Uses of Potassium Diformate in Animal Growth Promoter
Antibiotic growth promoters have been widely used in animal feed, with considerable success. Antimicrobial feed additives are widely used to improve the performance and ecology of animal production. Ban on antibiotics as growth promoters in the European Union, and the resulting pressures on meat exporters around the world have
increased interest on alternatives like herbs, herbal products, prebiotics, probiotics organic acids (formic, fumaric, citric, lactic, propionic etc.).
Organic acids and their salts have received much attention as alternatives to antibiotic growth promoters. These vary in the growth promoting effect and mode of action. Also, physical properties such as ease of handling, odor and corrosion during feed processing and on the farm should be taken into account when evaluating the different formulations.
Numerous studies have demonstrated that formic acid is effective against pathogenic bacteria and enhancing growth performance but strong odor and corrosiveness limit its use. To overcome these problems, Potassium Diformate has received attention as an alternative to formic acid because of its easiness to handle and also effective in enhancing growth performance. It is the first EU-approved alternative to feed antibiotics for pigs. The European Community has registered Potassium Diformate as the first non- antibiotic animal nutrition product with growth-promoting properties. The antimicrobial effect of Potassium Diformate reduces the general bacterial population in the gut especially harmful bacteria such as E. coli and Salmonella and promotes a more favorable microflora in the gut. This improves the animal’s growth performance and health status, while at the same time ensuring safer products for the consumer.
Potassium Diformate can be used in replacement of antibiotic or in combination with antibiotic and while doing so the dose of antibiotic may be lowered considerably. Such combination is going to yield better performance, when compared to antibiotic alone, because in addition to antimicrobial properties, Potassium Diformate has multifarious mode of action in promoting performance and feed efficiency, which the antibiotic growth promoters lack.
Potassium Diformate is a crystalline powder, where formic acid is linked with Potassium Diformate which dissociates to formic acid and potassium formate. Potassium formate in turn dissociates into potassium and formic acid. Thus each mole of Potassium Diformate contributes two moles of formic acid, which is an organic acid and shortest of the carboxylic acid and is the active component of Potassium Diformate.
USE OF POTASSIUM DIFORMATE IN PRESERVATION OF FISH MEAL :
Potassium Diformate may be suitably used as preservative for raw fish and fish by-products for feed use in all animal species/categories without withdrawal period at the maximum level of 9000 mg Potassium Diformate/kg raw fish.
USE OF POTASSIUM DIFORMATE IN POULTRY FEED:
In-feed antibiotics have been used for many years in the poultry industry as antibiotic growth promoters (AGP) to enhance both animal health status and productive performance . The mechanisms by which AGP improve growth performance are poorly understood, it is thought that the antibiotics may induce modifications of the gut micro flora which are beneficial to the host. Banning in-feed antibiotics for the mono-gastric animals, as in the European Union due to its huge problem for environmental conditions and human health, has put more pressure on animal nutritionists to innovate new alternatives to fill the gap left by removing AGP from the feed industry.
Acidifiers such as pure organic acids have been used as feed preservatives for protecting feed from microbial and fungal destruction. Thus, acidifiers could be used as powerful tool in maintaining the health of gastrointestinal tract of poultry, resulting in improving their performance. Acidifiers act as performance promoters by suppressing the growth of acid intolerance bacteria such as E-coli, salmonella spp., and Clostridium perfringens. Moreover, organic acids reduce pH in the stomach, which enhance pepsin activity, and increases the digestibility of nitrogen, phosphorus and minerals.
Numerous studies have demonstrated that formic acid is effective against pathogenic bacteria and enhancing growth performance, but strong odor and corrosiveness to gastrointestinal tract limit its use . Another important limitation is that the organic acids are rapidly metabolized in the fore-gut (crop to gizzard) of birds which reduces their impact on growth performance . Gut acidifiers are organic acid salts, such as Potassium Diformate, that have received attention as an alternative to formic acid due to its easiness to handle, little or no corrosive effect and also effective against pathogenic bacteria along whole gastrointestinal tract. Potassium Diformate is a crystalline powder, where the carbonyl group of formic acid links with hydroxyl group of potassium formate via a hydrogen bond, which dissociates to formic acid and potassium formate in the gut, thus formic acid enters the small intestine intact.
Dietary supplementation of formic acid and Potassium Diformate resulted in increase in body weight gain (BWG) and a numerical decrease in feed intake (FI) compared with the control group. The results of weight gain and feed intake reflected on feed conversion ratio (FCR) which was significantly improved in formic acid and Potassium Diformate supplemented groups compared with control one. The highest dressing percentage and breast muscle yield percentage were recorded in potassium diformate followed by formic acid and then control.
The reasons that organic acids or their salts improved performance in the broilers may be attributed to that the organic acids and their salts improve protein and energy digestibility by reducing microbial competition with the host for nutrients and endogenous nitrogen losses, lowering the incidence of sub-clinical infections and secretion of immune mediators, reducing the production of ammonia and other growth suppressing microbial metabolites. Moreover, gut acidification stimulates pancreatic enzyme secretion and activity and thus optimizes nutrient digestion and absorption in young animal, making amino acids more available for protein deposition within the body so improves carcass leanness (dressing %).
The improvement in BWG and FCR by Potassium Diformate supplementation was discussed by Christian and Mellor (2011) who concluded that double salts of organic acids, such as Potassium Diformate and sodium diformate, which reach the small intestine, have been shown to have a significant impact on nutrient utilization. Similarly, Helen and Christian (2010) who reported that the addition of Potassium Diformate at (0.1%, 0.3% and 0.5%) was found to enhance individual live weight and FCR with increasing dosage, the best results in respect of these parameters were obtained for a dosage of 0.3% Diformate. Tohru et al. (2011) recorded that dietary Potassium Diformate supplementation at 1% significantly increased the body weight of broiler chickens.
CRUDE PROTEIN DIGESTIBILITY COEFFICIENT:
Dietary supplementation of formic acid and Potassium Diformate resulted in increase in protein digestibility coefficient in poultry compared with the control one.
The increase in crude protein digestibility coefficient may be attributed to that organic acids raised gastric proteolysis and improved protein and amino acids digestibility as reported by Samanta et al. (2010). It was thought that the organic acids supplementation lowers the pH of the chime which might increase the pepsin activity and thus enhance the digestibility of protein (Afsharmanesh and Porreza, 2005). Proteolysis of proteins by pepsin produced peptides which activated the release of hormones including gastrin and cholecystokinin. The pancreatic secretion increased by organic acids led to better digestion of proteins due to the high concentration of trypsinogen, chymotrypsinogen A, chymotrypsinogen B, procarboxypeptidase A and procarboxypeptidase B (Adil et al., 2010). According to Van Der Sluis (2002), the positive effect of organic acids on digestion was related to a slower passage of feed in the intestinal tract, a better absorption of the necessary nutrients and less wet droppings.
Concerning the effect of Potassium Diformate on crude protein digestibility, it is speculated that Potassium Diformate supplementation improved epithelial cell proliferation in the gastrointestinal tract which might increase in N retention and CP digestibility coefficient. Selle et al. (2004) observed that dietary Potassium Diformate supplementation at 12 g/kg increased N retention by 5.6%.
GASTROINTESTINSL pH AND CAECAL MICROBIOAL CONTENT:
Dietary inclusion of formic acid and Potassium Diformate resulted in a significant reduction in the pH of crop, gizzard, duodenum, jejunum, ileum compared with the control one . The results revealed a numerical reduction in the pH of other gut portions (cecum and colon) with potassium diformate which was less than that with formic acid and the control group.
The results of cecal microbial content in different experimental groups revealed that there was a significant decrease in total clostridia and salmonella spp. isolated from the cecum of the groups supplemented with formic acid and Potassium Diformate compared with the control group. The results represented a numerical decrease of E. coli isolated from the cecum of Potassium Diformate fed group compared with that of the control one.
Regarding the antimicrobial effect of organic acid, it is suggested that the un-dissociated form of organic acids is the basic form by which they could exert their antimicrobial effect (Ostling and Lindgren, 1993 ). The Organic acids are lipid soluble in the un-dissociated form, in which they are able to passively diffuse through the microbial cell wall and disrupt the normal physiology of certain types of bacteria that we call ‘pH sensitive’ meaning that they cannot tolerate a wide internal and external pH gradient (Van Immerseel et al., 2006 ). Once in the cell, the acid releases the proton in the more alkaline environment, resulting in a decrease of intracellular pH leading to inhibition of the action of important microbial enzymes and nutrient transport systems, which inhibits the ability of the bacteria to multiply (Huyghebaert et al., 2011). Furthermore, the RCOO− anions produced from the acid can disrupt DNA andprotein synthesis, putting the organism under stress, so that it is unable to replicate rapidly (Russell and Diez-Gonzalez, 1998).
Van Immerseel et al.,2006, Naseri et al.,2012 concluded that the organic acid supplementation in poultry diet have a beneficial effect in controlling intestinal bacterial infection by Salmonella, Campylobacter and E. coli. Different studies by (Byrd et al., 2001, Açkgöz et al., 2011 Hamed and Hassan, 2013) indicated that addition of organic acid to the drinking water helps to reduce the level of pathogens in the water and the crop/proventriculus, to regulate gut micro flora. It is believed that the organic acid administration in feed or water mainly metabolized and absorbed in the upper gastro-intestinal segments of poultry as recorded by (Thompson and Hinton, 1997, Van Immerseel et al., 2006, Hassan et al., 2010)
Furthermore, the dissociation kinetics of organic acid salts such as Potassium Diformate permits a proportion of formic acid to pass through the fore-gut intact and enter the small intestinal tract. So that, the Potassium Diformate able to reduce C. perfringensand control necrotic enteritis in broiler flocks at (0.45%)
There is a significant increase in villus height of ileum in formic acid and Potassium Diformate fed group compared with the control group. Villus/crypt ratio showed a significant improvement in formic acid and Potassium Diformate compared with control group.
The increase of villus height may be attributed to the antimicrobial action of Potassium Diformate which reduces the growth and colonization of many pathogenic bacteria, therefore reduces the infectious and inflammatory process at the intestinal mucosa, leading to increased villus height and function of secretion (Loddi et al., 2004, Pelicano et al., 2005).
Franco et al. (2005) found a beneficial effect with the use of Potassium Diformate on the intestinal mucosa of broilers.
The immune system of birds is complex and is composed of several cells and soluble factors that must work together to produce a protective immune response. The lymphoid organs are the major constituents of the avian immune system. Experiment revealed that there was a significant increase in spleen lymphocyte count in formic acid and Potassium Diformate fed groups compared with control.
Several studies elucidated that organic acids could stimulate the natural immune response in poultry. The improvement in bird immunity could be related to the inhibitory effects of organic acids on gut system pathogens (Abdel-Fattah et al., 2008, Ghazalah et al., 2011.
From the above mentioned facts, it could be concluded that formic supplementation, irrespective of the form, had a beneficial effect on performance, and immunity of broiler chicken without having any significantly effects on blood biochemical parameters. Moreover, FA is effective against acid intolerant species such as E. coli, Salmonellaand Clostridium count in ceacum. However, Potassium Diformate is more effective than formic acid as little amount of formic acid reaches small intestine due to metabolism and absorption. While Potassium Diformate permits a proportion of formic acid to pass through the fore-gut intact and enter the small intestine.
USE OF POTASSIUM DIFORMATE IN AQUACULTURE FEED:
There is currently a great interest in the commercial use of organic acids/salts in aqua feeds, both to enhance the growth performance and to control disease. Dietary supplementation of 0.2% and 0.3% Potassium Diformate significantly improve the growth performance, protein digestibility and feed efficiency in fish.
To date, the mode of action of organic acid compounds has been speculated in fish. The reduction of the stomach and the upper gut pH in Potassium Diformate supplemented fishes may be the primary reason for improving the growth performance and protein digestibility. The lower gastric pH associated with a higher pepsin activity contributes to improve the protein digestibility and nitrogen retention.
Potassium Diformate supplemented diet markedly decreased the total bacterial counts in faeces. Because the low molecular weight lipophilic organic acids can diffuse across the cell membrane of gram-negative bacteria, acidification of their metabolism can lead to bacterial cell death. This may be the second reason for improving the growth performance.
Lowering of the gut pH with dietary Potassium Diformate has an eubiotic effect on fish beneficial lactic acid bacteria. Lactic acid bacteria are able to grow at a relatively low pH, which means that they are more resistant to organic acids/salts than gram-negative bacteria
These indigenous probiotic bacteria have the ability to colonise the intestinal surface and form a barrier, serving as the first defence to limit direct attachment or interaction of fish pathogenic bacteria to the gut mucosa. It was reported that dietary Potassium Diformate stimulates the colonisation of certain gut bacteria and inhibits the growth of others in fish. The eubiotic effect of Potassium Diformate on the proliferation of indigenous probionts may be the third reason for improving the growth performance because this gram-positive bacterium plays a vital role in fermentation of certain non-digestible carbohydrates and increases the availability of nutrients.
Not much is known about the use of acidifiers as immunostimulants in cultured fish. Potassium Diformate was able to modify microbial communities in fish guts, which in turn may account for its ability to initiate an immune response. It has been reported that the quantity and quality of immune cells in gut mucosa depend on the continuous stimulation provided by indigenous intestinal flora. Inclusion of Potassium Diformate in the fish diet has a significant impact on the cellular and humoral non-specific immunity of fish. This was obviously recorded in the results of the phagocytic activity, the lysozyme activity of the serum and the intestinal mucus. This could explain the indirect activation of the non-specific immunity of treated fish groups.
The antimicrobial effects of organic acids have been augmented with increased LAB densities and their antimicrobial products in the fish gut. The colonisation of LAB inhibits the attachment and invasion of the pathogenic bacteria, following the competitive exclusion theory of these probiotic bacteria against pathogen.
The results indicate the promising potential of acidifiers in fish diets and provide evidence to encourage aquafeed manufacturers to consider using such additives. The dietary inclusion of Potassium Diformate not only enhances the growth performance and the apparent protein digestibility of fish but it also has an eubiotic effect on the proliferation of indigenous LAB, which plays a prominent role in activation of the immune response against diseases.
USE OF POTASSIUM DIFORMATE IN PIG FEEDS :
Potassium Diformate brings about an acidic state within intestines of pigs, which helps to raise the assimilating enzymatic activity, then it can improve the taste of feedstuff, and increase feed intake, daily gain and feed efficiency of piglet and growing pig, and can also increase milk yield. The product can reduce Escherichia coli and Salmonella, increase beneficial bacteria, and decrease diarrhea occurrence rate through making the pH of intestines lower. It can also improve pig’s utilization ratio to nitrogen and phosphorus, and prevent piglet’s edema. The product can be used safely with a high efficacy having no toxicity, and residual characteristic. It does not make any harm to man, animal and environment.
When used in feed for pigs, the mixture of different sources of Potassium Diformate, including Potassium Diformate preservative-treated fish and fish by-products, shall not exceed the permitted maximum level in complete feedingstuffs of 18000 mg/kg complete feedingstuffs for weaned piglets and 12000 mg/kg complete feedingstuffs for sows and pigs for fattening
Maximum inclusion level of Potassium Diformate is 1.8% as registered by the European authorities which can improve weight gain up to 14%. Potassium Diformate contains the active ingredients free formic acid as well as formate has the strong anti microbial effect in stomach and also in duodenum. Potassium Diformate with its growth promoting and health enhancing effect has proven to be an alternative to antibiotic growth promoters. Its special effect on the micro flora is regarded as the main mode of action. 1.8% Potassium Diformate in growing pig diets also significantly increase Feed intake and feed conversion ratio was significantly improved where growing pig diets was supplemented with 1.8% Potassium Diformate. It also reduced pH in the stomach and duodenum. Potassium Diformate 0.9% significantly reduced the pH of duodenal digesta.
Recommended dosage for pigs
Stage: Dosages (%)
Sucking Pig: 0.6-1.4
Weaned Piglet: 0.6-1.2
Growing Pig: 0.6-1.0
Finishing Pig: 0.6
Pregnant Sow: 0.6
Lactating Sow: 0.6
MODE OF ACTION :
The primary mode of action is via an antimicrobial effect of formic acid and formate resulting from the dissociation of Potassium Diformate in the gastrointestinal tract. It is mainly the undissociated form of the formic acid that exerts the antimicrobial effect (Ostling and Lindgren, 1993). The concentration of the undissociated acid increases with decreasing the pH. Formic acid passively diffuses through the bacteria cell wall, interfering with the fine- tuned pH balance in the cytoplasm, which results in a fatal interruption of the energy balance and biochemical processes. There is also a suppression of the cells’ enzymes and nutrient transport systems, which inhibits the ability of the bacteria to multiply (Partanen and Mroz, 1999; Roth and Kirchgessner, 1998).
EFFECT ON GROWTH FEED INTAKE AND FEED CONVERSION
Paulicks et al. (1996) conducted a dose titration trial to evaluate the effect of increasing inclusion level of Potassium Diformate on performance of growing piglets. Potassium Diformate was added at 0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4 and 2.8% level to piglet starter corn- soybean based diet. Potassium Diformate improved daily weight 13%, daily feed intake 9% and feed conversion ratio 4% on average supplemented groups. Weight gain improved 22% compared to the untreated group with an addition of 2% Potassium Diformate. With a maximum inclusion level of 1.8% as registered by the European authorities weight gain can be improved up to 14%. Feed intake was significantly improved in same dose. Feed conversion ratio (FCR) improved linearly from 1.59 to 1.47 with an increasing level of Potassium Diformate.
Potassium Diformate is registered as a non antibiotic growth promoter with the purpose to replace in feed antibiotics ensuring safer products to the consumers. Therefore the benefits of using Potassium Diformate have to be compared to effect achieved with the conventional use of feed antibiotics. It has been demonstrated that Potassium Diformate significantly improves animal performance to an extent comparable to commonly used antibiotics. The performance effects of Potassium Diformate are mainly to its antimicrobial properties.
ANTIMICROBIAL EFFECT :
Although organic acid generally lower the pH value in the stomach and parts of the upper gastro intestinal tract and therefore enhance proteolytic activities, a major effect of Potassium Diformate lies in the alteration of the microbial flora within the gut. Evidence exists that, Potassium Diformate significantly reduce the total number of coliform bacteria in the duodenum, jejunum and rectum in host animal. The antimicrobial effect of Potassium Diformate in the gut is expressed in three ways.
There is a general reduction of the microbial number in the small intestine. As the microbial population is reduced, fewer nutrients are consumed by the micro flora. Here is also less microbial metabolites (e.g. ammonia) increase gut mucosa turnover. This increases the availability of dietary energy and nutrients to the host animal and reduces maintenance cost of the gut, resulting in increased growth rate and enhanced feed efficiency. Thus, the improvement in nutrient digestibility is probably associated with the change in the micro flora in the gut.
High concentration of ammonia in the gut has a negative effect on growth rate of pigs. Several researchers reported that, addition of PD in diet decrease the ammonia concentration in gut (Hebeler et al., 2000 and Fevrier et al., 1999).
This reduces the E. coli, Salmonella and overall exposure of the animal by these pathogenic bacteria as well as the toxins produced. The antimicrobial effect of Potassium Diformate is stronger against potential pathogens e.g. Coliform bacteria than towards the desirable bacteria such as lactic acid bacteria. This leads to a shift in the composition of microbes to a more balanced microflora in the gut, which also improves the general health status of the animals. Results from in vitro trials using 0.6 % Potassium Diformate (Knarreborg et al., 2000) and 1.8 % Potassium Diformate (Fevrier et al., 1999) shows that, Potassium Diformate reduced the population of both Coliform bacteria and Lactobacilli in vitro and in the stomach of piglets. The antimicrobial effect was stronger towards Coliform bacteria than towards Lactobacilli, resulting in an increased ratio between lactic acid bacteria and coliform bacteria in vitro and in the piglets.
Increased feed intake has been observed in several trials when Potassium Diformate has been added in the diets. This may be associated with a better quality and improved biosecurity of the feed or an improved health status of the animals. Salts of organic acids are often considered to be nearly inert in the feed. Granli et al. (2002) reported that, addition of 1.8 % Potassium Diformate significantly reduced the quantity of salmonella in contaminated feed. Potassium Diformate has a similar antimicrobial effect towards other types of bacteria, such as E. coli. The animal is therefore exposed to fewer in-feed pathogenic bacteria and there may be fewer toxic metabolites and hence reduced spoilage. The quality and palatability of the feed is improved when Potassium Diformate is included in the diets. As a consequence, feed intake and growth rate is increased. The antimicrobial effect of Potassium Diformate is considered to be the main mode of action. The strong antimicrobial effect in the gut results from a high concentration of both formic acid and lactic acid in stomach and duodenum as well as a reduction of pH.
THE pH LOWERING EFFECT:
The performance enhancing effects of organic acids and their salts extensively described in the literature. As reasons for these effects, the influence of organic acids on the feed, on the intestine and on the intermediate metabolism are discussed but are mainly the two latter
aspects seems to be more relevant. As piglets immediately after weaning have an inadequate HCl production in the stomach, the addition of organic acids helps to support the physiological digestive functions by decreasing the pH value in the stomach. Potassium Diformate contains an active ingredient free formic acid as well as formate. The strong anti microbial effect of Potassium Diformate can be explained by the high concentration of active ingredient present not only in stomach but also in duodenum (Daza et al., 2001). A more rapid reduction in the pH of the stomach stimulates the secretion of pepsin and pepsinogen, which may enhance dietary protein digestion. A reduced pH in the lumen also contributes to the antimicrobial effect of the additive. Lower pH conditions have a direct inhibitory effect on the bacteria Population in the lumen (Mroz et al, 2000).
EEFFECT ON NUTRIENT UTILIZATION :
Performance effects of organic acids are not only related to their effects on unfavorable microorganism and also the effect to lower the pH value in the gastro intestinal tract. Furthermore, the anion of the acid has a positive influence on the eubiosis among the intestinal micro- flora. All these effects relieve the intermediate metabolism and contribute to a higher performance. An improved nutrient utilization is partly a result of a decreased competition from microorganism for nutrients but is also a result of a more efficient enzymatic digestion of nutrients. Roth et al. (1998) reported that, application of 1.8% Potassium Diformate increased digestibility reflects primarily changes in the activity of the hindgut micro-flora. Since about 80% of the fecal nitrogen is of microbial origin the result obtained in their study indicate that the supplementation of Potassium Diformate reduce the amounts of fermentable nutrients entering the hindgut by improving the enzymatic digestion in the small intestine. They also suggesting that it may improve carcass leanness by making amino acids more available for protein deposition within the body. Partanene and Mroz (1999) stated that, the improvement in protein digestibility is expected to be greater with a protein source of a lower quality than a higher quality.
Potassium Diformate improves animal performance in terms of weight gain, feed intake and feed conversion. The improvements in performance are equal to growth promoters. Therefore Potassium Diformate with its performance and health enhancing properties is an effective alternative to feed antibiotics. Effect on the microflora is regarded as the main mode of action and no risk of developing resistance in microorganisms. It reduces the incidence of E. coli and Salmonella in meat products and therefore contribute to food safety.