and antioxidant activity. Kittens were fed meat based, canned diets for 10 weeks post-weaning. Weekly weight gain was increased (Table 2) in cats fed 1.14 wt % and 1.50 wt % dietary methionine compared to cats fed 0.77 wt % dietary methionine. The greater weekly growth rate resulted in heavier kittens at the end of the 10-week growth trial. The data demonstrate a greater methionine requirement for growth in young kittens than current NRC (1986) estimates. Thus, methionine was a limiting nutrient for growth in meat based canned diets.
Kittens fed a diet containing 1.50 wt % dietary methionine had greater blood taurine concentrations, oxygen radical absorptive capacity (ORAC), and vitamin E concentrations than kittens fed 0.77 wt % methionine at week 5 of the trial (Table 2). Whole blood taurine and serum vitamin E concentrations were greater at week 10 for kittens fed 1.50 wt % dietary methionine compared to kittens fed 0.77 wt % dietary methionine. Oxygen radical absorptive capacity was not increased by dietary methionine at week 10.
The data illustrate a link between dietary methionine and blood ORAC and vitamin E concentrations for kittens immediately following weaning. The increase in serum antioxidant levels (vitamin E) and free radical absorbing capacity (ORAC) in kittens fed greater dietary methionine suggests a positive relationship between dietary methionine and blood antioxidant activity. The response to dietary methionine was greater during the first five weeks of the trial, which were more stressful than the final five weeks of the trial.
NRC (1986) estimates for dietary methionine are 0.45 wt % and AAFCO (2001) estimates are 0.62% for growing kittens. The data provided in Tables 2 and 3 below indicate that the methionine requirement for kittens fed wet pet food is about 1.2 to about 1.5 wt % in order to improve antioxidant status and free radical absorption capacity.







TABLE 2







Effect of methionine supplementation on growth performance of kittens










Dietary Methionine, wt %
Contrast (P-value)














0.77
1.14
1.50
Linear
Quadratic
CV

















Weekly gain, g
95.00
107.50
122.14
0.35
0.06
21.92


Total gain, g
950.00
1075.00
1221.43
0.35
0.06
21.92


Final wt., g
1518.75
1612.50
1792.86
0.35
0.06
14.43
















TABLE 3







Effect of methionine supplementation on blood metabolites










Dietary Methionine, wt %
Contrast (P-value)













Metabolite
0.77
1.14
1.50
Linear
Quadratic
CV
















Week 5








Taurine
575.63
630.00
783.71
0.02
0.02
17.38


ORAC
2521.84
2694.51
3164.36
0.02
0.50
17.13


Vitamin E
15.63
19.86
30.19
0.01
0.14
20.96


Week 10


Taurine
625.75
616.13
784.57
0.02
0.18
18.39


ORAC
2972.53
2503.38
3013.31
0.86
0.02
15.88


Vitamin E
20.74
24.24
25.13
0.10
0.55
20.92

## Claims

1. A method for increasing blood antioxidant levels in a feline in need thereof, the method comprising feeding to the feline an effective amount of a diet comprising methionine in an amount of about 1.2 wt % to about 1.5 wt %, and cysteine in an amount of about 0.4 wt % to about 0.7 wt %, wherein the methionine and cysteine are present at an amount effective to provide beneficial blood antioxidant levels related to an increase in a taurine concentration, a vitamin E concentration, and/or a blood oxygen radical absorptive capacity in the feline's blood.

2. The method of claim 1 wherein the feline is a kitten.

3. The method according to claim 1, wherein increasing antioxidant levels provides a benefit selected from the group consisting of improved cognitive function, decreased brain aging, decreased DNA damage, decreased oxidative stress from exercise, improved immune function, improved management of diabetes, improved management of cardiovascular disease, improved management of gastrointestinal disease, increased growth performance in young animal and increased longevity in adult felines.

4. The method of claim 3 wherein increasing antioxidant levels increases growth performance in kittens.

5. A method for decreasing oxidative stress in a feline in need thereof comprising feeding to the feline an effective amount of a diet comprising a mixture of cysteine and methionine in an amount of about 1.6 wt % to about 2.2 wt %, wherein the mixture is present at an amount effective to provide beneficial blood antioxidant levels related to an increase in a taurine concentration, a vitamin E concentration, and/or a blood oxygen radical absorptive capacity in the feline's blood thereby decreasing oxidative stress, wherein said beneficial blood antioxidant levels provide a benefit to the feline selected from the group consisting of improved cognitive function, decreased brain aging, decreased DNA damage, decreased oxidative stress from exercise, improved immune function, improved management of diabetes, improved management of cardiovascular disease, improved management of gastrointestinal disease, increased growth performance in young animal and increased longevity in adult felines, and combinations thereof.

6. The method of claim 1 wherein the beneficial blood antioxidant levels is related to an increase in said taurine concentration.

7. The method of claim 1 wherein the beneficial blood antioxidant levels is related to an increase in said Vitamin E concentration.

8. The method of claim 1 wherein the beneficial blood antioxidant levels is related to an increase in said blood oxygen radical absorptive capacity.