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Ketosis in dairy cows: Prevention and therapy S. Dänicke

Institute of Animal Nutrition, Braunschweig, Germany Email: sven.daenicke@fli.de

Introduction Ketosis in dairy cows is characterized by increased levels of circulating ketone bodies, particularly of beta-hydroxy-butyrate (BHB), as a result of the inability of the liver to metabolize an excess of non-esterified fatty acids (NEFA) which is typically observed shortly after calving. In this period the energy intake of the cow increases more slowly than the milk energy output does ultimately resulting in a negative energy balance (NEB) and a stimulated lipolysis. Thus, the p.p. lipomobilization syndrome is accompanied by hyperketonaemia and hepatolipidosis (e.g. [1]). Based on the absence or presence of clinical symptoms in combination with the levels of BHB in blood circulation the hyperketonaemia is classified as either subclinical or clinical ketosis irrespective of pathogenesis. Most authors define a subclinical ketosis at BHB concentrations between ≥1.2 and ≤2.0 mMol/L although these thresholds should be considered a convention (e.g. [2-4]). Clinical signs are often paralleled by BHB concentrations of >2.0 mMol/L although they might be absent even at higher BHB levels. Considering this classification it becomes clear that a medical treatment is mostly confined to clinical cases while subclinical cases usually are not discovered and consequently not treated. Preventive measures need to be implemented in view of the significant incidence of subclinical ketosis, its adverse impact on dry matter intake and milk yield, and its association with clinical ketosis and other productions diseases, such as displaced abomasum, metritis and mastitis [2] but also with vaccination success ([5]). Based on the fact that a subclinical ketosis is at high risk to derail into a clinical ketosis prevention of the subclinical form concurrently reduces the incidence of clinical cases and should be the method of choice.

Prevention Preventive measures can be derived from factors putting cows at risk of development of a ketosis. Thus, energy intake shortly after calving should be stimulated while milk energy output could be decreased ultimately resulting in a less pronounced NEB. Energy intake is usually stimulated by gradual increase of the energy concentration of the ration within a period of approximately 2 weeks by means of increasing concentrate feed proportions. At the same time, high-quality roughage needs to be offered ensuring both a high energy concentration [6] and sufficient physically effective neutral detergent fibre (peNDF) (e.g. [7]).

The latter is particularly important to stimulate rumination and to avoid ruminal disorders such as subacute ruminal acidosis (SARA). Other measures to improve the energy supply include optimization of the dietary starch content resistant to rumen degradation in a way that such an amount of ingested starch reaches the small intestine which can be digested and absorbed without flooding the hindgut by undegraded starch. As bovine gluconeogenesis relies on rumen originating propionate feedstuffs consisting of gluconeogenesis its precursors such as propylene glycol are widely used around calving, either as a part of the ration or as drench, in order to provide substrates for gluconeogenesis whereby ketogenic pathways of metabolic intermediates are downregulated. Not only an increased energy supply has the potential to decrease the magnitude of the NEB but also a decreased milk energy output.

However, a decreased milk energy output during the first days after parturition by milking the cows only once a day is less popular because of long-persisting adverse effects on milk yield although this method is the most effective way to minimize p.p. NEB.

Therefore, alternatives for decreasing the milk energy output are aimed at decreasing the energy concentration of the milk and at the same time maintaining the milk yield. The milk fat content can effectively be reduced by feeding conjugated linoleic acids (CLA) which has a marked effect on the energy content of milk due to the high gross energy concentration of fat compared to carbohydrates and proteins. However, literature results are inconsistent regarding the net effect of feeding CLA on NEB showing in some cases a parallel increase in milk yield or a decrease in dry matter intake (DMI).

Besides energy intake and milk energy output, the extent of mobilization of body reserves also influences the magnitude of NEB.

However, particularly an excessive lipomobilization is known to trigger ketogenesis. Cows overconditioned at parturition are at higher risk for such a condition. Body condition score (BCS) is a suitable indicator for production, reproduction and health of cows.

It is simple to determine and particularly the loss of body condition after calving, expressed in BCS points, is related to NEB [8]. It was suggested that for many production and health traits the association to BCS was non-linear [8] which might hinder its usefulness as a predictor for all nutritional and metabolic states. Nevertheless, the optimal BCS according to a 5-point-scale ranges between 3.0 to 3.25; a lower BCS is associated to a compromised production and reproduction whereas a BCS higher than 3.5 is related to a reduced dry matter intake shortly after parturition and to an increased susceptibility to metabolic diseases, most notably to ketosis [8]. Thus, avoiding a too high BCS prior to calving is one of the key elements in preventive feeding strategies. Based on the common practice to offer diets as total mixed rations (TMR) for ad libitum consumption through the whole production cycle it is not always feasible to feed individual cows or groups of cows according to a target BCS. Grouping might even become questionable when the herd is too small. An alternative might be offering partial mixed rations consisting of roughage and a small portion of concentrate feed while most of the concentrate feed is assigned individually according to actual performance and/or BCS through transponder regulated automatic feeders. Although such a way of feeding is close to precision feeding the technical and personal expenditure still needs to be optimized.

Therapy Therapeutic measures that are used to treat a clinical ketosis might include dextrose infusion, treatment with dexamethasone, insulin, a butaphophan-cyanocobalamin combination product, and further measures discussed above; particularly oral propylene glycol treatment (for review see [9]).

References

[1] Dänicke, S. et al., Res Vet Sci, 2018. 116: p. 15-27. [2] Suthar, V.S. et al., J Dairy Sci, 2013. 96(5): p. 2925-38. [3] Duffield, T.F. et al., J Dairy Sci, 2009. 92(2):

p. 571-580. [4] Dirksen, G. et al., Parey-Verlag, Berlin-Wien, 2002. [5] Drong, C. et al., J Anim Physiol Anim Nutr, 2017. 101(4): p. 791-806. [6] Schmitz, R. et al., Arch Anim Nutr, 2018. 72(2): p. 100-120. [7] Zebeli, Q. et al., Livest Sci, 2010. 127(1): p. 1-10. [8] Roche, J.R. et al., J Dairy Sci, 2009. 92(12): p. 5769-5801. [9]

Gordon, J.L. et al., Vet Clin North Am Food Anim Pract, 2013. 29(2): p. 433-45.

Session 07: Metabolic status and risk of disease

The effect of monensin on dairy cows in relation to farm or breed

P. Karis, K. Ling, H. Jaakson, L. Post and M. Ots

Estonian University of Life Sciences, The Chair of Animal Nutrition, Tartu, Estonia Email: Priit.Karis@emu.ee

Introduction Ketosis is a common health problem for high-producing dairy cows at the beginning of lactation. The prevalence of subclinical ketosis in Europe is on average 25 % and it is costly for the farmers as the price is calculated to be 294 € per incident (Raboisson et al 2015). In European Union it is allowed to use monensin as a continuous-release intraruminal device for the reduction of incidence of ketosis in the peri-parturient dairy cow and heifer. Monensin is an antimicrobial agent that attaches to the cell membrane of mainly Gram-positive bacteria and interferes with their ion balance. The shift in the population of ruminal bacteria results in increased production of propionate, which is the main precursor for glucose production in ruminants. Our aim was to study the effect of monensin on high-yielding dairy cows on two farms with different breeds.

Materials and Methods The study was performed on two commercial farms (A, B) with multiparous cows fed grass silage based TMR. Annual milk yield per cow was 11400 kg on Farm A and 12400 kg on farm B. Rations metabolizable energy and protein content were as follows: close-up: Farm A – 10,4 MJ/kg, 85 g/kg; Farm B – 9,65 MJ/kg, 81 g/kg; lactation: Farm A - 11,9 MJ/kg, 102 g/kg,; FarmB - 11,9 MJ/kg, 113 g/kg. On farm A 223 Estonian Holstein (EH) (Groups: Experimental – Mon, n=98; Control – Con, n=125) and on farm B 30 crossbreeds of EH and Estonian Red cows (Mon, n=15; Con, n=14) were enrolled. Monensin continuous-release device (Kexxtone; Elanco®, Bad Homburg, Germany) was administered according to the manufacturer‘s recommendations three weeks before calving to Mon cows on both farms. The average body condition score (BCS) at monensin administration was 3.4±0.40 on farm A and 3.5±0.32 on farm B. Blood samples were taken on days 1, 7, 14, 21, 28, 42 relative to calving and analysed spectrophotometrically for NEFA and BHB. Mixed linear model was fitted separately for either farm in program

“R” considering the fixed effects of time, monensin, BCS, the interaction of time and monensin and the interaction of time and BCS, and the random effects of animal.

Results Time was a significant factor on both farms for both metabolites due to the dynamic use of body lipids postpartum. On Farm A monensin influenced the concentration of NEFA and the metabolite differed between groups on d21 (P=0.002). Thus, Mon cows used less body reserves at the beginning of lactation than Con cows. This brought along a noticeably lower BHB concentration in group Mon from d1 to d28 and overall and time specific monensin effect on BHB on farm A. Subclinical ketosis occurrence was also lower in Mon vs Con, 9% vs 3%, respectively. On the other hand, monensin effect was recorded neither on NEFA nor on BHB on farm B. The values of NEFA and BHB were numerically lower on farm B, except at calving, indicating a lower use of body lipids.

BCS and its interaction model estimates (data not shown) for NEFA were greater compared to monensin on both farms. However, BCS influenced BHB on farm A, but not on farm B.

Table 1 The dynamics of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) concentrations in cows either treated with monensin (Mon) or not (Con) on two farms. Values are expressed as LSM. * Indicate a difference within a farm (P<0.05).

Conclusions Breed or farm specific factors alter the effect of monensin. The use of monensin on farms with a low adipose tissue mobilization may not be profitable. Managing BCS on farm has a greater effect on body lipid mobilization than the use of monensin.

References

Raboisson, D., Mounié, M., Khenifar, E., Maigné, E. 2015. The economic impact of subclinical ketosis at the farm level: tackling the challenge of over-estimation due to multiple interactions. Prev. Vet. Med. 122:417–425.

Ketone bodies in milk of Polish Holstein-Friesian cows in early lactation – a big data study

Z. M. Kowalski1, M. Sabatowicz1, W. Jagusiak2, P. Gorka1 and A. Otwinowska-Mindur2

1Department of Animal Nutrition and Dietetics, University of Agriculture in Krakow, Poland; 2Department of Animal Breeding, University of Agriculture in Krakow, Poland

Email: rzkowals@cyf-kr.edu.pl

Introduction The system of monitoring of subclinical ketosis (SCK) in Polish dairy herds was introduced into the practice on April 1,

determined by FTIR method in test-day (TD) milk samples. Monthly, it considers about 90,000 milk recorded cows, which are within 6-60 days in milk (DIM). Since the start of a system, a big dataset has been collected on ketone bodies concentration in milk. In this study we present the data for Polish Holstein-Friesian cows, which comprise about 90% of milk recorded cows in Poland.

Materials and Methods The dataset was provided by Polish Federation of Cattle Breeders and Dairy Farmers. The dataset consisted of 3,857,160 TD milk samples collected in about 19,900 herds. The data were limited to a period from April 1., 2013 to March 31, 2017. The number of cows per herd ranged between 1 and 992, the average being 38. The number of samples per cow per lactation ranged from 1 to 2. Data were divided for primi- and multiparous cows and for two lactation stages (LS), i.e. 6-21 (1,186,181 milk samples) and 22-60 (2,670,979) DIM. Milk fat (F) and protein (P) were determined using the MilkoScanTM FT+ automatic milk analyzer (FOSS, Hillerod, Denmark). Milk BHB and ACE were determined by FTIR using the CombiFoss FT+ infrared spectrometer (FOSS, Hillerod, Denmark). To classify a cow as ketotic we used 3 criterions: ACE ≥ 0.150 mmol/L (A); BHB ≥ 0.100 mmol/L (B);

ACE ≥ 0.150 mmol/L or BHB ≥ 0.100 mmol/L (C). Additionally, the Pearson’s correlation coefficients between BHB, ACE, F, P, and F/P were calculated using the CORR procedure of SAS (2014).

Results According to the criterion (A, B, C), 18.9, 29.3, and 31.8% of milk samples were classified as originating from ketotic cows.

Irrespective of criterion, the percentage of ketotic cows was higher in 6-21 than 22-60 DIM (Table 1). The difference between LS in percentage of ketotic cows was greater for primiparous cows. Although milk fat content, as well as F/P were higher for ketotic than non-ketotic cows (Table 2), the correlation coefficients between BHB or ACE and F or F/P were less than 0.45. The correlation coefficients between BHB or ACE and milk protein content were much lower (close to 0). BHB and ACE were highly correlated (r2 =

~0.70). However, the ratio of ACE to BHB differed between LS. It was much higher in milk samples collected within 6-21 DIM, originated from non-ketotic1 and ketotic2 cows (criterion C)

Conclusions The results of a present study show that the prevalence of SCK in Poland is high. Especially high prevalence of SCK within 6-21 DM in primiparous cows should be considered in the heifer rearing programmes. Our big data study confirms poor usefulness of determination of milk fat content or milk fat to protein ratio, and especially milk protein content in monitoring of SCK.

Different ACE to BHB ratio in milk samples in 6-21 and 22-60 needs further studies.

Session 07: Metabolic status and risk of disease

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