Organic acids: Chemical structure, mechanism of action and benefits of their use

Introduction

Organic acids (OA) are used in swine nutrition via water or feed especially in the nursery phase due to their positive effects on:

• gastrointestinal health
• nutrient digestibility
• production performance

At the gastrointestinal level, OAs can act as acidifiers, bactericides, and bacteriostatics, actions that depend mainly on the pKa, partition coefficient (LogP Kow), and molecular weight of each OA and the pH of the medium in which they are found. Their effect depends on the dose and the combination of OA used, the feed formulation, and the pig's age- factors that make it difficult to compare between studies.

OAs are also used as feed preservatives, thanks to their ability to inhibit the growth of undesirable pathogenic bacteria, fungi, and yeasts in feed.

Chemical structure of organic acids

Biochemically, OAs are carboxylic acids characterized as organic compounds consisting of a fatty acid chain of variable length and one or more carboxyl groups (R-COOH) that are the H+ donor source.

OAs are weak acids, with different degrees of solubility in water and with reversible reaction capacity. We must differentiate OAs from inorganic acids, such as phosphoric acid or hydrochloric acid since the latter are strong acids that dissociate completely when they come into contact with water and have a high acidification capacity but they cannot penetrate the interior of bacteria. Moreover, their reaction is irreversible and their handling is complicated due to their high corrosiveness. Table 1 summarizes the main OAs used in swine nutrition with their chemical formula, pKa value, molecular weight, and LogP Kow value.

Table 1. Chemical formula, pKa value, molecular weight, and LogP Kow of the main organic acids used in swine nutrition (Dibner and Buttin, 2002; Zentek et al., 2011).

Main benefits of the use of organic acids in swine nutrition

1. Promote gastrointestinal health thanks to its bacteriostatic activity by reducing the pH of the medium through the release of its H+ ions and its bactericidal activity in its undissociated form.
2. Increase digestibility and absorption of nutrients such as protein and minerals, with high impact during the nursery phase due to acidification of stomach contents and modulation of the microbiota.
3. Preservative for raw materials and feed due to its ability to inhibit the growth of undesirable pathogenic bacteria, fungi, and yeasts.

Mechanism of action of organic acids in the digestive tract

Depending on the pH of the gastrointestinal medium and the pKa and LogP Kow of the OA, the OA can be in undissociated form (RCOOH, OA that keeps all its chemical structure intact) or in dissociated form (RCOO- + H+, OA that has released at least one H+ ion to the medium).

An undissociated OA has a high diffusion capacity through the membrane of the bacteria towards its cytoplasm, where the acid dissociates, altering the internal pH balance of the bacterial cytoplasm which will cause the suppression of the activity of its enzymatic systems and nutrient transport causing the lysis of the bacteria (Dibner and Buttin, 2002). While a dissociated OA has acidification capacity due to the release of H+ ions to the medium, inhibiting the growth of acid-sensitive bacteria such as Salmonella spp or E. coli and promoting positive effects on gastric and intestinal health that we will discuss later.

OAs that can release a single H+ such as formic acid are called monoprotic and OAs that can release more than one H+ such as citric acid are called polyprotic OAs. The chemical structure of the undissociated and dissociated forms of formic acid, lactic acid, and propionic acid is depicted in Figure 1.

But what determines whether a greater proportion of the acid is in dissociated or undissociated form at the gastrointestinal level? It depends basically on two factors: the pKa of the acid and the pH of the gastrointestinal environment.

The pKa of an OA (Table 1) is the pH value at which 50% of the acid remains dissociated and the remaining 50% undissociated. An OA has as many pKa values as there are carboxyl groups. In the case of polyprotic OAs, their pKa value increases with each dissociation so that the first release (pKa1) defines the acidification strength of the particular OA. If the pH of the medium is lower than the pKa of the OA, > 50% of the OA will be in undissociated form, whereas, if the pH of the medium is higher than the pKa of the OA, > 50% of the OA will be in dissociated form. Consequently, as the pH of the environment gets further above or below the pKa value of the OA, the percentage of dissociated or undissociated OA molecules increases, respectively (Figure 2).

At the physiological level, the lower the pKa value of OA, the greater the effect on gastric pH reduction and the lesser the antimicrobial effect on the distal portions of the intestinal tract.

Two OAs with a similar pKa and administered in the same dose may have different bactericidal capacities due to their molecular weight. For example, when administered in the same amount, formic acid has a greater bactericidal effect than lactic acid since its molecular weight is lower. This is because, for an equal amount, there will be more molecules of formic acid than of lactic acid: in 1 kg of lactic acid there are 11.1 moles, while in 1 kg of formic acid there are 21.7 moles.

An OAs action on microorganisms also depends on the complexity of their outer cell membrane/wall. Medium-chain fatty acids (MCFA) have a strong bactericidal action on Gram-positive bacteria such as Clostridium perfringens or Streptococcus spp, whereas short-chain fatty acids (SCFA) have a higher bactericidal activity on Gram-negative bacteria such as E. Coli, Campylobacter jejuni, or Salmonella spp. This is due to the octanol-water partition coefficient (LogP Kow, Table 1) of each SCFA, which indicates whether an acid has a more hydrophobic or hydrophilic character. In the case of MCFAs, these have LogP Kow values greater than 1.0, indicating their lipophilic character that allows them to interact more effectively with the cell membrane of Gram-positive bacteria, while the presence of lipopolysaccharides in the cell wall of Gram-negative bacteria confers resistance to MCFAs.

To enhance the action of OAs along the gastrointestinal tract, it is interesting to work with mixtures of OAs with different properties. Chaveerach et al. (2002) observed that the simultaneous combination of propionic acid, acetic acid, and formic acid offers a higher bactericidal power compared to the use of these acids individually. On the other hand, Hanczakowska et al. (2013) concluded that the inclusion of a 0.5% 1:1 mixture of propionic acid and formic acid and 0.2% capric acid positively impacts productive performance and increases nutrient digestibility of post-weaning piglets through improved intestinal mucosal health.

Some organic acids are used in the form of sodium, calcium, or potassium salts. Compared to free organic acids, the handling of salts during feed manufacture is easier due to their lower corrosiveness and they are generally odorless due to their solid form and lower volatility. At the physiological level, the salt is released at the gastric level, the undissociated OA reaching the intestinal level where it can act either by acidifying the medium or by acting as a bactericide depending on its pKa value. Examples of OA salts are sodium formate (1k237), sodium propionate (1k281), and calcium propionate (1a282). The combination of OA and OA salts with different pKa and LogP Kow values to achieve an acidifying and bactericidal action along the gastrointestinal tract is a good nutritional tool.

Organic acids and their salts can be used in swine nutrition in free or microencapsulated form. Microencapsulation prevents the acid from dissociating rapidly in the stomach, allowing the acids to act in the more distal parts of the intestine to act as bacteriostatics or bactericides (Cho et al., 2014).

In the next factsheet the main OAs used in swine nutrition and their mechanism of action will be described together with a brief bibliographic compilation of scientific studies on the effect of formic acid, lactic acid, and propionic acid on the gastrointestinal health and productive performance of pigs.