COMBINATION OF 25-HYDROXYVITAMIN D AND ANTIOXIDANTS/ANTI-INFLAMMATORIES FOR POULTRY OVARIAN HEALTH

Abstract

This invention relates to the use of the combination of 25-hydroxyvitamin D3 (“25-OH D3”) and antioxidants/anti-inflammatories (ascorbic acid vitamin E and canthaxanthin) to make a premix or feed which can ameliorate various problems observed in poultry which have been subject to overfeeding. Feeds containing the 25-OH D3 and antioxidants/anti-inflammatories and premixes are also provided.

Claims

1. A poultry feed comprising a supra-physiological dose of 25-Hydroxy vitamin D, ascorbic acid, Vitamin E and canthaxanthin for promoting ovarian health, wherein ovarian health is indicated by at least one indicia of ovarian health selected from the group consisting of: reduced ovarian degeneration, occurrence of ovarian degeneration at a later onset, no occurrence of ovarian degeneration; reduction in the amount of ovarian tumors, reduction in size of ovarian tumors, reduction in both size and number of ovarian tumors, occurrence of ovarian tumors at a later onset, and no occurrence of ovarian tumors.

2. The poultry feed according to claim 1, further comprising at least one further bio-active ingredient selected from the group consisting of: Vitamin D, Vitamin B2, Vitamin B6, Niacin, Zinc, Copper, Manganese, and Selenium.

3. The poultry feed according to claim 1, further comprising at least one bio-active ingredient selected from the group consisting of Vitamin D, Vitamin B2, Vitamin B6, Niacin, Pantothenic Acid, Folic Acid, Biotin, Zinc, Copper, Manganese, and Selenium.

4. The poultry feed according to claim 1, wherein the 25-hydroxy vitamin D is 25-hydroxy vitamin D3 (25-OH D3).

5. A method of promoting ovarian health in poultry, wherein ovarian health is indicated by at least one indicia of ovarian health selected from the group consisting of: reduced ovarian degeneration, occurrence of ovarian degeneration at a later onset, or no occurrence of ovarian degeneration; reduction in the amount of ovarian tumors, reduction in size of ovarian tumors, reduction in both size and number of ovarian tumors, occurrence of ovarian tumors at a later onset, and no occurrence of ovarian tumors; wherein the method comprises feeding poultry a feed comprising a supra-physiological dose of a combination of 25-Hydroxy vitamin D, ascorbic acid, Vitamin E and canthaxanthin.

6. The method according to claim 5, wherein the step of feeding poultry is practiced ad libitum.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0030] FIGS. 1-3 show pictures taken during the necropsy of broiler hens in response to ad libitum feed intake in combination with vitamin D and antioxidant inclusion. Hens were necropsied after 10 weeks of the feeding trial.

[0031] FIG. 1, top left shows an abnormal ventricle, as seen in the untreated group, as compared to a normal ventricle. The middle left and right show transudate within the pericardium. The lower row shows normal pericardia.

[0032] FIG. 2 shows ascites which were found in the abdominal cavity (top left) versus a normal abdominal cavity. The lower row shows tumor-like morphology in the ovary (left), degenerate morphology (center) and normal morphology (right).

[0033] FIG. 3 shows abnormal livers (cirrhosis, left) (fatty liver, center) and a normal liver (right).

[0034] As used throughout this specification and claims, the following definitions apply:

[0035] “25-OH D” refers to any form of 25-hydroxyvitamin D (i.e. either 25-OH D2 or 25-OH D3, or mixes thereof). 25-OH D3 specifically refers to 25-hydroxyvitamin D3; 25-OH D2 specifically refers to 25-hydroxyvitamin D2.

[0036] “Poultry” means any domesticated fowl, including chickens (including broiler, layers and breeding hens), ducks, geese, turkeys, quail, and ostriches.

[0037] “Hyperphagia” is excessive eating; the animal does not voluntarily limit its feeding.

[0038] “Ovarian health” in this invention relies on the following distinct measurable parameters: the amount of ovarian degeneration and ovarian tumors. Benefitting/improving ovarian health thus means that at least one of the following conditions is present upon feeding the combination of this invention: [0039] a) ovarian degeneration is lessened, occurs at a later onset, or does not occur [0040] b) ovarian tumors are reduced in number, reduced in size, reduced in both size and number, occur at a later onset, or do not occur.

[0041] “Ascorbic Acid” and “Vitamin C” are used interchangeably throughout the specification and claims.

[0042] It has been found in accordance with this invention, that the use of feed comprising 25-OH D3, vitamin E, canthaxanthin and ascorbic acid can specifically contribute to ovarian health. Broiler breeder females overfed during reproductive development not only produce excess large yellow ovarian follicles but also generate a greater number of atretic yellow follicles and commonly display erratic oviposition and defective egg syndrome (EODES) that include several reproductive problems such as follicular atresia, the production of soft-shelled or membranous eggs, double-yolked eggs, egg yolk peritonitis (presence of egg yolk in the abdominal cavity), multiple egg days and oviposition not occurring in sequence, resulting in increased production of unsettable eggs. Use of the feed/premix of this invention can lessen, reduce, ameliorate or eliminate each of these conditions.

[0043] Thus one aspect of this invention is a combination comprising 25-Hydroxy vitamin D, ascorbic acid, Vitamin E and canthaxanthin for use in a poultry feed promoting ovarian health, wherein ovarian health is indicated by at least one indicia of ovarian health selected from the group consisting of: [0044] a) reduced ovarian degeneration, occurrence of ovarian degeneration at a later onset, or no occurrence of ovarian degeneration; and [0045] b) reduction in the amount of ovarian tumors, reduction in size of ovarian tumors, reduction in both size and number of ovarian tumors, occurrence at a later onset, or no occurrence of ovarian tumors.

[0046] Specifically it has been found that feed comprising 25-OH D3, vitamin E, canthaxanthin and ascorbic acid can be used in an ad libitum feeding scheme, and will result in poultry which exhibit at least one of these characteristics: [0047] a) ovarian degeneration is lessened, occurs at a later onset, or does not occur; [0048] b) ovarian tumors are reduced in number, reduced in size, reduced in both size and number, occur at a later onset, or do not occur.

[0049] Hens with ovarian degeneration, large follicle atresia or tumors or other abnormal morphology such as internal ovulation, tend to have a lower egg production rate than in their past records. Hens with obesity and related dysregulations such as plasma lipids and ceramide or insulin and leptin level, or tissue cytokine and lipid content tend to have a rapid ovarian degeneration and other abnormalities and thereby a lower egg production rate which can be easily monitored.

Doses

[0050] 25-OH D3: The amount of 25-OH D3 can range from 15-200 μg/kg feed. Preferably, the amount of 25-OH D3 is from 35-150 μg/kg feed. For feed with a low dose of the combination of the invention, 35 μg per kg 25-OH D3/feed is preferred; for food with a medium dose of the combination, 69 μg per kg feed is preferred; and for food with a high dose of 150 μg feed is preferred.

[0051] Vitamin E: The amount of Vitamin E can range from 40-400 mg/kg feed. Preferably the amount is 80-300 mg/kg feed. For feed with a low dose of the combination of the invention, 80 mg/kg Vitamin E is preferred. For feed with a medium dose, 150 mg Vitamin E is preferred; for feed with a high dose, 300 mg/kg Vitamin E is preferred.

[0052] Canthaxanthin: The amount of canthaxanthin can range from 1-15 mg/kg feed. Preferably the amount is 3-12 mg/kg feed. For feed with a low dose of the combination of the invention, 3 mg/kg canthaxanthin is preferred. For feed with a medium dose, 6 mg canthaxanthin is preferred; for feed with a high dose, 12 mg/kg canthaxanthin is preferred.

[0053] Ascorbic Acid: The amount of ascorbic acid can range from 40-400 mg/kg feed. Preferably the amount is 100-300 mg feed. For feed with a low dose of the combination of the invention, 100 mg/kg ascorbic acid is preferred. For feed with a medium dose, 150 mg ascorbic acid is preferred; for feed with a high dose, 300 mg/kg ascorbic acid is preferred.

[0054] Thus specific preferred feeds of this invention comprise the following dosages (all amounts are per kg/feed):

Preferred Feed #1:

[0055] 25-OH D3: 15-200 μg, [0056] Vitamin E: 40-400 mg, [0057] Canthaxanthin: 1-15 mg; and [0058] Ascorbic acid: 40-400 mg.

Preferred Feed #2:

[0059] 25-OH D3: 35-150 μg, [0060] Vitamin E: 80-300 mg, [0061] Canthaxanthin: 3-12 mg, and [0062] Ascorbic acid: 80-300 mg
Preferred Feed #3: (Low dose feed) This feed is preferred for mildly obese poultry. [0063] 25-OH D3: 35 μg [0064] Vitamin E: 80 mg [0065] Canthaxanthin: 3 mg [0066] Ascorbic acid: 80 mg.
Preferred Feed #4 (medium dose feed) This feed is preferred for moderately to severely obese poultry: [0067] 25-OH D3: 69 μg [0068] Vitamin E: 150 mg [0069] Canthaxanthin: 6 mg [0070] Ascorbic acid: 150 mg.
Preferred Feed #5 (high dose feed) This feed is preferred for severely obese poultry: [0071] 25-OH D3: 150 μg [0072] Vitamin E: 300 mg [0073] Canthaxanthin: 12 mg [0074] Ascorbic acid: 300 mg.

Optional Additional Ingredients

[0075] To each of the feeds listed above, at least one of the additional ingredients may be added. Preferably at least one, and more preferably more than one of the following ingredients are added. In other embodiments, all the following ingredients are added: [0076] Vitamin D3—generally this is present in poultry diets at approximately 2500 IU per kg feed. In accordance with this invention, if desired, the amount of Vitamin D is increased to at least 3000 IU per kg. [0077] Vitamin B2: this can be added at 3-25 mg per kg; preferably from 6-20 mg/kg. For low dose feed, 6 mg/kg is preferred. For medium dose feed, 14 mg/kg is preferred; and for high dose feed 20 mg/kg is preferred. [0078] Niacin: this can be added at 25-300 mg per kg feed. Preferably it ranges from 60-200 mg/kg. For low dose feed, 60 mg/kg is preferred. For medium dose feed, 120 mg/kg is preferred; and for high dose feed 200 mg/kg is preferred. [0079] Pantothenic acid: this can be added at 10-120 mg per kg feed. Preferably it ranges from 15-80 mg/kg. For low dose feed, 15 mg/kg is preferred. For medium dose feed, 30 mg/kg is preferred; and for high dose feed 80 mg/kg is preferred. [0080] Folic acid: this can be added at 1-8 mg per kg feed. Preferably it ranges from 2-6 mg/kg. For low dose feed, 2 mg/kg is preferred. For medium dose feed, 4 mg/kg is preferred; and for high dose feed 6 mg/kg is preferred. [0081] Biotin: this can be added at 0.05-1.0 mg/kg feed. Preferably it ranges from 0.2-0.8 mg/kg. For low dose feed, 0.2 mg/kg is preferred. For medium dose feed, 0.4 mg/kg is preferred; and for high dose feed 0.8 mg/kg is preferred. [0082] Zinc: this can be added at 50-300 mg/kg feed. Preferably it ranges from 70-250 mg/kg. For low dose feed, 70 mg/kg is preferred. For medium dose feed, 125 mg/kg is preferred; and for high dose feed 250 mg/kg is preferred. [0083] Copper: this can be added at 5-50 mg/kg feed. Preferably it ranges from 10-30 mg/kg. For low dose feed, 10 mg/kg is preferred. For medium dose feed, 20 mg/kg is preferred; and for high dose feed 30 mg/kg is preferred. [0084] Manganese: this can be added at 50-300 mg/feed. Preferably it ranges from 80-270 mg/kg. For low dose feed, 80 mg/kg is preferred. For medium dose feed, 150 mg/kg is preferred; and for high dose feed 270 mg/kg is preferred. [0085] Selenium: this can be added at 0.05-0.6 mg/kg feed. Preferably it ranges from 0.1-0.4 mg/kg. For low dose feed, 0.1 mg/kg is preferred. For medium dose feed, 0.2 mg/kg is preferred; and for high dose feed 0.4 mg/kg is preferred.

[0086] The following non-limiting Examples are presented to better illustrate the invention.

EXAMPLES

Example 1

Materials and Methods

[0087] A total of thirty 45-week-old broiler breeder hens (ROSS 308) were obtained from a commercial flock for the study. A basal broiler breeder laying diet was formulated as shown in Table 1. The calculated nutrient composition is shown in Table 2.

TABLE-US-00001 TABLE 1 Ingredient composition of the basal broiler breeder laying diets. Composition %, w/w Corn 66.9 Soybean meal 22.2 Oil fat 1.67 Ca Carbonate (ground oyster shell) 6.36 Dicalcium phosphate 1.8 Choline-Cl (70%) 0.1 Mineral Premix.sup.1 0.1 Copper sulfate 0.05 Vitamin Premix.sup.2 0.1 .sup.1Mineral premix provided (per kg of diet for treatment groups 1, 2 and 3): Cu 18 mg; I 1.1 mg; Fe 80 mg; Mn 150 mg; Zn 125 mg; and Se 0.25 mg. .sup.2Refer to Table 2 for further detail.

TABLE-US-00002 TABLE 2 Vitamin premix composition (provided per kg of diet) Treatment 3 Treatments 1 and 2 3 = ad libitum feeding + 1 = restricted feeding 25-OH-D3 + Vitamin 2 = ad libitum feeding antioxidants/anti- A (IU) 10000 12000 D3 (IU) 2500 3000 E (mg) 100 150 K3 (mg) 3 5 B1 (mg) 3 3 B2 (mg) 8 14 B6 (mg) 6 8 B12 (mg) 0.03 0.03 Niacin (mg) 60 120 Pantothenic acid (mg) 18 30 Folic acid (mg) 1 4 Biotin (mg) 0.2 0.4 C (ascorbic acid) (mg) 0 150 25-OH-D3 (mcg) 0 69 Canthaxanthin (mg) 0 6

TABLE-US-00003 TABLE 3 Calculated nutrient composition (%) of the basal broiler breeder laying diets. Composition % w/w Crude protein 16 Crude fat 4.2 Calcium 3.1 Sodium 0.16 Total Phosphorus 0.64 Total ME 2910 kcal/kg

[0088] Diet was supplemented with or without 25-OH D3 at 69 mcg/kg diet in combination with antioxidants/anti-inflammatories (ascorbic acid, canthaxanthin) and enriched levels of selected vitamins. Hens were randomly allocated to 3 treatment groups according to feeding regimen (restricted and ad libitum) as follows:

1. Basal diet—restricted feeding (140 g/day)
2. Basal diet—ad libitum feeding
3. Basal diet—ad libitum feeding+25-OH-D3 at 69 mcg/kg diet+antioxidants/anti-inflammatories

[0089] They were individually-housed in wire cages placed in a controlled room with 14 h:10 h light:dark period and at a temperature of 25±3° C. Water was available ad libitum. The experimental period was lasted for 10 weeks. Three weeks after the feeding trial, some birds were used for relevant plasma parameter analyses. At the end of experiment, hens were euthanized and sacrificed for tissue sample collection for further studies.

Results and Discussion

25-Hydroxy D3 and Antioxidants/Anti-Inflammatories Lowered Mortality and Improved Egg Production, Ovarian Morphology and Plasma 1713 Estradiol Level

[0090] Secretion of estradiol is the hallmark of successful ovulatory follicles. In addition to its role in triggering the preovulatory surge of gonadotropins, estradiol is an important intra-ovarian growth, differentiation, and survival factor. Inclusion of 25-hydroxy D3 and antioxidants/anti-inflammatories reduced mortality and incidence of ovarian degeneration and ovarian-tumor-like morphology, increased egg production and sustained plasma estradiol levels in birds under ad libitum feed intake.

[0091] In the group of hens fed the 25-OH D3+antioxidant diet, a lower number of deaths was observed compared to those fed the non-supplemented diet ad libitum. Egg production was significantly higher, and the incident of degenerated ovaries and the incidence of ovarian tumors was lower in the group fed 25-OH D3+anti-oxidants compared to those fed ad-libitum.

CONCLUSIONS

[0092] Supplemental 25-hydroxy D3 and antioxidants/anti-inflammatories ameliorated deleterious effects associated with overfeeding of broiler breeder females by lowering mortality rate and improving ovary function and therefore reproductive performance of overfed broiler breeder hens.