Dr. MARIUM METHEW
(Doctorate in physiology and gastrology; Patuakhali Science and Technology University, Bangladesh)
Calciferol generates many extraskeletal effects because of the cholecalciferol receptor (VDR). A big effect is additionally the suppression of inflammatory processes. Because viosterol might be acknowledged as a “seasonal stimulus”, as defined by R. Edgar Hope-Simpson. The possible role of D within the prevention of the influenza virus. The foremost important point is to realize that the broad spectrum of this vitamin’s activity doesn’t exclude such an opening. Populations are needed to explore the preventive effect of cholecalciferol supplementation on viral influenza infections.
vitamin D; influenza; tract infections
The popularity of fat-soluble vitamins as a vitamin with a broad spectrum of activity continues to be growing. There are many papers published annually about its properties, including ensuring our bone health. Now, we all know that vitamin D is related to cancer, diabetes, cardiac, and gastrointestinal diseases, and, most interestingly, even with events of unknown etiology, like inflammatory bowel disease .
The phenomenon of its multidirectional activity is possible thanks to the presence of the VDR in most non-skeletal human cells. New perspectives on calciferol activity and targets are very important from, of course, the scientific point of view, but, and this is often crucial, because of increasing awareness of the deficiency of this vitamin in numerous populations across the globe and the need for its supplementation. Through the VDR, vitamin D can even modulate the innate and purchased system. This has prompted the concept of exploring the impact of fat-soluble vitamins on the efficacy of our system in fighting off difficult-to-treat viral infections, like influenza, especially because reaching and the optimal level of this “medicine” is reasonable and simple for everyone.
This paper aimed to present recent data on the possible role of the fat-soluble vitamin in modulating the immunologic response in influenza infection and its potential preventive and therapeutic potential therein disease. This review is predicated on an electronic search of articles within the PubMed database, including papers published mostly within the last eight years up until 2018 therein field. The relevant papers are also included. All research articles were found with a mixture of the subsequent keywords: vitamin D and influenza, ergocalciferol and respiratory illnesses, calciferol and influenza vaccines, and vitamin D and infections. Published articles included during this meta-analysis were selected supported the subsequent criteria: they have to are published in English or Polish, concerning the association between the reaction and D serum concentration or supplementation, and defining the kind of trial, the number of participants, outcome measure, and including statistical analysis.
- The Metabolism, Action, and Guidance Serum Concentration of viosterol
2.1. Metabolism cholecalciferol (D3) or Ergocalciferol (D2).
Metabolic pathways (Figure 1), common for both forms, active metabolite 1?,25–dihydroxy vitamin D3 (calcitriol, 1?,25(OH)2D), catalyzed by cytochrome P450-associated 25(OH)D(3)-1?-hydroxylase (CYP27B1), the enzyme present within the kidney but also in other extrarenal tissues, including immune cells [2–4]. thanks to a developed feedback circuit system, level and therefore the negative ones are phosphate level and fibroblast growth factor-23 (FGF-23).
Unlike the renal form, CYP27B1 present within the immune cells isn’t regulated by PTH, FGF-23, calcium, or phosphate signaling, but is stimulated by cytokines like tumor necrosis factor? (TNF ?) and interferon (IFN?) [4,6]. Injury and Toll-like receptor (TLR) activation . Extrarenal expression of that enzyme may be promoted by alternate pathogen recognition receptors (PRRs) .
Regulation of extrarenal 1?-hydroxylase is strongly passionate about the concentration of the circulating 25(OH)D . Both metabolites, 25(OH)D and 1?,25(OH)D, are transported within the bloodstream by the carrier vitamin D binding protein (DBP), with the next affinity of 25(OH)D thereto transporter . Degradation of both metabolites is catalyzed by CYP24A1, a multicatalytic enzyme that leads to 24-hydroxylation and therefore the formation of 24,25(OH)2D, and 1?,24,25(OH)2D, which are subsequently converted to calcitroic acid [2,5]. The circulating calcidiol could also be also converted by CYP24A1 to the inactive 25(OH)2D-26,23-lactone and 24,25(OH)2D .
Figure 1. Metabolic pathways of vitamin D. Abbreviations: CYP24A1 (cytochrome P450-associated 24-hydroxylase); CYP2R1 and CYP27A1 (cytochrome P450-associated 25-hydroxylases); CYP27B1 (cytochrome P450-associated 25(OH)D3-1?-hydroxylase); PTH (parathormone); FGF-23 (fibroblast growth factor-23); TNF? (tumour necrosis factor ?); IFN? (interferon ?). 2.2. Nongenomic and Genomic Action ,Probably via a membrane-bound, ergocalciferol regulates rapid cellular calcium efflux and calcium-activated chloride channel activity .
Affinity to the VDR is way higher for 1?,25(OH)2D (Ka = 10?10 M) than for 25(OH)D (Ka = 10?8 M) . Activation of that receptor is that the basis for the regulation of roughly 3% of the human genome, affecting immune and neurological functions and playing a job in the skin, cardiovascular, As was found in recent years, polymorphism in some enzymes and proteins associated with vitamin D, like DBP, CYP28B1, CYP2R1, CYP24A1, or VDR (especially polymorphs FokI, TaqI, ApaI, and BsmI), can affect the individual’s response to anti-infectious treatment, like interferon/ribavirin therapy in chronic viral hepatitis [13,14], susceptibility of the individuals to cancer, tuberculosis.
2.3. Guidance Serum Concentrations
The most valuable indicator of the body’s fat-soluble vitamin status is that the serum levels of 25(OH)D, Measurement of 1?,25(OH)2D to define vitamin D level within the organism isn’t recommended, as its serum half-life is barely some hours (ca. 7 h) [9,12]. The guidance serum concentration of 25(OH)D, which indicates an efficient level of cholecalciferol within the organism, is 30–80 ng/mL (ca. 75–200 nM/L). A severe fat-soluble vitamin deficiency is reflected in serum concentrations below 10 ng/mL [12,19–23].
As an Anti-Infective Agent. The clear functions of ergo-calciferol within the system are difficult to define because the response isn’t a static process and depends on the stage of infection. The VDR, which has also been detected in immunological cells, suggests that D can regulate some processes associated with immunity the endothelial cells lining the upper and lower tract can transform inactive metabolite 25(OH)D into active 1?,25(OH)2D. The possible role of fat-soluble vitamin in infectious diseases is implied by its impact on the innate and adaptive immune responses (Figure 2):
Figure 2. The role of D within the reaction. Abbreviations: PRRs (pathogen recognition receptors); TLRs (Toll-like receptors); NLRs (nucleotide-binding oligomerization domain (NOD)-like receptors (invariant NK T cells); Ig (immunoglobulin); DC (dendritic cells); Treg cells (regulatory T cells); HLA-DR (human leukocyte antigens); CD (costimulatory molecules); MHC (major; NO (nitric oxide).
3.1. viosterol and also the Innate Response
3.1.1. Pathogen Recognition Receptors—
PRRs the innate reaction is defined, generally, as nonspecific, The crucial points for the innate reaction are the Toll-like receptors (TLRs), being a subgroup of assorted intracellular innate PRRs which are present in macrophages, polymorph nuclear cells, monocytes, and epithelial cells. TLRs recognize molecules associated with the pathogen; as an example Such activated TLRs release and defenses [4,6,7,24,25]. Several TLRs affect or are stricken by VDR induction. as an example,. In turn, the increased expression of CYP27B1 in macrophages is that the indirect result of AMPs, which stimulates TLR2 .
As shown by Griller and The exact mechanism of TLR ligation-induced CYP27B1 production isn’t fully understood, allowing calcitriol to own more extensive effects on the immune reaction . Upon virus infection, pathogen-associated molecular patterns (PAMPs) also can be recognized by other PRRs, such as retinoic-acid-inducible gene-I (RIG-I)-like receptors and nucleotide binding-oligomerization domain (NOD)-like receptors (NLRs). ?,25(OH)2D via two VDREs within the NOD2 gene. The addition of lysosomal breakdown Int. J. Mol. Sci. 2018, 19, 2419 5 of 26 such as beta-defensin 2 expressions [7,29]. the early stage of the innate response. These cytokines, among others, induce synthesis PRR signaling also leads to the assembly of chemokine ligands (CXCLs), such These cells have an immune role, especially in bacterial immunity . Upregulation of TLRs can even involve other mechanisms. Neutrophils, unlike macrophages, express the VDR, but they are doing not show a full of life 1?-hydroxylase.
In such cases, the surface proteins, like the triggering receptor on myeloid cells-1 (TREM- 1) or transforming protein? (TGF?), present on the neutrophils or epithelial keratinocytes, respectively, may participate within the cell response to circulating 1?,25(OH)2D, including TLR signaling, via TREM-1, or by stimulation of CYP27B1 expression, via TGF? . TGF? can leukotrienes, compounds that participate among others, within the phagocytosis of bacteria . One of the features of the antibacterial innate response is that the destruction of the pathogens by autophagy . in keeping with Chun et al. , recent data suggest that this process is vital for the antibacterial response induced by fat-soluble vitamins against tubercle bacillus infection and are shown to inactivate the influenza virus .
In humans the human cathelicidin propeptide (hCAP18). the bulk of cathelicidin is stored in neutrophil granules, but also the opposite sorts of immune cells, as monocytes and NK and B lymphocytes can express hCAP18 . the active metabolite of cholecalciferol, 1?,25(OH)2D, via increased expression of the VDR . consistent with, which kills intracellular Mycobacterium tuberculosis. As was shown by Szymczak and Pawliczak ,. The lung epithelial cells, during viral infection, are capable of converting calcidiol into the active metabolite calcitriol, resulting in increased hCAP18 production. As shown by Beard et al. , cathelicidin expression in macrophages and keratinocytes is induced by CYP27B1, and if there’s no 25(OH)D, VDR, or CYP27B1, the power of these cells to supply cathelicidins is significantly impaired. Following Szymczak and Pawliczak , not only TLR signaling, but also cytokines like IL-4 and IFN? may affect the CYP27B1 expression. The presence of IFN? stimulates macrophage CYP27B1. it’s also interesting that 1?,25(OH)2D participates within the feedback mechanism that self-inhibits the hyperactivation of TLRs  .
As shown by Fitch et al. , in viral responses, even in supraphysiologic concentrations.
3.1.2. Antimicrobial Peptides
AMPs Vitamin D also regulates. CD4+ T-induced cells, via cytokine secretion, provide support to other immune cells, like CTLs, and the serum antibody response, via CD40:CD40 ligand costimulation of antigen-specific B cells [6,25–27,29,31]. Besides cytokine production, the role of Th cells includes the support of immunoglobulin production, macrophage activation, and production of eosinophils and mastocytes (Th2) .
The Th1-stimulated response is that the key for several bacterial and viral infections, but if it’s an uncontrolled process, it results in autoimmunity . What is the role of vitamin D in this form of immune response? It acts as a modulator of Th cell processes . the precise mechanism isn’t well-known. one among the reports focused on the flexibility of expressing VDR and CYP27B1 . it’s interesting to notice that, as reported by Jeffrey et al. , the form of vitamin D significant for the generation of Treg cells was non-DBP-bound 25(OH)D. Bruce et al.  mentioned that 1?,25(OH)2D regulates invariant NK T cells (iNKT), which might act as regulatory cells and participate within the interaction between innate and adaptive immunity.
The induction of iNKT is protective, including against autoimmune diseases. In turn, Sigmundsdottir et al.  indicate that 1?,25(OH)2D-stimulated chemokine receptor 10 (CCR10) the expression on T cells enables communication with other immune-competent cells because it recognizes CCL27 is secreted by keratinocytes throughout the organism. In vitro, 1?,25(OH)2D inhibits the expression of Th1 cytokines and stimulates Th2 cytokines. As shown previously, the opposite subgroup of Th cells, i.e., Th17 cells, secrete IL-17, playing a task in autoimmune processes [6,29]. Inhibition of Th1 cells was also noted in vivo, in mouse DC . Inverse associations between calciferol concentrations and disease activity in patients with inflammatory bowel disease, type 1 diabetes, disseminated sclerosis, autoimmune disease, or autoimmune thyroiditis have been noted . 1?,25(OH)2D looked as if it would limit autoimmune reactions, among other means, by inhibiting Th17 cell activity . other than that, 1?,25(OH)2D can decrease the flexibility to present antigens by the inhibition of DC maturation. The results of the decrease are that the diminished expression of the human leukocyte antigen HLA-DR and costimulatory molecules like CD40, CD80, and CD86.
This cytokine is thought to inhibit IL-12. 1?,25(OH)2Dtreated DC expressed less costimulatory MHC (major histocompatibility complex) II than intact cells . Accordingly, Th1 cell and macrophage production is diminished, although the power to induce Treg cells is maintained [6,25,28]. The induced IL-10 also suppresses Th1 and Th17 cells and thus the assembly of IFN?, IL-17, and IL-2, leading to immune tolerance . The above events make Th2 cells predominate.
As a result. In human monocytes in vitro, 1?,25(OH)2D was shown because the inhibitor of Th1 cell-mediated cytokines and tumor necrosis factor? (TNF?), and in vivo in mice, because of the suppressor of the secretion and production of Th17 cells by downregulation of IL-23 and -6 [6,25,28]. As shown by Bruce et al. , treatment of naïve CD4+ Th cells during Th17 cells priming with 1?,25(OH)2D inhibits IL-17 production. the opposite mechanism of immunomodulation associated with D is that the impact on the DC organic phenomenon, which is independent of the differentiation of those cells . As shown by Chun et al. , DC organic phenomenon is Based on animal studies, it absolutely was shown that the promotion of Th2 cells may have adverse effects on allergic diseases like asthma dermatitis through induction of the inflammatory processes . The increased production of Th2 cytokines (IL-4, -5, – 13), noted within the acute phase.
These effects, together with the suppression of IL-17 secretion, are accountable for the reduction of resistance to pathogens like Toxoplasma and Citrobacter [6,36,37]. Ehren et al.  as indicated by the conventional production of IFN? by CD4+ and CD8+ Th cells. In turn, Rajapakse et al.  Th1 cell activity. Following 1?,25(OH)2D treatment, reduced counts of CD4+, The cells and splenocytes Ryz et al.  showed the reduction of Th17 cells in Citrobacter rodentium-infected mice treated with 1?,25(OH)2D. per the impaired Th17 response, a defect within the production of antimicrobial peptide REG3? was reported. 1?,25(OH)2D impairs the antigen-presenting and lymph cell stimulatory capacity of monocytes and Suppression of IL-12 and IL-23, which are involved in Th1 differentiation, is because of the 1?,25(OH)2D-medi.
4.2.2. Studies Showing
No Relevant Effects, However, there’s still one fly within the ointment. There are in vitro and in vivo data, yet data resulting from human studies, which don’t prove any significance of fat-soluble vitamin supplementation in viral respiratory infections. Gui et al. . Although it decreased the influenza M gene (encoding the M protein associated with inflammatory response and virus replication), IL-6, and IFN? in A549 cells before and post-infection with H9N2 influenza, the authors found that it failed to affect virus replication in vitro and in vivo. Besides, the effect of 1?,25(OH)2D treatment was hooked into the stage of the illness.
As shown in vivo, increased the inflammatory response 4 to six days post-infection. Simultaneously, the expression of and 8. These effects were according to the amount of maximum weight loss and therefore the lung damage in calcitriol-treated mice. the rationale for the positive anti-inflammatory activity of 1?,25(OH)2D noted in A549 cells and also the opposite effect reported in mice during the later stage of infection isn’t clear.
The authors indicate two possible explanations. The primary is that the activity of vitamin D in vivo is complex and has an impression on such a big amount of pathways and mechanisms that it can affect one component of this method, but not the opposite. Secondly, avian influenza viruses like. This is often in agreement with the conclusion given by Grant and Giovanucci , who discussed, regarding the information showing that suppressing pro-inflammatory cytokines by fat-soluble vitamin failed to reduce the danger of death in mice infected with H5N1 viruses, that such an impact mustn’t be applied to the H1N1 infections in humans thanks to the differences in reaction.
The anti-inflammatory activity of 1?,25(OH)2D on A549. The authors noted that 1?,25(OH)2D treatment before or post-infection downregulated IL-6 and IL-8 RNA levels and decreased the levels of infection-induced TNF?, IFN?, and ISG15. 1?,25(OH)2D failed to affect viral clearance, similarly to findings reported by Gui et al. , but reduced autophagy and restored increased apoptosis seen within the H1N1 infection back to its constitutive level. In the studies presented by Jorde et al. ,
calciferol seemed to make influenza infection a significantly more prolonged disease than within the patients receiving placebo. Within the study, 569 subjects from 10 different clinical trials were included. Of the themes, 289 were randomized. The influenza-like disease was reported in 38 subjects within the calciferol group and 42 within the placebo group. In these groups, 25 and 26 subjects, respectively, showed clinical symptoms of influenza in line with the defined criteria. In the vitamin D group, the duration of the illness was significantly longer than within the placebo group (2–60 days versus 2–18 days; p = 0.007).
one in all the weaknesses of this study, as emphasized by the authors, was that the study was retrospective and relied on self-reported symptoms; thus, there wasn’t a definite diagnosis of influenza. As was given by the authors, a randomized controlled trial on the consequences of fat-soluble vitamin supplementation on influenza illness during the 2009 H1N1 pandemic revealed that influenza A or B occurred less within the calciferol group than in the placebo group only during the primary half the study. During the second month, the ergo calciferol group’s results were almost like those of the placebo group.
4.2. Human Studies on Influenza
Prevention by D of ergocalciferol for the prevention of influenza infections. However, there are data obtained in vitro or in vivo which denote the antiviral activity of cholecalciferol within the case of influenza. Nowadays, the final means that these considerations are senseless. it’s most significant to understand that the broad spectrum of ergocalciferol activity doesn’t exclude such a job. Some of the subsequent studies don’t strictly concern influenza infection, but also the influenza-like respiratory illnesses of tract infections (RIs) and pneumonia. However, the time period of the studies, i.e., October–March, or the winter months, doesn’t exclude influenza infections, commonest within the autumn and winter. per Cannell et al. , if fat-soluble vitamins may be a “seasonal stimulus”, as has already been mentioned during this paper, then cholecarciferol deficiency should predispose patients to respiratory infections.
4.2.1. Beneficial Effects
Moan et al. With vitamin D serum levels. The fundamental measure of the studies was 1980–2000. The ultimate conclusion of related to low fat-soluble vitamin levels during this season. The information supports the hypothesis that via sterol acts as a protector against influenza and pneumonia, although it’s not clear if it requires any help, or which mechanism dominates within the battle against viral infections. Laaksi et al. 
Conducted a placebo-controlled experimental procedure (October–March) which involved 164 volunteering young Finnish men (18–28 years of age) undergoing training. After six months of the study, the supplemented group showed a mean serum concentration of 25(OH)D (±SD) of 71.6 ± 22.9 nM/L (n = 58) .  pointed to the difficulty which is most vital for studies supported calciferol supplementation. The authors presenting the results of 26 eligible randomized controlled trials showed that ergocalciferol supplementation significantly reduced the danger of acute tract infection (RI), but the protective effects were observed in those receiving daily or weekly fat-soluble vitamin without additional bolus, and not in those receiving one or more bolus doses. Li-Ng in 2007, described above, showed that supplementation in women with a vitamin D deficit was more protective against colds and influenza than within the case of vitamin D-sufficient women . On the idea of the studies mentioned above, during which supplementation with fat-soluble vitamin and therefore the analogous higher serum concentration of this vitamin didn’t give the expected effect, Grant et al.  proposed a brand.
A new approach to vitamin D randomized controlled trials to supply true confirmation of the role of its vitamin dosing being sole to attain the targets set for achieved 25(OH)D concentrations. As shown by the authors, the belief that the vitamin D dose-response relationship is linear isn’t true. The supplemented D has no direct health. Grant et al.  proposed a design strategy that targets supplementation to the chosen baseline status while ensuring achievement of the required status. This might be done by checking 25(OH) D concentrations Int. J. Mol. Sci. 2018, 19, 2419 13 of 26 periodically during the trial, similarly because the baseline, and thru recruiting non-replete subjects. With such an approach, randomized controlled trials would have an increased potential for detecting causality.
Seasonality of fat-soluble vitamin Levels and Influenza Rate As shown by Shaman et al. , seasonal variation within the serum concentration of 25(OH)D observed influenza seasonality in temperate regions. So, the authors studied whether 25(OH)D levels may be accustomed to simulate influenza infection rates.
The studies were tired two regions of us. On the idea of best-fitting simulations which could reproduce the observed seasonal cycle of influenza, the authors concluded that it’s unlikely that differences due to the season in results suggest that influenza transmission is also passionate about various factors. On the premise of a reanalysis of laboratory experiments, Shaman et al.  revealed that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Also, Keep et al.  studied the impact of absolute humidity within the indoor school environment on virus survival. As noticed, classroom humidification is also a feasible approach to extend indoor absolute humidity to levels that will decrease influenza virus survival and transmission.
In turn, Yang et al.  studied others. They computed the monthly viral positive rate for 3 circulating influenza subtypes: A/H1N1, A/H3N2, and B, The impact of temperature, relative and absolute humidity, and precipitation, also as interactions among the above influenza subtypes on the epidemic dynamics of every influenza subtype were studied. Kroll et al.  mentioned the opposite factor conjugated with the extent of 25(OH)D and parathyroid hormone (PTH) concentrations, which are known to possess a reciprocal seasonal relationship with 25(OH)D , even in ergocalciferol-treated patients. This suggests that 25(OH)D is higher within the summer and lower in winter, while PTH shows the reverse pattern. Per the authors, Independently of the results of the conducted studies, which support or don’t support the positive role of ergocalciferol serum levels and supplementation within the prevention against influenza infections with influenza-related diseases, like RI and pneumonia, most of the authors agree that this subject deserves further study. Influenza infections?” remain open and need more clinical trials.
A summary of the results obtained within the human studies on the role of cholecalciferol within the upper respiratory tract infections\, pointed to the difficulty which is most vital for studies that supported calciferol supplementation. The authors presenting the results of 26 eligible randomized controlled trials showed that ergo-calciferol supplementation significantly reduced the danger of acute tract infection (RI), but the protective effects were observed in those receiving daily or weekly fat-soluble vitamin without additional bolus, and not in those receiving one or more bolus doses. i-Ng in 2007, described above, that showed that supplementation in women with a vitamin D-deficit was more protective against colds and influenza than within the case of vitamin D-sufficient women .
On the idea of the studies mentioned above, during which supplementation with fat-soluble vitamin and therefore the analogous higher serum concentration of this vitamin didn’t give the expected effect, Grant et al.  proposed a brand new approach to vitamin D randomized controlled trials to supply true confirmation of the role of its vitamin dosing being solely to attain the targets set for achieved 25(OH)D concentrations. As shown by the authors, the belief that the vitamin D dose-response relationship is linear isn’t true.
The supplemented D has no direct health. Grant et al.  proposed a design strategy that targets supplementation to the chosen baseline status while ensuring achievement of the required status. This might be done by checking 25(OH)D concentrations Int. J. Mol. Sci. 2018, 19, 2419 13 of 26 periodically during the trial, similarly because the baseline, and thru recruiting non replete subjects. With such an approach, randomized controlled trials would have an increased potential for detecting causality. Seasonality of fat-soluble vitamin Levels and Influenza Rate As shown by Shaman et al. , seasonal variation within the serum concentration of 25(OH)D observed influenza seasonality in temperate regions. So, the authors studied whether 25(OH)D levels may be accustomed simulate influenza infection rates.
The studies were tired two regions of the us. On the idea of best-fitting simulations which could reproduce the observed seasonal cycle of influenza, the authors concluded that it’s unlikely that differences due to the season in these results suggest that influenza transmission is also passionate about various factors. On the premise of a reanalysis of laboratory experiments, Shaman et al.  revealed that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Also, Koep et al.  studied the impact of absolute humidity within the indoor school environment on virus survival. As noticed, classroom humidification is also a feasible approach to extend indoor absolute humidity to levels that will decrease influenza virus survival and transmission. In turn, Yang et al.  studied others.
They computed the monthly viral positive rate for 3 circulating influenza subtypes: A/H1N1, A/H3N2, and B, the impact of temperature, relative and absolute humidity, and precipitation, also as interactions among the above influenza subtypes on the epidemic dynamics of every influenza subtype were. Kroll et al.  mentioned the opposite factor conjugated with the extent of 25(OH) D and parathyroid hormone (PTH) concentrations, which are known to possess a reciprocal seasonal relationship with 25(OH)D, even in ergo calciferol-treated patients. This suggests that 25(OH) D is higher within the summer and lower in winter, while PTH shows the reverse pattern. per the authors, in these observations,
Independently of the results of the conducted studies, which support or don’t support the positive role of ergocalciferol serum levels and supplementation within the prevention against influenza infections with influenza-related diseases, like RI and pneumonia, most of the authors agree that this subject deserves further study. resistance to influenza infections remains open and needs more clinical trials. A summary of the results obtained within the human studies on the role of cholecalciferol within upper respiratory tract infections.
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