and the available PDI covers protein expenditure (Dan-
iel et al., 2016), the observed increased PDI supply
leads to a predicted increased milk protein synthesis
of +48 g/d in EXP1 and +53 g/d in EXP2. Thus,
the observed marginal milk true protein yield obtained
with the extrusion of lupines in both experiments was
slightly lower than predicted.

In contrast to observations by Cantalapiedra-Hijar et al. (2016), the Δ¹⁵N<sub>animal-diet</sub> was not related to the PDI use efficiency estimated in these experiments. However, the lower PDI use efficiency with all extruded lupines than with raw lupines, partly agreed with the observed higher predicted PDI intake with all extruded lupines, as lower efficiency of MP utilization at higher predicted MP supply is classically observed (Metcalf et al., 2008; Moraes et al., 2018). Altogether, these observations suggest that the variations observed in N use efficiency for milk production with the highest temperature of extrusion (150°C) without addition of reducing sugars may be mainly related to ruminal N use efficiency rather than to absorptive or postabsorptive mechanisms.

Still, the extrusion at 150°C may have reduced the bioavailability of Lys in the intestine compared with the lower temperatures of extrusion applied in these experiments, as supported by the tendency (P = 0.09) toward an effect on the apparent total-tract digestibility of total Lys in EXP1 in line with the increased CML to total Lys proportion especially with EL3. Lysine is the AA most susceptible to glycation and its lower bioavailability in the intestine may result from overprotection from proteases and peptidases due to CML formation. Nevertheless, this may not have affected the dairy performance, as Lys may not have been limiting compared with Met as LysDI represented 6.6% of predicted PDI, which is close to LysDI requirements (i.e., 7.0% of PDI) according to INRA (2018). Furthermore, dietary Lys accounts for only around one-third of fecal Lys, whereas around two-thirds is of microbial or endogenous origin, which may have masked the effects of extrusion on the bioavailability of Lys in the intestine.

In both experiments, lupines extruded at 150°C in-
duced lower plasma taurine concentrations in compari-
son with raw lupines and lupines extruded at 115°C.
Taurine derives from cysteine following Met catabolism
through the transsulfuration pathway (Seymour et al.,
1990). It is not used for milk protein synthesis and is
therefore only sparingly taken up in the bovine mam-
mary gland. Only in EXP2, the plasma Met concentra-
tion was lower in cows fed ELS3 than in cows fed RLS,
despite the supplementation with rumen-protected Met
to reach 2.3% of MetDI in PDI in diets with lupines
extruded at 135°C and 150°C. Overall, this might sug-
gest also a lower intestinal bioavailability of Met, a
lower absorption, and consequently a less extensive ca-

tabolism of Met in cows fed lupines extruded at 150°C,
especially with added reducing sugars.

Eventually, the dietary inclusion of lupines has often
been reported to reduce milk fat concentration and yield
(Froidmont and Bartiaux-Thill, 2004) as a consequence
of their relatively high content of crude fat (9.6% in the
DM; INRAE-CIRAD-AFZ, 2022) compared with other
leguminous seeds. Thermo-mechanical treatments such
as extrusion may further increase the availability of the
lipids in the rumen and lead to the observed lower milk
fat content in EXP1 or tendency toward lower milk
fat content in EXP2 (Mendowski et al., 2021), which
was balanced out by higher milk yield in EXP1, and
tendency toward a higher milk yield in EXP2.

Apparent Total-Tract Digestibility, Partition,
and Excretion of CML

In addition to being potential proxies for ruminal CP degradability in feed production, dietary MRC such as CML are known to have immunomodulatory effects that may also be relevant in livestock (Teodorowicz et al., 2018). Current knowledge on the digestibility and partition of MRC is mainly based on research in humans and rodents, and therefore further investigations on dairy cows were required. In the present experiments, the apparent total-tract digestibility of CML in the total diet was lower (on average 41 vs. 71%) than previously reported by Mendowski et al. (2020), due to the relatively lower CML intake [416 ± 47 mg/d in present experiments vs. 748 ± 120 mg/d in the experiment by Mendowksi et al. (2020)] and similar fecal CML excretion [246 ± 39 mg/d in the present experiments vs. 226 ± 34 mg/d in the study by Mendowski et al. (2020)]. Furthermore, the estimated marginal increase in digestibility of CML with increasing CML intake from lupines (84%) was similar to the estimated digestibility of CML provided by faba beans (88%; Mendowski et al., 2020), whereas the marginal increase in digestibility of CML from the basal mixed ration was relatively lower (62%) and similar to the digestibility of CML provided by all dietary components except for the faba bean:linseed blend (60%) estimated by Mendowski et al. (2020). The absorption of free MRC with low molecular weight such as CML probably occurs by simple diffusion into the intestinal epithelial cells, whereas MRC included in dipeptides may be absorbed through the action of PEPT-1 transporters (Grunwald et al., 2006; Hellwig et al., 2011). Differences between marginal increases in CML digestibility observed for different feeds (lupines vs. basal mixed ration) suggest that CML available after ruminal degradation and enzymatic digestion may differ in chemical form by source. The CML in leguminous seeds might be available in the intestine rather in
free AA form, while CML from the basal mixed ration, in particular from forages, might be in peptides, or undigested proteins, implying more selective absorption into gastrointestinal epithelial cells.

Beyond the dietary supply and fecal excretion of CML measured in the present experiments, we cannot a priori exclude the formation and degradation of CML in the gastrointestinal tract. For example, isolated human gut bacteria have been reported to degrade CML in vitro (Hellwig et al., 2015; Bui et al., 2019). Recently, also a soil bacterium was found to degrade CML (Mehler et al., 2022). However, 5 *Escherichia coli* strains degraded CML only under aerobic conditions in vitro (Hellwig et al., 2019), and other bacteria capable of degrading CML were shown to have highly specialized mechanisms (Hellwig et al., 2015; Mehler et al., 2022), which to our knowledge have not yet been described in the ruminant digestive system.

To our knowledge, this is the first study reporting the partition of apparently digested CML between the urine and milk of dairy cows. We suppose that CML recovered in milk and urine did not derive from proteolysis and glycation occurring after urine and milk harvest, as the samples were frozen to -20°C immediately after collection and lyophilized before CML analysis. Our results showed that independently of the dietary treatment, lactating dairy cows excreted 26 ± 2.1% of the apparently digested CML in urine, whereas the secretion of CML in milk was limited to 0.63 ± 0.05% of the apparently digested CML. Previous literature reports indicate that urinary excretion of apparently digested CML accounts on average for 55% in rats (Alamir et al., 2013) and 26% in young adults (Delgado-Andrade et al., 2012), the kidneys being the main organ responsible for the removal of advanced glycation end products from the bloodstream and their excretion. However, a greater CML urinary excretion in relation to higher dietary CML intake was also observed in human infants, rodents, dogs, and cats (Šebeková et al., 2008; Alamir et al., 2013; Palasweenun et al., 2021). On the contrary, Delgado-Andrade et al. (2012) found proportionally lower urinary CML excretion at higher CML intake in young adults eating MRC-enriched meals. We did not observe any difference among dietary treatments in either experiment, either in the concentration of CML in urine and milk or in the absolute daily excretion of CML in urine or milk.

Although CML is one of the best studied advanced glycation end products in milk after thermal processing (Milkovska-Stamenova and Hoffmann, 2019; Wölk et al., 2021), to the best of our knowledge the quantitative relation between CML intake and absolute excretion and secretion has never been investigated

in any lactating animal. Schwarzenbolz et al. (2016) hypothesized a relation between the dietary intake of MRC and their concentration in bulk milk depending on the dairy production system (e.g., organic, conventional), but this hypothesis has never been tested under controlled experimental conditions. The concentration of CML in raw milk in the present study (33 ± 0.7 µg/kg) was relatively lower than that found in human breast milk (133 ± 83 µg/kg) by Dittrich et al. (2006) and in line with those previously found in bulk milk (on average 21 ± 0.3 µg/kg) from German organic and conventional farms (Schwarzenbolz et al., 2016). Nevertheless, the CML concentration in human breast milk was determined with an immunochemical assay, which may have different specificity for CML, whereas in the survey of Schwarzenbolz et al. (2016) and in our experiments CML was analyzed by LC-MS/MS, which limits to some extent between-species comparisons of the reported absolute CML concentrations in milk.

A substantial proportion of the ingested (i.e., 30 ± 1.8%) and apparently digested CML (i.e., 74 ± 2.2%) was not recovered in the analyzed excretory routes, which is in accordance with observations in other species, including humans (Delgado-Andrade et al., 2012) and rats (Alamir et al., 2013). Interestingly, the estimated amount of CML apparently retained in the body was higher with EL3 than with RL. Despite significantly higher CML supply with ELS3 than with all other treatments and a 55% numerically greater CML balance with ELS3 than RLS in EXP2, we observed no significant effect on the CML balance, hinting toward a low statistical power of EXP2. In mice, CML accumulates primarily in the kidneys but also in other tissues such as in the ileum, colon, and lungs, except in adipose tissue where it seems not to accumulate owing to its hydrophilic properties (Tessier et al., 2016). The endogenous formation of CML through oxidative reactions also at the body temperature (38-39°C) of dairy cows, as reported in other species such as humans (Thorpe and Baynes, 2002) and rodents (Alamir et al., 2013), was not evaluated in the present study but cannot be excluded a priori. Finally, any diurnal pattern in urinary CML concentration is not included in the present measurements and calculations of CML partition and excretion, which may limit to some extent the comparability of our results with those obtained in other species. Further investigations are warranted to determine the metabolism, tissue distribution, excretion kinetics, and possible deposition of CML and other dietary or endogenous advanced glycation end products, and their influence on inflammatory and oxidative status, as well as their long-term effects on the health status of dairy cows.
free AA form, while CML from the basal mixed ration, in particular from forages, might be in peptides, or undigested proteins, implying more selective absorption into gastrointestinal epithelial cells.

Beyond the dietary supply and fecal excretion of CML measured in the present experiments, we cannot a priori exclude the formation and degradation of CML in the gastrointestinal tract. For example, isolated human gut bacteria have been reported to degrade CML in vitro (Hellwig et al., 2015; Bui et al., 2019). Recently, also a soil bacterium was found to degrade CML (Mehler et al., 2022). However, 5 *Escherichia coli* strains degraded CML only under aerobic conditions in vitro (Hellwig et al., 2019), and other bacteria capable of degrading CML were shown to have highly specialized mechanisms (Hellwig et al., 2015; Mehler et al., 2022), which to our knowledge have not yet been described in the ruminant digestive system.

To our knowledge, this is the first study reporting the partition of apparently digested CML between the urine and milk of dairy cows. We suppose that CML recovered in milk and urine did not derive from proteolysis and glycation occurring after urine and milk harvest, as the samples were frozen to -20°C immediately after collection and lyophilized before CML analysis. Our results showed that independently of the dietary treatment, lactating dairy cows excreted 26 ± 2.1% of the apparently digested CML in urine, whereas the secretion of CML in milk was limited to 0.63 ± 0.05% of the apparently digested CML. Previous literature reports indicate that urinary excretion of apparently digested CML accounts on average for 55% in rats (Alamir et al., 2013) and 26% in young adults (Delgado-Andrade et al., 2012), the kidneys being the main organ responsible for the removal of advanced glycation end products from the bloodstream and their excretion. However, a greater CML urinary excretion in relation to higher dietary CML intake was also observed in human infants, rodents, dogs, and cats (Šebeková et al., 2008; Alamir et al., 2013; Palasweenun et al., 2021). On the contrary, Delgado-Andrade et al. (2012) found proportionally lower urinary CML excretion at higher CML intake in young adults eating MRC-enriched meals. We did not observe any difference among dietary treatments in either experiment, either in the concentration of CML in urine and milk or in the absolute daily excretion of CML in urine or milk.

Although CML is one of the best studied advanced glycation end products in milk after thermal processing (Milkovska-Stamenova and Hoffmann, 2019; Wölk et al., 2021), to the best of our knowledge the quantitative relation between CML intake and absolute excretion and secretion has never been investigated

in any lactating animal. Schwarzenbolz et al. (2016) hypothesized a relation between the dietary intake of MRC and their concentration in bulk milk depending on the dairy production system (e.g., organic, conventional), but this hypothesis has never been tested under controlled experimental conditions. The concentration of CML in raw milk in the present study (33 ± 0.7 µg/kg) was relatively lower than that found in human breast milk (133 ± 83 µg/kg) by Dittrich et al. (2006) and in line with those previously found in bulk milk (on average 21 ± 0.3 µg/kg) from German organic and conventional farms (Schwarzenbolz et al., 2016). Nevertheless, the CML concentration in human breast milk was determined with an immunochemical assay, which may have different specificity for CML, whereas in the survey of Schwarzenbolz et al. (2016) and in our experiments CML was analyzed by LC-MS/MS, which limits to some extent between-species comparisons of the reported absolute CML concentrations in milk.

A substantial proportion of the ingested (i.e., 30 ± 1.8%) and apparently digested CML (i.e., 74 ± 2.2%) was not recovered in the analyzed excretory routes, which is in accordance with observations in other species, including humans (Delgado-Andrade et al., 2012) and rats (Alamir et al., 2013). Interestingly, the estimated amount of CML apparently retained in the body was higher with EL3 than with RL. Despite significantly higher CML supply with ELS3 than with all other treatments and a 55% numerically greater CML balance with ELS3 than RLS in EXP2, we observed no significant effect on the CML balance, hinting toward a low statistical power of EXP2. In mice, CML accumulates primarily in the kidneys but also in other tissues such as in the ileum, colon, and lungs, except in adipose tissue where it seems not to accumulate owing to its hydrophilic properties (Tessier et al., 2016). The endogenous formation of CML through oxidative reactions also at the body temperature (38-39°C) of dairy cows, as reported in other species such as humans (Thorpe and Baynes, 2002) and rodents (Alamir et al., 2013), was not evaluated in the present study but cannot be excluded a priori. Finally, any diurnal pattern in urinary CML concentration is not included in the present measurements and calculations of CML partition and excretion, which may limit to some extent the comparability of our results with those obtained in other species. Further investigations are warranted to determine the metabolism, tissue distribution, excretion kinetics, and possible deposition of CML and other dietary or endogenous advanced glycation end products, and their influence on inflammatory and oxidative status, as well as their long-term effects on the health status of dairy cows.
## CONCLUSIONS

Extrusion of lupines numerically decreased enzymatic CP degradability, especially at the highest extrusion temperature (150°C) confirming our first hypothesis. The decreased CP degradability was associated with numerically increased CML concentration and CML to total Lys ratios, irrespective of reducing sugars, partially refuting our third hypothesis. The overall effects of the extrusion on milk production and composition were limited to lower milk urea concentrations and lower fat:protein ratio with lupines extruded at 150°C without greatly affecting N partition, partially refuting our second hypothesis. Milk yield and N use efficiency for milk production increased with extrusion at 150°C only without reducing sugars, in partial agreement with our second but largely refuting the third hypothesis. Regardless of reducing sugars, the $Δ^{15}N_{animal-diet}$ was lower with lupines extruded at 150°C than with raw lupines. CML appeared to be partially digested and then excreted mainly in urine and to a much lesser extent in milk.

## ACKNOWLEDGMENTS

These experiments were conducted in the framework of the PROLEVAL project supported by Valorex SAS (Combourtille, France) and financed by bpifrance (Paris, France). We gratefully acknowledge the committed help and technical support provided by F. Fournier, G. De Falvard, L. Mouly, and D. Roux (INRAE, Herbipôle, Saint-Genès-Champanelle, France) during the setting up and performance of the experiments, as well as L. Genestoux, C. Labonne, L. Salis, C. Selebran, I. Constant, and C. Chantelauze (INRAE, UMR Herbivores, Saint-Genès-Champanelle, France) during sampling and laboratory analyses. Many thanks also to C. Léridon (UniLaSalle, Beauvais, France) for the analysis of the Maillard reaction compounds, and to J. Pires (INRAE, UMR Herbivores) for statistical advice. Author contributions were as follows: E. Manzocchi contributed to the investigation, formal analysis, visualization, writing of original draft, and review and editing of text; A. Ferlay contributed to the conceptualization, supervision, investigation, formal analysis, review and editing, and funding acquisition; S. Mendowski contributed to the conceptualization, resources, methodology, review and editing, and project administration; G. Chesneau contributed to the conceptualization, resources, methodology, review and editing, and funding acquisition; P. Chapoutot contributed to the conceptualization, methodology, review and editing, and funding acquisition; S. Lemosquet contributed to the methodology,

resources, and review and editing; G. Cantalapiedra-Hijar contributed to the methodology, formal analysis, and review and editing; and P. Nozière contributed to the conceptualization, supervision, investigation, methodology, formal analysis, validation, review and editing, and funding acquisition. Data are available from the corresponding author upon reasonable request. The authors have not stated any conflicts of interest.

## REFERENCES

Alamir, I., C. Niquet-Leridon, P. Jacolot, C. Rodriguez, M. Orosco, P. M. Anton, and F. J. Tessier. 2013. Digestibility of extruded proteins and metabolic transit of N-carboxymethyllysine in rats. Amino Acids 44:1441-1449. https://doi.org/10.1007/s00726-012-1427-3.

Aufrère, J., D. Graviou, C. Demarquilly, R. Vérité, B. Michalet-Doreau, and P. Chapoutot. 1991. Predicting in situ degradability of feed proteins in the rumen by two laboratory methods (solubility and enzymatic degradation). Anim. Feed Sci. Technol. 33:97-116. https://doi.org/10.1016/0377-8401(91)90049-X.

Bazin, S. 1984. Grille de notation de l'état d'engraissement des vaches Pie Noires. Réseau national d'expérimentation et de démonstration en élevage bovin. Institut technique de l'élevage bovin, Paris, France.

Benchaar, C., R. Moncoulon, C. Bayourthe, and M. Vernay. 1994. Effects of a supply of raw or extruded white lupin seeds on protein digestion and amino acid absorption in dairy cows. J. Anim. Sci. 72:492-501. https://doi.org/10.2527/1994.722492x.

Bui, T. P. N., A. Troise, V. Fogliano, and W. M. de Vos. 2019. Anaerobic degradation of N-carboxymethyllysine, a major glycation end-product, by human intestinal bacteria. J. Agric. Food Chem. 67:6594-6602. https://doi.org/10.1021/acs.jafc.9b02208.

Cantalapiedra-Hijar, G., R. Dewhurst, L. Cheng, A. R. J. Cabrita, A. J. M. Fonseca, P. Nozière, D. Makowski, H. Fouillet, and I. Ortigues-Marty. 2018. Nitrogen isotopic fractionation as a biomarker for nitrogen use efficiency in ruminants: A meta-analysis. Animal 12:1827-1837. https://doi.org/10.1017/S1751731117003391.

Cantalapiedra-Hijar, G., H. Fouillet, J. F. Huneau, A. Fanchone, M. Doreau, P. Nozière, and I. Ortigues-Marty. 2016. Relationship between efficiency of nitrogen utilization and isotopic nitrogen fractionation in dairy cows: Contribution of digestion v. metabolism? Animal 10:221-229. https://doi.org/10.1017/S1751731115002025.

Cattaneo, L., F. Piccioli-Cappelli, A. Minuti, and E. Trevisi. 2023. Metabolic and physiological adaptations to first and second lactation in Holstein dairy cows: Postprandial patterns. J. Dairy Sci. 106:3576-3585. https://doi.org/10.3168/jds.2022-22685.

Chapoutot, P., O. Dhumez, A. Germain, and G. Chesneau. 2016. Influence of extrusion on nitrogen degradability of faba bean or lupine blends including urea. Page 564 in EAAP 67th Annual Meeting, Belfast. Wageningen Academic Publishers.

Chapoutot, P., O. Dhumez, S. Mendowski, G. Chesneau, and P. Nozière. 2020. L'extrusion des protéagineux modifie la dégradation dans le rumen et la digestibilité intestinale de l'azote, de la lysine et des composées de Maillard. Page 384 in 25. Rencontres autour des Recherches sur les Ruminants, Institut de l'Elevage, INRAE.

Correa-Luna, M., M. Johansen, P. Nozière, C. Chantelauze, S. M. Nasrollahi, P. Lund, M. Larsen, A. R. Bayat, L. A. Crompton, C. K. Reynolds, E. Froidmont, N. Edouard, R. Dewhurst, L. Bahloul, C. Martin, and G. Cantalapiedra-Hijar. 2022. Nitrogen isotopic discrimination as a biomarker of between-cow variation in the efficiency of nitrogen utilization for milk production: A meta-analysis. J. Dairy Sci. 105:5004-5023. https://doi.org/10.3168/jds.2021-21498.

Daniel, J. B., N. C. Friggens, P. Chapoutot, H. Van Laar, and D. Sauvant. 2016. Milk yield and milk composition responses to
## CONCLUSIONS

Extrusion of lupines numerically decreased enzymatic CP degradability, especially at the highest extrusion temperature (150°C) confirming our first hypothesis. The decreased CP degradability was associated with numerically increased CML concentration and CML to total Lys ratios, irrespective of reducing sugars, partially refuting our third hypothesis. The overall effects of the extrusion on milk production and composition were limited to lower milk urea concentrations and lower fat:protein ratio with lupines extruded at 150°C without greatly affecting N partition, partially refuting our second hypothesis. Milk yield and N use efficiency for milk production increased with extrusion at 150°C only without reducing sugars, in partial agreement with our second but largely refuting the third hypothesis. Regardless of reducing sugars, the $Δ^{15}N_{animal-diet}$ was lower with lupines extruded at 150°C than with raw lupines. CML appeared to be partially digested and then excreted mainly in urine and to a much lesser extent in milk.

## ACKNOWLEDGMENTS

These experiments were conducted in the framework of the PROLEVAL project supported by Valorex SAS (Combourtillé, France) and financed by bpifrance (Paris, France). We gratefully acknowledge the committed help and technical support provided by F. Fournier, G. De Falvard, L. Mouly, and D. Roux (INRAE, Herbipôle, Saint-Genès-Champanelle, France) during the setting up and performance of the experiments, as well as L. Genestoux, C. Labonne, L. Salis, C. Selebran, I. Constant, and C. Chantelauze (INRAE, UMR Herbivores, Saint-Genès-Champanelle, France) during sampling and laboratory analyses. Many thanks also to C. Léridon (UniLaSalle, Beauvais, France) for the analysis of the Maillard reaction compounds, and to J. Pires (INRAE, UMR Herbivores) for statistical advice. Author contributions were as follows: E. Manzocchi contributed to the investigation, formal analysis, visualization, writing of original draft, and review and editing of text; A. Ferlay contributed to the conceptualization, supervision, investigation, formal analysis, review and editing, and funding acquisition; S. Mendowski contributed to the conceptualization, resources, methodology, review and editing, and project administration; G. Chesneau contributed to the conceptualization, resources, methodology, review and editing, and funding acquisition; P. Chapoutot contributed to the conceptualization, methodology, review and editing, and funding acquisition; S. Lemosquet contributed to the methodology,

resources, and review and editing; G. Cantalapiedra-Hijar contributed to the methodology, formal analysis, and review and editing; and P. Nozière contributed to the conceptualization, supervision, investigation, methodology, formal analysis, validation, review and editing, and funding acquisition. Data are available from the corresponding author upon reasonable request. The authors have not stated any conflicts of interest.

## REFERENCES

Alamir, I., C. Niquet-Leridon, P. Jacolot, C. Rodriguez, M. Orosco, P. M. Anton, and F. J. Tessier. 2013. Digestibility of extruded proteins and metabolic transit of N-carboxymethyllysine in rats. Amino Acids 44:1441-1449. https://doi.org/10.1007/s00726-012-1427-3.

Aufrère, J., D. Graviou, C. Demarquilly, R. Vérité, B. Michalet-Doreau, and P. Chapoutot. 1991. Predicting in situ degradability of feed proteins in the rumen by two laboratory methods (solubility and enzymatic degradation). Anim. Feed Sci. Technol. 33:97-116. https://doi.org/10.1016/0377-8401(91)90049-X.

Bazin, S. 1984. Grille de notation de l'état d'engraissement des vaches Pie Noires. Réseau national d'expérimentation et de démonstration en élevage bovin. Institut technique de l'élevage bovin, Paris, France.

Benchaar, C., R. Moncoulon, C. Bayourthe, and M. Vernay. 1994. Effects of a supply of raw or extruded white lupin seeds on protein digestion and amino acid absorption in dairy cows. J. Anim. Sci. 72:492-501. https://doi.org/10.2527/1994.722492x.

Bui, T. P. N., A. Troise, V. Fogliano, and W. M. de Vos. 2019. Aerobic degradation of N-carboxymethyllysine, a major glycation end-product, by human intestinal bacteria. J. Agric. Food Chem. 67:6594-6602. https://doi.org/10.1021/acs.jafc.9b02208.

Cantalapiedra-Hijar, G., R. Dewhurst, L. Cheng, A. R. J. Cabrita, A. J. M. Fonseca, P. Nozière, D. Makowski, H. Fouillet, and I. Ortigues-Marty. 2018. Nitrogen isotopic fractionation as a biomarker for nitrogen use efficiency in ruminants: A meta-analysis. Animal 12:1827-1837. https://doi.org/10.1017/S1751731117003391.

Cantalapiedra-Hijar, G., H. Fouillet, J. F. Huneau, A. Fanchone, M. Doreau, P. Nozière, and I. Ortigues-Marty. 2016. Relationship between efficiency of nitrogen utilization and isotopic nitrogen fractionation in dairy cows: Contribution of digestion v. metabolism? Animal 10:221-229. https://doi.org/10.1017/S1751731115002025.

Cattaneo, L., F. Piccioli-Cappelli, A. Minuti, and E. Trevisi. 2023. Metabolic and physiological adaptations to first and second lactation in Holstein dairy cows: Postprandial patterns. J. Dairy Sci. 106:3576-3585. https://doi.org/10.3168/jds.2022-22685.

Chapoutot, P., O. Dhumez, A. Germain, and G. Chesneau. 2016. Influence of extrusion on nitrogen degradability of faba bean or lupine blends including urea. Page 564 in EAAP 67th Annual Meeting, Belfast. Wageningen Academic Publishers.

Chapoutot, P., O. Dhumez, S. Mendowski, G. Chesneau, and P. Nozière. 2020. L'extrusion des protéagineux modifie la dégradation dans le rumen et la digestibilité intestinale de l'azote, de la lysine et des composées de Maillard. Page 384 in 25. Rencontres autour des Recherches sur les Ruminants, Institut de l'Elevage, INRAE.

Correa-Luna, M., M. Johansen, P. Nozière, C. Chantelauze, S. M. Nasrollahi, P. Lund, M. Larsen, A. R. Bayat, L. A. Crompton, C. K. Reynolds, E. Froidmont, N. Edouard, R. Dewhurst, L. Bahloul, C. Martin, and G. Cantalapiedra-Hijar. 2022. Nitrogen isotopic discrimination as a biomarker of between-cow variation in the efficiency of nitrogen utilization for milk production: A meta-analysis. J. Dairy Sci. 105:5004-5023. https://doi.org/10.3168/jds.2021-21498.

Daniel, J. B., N. C. Friggens, P. Chapoutot, H. Van Laar, and D. Sauvant. 2016. Milk yield and milk composition responses to
change in predicted net energy and metabolizable protein: A meta-analysis. Animal 10:1975-1985. https://doi.org/10.1017/S1751731116001245.

Delgado-Andrade, C., F. J. Tessier, C. Niquet-Leridon, I. Seiquer, and M. Pilar Navarro. 2012. Study of the urinary and faecal excretion of N-ε-carboxymethyllysine in young human volunteers. Amino Acids 43:595-602. https://doi.org/10.1007/s00726-011-1107-8.

Dittrich, R., I. Hoffmann, P. Stahl, A. Müller, M. W. Beckmann, and M. Pischetsrieder. 2006. Concentrations of N-ε-Carboxymethyllysine in human breast milk, infant formulas, and urine of infants. J. Agric. Food Chem. 54:6924-6928. https://doi.org/10.1021/jf060905h.

Froidmont, E., and N. Bartiaux-Thill. 2004. Suitability of lupin and pea seeds as a substitute for soybean meal in high-producing dairy cow feed. Anim. Res. 53:475-487. https://doi.org/10.1051/animres:2004034.

Grunwald, S., R. Krause, M. Bruch, T. Henle, and M. Brandsch. 2006. Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems. Br. J. Nutr. 95:1221-1228. https://doi.org/10.1079/BJN20061793.

Haque, M. N., H. Rulquin, A. Andrade, P. Faverdin, J. L. Peyraud, and S. Lemosquet. 2012. Milk protein synthesis in response to the provision of an "ideal" amino acid profile at two levels of metabolizable protein supply in dairy cows. J. Dairy Sci. 95:5876-5887. https://doi.org/10.3168/jds.2011-5230.

Hellwig, M., C. Auerbach, N. Müller, P. Samuel, S. Kammann, F. Beer, F. Gunzer, and T. Henle. 2019. Metabolization of the advanced glycation end product N-ε-carboxymethyllysine (CML) by different probiotic *E. coli* strains. J. Agric. Food Chem. 67:1963-1972. https://doi.org/10.1021/acs.jafc.8b06748.

Hellwig, M., D. Bunzel, M. Huch, C. M. A. P. Franz, S. E. Kulling, and T. Henle. 2015. Stability of individual Maillard reaction products in the presence of the human colonic microbiota. J. Agric. Food Chem. 63:6723-6730. https://doi.org/10.1021/acs.jafc.5b01391.

Hellwig, M., S. Geissler, R. Matthes, A. Peto, C. Silow, M. Brandsch, and T. Henle. 2011. Transport of free and peptide-bound glycated amino acids: Synthesis, transepithelial flux at caco-2 cell monolayers, and interaction with apical membrane transport proteins. ChemBioChem 12:1270-1279. https://doi.org/10.1002/cbic.201000759.

Hobson, P. N., and C. S. Stewart. 1997. The Rumen Microbial Ecosystem. Springer.

Hofmann, T., A. C. Engling, S. Martens, O. Steinhöfel, and T. Henle. 2020. Quantification of Maillard reaction products in animal feed. Eur. Food Res. Technol. 246:253-256. https://doi.org/10.1007/s00217-019-03406-w.

Huhtanen, P., E. H. Cabezas-Garcia, S. J. Krizsan, and K. J. Shin-gfield. 2015. Evaluation of between-cow variation in milk urea and rumen ammonia nitrogen concentrations and the association with nitrogen utilization and diet digestibility in lactating cows. J. Dairy Sci. 98:3182-3196. https://doi.org/10.3168/jds.2014-8215.

INRA. 2018. INRA Feeding System for Ruminants. Wageningen Academic Publishers. https://doi.org/10.3920/978-90-8686-292-4

INRAE-CIRAD-AFZ. 2022. Feed tables: Composition and nutritive values of feeds for cattle, sheep, goats, pigs, poultry, rabbits, horses and salmonoids. Accessed Jan. 15, 2022. https://www feedtables.com/content/lupin-white.

ISO. (International Organization for Standardization). 1999. ISO 6492:1999 Animal feeding stuffs — Determination of fat content. International Organization for Standardization, Geneva, Switzerland.

ISO. (International Organization for Standardization). 2002. ISO 5984:2002 Animal feeding stuffs-Determination of crude ash. International Organization for Standardization, Geneva, Switzerland.

ISO. (International Organization for Standardization). 2004. ISO 15914:2004 Animal feeding stuffs — Enzymatic determination of total starch content. International Organization for Standardization, Geneva, Switzerland.

ISO. (International Organization for Standardization). 2008. ISO 16634-1:2008 Food products - Determination of the total nitrogen content by combustion according to the Dumas principle and

calculation of the crude protein content — Part 1: Oilseeds and animal feeding stuffs. International Organization for Standardization, Geneva, Switzerland.

Madsen, T. G., M. O. Nielsen, J. B. Andersen, and K. L. Ingvartsen. 2008. Continuous lactation in dairy cows: Effect on milk production and mammary nutrient supply and extraction. J. Dairy Sci. 91:1791-1801. https://doi.org/10.3168/jds.2007-0905.

Manzocchi, E., A. Ferlay, S. Mendowski, G. Chesneau, P. Chapoutot, S. Lemosquet, G. Cantalapiedra-Hijar, P. Nozière. 2023. Supplementary materials for: Manzocchi et al, J Dairy Sci 2022-22902. Recherche Data Gouv. V3. https://doi.org/10.57745/U4U77P.

Mehler, J., K. I. Behringer, R. E. Rollins, F. Pisarz, A. Klingl, T. Henle, R. Heermann, N. S. Becker, M. Hellwig, and J. Lassak. 2022. Identification of *Pseudomnoas asiatica* subsp. *bavariensis* str. JM1 as the first N-ε-carboxy(m)ethyllysine-degrading soil bacterium. Environ. Microbiol. 24:3229-3241. https://doi.org/10.1111/1462-2920.16079.

Mendowski, S., P. Chapoutot, G. Chesneau, A. Ferlay, F. Enjalbert, G. Cantalapiedra-Hijar, A. Germain, and P. Nozière. 2019. Effects of replacing soybean meal with raw or extruded blends containing faba bean or lupin seeds on nitrogen metabolism and performance of dairy cows. J. Dairy Sci. 102:5130-5147. https://doi.org/10.3168/jds.2018-15416.

Mendowski, S., P. Chapoutot, G. Chesneau, A. Ferlay, F. Enjalbert, G. Cantalapiedra-Hijar, A. Germain, and P. Nozière. 2020. Effects of pretreatment with reducing sugars or an enzymatic cocktail before extrusion of fava bean on nitrogen metabolism and performance of dairy cows. J. Dairy Sci. 103:396-409. https://doi.org/10.3168/jds.2019-17286.

Mendowski, S., P. Nozière, A. Ferlay, P. Denis, G. Chesneau, and P. Chapoutot. 2021. Raw or technologically treated proteaginous seeds as alternatives to soybean meal for dairy cows: Comparative evaluation by meta-analysis of in situ and in vivo digestive parameters, nitrogen partition and dairy performance. Anim. Feed Sci. Technol. 271:114758. https://doi.org/10.1016/j.anifeedsci.2020.114758.

Metcalf, J. A., R. J. Mansbridge, J. S. Blake, J. D. Oldham, and J. R. Newbold. 2008. The efficiency of conversion of metabolisable protein into milk true protein over a range of metabolisable protein intakes. Animal 2:1193-1202. https://doi.org/10.1017/S1751731108002140.

Milkovska-Stamenova, S., and R. Hoffmann. 2019. Diversity of advanced glycation end products in the bovine milk proteome. American Acids 51:891-901. https://doi.org/10.1007/s00726-019-02707-4.

Mura, H., M. Horiguchi, and T. Matsumoto. 1980. Nutritional independence among rumen bacteria, *Bacteroides amylophilus*, *Megasphaera elsdenii*, and *Ruminococcus albus*. Appl. Environ. Microbiol. 40:294-300. https://doi.org/10.1128/aem.40.2.294-300.1980.

Moraes, L. E., E. Kebreab, J. L. Firkins, R. R. White, R. Martineau, and H. Lapierre. 2018. Predicting milk protein responses and the requirement of metabolizable protein by lactating dairy cows. J. Dairy Sci. 101:310-327. https://doi.org/10.3168/jds.2016-12507.

Niquet-Léridon, C., and F. J. Tessier. 2011. Quantification of N-ε-carboxymethyl-lysine in selected chocolate-flavoured drink mixes using high-performance liquid chromatography-linear ion trap tandem mass spectrometry. Food Chem. 126:655-663. https://doi.org/10.1016/j.foodchem.2010.10.111.

Ogimoto, K., and S. Imai. 1981. Atlas of Rumen Microbiology. Japan Scientific Societies Press.

Omphalius, C., H. Lapierre, J. Guinard-Flament, P. Lamberton, L. Bahloul, and S. Lemosquet. 2019. Amino acid efficiencies of utilization vary by different mechanisms in response to energy and protein supplies in dairy cows: Study at mammary-gland and whole-body levels. J. Dairy Sci. 102:9883-9901. https://doi.org/10.3168/jds.2019-16433.

Palasweenun, P., E. A. Hagen-Plantinga, J. T. Schonewille, G. Koop, C. Butre, M. Jonathan, P. A. Wierenga, and W. H. Hendriks. 2021. Urinary excretion of advanced glycation end products in dogs and cats. J. Anim. Physiol. Anim. Nutr. (Berl.) 105:149-156. https://doi.org/10.1111/jpn.13347.
change in predicted net energy and metabolizable protein: A meta-analysis. Animal 10:1975-1985. https://doi.org/10.1017/S1751731116001245.

Delgado-Andrade, C., F. J. Tessier, C. Niquet-Leridon, I. Seiquer, and M. Pilar Navarro. 2012. Study of the urinary and faecal excretion of N-ε-carboxymethyllysine in young human volunteers. Amino Acids 43:595-602. https://doi.org/10.1007/s00726-011-1107-8.

Dittrich, R., I. Hoffmann, P. Stahl, A. Müller, M. W. Beckmann, and M. Pischetsrieder. 2006. Concentrations of N-ε-Carboxymethyllysine in human breast milk, infant formulas, and urine of infants. J. Agric. Food Chem. 54:6924-6928. https://doi.org/10.1021/jf060905h.

Froidmont, E., and N. Bartiaux-Thill. 2004. Suitability of lupin and pea seeds as a substitute for soybean meal in high-producing dairy cow feed. Anim. Res. 53:475-487. https://doi.org/10.1051/animres:2004034.

Grunwald, S., R. Krause, M. Bruch, T. Henle, and M. Brandsch. 2006. Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems. Br. J. Nutr. 95:1221-1228. https://doi.org/10.1079/BJN20061793.

Haque, M. N., H. Rulquin, A. Andrade, P. Faverdin, J. L. Peyraud, and S. Lemosquet. 2012. Milk protein synthesis in response to the provision of an “ideal” amino acid profile at two levels of metabolizable protein supply in dairy cows. J. Dairy Sci. 95:5876-5887. https://doi.org/10.3168/jds.2011-5230.

Hellwig, M., C. Auerbach, N. Müller, P. Samuel, S. Kammann, F. Beer, F. Gunzer, and T. Henle. 2019. Metabolization of the advanced glycation end product N-ε-carboxymethyllysine (CML) by different probiotic *E. coli* strains. J. Agric. Food Chem. 67:1963-1972. https://doi.org/10.1021/acs.jafc.8b06748.

Hellwig, M., D. Bunzel, M. Huch, C. M. A. P. Franz, S. E. Kulling, and T. Henle. 2015. Stability of individual Maillard reaction products in the presence of the human colonic microbiota. J. Agric. Food Chem. 63:6723-6730. https://doi.org/10.1021/acs.jafc.5b01391.

Hellwig, M., S. Geissler, R. Matthes, A. Peto, C. Silow, M. Brandsch, and T. Henle. 2011. Transport of free and peptide-bound glycated amino acids: Synthesis, transepithelial flux at caco-2 cell monolayers, and interaction with apical membrane transport proteins. ChemBioChem 12:1270-1279. https://doi.org/10.1002/cbic.201000759.

Hobson, P. N., and C. S. Stewart. 1997. The Rumen Microbial Ecosystem. Springer.

Hofmann, T., A. C. Engling, S. Martens, O. Steinhöfel, and T. Henle. 2020. Quantification of Maillard reaction products in animal feed. Eur. Food Res. Technol. 246:253-256. https://doi.org/10.1007/s00217-019-03406-w.

Huhtanen, P., E. H. Cabezas-Garcia, S. J. Krizsan, and K. J. Shin-gfield. 2015. Evaluation of between-cow variation in milk urea and rumen ammonia nitrogen concentrations and the association with nitrogen utilization and diet digestibility in lactating cows. J. Dairy Sci. 98:3182-3196. https://doi.org/10.3168/jds.2014-8215.

INRA. 2018. INRA Feeding System for Ruminants. Wageningen Academic Publishers. https://doi.org/10.3920/978-90-8686-292-4

INRAE-CIRAD-AFZ. 2022. Feed tables: Composition and nutritive values of feeds for cattle, sheep, goats, pigs, poultry, rabbits, horses and salmonoids. Accessed Jan. 15, 2022. https://www feedtables.com/content/lupin-white.

ISO. (International Organization for Standardization). 1999. ISO 6492:1999 Animal feeding stuffs — Determination of fat content. International Organization for Standardization, Geneva, Switzerland.

ISO. (International Organization for Standardization). 2002. ISO 5984:2002 Animal feeding stuffs-Determination of crude ash. International Organization for Standardization, Geneva, Switzerland.

ISO. (International Organization for Standardization). 2004. ISO 15914:2004 Animal feeding stuffs — Enzymatic determination of total starch content. International Organization for Standardization, Geneva, Switzerland.

ISO. (International Organization for Standardization). 2008. ISO 16634-1:2008 Food products - Determination of the total nitrogen content by combustion according to the Dumas principle and

calculation of the crude protein content — Part 1: Oilseeds and animal feeding stuffs. International Organization for Standardization, Geneva, Switzerland.

Madsen, T. G., M. O. Nielsen, J. B. Andersen, and K. L. Ingvartsen. 2008. Continuous lactation in dairy cows: Effect on milk production and mammary nutrient supply and extraction. J. Dairy Sci. 91:1791-1801. https://doi.org/10.3168/jds.2007-0905.

Manzocchi, E., A. Ferlay, S. Mendowski, G. Chesneau, P. Chapoutot, S. Lemosquet, G. Cantalapiedra-Hijar, P. Nozière. 2023. Supplementary materials for: Manzocchi et al, J Dairy Sci 2022-22902. Recherche Data Gouv. V3. https://doi.org/10.57745/U4U77P.

Mehler, J., K. I. Behringer, R. E. Rollins, F. Pisarz, A. Klingl, T. Henle, R. Heermann, N. S. Becker, M. Hellwig, and J. Lassak. 2022. Identification of *Pseudomnoas asiatica* subsp. *bavariensis* str. JM1 as the first N-ε-carboxy(m)ethyllysine-degrading soil bacterium. Environ. Microbiol. 24:3229-3241. https://doi.org/10.1111/1462-2920.16079.

Mendowski, S., P. Chapoutot, G. Chesneau, A. Ferlay, F. Enjalbert, G. Cantalapiedra-Hijar, A. Germain, and P. Nozière. 2019. Effects of replacing soybean meal with raw or extruded blends containing faba bean or lupin seeds on nitrogen metabolism and performance of dairy cows. J. Dairy Sci. 102:5130-5147. https://doi.org/10.3168/jds.2018-15416.

Mendowski, S., P. Chapoutot, G. Chesneau, A. Ferlay, F. Enjalbert, G. Cantalapiedra-Hijar, A. Germain, and P. Nozière. 2020. Effects of pretreatment with reducing sugars or an enzymatic cocktail before extrusion of fava bean on nitrogen metabolism and performance of dairy cows. J. Dairy Sci. 103:396-409. https://doi.org/10.3168/jds.2019-17286.

Mendowski, S., P. Nozière, A. Ferlay, P. Denis, G. Chesneau, and P. Chapoutot. 2021. Raw or technologically treated proteaginous seeds as alternatives to soybean meal for dairy cows: Comparative evaluation by meta-analysis of in situ and in vivo digestive parameters, nitrogen partition and dairy performance. Anim. Feed Sci. Technol. 271:114758. https://doi.org/10.1016/j.anifeedsci.2020.114758.

Metcalf, J. A., R. J. Mansbridge, J. S. Blake, J. D. Oldham, and J. R. Newbold. 2008. The efficiency of conversion of metabolisable protein into milk true protein over a range of metabolisable protein intakes. Animal 2:1193-1202. https://doi.org/10.1017/S1751731108002140.

Milkovska-Stamenova, S., and R. Hoffmann. 2019. Diversity of advanced glycation end products in the bovine milk proteome. American Acids 51:891-901. https://doi.org/10.1007/s00726-019-02707-4.

Mura, H., M. Horiguchi, and T. Matsumoto. 1980. Nutritional independence among rumen bacteria, *Bacteroides amylophilus*, *Megasphaera elsdenii*, and *Ruminococcus albus*. Appl. Environ. Microbiol. 40:294-300. https://doi.org/10.1128/aem.40.2.294-300.1980.

Moraes, L. E., E. Kebreab, J. L. Firkins, R. R. White, R. Martineau, and H. Lapierre. 2018. Predicting milk protein responses and the requirement of metabolizable protein by lactating dairy cows. J. Dairy Sci. 101:310-327. https://doi.org/10.3168/jds.2016-12507.

Niquet-Léridon, C., and F. J. Tessier. 2011. Quantification of N-ε-carboxymethyl-lysine in selected chocolate-flavoured drink mixes using high-performance liquid chromatography-linear ion trap tandem mass spectrometry. Food Chem. 126:655-663. https://doi.org/10.1016/j.foodchem.2010.10.111.

Ogimoto, K., and S. Imai. 1981. Atlas of Rumen Microbiology. Japan Scientific Societies Press.

Omphalius, C., H. Lapierre, J. Guinard-Flament, P. Lamberton, L. Bahloul, and S. Lemosquet. 2019. Amino acid efficiencies of utilization vary by different mechanisms in response to energy and protein supplies in dairy cows: Study at mammary-gland and whole-body levels. J. Dairy Sci. 102:9883-9901. https://doi.org/10.3168/jds.2019-16433.

Palasweenun, P., E. A. Hagen-Plantinga, J. T. Schonewille, G. Koop, C. Butre, M. Jonathan, P. A. Wierenga, and W. H. Hendriks. 2021. Urinary excretion of advanced glycation end products in dogs and cats. J. Anim. Physiol. Anim. Nutr. (Berl.) 105:149-156. https://doi.org/10.1111/jpn.13347.
Peyraud, J. L., C. Genest-Rulquin, and R. Vérité. 1988. Mesure de la digestion de l'azote des aliments dans l'intestin des ruminants par la technique des sachets mobiles. 1. Évaluation de la quantité de matières azotées indigestibles en sachet des principaux aliments. Reprod. Nutr. Dev. 28(Suppl. 1):129-130. https://doi.org/10.1051/rnd:19881139.

Schwarzenbolz, U., T. Hofmann, N. Sarmann, and T. Henle. 2016. Free Maillard reaction products in milk reflect nutritional intake of glycated proteins and can be used to distinguish “organic” and “conventionally” produced milk. J. Agric. Food Chem. 64:5071-5078. https://doi.org/10.1021/acs.jafc.6b01375.

Šebeková, K., G. Saavedra, C. Zumpe, V. Somoza, K. Klenovicsová, and I. Birlouez-Aragon. 2008. Plasma concentration and urinary excretion of N<sup>E</sup>-(carboxymethyl)lysine in breast milk- and formula-fed infants. Ann. N. Y. Acad. Sci. 1126:177-180. https://doi.org/10.1196/annals.1433.049.

Seymour, W. M., C. E. Polan, and J. H. Herbein. 1990. Effects of dietary protein degradability and casein or amino acid infusions on production and plasma amino acids in dairy cows. J. Dairy Sci. 73:735-748. https://doi.org/10.3168/jds.S0022-0302(90)78727-9.

Shen, J. S., Z. Chai, L. J. Song, J. X. Liu, and Y. M. Wu. 2012. Insertion depth of oral stomach tubes may affect the fermentation parameters of ruminal fluid collected in dairy cows. J. Dairy Sci. 95:5978-5984. https://doi.org/10.3168/jds.2012-5499.

Smith, P. H., H. C. Sweeney, J. R. Rooney, K. W. King, and W. E. C. Moore. 1956. Stratifications and kinetic changes in the ingesta of the bovine rumen. J. Dairy Sci. 39:598-609. https://doi.org/10.3168/jds.S0022-0302(56)94791-9.

Spanghero, M., and Z. M. Kowalski. 1997. Critical analysis of N balance experiments with lactating cows. Livest. Prod. Sci. 52:113-122. https://doi.org/10.1016/S0301-6226(97)00138-3.

Spanghero, M., and Z. M. Kowalski. 2021. Updating analysis of nitrogen balance experiments in dairy cows. J. Dairy Sci. 104:7725-7737. https://doi.org/10.3168/jds.2020-19656.

Teodorowicz, M., W. H. Hendriks, H. J. Wichers, and H. F. J. Savelkoul. 2018. Immunomodulation by processed animal feed: The role

of Maillard reaction products and advanced glycation end-products (AGEs). Front. Immunol. 9:2088. https://doi.org/10.3389/fimmu.2018.02088.

Tessier, F. J., E. Boulanger, and M. Howsam. 2021. Metabolic transit of dietary advanced glycation end-products—The case of N<sup>E</sup>-carboxymethyllysine. Glycoconj. J. 38:311-317. https://doi.org/10.1007/s10719-020-09950-y.

Tessier, F. J., C. Niquet-Léridon, P. Jacolot, C. Jouquand, M. Genin, A.-M. Schmidt, N. Grossin, and E. Boulanger. 2016. Quantitative assessment of organ distribution of dietary protein-bound <sup>13</sup>C-labeled N<sup>E</sup>-carboxymethyllysine after a chronic oral exposure in mice. Mol. Nutr. Food Res. 60:2446-2456. https://doi.org/10.1002/mnfr.201600140.

Thorpe, S. R., and J. W. Baynes. 2002. CML: A brief history. Int. Congr. Ser. 1245:91-99. https://doi.org/10.1016/S0531-5131(02)00881-6.

van Soest, P. J., and V. C. Mason. 1991. The influence of the Maillard reaction upon the nutritive value of fibrous feeds. Anim. Feed Sci. Technol. 32:45-53. https://doi.org/10.1016/0377-8401(91)90008-G.

Van Soest, P. J., J. B. Robertson, and B. A. Lewis. 1991. Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition. J. Dairy Sci. 74:3583-3597. https://doi.org/10.3168/jds.S0022-0302(91)78551-2.

Wölk, M., S. Milkovska-Stamenova, T. Schröter, and R. Hoffmann. 2021. Influence of seasonal variation and processing on protein glycation and oxidation in regular and hay milk. Food Chem. 337:127690. https://doi.org/10.1016/j.foodchem.2020.127690.

## ORCIDS

E. Manzocchi https://orcid.org/0000-0002-6397-8300

A. Ferlay https://orcid.org/0000-0002-0651-792X

S. Lemosquet https://orcid.org/0000-0002-1077-1285

G. Cantalapiedra-Hijar https://orcid.org/0000-0001-9486-8238

P. Nozière https://orcid.org/0000-0003-1727-8984
Peyraud, J. L., C. Genest-Rulquin, and R. Vérité. 1988. Mesure de la digestion de l'azote des aliments dans l'intestin des ruminants par la technique des sachets mobiles. 1. Évaluation de la quantité de matières azotées indigestibles en sachet des principaux aliments. Reprod. Nutr. Dev. 28(Suppl. 1):129-130. https://doi.org/10.1051/rnd:19881139.

Schwarzenbolz, U., T. Hofmann, N. Sarmann, and T. Henle. 2016. Free Maillard reaction products in milk reflect nutritional intake of glycated proteins and can be used to distinguish “organic” and “conventionally” produced milk. J. Agric. Food Chem. 64:5071-5078. https://doi.org/10.1021/acs.jafc.6b01375.

Šebeková, K., G. Saavedra, C. Zumpe, V. Somoza, K. Klenovicsová, and I. Birlouez-Aragon. 2008. Plasma concentration and urinary excretion of N<sup>E</sup>-(carboxymethyl)lysine in breast milk- and formula-fed infants. Ann. N. Y. Acad. Sci. 1126:177-180. https://doi.org/10.1196/annals.1433.049.

Seymour, W. M., C. E. Polan, and J. H. Herbein. 1990. Effects of dietary protein degradability and casein or amino acid infusions on production and plasma amino acids in dairy cows. J. Dairy Sci. 73:735-748. https://doi.org/10.3168/jds.S0022-0302(90)78727-9.

Shen, J. S., Z. Chai, L. J. Song, J. X. Liu, and Y. M. Wu. 2012. Insertion depth of oral stomach tubes may affect the fermentation parameters of ruminal fluid collected in dairy cows. J. Dairy Sci. 95:5978-5984. https://doi.org/10.3168/jds.2012-5499.

Smith, P. H., H. C. Sweeney, J. R. Rooney, K. W. King, and W. E. C. Moore. 1956. Stratifications and kinetic changes in the ingesta of the bovine rumen. J. Dairy Sci. 39:598-609. https://doi.org/10.3168/jds.S0022-0302(56)94791-9.

Spanghero, M., and Z. M. Kowalski. 1997. Critical analysis of N balance experiments with lactating cows. Livest. Prod. Sci. 52:113-122. https://doi.org/10.1016/S0301-6226(97)00138-3.

Spanghero, M., and Z. M. Kowalski. 2021. Updating analysis of nitrogen balance experiments in dairy cows. J. Dairy Sci. 104:7725-7737. https://doi.org/10.3168/jds.2020-19656.

Teodorowicz, M., W. H. Hendriks, H. J. Wichers, and H. F. J. Savelkoul. 2018. Immunomodulation by processed animal feed: The role

of Maillard reaction products and advanced glycation end-products (AGEs). Front. Immunol. 9:2088. https://doi.org/10.3389/fimmu.2018.02088.

Tessier, F. J., E. Boulanger, and M. Howsam. 2021. Metabolic transit of dietary advanced glycation end-products—The case of N<sup>E</sup>-carboxymethyllysine. Glycoconj. J. 38:311-317. https://doi.org/10.1007/s10719-020-09950-y.

Tessier, F. J., C. Niquet-Léridon, P. Jacolot, C. Jouquand, M. Genin, A.-M. Schmidt, N. Grossin, and E. Boulanger. 2016. Quantitative assessment of organ distribution of dietary protein-bound <sup>13</sup>C-labeled N<sup>E</sup>-carboxymethyllysine after a chronic oral exposure in mice. Mol. Nutr. Food Res. 60:2446-2456. https://doi.org/10.1002/mnfr.201600140.

Thorpe, S. R., and J. W. Baynes. 2002. CML: A brief history. Int. Congr. Ser. 1245:91-99. https://doi.org/10.1016/S0531-5131(02)00881-6.

van Soest, P. J., and V. C. Mason. 1991. The influence of the Maillard reaction upon the nutritive value of fibrous feeds. Anim. Feed Sci. Technol. 32:45-53. https://doi.org/10.1016/0377-8401(91)90008-G.

Van Soest, P. J., J. B. Robertson, and B. A. Lewis. 1991. Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition. J. Dairy Sci. 74:3583-3597. https://doi.org/10.3168/jds.S0022-0302(91)78551-2.

Wölk, M., S. Milkovska-Stamenova, T. Schröter, and R. Hoffmann. 2021. Influence of seasonal variation and processing on protein glycation and oxidation in regular and hay milk. Food Chem. 337:127690. https://doi.org/10.1016/j.foodchem.2020.127690.

## ORCIDS

E. Manzocchi https://orcid.org/0000-0002-6397-8300

A. Ferlay https://orcid.org/0000-0002-0651-792X

S. Lemosquet https://orcid.org/0000-0002-1077-1285

G. Cantalapiedra-Hijar https://orcid.org/0000-0001-9486-8238

P. Nozière https://orcid.org/0000-0003-1727-8984