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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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Inflammatory responses relate to distinct bronchoalveolar lavage lipidome in community-acquired pneumonia patients: a pilot study.
Zheng, Y, Ning, P, Luo, Q, He, Y, Yu, X, Liu, X, Chen, Y, Wang, X, Kang, Y, Gao, Z
Respiratory research. 2019;(1):82
Abstract
BACKGROUND Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance. Characterization of the lipidomic response to pneumonia and exploring the "lipidomic phenotype" can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. METHODS Lipid profiles of bronchoalveolar lavage fluid (BALF) samples were generated through untargeted lipidomic profiling analysis using high-performance liquid chromatography with mass spectrometry (HPLC-MS). Principal component analysis (PCA) was applied to identify possible sources of variations among samples. Partitioning clustering analysis (k-means) was employed to evaluate the existence of distinct lipidomic clusters. RESULTS PCA showed that BALF lipidomes differed significantly between CAP (n = 52) and controls (n = 68, including 35 healthy volunteers and 33 patients with non-infectious lung diseases); while no clear separation was found between severe CAP and non-severe CAP cases. Lactosylceramides were the most prominently elevated lipid constituent in CAP. Clustering analysis revealed three separate lipid profiles; subjects in each cluster exhibited significant differences in disease severity, incidence of hypoxemia, percentages of phagocytes in BALF, and serum concentrations of albumin and total cholesterol (all p < 0.05). In addition, SM (d34:1) was negatively related to macrophage (adjusted r = - 0.462, p < 0.0001) and PE (18:1p/20:4) was positively correlated with polymorphonuclear neutrophil (PMN) percentages of BALF (adjusted r = 0.541, p < 0.0001). The 30-day mortality did not differ amongst three clusters (p < 0.05). CONCLUSIONS Our data suggest that specific lower airway lipid composition is related to different intensities of host inflammatory responses, and may contribute to functionally relevant shifts in disease pathogenesis in CAP individuals. These findings argue for the need to tailor therapy based on specific lipid profiles and related inflammatory status. TRIAL REGISTRATION ClinicalTrials.gov (NCT03093220). Registered on 28 March 2017 (retrospectively registered).
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The effect of carvacrol on inflammatory mediators and respiratory symptoms in veterans exposed to sulfur mustard, a randomized, placebo-controlled trial.
Khazdair, MR, Boskabady, MH
Respiratory medicine. 2019;:21-29
Abstract
BACKGROUND The aim of this study was to evaluate the effect of carvacrol on serum level of inflammatory mediators and respiratory symptoms in the veterans exposed to sulfur mustard (SM). METHODS Twenty-one patients who were exposed to SM more than two decades' ago were divided to placebo and carvacrol (1.2 mg/kg/day) treated groups. Serum levels of Tumor Necrosis Factor-α (TNF-α), Monocyte chemotactic protein-1 (MCP-1), Vascular endothelial growth factor (VEGF), Epidermal growth factor (EGF), forced expiratory volume-one second (FEV1) and respiratory symptoms including; Chest wheeze (CW), night wheeze (NW), night cough (NC) and cough and wheeze during exercise (ECW) were assessed at the baseline (step 0), one and two months after starting treatment (step I and II, respectively). FINDINGS FEV1 value was significantly increased in carvacrol treated group in step II compared to step 0 (p < 0.001) and also increased in step II compared to step I (p < 0.05). The respiratory symptoms including; CW and NW was significant decreased in carvacrol treated group in step I and II compared to step 0 (p < 0.01 to p < 0.001), NC and ECW were significantly decreased only in step II compared to step 0 (p < 0.01, for both cases). The serum levels of TNF-α, EGF and VEGF were decrease in carvacrol treated group in step I and II compared to step 0 (p < 0.05 to p < 0.001). The serum level of MCP-1 was decrease in carvacrol treated group only in the step II compared to step 0 (p < 0.05). INTERPRETATION Two months' treatment with carvacrol reduced inflammatory cytokine and chemokine while increased anti-inflammatory cytokines and improved respiratory symptom and FEV1 value in SM exposed patients. CLINICAL TRIALS REGISTRY NUMBER This trial was registered under IRCT2014031617020N1 at http://www.irct.ir/.
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The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men.
Kresovich, JK, Bulka, CM, Joyce, BT, Vokonas, PS, Schwartz, J, Baccarelli, AA, Hibler, EA, Hou, L
Biological trace element research. 2018;(1):49-57
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Manganese is an essential nutrient that may play a role in the production of inflammatory biomarkers. We examined associations between estimated dietary manganese intake from food/beverages and supplements with circulating biomarkers of inflammation. We further explored whether estimated dietary manganese intake affects DNA methylation of selected genes involved in the production of these biomarkers. We analyzed 1023 repeated measures of estimated dietary manganese intakes and circulating blood inflammatory biomarkers from 633 participants in the Normative Aging Study. Using mixed-effect linear regression models adjusted for covariates, we observed positive linear trends between estimated dietary manganese intakes and three circulating interleukin proteins. Relative to the lowest quartile of estimated intake, concentrations of IL-1β were 46% greater (95% CI - 5, 126), IL-6 52% greater (95% CI - 9, 156). and IL-8 32% greater (95% CI 2, 71) in the highest quartiles of estimated intake. Estimated dietary manganese intake was additionally associated with changes in DNA methylation of inflammatory biomarker-producing genes. Higher estimated intake was associated with higher methylation of NF-κβ member activator NKAP (Q4 vs Q1: β = 3.32, 95% CI - 0.6, 7.3). When stratified by regulatory function, higher manganese intake was associated with higher gene body methylation of NF-κβ member activators NKAP (Q4 vs Q1: β = 10.10, 95% CI - 0.8, 21) and NKAPP1 (Q4 vs Q1: β = 8.14, 95% CI 1.1, 15). While needed at trace amounts for various physiologic functions, our results suggest estimated dietary intakes of manganese at levels slightly above nutritional adequacy contribute to inflammatory biomarker production.
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An Empirical Dietary Inflammatory Pattern Score Is Associated with Circulating Inflammatory Biomarkers in a Multi-Ethnic Population of Postmenopausal Women in the United States.
Tabung, FK, Giovannucci, EL, Giulianini, F, Liang, L, Chandler, PD, Balasubramanian, R, Manson, JE, Cespedes Feliciano, EM, Hayden, KM, Van Horn, L, et al
The Journal of nutrition. 2018;(5):771-780
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BACKGROUND The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans. OBJECTIVE We used the EDIP score, a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating concentrations of inflammatory biomarkers, to test the hypothesis that a pro-inflammatory dietary pattern is associated with inflammatory biomarker concentrations in a US multi-ethnic population. METHODS In this cross-sectional study, we calculated EDIP scores using baseline food frequency questionnaire data from 31,472 women, aged 50-79 y, in the Women's Health Initiative observational study and clinical trials. Circulating biomarkers outcomes at baseline were: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1 and 2, and adiponectin. We used multivariable-adjusted linear regression analyses to estimate absolute concentrations and relative differences in biomarker concentrations, overall and in subgroups of race/ethnicity and BMI (body mass index) categories. RESULTS Independent of energy intake, BMI, physical activity, and other potential confounding variables, higher EDIP scores were significantly associated with higher (lower for adiponectin) absolute concentrations of all 6 biomarkers. On the relative scale, the percentage of difference in the concentration of biomarkers, among women in the highest compared to the lowest EDIP quintile, was: CRP, +13% (P-trend < 0.0001); IL-6, +15% (P-trend < 0.0001); TNF-α, +7% (P-trend = 0.0007); TNFR1, +4% (P-trend = 0.0009); TNFR2, +5% (P-trend < 0.0001); and adiponectin, -13% (P-trend <0.0001). These associations differed by racial/ethnic groups and by BMI categories. Whereas the absolute biomarker concentrations were lower among European-American women and among normal-weight women, the associations with diet were stronger than among women of African-American or Hispanic/Latino origin and among overweight and obese women. CONCLUSIONS Findings demonstrate the successful replication of an empirical hypothesis-oriented a posteriori dietary pattern score in a multi-ethnic population of postmenopausal women, with subgroup differences by race/ethnicity and body weight. Future research needs to apply the score in non-US populations.
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Particulate metal exposures induce plasma metabolome changes in a commuter panel study.
Ladva, CN, Golan, R, Liang, D, Greenwald, R, Walker, DI, Uppal, K, Raysoni, AU, Tran, V, Yu, T, Flanders, WD, et al
PloS one. 2018;(9):e0203468
Abstract
INTRODUCTION Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. METHODS A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. RESULTS HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. CONCLUSIONS Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
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Effects of Guanidinoacetic Acid Loading on Biomarkers of Cardiometabolic Risk and Inflammation.
Ostojic, SM, Trivic, T, Drid, P, Stajer, V, Vranes, M
Annals of nutrition & metabolism. 2018;(1):18-20
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A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults.
Paniz, C, Bertinato, JF, Lucena, MR, De Carli, E, Amorim, PMDS, Gomes, GW, Palchetti, CZ, Figueiredo, MS, Pfeiffer, CM, Fazili, Z, et al
The Journal of nutrition. 2017;(9):1677-1685
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Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor necrosis factor α (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers.Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m2) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells.Results: Serum folate concentrations increased by ∼5-fold after the intervention (P < 0.001), and UMFA concentrations increased by 11.9- and 5.9-fold at 45 and 90 d, respectively, when compared with baseline (P < 0.001). UMFA concentrations increased (>1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number (P < 0.001) and cytotoxicity (P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d (P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d (P = 0.001 for both).Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp.
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Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.
Kirpich, IA, McClain, CJ, Vatsalya, V, Schwandt, M, Phillips, M, Falkner, KC, Zhang, L, Harwell, C, George, DT, Umhau, JC
Alcoholism, clinical and experimental research. 2017;(4):747-757
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BACKGROUND Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program. METHODS A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury). Group 1 (ALT < 40 U/l, 7M/8F) and Group 2 (ALT ≥ 40 U/l, 27M/6F) were identified. Plasma biomarkers of liver damage, endotoxemia, and inflammation were examined at baseline, day 8, and day 15 of the admission. The drinking history was also evaluated. RESULTS Sixty-nine percent of patients had elevated ALT and other markers of liver damage, including aspartate aminotransferase and cytokeratin 18 (CK18 M65 and CK M30) at baseline, indicating the presence of mild ALD. Elevated CK18 M65:M30 ratio suggested a greater contribution of necrotic rather than apoptotic hepatocyte cell death in the liver injury observed in these individuals. Females showed greater elevations of liver injury markers compared to males, although they had fewer drinks per day and shorter lifetime duration of heavy drinking. Liver injury was associated with systemic inflammation, specifically, elevated plasma tumor necrosis factor-alpha levels. Compared to patients without liver injury, patients with mild ALD had greater endotoxemia (increased serum lipopolysaccharide levels), which decreased with abstinence and this decrease preceded the drop in CK18 M65 levels. CONCLUSIONS The study documented the association of mild alcohol-induced liver injury and endotoxemia, which improved with 2 weeks of abstinence, in a subset of individuals admitted to an alcohol detoxification program.
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Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmö Diet and Cancer Cohort.
Dias, JA, Fredrikson, GN, Ericson, U, Gullberg, B, Hedblad, B, Engström, G, Borgquist, S, Nilsson, J, Wirfält, E
PloS one. 2016;(7):e0158959
Abstract
OBJECTIVE Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association. METHODS In the Malmö Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55-73 years at baseline (1991-96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression. RESULTS Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47-0.90), 0.63 (0.45-0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43-0.99), p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05-2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer. CONCLUSION Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.