{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:57:37Z","timestamp":1781326657729,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Guanidinoacetic acid (GAA) and methionine are two biologically active compounds related to cell energy metabolism. Both are metabolically linked, as the methyl group needed to transform GAA into creatine derives from S-adenonsylmethionine out of the homocysteine cycle. A broiler feeding study was conducted to evaluate potential interactions between 600 g\/t supplemental GAA and feed additives with methionine activity. The experimental design comprised two parts. Part one consisted of three dietary treatments in which DL-methionine (DL-Met) was added to meet sulfur amino acid recommendations (1), DL-Met was replaced with liquid methionine hydroxy analogue-free acid (MHA-FA) assuming an 80% methionine activity in the product (2), and DL-Met was added at 65% of the MHA-FA dose used in Treatment 2 (on a product weight basis). Treatments 1, 2, and 3 reflect the range of commercial practice with assuming bioefficacies of either 80% (Trt 2 vs. 1) or 65% (Trt 3 vs. 2) for MHA-FA relative to DL-Met. Part two followed a 2 \u00d7 4 factorial design. Either DL-Met or MHA-FA (assuming 80% methionine activity) was added to diets with gradually reduced apparent metabolizable energy (AME; standard, \u221225, \u221250, \u221275 kcal\/kg AME). For MHA-FA, a bioefficacy of 80% relative to DL-Met was applied in order to evaluate interactions with GAA efficiency assuming inadequate dietary Met+Cys supply with MHA-FA. AME-reduced diets were supplemented with 600 g\/t GAA to evaluate its energy-sparing potential. A total of 2784 male Cobb 500 broilers were equally assigned to 116 floor pens, resulting in 13 replicates (one treatment with 12) per treatment. A five-phase feeding program was introduced from 1 to 40 days of age. Body weights (BW) and feed intake (FI) were recorded in weekly intervals allowing for calculating weight gain (BWG) and feed conversion ratio (FCR). At termination of the experiment, three birds per pen were obtained for carcass analysis. The results revealed that an overestimation of the bioefficacy of MHA-FA relative to DL-Met significantly compromised broiler growth (p &lt; 0.05), while applying a bioefficacy of 65% for MHA-FA relative to DL-Met65 resulted in similar performance. However, on day 40, BW of broilers fed DL-Met65 were higher than with MHA-FA (p &lt; 0.05). It is concluded that an overestimation of the bioefficacy of MHA-FA relative to DL-Met bears the risk of compromised broiler performance while a bioefficacy of 65% allows at least similar, potentially even better, performance and economic advantages. There were basically no interactions between MHA-FA or DL-Met and graded ME levels with concomitant GAA supplementation regarding overall performance of broilers. This means that final BW of DL-Met-fed broilers were higher than those of MHA-FA broilers independent of dietary ME (p &lt; 0.05). In early feeding phases, interactions indicated that broiler performance (BW day 7, 21, p &lt; 0.05) diminished with dietary energy reduction with DL-Met supplementation while this was not the case with MHA-FA-fed broilers. However, with standard AME, DL-Met outperformed MHA-FA (p &lt; 0.05). Basically, GAA supplementation compensated AME reduction up to 50 kcal\/kg as there were no differences in BW, BWG, FCR, FI, or breast meat yield. Additionally, \u221275 kcal\/kg AME was compensated by GAA only up to a broiler age of 21 days.<\/jats:p>","DOI":"10.3390\/ani16121811","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T01:52:08Z","timestamp":1781229128000},"page":"1811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of DL-Methionine or Methionine Hydroxy Analogue-Free Acid Supplementation on Growth Performance and Carcass Yield of Broilers Fed Reduced Energy Diets with Guanidinoacetic Acid Supplementation"],"prefix":"10.3390","volume":"16","author":[{"given":"Patr\u00edcia Tomazini","family":"Medeiros","sequence":"first","affiliation":[{"name":"Veterinary Sciences, Federal University of Paran\u00e1, Curitiba 80035-050, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2483-1506","authenticated-orcid":false,"given":"Andreas","family":"Lemme","sequence":"additional","affiliation":[{"name":"Evonik Operations GmbH, 63457 Hanau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7700-0215","authenticated-orcid":false,"given":"Victor","family":"Naranjo","sequence":"additional","affiliation":[{"name":"Evonik Guatemala, Guatemala City 01010, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariane","family":"Possamai","sequence":"additional","affiliation":[{"name":"Vibra Foods, Montenegro 92521-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Rancatti","sequence":"additional","affiliation":[{"name":"Vibra Foods, Pato Branco 85503-378, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-7731","authenticated-orcid":false,"given":"Alex","family":"Maiorka","sequence":"additional","affiliation":[{"name":"Veterinary Sciences, Federal University of Paran\u00e1, Curitiba 80035-050, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Daszkiewicz, T. (2022). Food Production in the Context of Global Developmental Challenges. Agriculture, 12.","DOI":"10.3390\/agriculture12060832"},{"key":"ref_2","unstructured":"Food and Agriculture Organization of the United Nations (2025). Meat Market Review-Emergina Trends and Outlook in 2025, FAO."},{"key":"ref_3","unstructured":"OECD Food and Agriculture Organization of the United Nations (2023). OECD-FAO Agricultural Outlook 2023\u20132032, OECD Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/00439339.2020.1865117","article-title":"Optimisation of dietary energy utilisation for poultry\u2014A literature review","volume":"77","author":"Musigwa","year":"2021","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Metwally, A.E., Abdel-Wareth, A.A.A., Saleh, A.A., and Amer, S.A. (2020). Are the energy matrix values of the different feed additives in broiler chicken diets could be summed?. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02600-3"},{"key":"ref_6","first-page":"103","article-title":"Efficiency of xylanase. emulsifier. and guanidinoacetic acid in restoring energy deficit in male broilers fed low metabolisable energy diets","volume":"14","author":"Khalil","year":"2024","journal-title":"J. Adv. Vet. Res."},{"key":"ref_7","unstructured":"Schwarz, C. (2016). The energy effect of guanidino acetic acid in phytase-supplemented broiler diets. Verarbeitung von Futtermitteln F\u00fcr Die Mischfutterherstellung: Tagungsband: 15. BOKU-Symposium Tierern\u00e4hrung. 07. April 2016. Wien, Institut f\u00fcr Tierern\u00e4hrung Tierische Lebensmittel und Ern\u00e4hrungsphysiologie Department f\u00fcr Agrarbiotechnologie Universit\u00e4t f\u00fcr Bodenkultur Wien."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.3382\/ps\/pew083","article-title":"Digestibility and metabolism of dietary guanidino acetic acid fed to broilers","volume":"95","author":"Tossenberger","year":"2016","journal-title":"Poult. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1080\/00439339.2020.1716651","article-title":"Guanidinoacetic acid as a feed supplement for poultry","volume":"76","author":"Khajali","year":"2020","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_10","first-page":"102","article-title":"Digestibility of guanidinoacetic acid is 100% in broilers while availability depends on dosage and dietary arginine supply","volume":"97","author":"Lemme","year":"2018","journal-title":"Poult. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1016\/j.psj.2020.05.023","article-title":"Guanidinoacetic acid supplementation improves feed conversion in broilers subjected to heat stress associated with muscle creatine loading and arginine sparing","volume":"99","author":"Majdeddin","year":"2020","journal-title":"Poult. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102653","DOI":"10.1016\/j.psj.2023.102653","article-title":"Effects of feeding guanidinoacetic acid on oxidative status and creatine metabolism in broilers subjected to chronic cyclic heat stress in the finisher phase","volume":"102","author":"Majdeddin","year":"2023","journal-title":"Poult. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3382\/ps.2011-01585","article-title":"Supplementation of guanidinoacetic acid to broiler diets: Effects on performance. carcass characteristics. meat quality. and energy metabolism","volume":"91","author":"Michiels","year":"2012","journal-title":"Poult. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"890","DOI":"10.3382\/ps\/pex378","article-title":"Efficacy of guanidinoacetic acid on growth and muscle energy metabolism in broiler chicks receiving arginine-deficient diets","volume":"97","author":"DeGroot","year":"2018","journal-title":"Poult. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbadis.2005.09.004","article-title":"Mitochondrial creatine kinase in human health and disease","volume":"1762","author":"Schlattner","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","unstructured":"Salomons, G.S., and Wyss, M. (2007). The creatine kinase phosphotransfer network: Thermodynamic and kinetic considerations. the impact of the mitochondrial outer membrane and modelling approaches. Creatine and Creatine Kinase in Health and Disease: From Cell Deconstruction to System Reconstruction, Springer."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1080\/00439339.2025.2511985","article-title":"Guanidinoacetic acid as a functional additive in broiler nutrition: Insights into performance. carcass. antioxidant capacity. and health","volume":"81","author":"Alsenosy","year":"2025","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100324","DOI":"10.1016\/j.japr.2022.100324","article-title":"Reducing broiler breast myopathies through supplementation of guanidinoacetic acid in broiler diets","volume":"32","author":"Maynard","year":"2023","journal-title":"J. Appl. Poult. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104105","DOI":"10.1016\/j.psj.2024.104105","article-title":"Effect of arginine. glycine + serine concentrations. and guanidinoacetic acid supplementation in vegetable-based diets for chickens","volume":"103","author":"Campos","year":"2024","journal-title":"Poult. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106692","DOI":"10.1016\/j.psj.2026.106692","article-title":"A meta-analysis of the effects and relationship between guanidinoacetic acid and the growth performance of broiler chickens","volume":"105","author":"Gao","year":"2026","journal-title":"Poult. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/00071668.2016.1257779","article-title":"Interactive effects of temperature and dietary supplementation of arginine or guanidinoacetic acid on nutritional and physiological responses in male broiler chickens","volume":"58","author":"Golian","year":"2017","journal-title":"Br. Poult. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and creatinine metabolism","volume":"80","author":"Wyss","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lemme, A., Naranjo, V., and de Paula Dorigam, J.C. (2020). Utilization of Methionine Sources for Growth and Met+Cys Deposition in Broilers. Animals, 10.","DOI":"10.3390\/ani10122240"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lemme, A., Li, Z., and Dorigam, J. (2024). Meta-Analyses of Methionine Source Concept Validation Trials in Broilers. Animals, 14.","DOI":"10.3390\/ani14121771"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102118","DOI":"10.1016\/j.psj.2022.102118","article-title":"Response to Letter to the Editor titled: Issues with a meta-analysis assessing the efficacy of different sources of methionine supplementation by A. Lemme and H-P Piepho","volume":"101","author":"Uddin","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100894","DOI":"10.1016\/j.animal.2023.100894","article-title":"Systematic review and meta-analysis of the methionine utilization efficiency in piglets receiving different methionine sources","volume":"17","author":"Souza","year":"2023","journal-title":"Animal"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101143","DOI":"10.1016\/j.animal.2024.101143","article-title":"Multitissue transcriptomics demonstrates the systemic physiology of methionine deficiency in broiler chickens","volume":"18","author":"Romero","year":"2024","journal-title":"Animal"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.nutr.19.1.217","article-title":"Homocysteine metabolism","volume":"19","author":"Selhub","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/ps\/85.1.90","article-title":"Homocysteine remethylation in young broilers fed varying levels of methionine. choline. and betaine","volume":"85","author":"Pillai","year":"2006","journal-title":"Poult. Sci."},{"key":"ref_30","unstructured":"Lemme, A., Gobbi, R., and Esteve-Garcia, E. (2010, January 23\u201327). Effectiveness of creatine sources on performance of broilers at deficient or adequate methionine supply. Proceedings of the 13th European Poultry Conference, Tours, France."},{"key":"ref_31","unstructured":"(2022). Cobb500\u2122 Broiler Performance & Nutrition Supplement, Cobb-Vantress Inc."},{"key":"ref_32","unstructured":"National Institute of Standards and Technology (2026, May 25). e-Handbook of Statistical Methods: Detection of Outliers, Available online: https:\/\/www.itl.nist.gov\/div898\/handbook\/eda\/section3\/eda35h.htm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/00071668.2021.2014399","article-title":"Feeding guanidinoacetic acid to broiler chickens can compensate for low dietary metabolisable energy formulation","volume":"63","author":"Pirgozliev","year":"2022","journal-title":"Br. Poult. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.4081\/ijas.2014.3269","article-title":"The Relationship Between Guanidino Acetic Acid and Metabolisable Energy Level of Diets on Performance of Broiler Chickens","volume":"13","author":"Abudabos","year":"2014","journal-title":"Ital. J. Anim. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"35. Ale Saheb Fosoul, S.S., Azarfar, A., Gheisari, A., and Khosravinia, H. (2018). Energy utilisation of broiler chickens in response to guanidinoacetic acid supplementation in diets with various energy contents. Br. J. Nutr., 120, 131\u2013140.","DOI":"10.1017\/S0007114517003701"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"477","DOI":"10.11118\/actaun201462030477","article-title":"Effects of Guanidinoacetic Acid Supplementation to Broiler Diets with Varying Energy Content","volume":"62","author":"Heger","year":"2014","journal-title":"Acta Univ. Agric. Silvic. Mendel. Brun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3382\/japr.2012-00575","article-title":"Effects of guanidinoacetic acid supplementation to broiler diets with varying energy contents","volume":"22","author":"Mousavi","year":"2013","journal-title":"J. Appl. Poult. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"skae001","DOI":"10.1093\/jas\/skae001","article-title":"Inclusion of guanidinoacetic acid in a low metabolizable energy diet improves broilers growth performance by elevating energy utilization efficiency through modulation serum metabolite profile","volume":"102","author":"Cao","year":"2024","journal-title":"J. Anim. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"281","DOI":"10.17221\/11\/2021-CJAS","article-title":"Effects of dietary energy level and guanidino acetic acid supplementation on growth performance. carcass quality and intestinal architecture of broilers","volume":"66","author":"Ceylan","year":"2021","journal-title":"Czech. J. Anim. Sci."},{"key":"ref_40","unstructured":"Dorigam, J., Bauer, L., Kl\u00fcnemann, M., and Lemme, A. (2024). Method for Giving a Recommendation on the Dietary Energy of a Poultry Diet. (Patent IPC: A23K 20\/142)."},{"key":"ref_41","unstructured":"Lemme, A., H\u00e4lker, W., Mersmann, H., Bauer, L., Naatjes, M., Guhe, M., and Westendarp, H. (2025, January 23\u201326). Energy-and arginine-sparing suggested by GuanAMINO recommendation tool successfully validated in large-scale broiler trial. Proceedings of the 24th European Symposium on Poultry Nutrition, Maastricht, The Netherlands."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1093\/ps\/84.10.1584","article-title":"Growth. body composition. and marginal efficiency of methionine utilization are affected by nonessential amino acid nitrogen Supplementation in Male Broiler Chicken","volume":"84","author":"Fatufe","year":"2005","journal-title":"Poult. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3382\/japr\/pfw002","article-title":"Effects of dietary lysine and methionine supplementation on Ross 708 male broilers from 21 to 42 d of age (I): Growth performance. meat yield. and cost effectiveness","volume":"25","author":"Zhai","year":"2016","journal-title":"J. Appl. Poult. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Maynard, C.W., Gilbert, E., Yan, F., Cline, M.A., and Dridi, S. (2023). Peripheral and Central Impact of Methionine Source and Level on Growth Performance, Circulating Methionine Levels and Metabolism in Broiler Chickens. Animals, 13.","DOI":"10.3390\/ani13121961"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1590\/S1516-35982014000300006","article-title":"Bioavailability of different methionine sources for growing broilers","volume":"43","author":"Pozza","year":"2014","journal-title":"Rev. Bras. Zootec."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100478","DOI":"10.1016\/j.japr.2024.100478","article-title":"Effects of methionine supplement sources and crude protein on Ross 708 male broiler performance and carcass yield","volume":"33","author":"Boontarue","year":"2024","journal-title":"J. Appl. Poult. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1080\/00071668.2019.1631447","article-title":"Effects of methionine and guanidinoacetic acid supplementation on performance and energy metabolites in breast muscle of male broiler chickens fed corn-soybean diets","volume":"60","author":"Majdeddin","year":"2019","journal-title":"Br. Poult. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/00071668.2020.1720909","article-title":"Guanidinoacetic acid supplementation is favourable to broiler diets even containing poultry by-product meal","volume":"61","author":"Ceylan","year":"2020","journal-title":"Br. Poult. Sci."},{"key":"ref_49","first-page":"14","article-title":"Positiver Effekt auf Energiestoffwechsel","volume":"12","author":"Albiker","year":"2015","journal-title":"Schweiz. Gefl\u00fcgelzeitung"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e20220071","DOI":"10.37496\/rbz5220220071","article-title":"Metabolizable energy equivalence of guanidinoacetic acid in corn soybean meal-based broiler diets","volume":"52","author":"Salgado","year":"2023","journal-title":"Rev. Bras. Zootec."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/1828051X.2017.1305260","article-title":"Effect of wheat-soy diet nutrient density and guanidine acetic acid supplementation on performance and energy metabolism in broiler chickens","volume":"16","author":"Golian","year":"2017","journal-title":"Ital. J. Anim. Sci."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/12\/1811\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:34:11Z","timestamp":1781325251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/12\/1811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ani16121811"],"URL":"https:\/\/doi.org\/10.3390\/ani16121811","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]}}}