The science is clear: Betaine cannot replace methionine

@Kalyani Sarode

Dear Kalyani Sarode, your remark adds an aspect which we usually do not emphasize a lot in context of whether or not betaine can replace supplemental methionine. Indeed, also cobalamine (B12) has an - at least - as important role for remethylating homocysteine to methionine - which actually reduces the importance of betaine in this context.

You remind me to be scientifically correct. While, for sure, betaine is not a building block, it cannot replace methionine in protein building. However, as betaine (and choline) cannot donate its methyl group directly to creatine formation (where the vast majority of methionine methyl groups are donated to) but can only remethylate homocysteine, it de facto cannot replace methionine but only improve the remethylation process.

Indeed, as e.g. Pillai et al., 2006, demonstrated the addition of betaine was effective in a methionine deficient situation only. This is an evidence that the methionine remethylation process was improved - so, homocysteine was more often remethylated before leaving towards the transsulfuration pathway. However, first: commercial (broiler) feed is not deficient in methionine and second: in a marginal methionine supply, betaine cannot replace suplemental methionine but improve it.

The question is whether in a commercial environment betaine can replace supplemental methionine. The answer is: it cannot. Indeed, if methionine is overspecified (above requirement) you may replace the surplus (which would be degraded anyway) with anything without affecting the performance or health of the animal - or you simply reduce the specification.

@Dr. Andreas Lemme, While it is clear that betaine cannot substitute for the essential amino acid and structural functions of methionine, the discussion around partial sparing in broiler nutrition deserves a more nuanced look.

When dietary levels of methionine and cysteine are sufficient to meet the bird’s requirement for protein synthesis and tissue building, supplemental betaine can effectively spare a portion of added DL-methionine by fulfilling the demand for labile methyl groups via the betaine-homocysteine methyltransferase (BHMT) pathway.

This partial substitution is well-supported in literature across various production conditions:

Performance & Carcass Traits: Research evaluating the "Effect of Betaine Partially Replaced with Methionine on Performance and Carcass Quality of Broiler Birds" demonstrates that growth parameters and slaughter yields can be maintained when betaine covers methyl donation.

Metabolic & Morphological Parameters: Studies such as the "Effect of replacement different methionine levels and sources with betaine on blood metabolites, breast muscle morphology and immune response in heat-stressed broiler chickens" confirm that muscle integrity, metabolic indicators, and immune parameters remain robust under partial substitution.

Thermal Stress Conditions: Trials on the "Evaluation of Betaine and Methionine Replacement for Improving Performance and Meat Quality for Broilers reared under Higher Temperature Conditions" further highlight how betaine supports both meat quality and physiological status under elevated temperatures.

"Rather than asking whether betaine can replace methionine, shouldn't the real formulation question be: up to what percentage can betaine safely spare supplemental DL-methionine without compromising performance?"

Dear @Dr. Andreas Lemme - thank you for the trial data!

May I ask you to share more details about the nutritional parameters (CP, Meth., M+C, resp. M+C/ dig. Lys) as well about the environmental trial conditions?

Thank you in advance!

With kind regards,
Ana Gavrau

@Gene Pesti There might be som selenium levels involved on wheat or supplemental Se?.

@Gene Pesti Dear Gene, thank you for this contribution. I guess it underpins that it is worthwhile to go back to metabolic pathways and to learn (and maybe undertand) about the manyfold interactions.

Dear @Gene Pesti - I always appreciate your valuable contribution, thank you!
Allow me to emphasize that, according to human scientific data, the folate metabolism pathway in the methylation, or more precisely - remethylation, has been observed mainly during fasting cures.

Methionine is vital, there is no doubt about, and the methylation starts with methionine. When it comes to betaine, I'm reluctant to use the term "replacement", but betaine can complement methionine. This fact is supported by several scientific studies. Moreover is demonstrated practically in the European organic farming, where no synthetic amino acids are allowed to be added, and additionally to high-protein sources in the feed formulation (such as corn gluten meal, wheat gluten, or potato protein) 2 kg of betaine/ t of feed, is added in the formulation and it works very well.

Thank you also for your comment on glycine. As you well know, betaine also contributes to glycine formation (after it donates its CH3 group to homocystine, the remaining two methyl groups form dimethylglycine ? sarcosine ? glycine).
It is also important to mention that "organic" means also better housing conditions, than conventional industrial production; in contrast, higher stocking density and additional stress factors often lead to osmotic disturbances. Under such conditions, the first response physiologically required of the body is, the osmorelulatory response - were the other important function of betaine plays a crucial role - acting as an organic osmolyte, a kind of "first aid".

Thank you.

All best and kind regards,
Ana Gavrau

@Ana Gavrau Thank you. First, I don't think animals producing urea should ever be compared to those producing uric acid, which requires methyls in its synthesis.
I don't understand your comment "It is also important to mention that "organic" means also better housing conditions, than conventional industrial production". Chickens are socialists at heart. The vast majority will lay around in front of the feeders and waterers all day if given the choice. Only a few will go outside and imitate chickens that had to search for food. The few that go outside collect plenty of diseases to bring back to the birds crowding the feeders. I know of one producer that has some birds in cages and some with access to a range. After one laying cycle mortality was 2% for birds kept nice and dry and warm and isolated from disease. The unlucky birds with outside access had 20% mortality. I must admit that welfare was much better for neighborhood foxes and hawks, etc. near the free range group.

Dear @Gene Pesti - Thank you for your feedback! Regarding the comparison I was refering only from the availability point of view of the methyl groups, but ok, well noted.

About the EU organic poultry farming, I'm not saying that I agree with the regulatory framwork, and yes you're right when it commes to diseases from outside, specifically at the very beginning; in organic eggs were also higher dioxin levels detected, than in conventional farms, at least in Austria; but those regulatory frames are in place...and farmers, nutritionists and feed producers must find proper solutions.

In fact, this presents a real challenge, given all the limitations, and with regard to sustainability... oops – they are not really sustainable, particularly because of the high crude protein content required to meet the nutritional needs for amino acids!
For many feed manufacturers, the solution therefore lies in formulating feeds with protein-rich and bioavailable sources – such as potato protein – as a valuable source of methionine and adding natural betaine; as well other natural feed additives improving gut health.

By better husbandry, I meant lower stocking densities and improved environmental conditions. To illustrate this more clearly, I cordially invite you to a virtual visit to an organic farm in Austria. Simply follow the link below.
https://www.youtube.com/watch?v=I2RUBJ2tNe4

@Ana Gavrau Thanks for the invite, but I have seen several "biological" farms in France and they are very nice. I could not tell how happy their chickens were, but I'm not a specialist in that area. I do know that there are some breeds that appear much more content and docile in cages than others. Those are the ones I would choose to work.

@Gene Pesti - YOU are welcome dear Prof. Dr. Pesti!
Indeed, the biological/ organic farms are really nice and I like the philosophy behind them; however, I believe the industry would welcome more flexibility from regulatory point of view – especially with regard to feeding.
As a passionate animal nutritionist, I really appreciate and respect your work. Thank you!

@Ana Gavrau Thank you for your comment, Ana. As I do not want to repeat myself just a quick comment on the glycine.

If you start modelling glycine metabolism in order to understand where the big quantities of Gly would coming from and would be needed in the metabolism, you will find out that Gly from betaine degradation makes only a tiny share - still if you formlate for min. Gly-equivalents it may (only very little) impact dietary protein if Gly-equivalents are limiting. Interestingly and specifically for birds, next to Gly as building block, the next very big portion of metabolic Gly is needed for uric acid formation - so 1/4 or 1 of 4 N carried by uric acid comes from Gly....but this is another story and only indirectly related to the above betaine topic.

@luciano Pinotti, My position focuses strictly on partial substitution. Empirical literature indicates that betaine can safely spare dietary methionine and choline within a partial replacement window—typically around 15% to 25%—by taking over the transmethylation burden.

Dear @luciano Pinotti - regarding your comment "75% of the dietary choline requirement must be supplied as choline" - this percentage also includes the native source of choline, from the single feed ingredients- for e.g. for soybean meal 2790 ppm/ kg according to NRC; 2545 ppm/ according to INRA.

It is generally accepted and confirmed by INRA and NRC data, that 1000 -1200 ppm of choline are available in the final feed as native (corn, soybean meal, rice bran...). From the perspective of practical feed formulation – for example, in a starter feed for broiler chickens – with a recommended total choline content of 1700 ppm/kg, only the portion above 1000 ppm is supplemented with choline chloride. In my experience, this proportion corresponds to the portion required as a methyl group donor – more or less the 25% you also described. However, betaine fulfills the function as a methyl group donor more efficiently, as no metabolic conversion is required, as it can donate the CH3 directly, via the BHMT pathway- for the remethylation.

Dear @Ana Gavrau, I fully agree, although the bioavailability of naturally occurring choline may be limited. Moreover, I am convinced that betaine, choline, methionine, folates, and vitamin B12 should be considered as part of an integrated metabolic network rather than as isolated nutrients.

@luciano Pinotti And dietary protein level. Since methyl groups are required for creatine and uric acid synthesis, nitrogen balance is also a factor. A very important one, I think. Young chicks depositing most of their amino acid intake into body protein should require many fewer labile methyls for uric acid synthesis. Us old roosters in net nitrogen balance oxidize all our amino acid intake. For birds, that means much more uric acid synthesis and a higher methyl need.

Dear @luciano Pinotti thank you, I completely agree with you. When it comes to the bioavailability of naturally occuring choline, according to literature it may be 100% in corn, but 60-75% in SBM; I considered 50% a safe assumption. I believe we are all aware of the different roles of the individual components involved in methylation, and we know that these are not physiologically isolated from each other. However, in challenging times—faced with high prices for individual feed components—nutritionists look for ways to reduce feed costs; in practice, they rely on what works.