ReaShure Rumen-protected Choline: Providing an Essential Nutrient that is Deficient for Transition Dairy Cows

Transcription

1 ReaShure Rumen-protected Choline: Providing an Essential Nutrient that is Deficient for Transition Dairy Cows Ric R. Grummer Ruminant Technical Director Balchem Corp., New Hampton, NY Emeritus Professor Department of Dairy Science University of Wisconsin-Madison

2 History of the Dairy NRC Year Published Years Between ?? ?? At best- 15

3 Are We Due for New One?? 1998 Swine New Committee Working: 2013? 2000 Beef 2015? 2001 Dairy 2016?

4 Choline Dairy NRC 2001 The establishment of a choline requirement, either for lactating dairy cow, or a transition cow in the late dry period and in early lactation, will require more extensive feeding experiments than available at the time of this publication. Given the uncertainty for publishing the next NRC- Time to re-evaluate??? Balchem is logical leader of discussion.

5 An essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health, and thus must be obtained from a dietary source.

6 Are Transition Cows Deficient in Dietary Choline?? Two Important Questions: Q#1: Do they exhibit deficiencies symptoms?? Q#2: Can the deficiency symptom be alleviated via supplementation??

7 Q#1:Do they exhibit deficiencies symptoms?? What is the classic deficiency symptom? Fatty liver (consistent across species) Choline is required for phoshpatidylcholine synthesis which is required for fat export out of the liver as very low density lipoprotein (VLDL) Cole et al., 2011 NEFA from adipose tissue Choline PC TG Protein VLDL C Mammary Tissue CE Liver

8 Q#1:Do they exhibit deficiencies symptoms?? Definitely!! >50% of fresh cows have moderate to severe fatty liver (5% or more fat, wet basis) Reid, 1980 (England) Mazur et al., 1988 (France) Schafer et al., 1991 (Germany) Grummer, 1993 (USA) Jorritsma et al (Netherlands)

9 Why Are Cow So Susceptible to Fatty Liver?? Hepatic requirement for choline is high Absorption of dietary choline is low Endogenous synthesis of choline is probably insufficient

10 Hepatic requirement for choline is high Fatty acid uptake by the liver is determined by two major factors NEFA concentration in blood Blood flow to the liver

11 NEFA, um Plasma NEFA Day relative to calving Grummer, 1993

12 Blood Flow to the Liver Reynolds et al., 2003

13 Calculated NEFA uptake by liver during the transition period. (Reynolds et al., 2003) g/d * Day relative to parturition

14 Strain on the Liver The liver weighs 20 lb and can accumulate over 1 lb of fat by the day after calving (Drackely, 2001)! One point of BCS loss will deliver ~10-12 lb of fat to the liver! Normal liver Fatty Liver

15 Absorption of dietary choline is low Dr. R. Erdman (1992) Feed intake: 30 g/d Escaping ruminal breakdown: 1g/d Ruminal production: 0 g/d Supply to intestine: 1 g/d

16 [1-14C]-Oleate Exported as 14C-TG umol/gm dry cell Insufficient Choline is Probably the Reason for Low Rates of TG Export From the Liver in Ruminants 16 Rat Goat Time of Incubation (hours) 4 Kleppe et al., 1988

17 Q#2:Can the deficiency symptom be alleviated via protected choline supplementation?? Wageningen University and Research Center Zom et al., 2011 Performance study: 38 multiparous HF dairy cows Trt 3 wks pre-calving to 6 wks post-calving DMI, milk yield, blood parameters (glucose, NEFA, BHB) Liver metabolism: 16 cows from performance study Liver biopsy at wks -3, 1, 3 and 6 TAG

18 Feeding 60 g/d ReaShure from 3 wk Precalving to 6 wk Post Reduces Liver Triglyceride * * Zom et al., 2011

19 MTTP Gene Expression P < 0.05 Dotted line = control Solid line = choline Goselink et al., 2012, submitted to J. Dairy Sci.

20 So transition cows are deficient in choline and get fatty liver- so what???? Does alleviating the deficiency translate into something that is of economic importance to the producer???

21 Pathophysiology of Fatty Liver Damage to cell structures Reduced capacity to Make glucose Detoxify urea Synthesize proteins Respond to hormones What about: Milk production? Immune response? Reproductive efficiency?

22 Association of fat build up in the liver with reproductive performance in dairy cows. G. Bobe, J. W. Young, and D. C. Beitz. J. Dairy Sci. 87: Parameter Association 1 Reference First ovarian activity ++ Reid et al., 1983; Rukkwamsuk et al., 1999 First ovulation + Reid et al., 1983 First estrus + Paulová et al., 1990; Jorritsma et al., 2000 First insemination + Reid et al., 1983 Days open ++ Heinonen et al., 1987; Paulová et al., 1990 Pregnancy rate ++ Haraszti et al., 1982; Jorritsma et al., 2000 Services/cow + Schäfer et al., 1988; Paulová et al., The number of + signs represent slight, moderate, or strong detrimental association of fatty liver.

23 1st Service Conception Rate ReaShure improves 1 st Service Conception rates Control ReaShure 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% University of Missouri 62 Cows* WI Trial # 1 92 Cows** WI Trial # Cows** NY Trial 725 Cows** CA Field Trial 300 Cows** UC Davis California 362 Cows*** *Journal of Dairy Science, Vol 87, (Supl.1):334 ** Balchem Technical research Reports: 2004:3-5, 2005:2 *** Lima etal 2006 ADSA Abstract 23

24 Effect of RPC on Ketosis P = Lima et al., 2012

25 Effect of RPC on Health P = * Includes clinical ketosis Lima et al., 2007, 2012

26 Meta Analysis of 13 Transition Cow Studies Examining Supplementation of Ruminally Protected Choline- Objective: To pool data from multiple transition cow studies to determine if there are statistically significant production responses to supplementing rumen protected choline

27 About the Studies 12/13 studies fed pre- and postfresh; 1 study fed prefresh only (to heifers only) Feeding prepartum began anywhere from -7 to -28 d prior to calving; most -21 d Feeding postpartum: anywhere from 0 to 120 d postpartum Values used from each study represented a wide variation in time frames. Each study weighted by size and variation

28 Studies Included Study CholineDose Product Duration Exp. Unit Parity Hartwell et al. 0,6,12 Capshure -21 to M Zom et al. 15 ReaShure -21 to M Lima et al. #1 15 ReaShure -25 to 80 4 (pen) M, P Lima et al. #2 15 ReaShure -22 to 0 5 (pen) P Oelrichs et al. 15 ReaShure -28 to M, P Zahra et al. 14 ReaShure -25 to28 91 M, P Piepenbrink et al. 11,15, 19 ReaShure -21 to M Janovick et al. 15 ReaShure -21 to M Elek et al. 25/50 Norcol to M, P Ardalan et al. 14 Col to M, P Pinotte et al. 20 Overcholine 45% -14 to M Xu et al. #1 7.5 Not reported -7 to 21 7 M Xu et al. #2 11,22,33 Not reported -15 to 15 9 M, P

29 DMI, lb/d +1.6 lb/d P =.0042, SEd =.46

30 Milk Yield, lb/d +4.9 lb/d P <.0001, SEd =.75

31 Milk Yield (lb/d) by Study

32 ECM Yield, lb/d +5.9 lb/d P =.0038, SEd = 1.33

33 % or lb/d Real Results Challenge- All Herds -23% All 21 herds stayed on ReaShure after RRC +7.4% -49% -67% -46% -22% -46% (15) (8) (18) (19) (15) (9) (18)

34 % or lb/d Real Results Challenge- All Herds +6.4% All 15 herds stayed on ReaShure after RRC -73% -58% -50% -50% -50% -29% (12) (6) (14) (13) (8) (5) (12)

35 ReaShure ROI Calculator MILK Per Cow 100 cow/year (+4.9 lb/d average of 13 univ. studies; $17/cwt; 90 d) $ $5,116 HEALTH (Santos and Lima, 2009) $71.59 $6,608 REPRO (28 vs 41% CR; 4 field studies, 2 univ. studies) $ 8.19 $ 756 ReaShure Investment $19.54 $1,804 Feed Cost (1.6 cents/lb; 90 d) $17.28 $1,595 Net Return on ReaShure $98.31 $9,081 ROI

36 Other products to consider for transition dairy cows??

37 Methionine as a lipotropic agent?? Methyl donor for synthesis of choline Amino acid precursor for apolipoproteins Relatively little data Fatty liver studies: no effect on liver triglyceride Bertics and Grummer (1999) HMB using feed restricted dry cows Piepenbrink et al., (2004) HMB using transition cows Osorio et al., (2011) Smartamine or Metasmart to transition cows 37

38 Monensin- Mode of Action Antibiotic that alters rumen microflora and rumen fermentation Increases proprionate production (glucose precursor) and decreases methane production in the rumen Improves the efficiency of dietary energy utilzation Improved energy status equals increased insulin (?) 38

39 Monensin- Results Results: Decreases FA mobilization (positive mechanism; 7% reduction in blood NEFA; Duffield et al., 2008) Decreases blood ketones (BHBA, 13%, Duffield et al., 2008) Does not decrease fatty liver (Zahra et al., 2006; Chung et al., 2008)?? Milk yield (+2.3%), DMI (-2.3%), Fat % (-3.2%), Prod. Effic. (+2.4%) (Duffield et al., 2008)

40 Positioning Monensin Monensin ( mg/d): Can reduce fatty acid mobilization via a favorable mechanism (improved energy status of cow) Can reduce the incidence of ketosis, but perhaps not potent enough to reduce fatty liver Does not have direct effects on liver Synergistic to choline??? Feed starting at -21 d prepartum to 21 d postpartum (and longer for increases in feed efficiency)

41 Chromium- Mode of Action Essential nutrient for humans and animals As a constituent of chromodulin (glucose tolerance factor), potentiates the action of insulin If it increases insulin sensitivity, it should reduce fatty acid mobilization (negative mechanism) Cow purposefully become less sensitive to insulin at parturition: To reduce glucose uptake by insulin sensitive tissues (e.g. muscle, adipose) and direct glucose to insulin insensitive tissues (mammary) Increase fatty acid mobilization Why would you want to counteract that??

42 Chromium and Transition Cows-Performance Study Source Duration Prepartum DMI 1, kg/d Hayirli et al., 2001 Pechova et al., 2003 Smith et al., 2005&2008 Mcnamara & Valdez, 2005 Sadri et al., 2009 Soltan, 2010 Rockwell & Allen, 2011 Cr-Met (8 mg/d) Cr-yeast (10 mg/d) Cr-Met (8 mg/d) Cr-Prop (10 mg/d) Cr-Met (10 mg/d) Cr-? (6 mg/d) Cr-Prop (8 mg/d) Postpartum DMI 1, kg/d Milk or ECM yield 2, kg/d -28 to +28 d to +30 d NR NR NS -21 to +28 d NS to +35 d NS NS/ NS/ to 28 d NS NS NS -21 to 84 d NR NS/ to +28 d NR NS NS/ If multiple doses, maximum response reported 2 ECM if provided 3 NS during time of supplementation (1-35 DIM), Significant for 1-90 DIM 4 NS during the entire postpartum period, Significant for d NS during time of supplementation (1-28 DIM), Significant for DIM NS = P.15 NR = not reported

43 Chromium and Transition Cows-Metabolics Study Pre NEFA, meq/l Post NEFA, meq/l Post Glucose, mg/dl Post GTT Post Liver TG Hayirli et al., NS NS +/- 1 NS Pechova et al., 2003 NR NS NR NR Smith et al., 2005&2008 NS NS NS NR NS Mcnamara and Valdez, 2005 NS NS NS NR NR Sadri et al., 2009 NR NR NR NR NR Soltan, NS NR NR NS = nonsignificant, P.15, NR = not reported 1 lowered peak glucose, slowed glucose CR 2 response not seen until week at 2 and 4 wk postpartum

44 Niacin Generic name; two forms Nicotinic acid (NA) & Nicotinamine (NAM) Antilipolytic (pharmacological doses) NA but not NAM (human data) Microbes can convert NAM to NA Common feed additive to prevent ketosis Ruminal synthesis ~1.5 g/d, potential requirement ~.25 g/d (Erdman, 1992)

45 Past Research- Feeding Trials with Free Niacin Meta-analysis 27 studies (Schwab et al., 2005) 6 g/d: no lactation response 12 g/d +0.4 kg milk, P = g fat, P = g protein, P = 0.08 No effect on plasma NEFA, BHBA (NRC, 2001; Schwab et al., 2005) As much as 98% of supplemental free niacin degraded in the rumen

46 NiaShure: Also an Antilipolytic Compound Resent research feeding 8 or 16 g nicotinic acid (as NiaShure)/d to transition cows: Reduces peak NEFA concentration (UW and KS) Reduces liver TG? UW) No effect on milk production (UW and KS) Decreased energy corrected milk production (UW) for first 3 weeks after calving

47 NEFA (μeq/l) UW Study- Plasma NEFA 1200 * C RPN Day relative to calving 47

48 Interactions?? Each supplement has a different mode of action Can they have additive effects?? There are no known interactions A possible interaction: 48 Cows with less fat in the liver should be capable of higher rates of gluconeogenesis Monensin provides additional propionate for gluconeogenesis Therefore, one could speculate that benefits of feeding monensin (i.e., enhanced gluconeogenesis) may be higher for cows fed choline

49 Strategies to Prevent Fatty Liver/Ketosis 1.Decrease mobilization of fat from adipose tissue 2.Increase fat (VLDL) transport out of the liver Adipose TAG Fatty Acid Glycerol Mobilized Fat NEFA NEFA Oxid AcCoA Ketone TAG CO 2 VLDL Stored TAG Negative EB Hormonal changes at calving Liver

50 Summary Will there be a next NRC?? When?? >2016 Uncertainty surrounding next NRC dictates that the industry must continuously evaluate nutrient requirements, e.g., choline Transition cows experience great changes in energy balance and increases in fatty acid mobilization. IT IS NORMAL! IT SUPPORTS LACTATION! Cows are clearly deficient in choline as evidenced by the increase in liver fat and the ability of supplemental choline to moderate the increase!

51 Summary Supplementation of rumen-protected choline enhances cow performance, health, and reproduction. Choline should be treated no differently than Vit. A, D, E and Ca, P, etc. You would not intentionally formulate diets to be deficient.. Feed 60 g ReaShure/d (~15 g choline) from 3 wk pre- to 3 wk postcalving.

52 Thank You!

53 Commonly Asked Questions: Choline Do you have to feed 60 g Reasure/day?? Cornell research compared 0, 45, 60 and 75 g/d and greatest reduction in liver fat or greatest increase in liver glycogen was observed at either 60 or 75 g/d 53

54 Commonly Asked Questions: Choline When should you feed ReaShure? From 21 d prepartum to 21 d postpartum Feeding for longer periods of time postpartum may be beneficial, but research to test that idea has not been conducted 54

55 Commonly Asked Questions: Choline Can I just feed Reashure prepartum? Just Postpartum? Liver Fat % Feed pretpartum to prevent fatty liver Feed postpartum to alleviate fatty liver and prevent further accumulation Day relative to calving 55

56 Theoretical effects of feeding ReaShure Pre, Post or Pre and Postpartum Liver Fat % Day relative to calving Pre Only Post Only Pre and Post 56

57 Commonly Asked Questions: Choline Should I use ReaShure for all cows or just those herds having a problem? All cows! Numerous studies suggest a high incidence rate of fatty liver in fresh cows; not just in over conditioned or sick cows. Almost all the data collected to date has been from normal cows Milk, SCK/health, and repro Choline is an essential nutrient that is deficient in transition dairy cows

58 Commonly Asked Questions: Choline How can I justify feeding such an expensive additive?!?! Remember: it is an essential nutrient, not an additive! Fatty liver is the classic deficiency symptom in non-rumininant animals studied to date Certainly, the cow is deficient in choline when NEFA are peaking and feed intake depressed!! Other times??? 58

59 Commonly Asked Questions: Choline How can I justify feeding such an expensive additive?!?! Think of it as inexpensive insurance!! Cost of producing milk ($17.50/100 lb average for WI farms 07/ 08; 22,000 milk): $3,850 Cost of feeding ReaShure: $13 13/3850 =.3% of total cost of producing milk! ROI = 8 to 10 59

60 Commonly Asked Questions: Choline How does ReaShure improve milk production and reproductive performance? ReaShure Protected Choline Spare methionine Increases Fat Export Out of the Liver Improves Cow Health Decreases the Prevelance of Fatty Liver and Ketosis Increases Hepatic Gluconeogenesis Increases Milk Production Increases Reproductive Performance

61 Commonly Asked Questions: Choline Are all encapsulated choline products the same? True encapsulation Matrix encapsulation No compound at surface High protection & stability Compound at surface Reduced protection & stability