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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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Pharmacodynamics of Oral Cholecalciferol in Healthy Individuals with Vitamin D Deficiency: A Randomized Open-Label Study.
Fassio, A, Gatti, D, Rossini, M, Benini, C, Fracassi, E, Bertoldo, E, Viapiana, O, Milleri, S, Gatti, M, Adami, G
Nutrients. 2021;(7)
Abstract
Comparative pharmacodynamic (PD) analyses on different dosing schedules for cholecalciferol supplementation are limited. This was an open-label, randomized, parallel-group study involving 75 healthy individuals deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. Regulators of calcium and phosphate homeostasis, bone turnover markers and Wnt inhibitors were measured at baseline, Day 28, 53, 84, and 112. The 1,25OH2D increased at each time point. The increase was greater (p < 0.05) for group A vs. B and C at Day 28, and vs. group B at Day 56. No significant difference among groups was observed for the other biomarkers. The 24,25OH2D remained stable over time. PTH decreased at Day 84 and FGF-23 increased at all time points. CTX-I and PINP increased slightly at Day 28. BALP decreased from Day 56 onward. Dkk-1 increased from Day 56 onward, while sclerostin did not show significant changes. In healthy individuals deficient in vitamin D, vitamin D supplementation exerted effects on multiple regulators of calcium, phosphate and bone metabolism, without marked differences using the three regimens.
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Serum Vitamin Profile in Oral Lichen Planus Patients in Southwest of Iran.
Rezazadeh, F, Haghighat, S
BioMed research international. 2021;:8627435
Abstract
INTRODUCTION Oral lichen planus (OLP) is a chronic mucocutaneous disease. It is mainly an immune system-related disorder. Vitamins can modulate immune system functions, and thus, vitamin deficiency might have roles in exacerbating OLP. We aim to determine the serum levels of vitamins A, B12, C, D3, and E in OLP patients. METHODS AND MATERIALS 34 OLP patients referred to Shiraz Dental School entered the study. Blood samples were collected and levels of A, B12, C, D3, and E vitamins were measured in serum. 43 healthy people were also included as the control group. Serum levels of vitamins were measured by HPLC (A, B12, D3, and E) and Kiazist analyzing kit (vitamin C). RESULTS Most of the patients were female (62.3%), and the mean age of patients was 48.03 ± 11.57. Serum levels of vitamins A, C, and E were lower in OLP patients in comparison with the healthy group; however, the difference was not significant. Vitamins B12 and D3 were higher in the OLP group but the difference was not significant. CONCLUSION Serum levels of vitamins A, B12, C, D3, and E do not have a significant difference in OLP patients and healthy groups. These vitamins may not have a considerable role in OLP pathogenesis in the southwest of Iran.
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Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial.
Rysavy, MA, Li, L, Tyson, JE, Jensen, EA, Das, A, Ambalavanan, N, Laughon, MM, Greenberg, RG, Patel, RM, Pedroza, C, et al
The Journal of pediatrics. 2021;:78-85.e5
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OBJECTIVE To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION ClinicalTrials.gov NCT01203488.
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Multi-omic analysis of stroke recurrence in African Americans from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
Davis Armstrong, NM, Spragley, KJ, Chen, WM, Hsu, FC, Brewer, MS, Horn, PJ, Williams, SR, Sale, MM, Worrall, BB, Keene, KL
PloS one. 2021;(3):e0247257
Abstract
African Americans endure a nearly two-fold greater risk of suffering a stroke and are 2-3 times more likely to die from stroke compared to those of European ancestry. African Americans also have a greater risk of recurrent stroke and vascular events, which are deadlier and more disabling than incident stroke. Stroke is a multifactorial disease with both heritable and environmental risk factors. We conducted an integrative, multi-omic study on 922 plasma metabolites, 473,864 DNA methylation loci, and 556 variants from 50 African American participants of the Vitamin Intervention for Stroke Prevention clinical trial to help elucidate biomarkers contributing to recurrent stroke rates in this high risk population. Sixteen metabolites, including cotinine, N-delta-acetylornithine, and sphingomyelin (d17:1/24:1) were identified in t-tests of recurrent stroke outcome or baseline smoking status. Serum tricosanoyl sphingomyelin (d18:1/23:0) levels were significantly associated with recurrent stroke after adjusting for covariates in Cox Proportional Hazards models. Weighted Gene Co-expression Network Analysis identified moderate correlations between sphingolipid markers and clinical traits including days to recurrent stroke. Integrative analyses between genetic variants in sphingolipid pathway genes identified 29 nominal associations with metabolite levels in a one-way analysis of variance, while epigenomic analyses identified xenobiotics, predominately smoking-associated metabolites and pharmaceutical drugs, associated with methylation profiles. Taken together, our results suggest that metabolites, specifically those associated with sphingolipid metabolism, are potential plasma biomarkers for stroke recurrence in African Americans. Furthermore, genetic variation and DNA methylation may play a role in the regulation of these metabolites.
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The Effects of Vitamin D Supplementation on Lipid and Inflammatory Profile of Healthy Adolescent Boys: A Randomized Controlled Trial.
Yarparvar, A, Elmadfa, I, Djazayery, A, Abdollahi, Z, Salehi, F, Heshmat, R
Nutrients. 2020;(5)
Abstract
BACKGROUND Deficiency of vitamin D, an anti-inflammatory micronutrient with some favorable effects on lipid profiles, has been found to be highly prevalent in adolescents. We aimed to investigate the effect of a school-based vitamin D supplementation regimen on the correction of vitamin D deficiency as well as lipid and inflammatory profiles of healthy adolescent boys. METHODS In this randomized single-blind placebo-controlled trial, seventy-one healthy adolescent boys (age 17 years old) were recruited from one high school in Tehran, Iran, and randomly assigned to two groups. The supplement group received vitamin D pearls at a dose of 50,000 IU monthly for 6 months, this dose is indeed defined by the Ministry of Health in Iran for a potential national school-based vitamin D supplementation program. The other group was given placebo pearls for the same duration. Before and after the treatment, the serum levels of 25-hydroxy vitamin D (25(OH) D), parathyroid hormone (PTH), retinol, lead (Pb), the lipid profile and the inflammatory biomarkers were measured and compared. RESULTS Between-groups statistical analysis showed that a dose (50,000 IU/month) vitamin D significantly increased the serum levels of 25-hydroxyvitamin D (25 (OH) D) (p < 0.001) and decreased serum levels of PTH (p = 0.003). No significant change was observed in serum levels of retinol and Pb. Between-group analysis revealed that the serum levels of TG (P = 0.001) decreased while an increase in serum levels of HDL (p = 0.021) was observed (p < 0.05). Both the within- and between-group analysis showed that serum tumor necrosis factor receptor 2 (TNFR2) concentration declined while serum interleukin-10 (IL-10) increased in response to vitamin D supplementation (p < 0.05). CONCLUSION A supplementation regimen of (50,000 IU/month) vitamin D in a context with high rates of vitamin deficiency has shown positive impacts on the serum vitamin D, lipid profile and inflammatory biomarkers in healthy adolescent boys.
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Effect of 8-week of dietary micronutrient supplementation on gene expression in elite handball athletes.
Molina-López, J, Ricalde, MAQ, Hernández, BV, Planells, A, Otero, R, Planells, E
PloS one. 2020;(5):e0232237
Abstract
PURPOSE A study was made of the changes in gene expression in elite handball athletes, comparing gene modulation before, after and in the absence of an 8-week nutritional intervention with multivitamin/mineral supplements. METHODS Thirteen elite handball athletes (aged 22.9 ± 2.7 years) and 13 sedentary controls (aged 20.9 ± 2.8 years) were included. Three timepoints were established: T0 (baseline conditions); T8 (after 8 weeks of supplementation with a multivitamin/mineral complex); and T16 (after 8 weeks in the absence of supplementation). The expressions of a total 112 of genes were evaluated by RT-qPCR analysis with the QuantStudioTM 12K Flex Real-Time PCR System. RESULTS The analysis revealed different gene regulation profiles of genes implicated in cell communication, cell energy metabolism, inflammation and the immune system, oxidative stress and muscle function in athletes compared to sedentary controls under resting conditions (upregulated genes: effect size = large, ƞ2 = 1.011 to 1.398, p < 0.05; downregulated genes: effect size = large, ƞ2 = 0.846 and 1.070, p < 0.05, respectively). The nutritional intervention encouraged gene upregulation in elite athletes (p < 0.05). In a follow-up investigation, the IRAK1, CD81, ITGB1, ACADS PDHA2 and GPX1 genes were downregulated in athletes, with a moderate main effect for time-by-group interaction (ηP2 = 0.099 to 0.133; p < 0.05). Additionally, nutritional genes such as MTHFR and THTPA revealed a moderate effect over all the timepoints and group interaction in the study (ηP2 = 0.070 to 0.092; p < 0.05). CONCLUSIONS Elite handball athletes showed a different expression profile in reference to key genes implicated in several sports performance-related functions compared to the sedentary controls, in addition to modulation of gene expression after multivitamin/mineral supplementation.
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Intratrial Exposure to Vitamin D and New-Onset Diabetes Among Adults With Prediabetes: A Secondary Analysis From the Vitamin D and Type 2 Diabetes (D2d) Study.
Dawson-Hughes, B, Staten, MA, Knowler, WC, Nelson, J, Vickery, EM, LeBlanc, ES, Neff, LM, Park, J, Pittas, AG, ,
Diabetes care. 2020;(12):2916-2922
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OBJECTIVE Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). RESEARCH DESIGN AND METHODS The D2d study compared the effect of daily supplementation with 100 μg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of <50, 75-99, 100-124, and ≥125 nmol/L were compared with those with levels of 50-74 nmol/L (the range considered adequate by the National Academy of Medicine) in the entire cohort and by trial assignment. RESULTS There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68-0.82) among those assigned to vitamin D and 0.90 (0.80-1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100-124 and ≥125 nmol/L were 0.48 (0.29-0.80) and 0.29 (0.17-0.50), respectively, compared with those who maintained a level of 50-74 nmol/L. CONCLUSIONS Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.
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Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a.
Hupperts, R, Smolders, J, Vieth, R, Holmøy, T, Marhardt, K, Schluep, M, Killestein, J, Barkhof, F, Beelke, M, Grimaldi, LME, et al
Neurology. 2019;(20):e1906-e1916
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OBJECTIVE In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. METHODS Eligible patients with RRMS treated with SC interferon-β-1a (IFN-β-1a) 44 μg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-β-1a plus placebo (n = 116) or SC IFN-β-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. RESULTS At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; p = 0.035). CONCLUSIONS SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-β-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. CLINICALTRIALSGOV IDENTIFIER NCT01285401. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that for patients with RRMS treated with SC IFN-β-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.
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Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D3 levels and survival among patients with metastatic colorectal cancer.
Yuan, C, Renfro, L, Ambadwar, PB, Ou, FS, McLeod, HL, Innocenti, F, Meyerhardt, JA, Wolpin, BM, Goldberg, RM, Grothey, A, et al
Cancer causes & control : CCC. 2019;(7):757-765
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PURPOSE The relationships of genetic variation in the vitamin D pathway with circulating 25-hydroxyvitamin D3 [25(OH)D] levels and survival remain largely unknown for patients with metastatic colorectal cancer (mCRC). METHODS Among 535 patients participating in a randomized trial of chemotherapy for mCRC, we prospectively measured baseline plasma 25(OH)D and examined 124 tagging single-nucleotide polymorphisms (SNPs) within seven genes in the vitamin D pathway, including five SNPs associated with circulating 25(OH)D levels in previous genome-wide association studies (GWAS). We evaluated whether these SNPs were associated with plasma 25(OH)D levels and patient outcome (overall survival, time to progression, and tumor response), using linear, logistic, and Cox proportional hazards regression. RESULTS We observed a significant association between 25(OH)D levels and an additive genetic risk score determined by the five GWAS-identified SNPs (p = 0.0009). We did not observe any direct association between 25(OH)D-associated SNPs, individually or as a genetic risk score, and patient outcome. However, we found a significant interaction between 25(OH)D levels and rs12785878 genotype in DHCR7 on overall survival (pinteraction = 0.02). CONCLUSION Germline genetic variation in the vitamin D pathway informs baseline 25(OH)D levels among patients with mCRC. The association between 25(OH)D levels and overall survival may vary by DHCR7 genotype. ClinicalTrials.gov Identifier: NCT00003594 ( https://clinicaltrials.gov/ct2/show/NCT00003594 ).