Exploring the Immune-Boosting Functions of Vitamins and Minerals as Nutritional Food Bioactive Compounds: A Comprehensive Review.

Food components have long been recognized to play a fundamental role in the growth and development of the human body, conferring protective functionalities against foreign matter that can be severe public health problems. Micronutrients such as vitamins and minerals are essential to the human body, and individuals must meet their daily requirements through dietary sources. Micronutrients act as immunomodulators and protect the host immune response, thus preventing immune evasion by pathogenic organisms. Several experimental investigations have been undertaken to appraise the immunomodulatory functions of vitamins and minerals. Based on these experimental findings, this review describes the immune-boosting functionalities of micronutrients and the mechanisms of action through which these functions are mediated. Deficiencies of vitamins and minerals in plasma concentrations can lead to a reduction in the performance of the immune system functioning, representing a key contributor to unfavorable immunological states. This review provides a descriptive overview of the characteristics of the immune system and the utilization of micronutrients (vitamins and minerals) in preventative strategies designed to reduce morbidity and mortality among patients suffering from immune invasions or autoimmune disorders.

The effects of a fermented rapeseed meal or/and soybean meal additive on the blood lipid profile and immune parameters of piglets and on minerals in their blood and bone.

The aim of the study was to assess the effect of the inclusion of dried fermented soybean and/or rapeseed meal in piglet feed on immune parameters, blood lipid parameters, and mineral content in the blood and metacarpal bones. The study was conducted on 150 28-day-old piglets divided into 5 groups. Piglets in the control group (C) received a standard diet with soybean meal. Animals in group FR (group receiving a diet with 8% FRSM) received a diet in which a portion of the soybean meal was replaced with 8% dried fermented rapeseed meal (FRSM). Animals in group FR/FS received a diet in which a portion of the soybean meal was replaced with 6% FRSM and 2% fermented dried soybean meal (FSBM). The piglets in group FS/FR received a diet with 6% FSBM and 2% FRSM. Group FS received a diet in which a portion of the soybean meal was replaced with an 8% share of FSBM. The inclusion of 8% or 6% fermented rapeseed meal (group FR or FR/FS) in the diet of piglets had a beneficial effect on their immune status, as evidenced by the increase in plasma levels of IgG and IgA and the decrease in IL-6 relative to the control group. It also significantly increased the concentrations of minerals, i.e. P, Ca and Zn, in the blood plasma and metacarpal bones of piglets and improved the availability of iron, a key bioelement involved in haemoglobin. The use of 8% or 6% fermented soybean meal in the diet (groups FS and FS/FR) of piglets had a positive effect on blood lipid parameters, reducing CHOL and LDL-cholesterol in the plasma. In conclusion, the fermentation process enables better utilization of rapeseed or soybean meal by pigs. Dried fermented rapeseed meal could partially replace protein components from GMO (genetically modified ogranism) crops (soybean meal) used in diets for pigs.

NUTRITION AND HEALTH: COMPANION ANIMAL APPLICATIONS: Functional nutrition in livestock and companion animals to modulate the immune response.

Advances in the understanding of how the immune system functions in response to diet have altered the way we think about feeding livestock and companion animals on both the short (weeks/months) and long-term (years) timelines; however, depth of research in each of these species varies. Work dedicated to understanding how immune function can be altered with diet has revealed additional functions of required nutrients such as vitamins D and E, omega-3 polyunsaturated fatty acids (PUFA), and minerals such as zinc, while feed additives such as phytogenics and probiotics add an additional layer of immunomodulating potential to modern diets. For certain nutrients such as vitamin D or omega-3 PUFA, inclusion above currently recommended levels may optimize immune function and reduce inflammation, while for others such as zinc, additional pharmacological supplementation above requirements may inhibit immune function. Also to consider is the potential to over-immunomodulate, where important functions such as clearance of microbial infections may be reduced when supplementation reduces the inflammatory action of the immune system. Continued work in the area of nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in both livestock and companion animals. This review collects examples from several species to highlight the work completed to understand how nutrition can be used to alter immune function, intended or not.

Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1.

Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1ß by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs.

Effects of Long-Term Mineral Block Supplementation on Antioxidants, Immunity, and Health of Tibetan Sheep.

Tibetan sheep have been observed with mineral deficiencies and marginal deficiencies in Qinghai-Tibetan Plateau. Adequate amounts of essential minerals are critical to maximize the productivity and health of livestock. The objectives of this study were to evaluate the effects of 6 months of mineral block supplementation on the antioxidants, immunity, and health of Tibetan sheep. The study was conducted in Qinghai-Tibetan Plateau. The consumed values of mineral blocks were measured. Blood samples were collected at the end of the experiment to evaluate the trace elements, malondialdehyde (MDA) and glutathione (GSH) activities, and antioxidant enzyme activities. Additionally, levels of IgA, IgG, IgM, IL-2, IL-12, tumor necrosis factor-α (TNF-α), triiodothyronine (T3), tyroxine (T4), and insulin-like growth factor-1 (IGF-1) were determined. The toxic effects of the mineral block were also monitored. For Tibetan sheep, the average consumed value of mineral block was 13.09 g per day per sheep. Mineral block supplementation significantly increased the serum levels of Mn, Fe, and Se (P < 0.01), decreased the level of MDA (P < 0.05), and increased GSH activity (P < 0.05). Additionally, the mineral block-treated sheep blood had greater total antioxidative capacity (T-AOC) and total superoxide dismutase (T-SOD) activities (P < 0.01 or P < 0.05) than control sheep. Moreover, the mineral block supplementation improved the levels IgA, IgM, and IGF-1 (P < 0.01 or P < 0.05). Additionally, there were no significant histopathological changes in the organs of Tibetan sheep after long-term treatment with the mineral block. The results demonstrated that the mineral block was non-toxic and safe; the protective effects of the mineral block might be caused by an increase in the antioxidant defense system, as well as an increase in the benefits from immunity-related parameters.

Correlation of the composition of biominerals with their ability of stimulating intracellular DNA sensors and inflammatory cytokines.

Biominerals (or microcalcification) deposited in soft tissues are associated with a number of pathogeneses and cancer progressions. Biominerals have also shown promise for DNA delivery and tissue engineering. Biominerals themselves may stimulate NALP3 inflammasomes, and DNA delivered by biominerals can potentially engage with intracellular DNA sensors, resulting in unwanted inflammatory responses. In this study, a library of biominerals doped with or without DNA is formed through surface-induced biomineralization. It is demonstrated that empty biominerals stimulate NALP3 inflammasomes and induce the production of IL-1ß. They are also able to activate mouse embryonic fibroblasts (MEFs) and induce inflammatory cytokines, i.e. IL-6. DNA delivered by biominerals escapes the detection of TLR9, but activates DAI and inflammasomes. Furthermore, it is shown that the level of both IL-1ß and IL-6 is correlated with the composition of biominerals, in particular the ratio of Mg(Sr) to Ca, and the pH sensitivity of biominerals. These results provide insights into the design of safe and effective DNA delivery systems and biocompatible implants as well as the understanding of the pathogeneses of biominerals deposited in soft tissues.

An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

How minerals may influence the development and expression of immunity to endoparasites in livestock.

This review attempts to explain how dietary mineral intake may affect the immune system, with particular reference to gastrointestinal nematode infestations of livestock, and considers its significance for other gut infections as well as for other species. Of the 56 minerals found in mammalian tissues, 16 are currently considered to be essential, and a further 13 probably essential, for cell and tissue function. To date, eight of these have been shown to affect the function of the mammalian immune system directly. Nine others have roles in physiological pathways such as neurological or endocrine function, or protein or carbohydrate metabolism, which in turn regulate the immune system. The remainder may in the future be shown to have immunologically specific roles. The pathogenesis of mineral effects on immunity involves a number of pathways and molecular mechanisms. Major areas requiring further investigation are the relationship between deficiency of minerals and in vivo immune-mediated protection against disease, in particular diseases of the mucosa, and the mechanisms by which the minerals or their deficiency exert their effect on immunity. Research is also required into the possibility that animals in the process of acquiring gut immunity have higher requirements for minerals.

Influence of stress and nutrition on cattle immunity.

Today, the scientific community readily embraces the fact that stress and nutrition impact every physiologic process in the body. At last, the specific mechanisms by which stress and nutrition affect the immune function are being elucidated. The debate among animal scientists concerning the definition and quantification of stress as it relates to animal productivity and well-being is ongoing. However, an increased appreciation and understanding of the effects of stress on livestock production has emerged throughout the scientific community and with livestock producers. The intent of this article is to provide an overview of the general concepts of stress and immunology, and to review the effects of stress and nutrition on the immune system of cattle.

Nutrition and immune function.

The complexity of the immune system allows for a multitude of potential avenues for nutrient modulation, but this also increase the challenge of producing a predictable in vivo response. Because the immune response is a cascade of biologic events, development of nutritional support paradigms cannot and should not be made in a vacuum or with the expectation of a singular response. It is absolutely imperative that the clinician/nutritionist understand the differences in metabolIc and physiologic responses to disease states (ie, shock, trauma, organ-specific dysfunction) so as to maximize immunocompetence through specialized feeding practices. This level of understanding is invaluable, especially when considering the possible benefit of nutrient combinations for immunomodualtion.

Immunostimulatory effects of the anionic alkali mineral complex Barodon on equine lymphocytes.

Previous studies have shown that the anionic alkali mineral complex BARODON has an immunoenhancing effect on pigs as an adjuvant and as a nonspecific immunostimulant. Likewise, the equine immune system has been defined with various monoclonal antibodies specific to equine leukocyte differentiation antigens to determine the possibility of enhancing equine resistance to respiratory diseases and promoting other immunostimulatory effects with the application of BARODON. Compared with the control group, after 3 weeks of treatment, BARODON-treated groups showed higher proportions of cells (P < 0.05) expressing major histocompatibility complex class II and CD2, CD4(+), CD4(+) CD25(+), CD8(+), and CD8(+) CD25(+) T lymphocytes, dendritic cells, and surface immunoglobulin M(+) B lymphocytes in peripheral blood, as well as enhanced cell proliferative responses with phytohemagglutinin and increased phagocytic activity against Streptococcus equi and Staphylococcus aureus strains with high antibiotic resistance, the bacteria frequently identified as etiologic agents of equine respiratory diseases at the Seoul Race Park in Seoul, Korea. This study shows that BARODON may act as an immunostimulator and can be an effective alternative to antimicrobial feed additives for nonspecific improvements in equine immune responses, particularly against respiratory diseases.

Host immune responses against hog cholera virus in pigs treated with an ionized alkali mineral complex.

To determine the immune responses in pigs to hog cholera virus after treatment with an ionized alkali mineral complex (IAMC), 40 healthy pigs (28-32 days old) from a commercial swine farm were purchased and housed into 4 groups (n=10 each). All pigs were vaccinated intramuscularly (1 ml) with an attenuated live hog cholera virus (HCV, LOM strain) at 28-32 days old and challenged with a virulent hog cholera virus at 8 weeks after vaccination. Each group was treated with PowerFeel sprayed diet as 0.05% (w/w) in a final concentration (T-1, n=10), a diet mixed with SuperFeed as 3% (w/w) in a final concentration (T-2, n=10), or a diluted PowerFeel solution (1:500, v/v) as drinking water (T-3, n=10), respectively. A group (n=10) served as a non-treated control. Proportions of expressing CD2+ and CD8+ cells increased significantly (p<, 0.05) at 8-week post-application. Mean antibody titers of each group against HCV gradually increased to higher levels after vaccination and with challenge of the virulent virus. In conclusion, the IAMC-treated diets can be helpful for the improvement of growth in pigs with proper vaccination program, while the IAMC-treated diets have no effects on the clinical protection against hog cholera.

Host Immune Responses Against Hog Cholera Virus in Pigs Treated with an Ionized Alkali Mineral Complex

To determine the immune responses in pigs to hog cholera virus after treatment with an ionized alkali mineral complex (IAMC), 40 healthy pigs (28-32 days old) from a commercial swine farm were purchased and housed into 4 groups (n=10 each). All pigs were vaccinated intramuscularly (1 ml) with an attenuated live hog cholera virus (HCV, LOM strain) at 28-32 days old and challenged with a virulent hog cholera virus at 8 weeks after vaccination. Each group was treated with PowerFeelTM sprayed diet as 0.05% (w/w) in a final concentration (T-1, n=10), a diet mixed with SuperFeedTM as 3% (w/w) in a final concentration (T-2, n=10), or a diluted PowerFeelTM solution (1:500, v/v) as drinking water (T-3, n=10), respectively. A group (n=10) served as a non-treated control. Proportions of expressing CD2+ and CD8+ cells increased significantly (p<, 0.05) at 8-week post-application. Mean antibody titers of each group against HCV gradually increased to higher levels after vaccination and with challenge of the virulent virus. In conclusion, the IAMC-treated diets can be helpful for the improvement of growth in pigs with proper vaccination program, while the IAMC-treated diets have no effects on the clinical protection against hog cholera.

Elite athlete immunology: importance of nutrition.

Immunosuppression in athletes involved in heavy training is undoubtedly multifactorial in origin. Training and competitive surroundings may increase the athlete's exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, improper nutrition can compound the negative influence of heavy exertion on immunocompetence. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. The poor nutritional status of some athletes may predispose them to immunosuppression. For example, dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and B vitamins is particularly important but the dangers of over-supplementation should also be emphasized; many micronutrients given in quantities beyond a certain threshold will in fact reduce immune responses and may have other toxic effects that are detrimental to health. Although it is impossible to counter the effects of all of the factors that contribute to exercise-induced immunosuppression, it has been shown to be possible to minimize the effects of many factors. Athletes can help themselves by eating a well-balanced diet that includes adequate protein and carbohydrate, sufficient to meet their energy requirements. This will ensure a more than adequate intake of trace elements without the need for special supplements. Consuming carbohydrate (but not glutamine) during exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immunosuppression. By adopting sound nutritional practice, reducing other life stresses, maintaining good hygiene, obtaining adequate rest and spacing prolonged training sessions and competition as far apart as possible, athletes can reduce their risk of infection.

Nutritional aspects of immunosuppression in athletes.

The literature suggests that a heavy schedule of training and competition leads to immunosuppression in athletes, placing them at a greater risk of opportunistic infection. There are many factors which influence exercise-induced immunosuppression, and nutrition undoubtedly plays a critical role. Misinterpretation of published data and misleading media reports have lead many athletes to adopt an unbalanced dietary regimen in the belief that it holds the key to improved performance. Some sports have strict weight categories, whilst in others low body fat levels are considered to be necessary for optimal performance or seen as an aesthetic advantage. This leads some athletes to consume a diet extremely low in carbohydrate content which, whilst causing rapid weight loss, may have undesirable results which include placing the athlete at risk from several nutrient deficiencies. Complete avoidance of foods high in animal fat reduces the intake of protein and several fat-soluble vitamins. On the other hand, diets with a very high carbohydrate content are usually achieved at the expense of protein. In addition, anecdotal and media reports have often promoted the supposed performance benefits of certain vitamins and minerals, yet most athletes do not realise that micronutrient supplementation is only beneficial when correcting a deficiency, and to date there is little scientific evidence to substantiate claims that micronutrients act as an ergogenic aid. Moreover, excessive intakes of micronutrients can be toxic. Deficiencies or excesses of various dietary components can have a substantial impact on immune function and may further exacerbate the immunosuppression associated with heavy training loads. This review examines the role of nutrition in exercise-induced immunosuppression and the effect of both excessive and insufficient nutrient intake on immunocompetence. As much of the present literature concerning nutrition and immune function is based on studies with sedentary participants, the need for future research which directly investigates the relationship between exercise, training, immunity and nutrition is highlighted.