*Dr. Thomas R. Overton is professor of dairy management in the Cornell University department of animal science.
Research conducted during the past 15 years supports roles for both choline and methionine in transition cow nutrition.
CHOLINE and methionine both play essential roles in mammalian metabolism.
Choline is a quasi-vitamin that has a variety of functions, including as the predominant phospholipid contained in the membranes of all cells in the body (as phosphatidylcholine), as a component of the neurotransmitter acetylcholine and as a direct precursor to betaine in methyl metabolism (Figure). Furthermore, choline deficiency in monogastric species results classically in fatty liver development, among other symptoms.
Methionine is an essential amino acid and building block for protein and typically is considered one of the two most limiting amino acids for the production of milk and milk protein in lactating dairy cows.
Methionine can contribute to biosynthesis of phosphatidylcholine through its role as a methyl donor. In a study conducted a number of years ago using lactating goats and radio-labeled choline and methionine to determine the kinetics and interconversions between the two compounds, 6% of the choline pool was derived from methionine (Emmanuel and Kennelly, 1984).
Choline and methionine each have been the focus of a number of transition cow studies over the past 10-15 years, and both have demonstrated positive effects on cow productivity during early lactation.
Given the interrelationships described above, questions have been asked regarding the potential substitution of methionine for choline or if supplemental choline is needed at all if methionine is already being supplemented.
However, if examining the literature focused on the dairy cow, there is little evidence that methionine can meaningfully substitute for choline; rather, each of these nutrients has distinct effects on the transition cow.
Transition cow research
Piepenbrink and Overton (2003) determined that cows fed rumen-protected choline (RPC) during the precalving period and on through early lactation tended to have increased fat-corrected milk yields (average response of 5.3 lb. per day) during early lactation, along with a trend for decreased storage of radio-labeled palmitate as liver triglycerides in vitro and increased concentrations of liver glycogen, implying improved liver metabolism.
Diets in this study were formulated to meet grams per day requirements for methionine using corn gluten meal. Effects on blood non-esterified fatty acids (NEFAs) and beta-hydroxybutyrate (BHBA) were not significant.
Zahra et al. (2006) reported that cows fed RPC had increased milk yield (2.6 lb. per day) during early lactation, but the effects of RPC supplementation on blood NEFAs and BHBA, along with liver composition, were not significant.
Cooke et al. (2007) evaluated whether RPC supplementation could prevent and alleviate triglyceride accumulation in the liver using a feed restriction model in dry cows. Supplementation of RPC during the feed restriction decreased plasma NEFAs and decreased liver triglyceride accumulation, the latter by nearly 50% compared to controls. Furthermore, RPC supplementation during the refeeding period following feed restriction resulted in more rapid clearance of triglycerides from the liver.
Zom et al. (2011) reported that supplementation with RPC did not affect blood metabolites but decreased the liver triglyceride content during early lactation; further examination (Goselink et al., 2013) of the changes in gene expression in the liver from this study suggested that RPC supplementation resulted in increased expression of genes related to processing of fatty acids and very low-density lipoprotein assembly.
Elek et al. (2008 and 2013) determined that cows fed RPC produced 5.5 lb. per day more fat-corrected milk (9.7 lb. per day more milk) during early lactation, and these effects were underpinned by decreased liver triglyceride and circulating BHBA concentrations for cows fed RPC.
In addition to these results, other studies also have demonstrated production responses to RPC supplementation that were either statistically significant — 5.3 lb. per day more milk in Scheer et al. (2002); 6.4 lb. per day more milk in Pinotti et al. (2003), and 4.0 lb. per day more fat-corrected milk in one experiment plus 1.8 lb. per day more milk in a second experiment by Lima et al. (2007) — or statistically non-significant — 5.1 lb. more fat-corrected milk in Janovick-Guretzky et al. (2006).
Methionine. There are also several studies that have evaluated the effects of methionine supplementation beginning during the prepartum period and continuing into early lactation.
Overton et al. (1996) fed cows either 0 or 20 g per day of rumen-protected methionine (RPM) beginning 7-10 days before calving and continuing into lactation. Cows fed RPM produced 6.0 lb. more fat-corrected milk during early lactation.
Socha et al. (2005) fed cows either 10.5 g per day of RPM or 10.2 g per day of RPM plus 16.0 g per day of rumen-protected lysine (RPL) beginning 14 days before expected calving and continuing through early lactation. Cows fed RPM plus RPL produced more milk during early lactation than those fed RPM alone; milk yield of cows fed the basal diets was intermediate.
Supplementation of RPM and RPM plus RPL increased milk protein content when cows were fed 18.5% crude protein diets during the postpartum period. Amino acid supplementation did not affect milk protein content when cows were fed 16% crude protein diets postpartum.
Effects of amino acid supplementation on liver and energy metabolism were not evaluated in either the Overton et al. (1996) or Socha et al. (2005) studies.
Piepenbrink et al. (2003) determined the effects of feeding an analog of methionine called 2-hydroxy-4-(methylthio)-butanoic acid (HMB) to periparturient cows on production and metabolism. They reported that feeding an intermediate level of HMB increased milk yield by 6.6 lb. per day. However, comprehensive evaluation of the effects of HMB on metabolism (circulating concentrations of NEFAs and BHBA, liver concentrations of triglyceride and glycogen, in vitro assessment of liver propionate and palmitate metabolism) suggested that the production responses were not underpinned by changes in liver metabolism.
These responses were supported by Bertics and Grummer (1999), who used a research model similar to the one described above for choline to evaluate responses of liver triglyceride accumulation during feed restriction and depletion during refeeding to HMB supplementation. In this study, HMB supplementation did not affect either triglyceride accumulation or depletion during the two phases of the experiment.
More recently, Ordway et al. (2009) evaluated feeding either the isopropyl ester of HMB (HMBi) or RPM to cows beginning during the prepartum period and continuing into early lactation. They determined that supplementation of HMBi and RPM did not affect yields of milk or fat-corrected milk as the average milk yields were 95.7, 95.9 and 92.6 lb. per day for cows fed the basal diet, HMBi and RPM, respectively. However, the milk protein percentage was increased by feeding both HMBi and RPM. The effects of methionine supplementation on liver and energy metabolism were not determined in the experiment.
Preynat et al. (2009 and 2010) fed cows RPM with or without intramuscular injections of folic acid and vitamin B12 during the transition period and early lactation. Feeding RPM did not affect milk yield (83.3 lb. versus 83.0 lb. per day for control and RPM, respectively) but increased milk crude protein percentage (2.94% versus 3.04%). Interestingly, liver concentrations of triglycerides were increased in cows fed RPM in this study.
Finally, Osorio et al. (2013) fed cows either a basal ration or the basal ration supplemented with either HMBi or RPM beginning 21 days before expected calving and continuing through the postpartum period.
Cows fed methionine had large increases in milk yield compared to controls — 5.3 lb. more per day for HMBi and 9.5 lb. more per day for RPM. However, effects of the two sources of methionine on blood NEFAs and BHBA and liver triglyceride content were not significant. Interestingly, cows fed supplemental methionine had greater phagocytosis in blood neutrophils harvested at 21 days postpartum, suggesting improved immune function.
In summary, research conducted during the past 15 years supports roles for both choline and methionine in transition cow nutrition. However, there are several important considerations.
The number of studies from which to draw both production and metabolism results and the consistency of production responses among these studies are much greater for choline than for methionine. Furthermore, there are several studies among these that clearly demonstrate improved liver metabolism and decreased triglyceride accumulation in cows fed RPC as potential underpinnings for these production responses. This biological mechanism is consistent with the classical choline deficiency symptom of fatty liver that has been well-illustrated in monogastric species.
The research currently available for supplementation of methionine sources to transition cows suggests the potential for production responses as well; however, the mechanism of response does not appear to relate to liver metabolism and perhaps relates to either immune function or methionine's role as a potentially limiting amino acid during the transition period and early lactation.
Bertics, S.J., and R.R. Grummer. 1999. Effects of fat and methionine hydroxy analog on prevention or alleviation of fatty liver induced by feed restriction. J. Dairy Sci. 82:2731-2736.
Cooke, R.F., N. Silva del Rio, D.Z. Caraviello, S.J. Bertics, M.H. Ramos and R.R. Grummer. 2007. Supplemental choline for prevention and alleviation of fatty liver in dairy cattle. J. Dairy Sci. 90:2413-2418.
Elek, P., T. Gaal and F. Husveth. 2013. Influence of rumen-protected choline on liver composition and blood variables indicating energy balance in periparturient dairy cows. Acta Vet. Hung. 61:59-70.
Elek, P., J.R. Newbold, T. Gaal, L. Wagner and F. Husveth. 2008. Effects of rumen-protected choline supplementation on milk production and choline supply of periparturient dairy cows. Animal 2:1595-1601.
Emmanuel, B., and J.J. Kennelly. 1984. Kinetics of methionine and choline and their incorporation into plasma lipids and milk components in lactating goats. J. Dairy Sci. 67:410-415.
Goselink, R.M.A., J. van Baal, H.C.A. Widjaja, R.A. Dekker, R.L.G. Zom, M.J. de Veth and A.M. van Vuuren. 2013. Effect of rumen-protected choline supplementation on liver and adipose gene expression during the transition period in dairy cattle. J. Dairy Sci. 96:1102-1116.
Janovick-Guretzky, N.A., D.B. Carlson, J.E. Garrett and J.K. Drackley. 2006. Lipid metabolite profiles and milk production for Holstein and Jersey cows fed rumen-protected choline during the periparturient period. J. Dairy Sci. 89:188-200.
Lima, F.S., M.F. Sa Filho, L.F. Greco, F. Susca, V.J.A. Magalhaes, J. Garrett and J.E.P. Santos. 2007. Effects of feeding rumen-protected choline (RPC) on lactation and metabolism. J. Dairy Sci. 90(suppl. 1):174(abstr.).
Ordway, R.S., S.E. Boucher, N.L. Whitehouse, C.G. Schwab and B.K. Sloan. 2009. Effects of providing two forms of supplemental methionine to periparturient Holstein dairy cows on feed intake and lactational performance. J. Dairy Sci. 92:5154-5166.
Osorio, J.S., P. Ji, J.K. Drackley, D. Luchini and J.J. Loor. 2013. Supplemental Smartamine M or MetaSmart during the transition period benefits postpartal cow performance and blood neutrophil function. J. Dairy Sci. 96:6248-6263.
Overton, T.R., D.W. LaCount, T.M. Cicela and J.H. Clark. 1996. Evaluation of a ruminally protected methionine product for lactating dairy cows. J. Dairy Sci. 79:631-638.
Piepenbrink, M.S., and T.R. Overton. 2003. Liver metabolism and production of cows fed increasing amounts of rumen-protected choline during the periparturient period. J. Dairy Sci. 86:1722-1733.
Piepenbrink, M.S., A.L. Marr, M.R. Waldron, W.R. Butler, T.R. Overton, M. Vazquez-Anon and M.D. Holt. 2004. Feeding 2-hydroxy-4-(Methylthio)-Butanoic Acid to periparturient dairy cows improves milk production but not hepatic metabolism. J. Dairy Sci. 87:1071-1084.
Pinotti, L., A. Baldi, I. Politis, R. Rebucci, L. Sangalli and V. Dell'Orto. 2003. Rumen-protected choline administration to transition cows: Effects on milk production and vitamin E status. J. Vet. Med. 50:18-21.
Preynat, A., H. Lapierre, M.C. Thivierge, M.F. Palin, N. Cardinault, J.J. Matte, A. Desrochers and C.L. Girard. 2010. Effects of supplementary folic acid and vitamin B12 on hepatic metabolism of dairy cows according to methionine supply. J. Dairy Sci. 93:2130-2142.
Preynat, A., H. Lapierre, M.C. Thivierge, M.F. Palin, J.J. Matte, A. Desrochers and C.L. Girard. 2009. Influence of methionine supply on the response of lactational performance of dairy cows to supplementary folic acid and vitamin B12. J. Dairy Sci. 92:1685-1695.
Scheer, W.A., M.C. Lucy, M.S. Kerley and J.N. Spain. 2002. Effects of feeding soybeans and rumen-protected choline during late gestation and early lactation on performance of dairy cows. J. Dairy Sci. 85(suppl. 1):276(abstr.).
Socha, M.T., D.E. Putnam, B.D. Garthwaite, N.L. Whitehouse, N.A. Kierstead, C.G. Schwab, G.A. Ducharme and J.C. Robert. 2005. Improving intestinal amino acid supply of pre- and postpartum dairy cows with rumen-protected methionine and lysine. J. Dairy Sci. 88:1113-1126.
Zahra, L.C., T.F. Duffield, K.E. Leslie, T.R. Overton, D. Putnam and S.J. LeBlanc. 2006. Effects of rumen-protected choline and monensin on milk production and metabolism of periparturient dairy cows. J. Dairy Sci. 89:4808-4818.
Zom, R.L.G., J. van Baal, R.M.A. Goselink, J.A. Bakker, M.J. de Veth and A.M. van Vuuren. 2011. Effect of rumen-protected choline on performance, blood metabolites and hepatic triacylglycerols of periparturient dairy cattle. J. Dairy Sci. 94:4016-4027.