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Review of the chemistry, metabolism, and dose response of two supplemental methionine sources and the implications in their relative bioefficacy

  • M. VÁZQUEZ-AÑÓN (a1), G. BERTIN (a2), Y. MERCIER (a3), G. REZNIK (a1) and J-L. ROBERTON (a3)...


This review examines the relative bioefficacy of 2-hydroxy-4-(methylthio) butanoic acid (HMTBA) and DL-methionine (DL-Met) which includes chemical, metabolic, nutritional, and statistical aspects of its bioefficacy. The chemical, enzymatic and biological differences and similarities between these two products are explained and the evidence and reasons for HMTBA relative bioefficacy to DL-Met in monogastric animals are discussed. In addition, appropriate statistical methods for comparing the bioefficacy of these two products for successful use of each product are provided. HMTBA is an organic acid precursor of L-Met. The chemical structure differences between HMTBA and DL-Met leads to differences in how and where the two materials are absorbed, enzymatically converted to L-Met and used by the animal. Because of these differences, when the two compounds are supplemented into animal feeds in graded doses, they do not produce dose response curves of the same form due in part to differences in intake and metabolism at the extremes of the dose response curves. At deficient levels of the response curve, HMTBA fed animals may exhibit lower feed consumption and growth than DL-Met while at requirement levels they may have greater feed consumption and growth. This review provides biological evidence for why these differences in growth response occur and demonstrates that lower growth, whether for DL-Met or HMTBA, does not mean that either product is being converted to methionine inefficiently. Since the two products have different dose response curves, statistically valid methods are provided for unbiased determination of relative bioefficacy across tested dose ranges. Field nutritionists typically feed commercial doses of HMTBA or DL-Met at a total sulphur amino acid dietary level capable of achieving maximum performance. At these commercial levels, and based on the evidence, the full relative bioefficacy of HMTBA relative to DL-Met is discussed.


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AGOSTINI, P., DALIBARD, P., MERCIER, Y., VAN DER AAR, P. and VAN DER KLIS, J.D. (2015a) Comparison of methionine sources around requirement levels using a methionine efficacy method in 0 to 28 day old broilers. Poultry Science 95: 560-569.
AGOSTINI, P., BUTTIN, P. and VAZQUEZ-AÑON, M. (2015b) The relative value of Methionine Hydroxy Analogue (HMTBA) compared to DL-methionine (DL-Met) at different methionine levels in commercial broiler diets from 0 to 38 days of age. 20th European Symposium on Poultry Nutrition. August 24-27, 2015. Prague, Czech Republic. Page 223.
AGRI STATS, INC. (2004) Annual Feed Nutrient Profile Report. January to December 2004 ed. AgriStat, Inc., Fort Wayne, IN.
BLAIR, M.E. (1983) Methionine bioassays and methionine-choline sulfate relationships in practical-type diets for young turkeys. MS Thesis. Virginia Tech, Blacksburg.
BRUYER, D.C. and VANBELLE, M. (1990a) Efficacite compare pour la croissance du poussin de differentes sources de methionine . Annales de Zootechnie 39: 45-51.
BRUYER, D.C. and VANBELLE, M. (1990b) Estimation of bioavailable methionine hydroxy analogue free acid dimer for poultry and pits. Publication # 57-1990 de l'Unite de Biochimie de la Nutrition, Lauvain-la-Neuve.
DAENNER, E. and BESSEI, W. (2003) Influence of supplementation with liquid DL-methionine hydroxy analogue-free acid (Alimet) or DL-methionine on performance of broilers. Journal of Applied Poultry Research 12: 101105.
DIBNER, J.J. and KNIGHT, C.D. (1984) Conversion of 2-hydroxy-4-(methylthio) butanoic acid to L-methionine in the chick: A stereospecific pathway. Journal of Nutrition 114: 1716-1723.
DIBNER, J.J., ATWELL, C.A. and IVEY, F.J. (1992) Effect of heat stress on 2-hydroxy-4-(methylthio) butanoic acid and DL-methionine absorption measured in vitro . Poultry Science 71: 1900-1910.
DIBNER, J.J. (2003) Review of the metabolism of DL-2-hydroxy-4-(methylthio) butanoic acid. World's Poultry Science 59: 99-110.
ENTHOVEN, P., VAN DEN HOVEN, S. and VAN DIJK, A. (2002) Antibacterial properties of 2-hydroxy-4(methylthio) butanoic acid (HMB, Alimet). Eur. Ass. Of Anim. Prod Proc. (EEAP) Cairo.
FINNEY, D.J. (1978) Statistical methods in biological assay. (3rd Edition) Griffin, London.
GERAERT, P.-A., GRAULET, P., MERCIER, Y., BECKER, P.M. and VAN DER KLIS, J.D. (2005) The bactericidal effect of methionine hydroxyl analog. Australian Poultry Science Symposium 17.
GONZALEZ-ESQUERRA, R., VÁZQUEZ-AÑÓN, M., HAMPTON, T., YORK, T., FEINE, S., WUELLING, C. and KNIGHT, C.D. (2007) Evidence of a different dose response in turkeys when fed 2-hydroxy-4(methylthio) butanoic acid versus DL-methionine. Poultry Science 86: 517- 524.
HARMS, R.H. and RUSSELL, G.B. (1994) A comparison of the bioavailability of DL-methionine and methionine hydroxyl analogue acid for the commercial laying hen. Journal of Applied Poultry Research 3: 1-6.
HOEHLER, D., LEMME, A., ROBERSON, K. and TURNER, K. (2005) Impact of methionine sources on performance in turkeys. Journal of Applied Poultry Research 14: 296-305.
JANSMAN, A.J.M., KAN, C.A. and WIEBENGA, J. (2003) Comparison of the biological efficacy of DL-methionine and hydroxyl-4-methylthiobutanoic acid (HMB) in pigs and poultry. ID-Lelystad No. 2209.
KNIGHT, C.D., DIBNER, J.J., GONZALEZ-ESQUERRA, R. and VÁZQUEZ-AÑÓN, M. (2006) Differences in broiler growth rates when methionine (MET) sources are fed in deficiency or excess are equalised when feed consumption is equalised. Poultry Science 85 (Suppl. 1): P191 (Abstr.).
KNIGHT, C.D., WUELLING, C.W., ATWELL, C.A. and DIBNER, J.J. (1994) Effect of intermittent periods of high environmental temperature on broiler performance responses to sources of methionine activity. Poultry Science 73: 672-639.
KNIGHT, C.D. and DIBNER, J.J. (1984) Comparative absorption of 2-hydroxy-4- (methylthio) butanoic acid and L-methionine in the broiler chick. Journal of Nutrition 114: 2179-2186.
KRATZER, D.D. and LITTELL, R.C. (2006) Appropriate analyses to compare dose responses of two methionine sources. Poultry Science 85: 947-954.
LAWSON, C.Q. and IVEY, F.J. (1986) Hydroylysis of 2-hydroxy-4-(methylthio) butanoic acid in two model systems. Poultry Science 65:1749-1753.
LITTELL, R.C., LEWIS, A.J. and HENRY, P.R. (1995) Statistical evaluation of bioavailability assays, in: Bioavailability of Nutrients for Animals, Amino Acids, Minerals, and Vitamins. Academic Press, San Diego, CA. 1995.
LOBLEY, G.E., WESTER, T.A., CALDER, A.J., PARKER, D.S., DIBNER, J.J. and VÁZQUEZ-AÑÓN, M. (2006) Absorption of 2-hydroxy-4-(methylthio) butyrate (HMTBA) and conversion to met in lambs. Journal of Dairy Science 89: 1072-1080.
LIU, Z., BATEMAN, A., BRYANT, M.M., ZINNER, B. and ROLAND, D.A. (Sr) (2005) Performance comparisons between DL-methionine and DL-methionine hydroxy analogue in layers on an unequal molar basis. Journal of Applied Poultry Research 14: 569-575.
LIU, Z., BATEMAN, A., BRYANT, M., ABEBE, A. and ROLAND, D. (2004) Estimation of Bioavailability of DL-Methionine Hydroxy Analogue Relative to DL-Methionine in Layers with Exponential and Slope-Ratio Models. Poultry Science 83: 1580-1586.
MCCOLLUM, M., VAZQUEZ-ANON, M., DIBNER, J.J. and WEBB, K.E. (2000) Absorption of 2-hydroxy-4-(methylthio)butanoic acid by isolated sheep ruminal and omasal epithelia . Journal of Animal Science 78: 1078-1083.
MARTIN-VENEGAS, R., SORIANO-GARCIA, J.F., VINARDELL, M.P., GERAERT, P.A. and FERRER, R. (2006) Oligomers are not the limiting factor in the absorption of DL-2-hydroxy-4-(methylthio) butanoic acid in the chicken small intestine. Poultry Science 85: 56-63.
MARTIN-VENEGAS, R., RODRIGUEZ-LAGUNAS, M.J., GERART, P.A. and FERRER, R. (2007) DL- 2-hydroxy-4(methylthio) butanoic acid absorption across the apical membrane in Caco-2 cell monolayers. Journal of Nutrition 137: 49-54.
MARTIN-VENEGAS, R., BRUFAU, M.T., GUERRERO-ZAMORA, A.M., MERCIER, Y., GERAERT, P.A. and FERRER, R. (2013) The methionine precursor DL-2-hydroxy-(4-methylthio) butanoic acid protects intestinal epithelial barrier function. Food Chemistry 141 (3): 1702-1709.
MONTANHINI NETO, R., CECCANTINI, M. and FERNANDES, J.I.M. (2013) Effects of methionine source, arginine:lysine ratio and sodium chloride level in the diets of grower broilers reared under high-temperature conditions. Brasilian Journal of Poultry Nutrition 15 (2): 151-160.
MOTL, M.A., FRITTS, C.A. and WALDROUP, P.W. (2005) Influence of dietary sodium level on utilisation of methionine from DL-Methionine and liquid methionine-hydroxy analogue. Journal of Applied Poultry Research 14: 147-155.
NOLL, S.L., WAIBEL, P.E., COOK, R.D. and WITMER, J.A. (1984) Biopotency of methionine sources for young turkeys. Poultry Science 63: 2458-2470.
REID, B.L., MADRID, A. and MAIORINO, P.M. (1982) Metabolism and nutrition-relative biopotency of three methionine sources for laying hens. Poultry Science 61: 726-730.
RICHARDS, J.R., ATWELL, C.A., VÁZQUEZ-AÑÓN, M. and DIBNER, J.J. (2005) Comparative in vitro and in vivo absorption of 2-hydroxy-4-(methylthio) butanoic acid and DLmethionine in the broiler chicken. Poultry Science 84: 1397-1405.
SAUER, N., EMRICH, K., PIEPHO, H.P., LEMME, A., REDSHAW, M.S. and MOSENTHIN, R. (2008) Meta-analysis of the relative efficiency of methionine-hydroxy-analogue-free-acid compared with DL-methionine in broilers using nonlinear mixed models. Poultry Science 87: 2023-2031.
SWENNEN, Q., GERAERT, P.A., MERCIER, Y., EVERAERT, N., STINCKENS, A., WILLEMSEN, H., LI, Y., DECUYPERE, E. and BUYSE, J. (2011) Effects of dietary protein content of 2-hydroxy-4-(methylthio) butanoic acid or DL methionine supplementation on performance and oxidative status of broiler chickens. British Journal of Nutrition 106: 1845-1854.
SCHUTTE, J.B. and DE JONG, J. (1996) Biological efficacy of DL-methionine hydroxy analog free acid compared to DL-methionine in broiler chicks as determined by performance and breast meat yield. Agribiological Research 49: 74-82.
SCOTT, M.L. and SHURMAN, J.G. (1987) Studies on the comparative utilisation of synthetic sources of methionine activity in laying pullets. Nutrition Reports International 36: 1043-1052.
SUGAHARA, K. and KUBO, T. (1992) Involvement of food intake in the decreased energy retention associated with single deficiencies of lysine and sulphur-containing amino acids in growing chicks . British Poultry Science 33: 805-814.
VAN WEERDEN, E.J., SCHUTTE, J.B. and BERTRAM, H.L. (1984) Comparison of DL-methionine, DL-methionine-Na, DL-methionine hydroxyl analogue-Ca, and DL-methionine hydroxyl analogue-free acid with layers. Poultry Science 63: 1793-1799.
VÁZQUEZ-AÑÓN, M., WEHMEYER, M., WUELLING, C.W., HAMPTON, T., KNIGHT, C.D. and DIBNER, J.J. (2003) Differential response to 2-hydroxy-4-(methylthio) butanoic acid and DL-methionine above requirement on broilers and pig performance and iron metabolism. Pages 725-729 in Progress in Research on Energy and Protein Metabolism. EAAP publication No 109. Rostock-Warnemunde, Germany.
VÁZQUEZ-AÑÓN, M., KRATZER, D., GONZALEZ-ESQUERRA, R., YI, I.G. and KNIGHT, C.D. (2006a) A multiple regression model approach to contrast the performance of 2-hydroxy-4-(methylthio) butanoic acid and DL-methionine supplementation tested in broiler trials that are reported in the literature. Poultry Science 85: 693-705.
VÁZQUEZ-AÑÓN, M., GONZALEZ-ESQUERRA, R., SALEH, E., HAMPTON, T., RICTHER, S., FIRMAN, J. and KNIGHT, C.D. (2006b) Evidence for 2-hydroxy-4-(methylthio) butanoic acid and DL-methionine having a different dose-response in growing broilers. Poultry Science 85: 1409-1420.
VEDENOV, D. and PESTI, G.M. (2010) An economic analysis of a methionine source comparison response model. Poultry Science 89: 2514-2520.
WESTER, T.J., VÁZQUEZ-AÑÓN, M., DIBNER, J.J., PARKER, D.S., CALDER, A.J. and LOBLEY, G.E. (2006) Hepatic metabolism of 2-hydroxy-4-thiomethylbutyrate (HMTBA) in growing lambs. Journal of Dairy Science 89: 1062-1071.
WILLEMSEN, H., SWENNEN, Q., EVERAERT, N., GERAERT, P.-A., MERCIER, Y., STINCKENS, A., DECUYPERE, E. and BUYSE, J. (2011) Effects of dietary supplementation of methionine and its hydroxy analog DL-2-hydroxy-4-(methylthio) butanoic acid on growth performance, plasma hormone levels, and the redox status of broiler chickens exposed to high temperatures. Poultry Science 90: 2311-2320.
ZOU, L., WANG, D., LIU, J., BAI, Y., LIANG, Z. and ZHANG, T. (2015) Effects of DL-2-hydroxy-4-(methylthio) butanoic acid on broilers at different dietary inclusion rates. British Poultry Science 56: 337-344.
ZHANG, S., WONG, E.A. and GILBERT, E.R. (2015) Bioavailability of different dietary supplemental methionine sources in animals. Frontiers in Bioscience Elite 7: 478-490.
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World's Poultry Science Journal
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