{"id":208245,"date":"2024-02-20T06:33:42","date_gmt":"2024-02-20T05:33:42","guid":{"rendered":"https:\/\/ew-nutrition.com\/organic-acids-play-crucial-role-zinc-oxide-replacement\/"},"modified":"2024-02-20T06:33:42","modified_gmt":"2024-02-20T05:33:42","slug":"organic-acids-play-crucial-role-zinc-oxide-replacement","status":"publish","type":"post","link":"https:\/\/ew-nutrition.com\/en-uk\/organic-acids-play-crucial-role-zinc-oxide-replacement\/","title":{"rendered":"Organic acids can play a crucial role in zinc oxide replacement"},"content":{"rendered":"<p><em><span style=\"font-size: 12pt;\">Dr. Inge Heinzl, Editor EW Nutrition &amp;<\/span><\/em><br \/>\n<em><span style=\"font-size: 12pt;\">Juan Antonio Mesonero Escuredo, GTM Swine\/GPM Organic Acids EW Nutrition<\/span><\/em><\/p>\n<p>The use of high levels of Zinc Oxide (ZnO) in the EU before 2022 was one of the most common methods to prevent postweaning diarrhea (PWD) in pig production. Pharmacologically high levels of ZnO (2000-3000 ppm) increase growth and reduce the incidence of enteric bacterial diseases such as post-weaning diarrhea (PWD)( <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.researchgate.net\/profile\/Gretchen-Hill-3\/publication\/12957454_Early_and_Traditionally_Weaned_Nursery_Pigs_Benefit_from_Phase-Feeding_Pharmacological_Concentrations_of_Zinc_Oxide_Effect_on_Metallothionein_and_Mineral_Concentrations\/links\/004635379ed81de640000000\/Early-and-Traditionally-Weaned-Nursery-Pigs-Benefit-from-Phase-Feeding-Pharmacological-Concentrations-of-Zinc-Oxide-Effect-on-Metallothionein-and-Mineral-Concentrations.pdf\" target=\"_blank\" rel=\"noopener\">Carlson et al., 1999<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/10784192\/\" target=\"_blank\" rel=\"noopener\">Hill et al., 2000<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/d1wqtxts1xzle7.cloudfront.net\/67977921\/2001_Nutrition_N-CS_effect_of_pharmaco20210710-3712-o8be2h.pdf?1625944646=&amp;response-content-disposition=inline%3B+filename%3D2001_Nutrition_N_CS_effect_of_pharmacol.pdf&amp;Expires=1707737185&amp;Signature=EQ-Rv7G94PKQK5rBcfzarYJzAhJEfVz2KzTPM84VCE1Zof8QVD~VFwGjXV2halweh6P1zhqEKp1cHvmwXx8JutE3TCZ4EBbmPuaY4v9pOV0V~4tAiqCNSui1oDVc8QYVDR9ACCdMmrPF7XpWEUDCIyFirS407~~X11-ShhatNca8FvMe0NU2xE76X3sSAB4NgRlFxspYyJ4sackZMNJ2s1u9dws6hBGSgR7YFYlCxQLDwd0pny7HTQv4nfrdiMK8D8N0u-CWhop6cJ1m4RnSuZoO30ioa1QIygaouufXyigAokEEqzg-LuccswbfdHTItErqk87F9Le~RxCtOsHEjQ__&amp;Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA\" target=\"_blank\" rel=\"noopener\">Hill et al., 2001<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/030162269500039N\" target=\"_blank\" rel=\"noopener\">Poulsen &amp; Larsen, 1995<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/svineproduktion.dk\/services\/-\/media\/974C5E0158294FB79A9BDCD78B92A92D.ashx\" target=\"_blank\" rel=\"noopener\">De Mille et al., 2019<\/a><\/span>).<\/p>\n<p>However, ZnO showed adverse effects, such as the accumulation of heavy metal in the environment, the risk for antimicrobial resistance (AMR), and problems of mineral toxicity and adverse growth effects when feeding it longer than 28 days (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S016041201732069X\" target=\"_blank\" rel=\"noopener\">Jensen et al., 2018<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0378113511000794\" target=\"_blank\" rel=\"noopener\">Cavaco et al., 2011<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26322131\/\" target=\"_blank\" rel=\"noopener\">Vahjen, 2015<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/animine.eu\/wp-content\/uploads\/2020\/12\/2014-Metallomics-Zn-review-Romeo.pdf\" target=\"_blank\" rel=\"noopener\">Romeo et al., 2014<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6857036\/\" target=\"_blank\" rel=\"noopener\">Burrough et al., 2019<\/a><\/span>). To replace ZnO in pig production, let us first look at its positive effects to know what we must compensate for.<\/p>\n<h2>ZnO has a multifactorial mode of action<\/h2>\n<p>ZnO shows several beneficial characteristics that positively influence gut health, the immune system, digestion, and, therefore, also overall health and growth performance.<\/p>\n<p style=\"text-align: center;\"><img decoding=\"async\" class=\"size-full wp-image-208180 aligncenter\" title=\"Figure\" src=\"https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1.png\" alt=\"Figure\" width=\"900\" height=\"249\" srcset=\"https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1.png 900w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-280x77.png 280w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-150x42.png 150w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-120x33.png 120w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-36x10.png 36w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-225x62.png 225w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-80x22.png 80w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-48x13.png 48w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-64x18.png 64w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-28x8.png 28w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-500x138.png 500w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-170x47.png 170w, https:\/\/ew-nutrition.com\/wp-content\/uploads\/articles\/organic-acids-can-play-a-crucial-role-in-zinc-oxide-replacement\/figure-1-24x7.png 24w\" sizes=\"(max-width: 900px) 100vw, 900px\" \/><span style=\"font-size: 10pt;\">Figure 1. Beneficial effects and ZnO mode of action in postweaning piglets<\/span><\/p>\n<h3>1.\u00a0\u00a0 ZnO acts as an antimicrobial<\/h3>\n<p>Concerning the antimicrobial effects of ZnO, different possible modes of action are discussed:<\/p>\n<ul>\n<li>ZnO in high dosages generates reactive oxygen species (ROS) that can damage the bacterial cell walls (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0927775714005172\" target=\"_blank\" rel=\"noopener\">Pasquet et al., 2014<\/a><\/span>)<\/li>\n<li>The death of the bacterial cell due to direct contact of the metallic Zn to the cell (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acsbiomaterials.6b00035\" target=\"_blank\" rel=\"noopener\">Shearier et al., 2016<\/a><\/span>)<\/li>\n<li>Intrinsic antimicrobial properties of the ZnO<sup>2+<\/sup> ions after dissociation. The uptake of zinc into cells is regulated by homeostasis. A concentration of the ZnO<sup>2+<\/sup> ions higher than the optimal level of 10<sup>-7<\/sup> to 10<sup>-5<\/sup> M (depending on the microbial strain) allows the invasion of Zn<sup>2+<\/sup> ions into the cell, and the zinc starts to be cytotoxic (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/academic.oup.com\/cid\/article-abstract\/5\/1\/137\/438721?redirectedFrom=fulltext\" target=\"_blank\" rel=\"noopener\">Sugarman, 1983<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/0009279789900859\" target=\"_blank\" rel=\"noopener\">Borovansk\u00fd et al., 1989<\/a><\/span>).<\/li>\n<\/ul>\n<p>ZnO shows activity against, e.g., <em>Staphylococcus aureus, Pseudomonas aeruginosa, E. coli,<\/em> <em>Streptococcus pyogenes<\/em>, and other enterobacteria<em> (<\/em>Ann et al., 2014; Vahjen et al., 2016). However, Roselli et al. (2003) did not see a viability-decreasing effect of ZnO on ETEC.<\/p>\n<h3>2.\u00a0\u00a0 ZnO modulates the immune system<\/h3>\n<p>Besides fighting pathogenic organisms as described in the previous chapter and supporting the immune system, ZnO is an essential trace element and has a vital role in the immune system. ZnO improves the innate immune response, increasing phagocytosis and oxidative bursts from macrophages and neutrophils. It also ameliorates the adaptative immune response by increasing the number of T lymphocytes (T cells) in general and regulatory T lymphocytes (T-regs) in particular. These cells control the immune response and inflammation (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9705703\/#:~:text=Furthermore%2C%20although%20the%20mechanisms%20are,T%20cell%20numbers(72).\" target=\"_blank\" rel=\"noopener\">Kloubert et al., 2018<\/a><\/span>). Macrophage capacity for phagocytosis <span style=\"text-decoration: underline;\"><a href=\"Phagocytosis%20by%20macrophages%20in%20zinc-deficient%20rats\" target=\"_blank\" rel=\"noopener\">(Ercan and Bor, 1991<\/a><\/span>) and to kill parasites (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1385514\/#:~:text=Pretreatment%20of%20MPM%20from%20zinc,the%20effects%20of%20zinc%20deficiency.\" target=\"_blank\" rel=\"noopener\">Wirth et al., 1989<\/a><\/span>), and also the killing activity of natural killer cells depends on Zn (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S1756464618303621#:~:text=Zinc%20supplementation%20induces%20killing%20activity,boosts%20the%20NK%20cell%20cytotoxicity.\" target=\"_blank\" rel=\"noopener\">Rolles et al., 2018<\/a><\/span>). By reducing bacterial adhesion and blocking bacterial invasion, ZnO disburdens the immune system (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/jn.nutrition.org\/article\/S0022-3166(22)16167-5\/pdf\" target=\"_blank\" rel=\"noopener\">Roselli et al., 2003<\/a><\/span>).<\/p>\n<p>ZnO reduces the expression of several proinflammatory cytokines induced by ETEC (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/jn.nutrition.org\/article\/S0022-3166(22)16167-5\/pdf\" target=\"_blank\" rel=\"noopener\">Roselli et al., 2003<\/a><\/span>). Several studies have also shown a modulation effect on intestinal inflammation, decreasing levels of IFN-\u03b3, TNF-\u03b1, IL-1\u00df and IL-6, all pro-inflammatory, in piglets supplemented with ZnO (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/27339255\/\" target=\"_blank\" rel=\"noopener\">Zhu et al., 2017<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1751731115001329?via%3Dihub\" target=\"_blank\" rel=\"noopener\">Grilli et al., 2015<\/a><\/span>).<\/p>\n<h3>3.\u00a0\u00a0 ZnO improves digestion and promotes growth<\/h3>\n<p>Besides protecting young piglets against diarrhea, the goal is to make them grow optimally. For this target, an efficient digestion and a high absorption of nutrients is essential. Stimulating diverse pancreatic enzymes such as amylase, carboxypeptidase A, trypsin, chymotrypsin, and lipase increases digestibility (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.researchgate.net\/publication\/6704524_Influence_of_dietary_zinc_and_copper_on_digestive_enzyme_activity_and_intestinal_morphology_in_weaned_pigs\" target=\"_blank\" rel=\"noopener\">Hedemann et al., 2006<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0946672X15000103?via%3Dihub\" target=\"_blank\" rel=\"noopener\">Pieper et al., 2015<\/a><\/span>). However, Pieper et al. (2015) also showed that a long-term supply of very high dietary zinc triggers oxidative stress in the pancreas of piglets.<\/p>\n<p>By stimulating the secretion of ghrelin at the stomach level and thereby promoting the release of insulin-like growth factor (IGF-1) and cholecystokinin (CCK), ZnO enhances muscle protein synthesis, cell proliferation, and feed intake (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18926680\/#:~:text=Addition%20of%20ZnO%20to%20culture,at%20the%20post%2Dtranscriptional%20level.\" target=\"_blank\" rel=\"noopener\">Yin et al., 2009<\/a><\/span>; <span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/10801966\/#:~:text=Zinc%20participates%20in%20the%20regulation,')tetraphosphate(5')%2Dadenosine.\" target=\"_blank\" rel=\"noopener\">MacDonald et al., 2000<\/a><\/span>)).<\/p>\n<p>The result of improved digestion is increased body weight and average daily gain, which can be seen, e.g., in a study by Zhu et al. (2017).<\/p>\n<h3>4.\u00a0\u00a0 ZnO protects the intestinal morphology<\/h3>\n<p>ZnO prevents the decrease of the trans-endothelial electrical resistance (TEER), usually occurring in the case of inflammation, by downregulating TNF-\u03b1 and IFN-\u03b3. TNF-\u03b1, as well as IFN-\u03b3, increase the permeability of the epithelial tight junctions and, therefore, the intestinal barrier (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3724223\/pdf\/nihms267589.pdf\" target=\"_blank\" rel=\"noopener\">Al-Sadi et al., 2009<\/a><\/span>).<\/p>\n<p>The enterotrophic and anti-apoptotic effect of ZnO is reflected by a higher number of proliferating and PCNA-positive cells and an increased mucosa surface in the ileum (higher villi, higher villi\/crypt ratio)(<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1751731115001329?via%3Dihub\" target=\"_blank\" rel=\"noopener\">Grilli et al., 2015<\/a><\/span>). <span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/27339255\/\" target=\"_blank\" rel=\"noopener\">Zhu et al. (2017<\/a><\/span>) also saw an increase in villus height in the duodenum and ileum and a decrease in crypt depth in the duodenum due to the application of 3000 mg of ZnO\/kg. Additionally, they could notice a significant (P&lt;0.05) upregulation of the mRNA expression of the zonula occludens-1 and occluding in the mucosa of the jejunum of weaned piglets.<\/p>\n<p>In a trial conducted by <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0022316622161675\" target=\"_blank\" rel=\"noopener\">Roselli et al. (2003)<\/a><\/span>, the supplementation of 0.2 mmol\/L ZnO prevented the disruption of the membrane integrity when human Caco-2 enterocytes were challenged with ETEC.<\/p>\n<h3>5.\u00a0\u00a0 ZnO acts antioxidant<\/h3>\n<p>The antioxidant effect of ZnO was shown in a study conducted by <span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/27339255\/\" target=\"_blank\" rel=\"noopener\">Zhu et al., 2017<\/a><\/span>. They could demonstrate that the concentration of malondialdehyde (MDA), a marker for lipid peroxidation, decreased on day 14 or 28, and the total concentration of superoxide dismutase (SOD), comprising enzymes that transform harmful superoxide anions into hydrogen peroxide, increased on day 14 (P&lt;0.05). Additionally, Zn is an essential ion for the catalytic action of these enzymes.<\/p>\n<h2>Which positive effects of ZnO can be covered by organic acids (OAs)?<\/h2>\n<h3>1.\u00a0\u00a0 OAs act antimicrobial<\/h3>\n<p>OAs, on the one hand, lower the pH in the gastrointestinal tract. Some pathogenic bacteria are susceptible to low pH. At a pH&lt;5, the proliferation of, e.g., Salmonella, E. coli, and Clostridium is minimized. The good thing is that some beneficial bacteria, such as lactobacilli or bifidobacteria, survive as they are acid-tolerant. The lactobacilli, on their side, can produce hydrogen peroxide, which inhibits, e.g., Staphylococcus aureus or Pseudomonas spp. (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31195444\/\" target=\"_blank\" rel=\"noopener\">Juven and Pierson, 1996<\/a><\/span>).<\/p>\n<p>Besides this more indirect mode of action, a more direct one is also possible: Owing to their lipophilic character, the undissociated form of OAs can pass the bacterial membrane (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19087448\/\" target=\"_blank\" rel=\"noopener\">Partanen and Mroz, 1999<\/a><\/span>). The lower the external pH, the more undissociated acid is available for invading the microbial cells. Inside the cell, the pH is higher than outside, and the OA dissociates. The release of hydrogen ions leads to a decrease in the internal pH of the cell and to a depressed cell metabolism. To get back to \u201cnormal conditions\u201d, the cell expels protons. However, this is an energy-consuming process; longer exposure to OAs leads to cell death. The anion remaining in the cell, when removing the protons, disturbs the cell&#8217;s metabolic processes and participates in killing the bacterium.<\/p>\n<p>These theoretical effects could be shown in a practical trial by <span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.animbiosci.org\/journal\/view.php?doi=10.5713\/ajas.2013.13411\" target=\"_blank\" rel=\"noopener\">Ahmed et al.<\/a><\/span> (2014). He fed citric acid (0.5 %) and a blend of acidifiers composed of formic, propionic, lactic, and phosphoric acid + SiO<sub>2<\/sub> (0.4 %) and saw a reduction in fecal counts of Salmonella and E. coli for both groups<em>.<\/em><\/p>\n<h3>2.\u00a0\u00a0 OAs modulate the immune system<\/h3>\n<p>The immune system is essential in the pig&#8217;s life, especially around weaning. Organic acids have been shown to support or stimulate the immune system. Citric acid (0.5%), as well as the blend of acidifiers mentioned before (Ahmed et al., 2014), significantly increased the level of serum IgG. IgG is part of the humoral immune system. They mark foreign substances to be eliminated by other defense systems.<\/p>\n<p><span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.hindawi.com\/journals\/bmri\/2019\/6416187\/\" target=\"_blank\" rel=\"noopener\">Ren et al.<\/a><\/span> (2019) could demonstrate a decrease in plasma tumor necrosis factor-\u03b1 that regulates the activity of diverse immune cells. He also found lower interferon-\u03b3 and interleukin (Il)-1\u00df values in the OA group than in the control group after the challenge with ETEC. This trial shows that inflammatory response can be mitigated through the addition of organic acids.<\/p>\n<h3>3.\u00a0\u00a0 OAs improve digestion and promote growth<\/h3>\n<p>In piglets, the acidity in the stomach is responsible for the activation and stimulation of certain enzymes. Additionally, it keeps the feed in the stomach for a longer time. Both effects lead to better digestion of the feed.<\/p>\n<p>In the stomach, the conversion of pepsinogen to pepsin, which is responsible for protein digestion, is catalyzed under acid conditions (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.jbc.org\/article\/S0021-9258(19)41649-9\/pdf\" target=\"_blank\" rel=\"noopener\">Sanny et al., 1975<\/a><\/span>)group. Pepsin works optimally at two pH levels: pH 2 and pH 3.5 (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1196751\/\" target=\"_blank\" rel=\"noopener\">Taylor, 1959<\/a><\/span>). With increasing pH, the activity decreases; at pH 6, it stops. Therefore, a high pH can lead to poor digestion and undigested protein arriving in the intestine.<\/p>\n<p>These final products of pepsin protein digestion are needed in the lower parts of the GIT to stimulate the secretion of pancreatic proteolytic enzymes. If they do not arrive, the enzymes are not activated, and the inadequate protein digestion continues. Additionally, gastric acid is the primary stimulant for bicarbonate secretion in the pancreas, neutralizing gastric acid and providing an optimal pH environment for the digestive enzymes working in the duodenum.<\/p>\n<p>As already mentioned, the pH in the stomach influences the transport of digesta. The amount of digesta being transferred from the stomach to the small intestine is related to the acidity of the chyme leaving the stomach and arriving in the small intestine. Emptying of the stomach can only take place when the duodenal chyme can be neutralized by pancreatic or other secretions (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.karger.com\/Article\/FullText\/142726\" target=\"_blank\" rel=\"noopener\">Pohl et al., 2008<\/a><\/span>); so, acid-sensitive receptors provide feedback regulation and a higher pH in the stomach leads to a faster transport of the digesta and a worse feed digestion.<\/p>\n<h3>4.\u00a0\u00a0 OAs protect the intestinal morphology<\/h3>\n<p>Maintaining an intact gut mucosa with a high surface area is crucial for optimal nutrient absorption. Research suggests organic acids play a significant role in improving mucosal health:<\/p>\n<p>Butyric acid promotes epithelial cell proliferation, as demonstrated in an <em>in vitro<\/em> pig hindgut mucosa study (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.researchgate.net\/publication\/15642814_Effect_of_n-butyric_acid_on_epithelial_cell_proliferation_of_pig_colonic_mucosa_in_short-term_culture\" target=\"_blank\" rel=\"noopener\">Sakata et al., 1995<\/a><\/span>). Fumaric acid, serving as an energy source, may locally enhance small intestinal mucosal growth, aiding in post-weaning epithelial cells\u2019 recovery and increasing absorptive surface and digestive capacity (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/academic.oup.com\/jas\/article-abstract\/77\/11\/2974\/4653425?redirectedFrom=fulltext\" target=\"_blank\" rel=\"noopener\">Blank et al., 1999<\/a><\/span>). Sodium butyrate supplementation at low doses influences gastric morphology and function, thickening the stomach mucosa and enhancing mucosal maturation and differentiation (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18641186\/\" target=\"_blank\" rel=\"noopener\">Mazzoni et al., 2008<\/a><\/span>).<\/p>\n<p>Studies show that organic acids affect gut morphology, with a mixture of short-chain and mid-chain fatty acids leading to longer villi (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/www.researchgate.net\/publication\/296055201_Influence_of_medium-chain_fatty_acids_and_short-chain_organic_acids_on_jejunal_morphology_and_intra-epithelial_immune_cells_in_weaned_piglets\" target=\"_blank\" rel=\"noopener\">Ferrara et al., 2016<\/a><\/span>) and Na-butyrate supplementation increasing crypt depth and villi length in the distal jejunum and ileum (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/15608361\/\" target=\"_blank\" rel=\"noopener\">Kotunia et al., 2004<\/a><\/span>). However, the villi length and mucosa thickness in the duodenum were reduced. Dietary sodium butyrate has been linked to increased microvilli length and cecal crypt depth in pigs (<span style=\"text-decoration: underline;\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/2100936\/#:~:text=Pigs%20weighing%207%20to%20102,utilization%20was%20reduced%20by%2011.8%25.\" target=\"_blank\" rel=\"noopener\">G\u00e1lfi and Bokori, 1990<\/a><\/span>).<\/p>\n<h3>5.\u00a0\u00a0 OAs show antioxidant activity<\/h3>\n<p>The last characteristic, the antioxidant effect, cannot be provided at the same level as with ZnO; however, <span style=\"text-decoration: underline;\"><a href=\"https:\/\/link.springer.com\/article\/10.1007\/s10068-019-00637-1\" target=\"_blank\" rel=\"noopener\">Zhang et al. (2019)<\/a><\/span> attest to OAs a certain antioxidant activity. Oxalic, citric, acetic, malic, and succinic acids, which were extracted from Camellia oleifera, also showed good antioxidant activity in a trial conducted by <span style=\"text-decoration: underline;\"><a href=\"https:\/\/link.springer.com\/article\/10.1007\/s10068-019-00637-1\" target=\"_blank\" rel=\"noopener\">Zhang et al. (2020)<\/a><\/span>.<\/p>\n<h2>Organic acids are an excellent tool to compensate for the ban on ZnO<\/h2>\n<p>The article shows that organic acids have similar positive effects as zinc oxide. They act antimicrobial, modulate the immune system, maintain the gut morphology, fight pathogenic microbes, and also act \u2013 slightly \u2013 antioxidant. Additionally, they have a significant advantage: they are not harmful to the environment. Organic acids used in the proper pH range and combination are good tools for replacing zinc oxide.<\/p>\n<p>References on request<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Dr. Inge Heinzl, Editor EW Nutrition &amp; Juan Antonio Mesonero Escuredo, GTM Swine\/GPM Organic Acids EW Nutrition The use of high levels of Zinc Oxide (ZnO) in the EU before 2022 was one of the most common methods to prevent postweaning diarrhea (PWD) in pig production. Pharmacologically high levels of ZnO (2000-3000 ppm) increase growth&#8230;<\/p>\n","protected":false},"author":5,"featured_media":208224,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[9204,8039,9165,7796,8362,9140,8363,8031,8043,8778,7779],"tags":[],"class_list":["post-208245","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-acidomix-en-uk","category-antibiotic-reduction-en-uk-2","category-diarrhea-en-uk","category-feed-en-uk","category-feed-hygiene-en-uk","category-gut-health-en-uk-2","category-organic-acids-en-uk","category-pig-en-uk","category-pig-gut-health-en-uk","category-pig-nutrition-en-uk","category-piglet-en-uk"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v26.5 (Yoast SEO v27.4) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Organic acids can play a crucial role in zinc oxide replacement - EW Nutrition<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ew-nutrition.com\/en-uk\/organic-acids-play-crucial-role-zinc-oxide-replacement\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Organic acids can play a crucial role in zinc oxide replacement\" \/>\n<meta property=\"og:description\" content=\"Dr. Inge Heinzl, Editor EW Nutrition &amp; Juan Antonio Mesonero Escuredo, GTM Swine\/GPM Organic Acids EW Nutrition The use of high levels of Zinc Oxide (ZnO) in the EU before 2022 was one of the most common methods to prevent postweaning diarrhea (PWD) in pig production. 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