Methionine's antibacterial effect

by Suzi Fraser Dominy
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Microorganisms impact the performance and economics of animal production. Control of microorganisms in animal feed remains an ongoing challenge for the industry, even more so as today’s consumers focus on the health and safety of the meat they feed their families.

The eradication of pathogens plays a critical role in assuring the wellbeing and performance of the animal. Animal producers need to manage pathogens for two main reasons. First and foremost, they must control pathogens to protect the health of the animal. Gut bacteria compete for nutrients and can be detrimental to the health and performance of the animal. Second, and of growing importance, they must reduce pathogens as part of their program to control food-borne diseases. One organic acid in particular, Methionine hydroxy analogue (HMB), can play an important role in reducing bacterial numbers.

The U.K. feed industry has made important contributions to reducing Salmonella cases since the mid ‘90s. Attention to this issue remains an important topic as Europe discusses feed monitoring alternatives and impending legislation may require compliance with bacteriological standards in the future.


Two main alternatives offer viable control of bacteria in the feed: thermal and chemical methods. Heat treatment, already widely applied on breeder diets, is costly but efficient. However, the challenge with heat treatment alone is to avoid recontamination between treatment of the feed and consumption by the animal.

Chemical treatments can either serve as an alternative to heat treatment or be applied in addition to heat treatment to prevent recontamination. When used in conjunction with heat treatment, less chemical additives are required.

The main chemical alternatives used in the feed industry today are either organic acids or formaldehyde. Although formaldehyde is quite efficient and has been used extensively in U.K., it does not have any regulatory status, and its prohibition in feed remains a pending issue at the E.U. Commission. Organic acids, on the other hand, are used commonly in feeds throughout Europe and around the world.

Whereas microorganism control begins in the diet with heat treatment and/or chemical intervention, this control strengthens in the stomach acid when, and only when, organic acids are used. The advantage of certain organic acids is that their antibacterial activity is boosted at low pH, increasing their impact when present in areas of the gut such as the stomach.


Organic acids occur as either straight or branched carbon chains with one or more carboxylic acid groups (COOH) attached. The extensive variety of organic acids commonly used in feed includes formic, fumaric, citric, lactic and propionic acids. In addition, the organic acid status of liquid analogue methionine (HMB), has generated much recent interest.

Most food production animals, especially pigs, poultry and cattle, require supplemental methionine for proper growth and reproduction. When feeding HMB as the methionine source, producers also receive the added organic acid benefit.

HMB is a hydroxy acid (like lactic acid), with four carbons and a methyl-thio radical. Its pKa (acid-base ionization constant) of 3.6 is slightly below the formic acid pKa of 3.75, making HMB a strong organic acid. This is not the case for d,l-methionine were the amine radical neutralizes the carboxyl radical.

Both industrial sources of methionine supply the same L-methionine activity by similar pathways, and the U.S. National Research Council (NRC) states their equivalence in their publication Nutrient Recommendations for Swine (NRC 1998). Recent work conducted at the ILOB Institute in the Netherlands also confirms the equivalency of HMB and d,l-methionine. (Report TNO 99.02).


Some organic acids have the ability to enter bacteria by simple diffusion, decreasing the internal pH of the cells. This causes the bacteria to divert metabolic energy from growth and multiplication and can eventually result in cell death. This effect is specific to certain organic acids and is pH dependent.

In recent studies using an in vitro model, the Dutch research lab CCL-Nutricontrol (Cooperative Central Laboratory, part of the Dutch Cehave International feed milling group), demonstrated an antibacterial effect of HMB similar or even superior to formic acid. Results showed that methionine hydroxy analogue has antibacterial effect on E-coli, Campylobacter and Salmonella. CCL also concluded that there was an added and possibly a synergistic effect when formic and HMB were used together. (See Graphs 1-4.)

The use of organic acids in animal diets has steadily taken on added significance in recent years, due mainly to a trend to remove antibiotic growth promoters from the diet. This new evidence of the positive impact they can have in helping to keep animals and consumers safe from pathogens adds to its attraction as a valuable feed ingredient. Of even greater interest, methionine hydroxy analogue offers producers the added value of not only serving as a highly-effective methionine source, but also as an efficient organic acid with proven antibacterial properties.





Additional research on HMB’s positive side effects

The organic acid properties of HMB have been demonstrated in recent research findings at CCL in the Netherlands. The first indication of an organic acid "side effect" of HMB was seen in Denmark at the Danske Slagterier on piglets. In a diet with no growth promoters, replacing d,l-methionine with HMB on an equimolar basis improved growth significantly in a way similar to that of an organic acid mix. This effect was confirmed in other trials.

Alimet Trials at Danske Slagterier: HMB performance is shown as a percentage compared to d,l-methionine control diet for feed intake (DFI), weight gain (DWG and feed conversion, during the two periods of the trial, 4 to 6 weeks, (post weaning) and 6 to 10 weeks, and for the total period. HMB response was similar in the first period post weaning in the two trials.



In vitro model used at CCL:

Single bacteria cultivation took place in a broth buffered at a constant pH independently of organic acid (OA) added, either at pH 6.75 or at low pH 4.5, to simulate the acidic conditions in the stomach. Initial populations are established at 5 log cfu/ml, and colony counts are performed after four hours incubation with the different treatments. Variation of 0.25 log are considered significant.