Vision on Atlanta (USA) - January 26, 2016

Gilbert M. Weber, PhD Senior Science Fellow Animal Nutrition & Health DSM Nutritional Products, Kaiseraugst (Switzerland) What is the Reason for Production Problems such as … Dry / Scaly Skin Paralysis / Lameness Fertility Problems

Low Immune Response Deformed /Brittle Bones

Poor Absorption of Nutrients Ascites Diarrhoea

Perosis Necrosis of Heart Fibers Muscular Myopathy

Fatty Liver and Kidney Syndrome Cervical Paralysis

Osteomalacia Pododermatitis Hepatic Necrosis

Susceptibility to Infection Inflamed Mouth Resorption Disorders

Depression of Appetite Increased Blood-clotting Time

Vitamin Deficiencies Page 2 The Century of the Vitamins

1929-1967: 12 Nobel Prices awarded to 20 Scientists for Synthesis, Characterization und Elucidation of Function of the Vitamins

1912: Term “Vitamins” 1946: First Large- 2011: 12. Edition of the coined by scale, industrial Recommendation Folder Casimir Funk Synthesis of Vitamin A DSM Vitamin Supplementation by Roche Guidelines for Domestic Animals published

1900 1950 2012 1934-87: Development of industrial Production Processes for Vitamins by Roche, starting with Vitamin C 1906-41: 13 Vitamins identified and characterized

Page 3 It is Time for an Update of the DSM Vitamin Supplementation Guidelines

Page 4 Vitamins: Definitions and Functions • Vitamins are essential micronutrients, required for optimum health and normal physiological functions such as growth, development, maintenance or reproduction of the animal. • Most vitamins cannot be synthesized by the animals and therefore they must be obtained from the feed. • Vitamins exercise catalytic functions; they facilitate both synthesis and degradation of the nutrients, thereby controlling the metabolism. • Vitamins are classified into two groups: • Fat-soluble (4): vitamin A (retinol), vitamin D (calciferols), vitamin E (tocopherols), vitamin K (phylloquinone

• Water soluble (9): vitamins B1 (thiamin), B2 (), B6 (pyridoxine), B12 (cobalamin), niacin (vitamin PP), pantothenic acid (vitamin B5), folic acid (vitamin M), (vitamin H), vitamin C (ascorbic acid).

Page 5 Factors influencing Vitamin Requirements Genetics/ Breed Temperature Life Stage /Humidity

Infectious Vitamin Feed Pressure Demand Composition

Housing Stress Conditions

Performance

Page 6 Consequences of Insufficient Dietary Supply of Vitamins • In case of a temporary or chronic undersupply with vitamins, animals will suffer from subclinical deficiency, impacting on performance, health and welfare. • Clinical results in growth , deterioration of feed conversion as well as in irreversible serious disorders of various origin, which can lead to death of the affected animal.

Page 7 Vitamin Deficiencies in Poultry

Encephalomalacia – - Vitamin D3 Perosis - Biotin Vitamin E (and Selenium)

Fatty Liver Hemorrhagic Vitamin B1 Deficiency Vitamin B Deficiency Syndrome (FLHS) Vitamin B12 2 and E Deficiencies

Page 8 Vitamin Deficiencies in Swine

Vitamin E deficiency: Mulberry Heart Disease : toxic liver dystrophy Pantothenic acid deficiency: splayed hind legs

Biotin deficiency: severe Left: healthy new-born piglet. necrosis along coronet, Right: piglet from a vitamin C- initial necrosis in skin. deficient sow, showing navel bleeding Page 9 The OVN™ Concept Optimum Vitamin Nutrition (OVNTM) is about feeding animals high quality vitamins in the right amounts and ratios appropriate to their life stage and growing conditions.

Optimum Vitamin Nutrition is a cost-effective range of vitamin supplementation optimizing • Animal Health and Welfare • Performance • Quality and Nutritional Value of Animal-origin Foods

Page 10

Optimum Vitamin Nutrition Graph

esponse R

Special Applications • Above optimum levels • Optimizing certain Animal Optimum NRC attributes such as • Offsetting factors immunity, meat quality, influencing vitamin bone health, etc. Sub-optimum requirement • Above NRC levels • Permitting optimum health, productivity Average Average • Preventing clinical Deficient deficiency signs and and food quality and • Below NRC levels disorders nutritional value • Animals at risks of • Inadequate to permit developing clinical optimum health and deficiency signs and productivity disorders Total Vitamin Intake

Page 11 Effect of Optimum Vitamin Nutrition on Performance and Meat Yield of Broilers

Body Weight (g) FCR (g/g) 2000 1.5

1000 1 a b 0.5 a b 0 0 0-21 days 0-40 days 0-21 days 0-40 days Industry OVN Industry OVN

380 15.5 360 15 340 14.5 320 a b 14 a b 300 13.5 Breast weight (g) Breast yield (%) Industry OVN Industry OVN

Perez-Vendrell and Weber, 2007

Page 12 OVN Trials in Poultry: 2000 - 2013

Authors Year Country ROI 1. Coelho 2000 USA n.a. 2. Perez-Vendrell et al. (IRTA) 2002 Spain n.a. 3. Perez-Vendrell and Weber (IRTA) 2007 Spain n.a. 4. Zhang et al.* 2011 China 13:1 5. Araujo et al. 2012 Brazil 5:1 6. Iglesias et al. (Granja Tres Arroyos, Cobb) 2012 Argentina 2:1 7. Aviagen Product Dev. Center 2012 USA 3:1 8. NKP FARM 2012 Thailand n.a. 9. Aviforum 2013 Switzerland 2,8:1 10. INRA & ITAVI 2013 France 5,2:1 * Trial on layers

Page 13 Impact of Genetic Improvement on Vitamin Supplementation

The improved efficiency reduces vitamin intake per unit of productivity and dictates the need for more dietary vitamin

1985 2005 ∆/year Layer (1 kg) 2.7 IU/egg 2.1 IU/egg -1.1% Broiler (2 kg) 40 IU/kg gain 34 IU/kg gain -0.8% Turkey (14 kg) 55 IU/kg gain 48 IU/kg gain -0.6% All diets containing 20 IU Vitamin E/kg feed

Genetic driven improved performance requires each year an adjustment of vitamin supplementation in the range of 1%

Leeson, 2007

Page 14 Broilers & Broiler Breeders

• Many changes were made when producing the 2011 Vitamin Supplementation Guidelines • After 5 years, a few adjustments have been required • All vitamin levels are perfectly fitting with genetic companies Broilers & Broiler Breeders Changes

Broilers Category Phase Vitamin Change 2011 2016 Rationale Broilers Starter A min 10,000 12,000 Aligned with Genetic Companies

D min 3,000 4,000 Aligned with Genetic Companies suggesting a straight requirement of 5,000 IU/kg

In the footnote is recommended for optimum immune function to increase level up E max 300 200 to 300 mg/kg A minimum requirement has been set e.g. by Oiolo, 1991 and Whitehead, 2000 Biotin min 0.2 0.25 around from 0.2 to 0.25 mg/kg Grower D min 3,000 4,000 Aligned with Genetic Companies suggesting a straight requirement of 5,000 IU/kg 0.25 - A minimum requirement has been set e.g. by Oiolo, 1991 and Whitehead, 2000 Biotin range 0.2 - 0.3 0.40 around from 0.2 to 0.25 mg/kg Finisher D min 3,000 4,000 Aligned with Genetic Companies suggesting a straight requirement of 5,000 IU/kg 0.25 - A minimum requirement has been set (e.g. Oiolo, 1991; Whitehead, 2000) around Biotin range 0.2 - 0.3 0.40 from 0.2 to 0.25 mg/kg Starter/Grower Aligned with Genetic Companies suggesting a straight requirement of 4,000 - 5,000 Breeders D max 4,000 5,000 (Pullets) IU/kg In the footnote is recommended for optimum immune function to increase level up E range 80 - 100 100 - 150 to 300 mg/kg

B1 max 3 3.5 Slight increase for ensuring adequate plasma levels (Olkowski and Classen, 1999)

B2 range 6 - 8 8 - 10 Aligned with Genetic Companies (recommendation is up to 12 mg/kg) Aligned with Genetic Companies; higher levels can be recommended in case of foot B range 3 - 5 4 - 6 6 problems Aligned with Genetic Companies; already in 1997 Whitehead was recommending 2.0 Folic acid max 2 2.5 to 2.5 as minimum A minimum requirement has been set (e.g. Oiolo, 1991; Whitehead, 2000) around Biotin min 0.2 0.25 from 0.2 to 0.25 mg/kg Turkeys & Turkey Breeders

• Many changes were made when producing the 2011 Vitamin Supplementation Guidelines • After 5 years, a few adjustments have been required • All vitamin levels are perfectly fitting with genetic companies Turkeys & Turkey Breeders Changes

Turkeys Category Phase Vitamin Change 2011 2016 Rationale In the footnote it is recommended for optimum immune function to Turkey Starter E range 100 - 250 150 - 200 increase level up to 300 mg/kg

Grower no changes -

Finisher 1 no changes -

Aligned with Genetic Companies suggesting a straight requirement of Finisher 2 D range 2,000 - 3,000 3,000 - 4,000 4,000 IU/kg In the footnote it is recommended for optimum immune function to Breeders Starter E max 250 150 increase level up to 300 mg/kg

Grower no changes -

Layers and no changes - male breeders Layers & Other Poultry

• Many changes were made when producing the 2011 Vitamin Supplementation Guidelines • After 5 years, a few adjustments have been required • All vitamin levels are perfectly fitting with genetic companies Layers & Other Poultry Changes

Layers and other poultry species Category Phase Vitamin Change 2011 2016 Rationale In the footnote it is recommended for optimum immune Hens and Duck Layers Starter (Pullets) E max 100 70 function increase level up to 100 mg/kg

Rearing (Pullets) D range 2,000 - 3,000 3,000 - 4,000 Alignment with genetic companies

Layers no changes -

Pullets, Layers Breeders no changes - and Male Breeders

Ducks and Geese B2 range 7.0 - 9.0 5.0 - 7.0 Lower levels as given for the full grow-out phases Partridges, no changes - Quails and Pheasants

Ostrich and Emu no changes - Vitamin Trials in Swine: 1995 - 2012 Authors Vitamins Year Country ROI 1. Stahly et al. Group B 1995 USA n.a. 2. Lindemann et al. Group B 1999 USA n.a. 3. Castaing et al. OVN 2001 France 2,5:1 4. Weiss and Quanz OVN 2002 Germany 2,5:1 5. Commercial trial* OVN 2004 Spain + 6. Commercial trials (3 sites)* OVN 2005 Germany + 7. Stahly et al. Group B 2007 USA n.a. 8. IRTA (sows) OVN 2011 Spain n.a. 9. IRTA (pigs) OVN 2012 Spain n.a.

* ROI was not calculated but a positive net benefit was measured

Page 21 Swine

• Many changes were made when producing the 2011 Vitamin Supplementation Guidelines • After 5 years, a few adjustments have been required • All vitamin levels are perfectly fitting with genetic companies Swine Changes

Swine Category Phase Vitamin Change 2011 2016 Rationale Fattening To better prevent hoof problems; industry practice for higher levels reported Pre-starter Biotin range 0.2 - 0.4 0.3 - 0.5 Pigs in some markets

C range 100 - 200 200 - 250 J. R. Bergstrom and M. S. Edmonds 2014 MW-ASAS, Abstract #189

Starter Biotin range 0.2 - 0.4 0.3 - 0.5 Wilt and Carlson, 2009

Grower no changes -

Finisher no changes -

Replacement Breeders K range 1.5 - 3.0 2.0 - 3.5 Some genetic companies recommend up to 4.0 to 4.5 gilts

B6 range 3.5 - 5.5 5.0 - 8.0 Dalto et al., 2015 Aligned with some industry practices and genetic companies recommending Niacin range 20 - 30 25 - 35 35 mg/kg Aligned with some industry practices and genetic companies recommending Sows Niacin min 25 30 also >40 mg/kg Aligned with some industry practices and genetic companies recommending Pantothenic range 30 - 35 35 - 40 35 mg/kg

Boars Niacin min 25 30 Aligned with some industry practices and genetic companies Challenges on Poultry under Production Conditions

Stocking Lighting Noise Litter Temperature Air Quality Humidity Density Conditions Level Quality Changes

Release of Free Radicals Immune Stress Diseases Inflammation Disorders /Reactive Oxygen Species Response

Accelerated Metabolic Rate

Higher Vitamin Requirements

Page 24 Immune Responses and Health • Infectious diseases can spread quickly throughout a broiler or a turkey flock. • The efficacy of the immune system, which is the primary line of defense, is dependent on an adequate nutrient supply for the development of its key organs, for the rapid expansion of effector cells and for the subsequent synthesis of antibodies.

• Among the micronutrients, the vitamins A, D3 ® and its metabolite 25-OH-D3 (Hy•D ) as well as the vitamins E and C were demonstrated to have a direct modulating activity on the immune system (Klasing, 1998).

Page 25 Vitamin E: Humoral Immune Response in Broilers • Female broiler chicks (day-old) 5.0 • 4 dietary treatments: 4.5 • Basal diet (20 ppm Vit E) 4.0 • Basal diet + 100 ppm Vit E 3.5 • Basal diet + 200 ppm Vit E 3.0 • Basal diet + 300 ppm Vit E 2.5 • Vaccination at 28 days of age with 2.0

inactivated and emulsified (log2) Titers Antibody HI 1.5 Newcastle disease virus 1.0 • Blood sample on days 7, 14, 21, 28, 7 14 21 28 38 48 58 38, 48 and 58 Days after Vaccination

Basal Diet BD + 100 ppm Vit E

BD + 200 ppm Vit E BD + 300 ppm Vit E

Franchini et al., 1986

Page 26 Skeletal Problems / Leg Disorders

® • 25-OH-D3 [Hy•D ], the first metabolite in the activation cascade of vitamin D3 is more readily available to provide the classical benefits of vitamin

D3, i.e. better calcium and phosphorus utilization, improved bone mineralization and prevention of bone disorders (rickets, TD). • Tibial dyschondroplasia (TD): • delayed mineralization of the cartilage in the growth plates of long bones • can result in bending or twisting of the bones • induce lameness • considered to be painful. ® • Vitamin D3 metabolites (e.g. 25-OH-D3 [Hy•D ]) reduce both incidence and severity of TD.

Page 27 Hy•D and Tibial Dyschondroplasia

ROSLIN INSTITUTE AUBURN UNIVERISTY

12 Control D3 Hy•D (75 µg/kg) (75 µg/kg) 10 Normal Tibial 35.0% 88.0% Growth Plates: 8

6 Abnormal Tibial Growth Plates: 4

Severity 0 25.0% 2.0% affected % Birds 2 Severity 1 12.5% 2.0% 0 Severity 2 16.7% 6.0% TD Severity TD Incidence

Severity 3 10.4% 2.0% D3: 2’760 IU/kg Hy•D: 68.9 µg/kg 100.0% 100.0% Hy•D: 344 µg/kg

Page 28 Stress: Transport and Others • Stress of transport of broilers to the slaughterhouse: • can reduce the quality of the end product • is recognized as welfare issue. • High levels of vitamin C (applied via the drinking water just before catch): • calm down the birds during transport • improve important sensory properties of the meat (field observation). • Elevated levels of vitamin E reduce the negative impact of heat stress on laying performance in hens (Bollengier-Lee et al., 1999).

Page 29 Pododermatits: A Welfare Issue

Page 30 Surface of Reticulate Scales at Digital Foot Pad of Turkeys

Biotin Group (2000 mcg/kg) Control Group (200 mcg/kg)

Buda et al., 2000

Page 31 Claw Problems in Pigs due to Biotin Deficiency

Page 32 End Product Quality • Meat is an important component of the daily nutrition: • it represents a reliable source of vitamins, particularly of the B-group • supplementation of meat-type poultry with higher levels of vitamins improves the nutritional value of the end product. • When supplemented to poultry at elevated levels, vitamin E interferes with lipid oxidation in fresh and processed meat and thereby reduces quality deterioration through oxidative rancidity and drip loss. • Eggs represent a perfect vehicle for the transfer of vitamins to humans: • most dietary vitamins are readily deposited in the egg yolk and accordingly are enriching eggs with essential micronutrients.

Page 33 The OVN™ Concept: Summary • Recent research on vitamin requirement of modern farm animals under current husbandry conditions is limited; tabular recommendations may underestimate the actual needs of poultry. • Clinical / subclinical vitamin deficiency can still occur: • optimum vitamin supplementation prevents from deficiency and helps to entirely exploit the genetic performance potential of livestock. • Superior dietary supplementation levels of certain vitamins do provide additional value, such as improved stress and disease resistance, adequate welfare or better product quality.

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