The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies.

Chronic low-grade inflammation accompanies obesity and its related chronic conditions. Both peripheral blood mononuclear cells (PBMCs) and cell lines have been used to study whether vitamin D has immune modulating effects; however, to date a detailed systematic review describing the published evidence has not been completed. We therefore conducted a systematic review on the effect of vitamin D on the protein expression and secretion of inflammatory markers by human-derived immune cells. The review was registered at the International Prospective Register for Systematic Reviews (PROSPERO, Registration number CRD42015023222). A literature search was conducted using Pubmed, Science Direct, Scopus, Web of Science and Medline. The search strategy used the following search terms: Vitamin D or cholecalciferol or 1,25-dihydroxyvitamin or 25-hydroxy-Vitamin D and Inflam* or cytokine* and supplement* or cell*. These terms were searched in the abstract, title and keywords. Inclusion criteria for study selection consisted of human-derived immune cell lines or cellular studies where PBMCs were obtained from humans, reported in the English language, and within the time period of 2000 to 2015. The selection protocol was mapped according to PRISMA guidelines. Twenty three studies (7 cell line and 16 PBMCs studies) met our criteria. All studies selected except one used the active metabolite 1,25(OH)2, with one study using cholecalciferol and two studies also using 25(OH)D. Four out of seven cell line studies showed an anti-inflammatory effect where suppression of key markers such as macrophage chemotactic protein 1, interleukin 6 and interleukin 8 were observed. Fourteen of sixteen PBMC studies also showed a similar anti-inflammatory effect based on common inflammatory endpoints. Mechanisms for such effects included decreased protein expression of toll-like receptor-2 and toll-like receptor-4; lower levels of phosphorylated p38 and p42/42; reduced expression of phosphorylated signal transducer and activator of transcription 5 and decreased reactive oxygen species. This review demonstrates that an anti-inflammatory effect of vitamin D is a consistent observation in studies of cell lines and human derived PBMCs

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

The role of vitamin D status in the bioenergetics of inflammation

This thesis investigates the role of vitamin D metabolites 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D in human bioenergetics and inflammation. The evidence presented comes from a narrative review, two systematic reviews, two cross-sectional studies and an observational longitudinal study design. Collectively, the thesis supports a modulatory role for vitamin D in whole body and cellular bioenergetics and inflammation. Future studies could build on these findings; establishing a causal role for vitamin D in inflammation and energy metabolism

Certain Dietary Patterns Are Beneficial for the Metabolic Syndrome: Reviewing the Evidence

The metabolic syndrome (MetS) is a global public health issue of increasing magnitude. The Asia-Pacific region is expected to be hardest hit due to large population numbers, rising obesity, and insulin resistance (IR). This review assessed the protective effects of dietary patterns and their components on MetS. A literature search was conducted using prominent electronic databases and search terms that included in combination: diet, dietary components, dietary patterns, and metabolic syndrome. Articles were restricted to prospective studies and high quality randomized controlled trials that were conducted on humans, reported in the English language, and within the time period of 2000 to 2012. Traditional factors such as age, gender, physical activity, and obesity were associated with risk of MetS; however, these potential confounders were not always accounted for in study outcomes. Three dietary patterns emerged from the review; a Mediterranean dietary pattern, dietary approaches to stop hypertension diet, and the Nordic Diet. Potential contributors to their beneficial effects on prevalence of MetS or reduction in MetS components included increases in fruits, vegetables, whole grains, dairy and dairy components, calcium, vitamin D, and whey protein, as well as monounsaturated fatty acids, and omega-3 fatty acids. Additional prospective and high quality randomized controlled trial studies that investigate Mediterranean dietary pattern, the dietary approaches to stop hypertension diet, and the Nordic Diet would cement the protective benefits of these diets against the MetS

Vitamin D status and calcium intake in systemic inflammation, insulin resistance and the metabolic syndrome: An update on current evidence

Background: Insufficient vitamin D status and inadequate intakes of calcium are a global concern and appear to be inversely linked to the global explosion in prevalence of the metabolic syndrome (MetS). Scope and approach: This review provides an update of the current evidence on causal linkages between these nutrients and MetS. We adopted a simplified model that explored the effects of vitamin D and calcium on systemic inflammation and insulin resistance (IR), as initial derangements in the progression to MetS. We selected systematic reviews (SR) and meta-analyses (MA) of randomized controlled trials (RCTs) or large scale observational studies to better understand the evidence base in the area. Key findings and conclusions: Observational data provided the best evidence for an inverse association between vitamin D status and presence of MetS. There was no convincing evidence from RCTs, except when participants with impaired glucose tolerance were studied. The influence of dietary calcium on systemic inflammation, IR and MetS has been inadequately studied to allow a firm conclusion. However, cellular and molecular evidence support a role for intra-cellular calcium in related disease states. Future long-term RCTs in adequately sampled participant groups are needed. Central to uncovering such extra-skeletal effects is the endpoint of interest, the selection of the study population, the potential of prior genotyping, consensus on ‘optimal’ vitamin D status, and the duration required of future trials. The concomitant study of mechanistic pathways in such trials could uncover potential targets for functional food development and drug therapy

Vitamin D supplementation and body weight status: a systematic review and meta-analysis of randomized controlled trials

Vitamin D is anticipated to have many extra-skeletal health benefits. We questioned whether supplementation with the vitamin influenced body weight and composition. A systematic review and meta-analysis was conducted on high-quality, randomized controlled trials (RCTs) that had supplemented vitamin D without imposing any caloric restriction. Eighteen trials reporting either body weight, body mass index (BMI), fat mass (FM), percentage fat mass (%FM) or lean body mass (LBM) met our criteria. Twelve studies provided the required data for the meta-analysis. Vitamin D supplementation did not influence the standardized mean difference (SMD) for body weight, FM, %FM or LBM. A small but non-significant decrease in BMI (SMD = -0.097, 95% confidence interval: [-0.210, 0.016], P = 0.092) was observed. Meta-regression confirmed that neither the absolute vitamin D status achieved nor its change from baseline influenced the SMD of any obesity measure. However, increasing age of the subjects predicted a shift in the SMD for FM towards the placebo treatment, whereas a greater percentage of women in these studies favoured a decrease in FM following vitamin D. Vitamin D supplementation did not decrease measures of adiposity in the absence of caloric restriction. A potential confounding by age and gender was encountered

Cell studies examining the impact of vitamin D on inflammation.

<p>25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂), interferon gamma IFN-γ, interleukin 1β (IL1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), interleukin 21 (IL-21), monocyte chemotatic protein-1 (MCP-1), no change NC, peripheral blood mononuclear cells (PBMCs), tumor necrosis factor alpha (TNF- α).</p><p>^a Health status of participants unknown</p><p>^b Study conducted in participants with inadequate vitamin D status (serum 25(OH)D < 50 nM</p><p>Cell studies examining the impact of vitamin D on inflammation.</p

Overview of VDR-mediated regulation of cytokine transcription, production and secretion in immune cells.

<p>Interaction of VD3 and VDR leads to anti-inflammatory effects through negative regulation of NFκB and STAT1/5-mediated signalling. This results in decreased transcription of TNF-α, IL-6, MCP1 and IL-12β. VDR activation promotes increased intracellular glutathione levels that partially or fully attenuates excessive ROS production (ROS can activate pro-inflammatory NFκB signalling). Activated VDR regulates transcription of IL-2 and IL-10 through epigenetic and conformational changes in the promoter region of these genes. VDR association with the promoter region occurs in a cyclic fashion, which leads to initial gene suppression, followed by upregulation of IL-2 and IL-10 expression after 48 hours. Pro-inflammatory effects of VD3 were reported and suggested to be linked to increased IL-1β production possibly related to increased ERK1/2 phosphorylation and the transcription factor CEBPβ. The VDR is believed to modulate pro-inflammatory TLR expression both positively and negatively, but the mechanisms are unknown. Plasma membrane associated VDR may induce rapid effects through non-genomic pathways such as modulation of intracellular calcium levels, parathyroid hormone G-protein coupled or other second messenger systems. Non-genomic pathways may cooperate with genomic pathways to influence gene expression. CCAAT/enhancer binding protein beta (CEBPβ), extracellular signal-regulated kinase1/2 (ERK1/2), janus kinase (JAK), monocyte chemotatic protein1 (MCP-1), nuclear factor kappa light chain enhancer of activated B cells (NFκB), mitogen activated protein kinase (p38 MAPK), retinoid X receptor (RXR), reactive oxygen species (ROS), signal transducer and activator of transcription1/5 (STAT1/5), toll-like receptor-2/4 (TLR2/4), tumour necrosis factor alpha (TNF-α), vitamin D3 (VD3), vitamin D receptor (VDR).</p

PRISMA flow diagram depicting the systematic study selection process.

<p>PBMC, peripheral blood mononuclear cells.</p

Efficacy of a weight loss program prior to robot assisted radical prostatectomy in overweight and obese men with prostate cancer

Background Obesity in prostate cancer patients is associated with poor prostate-cancer specific outcomes. Exercise and nutrition can reduce fat mass; however, few studies have explored this as a combined pre-surgical intervention in clinical practice. Purpose This study examined the efficacy of a weight loss program for altering body composition in prostate cancer patients prior to robot assisted radical prostatectomy (RARP). Methods A retrospective analysis of 43 overweight and obese prostate cancer patients, aged 47–80 years, who completed a very low-calorie diet (~3000–4000 kJ) combined with moderate-intensity exercise (90 min/day) prior to RARP. Whole body and regional fat mass (FM) and lean mass (LM) were assessed by dual-energy x-ray absorptiometry pre- and post-program. Body weight, waist circumference, and blood pressure were assessed weekly, with surgery-related adverse effects recorded at time of surgery and follow-up appointments. Results With a median of 29 days (IQR: 24–35days) on the program, patients significantly (p \u3c 0.001) reduced weight (−7.3 ± 2.9 kg), FM (−5.0 ± 2.6 kg), percent body fat (−3.1 ± 2.5%), trunk FM (−3.4 ± 1.8 kg), LM (−2.4 ± 1.8 kg), and appendicular LM (−1.2 ± 1.0 kg). Lower weight, FM, percent FM, trunk FM, and visceral FM were associated with less surgery-related adverse effects (rs = 0.335 to 0.468, p \u3c 0.010). Systolic and diastolic blood pressure were reduced (p \u3c 0.001) by 15 ± 22 and 8 ± 10 mmHg, respectively over the weight loss intervention. Conclusion Undertaking a combined low-calorie diet and exercise program for weight loss in preparation for RARP resulted in substantial reductions in FM, with improvements in blood pressure, that may benefit surgical outcomes