US20180271118A1 - Combination of 25-hydroxyvitamin d and antioxidants/anti-inflammatories for poultry ovarian health - Google Patents

Combination of 25-hydroxyvitamin d and antioxidants/anti-inflammatories for poultry ovarian health Download PDF

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US20180271118A1
US20180271118A1 US15/542,091 US201615542091A US2018271118A1 US 20180271118 A1 US20180271118 A1 US 20180271118A1 US 201615542091 A US201615542091 A US 201615542091A US 2018271118 A1 US2018271118 A1 US 2018271118A1
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ovarian
vitamin
feed
combination
health
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Shuen Ei CHEN
Thau Kiong Chung
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DSM IP Assets BV
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/174—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23K50/00—Feeding-stuffs specially adapted for particular animals
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    • A23K20/179—Colouring agents, e.g. pigmenting or dyeing agents
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Definitions

  • This invention relates to the combination of 25-hydroxyvitamin D (“25-OH D3” and/or “25-OH D2”) and antioxidants/anti-inflammatories (ascorbic acid, Vitamin E and canthaxanthin) for use in poultry feed to benefit ovarian health.
  • 25-hydroxyvitamin D (“25-OH D3” and/or “25-OH D2”)
  • antioxidants/anti-inflammatories ascorbic acid, Vitamin E and canthaxanthin
  • This combination of nutritional supplements protects poultry against various adverse effects in the ovaries which are associated with hyperphagia such as increased ovarian degeneration and increased tumor formation. It also relates to feed and feed premixes containing the combination of 25-hydroxyvitamin D and the antioxidants/anti-inflammatories for use in protecting ovarian health.
  • LHRH luteinizing hormone releasing hormone
  • FSH follicle stimulating hormone
  • the ovary of an immature pullet has only small undifferentiated follicles invisible to the naked eye. These follicles, upon sexual maturity, increase in size to form an array of small follicles as well as a hierarchy of large follicles varying in size.
  • the small follicles produce estrogen after hypothalamic maturation.
  • the large yellow follicles are usually defined as being greater than 1 cm in diameter, and their numbers are directly influenced by lighting program, plane of nutrition and breeder age. Progesterone released from the largest follicle triggers the ovulation process. Mature follicles are capable of producing progesterone only a few hours prior to ovulation.
  • the liver is a key organ in egg production as it is the site of lipogenesis, leading to formation of fatty acids and subsequently triglycerides that contribute to egg yolk formation, which is in turn driven by estrogen.
  • the skeletal system is intimately associated with egg production for its role in mobilizing, storing and releasing calcium under the influence of estrogen.
  • Hyperphagia and therefore adiposity occurs in broiler breeder females as a consequence of genetic selection for rapid growth in broiler chickens.
  • Overfeeding-induced ovarian dysfunction and reproductive inefficiency as well as metabolic disorders like ascites, sudden death syndrome and fatty liver in broiler breeder females is a consequence of lipotoxicity development as result of fuel overloading the biological system. Therefore, the challenge of managing modern female broiler breeder strains is the inability of these hens to adequately self-regulate feed intake during growth and development to achieve an optimal body weight and composition to support efficient egg and chick production.
  • broiler breeder females are subject to a high degree of restricted feeding regimen.
  • the primary mechanism in which feed restriction benefits reproductive efficiency in broiler breeder females is the control of follicle development or rather limiting the formation of excessive numbers of ovarian yellow follicles arranged in multiple hierarchies.
  • 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.
  • EODES erratic oviposition and defective egg syndrome
  • Hy•D® (registered trademark for 25-OH-D3; available from DSM Nutritional Products, Switzerland has been used to promote bone health in poultry.
  • WO2010/057811 DSM IP ASSETS, BV
  • MAXICHICK The combination of 25-OH D3 and canthaxanthin has also been used in poultry.
  • WO2010/057811 DSM IP ASSETS, BV
  • the combination is commercially available under the trademark MAXICHICK.
  • MAXICHICK There is no mention in the patent publication of the inclusion of ascorbic acid, the use of high vitamin E levels, nor the uses to benefit ovarian health.
  • Vitamin C is often not included as a supplement in poultry diets, as chicken, under normal rearing conditions can produce sufficient Vitamin C. However, it has been used in some specific conditions, such as in heat stress situations.
  • Vitamin E is generally added to poultry feed. Recommended doses for broilers tends to range from about 50-100 IU/kg feed, depending on the age of the animal.
  • WO14/202433 (DSM IP ASSETS B.V) teaches the combination of canthaxanthin and 25-OH D3 to improve internal egg quality, i.e. enhancing the strength of vitelline membrane that envelopes the yolk. There is no teaching to add ascorbic acid to the combination, nor for its use in ameliorating the adverse effects of hyperphagia-related obesity.
  • WO14/191153 (DSM IP ASSETS B.V) teaches the combination of canthaxanthin and at least one of Vitamin C, Vitamin E, selenium, and optionally at least one of thymol, eugenol, vanillin and gamma-terpinene can improve immune statues, bone health, skeletal development and growth and feed conversion, particularly when flocks are subject to stress associated with vaccination.
  • antioxidants of this invention comprise the combination of ascorbic acid, vitamin E and canthaxanthin, although it has also been found, in accordance with this invention that they antioxidants also possess anti-inflammatory activities and thus are referred to as “antioxidant/anti-inflammatories”.
  • one aspect of this invention is the combination of 25-OH D3, canthaxanthin, vitamin E and ascorbic acid to benefit ovarian health.
  • Another embodiment is the combination of 25-OHD2, canthaxanthin, Vitamin E and ascorbic acid to benefit ovarian health.
  • Another embodiment is the combination of 25-OHD3, 25-OHD2, canthaxanthin, Vitamin E and ascorbic acid to benefit ovarian health.
  • 25-OH D2 and 25-OH D3 may act in a similar fashion after administration, it is envisioned that either may be used separately in combination with antioxidants/anti-inflammatories/anti-inflammatories, or a mixture of both 25-OH D3 and 25-OH D2 may be used in combination with antioxidants/anti-inflammatories/anti-inflammatories. If used together, the ratio of 25-OH D3: 25-OH D3 is not a critical part of the invention.
  • Another aspect of this invention is the combination of 25-OH D, canthaxanthin, vitamin E and ascorbic acid, which optionally further comprises at least one further bio-active ingredient selected from the group consisting of:
  • a further aspect is the combination of 25-OH D, canthaxanthin, vitamin E and ascorbic acid which optionally further comprises at least one further bio-active ingredient selected from the group consisting of Vitamin D, Vitamin B2, Vitamin B6, Niacin, Pantothenic Acid, Folic Acid, Biotin, Zinc, Copper, Manganese, Selenium, and combinations thereof to benefit ovarian health.
  • the 25-OH D is 25-OH D3.
  • the further bio-active ingredient includes biotin.
  • the further bio-active ingredient includes Vitamin D and biotin.
  • the further bio-active ingredient includes all the aforementioned optionally bio-active ingredients.
  • Another aspect of this invention is a poultry feed which benefits ovarian health comprising the combination of 25-OH D2 or 25-OH D3 or mixtures thereof, ascorbic acid, Vitamin E and canthaxanthin.
  • poultry feed which benefits ovarian health comprising the combination of 25-OH D, canthaxanthin, vitamin E and ascorbic acid, which optionally further comprises at least one further bio-active ingredient selected from the group consisting of: Vitamin D, Vitamin B2, Vitamin B6, Niacin, Zinc, Copper, Manganese, Selenium and combinations thereof.
  • the 25-OH D is 25-OH D3.
  • the further bio-active ingredients include at least Vitamin D and Selenium. In some cases, all the further bio-active ingredients are added.
  • Another embodiment is poultry feed benefiting ovarian health comprising the combination of 25-OH D, canthaxanthin, vitamin E and ascorbic acid, which optionally further comprises at least one further bio-active ingredient selected from the group consisting of: Vitamin D, Vitamin B2, Vitamin B6, Niacin, Pantothenic Acid, Folic Acid, Biotin, Zinc, Copper, Manganese, Selenium and combinations thereof.
  • the further bio-active ingredient includes biotin.
  • the 25-OH D is 25-OH D3.
  • the further bio-active ingredient includes Vitamin D and biotin.
  • the further bio-active ingredient includes all the aforementioned optionally bio-active ingredients.
  • premixes for poultry feed that benefits ovarian health which comprise the combination of 25-OH D, vitamin E, ascorbic acid and canthaxanthin.
  • the 25-OH D is 25-OH D3.
  • the feed and premix also comprises at least one further bio-active ingredient selected from the group consisting of:
  • premixes for poultry feed which benefits ovarian health which further comprise at least one further bio-active ingredient selected from the group consisting of: Vitamin D, Vitamin B2, Vitamin B6, Niacin, Pantothenic Acid, Folic Acid, Biotin, Zinc, Copper, Manganese, Selenium and combinations thereof.
  • the further bio-active ingredient includes biotin.
  • the further bio-active ingredient includes Vitamin D and biotin.
  • the further bio-active ingredient includes all the aforementioned optionally bio-active ingredients.
  • the 25-OH D and antioxidants/anti-inflammatories of this invention are all used in poultry which are fed a complete diet, so they are not vitamin/mineral deficient.
  • the 25-OH D and antioxidant/combination of this invention is not acting to remedy a vitamin or other nutrient deficiency. It can be considered a supra-physiological dosage.
  • the animals When using the poultry feed of this invention, the animals may be fed ad libitum and the ill effects on ovarian health normally experienced will be experienced to a lesser degree or not at all. This results in easier flock management, and eliminates the problems encountered where the flock is fed a restricted diet, but certain individual birds still exhibit hyperphagia, and may show aggressive behaviors towards other birds.
  • 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.
  • 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.
  • 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).
  • FIG. 3 shows abnormal livers (cirrhosis, left) (fatty liver, center) and a normal liver (right).
  • 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.
  • Pigtry means any domesticated fowl, including chickens (including broiler, layers and breeding hens), ducks, geese, turkeys, quail, and ostriches.
  • “Hyperphagia” is excessive eating; the animal does not voluntarily limit its feeding.
  • “Ovarian health” in this invention relies on the following distinct measurable parameters: the amount of ovarian degeneration and ovarian tumors. Benefiting/improving ovarian health thus means that at least one of the following conditions is present upon feeding the combination of this invention:
  • feed comprising 25-OH D3, vitamin E, canthaxanthin and ascorbic acid
  • 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.
  • 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:
  • 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:
  • the amount of 25-OH D3 can range from 15-200 ⁇ g/kg feed.
  • the amount of 25-OH D3 is from 35-150 ⁇ g/kg feed.
  • 35 ⁇ g per kg 25-OH D3/feed is preferred; for food with a medium dose of the combination, 69 ⁇ g per kg feed is preferred; and for food with a high dose of 150 ⁇ g feed is preferred.
  • 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.
  • 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.
  • 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.
  • At least one of the additional ingredients may be added.
  • at least one, and more preferably more than one of the following ingredients are added.
  • all the following ingredients are added:
  • 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.
  • 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 6.36 oyster shell) Dicalcium phosphate 1.8 Choline-Cl (70%) 0.1 Mineral Premix 1 0.1 Copper sulfate 0.05 Vitamin Premix 2 0.1 1 Mineral 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. 2 Refer to Table 2 for further detail.
  • 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:
  • 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
  • estradiol 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.
  • 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.

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