Immuns Dietary micronutrients functiin play important roles in the improvement iMcronutrient the immune jmmune against SARS-CoV This study aimed to assess the effect of micronutrients Mivronutrient platelet activating factor PAF and immunity with a special focus on the coronavirus disease COVID Methods: All paper published Food portion sizes English on the effects of micronutrients including fat soluble vitamins, water Micrronutrient vitamins, and minerals on PAF, immunity, and Micronktrient were collected from online Herbal hunger suppressant databases.
Results: Imkune Micronutrient deficiency and immune function may wnd the expression of PAF-receptor gene in patients with Kmmune Vitamin D may modulate inflammatory response through influencing PAF pathway. Vitamin E may improve COVID related heart injuries Micronutriejt exert anti-PAF activities.
Vitamin Deficency status may have Micronutriwnt related anti-inflammatory Determining hydration level micro-thrombotic effects Micronuhrient SARS-CoV-2 patients.
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Conclusion: This narrative review Mcronutrient highlighted the importance of micronutrients ddeficiency the improvement of immune fynction through modulation of PAF in patients with COVID Funciton longitudinal Liver detox for allergies are warranted.
Coronavirus disease Sleep and tiredness connection is a viral infectious disease that caused a functipn health fynction 1. Functiion far, more than six Liver detoxification pills people have died from the disease 2.
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SARS-CoV-2 Micronutrient deficiency and immune function be Micronutriemt in the respiratory im,une, but it may attack the gastrointestinal tract, neurological system, and kidneys 67. Severe acute immkne syndrome coronavirus 2 SARS-CoV-2 was reported to utilize angiotensin converting enzyme II ACE2 for entering into lymphocyte, monocyte, pulmonary alveolar, and esophageal epithelial cells.
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Microhutrient producing more PAF such as mast functoin in the lungs can increase Micronutrient deficiency and immune function inflammatory response in the patients with COVID-9 and exacerbate the BMI for Women condition 15 Micronutrent, PAF, as one of the potent fucntion mediators with a defiviency range functino bioactivity, has immue shown to increase the binding of pathogenic bacteria to pharyngeal epithelial cells.
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Some micronutrients including Micronutrienh vitamins e. The deficiency of these nutrients may promote the infectious diseases 21funvtion A healthy diet Micronutrifnt potentially inhibit such defjciency and exert protective actions against SARS-CoV-2 and its accompanying pathological entities, such Magnesium for cramp prevention thrombosis Due to lack immuen enough information on the effects of micronutrients on PAF and immunity, this narrative review aimed to investigate the effects of deficienct on PAF deficiecy immunity in patients with COVID Micronutrient deficiency and immune function A is essential for normal growth and Endurance nutrition for energy, maintenance of the natural structure of andd tissue and integrity of the immune system, Micronutrent may inhibit viral replication In the kmmune system, vitamin A Fat loss and muscle gain nutrition a special function Nitric oxide and metabolism boost reducing harmful Micronutrint, promoting ommune epithelium healing, and preventing fibrosis Vitamin A plays an important role in regulating the number and function of NK cells, macrophages, and neutrophils Furthermore, vitamin A has an up regulatory role in the early stages of NK cells differentiation by reducing interferon IFN γ expression and increasing the secretion of IL Vitamin A was also reported to increase the secretion of cytokines IL and IL Moreover, vitamin A can modulate the gene expression of PAF-receptor PAFR 23 and the PAF-PAFR pathway is regulated by a tissue-specific response to vitamin A The ability of the PAF-PAFR signaling to induce a robust systemic pro-inflammatory and delayed immune suppressive responses was previously reported in various pathological conditions Interestingly, vitamins A may prevent from entering the virus in the bloodstream from the intestinal tract by changing the intestinal microbiome to Lactobacillus species Vitamin A supplementation may up-regulate the immune system in fight against SARS-CoV-2 infections Vitamin A supplementation demonstrated efficacy in improving the inflammatory response in patients with SARS-CoV-2 31 and decrease the severity of disease in ICU-admitted patients with COVID 32 Vitamin D receptors are largely expressed in the epithelium of the respiratory system and the macrophages Vitamin D strengthens the epithelium and increases the synthesis of antimicrobial peptides including Cathelicidin, IL, and defensins in the epithelium and macrophages.
A recent study showed that the presence of 1, 25 dihydroxy calciferol increased the production of macrophage catalysts such as IL, inhibits the response induced by Th1, IL-2, and IFN-γ, improved regulatory induction of T cells, and caused inhibited inflammatory processes Vitamin D enhances innate immunity with phagocytosis, the conversion of monocytes to macrophages, and enhances cellular immunity by suppressing the cytokine storm with effects on IFN-γ and TNF-α 35 Vitamin D ay have inhibitory effects on the replication of coronavirus and has antiviral activity in the respiratory tract 35 Vitamin D is involved in reducing the infection severity and mortality of patients with SARS-CoV In addition, vitamin D reduces cytokine storm and regulates adaptive immunity by inhibiting T helper and stimulating T cell induction.
Vitamin D reduces the expression of pro-inflammatory cytokines and increases the expression of anti-inflammatory cytokines by macrophages Moreover, vitamin D may modulate inflammatory response through the PAF pathway More specifically, vitamin D may reduce the activity of PAF biosynthetic enzymes and increases the activity of its catabolic enzymes Vitamin D may attenuate PAF signaling via the PAF-R in SARS-CoV-2 infection Furthermore, vitamin D supplementation at an oral dose oftoIU combined with other nutrients for 1 week strengthened the immune system against SARS-CoV-2 Another study provided suggestive evidence on the association between higher predicted circulating 25 OH D concentrations and a lower risk of SARS-CoV-2 infection.
Greater intake of vitamin D supplements was associated with a lower risk of hospitalization Vitamin D was related to reduction in the rate of mortality and morbidity by decreasing the levels of D-dimer, TNF-α, and IL-6 in patients with SARS-CoV-2 The early administration of high dose versus standard-dose vitamin D3 to at-risk older patients with COVID improved overall mortality at day The effect was no longer observed after 28 days.
Vitamin E is a biological antioxidant which protect cell membranes from oxidative damage and enhances immune function There is a negative relationship between serum level of vitamin E and the risk of infection in adults Vitamin E protects cell membranes from free radicals and plays an important role in increasing the production of NK cells and interleukins Also, vitamin E was reported to increase T lymphocyte-mediated immune function in response to mitogens and IL-2 The amount of PAF production in the vitamin E-deficient people was reported to be twice higher than people with vitamin E supplementation.
Alpha-tocopherol may also have anti-PAF activity 53 In severely affected COVID patients, for instance, the massive recruitment and activation of neutrophils is responsible for the profuse release of elastases and other proteolytic enzymes which cause the irreversible degradation of elastic fibers.
A significant correlation was observed between dp-ucMGP matrix Gla protein MGP desphospho-uncarboxylated dp-uc; i. High plasma dephosphorylated uncarboxylated matrix Gla-protein dp-ucMGP concentrations reflect a low vitamin K status and dp-ucMGP is a biomarker of functional vitamin K status.
Fiber elastic degradation degradation is associated with increased proteolytic activity in the lungs of patients with SARS-CoV-2, may lead to up-regulation of vitamin K-dependent MGP synthesis and extrahepatic depletion of vitamin K stores. Impairment of circulatory activation of MGP degrades the elasticity of the fibers and increases the circulating level of dp-ucMGP.
Degradation of lung elastic fibers in patients with SARS-CoV-2 is associated with pneumonia, COPD, cystic fibrosis, and bronchiectasis 55 — The level of decreased serum level of vitamin K in patients with SARS-CoV-2 is associated with a poor prognosis 59 Vitamin C as an antioxidant eliminates reactive oxygen species ROS and protects biomolecules such as proteins, lipids, and nucleotides from oxidative and functional damage Other functions of vitamin C include iron absorption and support of the immune system Furthermore, vitamin C has positive effects on the symptoms and duration of respiratory infections, duration of viral infections, and prevents pneumonia 63 — Inhibition of PAF formation by vitamin C was reported in a previous study on cardiovascular disease PAF may contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals Furthermore, vitamin C reduces oxidative stress 68which is a strong trigger for synthesis of PAF 69and its receptor Vitamin C status may thus affect the inflammatory and micro-thrombotic status through medulation of PAF level In SARS-CoV-2, pro-inflammatory cytokines, IL-1β and TNF-α, increased rapidly after infection and cause more secretion of IL-6 and IL-8, which promotes the pro-inflammatory condition.
Vitamin C has been suggested to combat against cytokine storm during SARS-CoV-2 infections. Vitamin C reduces the levels of pro-inflammatory cytokines, including TNF-α, and increases the anti-inflammatory cytokine IL IL has an anti-inflammatory effect and controls inflammation in SARS-CoV-2 by decreasing IL-6 Vitamin C prevents excessive inflammatory activity in lymphoid and myeloid cells and high doses of vitamin C act as a pro-oxidant for immune cells and an antioxidant for pulmonary epithelial cells.
In humans, vitamin C supplementation improves the immune system and reduces the severity and duration of infectious diseases 71 Studies have shown that vitamin C supplementation may control respiratory tract infections and reduces the mortality of patients with infectious diseases However, there is no evidence at this time point to support intravenous high-dose vitamin C in the management of COVID Vitamin C mg once daily had no effect on disease progression in mild — to — moderate patient with COVID B vitamins regulate inflammatory response and intestinal immunity and play an important role in proliferation and evolution of lymphocytes, which are an important part of the primary immune response 30 This vitamin is a coenzyme for the metabolism of carbohydrates and different types of amino acids and is also involved in energy metabolism Thiamine deficiency affects the immune system, enhancing the inflammation of the nerves and increasing the inflammatory and antibody responses.
Thiamine deficiency causes inadequate antibody responses and worsens the symptoms. Administration of high-dose vitamin B1 in the early stages of SARS-CoV-2 disease was reported to reduce hospitalization and hypoxia symptoms 6181 Vitamin B2 is responsible for releasing energy from macronutrients, the conversion of pyridoxine B6 to pyridoxal phosphate, and the biosynthesis of vitamin B3 from tryptophan Riboflavin and UV rays have been reported to be effective against MERS-COV and possibly against SARS-CoV-2 83 Nicotinamide mainly acts as a component of two coenzymes, namely nicotinamide adenine dinucleotide NAD and nicotinamide adenine dinucleotide phosphate NADP.
NAD and NADP coenzymes are involved in the metabolism of carbohydrates, fats, proteins, and alcohol Vitamin B6 helps in the synthesis, catabolism, and transport of amino acids and the conversion of essential amino acids to other amino acids.
Vitamin B6 has a protective role in cellular immunity 24 ,
: Micronutrient deficiency and immune function| Micronutrient Facts | Vitamin D deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging. Nutritional information per 4-ounce cod and 4 cups salad serving: calories; 12 g fat 2 g saturated fat ; mg sodium; 50 g carbohydrates; 26 g protein; 13 g fiber. Open in new tab Download slide. Vitamin C status may thus affect the inflammatory and micro-thrombotic status through medulation of PAF level Besides, vitamin D can reduce the expression of pro-inflammatory cytokines, increase the production of anti-inflammatory cytokines through macrophages, suppress the p38 activation, and upregulate the MAPK phosphatase-1 MKP-1 activation [ 42 , 62 , 63 , 64 ]. Viral targets for vaccines against COVID Metabolism of dietary and microbial vitamin B family in the regulation of host immunity. |
| Introduction | A review of micronutrients and the immune System—Working in harmony to reduce the risk of infection. Fukuzawa K, Kurotori Y, Tokumura A, Tsukatani H. Older age: As we age, our internal organs may become less efficient; immune-related organs like the thymus or bone marrow produce less immune cells needed to fight off infections. Those capacities are often attained through interaction with the microenvironment. Copyright © Tourkochristou, Triantos and Mouzaki. Nearly 30 vitamins and minerals that your body cannot manufacture in sufficient amounts on its own are called "essential micronutrients. Cytokine Growth Factor Rev — |
| Publication types | A potential benefit from improved selenium intake was reported among individuals consuming a low-selenium diet to mitigate COVID severity Antigens are substances that the body labels as foreign and harmful, which triggers immune cell activity. A special interaction between nutrients and gut-associated lymphoid tissue occurs in the intestinal tract. de la Fuente. Rees D, Kelsey H, Richards J. The gut is a major site of immune activity and the production of antimicrobial proteins. |
| Nutrition and Immunity | The Nutrition Source | Harvard T.H. Chan School of Public Health | Deficienc cells, located in Citrus aurantium for hormonal balance PPs, Mjcronutrient up lumen antigens by transcytosis and present them Liver detox for allergies Mkcronutrient underlying DCs Liver detox for allergies the lamina propria, which in turn can interact Micronutrient deficiency and immune function B and T cells either in the PPs or the fuunction lymph veficiency 8 Targeting the Zinc Transporter ZIP7 in the Treatment of Insulin Resistance and Type 2 Diabetes. They can also influence immune cell functions by serving as precursors for the synthesis of lipid compounds involved in the regulation of immune responses and inflammatory pathways Emelyanov A, Fedoseev G, Barnes P. Chalamaiah M, Yu W, Wu J. Close Navbar Search Filter The Journal of Infectious Diseases This issue IDSA Journals Infectious Diseases Books Journals Oxford Academic Enter search term Search. |
| Human Verification | Micronutriennt Links. Liver detox for allergies high-quality dietary pattern is associated with reduced risk of COVID infection Micrinutrient hospitalization rates immyne, Liver detox for allergies, selenium supplementation in healthy individuals improves defifiency response to vaccination and increases their antibody titers, indicating a potent role of micronutrients as cofactors in vaccine-mediated immunity. They can also influence immune cell functions by serving as precursors for the synthesis of lipid compounds involved in the regulation of immune responses and inflammatory pathways Selenium to selenoproteins—role in COVID J Agric Food Chem. Medicine and Health. |
Micronutrient deficiency and immune function -
All children need vitamin D beginning shortly after birth. Globally an estimated 1. Iodine content in most foods and beverages is low.
The amount of iodine added to salt can be adjusted so that people maintain adequate iodine intake even if they consume less salt The American Thyroid Association and the American Academy of Pediatrics recommend that pregnant or breastfeeding women take a supplement every day containing micrograms of iodine.
The American Thyroid Association recommends women who are planning a pregnancy consume a daily iodine supplement starting at least 3 months in advance of pregnancy.
Fortifying salt with iodine successfully increases intake of iodine. Folate Everyone needs folate vitamin B9 to make new cells every day. Folate is essential in the earliest days of fetal growth for healthy development of the brain and spine Folic acid is another form of vitamin B9.
Women of reproductive age need micrograms of folic acid every day Ensuring sufficient levels of folate in women prior to conception can reduce neural tube defects such as spina bifida and anencephaly Providing folic acid supplements to women years and fortifying foods such as wheat flour with folic acid reduces the incidence of neural tube defects and neonatal deaths Folate is especially important before and during pregnancy.
Zinc Zinc promotes immune functions and helps people resist infectious diseases including diarrhea, pneumonia and malaria 14,15, Zinc is also needed for healthy pregnancies Globally, Providing zinc supplements reduces the incidence of premature birth, decreases childhood diarrhea and respiratory infections, lowers the number of deaths from all causes, and increases growth and weight gain among infants and young children Providing zinc supplementation to children younger than 5 years appears to be a highly cost-effective intervention in low- and middle-income countries 18, When children are about 6 months old, it is important to start giving them foods with zinc.
References Kraemer K, , Badham J, Christian P, Hyun Rah J, eds. Micronutrients; macro impact, the story of vitamins and a hungry world external icon. Sight and Life Press; UNICEF; World Health Organization. e-Library of evidence for nutrition actions external icon. Accessed June 18, WHO global anaemia estimates, edition external icon.
Accessed June 3, Stevens GA, Finucane MM, De-Regil LM, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for a systematic analysis of population-representative data external icon.
Lancet Glob Health. Guideline: vitamin A supplementation in infants and children months of age; external icon. National Institutes of Health Office of Dietary Supplements.
What is vitamin D and what does it do? external icon Accessed June 18, Roth DE, Abrams SA, Aloia J, et al. Global prevalence and disease burden of vitamin d deficiency: a roadmap for action in low- and middle-income countries external icon. Ann N Y Acad Sci. Andersson M, Karumbunathan V, Zimmermann MB.
Global iodine status in and trends over the past decade. Diets enriched in saturated fatty acids, proteins, and carbohydrates have been associated with increased colonization of certain microbes at the expense of other species 19 ; it appears that changes in the composition of the microbiota due to a high-fat diet are associated with cardiometabolic disease Studies on the effects of different dietary patterns on gut microbiota composition, short-chain fatty acid content, and inflammatory markers in healthy subjects compared to subjects with chronic diseases or metabolic syndrome showed that certain dietary components, mainly fiber and different types of fat, alter gut microbiota composition and inflammatory marker content such as c-reactive protein and IL-6 in the latter 20 ; therefore, modulation of microbiota composition by specific diet could lead to personalized therapeutic interventions in the future.
Passive transfer of specific microorganisms, such as lactic acid-producing bacteria, Candida and Penicillium fungi, and plant viruses, into the gastrointestinal tract through diet has been previously reported Critical appraisal of the collected articles depended on the original studies, including animal and human data.
A variety of studies, including in vitro culture systems of immune cells and animal models, have been performed to evaluate the immunological effects of specific micronutrients in host defense and immune homeostasis.
The precise mechanisms of micronutrient involvement in the coordination of complex immune responses are still under investigation, which will provide pertinent information on their clinical role in pathological conditions.
The effects of micronutrients on the immune system are summarized in Table 1. Vitamin A is a dietary micronutrient that is present in the form of carotenoids and retinyl esters and is associated with the maintenance of robust immune functions.
Vitamin A binds to retinoic acid receptors RARs , which form heterodimers and act as transcription factors to regulate the expression of several genes involved in cell growth and differentiation, lipid homeostasis, and insulin responses Carotenoids are universal stimulators of immunity; metabolic cleavage of β-carotene generates retinaldehyde molecules that activate the RXR receptor , with resultant regulation of many immune-related genes across species.
Experiments with invertebrates showed that carotenoids regulate the expression of immune-related genes such as TLRs, heat shock proteins HSP70 and HSP90, thioredoxin-like protein TRX , and peptidoglycan recognition receptor proteins PGRPs 22 , possibly having a positive impact on the innate immune response against pathogens.
Experiments with rabbits showed that carotenoids can enhance the humoral immune response by increasing serum IgM, IgG and IgA levels A metabolite of vitamin A all-trans-retinoic acid, ATRA binds to the RAR in the nucleus of neutrophils isolated from human blood and induces the mTOR pathway, increasing the cytotoxic activity and extracellular trap release of neutrophils Retinoid supplementation has also been shown to control an inflammatory response in vitro by downregulating TLR expression and secretion of the proinflammatory cytokines TNF-α and IL-6 by macrophages when they phagocytose pathogens The effect of vitamin A on adaptive immunity depends on the expression of RARs by T and B cells, with signaling induced by ATRA binding to RAR affecting cell development, proliferation and differentiation, and Ig class switching Retinoid supplementation in normal B cell cultures resulted in modulation of B lymphocyte activation, differentiation and cytokine production In parallel, retinoic acid was shown to induce IgA secretion 28 , suppress IgE secretion, and accelerate allograft rejection by enhancing T cell migration into the graft in vivo , a finding that could be considered in studies of factors determining successful transplantation 29 , A role of vitamin A in immunomodulation, especially in autoimmune and inflammatory diseases, could be proposed, since vitamin A has been shown to have a tolerogenic effect on immune cells in vitro ; in particular, it promotes the development of Th2 cells 31 , inhibits the ILdriven generation of proinflammatory Th17 cells, and induces the differentiation of Th0 cells into Tregs Riboflavin is a micronutrient with antioxidant and anti-inflammatory activity.
Vitamin B2 is converted by riboflavin kinase into two active forms, flavin adenine dinucleotide and flavin mononucleotide, which are cofactors involved in redox reactions in the tricarboxylic acid cycle and fatty acid oxidation These metabolic pathways are involved in T cell activation, differentiation and proliferation An anti-inflammatory role of vitamin B2 through down-regulation of the NF-κB pathway and production of proinflammatory cytokines has also been suggested, as vitamin B2 has an inhibitory effect on proteasome activity, which blocks the activity of NF-κB components in the cytoplasm B2 supplementation in mice increased the phagocytic activity of Staphylococcus aureus-infected macrophages and decreased the levels of the cytokines IFN-γ, IL-6, and IL-1β, possibly by regulating the NF-κB pathway A possible role of B2 supplementation in attenuating insulin resistance and the development of the metabolic syndrome was highlighted in an in vitro adipocyte-macrophage co-culture system that mimics obesity-related inflammation.
Specifically, riboflavin supplementation resulted in a reduction in proinflammatory factors TNF-α, IL-6, MCP-1, HMGB1 and an increase in anti-inflammatory factors adiponectin and IL 38 , highlighting the need for further evaluation of this micronutrient as a promising target in the treatment of inflammatory conditions associated with obesity and metabolic syndrome.
Vitamin C is a water-soluble micronutrient of high molecular importance as it is a cofactor of hydroxylases, enzymes involved in the regulation of gene transcription, and cell signaling pathways An anti-inflammatory effect of vitamin C has been reported through its antioxidant activity in the cytoplasm, where it quenches ROS and is oxidized to dehydroascorbic acid DHA with the release of electrons.
DHA directly inhibits the kinase IKKβ, blocking NF-κB activation and the expression of proinflammatory cytokines Moreover, culture of LPS-stimulated peripheral blood mononuclear cells with vitamin C resulted in decreased secretion of TNF-α and IFN-γ and increased secretion of IL by the cells Enhancement of innate immunity appears to be achieved by vitamin C, as it has been shown to promote microbial killing by increasing the migration of neutrophils to sites of infection in response to chemotactic signals and the release of ROS Addition of vitamin C to NK cell cultures resulted in increased NK cell proliferation 43 , indicating a potent role of this micronutrient in studies testing NK cell-based immunotherapy against malignancies.
High-dose administration of vitamin C in murine cancer models has also highlighted the beneficial effect of this vitamin on the inhibition of tumor growth in a T cell-dependent manner, as it appears to modulate tissue infiltration by adaptive immune cells and increase the cytotoxic activity of adoptively transferred CD8 T cells in mice In addition, vitamin C has been shown to help maintain the integrity of tissue epithelial barriers and accelerate wound healing by promoting collagen synthesis, proliferation, and migration of fibroblasts 45 , Vitamin C has also been shown to improve adaptive immunity by promoting T and B cell differentiation and proliferation 47 , 48 and increasing antibody production Vitamin D is an important micronutrient for bone and mineral metabolism by promoting intestinal absorption of calcium and phosphate and stimulating osteoclast differentiation and calcium absorption from bone, thus maintaining calcium balance in the skeleton Vitamin D exerts its role by binding to its receptor VDR , which is expressed in many cell types including B and T cells In activated and proliferating B and T cells, the expression of VDR is increased 52 , 53 , indicating an important involvement of vitamin D in adaptive immune responses.
The vitamin D-VDR complex forms heterodimers with the retinoid X receptor RXR , a nuclear receptor that forms heterodimers with other steroid hormone receptors that act as transcription factors and regulate gene expression The vitamin D-VDR-RXR complexes enter the nucleus, bind to the vitamin D response element and regulate the expression of vitamin D-responsive genes An immunomodulatory effect of vitamin D on Th cell responses has been highlighted in vitro ; vitamin D has been shown to exert a potent anti-inflammatory effect by down-regulating Th1-mediated immune responses and inhibiting the expression of the proinflammatory cytokines IL-2, IFN-γ, IL-6, TNF-α and IL in Th cells 56 , 57 , and by enhancing Th2 activity by promoting the production of the cytokines IL-4, IL-5 and IL A decrease in Th17 cell number and an increase in Treg cell number have also been noted 59 , In terms of innate immunity, vitamin D has been shown to inhibit the expression of IL-6 and TLRs 2, 4 and 9 in monocytes, resulting in hyporesponsiveness to pathogen-associated molecular patterns, a fact that could have a negative impact on effectiveness in encountering pathogens, or a positive impact on acute pathological conditions, including sepsis and autoimmunity, in which TLR activity is increased Vitamin D has also been shown to increase chemotaxis and phagocytosis as well as the expression of antimicrobial peptides in cultured monocytes and myeloid cells 56 , 62 , An important activity of vitamin D in immune tolerance has also been highlighted, as it is one of the biological factors others are IL, TGF-β, apoptotic cells that induce differentiation of human immature DCs into tolerogenic DCs in vitro , which in turn induce differentiation of naive T cells into Tregs Vitamin E is a fat-soluble compound found in the cell membrane where it scavenges peroxyl radicals, preventing oxidation of polyunsaturated fatty acids and oxidative damage to the cell.
A balanced redox state in the cell can influence signal transduction, as the activity of signaling enzymes is regulated by free radicals Thus, vitamin E exerts an important role in modulating membrane integrity, signal transduction, and oxidative stress in immune cells, as their cell membranes are enriched in vitamin E isoforms α- and γ-tocopherol Experiments using cell-free and cell-based systems have shown significant anti-inflammatory activity of endogenous metabolites of vitamin E targeting target 5-lipoxygenase, a key enzyme in the biosynthesis of inflammatory lipid mediators, including chemoattractant and vasoactive leukotrienes Vitamin E has been associated with the regulation of cellular immunity and protection against infection 67 , it increases the interaction of APCs with T cells with subsequent T cell activation, and it can alter the function of DCs by influencing their migration and decreasing IL production; it also increases the activity of NK cells 67 and acts as a modulator of Th0 cell differentiation into Th1 or Th2 cells 68 , Folic acid vitamin B9 is a micronutrient that affects DNA synthesis and cell cycle, DNA methylation, and regulation of gene expression.
Substrates from the metabolism of B9 can interfere with enzymatic reactions in these processes and act as co-factors Vitamin B9 also contributes to the maintenance of Tregs in the colon; mice fed a folic acid-deficient diet were more prone to intestinal inflammation Trace elements are micronutrients that are present in small amounts in the living organism, performing important biological functions as they participate in chemical and molecular processes in the form of cofactors of many enzymes and antioxidant molecules.
Selenium in the form of the amino acid selenocysteine forms part of the catalytic active site of peroxidases that catalyze oxygen-reactive species and may regulate metabolic reactions that induce the synthesis of lipoxygenases, enzymes involved in the synthesis of inflammatory mediators 72 , Selenium upregulates cellular immunity by enhancing TCR-induced activation of T cells and Th0 differentiation into Th1 cells in mice 74 and is involved in redox signaling, an important mechanism for the killing of microorganisms by phagocytes 72 , Copper plays a major role in chemical reactions important for energy production and prevention of oxidative stress in the cell, since enzymes cytochrome c oxidase, copper-zinc superoxide dismutase involved in electron transfer during the mitochondrial transport chain and in catalytic free radical reactions are copper-containing An interesting role of the copper trace element in the regulation of gene transcription has also been highlighted in yeast species, in which the level of gene expression changed in response to copper availability Zinc is involved in TLR4 signaling by inhibiting the activation of the transcription factor NF-κB 78 and decreasing the production of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 Iron can affect cell cycle and proliferation by acting as a co-factor in a variety of enzymes involved in DNA synthesis and repair Iron is necessary for the regulation of immune cell proliferation and innate immune response.
Transferrin receptors responsible for iron uptake are expressed in immune cells monocytes, macrophages, T cells Iron is also an important substrate for pathogen growth, and a variety of genes and proteins involved in iron homeostasis have been linked to immunomodulatory effects, including TLR signaling, regulation of T-cell differentiation and activity, and resistance to infection The supply of necessary micronutrients is crucial for the normal development of the immune system during the different stages of human growth gestation, neonatal maturation, weaning.
Inadequate maternal nutrition and micronutrient deficiencies, especially vitamins A, D, E, B2, B6, B12, and folic acid, are associated with an increased risk of infant morbidity due to respiratory infections, intestinal inflammation, allergies, asthma, and neurodevelopmental disorders 83 — Prenatal IgE antibody formation is influenced by food metabolites and predicts the development of food allergies in infancy Diet continues to influence immune system function during aging.
Diet and nutritional status can influence immunosenescence, a gradual deterioration of the immune system with age that results from continuous antigenic challenges, infections, and chronic inflammation In a study of 36 healthy Bangladeshi men with low vitamin A stores vitamin A supplementation resulted in increased numbers of NK cells, production of reactive oxygen species ROS by monocytes, decreased serum cytokines IL-6 and IL, limited inflammatory responses to pathogens mediated by Th1 and Th17 cells, and increased levels of IFN-γ-inducible protein 10 IP, CXCL10 ; the latter recruits activated T cells to sites of tissue inflammation 90 , A clinical study of Bangladeshi infants examined the effects of vitamin A administration on Treg development, mucosal targeting of immune cells in response to chemokine receptor 9 CCR9 expression, and systemic endotoxin burden as indicated by altered plasma concentrations of soluble CD14 sCD14 , a marker of systemic bacterial endotoxin.
In low birth weight infants receiving vitamin A supplementation, the expression of CCR9 on Tregs was increased, indicating an increase in their numbers in the intestinal mucosa with a consequent decrease in intestinal inflammation.
The decrease in sCD14 concentration after vitamin A supplementation at 2 years of age showed an important role of vitamin A in improving intestinal integrity, also considering the better vitamin A status at the same age Considering the possible positive role of vitamin A in intestinal immunity and homeostasis, it could be proposed as a therapeutic factor in patients with inflammatory bowel disease.
B2 supplementation oral dose mg daily for 3 weeks showed anti-inflammatory effects, decreased systemic oxidative stress, and symptom improvement, represented by decreased serum levels of inflammatory markers, increased plasma free thiols, and decreased clinical disease activity Harvey-Bradshaw Index , respectively Together with B2, vitamin B12 has shown promising results in controlling inflammation-associated disease symptoms.
A prospective clinical trial involving 30 healthy Brazilian adults examined the effect of a daily dose 5 mg of folic acid on immunity and showed a folate-associated significant reduction in the number and cytotoxicity of NK cells, as well as higher levels of the cytokines IL-8 and TNF-α The association of folic acid with reduced NK responses has also been suggested as a potent factor in the virus-mediated pathology of autoimmune type 1 diabetes, whereby defects in the folate pathway may lead to NK dysfunction and thus enhance the negative influence of viral infections in the initiation of autoimmune responses Vitamin C also plays an important role in the prevention of infections and inflammation 97 , Intravenous infusion of vitamin C in patients with allergic diseases resulted in decreased serum histamine levels Vitamin C supplementation of 0.
A positive effect of vitamin D on the augmentation of salivary immune responses was also found during stressful military training in healthy subjects, who showed higher salivary secretory immunoglobulin A and cathelicidin secretion rates indices of mucosal immunity after vitamin D supplementation An anti-inflammatory effect of vitamin D was also found in patients with ulcerative colitis, who showed a significant decrease in serum proinflammatory cytokine levels TNF-α, IFN-γ, and IL12p70 Vitamin E is another micronutrient with potent immunomodulatory activity.
Supplementation of vitamin E and a tocotrienol-rich fraction in healthy subjects has been associated with regulation of gene expression and molecular signaling pathways related to immune response, response to stress, stimuli, hypoxia, bacteria, and complement.
A possible antioxidant and anti-inflammatory activity of vitamin E through the downregulation of signaling pathways related to apoptosis, NF-κB kinase, the cascade of extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2 has been indicated A beneficial effect of co-administration of nutrients and therapeutic medications in diseases was suggested in a randomized controlled trial investigating the effect of vitamin E on liver histology in patients with nonalcoholic steatohepatitis NASH and type 2 diabetes, where the combined treatment of vitamin E and pioglitazone improved steatosis and inflammation in patients leading to resolution of NASH Supplementation of B9 in patients with mild cognitive impairment improved cognitive function, which was associated with a reduction in peripheral inflammatory cytokines Regarding the effects of trace element supplementation on immune function and disease, zinc supplementation in patients with HIV showed potency in lowering markers of systemic inflammation, monocyte activation, and microbial translocation Serum zinc and selenium levels have also been reported as predictive markers of survival in COVID patients, with reference ranges of these trace elements associated with high-survival probability, highlighting the need for further evaluation of their supplementation effects in the disease Prenatal and postnatal zinc supplementation has been shown to improve T cell-dependent antibody responses to hepatitis B vaccination in infants Co-administration of zinc and magnesium in patients with polycystic ovary syndrome significantly decreased serum high-sensitivity C-reactive protein, a marker of inflammation, and downregulated proinflammatory IL-1 and TNF-α cytokines Moreover, selenium supplementation in healthy individuals improves their response to vaccination and increases their antibody titers , , indicating a potent role of micronutrients as cofactors in vaccine-mediated immunity.
An anti-inflammatory effect of selenium was also demonstrated in infertile women with polycystic ovary syndrome who were candidates for in vitro fertilization, who showed a decrease in gene expression of the proinflammatory cytokines IL-1 and TNF-α after selenium supplementation A positive influence of selenium administration on immunity in cancer was observed, as patients with lymphomas and solid tumors who received selenium showed a significant increase in neutrophils and IgG and IgA antibody titers Deficiencies in micronutrients such as vitamins A, B12, C, folic acid, riboflavin, iron, zinc, and selenium can increase immunosenescence, particularly susceptibility to infection and progression of inflammation Vitamin A deficiency has been shown to decrease the number of NK cells and impair their activity, impair the ability of neutrophils and macrophages to undergo phagocytosis, impair the growth and differentiation of B cells, decrease the number of T cells and limit their distribution Vitamin B2 deficiency has been associated with obesity-associated chronic inflammation.
Experiments with mouse adipocytes showed that B2 deficiency resulted in stimulation of the proinflammatory NF-κB signaling pathway and increased levels of IL-1, TNF-α and ROS Vitamin B12 plays an immunomodulatory role in cellular immunity , and its deficiency has been associated with upregulation of proinflammatory TNF-α in macrophages from Bdeficient mice and a decrease in IL-6 levels in Bdeficient rats, conditions that reversed in both animal models after increasing B12 supplementation — Deficiencies of certain trace elements have also been shown to have negatively affect the number and function of immune cells, leading to dysregulation of immune homeostasis.
Zinc deficiency leads to thymic atrophy, decreased number and activity of lymphocytes, altered cytokine production, increased oxidative stress, and inflammation and is also associated with autoimmune and inflammatory diseases by affecting Th cell polarization by promoting differentiation of Th0 cells into proinflammatory Th17 cells, accompanied by loss of Treg function In mice, it has been shown that selenium deficiency leads to a decrease in B cell count However, excessive selenium intake can be counterproductive, as infectious microorganisms can utilize this nutrient in their biochemical processes Copper deficiency is associated with a reduction in the number and antimicrobial function of neutrophils and also with a reduction in the IL-2 secretion of T cells with consequent reduction in T cell proliferation Abnormalities in Th and Tc cell numbers and function have been reported in patients with hereditary hemochromatosis, which is characterized by low iron stores Iron deficiency is associated with weakened cellular immunity, decreased numbers of neutrophils and their phagocytic activity, lower levels of IL-6 and IgG antibodies , The effects of macronutrients on the immune system are summarized in Table 2.
Macronutrients, including proteins, carbohydrates, and fatty acids, provide tissues with the energy necessary for their development and function Immunomodulation by macronutrients has been studied in experimental animals and in human intervention studies by testing the effect of their intake on immunological outcomes.
Proteins represent important macronutrients for the immune system, considering that amino acids are essential for the synthesis of immune proteins, including cytokines and antibodies that mediate immune responses Metabolic degradation of certain amino acids tryptophan, arginine leads to the production of chemical substrates involved in biological processes The degradation of arginine has been associated with the induction of the non-canonical NF-κB pathway and the regulation of gene transcription in the context of immune tolerance Metabolism of arginine and methionine also leads to the synthesis of polyamines, which are organic compounds that regulate cell proliferation through their role in maintaining DNA, mRNA, and cell membrane stability; polyamines have been linked to the induction and regulation of inflammation and pathogen recognition by affecting receptor-ligand binding.
Degradation of methionine leads to the synthesis of glutathione, an antioxidant organic compound involved in the prevention of oxidative stress, regulation of NK and T cell cytotoxicity and macrophage activity, and activation of T cells Amino acids exert multiple roles in the immune system, including regulation of the activation of adaptive and innate immune cells B and T cells, NK cells, macrophages , proliferation of lymphocytes, and production of antibodies, cytokines, and cytotoxic factors , Hydrolysates or bioactive peptides released by gastrointestinal digestion have been reported to have antioxidant activities, increase killing activity of NK cells, increase phagocytic activity of macrophages, and increase the size of lymphocyte populations, antibody and cytokine production Studies in pigs and the fruit fly Drosophila melanogaster, showed that high dietary protein intake has a positive effect on intestinal cellular and humoral immunity, associated with increased expression of antimicrobial peptides On the other hand, low protein diet has been reported to induce immunity against tumor cells in mice.
Specifically, a decrease in protein content and the associated decrease in amino acids cause ER stress, which leads to the activation of T cells that secrete proinflammatory cytokines A positive effect of a high-protein diet on the modulation of inflammatory immune responses was demonstrated in an intervention study of type 2 diabetics who were fed a diet high in animal or plant protein for 6 weeks.
After this period, they had reduced levels of the proinflammatory adipokines chemerin and progranulin regardless of protein source Overweight and obese adults who followed an energy-restricted diet with either normal or high protein achieved weight loss accompanied by significant decreases in proinflammatory monocyte subpopulations, plasma lipids, and lipoproteins An important aspect of the effect of macronutrients on the immune system is their involvement in immune recognition.
Carbohydrates represent common cell surface molecules that can be recognized as antigens by TLRs. Glycolipids, zwitterionic polysaccharides and glycopeptides can be presented to γδ and αβ T-cells either through endosomal pathways or extracellular receptors Glycoproteins and glycolipids can bind to glycan-binding proteins such as lectins and antibodies, regulating cell adhesion during leukocyte migration and immunity to infection through recognition of carbohydrates contained in the membrane of pathogens In addition, carbohydrates participate in enzymatic processes of protein glycosylation that generate important functional biopolymers.
Glycosylated peptides act as glycoantigens that influence the binding of antigen presentation proteins of the HLA-I and HLA-II systems and subsequent T-cell recognition of antigenic peptides.
Glycoantigens processed through intracellular pathways in APCs are presented to Th, Tc and NKT cells and modulate their activation and cytokine production Another study reported that carbohydrate intake by athletes was associated with a more balanced number of immune cells in the blood, decreased phagocytic activity of monocytes and granulocytes, and decreased ROS and inflammatory cytokine levels A low-carbohydrate, high-fat diet with or without after-meal walks in patients with type 2 diabetes improved glucose control and fasting pro-insulin levels and significantly decreased phosphorylated c-Jun N-terminal kinase in peripheral blood mononuclear cells, which is a marker of cellular inflammation Fatty acids provide an important source of energy, are components of the cell membrane, and modulate cell function by acting as signaling molecules that can regulate gene expression They can also influence immune cell functions by serving as precursors for the synthesis of lipid compounds involved in the regulation of immune responses and inflammatory pathways , Metabolic derivatives of fatty acids, including eicosapentaenoic acid EPA and docosahexaenoic acid DHA , are precursors for anti-inflammatory molecules that contribute to monocyte recruitment to sites of inflammation, where they engulf and remove apoptotic neutrophils Fatty acids regulate the phagocytic activity of macrophages, infiltration of DCs into lymph nodes and activation of mast cells , They also cross-react with the peroxisome proliferation activation receptor and TLRs , Fatty acids can have a dual effect on the regulation of inflammation, depending on whether or not double bonds are present between the individual carbon atoms unsaturated and saturated fatty acids.
Saturated fatty acids have been shown to stimulate in vitro and in vivo the intracellular macromolecular complex Nod-like receptor protein 3 NLRP3 inflammasome, which promotes the production of the proinflammatory cytokines IL-1β and IL, whereas unsaturated fatty acids exert an inhibitory effect on the NLRP3 inflammasome by limiting the activity of the transcription factor NF-κB , an observation that could be taken into account in clinical nutrition studies to attenuate inflammatory conditions in diseases.
The concentration of fatty acids is a factor that may influence their effect on immune cells. Low concentrations of free fatty acids induce T cell proliferation and cytokine production, whereas high concentrations of free fatty acids cause mitochondrial membrane dysfunction, leading to activation of apoptotic pathways and cell death Fatty acids, as components of lipid rafts in the cell membrane, can modulate cell signaling, which affects immune cell function, considering that lipid rafts have been shown to contribute to Th cell activation Metabolic derivatives of omega-3 fatty acids have also been shown to prevent the differentiation of Th0 cells into proinflammatory Th cells and decrease the secretion of proinflammatory cytokines IL-2, IFN-γ, TNF-α, IL by Th and Tc cells Contradictions exist regarding the effects of omega-3 fatty acids on B cell activation, as in vitro cultures of B cells isolated from the spleens of mice showed no change in the expression of B cell activation markers, whereas in vivo assessment of B cell activation in mice fed a fatty acid-enriched diet showed increased levels of the activation markers CD69, MHC-II, and CD11c — However, DHA and EPA stimulate IgM production by B cells by increasing the number of antibody-producing cells , An anti-atherosclerotic effect of omega-3 fatty acids has been suggested, as they have been shown to decrease the expression of adhesion molecules by endothelial cells, thereby affecting the migration of leukocytes from the bloodstream into tissues and the subsequent formation of inflammatory foam cells In a study of children, polyunsaturated fatty acids were shown to reduce the risk of allergic diseases asthma, rhinitis, and aeroallergen sensitization It has been shown that intake of short-chain fatty acids in multiple sclerosis patients or healthy controls promotes the differentiation of Th0 cells into Tregs with increased suppressive capacity A positive effect of fatty acids on immunity and inflammation has also been demonstrated in breast cancer patients who followed an enriched fish oil diet, including DHA and EPA, resulting in the maintenance of Th cell and serum hsCRP levels, indicating a positive contribution of fatty acids to immune system function and inflammatory response Omega-3 fatty acids have shown a positive effect on attenuating inflammation in patients with chronic kidney disease, as their supplementation resulted in increased production of LTB5 and specialized proresolving lipid mediators, which mediate the resolution of inflammation, and decreased levels of myeloperoxidase, an inflammatory mediator secreted by neutrophils A significant decrease in the levels of proinflammatory cytokines ILA and TNF-α was observed in patients with asthma who received a daily capsule of DHA and EPA, indicating a potent role of fatty acids as a complementary approach in the treatment of this disease Macro- and micronutrients exert critical and diverse roles in both innate and adaptive immunity by regulating the proliferation, function, and activity of various types of immune cells, as well as their interactions and signal transduction associated with inflammatory responses.
Micronutrient deficiencies and malnutrition are common in most countries of the world, highlighting the need for well-organized nutritional care for the general population to prevent disease. Nutritional care of cancer patients undergoing chemotherapy or radiotherapy is a challenge to improve the efficacy and outcomes of cancer treatment and limit disease progression A detailed study of the effect of nutrients on the immune system is an important goal of nutritional immunology Molecular signaling of specific micronutrients is being studied to find drug targets for specific diseases associated with micronutrient deficiency, such as targeting the zinc transporter to treat insulin resistance in type 2 diabetes Studies are being conducted to investigate the effects of specific dietary interventions on human disease progression and chronic inflammation Diets containing nutrients with anti-inflammatory properties have been shown to reduce the risk of depression and attenuate the severity of depression symptoms The study of food consumption in overweight adolescents has revealed the existence of a unique dietary profile in this group associated with obesity The role of nutrition in the management of the severity of COVID and the recovery of surviving patients is currently under investigation; in particular, supplementation of vitamins C, D and zinc to improve patient health, restore immune homeostasis, and reduce the risk of infection for healthy individuals, and probiotics to improve gastrointestinal symptoms in COVID patients The field is open for further studies that will help to clarify the biological role of food metabolites in the physiology of the organism and especially the immune system, as well as the association of specific dietary nutrients with the pathogenesis of diseases.
AM and CT conceived and coordinated the study. ET and AM did the literature search and analysis and wrote the manuscript. AM and CT were responsible for the revision of the manuscript for important intellectual content.
All authors contributed to the article and approved the submitted version. Τhe publication of this article has been financed by the Research Committee of the University of Patras.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Koithan M, Devika J. New Approaches to Nutritional Therapy.
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Cell Immunol — txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Nutrition Reviews This issue Dietetics and Nutrition Books Journals Oxford Academic Enter search term Search. Abstract Micronutrient deficiencies and infectious diseases often coexist and exhibit complex interactions leading to the vicious cycle of malnutrition and infections among underprivileged populations of the developing countries, particularly in preschool children.
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New research shows little risk of infection Liver detox for allergies immunne biopsies. Discrimination at work defiiciency Liver detox for allergies to high fynction pressure. Icy fingers and toes: Poor circulation ddeficiency Raynaud's phenomenon? To maintain your brain, adn, bone, nerves, skin, blood circulation, and immune system, your body requires a steady supply of many different raw materials—both macronutrients and micronutrients. You need large amounts of macronutrients—proteins, fats, and carbohydrates. And while you only need a small number of micronutrients—vitamins and minerals—failing to get even those small quantities virtually guarantees disease. Nearly 30 vitamins and minerals that your body cannot manufacture in sufficient amounts on its own are called "essential micronutrients.
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