Vitamin A is an essential micronutrient that cannot be synthesized by non-ruminants and must be obtained through the diet. Although certain plant pigments called carotenoids may yield retinoids metabolically, only a small percentage of them can be converted into vitamin A precursors in mammals and birds (Surai et al., 2003; Combs and McClung, 2017). Due to practical considerations, the naturally occurring vitamin A and carotenoid levels in feed ingredients are not typically taken into account during diet formulation, and instead, the total retinol requirement is satisfied through dietary supplementation of retinyl acetate (Darroch, 2000).

Vitamin A refers to three distinct chemical compounds, each with unique properties and functions in the body: retinol, an alcohol; retinal, an aldehyde; and retinoic acid (Carazo et al., 2021). As a fat-soluble vitamin, retinol is required for a range of biological processes, including vision, reproduction, growth, and development, but perhaps most importantly, it is essential for immune system function (Huang et al., 2018). The immune system defends the body against pathogens and other harmful substances, and vitamin A is known to modulate the immune response (Gürbüz and Aktac, 2022). A deficiency or suboptimal supply in retinol can lead to an increased susceptibility to infections and a compromised immune system function (Ahmad et al., 2009). Therefore, understanding the role of vitamin A in nutritional immunology of non-ruminants is critical for improving animal health and productivity, as well as for developing effective dietary strategies to optimize vitamin A supply.

When it comes to meat consumption, pork and poultry account for 75% of land animals consumed worldwide (den Hartog and Ravindran, 2019). This translates to approximately 16% of the dietary protein contribution in humans (Smith et al., 2022). Meanwhile, in both children and adults, eggs have been identified as a cost-effective source of protein delivery, contributing approximately 2.7% and 3.7% of the total dietary protein intake, respectively (Papanikolaou and Fulgoni, 2020). Therefore, optimizing immune system function in pigs and poultry is important for several reasons. Firstly, it helps to ensure animal welfare by reducing the risk of disease and minimizing the need for antibiotics, which can have negative effects on animal health and food safety. Secondly, a healthy immune system can improve production efficiency, leading to better growth rates and meat quality, which in turn can benefit farmers and consumers (Niu et al., 2022). Furthermore, reducing disease in livestock can also have a positive impact on human health by reducing the risk of zoonotic diseases (Thumbi et al., 2015).

This review paper aims to provide a comprehensive overview of the current state of knowledge on the interaction between vitamin A and the immune system in non-ruminant animals. Specifically, this review will cover the following topics: (1) the metabolism and functions of vitamin A, (2) the impact of vitamin A deficiency on non-ruminant immune function, (3) the immunomodulatory effects of vitamin A supplementation, (4) effect of hypervitaminosis A on immune function and (5) the potential applications of retinol as an immuno-micronutrient for improving health and preventing diseases in swine and poultry.

Overall, this review paper is intended to provide valuable insights into the role of vitamin A in nutritional immunology of non-ruminants and highlight the current gaps and opportunities for further research in this field.

The digestion and absorption of dietary vitamin A occur in the small intestine of birds and mammals. Retinol is released into the intestinal lumen when pancreatic esterases hydrolyze vitamin A esters (Reboul, 2013). After hydrolysis, retinol is incorporated into mixed micelles comprising of bile salts and other lipids, which facilitates efficient absorption. Once absorbed, the retinol is re-esterified in the enterocytes and integrated into chylomicrons, which then enter the lymphatic system and bloodstream transporting vitamin A to the liver (O’Byrne and Blaner, 2013). Vitamin A is stored as retinyl esters in hepatocytes, stellate, and parenchymal cells, which are specialized cells found in the hepatic system (Haaker et al., 2020). When needed, retinyl esters are hydrolyzed to release retinol, which can then be transported to target tissues via plasma retinol-binding protein (RBP) through complexation with transthyretin (Raghu and Sivakumar, 2004; Steinhoff et al., 2022). Cells that express the membrane protein STRA6 mediate the cellular uptake of retinol by taking up the retinol-RBP complex (Kelly and von Lintig, 2015). Within the cell, vitamin A is usually converted into its active form, retinoic acid, by two sequential oxidation reactions catalyzed by retinol dehydrogenases and retinal dehydrogenases (Bchini et al., 2013).

Retinoic acid is the active form of vitamin A, which binds to nuclear receptors such as retinoic acid receptors (RARs) and retinoid X receptors (RXRs) to exert its biological effects (McKenna, 2012; Al Tanoury et al., 2013). RARs and RXRs form heterodimers that bind to specific DNA sequences and regulate the transcription of target genes (le Maire et al., 2019). Co-regulatory proteins such as co-activators and co-repressors can modulate the transcriptional activity of RARs and RXRs (Cordeiro et al., 2019). The RAR-RXR heterodimer controls the expression of target cistrons involved in various physiological functions such as vision, immunity, and cell differentiation (Li et al., 2021).

The importance of vitamin A in vision lies in its role as a fundamental component of the visual pigment rhodopsin. Rhodopsin is located in the retinal rods and is crucial for vision under low-light conditions (Park, 2014). Light striking the retina results in a conformational change in rhodopsin, leading to the initiation of a signaling cascade that ultimately culminates in visual perception (Palczewski, 2014). Rhodopsin is made up of two components: opsin, which is a protein, and 11-cis-retinal, the chromophore that is derived from retinol (Ortega and Jastrzebska, 2019). Consequently, if left untreated, a deficiency of vitamin A may result in night blindness and ultimately progress to complete blindness in animals (Debelo et al., 2017).

One of the most important functions of vitamin A in growth is its role in promoting cellular differentiation. During embryonic development and throughout growing period, retinol is necessary for the proper differentiation of cells into specialized tissues and organs (Gudas and Wagner, 2011). In particular, vitamin A plays a crucial role in the growth and upkeep of epithelial tissues found in vital areas like the skin, respiratory system, urinary and digestive tract (Timoneda et al., 2018). These tissues act as a barrier against pathogens and environmental insults constituting an important part of the immune system (Jafari and Rohn, 2022). Furthermore, they are essential for nutrient absorption and gas exchange.

In addition to its role in cellular differentiation, vitamin A is also important for bone growth and development. Retinol deficiency in pigs and poultry has been shown to impair bone growth and increase the risk of bone malformations (Palludan, 1961; EFSA (European Food Safety Authority), 2013; Abd El-Wahab et al., 2017). This can be attributed, at least in part, to the role of vitamin A in promoting the production and activation of osteoblasts, which are the cells responsible for building new bone tissue (Chiba et al., 1996). Retinol is also involved in the regulation of bone resorption, which is the natural process of breaking down old bone tissue and replacing it with new bone tissue (Yee et al., 2021).

Finally, retinol is indispensable for reproductive health in birds and mammals (Lindemann et al., 2008; Chen et al., 2015). It is essential for the proper development and maintenance of reproductive organs, including the testes, ovaries, and uterus (Clagett-Dame and Knutson, 2011). Furthermore, retinoic acid is necessary for the differentiation of germ cells, which eventually give rise to eggs and sperm (Endo et al., 2019). Retinol also promotes the differentiation of Leydig cells, which produce testosterone in males, and theca cells, which produce estrogen in females (Yang et al., 2018).

Thus, vitamin A is a crucial micronutrient with diverse physiological functions, and its deficiency can cause health problems, emphasizing the importance of adequate intake.

Retinoids are recognized as one of the most crucial substances that exert a profound influence on the immune system of non-ruminant animals (Dalloul et al., 2002; Chattha et al., 2013; Hu et al., 2020; Amimo et al., 2022; Wan et al., 2022). They affect the differentiation, proliferation, and functionality of various immune cells, including T cells, B cells, natural killer (NK) cells, and dendritic cells (Oliveira et al., 2018). Retinoids regulate the expression of genes that are involved in immune function, including those controlling inflammation and cytokine production (Pino-Lagos et al., 2010). Insufficient vitamin A intake impairs immune cell function and modifies gene expression, resulting in reduced immune responses and increased susceptibility to infection in pigs and poultry (Ahmad et al., 2009; Pino-Lagos et al., 2010; Vlasova et al., 2013; Chepngeno et al., 2022; Zhang et al., 2023).

Green and Mellanby (1928) were the first to discover the role of vitamin A in immune modulation, which led to its recognition as “the anti-infective vitamin”. Currently, retinol is one of the most investigated micronutrients regarding immune function (Villamor and Fawzi, 2005; Gürbüz and Aktac, 2022).

Vitamin A is crucial in maintaining the epithelial barrier, acting as the first line of defense against various infections (Huang et al., 2018). In instances of vitamin A deficiency, observed in the research conducted by Cortes et al. (2006), birds demonstrated clinical signs of squamous metaplasia and hyperkeratinization of glandular epithelium in numerous mucosal surfaces, including the esophagus, bursa of Fabricius, proventriculus, and nasal glands. Similar symptoms can be observed in different tissues of mammals experiencing hypovitaminosis A (Baldwin et al., 2012). However, the immunoregulatory effects of retinol go beyond its role in preserving the integrity of the epithelium and mucus layers.

According to Ahmad et al. (2009), insufficient vitamin A levels can significantly impact the immune system’s antibody response. In particular, animals with low levels of this vitamin exhibit diminished IgM and IgG response, reduced production of specific IgM antibodies, and decreased salivary IgA antibody levels during infections (Stephensen, 2001; Hu et al., 2020 and Zhou et al., 2021). For instance, early studies by Harmon et al. (1963) found that pigs with vitamin A deficiency produced less than 10% of the antibody quantity compared to control pigs given vitamin A supplementation.

Vitamin A deficiency can have a significant impact on immune function, even before other symptoms become apparent. In fact, a seminal study by Friedman and Sklan (1989) using an avian model showed that vitamin A deficiency initially impairs serum antibody responses. However, this impairment can be rapidly reversed with the administration of retinyl acetate supplementation, highlighting the importance of early detection and intervention. Similar results were reported by Davis and Sell (1989) in broilers, where chicks fed a vitamin A-deficient diet showed significantly lower serum antibody responses to Newcastle disease virus (NDV) vaccination.

In viral infections, cell-mediated immune responses play an important role, and vitamin A deficiency can inhibit them. An investigation by Sijtsma et al. (1990) indicated that vitamin A deficiency decreased cytotoxic T lymphocyte activity against NDV-infected cells in chickens. As a result, the death of virus-infected cells may be delayed, increasing morbidity in birds infected with the virus.

In a more recent study, clinical signs of vitamin A deficiency in broiler chickens infected with NDV were observed, including greenish-white droppings, ruffled feathers, and leg weakness (Rizvi et al., 2003). Furthermore, vitamin A-deficient broilers showed a lower immune response to the virus, as demonstrated by a lower geometric mean titer compared to those with adequate vitamin A intake.

An array of endogenous retinoic acid metabolites has been shown to possess biological activity. Among them, 14-hydroxy-4,14-retro-retinol (14-HRR) and 3,14-di-OH-retinol are involved in the proliferation of T and B cells (Schuchardt, 2007). For example, 14-HRR is essential for the growth of B lymphocytes and activation of T lymphocytes (Carazo et al., 2021). Whether in insects or mammals, nearly every cell in the body has the capacity to convert all-trans retinol to 14-HRR, indicating the widespread conservation of this biochemical pathway (Blomhoff and Blomhoff, 2006). 14-HRR is structurally similar to retinoic acid, but with a hydroxyl group at position 14 and a reversed double bond at positions 4 and 14. In birds and animals, 14-HRR has been shown to enhance the proliferation of lymphocytes in response to mitogens as well as, it has been found to increase the production of cytokines by lymphocytes such as interferon‐gamma, interleukin-2 or tumor necrosis factor (Mao et al., 2000).

Several studies have shown that subclinical vitamin A deficiency in animals can lead to immune dysfunction, compromising both innate and adaptive immune responses. Chattha et al. (2013) found that hypovitaminosis A in pigs impairs mucosal and systemic adaptive B and T lymphocyte responses as well as imbalances innate and adaptive cell distribution. Researchers reported that vitamin A deficient pigs had greater CD8 T cell frequencies in blood, spleen, duodenum, ileum, and lower frequencies of CD4 T cells in ileum after a challenge with a virulent rotavirus (RV; Figure 1 ). Further, plasmacytoid dendritic cells were found in significantly higher numbers in intestinal tissues and conventional dendritic cells in all tissues examined pre-challenge, suggesting dysregulation of overall immune responses in vitamin A-deficient swine. As well, low-vitamin A diets significantly reduced the CD4:CD8 T-cell ratios in chicken (Lessard et al., 1997).

In neonatal piglets, Kandasamy et al. (2014) examined the impact of vitamin A deficiency on the immune response to the rotavirus (RV) vaccine and subsequent infection. The results showed that vitamin A deficient piglets had compromised immune responses, higher fecal virus shedding, and lower protective efficacy against infection compared to vitamin A sufficient animals (100,000 IU at d 6, 16 and 28 of age). Vitamin A deficient piglets also had persistently elevated levels of pro-inflammatory mediator IL-8 and lower anti-inflammatory cytokine IL-10 responses, suggesting more severe inflammatory reactions. The study concluded that vitamin A deficiency impairs the immune response to the rotavirus vaccine and reduces vaccine efficacy against infection. Oral vitamin A supplementation concurrent with the vaccine did not improve vaccine efficacy in vitamin A deficient piglets. Thus, the studies of Lessard et al. (1997); Chattha et al. (2013) and Kandasamy et al. (2014) demonstrate the important role of vitamin A in maintaining a balanced and functional immune system in animals, as its deficiency can lead to dysregulation of innate and adaptive immune responses.

In chicks, Davis and Sell (1983) demonstrated that vitamin A deficiency impaired lymphocyte proliferation in response to mitogenic stimulation and reduced the growth of the bursa of Fabricius and thymus, both of which are crucial in the development and maturation of different types of white blood cells (e.g., lymphocytes) that are essential for proper immune system function (Schat, 2022).

Dalloul et al. (2002) conducted a study to investigate the impact of vitamin A deficiency on the intestinal immune response and disease susceptibility to coccidiosis in broiler chickens infected with Eimeria acervulina. The researchers found that birds fed a vitamin A-deficient diet had fewer intraepithelial lymphocytes expressing surface markers CD3, CD4, CD8, αβTCR, and γβTCR, regardless of whether they were challenged with Eimeria or not. Moreover, the vitamin A-deficient birds shed significantly more Eimeria oocysts and produced lower levels of interferon-γ than birds on a vitamin A-supplemented diet, indicating that vitamin A deficiency can compromise local immune defenses and increase disease susceptibility in broiler chickens.

Vitamin A is known to be essential for maintaining the integrity of various systems in the body, including the gastrointestinal tract. In a study by Idi et al. (2007), the effect of vitamin A deficiency on chickens infected with Ascaridia galli eggs was investigated. The results indicated that vitamin A plays a crucial role in moderating A. galli infection in poultry.

The impact of hypovitaminosis A on respiratory infections in young animals is well established. To address this issue, McGill et al. (2019) recently carried out an investigation on bovine respiratory syncytial virus (BRSV), a pathogen that causes lower respiratory tract disease. The researchers developed a nanovaccine that contained BRSV proteins encapsulated in polyanhydride nanoparticles. However, when tested on calves with vitamin A deficiency, the vaccine did not produce the desired response, and the animals were not protected from BRSV challenge. Interestingly, the study also revealed that acute BRSV infection had a negative effect on both serum and liver retinol levels. These results underscore the crucial role of vitamin A in regulating respiratory mucosa immunity in animals. The calf model used in the study proved to be a valuable tool for investigating the impact of nutritional status on mucosal immunity and viral infections.

Romagnani (1999) note that Type 1 T helper (Th1) cells generate interferon-gamma, interleukin-2, and tumor necrosis factor-beta, which activate macrophages and facilitate cell-mediated immunity and phagocyte-dependent protective responses. On the other hand, type 2 Th (Th2) cells produce IL-4, IL-5, IL-10, and IL-13, promoting robust antibody production, eosinophil activation, and the inhibition of various macrophage functions, thereby providing phagocyte-independent protective responses. Th1 cells generally emerge after infections caused by intracellular bacteria and some viruses, while Th2 cells are more prevalent in response to infestations caused by gastrointestinal nematodes.

Cantorna et al. (1994) discovered that vitamin A has at least three important functions that help to balance Th1 and Th2 activities. These functions include directly down-regulating the secretion of interferon‐gamma by Th1 cells, reducing the function of activated antigen presenting cells, and promoting the growth and/or differentiation of Th2 cells. The antigen-presenting cells play a central role in vitamin A’s immune system functions (Duriancik et al., 2010). This imbalance between regulatory Th1 and Th2 cells is believed to be a contributing factor to poor antibody-mediated immunity in cases of hypovitaminosis A.

Amimo et al. (2022) observed that, generally, there is a tri-directional relationship between vitamin A deficiency, immune response, and infections. Vitamin A deficiency affects the immune system and makes it more susceptible to infection, and infection decreases the absorption of vitamin A, resulting in secondary retinol deficiency in animals.

Hence, it is acknowledged that retinol and its metabolites are important substances for immune function, as studies have revealed that vitamin A deficiency can considerably affect the immune system’s antibody response and impair the proliferation and function of immune cells.

In conclusion, it is important to make some critical remarks. Although the overwhelming majority of research suggest that inadequate vitamin A intake can impair immune system function, the optimal level of vitamin A required for maintaining immune health remains unclear. Furthermore, excessive intake of vitamin A can lead to hypervitaminosis A, which may cause certain adverse effects. Thus, it is essential to strike a balance in the recommended vitamin A intake level for immune health to avoid potential negative consequences.

Supplementation of vitamin A in diets of non-ruminants has been used as a strategy to enhance immunity and health. However, several immunomodulatory effects of supplemental vitamin A on different aspects of the immune system in pigs and poultry are still a matter of debate and require further investigation.

Hypervitaminosis A is a condition that can be induced when animals, including swine and poultry, consume excessive amounts of retinol. Although vitamin A is indispensable for proper nutrition, it is crucial to maintain a balanced intake to avoid adverse effects.

The susceptibility to hypervitaminosis A in animals can be influenced by several factors, including breed, age, the level of vitamin A dosage, the form of vitamin used, the route and frequency of its administration, as well as factors involved in the absorption of fat-soluble vitamins (Sideeg, 1996).

When birds and mammals are exposed to excessively high levels of vitamin A, it can potentially have detrimental effects on their immune function. A study conducted by Yuan et al. (2014) demonstrated this by investigating the effects of different vitamin A supplementation levels on broiler breeders. Increasing vitamin A supplementation from 5,000 IU/kg to 20,000 IU/kg of feed resulted in an increase in NDV antibody titer. However, a further increase to 35,000 IU/kg led to a decrease in this parameter. In contrast, Coskun et al. (1998) reported no significant effects of dietary supplementation with vitamin A at levels up to 24,000 IU/kg on the immune response of Hisex-brown laying hens. According to their findings, there were no notable changes in the levels of T lymphocytes in the peripheral blood, plasma cell counts in the spleen, or antibody titers against NDV in response to the supplementation.

Sklan et al. (1994) and Sklan et al. (1995) conducted studies to investigate the effect of increasing doses of vitamin A, up to 44,000 IU/kg feed, on the growth and antibody production in broiler chickens and turkeys. The results of their research showed that both antibody production and T cell proliferative response reached a plateau at approximately 20,000 IU of vitamin A supplementation. However, at the highest supplementation level of 44,000 IU/kg feed, there was a reduction in these parameters, indicating a bell-shaped response. Guo et al. (2019) reported similar findings in a more recent study in broilers.

Swine seem to be much more tolerant to higher supplementation levels of retinol compared to poultry. For instance, a study conducted on piglets weighing 8 kg initially and up to 90 kg investigated the effects of feeding very high doses of vitamin A, reaching up to 220,000 IU/kg of feed (Blair et al., 1992). The researchers found no clinical signs of toxicity and observed no adverse effects on bone health. However, they did note an increase in plasma and liver levels of vitamin A as a result of the supplementation.

Recent studies have indicated that high intake of vitamin A can result in the development of resistance to hypervitaminosis A. In a study by Bozhkov et al. (2021), experimental animals were administered vitamin A daily at a dose of 300 IU/100 g of body weight. It was observed that vitamin A accumulated in the liver, reaching a concentration of 250-300 mg/g. Surprisingly, subsequent administrations of vitamin A led to a decrease in its content in the liver, suggesting the presence of a potential resistance mechanism.

Additional research, such as the study by Arts et al. (2015), has indicated that hypervitaminosis A in mammals could compromise the immune response, rendering them more susceptible to infections and diseases. It is believed that excessive vitamin A can disrupt the balance and activation of immune cells, thus interfering with the intricate network of immune responses. This notion is supported by studies conducted on rats, where the administration of vitamin A significantly higher than their dietary requirements (8,000 and 15,000 IU/kg body weight) had a stimulatory effect on total white blood cell and neutrophil counts, while inhibiting basophil and total lymphocyte counts (Mahassni and Al-Shaikh, 2013).

Moreover, excessive intake of vitamin A can have an impact on the production of antibodies, which play a crucial role in recognizing and targeting specific pathogens. This can potentially compromise the ability of swine and poultry to effectively combat infections and maintain optimal immune responses. In a study conducted on viral pneumonia interventions (Cui et al., 2000), animals that were fed a very high level of vitamin A (250,000 IU/kg diet) demonstrated greater salivary immunoglobulin IgA responses compared to the control group (4,000 IU/kg diet). Conversely, the control group exhibited significantly higher serum IgG responses compared to the high-level group (P = 0.028). Additionally, the production of interferon-gamma (IFN-gamma), a Th1 cytokine, was found to be lower in the high-level diet group.

It is important to note that the negative effects of hypervitaminosis A on immune function in swine and poultry are typically observed when animals are exposed to extremely high levels of the vitamin for extended periods. It is extremely rare for such excessive intake to occur under normal feeding conditions (EFSA (European Food Safety Authority), 2008). Therefore, proper nutritional management and regular monitoring of vitamin A levels in animal diets are essential to prevent the development of hypervitaminosis A and maintain optimal immune function.

Vitamin A has emerged as a promising immuno-micronutrient for optimizing health and disease prevention in pig and poultry production (Alagawany et al., 2020; Lauridsen et al., 2021). The above-mentioned studies have demonstrated that vitamin A supplementation can effectively enhance the immune response and reduce the incidence and severity of infectious diseases in non-ruminants. However, it is important to note that further research is needed to fully understand the optimal dosage and potential interactions with other nutrients in order to maximize the benefits of vitamin A supplementation in non-ruminant production.

There are various ways how to administer vitamin A to pigs and domestic fowl:

Yet, it is always important to take into account the local regulatory requirements and conditions of use for retinyl esters. For example, in the European Union, the use of vitamin A in water must adhere to specific guidelines. The concentration of vitamin A in water, when combined with the amount of vitamin A already present in the feed, must not exceed the recommended intake levels for certain species/categories (EFSA (European Food Safety Authority), 2013). These intake levels are determined based on the maximum content of vitamin A that is authorized for use in feed. EFSA (European Food Safety Authority) (2013) proposes the following maximum contents for vitamin A in complete feeds:

Pigs: piglets (weaned or suckling) 16 000 IU/kg complete feed; pigs for fattening 6 500 IU/kg complete feed; sows: 12 000 IU/kg complete feed.

Poultry: chickens (including all minor poultry species) in the first 14 days of life and turkeys in the first 28 days of life 20 000 IU/kg complete feed; all poultry (for fattening, reared for laying, laying and breeding) 10 000 IU/kg complete feed.

When determining the vitamin A requirements for pigs and poultry, it is crucial to consider the type of administration, the animal’s age, and production stage. The type of vitamin A administration can affect the bioavailability and absorption of vitamin A, which in turn can impact the animal’s overall vitamin A status and requirements. Young animals generally have higher vitamin A needs than mature animals, as they require vitamin A for growth and development (McDowell, 2000). Moreover, the necessary level of vitamin A may vary based on the purpose, with higher amounts required for maintaining a healthy immune system compared to performance or reproduction (McDowell, 2006). Generally, a factorial approach is indispensable in determining the precise vitamin A requirements as it considers a range of factors that influence the animal’s vitamin A needs, such as age, sex, physiological status, and other dietary factors.

A healthy immune system is critical for swine and poultry production because it helps prevent and control infectious diseases, which can lead to reduced productivity, increased mortality, and economic losses for farmers and integrators (Lauridsen, 2019; Raja Kumari Kallam and Sejian, 2021). Infectious diseases can spread quickly in animal populations, and in severe cases, can cause significant damage to the entire herd or flock (Machalaba et al., 2015). A strong immune system also helps animals better cope with environmental stressors, such as changes in temperature, nutrition, or vaccination (Scarola et al., 2019). In addition to its role in preventing and controlling infectious diseases, a healthy immune system also contributes to overall animal health and well-being. Animals with a strong immune system are more likely to grow and develop optimally, have better reproductive performance, and have lower incidences of other health problems (Doeschl-Wilson et al., 2009). Retinol, with its well-earned nickname “the anti-infective vitamin”, can be considered a pivotal vitamin in immune modulation among all vitamins. Therefore, maintaining a healthy immune system is critical for non-ruminant production, and farmers must take appropriate measures to ensure that their animals receive the right amount of vitamin A, correct dietary levels of other nutrients, appropriate vaccination, and management practices to support optimal immune function. In general, vitamin A requirements are affected by a variety of environmental, genetic, and nutritional factors, highlighting the need for a comprehensive approach when determining vitamin A needs (Chen et al., 2015).

Failure to address immune system health in non-ruminant production can result in devastating consequences not only for animal welfare but also for public health, as infectious diseases in animal populations can also pose a threat to human health through zoonotic transmission. Therefore, it is imperative that farmers and integrators prioritize immune system health as a critical component of their management practices to ensure both the well-being of their animals and the safety of the public.

Overall, the potential applications of vitamin A as an immuno-micronutrient for improving health and preventing diseases in pigs and poultry are promising. However, further research is needed to determine the optimal dosage and timing of retinol supplementation/administration for different stages of growth and production systems, as well as its potential interactions with other nutrients and feed ingredients. Nonetheless, in the practical usage of vitamin A, the respective local legal regulations must be considered and therefore any application must always be carried out within the framework of the legal provisions.

Based on this scientific review, the following conclusions and recommendations can be drawn:

Firstly, vitamin A is essential for various physiological processes, including vision, growth, and immunity. It is primarily obtained from dietary sources and is metabolized into its active form, retinoic acid, which regulates gene expression and immune function.

Secondly, vitamin A deficiency can impair immune function in non-ruminants, leading to increased susceptibility to infections, reduced vaccine efficacy, and compromised gut health. Hypovitaminosis A also affects the integrity of mucosal barriers and can lead to inflammation and oxidative stress.

Thirdly, retinol plays a crucial role in regulating both innate and adaptive immune responses. It enhances the activity of immune cells, such as T cells, B cells, and NK cells, and promotes the production of cytokines, antibodies, and immunoglobulins. Vitamin A also regulates gut-associated lymphoid tissue and maintains the integrity of the gut barrier.

Lastly, supplementation with vitamin A has been shown to improve growth, immune function, and disease resistance in swine and poultry. It can enhance the immune response to vaccines, reduce the incidence of parasitic, respiratory and enteric diseases, and improve the quality of meat and eggs.

Based on these findings, it is recommended that non-ruminant diets are formulated to meet the vitamin A requirements to ensure optimal immune function and disease resistance. Additionally, higher supplementation/administration with vitamin A may be beneficial in situations where animals are at risk of deficiency, such as during periods of stress or disease challenge. Further research is needed to optimize the use of vitamin A as an immuno-micronutrient and to explore its potential as a tool for improving animal health and welfare.

YS wrote the manuscript and WP edited, reviewed, and approved the manuscript for publication.