Rumen-protected methionine’s role in cow health and productivity extends beyond milk production to support immune function, metabolism, and resilience during stress. Emerging research highlights its impact on immunometabolism, mTOR signaling, and antioxidant pathways. Across challenges such as the transition period or subclinical mastitis, dietary interventions can influence performance, inflammation, and oxidative stress—raising questions about how targeted amino acid nutrition shapes long-term health, efficiency, and sustainability in dairy herds.
Global Ruminant Technical & Scientific Support Manager
Adisseo
Global Ruminants and Operational Marketing Director
Adisseo
In today’s dairy landscape, staying competitive means going beyond simply producing more milk. It’s about producing it efficiently, sustainably, and with the long-term health and resilience of cows in mind. Cow health is now recognized not just as an animal welfare concern, but as a core driver of productivity, profitability, and environmental performance.
At the heart of this evolution is nutrition, and amino acid (AA) balancing. Of particular interest is the AA methionine (Met) which can be fed to not only maximize milk yield and components, but to also support the immune system, metabolism, and lifetime performance of dairy cattle, especially during periods of stress.
WHY COW HEALTH DETERMINES DAIRY SUCCESS
Health has always mattered on the farm, but the stakes are higher than ever. Common issues like mastitis, metabolic disorders, and immune suppression don’t just affect production today, they influence the cow’s productive lifespan, reproduction, and the economic viability of the farm.
Sick cows cost more, produce less, and are culled earlier. Whereas healthier cows stay in the herd longer, perform better, and require fewer interventions. Focusing on improved health means optimizing the entire system, from nutrient metabolism to feed efficiency, fertility and labor.
IMMUNOMETABOLISM: NEW FRONTIER IN DAIRY NUTRITION
Over the last two decades, we have learned that the immune system and metabolism are very interconnected, leading to the emergence of the field of immunometabolism (Basso et al., 2024). In dairy cattle, research in this area is helping us to understand how metabolism and immune function influence production, with a specific emphasis on how nutrition influences immunometabolism. One of the major regulators of immunometabolism via nutrition is mechanistic target of rapamycin (mTOR), which is sensitive to nutrients such as Met.
A core aspect of immunometabolism is the investigation of how dietary and metabolic interventions can enhance immune health and responses to stressors. Researchers have explored how a variety of nutrients may influence and support immunometabolism, but of particular interest have been AA (Miyajima, 2020). Likely, the first thing that comes to mind when thinking about AA is their need for protein synthesis. However, there is growing knowledge that AA have functional roles beyond protein synthesis
THE CLASSICAL FUNCTIONS OF METHIONINE AND mTOR
Methionine an AA that has been recognized for its extensive functional roles:
• One-carbon metabolism: Met is metabolized in these pathways, via which it provides methyl donors and enhances production of the antioxidants glutathione (GSH) and taurine (Coleman et al., 2020).
• mTOR activation: Met is a known activator of mTOR, a nutrient-sensitive kinase (enzyme that transfers a phosphate group) that integrates signals from growth factors, energy and AA. In response to AA, mTOR itself is phosphorylated and subsequently activates pathways of protein and fatty acid synthesis (Laplante & Sabatini, 2009). This is a key mechanism behind increases in milk protein and fat when rumen-protected methionine (RPM) is added to dairy cow diets.
These roles highlight how Met supports immunometabolism in dairy cows.
NOVEL INSIGHTS INTO THE ROLE OF METHIONINE IN IMMUNE FUNCTION
Beyond its effects on protein and fat synthesis, emerging research is indicating that mTOR is an important component of immunometabolism due to its key role in detecting and directing cellular processes.
In immune cells specifically, mTOR regulates protein synthesis and cell proliferation, as well as integrates metabolic signals during immune cell activation (Weichhart et al., 2008). Moreover, mTOR target proteins have been reported to mediate inflammatory responses in immune cells, suggesting that Met can enhance immunometabolism not only through antioxidant pathways, but also via mTOR signaling (Figure 1).
MODULATION OF IMMUNOMETABOLISM WITH METHIONINE
While the transition period is one of the most challenging times in the life of dairy cattle, it has been well-documented that enhancing Met supply through RPM improves immunometabolism in transition cows via better liver function, greater GSH production, lower oxidative stress and inflammation, and improved immune function (Coleman et al., 2020). These improvements in immunometabolic markers have been associated with not only better dry matter intake (DMI) and performance, but also better health. Moreover, Met supplementation supports immunometabolism and sustains performance during heat stress through reductions in oxidative stress, as well as improved mTOR signaling in the mammary gland and liver. However, one question was whether Met supplementation could also improve the health and performance of dairy cows in response to a specific health disorder, such as mastitis, and if Met influences mTOR signaling of immune cells.
BENEFITS OF METHIONINE DURING A SUBCLINICAL MASTITIS CHALLENGE
Those questions were tackled by a recent publication utilizing a subclinical mastitis challenge (SMC; Paz et al., 2024). In that study, cows (145 ± 51 days in milk) fed Smartamine® M (SM) (0.09% dry matter; +13.4 g metabolizable Met; 2.53 Lys:Met) for 21 d prior to a subclinical mastitis challenge (SMC) with Streptococcus uberis demonstrated:
• Improved milk production: Despite no difference in DMI, SM cows produced more milk fat, protein, and energy corrected milk (ECM) (Figure 2) during the first 72 h post-challenge vs. cows not fed supplemental Met (CON), highlighting the importance of Met for sustaining production during a period of stress.
• Less inflammation and oxidative stress: Cows fed Met showed favorable changes in liver and plasma biomarkers (GSH and the genes that synthesize it, reactive oxygen species and inflammatory markers) during the SMC, indicating lower local and systemic oxidative stress and inflammation, likely supporting improved performance.
In Met-supplemented cows, phosphorylation of the mTOR pathway proteins AKT, S6RP, and 4EBP (key players regulating the initiation of protein synthesis) was increased in milk and blood immune cells. This indicates greater activation of protein synthesis (Laplante & Sabatini, 2009), which could drive immune cell activation and function compared to CON. Indeed, there was evidence of this in leukocytes, where they also reported that SM cows tended to have greater expression of the mTOR target L-selectin, a mediator of leukocyte migration to sites of inflammation. Together these results suggest that Met improved immune responsiveness via mTOR, helping cows to better manage the immunometabolic stress of the SMC.
Altogether, across multiple stressors, Met supplementation modulates immunometabolism of dairy cows. The responses to Met are driven in part by enhanced mTOR activation in immune cells. This activation, combined with the other immunometabolic benefits of Met, sets dairy cows up to perform better during a health challenge. Such improvements point towards the essentiality of Met in preparing cows to handle the negative effects of a stressor such as subclinical mastitis.
TURNING HEALTH INTO MEASURABLE VALUE
These benefits of AA balancing on health can now be quantified using Milk$mart, Adisseo’s AA benefit calculator. With this program, farmers and nutritionists can estimate the financial return of Met supplementation on production, reproduction, health and income over feed cost.
HEALTHIER COWS, SMALLER CARBON FOOTPRINT
There’s also an environmental dimension to health. By improving health and performance through AA balancing, Adisseo solutions contribute to more efficient farming. According to a French ISO-certified farm study (Blonk), this can lead to up to a 15% reduction in the carbon footprint of dairy operations.
Indeed, healthier cows stay in the herd longer, produce more milk per day, and waste fewer resources. This means fewer emissions per liter of milk produced and a more sustainable dairy supply chain.
CONCLUSION
Investing in cow health starts with nutrition. Supplying rumen-protected methionine via Smartamine® M or MetaSmart® does more than just maximize milk production, it activates biological systems that help cows withstand stress, recover faster, and perform longer. This leads to healthier cows that are more productive throughout their lives, meaning more profitable and sustainable milk production on farms.
References
1. Basso, P. J., T. Gauthier, F. Palomares, S. López-Enríquez, S. Tsai. 2024. Editorial: Immunometabolism: bridging the gap between immunology and nutrition. Front. Nutr. 11:1436894
2. D. N., V. Lopreiato, A. Alharthi, and J. J. Loor. 2020. Amino acids and the regulation of oxidative stress and immune function. J. Anim. Sci. 98(Suppl. 1):S175-S193
3. Laplante, M., and D. M. Sabatini. 2009. mTOR signaling at a glance. J. Cell Sci. 122:3589
4. Paz, A., T. C. Michelotti, M. Suazo, J. Bonilla, M. Bulnes, A. Minuti, D. Luchini, E. Trevisi, A. F. Lima, J. Halfen, M. Rovai, and J. S. Osorio. 2024. Rumen-protected methionine supplementation improves lactation performance and alleviates inflammation during a subclinical mastitis challenge in lactating dairy cows. J. Dairy Sci. 107:10761-10775
5. Weichhart, T., G. Constantino, M. Poglitsch, M. Rosner, M. Zeyda, K. M. Stuhlmeier, T. Kolbe, T. M. Stulnig, W. H. Horl, M. Hengstschlager, M. Muller, and M. D. Saemann. 2008. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29:565-577
About Dr. Danielle Sherlock
A Global Ruminant Technical & Scientific Support Manager at Adisseo, Dr. Danielle Sherlock received her B.S. and M.Sc. degrees in Animal Science form The Ohio State University, and her PhD in Animal Science from the University of Illinois at Urbana-Champaign prior to joining Adisseo. Her doctoral research investigated the impact of methyl donors on immunometabolism during periods of stress in dairy cattle. Sherlock joined Adisseo in 2021 and is based in Madison, Wisconsin, USA, where she develops and manages research projects in Ruminant Nutrition and Health.About Dr. Anne-Sophie Conjat
Graduating as a Doctor of Veterinary Medicine in France in 2001, Dr. Anne-Sophie Conjat later completed a Master’s degree in Business. She began her career in the veterinary pharmaceutical industry before joining Adisseo in 2015 as Global Category Manager for Selisseo, a role she held for six years. In 2021, she transitioned to the ruminant business segment and is now fully dedicated to marketing.
