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Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.
Markun, S, Gravestock, I, Jäger, L, Rosemann, T, Pichierri, G, Burgstaller, JM
Nutrients. 2021;(3)
Abstract
Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
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Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.
Murai, IH, Fernandes, AL, Sales, LP, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, Macedo, MB, Dalmolin, HHH, et al
JAMA. 2021;(11):1053-1060
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IMPORTANCE The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. INTERVENTIONS Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURES The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. RESULTS Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. CONCLUSIONS AND RELEVANCE Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04449718.
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Role of vitamins and minerals as immunity boosters in COVID-19.
Kumar, P, Kumar, M, Bedi, O, Gupta, M, Kumar, S, Jaiswal, G, Rahi, V, Yedke, NG, Bijalwan, A, Sharma, S, et al
Inflammopharmacology. 2021;(4):1001-1016
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) known as coronavirus disease (COVID-19), emerged in Wuhan, China, in December 2019. On March 11, 2020, it was declared a global pandemic. As the world grapples with COVID-19 and the paucity of clinically meaningful therapies, attention has been shifted to modalities that may aid in immune system strengthening. Taking into consideration that the COVID-19 infection strongly affects the immune system via multiple inflammatory responses, pharmaceutical companies are working to develop targeted drugs and vaccines against SARS-CoV-2 COVID-19. A balanced nutritional diet may play an essential role in maintaining general wellbeing by controlling chronic infectious diseases. A balanced diet including vitamin A, B, C, D, E, and K, and some micronutrients such as zinc, sodium, potassium, calcium, chloride, and phosphorus may be beneficial in various infectious diseases. This study aimed to discuss and present recent data regarding the role of vitamins and minerals in the treatment of COVID-19. A deficiency of these vitamins and minerals in the plasma concentration may lead to a reduction in the good performance of the immune system, which is one of the constituents that lead to a poor immune state. This is a narrative review concerning the features of the COVID-19 and data related to the usage of vitamins and minerals as preventive measures to decrease the morbidity and mortality rate in patients with COVID-19.
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Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.
Pham, VT, Calatayud, M, Rotsaert, C, Seifert, N, Richard, N, Van den Abbeele, P, Marzorati, M, Steinert, RE
Nutrients. 2021;(4)
Abstract
Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.
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Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations.
van Atteveld, JE, Verhagen, IE, van den Heuvel-Eibrink, MM, van Santen, HM, van der Sluis, IM, Di Iorgi, N, Simmons, JH, Ward, LM, Neggers, SJCMM
Cancer medicine. 2021;(13):4177-4194
Abstract
BACKGROUND Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. METHODS We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25-hydroxyvitamin D (25OHD) levels and BMD Z-scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. RESULTS Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z-scores, while 25OHD as a continuous variable was not significantly associated with BMD Z-scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). CONCLUSION There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels <20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year-long.
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Vitamin C May Increase the Recovery Rate of Outpatient Cases of SARS-CoV-2 Infection by 70%: Reanalysis of the COVID A to Z Randomized Clinical Trial.
Hemilä, H, Carr, A, Chalker, E
Frontiers in immunology. 2021;:674681
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Factors Contributing to Vitamin D Status at Hospital Admission for Pulmonary Exacerbation in Adults With Cystic Fibrosis.
Bhimavarapu, A, Deng, Q, Bean, M, Lee, N, Ziegler, TR, Alvarez, J, Tangpricha, V
The American journal of the medical sciences. 2021;(1):75-82
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BACKGROUND Individuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF. METHODS This was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS A total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p<0.05). CONCLUSIONS Sunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.
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Supplementation with vitamin D in the COVID-19 pandemic?
Hadizadeh, F
Nutrition reviews. 2021;(2):200-208
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The coronavirus disease 2019 (COVID-19) pandemic was declared a public health emergency of international concern by the World Health Organization. COVID-19 has high transmissibility and could result in acute lung injury in a fraction of patients. By counterbalancing the activity of the renin-angiotensin system, angiotensin-converting enzyme 2, which is the fusion receptor of the virus, plays a protective role against the development of complications of this viral infection. Vitamin D can induce the expression of angiotensin-converting enzyme 2 and regulate the immune system through different mechanisms. Epidemiologic studies of the relationship between vitamin D and various respiratory infections were reviewed and, here, the postulated mechanisms and clinical data supporting the protective role of vitamin D against COVID-19-mediated complications are discussed.
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Phosphate Concentrations and Modifying Factors in Healthy Children From 12 to 24 Months of Age.
Koljonen, L, Enlund-Cerullo, M, Hauta-Alus, H, Holmlund-Suila, E, Valkama, S, Rosendahl, J, Andersson, S, Pekkinen, M, Mäkitie, O
The Journal of clinical endocrinology and metabolism. 2021;(10):2865-2875
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CONTEXT Phosphate homeostasis and its modifiers in early childhood are inadequately characterized. OBJECTIVE To determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age. DESIGN This study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age 2 weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months. MAIN OUTCOME MEASURES Plasma phosphate concentrations at 12 and 24 months of age. RESULTS Mean (SD) phosphate concentration decreased from 12 months (1.9 ± 0.15 mmol/L) to 24 months (1.6 ± 0.17 mmol/L) of age (P < 0.001 for repeated measurements). When adjusted by covariates, such as body size, creatinine, serum 25-hydroxyvitamin D, intact and C-terminal fibroblast growth factor 23, mean plasma phosphate was higher in boys than girls during follow-up (P = 0.019). Phosphate concentrations were similar in the vitamin D intervention groups (P > 0.472 for all). Plasma iron was associated positively with plasma phosphate at both time points (B, 0.006 and 0.005; 95% CI, 0.004-0.009 and 0.002-0.008; P < 0.001 at both time points, respectively). At 24 months of age, the main modifier of phosphate concentration was plasma creatinine (B, 0.007; 95% CI 0.003-0.011, P < 0.001). CONCLUSION Plasma phosphate concentration decreased from age 12 to 24 months. In infants and toddlers, the strongest plasma phosphate modifiers were sex, iron, and creatinine, whereas vitamin D supplementation did not modify phosphate concentrations.
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EFFECTS OF VITAMIN D SUPPLEMENTATION DURING PREGNANCY ON NEWBORNS AND INFANTS: AN INTEGRATIVE REVIEW.
Dutra, LV, Souza, FIS, Konstantyner, T
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2021;:e2020087
Abstract
OBJECTIVE To identify the effects of vitamin D supplementation during pregnancy on newborns and infants. DATA SOURCES The present study is an integrative review of literature based on clinical trials published in journals indexed in the PubMed and Web of Science databases. Two searches were carried out, starting with the association (and) of the health term "vitamin D" with "pregnancy". In the search for information, selection criteria were established, and there was no language limitation and year of publication. DATA SYNTHESIS The final selection resulted in 44 clinical trials, most of which were randomized and double blind, which were carried out in outpatient clinics, referral hospitals and universities, mainly in Europe. The samples studied were predominantly of newborns. In these 44 trials, 23 types of different doses of vitamin D during pregnancy, with different doses, regimens and times of use, and 14 different outcomes were studied in newborns (NB) and infants. Of the 44 studies performed, 35 showed statistically significant beneficial effects of vitamin D supplementation during pregnancy on newborns and infants compared to control groups. CONCLUSIONS Vitamin D supplementation during pregnancy for at least three months before delivery has the potential of positively influencing calcium metabolism, physical growth and immune system development in newborns and infants. However, there is insufficient knowledge to define the optimal dose and to guarantee the absence of possible long-term adverse effects.