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Vitamin D3 as Potential Treatment Adjuncts for COVID-19.
Malaguarnera, L
Nutrients. 2020;(11)
Abstract
Severe acute respiratory syndrome coronavirus type (SARS-CoV2, also known as COVID-19), which is the latest pandemic infectious disease, constitutes a serious risk to human health. SARS-CoV2 infection causes immune activation and systemic hyperinflammation which can lead to respiratory distress syndrome (ARDS). ARDS victims are characterized by a significant increase in IL-6 and IL-1. Macrophage activation, associated with the "cytokine storm", promotes the dysregulation of the innate immunity. So far, without vaccines or specific therapy, all efforts to design drugs or clinical trials are worthwhile. Vitamin D and its receptor vitamin D receptor (VDR) exert a critical role in infections due to their remarkable impact on both innate and adaptive immune responses and on the suppression of the inflammatory process. The protective properties of vitamin D supplementation have been supported by numerous observational studies and by meta-analysis of clinical trials for prevention of viral acute respiratory infection. In this review, we compare the mechanisms of the host immune response to SARS-CoV2 infection and the immunomodulatory actions that vitamin D exerts in order to consider the preventive effect of vitamin D supplementation on SARS-CoV2 viral infection.
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2.
Efficiency of Vitamin D Supplementation in Healthy Adults is Associated with Body Mass Index and Baseline Serum 25-Hydroxyvitamin D Level.
Žmitek, K, Hribar, M, Hristov, H, Pravst, I
Nutrients. 2020;(5)
Abstract
Vitamin D (VitD) has a critical role in phosphorous-calcium metabolism as well as an important role in the immune system. In the human body, VitD is synthesized as cholecalciferol in the skin, but this process requires sunlight (UVB) radiation. Numerous reports showed high prevalence of VitD deficiency, particularly during the winter season, indicating the importance of VitD supplementation. Various factors can affect the absorption of VitD, including dosage and formulation. The primary study objective was to examine the efficiency of supplementation with three different formulations containing cholecalciferol in comparison with the control group. The secondary objective was to identify other factors affecting increase in serum 25-OH-VitD. A randomized controlled intervention study was conducted in Slovenia during wintertime (January- March) on 105 apparently healthy subjects (aged 18-65 years) with suboptimal VitD status (25-OH-VitD 30-50 nmol/L). Subjects were randomized into four groups: three treatment groups receiving (A) capsules with starch-adsorbed VitD, (B) oil-based Valens VitD oral spray, or (C) water-based Valens VitD oral spray and a control group (D) which did not receive supplemental VitD. Two months of supplementation with cholecalciferol (1000 IU; 25 µg daily) resulted in significant increase in serum 25-OH-VitD levels in comparison with control group (pooled Δc 32.8 nmol/L; 95% CI: 23.0, 42.5, p < 0.0001). While we did not observe any significant differences between the tested formulations, the efficiency of supplementation was associated with body mass index and baseline serum 25-OH-VitD level. Higher supplementation efficiency was observed in participants with normal body weight (BMI < 25) and in those with more pronounced VitD insufficiency. We also determined that tested dosage was not sufficient to achieve recommended 25-OH-VitD levels in all subjects.
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3.
Serum vitamin D level was not associated with severity of ventilator associated pneumonia.
Yaghoobi, MH, Taher, A, Seifrabie, MA, Sabahi, M, Rahimi-Bashar, F
Romanian journal of internal medicine = Revue roumaine de medecine interne. 2019;(1):55-60
Abstract
BACKGROUND AND OBJECTIVE Vitamin D deficiency is considered one of the most common nutritional deficiencies associated with weakened immune system and increased likelihood of sepsis. The current study was conducted to investigate the association between serum vitamin D level and the severity and prognosis of ventilator associated pneumonia (VAP) in inpatients in intensive care unit (ICU). METHODS Eighty-four consecutive patients with VAP were enrolled in this observational, prospective study conducted in the ICU of Besat Hospital, Hamadan. The patients were examined for serum 25-hydroxyvitamin D (vitD3) level and VAP severity and prognosis. Clinical pulmonary infection score was used for the diagnosis, and Sequential Organ Failure Assessment (SOFA) Score was used to determine the severity of VAP. RESULTS Low level serum vitD3 (under 30 ng/mL) was found in 66 (78.6%) patients. In this series of VAP patients, there were no significant differences in blood culture results, 14 and 28-day sepsis-associated mortality, mechanical ventilation duration, or SOFA Score on days 3, 7, and 14 between the low level and normal level vitD3 patients (p > 0.05). CONCLUSION Serum vitD3 level was not associated with mortality from VAP or complications due to sepsis in the inpatients in the ICU.
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4.
Intralesional Vitamin D3 in Recalcitrant Palmoplantar and Periungual Warts: A Prospective, Observational Study.
Priya, A, Adil, M, Amin, SS, Mohtashim, M, Bansal, R, Alam, M
Acta dermatovenerologica Croatica : ADC. 2019;(4):215-224
Abstract
Cutaneous warts are particularly difficult to treat with conventional treatment on sites such as the palms, soles, and periungual region. Immunotherapy boosts the host immune response and helps clear warts with less chance of recurrence. Vitamin D plays an important role in proliferation and differentiation of keratinocytes. The aim of this observational study was to study the efficacy and safety of intralesional vitamin D immunotherapy in the treatment of recalcitrant palmoplantar and periungual warts. Patients who had palmoplantar and periungual warts for more than 6 months and were non-responsive to at least two conventional treatment modalities were selected for the study. A maximum of four warts were injected with 0.2 mL of lignocaine (20 mg/mL), followed by intralesional injection of 0.2-0.5 mL of vitamin D3 (15 mg/mL), every 2 weeks for a maximum of four sessions. Response was assessed based on the reduction in the number of warts. A total of 63 patients were included in the study. The mean number of intralesional vitamin D3 injections required for complete clearance was 3.05±0.83 (mean ± Standard Deviation). Complete response was observed in 56 (88.9%) patients. Maximum clearance was observed in periungual warts (92.9%), followed by palmar warts (90.0%) and plantar warts (86.2%). The most common adverse effect was pain during injection (100.0%) and local swelling (25.4%). Two patients developed recurrence during follow-up. Immunotherapy with vitamin D3 appears to be an effective, inexpensive, and safe treatment in recalcitrant palmoplantar and periungual warts.
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5.
Correlation of different cellular assays to analyze T cell-related cytokine profiles in vitamin D3-supplemented patients with multiple sclerosis.
Rolf, L, Smolders, J, van den Ouweland, J, Hupperts, R, Damoiseaux, J
Molecular immunology. 2019;:198-204
Abstract
Different laboratory approaches have been exploited to analyze an effect of vitamin D3 supplements on T cell cytokine profiles in multiple sclerosis, with poorly reproducible results. We assessed the correlation between intra-cellular flowcytometry analysis of CD4 T cell-enriched CD3+CD8- lymphocytes after PMA/ionomycin stimulation directly ex-vivo or after 72 h pre-stimulation with anti-CD3, and cytokine levels excreted in culture supernatants. Pre-stimulation with anti-CD3 resulted in higher proportions of cells positive for IFN-γ, IL-17 A, IL-4, IL-10 and GM-CSF (all P < 0.001), but not TNF-α. Positive correlation between approaches was highly variable, but most eminent for IFN- γ and IL-4 (R = 0.608-0.612 and R = 0.677-0.777, resp., all P < 0.001). No effect of 16-weeks vitamin D3 supplements on any outcome was found except for a decreased TNF-α concentration in culture supernatants. Choice of immune-assay is, apparently, a relevant confounder for the reproducibility of individual studies.
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6.
An Innovative Technique in Local Antibiotic Delivery Method in Open Infected Wounds of the Musculoskeletal System.
Shekhar, C
The international journal of lower extremity wounds. 2019;(2):153-160
Abstract
Bone and soft tissue infections are difficult problems in orthopedic surgery. Infections resulting in chronic osteomyelitis if established are difficult to eradicate. The delivery of local antibiotics for the treatment of open infected wounds of the musculo skeletal system is a more logical approach to treat these infections. Antibiotics given systemically are unable to achieve minimum inhibitory concentration in areas of infected wounds which are ischemic or relatively avascular. And also these antibiotics given over a prolonged period lead to significant toxicity and side effects and emergence of resistant bacteria. The author has been treating difficult cases of infected wounds sustained in road accidents, wounds (diabetic ulcers) in Diabetes Mellitus with necrotizing fasciitis and post operative infections with discharging sinuses with infected implants inside by his own innovative method of antibiotic delivery. The infected open wounds have been treated by application of Vitamin D3 granules impregnated with Tobramycin or Tobramycin and Vancomycin combined. All the patients responded successfully to this novel method of treatment which is extremely simple, effective, low cost, without any complications or side effects and has shown excellent results. Not only the Vitamin D3 granules act as a carrier of the antibiotic locally but also have properties of boosting immunity, and promote tissue healing. It also produces an antibiotic like substance Cathelicidin which kills bacteria and promotes growth of the bone and restores the bone mineral density.
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7.
Effects of vitamin D supplementation on salivary immune responses during Marine Corps basic training.
Scott, JM, Kazman, JB, Palmer, J, McClung, JP, Gaffney-Stomberg, E, Gasier, HG
Scandinavian journal of medicine & science in sports. 2019;(9):1322-1330
Abstract
Vitamin D's role in regulating immune responses may increase during periods of elevated psychological and physiological stress. Due to the high demands placed on US Marine Corps recruits undergoing 12 weeks of basic military training, we hypothesized that vitamin D status would be related to markers of innate mucosal immunity, and daily vitamin D supplementation would augment immune responses during training. Males (n = 75) and females (n = 74) entering recruit basic training during the summer and winter volunteered to participate in a randomized, double-blind, placebo-controlled study. Subjects received either 1000 IU vitamin D3 + 2000 mg calcium/d (n = 73) or placebo (n = 76) for 12 weeks. Saliva samples were collected pre-training, during (weeks 4 and 8), and post-training (week 12) in order to determine salivary SIgA and cathelicidin (indices of mucosal immunity) and α-amylase (indicator of stress). Initial (baseline) and post-training serum 25(OH)D levels were measured. Results were as follows: serum 25(OH)D levels were 37% higher in recruits entering training in summer compared with winter. A positive relationship was observed between baseline 25(OH)D levels and SIgA secretion rates (-SR). When stress levels were high during summer training, baseline 25(OH)D levels contributed to an increase in salivary secretory immunoglobulin A secretion rates (SIgA-SR) and cathelicidin-SR, the latter only in males. Vitamin D supplementation contributed to the changes in SIgA-SR and cathelicidin-SR, specifically SIgA-SR was higher in the treatment group. These data highlight the importance of vitamin D and mucosal immune responses during arduous basic military training when stress levels are increased.
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8.
Effect of vitamin D3 supplementation on HIV-infected adults: a systematic reviewVitamin Dӡ Supplementation on HIV-Infected Adults: A Systematic Review.
Teixeira, NDSCCA, Pereira, BM, Oliveira, IKF, Lima, CHR, Carvalho, CMRG, Nunes, IFOC, Costa, DL, Paiva, AA
Nutricion hospitalaria. 2019;(5):1205-1212
Abstract
Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections.
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9.
Nutrigenomics of Vitamin D.
Carlberg, C
Nutrients. 2019;(3)
Abstract
Nutrigenomics studies how environmental factors, such as food intake and lifestyle, influence the expression of the genome. Vitamin D₃ represents a master example of nutrigenomics, since via its metabolite 1α,25-dihydroxyvitamin D₃, which binds with high-affinity to the vitamin D receptor, the secosteroid directly affects the epigenome and transcriptome at thousands of loci within the human genome. Vitamin D is important for both cellular metabolism and immunity, as it controls calcium homeostasis and modulates the response of the innate and adaptive immune system. At sufficient UV-B exposure, humans can synthesize vitamin D₃ endogenously in their skin, but today's lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation with pills. The individual's molecular response to vitamin D requires personalized supplementation with vitamin D₃, in order to obtain optimized clinical benefits in the prevention of osteoporosis, sarcopenia, autoimmune diseases, and possibly different types of cancer. The importance of endogenous synthesis of vitamin D₃ created an evolutionary pressure for reduced skin pigmentation, when, during the past 50,000 years, modern humans migrated from Africa towards Asia and Europe. This review will discuss different aspects of how vitamin D interacts with the human genome, focusing on nutritional epigenomics in context of immune responses. This should lead to a better understanding of the clinical benefits of vitamin D.
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10.
Vitamin D: A Micronutrient Regulating Genes.
Carlberg, C
Current pharmaceutical design. 2019;(15):1740-1746
Abstract
BACKGROUND At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). METHODS This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. RESULTS Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. CONCLUSIONS The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.