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Evonik Animal Nutrition

The science is clear: Betaine cannot replace methionine

Published: August 24, 2026
Source : ANDREAS LEMME
The science is clear: Betaine cannot replace methionine - Image 1
BETAINE CAN NOT REPLACE METHIONINE
Nutritionists constantly seek opportunities to reduce diet costs while maintaining optimal animal performance. When ingredient prices rise, nutritionists search for ways to reduce their use or replace them with alternative ingredients.
With respect to methionine (Met), it is sometimes claimed that supplemental betaine (BET) has the potential to replace a substantial portion of supplemental DL-Met. Indeed, BET and Met are connected, as BET can donate a methyl group (CH3; 1) to remethylate homocysteine to form Met. Met, in turn, can donate a methyl group towards creatine formation (2), releasing homocysteine. This pathway is known as the homocysteine cycle. BET cannot directly participate in creatine synthesis. Although BET can be formed out of choline (3), choline itself cannot donate a methyl group directly into the homocysteine cycle. By definition, BET cannot replace Met, but it may increase the number of homocysteine remethylation cycles. It has been reported that, under adequate Met supply, homocysteine undergoes remethylation 1.5 to 2 times until it is transformed into cysteine (4) or further degraded [1]. When only half of dietary Met is given, the number of remethylation cycles only doubled [1].
The science is clear: Betaine cannot replace methionine - Image 2
Consequently, BET has limited potential to improve Met metabolism via the homocysteine cycle, and only under Met deficient conditions. Such conditions do not occur in commercial diets. In fact, the opposite is often true. Dietary Met often exceeds the optimal concentration as the exact requirement is difficult to estimate for specific production conditions due to the involvement of Met in numerous metabolic pathways [2]. In addition, between-batch variations of the nutritional profile of macro feed ingredients force nutritionists to implement safety margins, often resulting in luxury rather than marginal Met supply. If Met is oversupplied, the surplus can be replaced with any other compound, including BET, or simply be reduced.
A trial with male broilers (130 birds/pen; 6 pens/ trt), in which equimolar levels of DL-Met or BET were added to Met+Cys deficient starter (0-10d), grower (11-27d) and finisher (28-42d) diets, demonstrated that BET had neither a beneficial impact on growth performance nor the potential to replace DL-Met [3]. Accordingly, addition of 0.04 or 0.08% DL-Met significantly increased final body weights by 31 or 44%, respectively, whereas equimolar additions of 0.04 or 0.08% BET had no positive impact. Moreover, gradual replacement of DL-Met with BET did not suggest any Met-sparing potential for BET. The significant reduction in body weight with increasing BET supplementation does not indicate more efficient metabolic utilization of Met.
The growth study provided evidence that dietary addition of BET cannot replace supplemental DL-Met at or below Met+Cys requirement. This finding is substantiated by the mode of action of the homocysteine cycle. If replacing DL-Met with BET does not compromise animal performance, then only surplus Met above the required amount has been replaced. Therefore, adjusting the dietary Met+Cys specification is advisable in order to minimize diet costs.

1. Selhub, J. Homocysteine metabolism. Annu. Rev. Nutr. 1999, 19, 217–246, doi:10.1146/annurev.nutr.19.1.217.

2. Klünemann, M.; Romero, L.F.; Acman, M.; Milfort, M.C.; Fuller, A.L.; Rekaya, R.; Aggrey, S.E.; Payling, L.M.; Lemme, A. Multi-tissue transcriptomics demonstrates the systemic physiology of methionine deficiency in broiler chickens. animal 2024, 101143, doi:10.1016/j.animal.2024.101143.

3. Müller, M.; Lemme, A.; Machander, V. Potential of betaine to replace methionine in broiler nutrition. Proceedings of 21st European Symposium on Poultry Nutrition; #2.36 pp 4

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Authors:
Dr. Andreas Lemme
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Martin Smith, Victor Naranjo Haro
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Leon Broom
29 de septiembre de 2026
Interesting discussion and great batting by both sides for their respective 'teams'. As a casual observer, some of the statements seem a little too absolute and imply that these compounds behave in linear, siloed, non-interacting ways in the body. Betaine clearly cannot replace methionine as an amino acid, but that does not mean it cannot spare dietary methionine. Methionine and potentially betaine can or could contribute indirectly to the broader one-carbon metabolism that supports purine synthesis and uric-acid formation. Homocysteine remethylation is also responsive to metabolic demand, and there does not appear to be an established fixed ceiling that applies under all physiological conditions; the extent of recycling is likely to depend on factors such as diet, production conditions and health status. Oversupply of methionine is only one possible explanation when betaine appears to replace methionine without impairing performance. If more definitive experiments are needed to distinguish these explanations, then the appropriate conclusion is that the question remains unresolved—not that a methionine-sparing effect has been ruled out.
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Dr. Andreas Lemme
28 de septiembre de 2026
I see a lively discussion developed on this topic but would not agree. I can of course understand position of @Ana as a representative of a betaine producer. Still, the argumentation chain is as follows:

1) there is no methyl group needed for uric acid formation and no direct involvement of methionine nor betaine in this process.
2) betaine cannot transfer the methyl group to the creatine formation but can only remethylate homocysteine to methionine.
3) Research summarised by Selhub (1999), Lamers et al. (2011) and Kalhan et al (2011) clearly indicate that homocysteine is maximal 4 times recycled before it leaves torwards the transsulfuration pathway which suggests a limited capacity of betaine to recycle homocysteine. In addition, this process is in competition / interaction with remethylation by vitamine B12 which would further reduced the importance of betaine in this context.
4) Especially at marginal or deficient dietary Met supply the effectiveness of remethylation is increased. However, this is not a situation we find in commercial broiler feeds. Thus, betaine will not have a sparing effect (which has been shown by several authors)
5) If dietary methionine can partly be replaced by betaine without impacting performance, this is only possible because of a (relative) over-supply with methionine. It is suggested to simply reduce dietary Met+Cys specifications instead.
6) Careful reading of publications postulating a methionine replacement or sparing potential of betaine will reveal that always important treatments are missing which would make a scientifically sound conclusion possible.
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luciano Pinotti
20 de septiembre de 2026
Yes, the statement is generally correct, but it should be expressed more precisely.

Betaine may partially spare dietary methionine through its function as a methyl-group donor; however, it cannot fully replace methionine because it does not provide the amino acid functions required for protein synthesis. Similarly, betaine can substitute only for the methyl-donor function of choline and not for the structural functions of choline per se. Lowry et al. (1987) demonstrated in poultry that approximately 75% of the dietary choline requirement must be supplied as choline, whereas only 25% can be met by betaine. This limitation is likely due to the fact that betaine cannot be reduced back to choline (Pinotti et al., 2002)."
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Gene Pesti
9 de septiembre de 2026
It is hard to evaluate much of the data in this area because there are so many factors involved. In my early work we were not controlling folic acid levels, a mistake. I am glad that one of my students and I were the ones that figured it out.

Wheat products can contain up to 4000mg/kg betaine. Animal products and most other plant products have some. Corn and soy have none that we could detect.

At least at one time, American organic broiler producers were limited to 2 pounds of methionine per ton of feed. It was thought by some producers that organic birds did better on wheat than corn based feeds. I wondered if it had something to do with re-methylating homocysteine by the betaine that was unaccounted for. Or was it because the choline and betaine were being oxidized and de-methylated to form glycine? Is that a possible factor, especially in low protein feeds? Or something else?

I do think it is important to have plenty of folate and vitamin B12 when determining choline needs. Plenty of folate, B12, choline and cystine when determining methionine requirements. I chose the order from what I think is the least to most expensive nutrients. Actually, we could never demonstrate a B12 requirement even with low choline feeds with chicks on wire floors after the first week. And there is a compound called dimethylthetin with methylating activity. It is found in shellfish and ?? I hope this is of value to you.
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Kalyani Sarode
3 de septiembre de 2026

You are correct, Dr. Lemme, that betaine cannot replace methionine’s essential amino-acid function. However, when betaine is value-added with metabolic cofactors such as vitamins B12 and B6, it can support a controlled partial reduction of supplemental methionine.

Methionine metabolism involves three interconnected pathways: transmethylation, remethylation and transsulfuration. Betaine donates methyl groups through the BHMT pathway, vitamin B12 supports folate-dependent remethylation, and vitamin B6 acts as a cofactor in transsulfuration.

Therefore, the scientifically accurate conclusion is not that “betaine can never replace methionine,” but that it cannot replace methionine incorporated into body proteins or eliminate the animal’s minimum digestible methionine and total sulfur amino-acid requirements.

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