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Effect of supplementation with omega-3 fatty acids on hypertriglyceridemia in pediatric patients with obesity.
Del-Río-Navarro, BE, Miranda-Lora, AL, Huang, F, Hall-Mondragon, MS, Leija-Martínez, JJ
Journal of pediatric endocrinology & metabolism : JPEM. 2019;(8):811-819
Abstract
Background The beneficial effects of treating hypertriglyceridemic adults with omega-3 fatty acids have been reported. However, information regarding omega-3 treatment of pediatric patients is limited. To evaluate the efficacy and safety of administering omega-3 fatty acids (3 g/day for 12 weeks) to children/adolescents with obesity and hypertriglyceridemia. Methods A randomized, double-blind, placebo-controlled, parallel study involving pediatric patients (10-16 years old) with obesity and hypertriglyceridemia was conducted. The National Center for Health Statistics (CDC) defines obesity as a body mass index (BMI) ≥95th percentile. Subjects with triglyceride concentrations ranging from 150 to 1000 mg/dL were randomized into two groups: those receiving omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) (n = 65) and those receiving a placebo (n = 65) for 12 weeks. Serum triglyceride concentrations were always measured from 8 to 9 am after a 12-h fast. Results By the end of treatment, triglyceride concentrations had decreased by 39.1% in the omega-3 group and 14.6% in the placebo group (p < 0.01). The incidence of adverse gastrointestinal events (e.g. flatulence, belching) was 41.2% and 6.2% in the omega-3 and placebo groups, respectively (p < 0.01). There were no serious drug-related adverse events. Conclusions Supplementation with 3 g/day of omega-3 fatty acids is a safe and effective option for treating hypertriglyceridemia in children and adolescents with obesity.
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Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis.
Rahimlou, M, Asadi, M, Banaei Jahromi, N, Mansoori, A
Clinical nutrition ESPEN. 2019;:16-28
Abstract
BACKGROUND & AIMS Several randomized clinical trials (RCTs) have investigated the effect of Alpha - Lipoic Acid (ALA) supplementation on metabolic parameters, with conflicting results. Therefore, the present study assessed the effect of ALA on some glycemic and inflammatory parameters. METHODS A comprehensive literature search was conducted up from inception to July 2018 on PubMed, Scopus, Cochrane databases, Google Scholar, ProQuest, Web of Science, and Embase. From among eligible trials, 41 articles were selected for the meta-analysis. Two reviewers independently assessed the risk of bias and extracted data from the included studies. Meta-analyses using the random-effects model were performed to analyze the data. RESULTS Based on the Cochrane risk of bias tool, 19 articles had a good quality, 16 trials had a poor quality and 6 trials had a fair quality. The results demonstrated the significant effect of ALA on Fasting Blood Sugar (FBS) (weighted mean difference (WMD)) = -6.57, 95% confidence interval (CI: -11.91 to -1.23, P = 0.016), Hemoglobin A1c (HbA1c) (WMD = -0.35, 95% CI: -0.55 to -0.15, P = 0.004), Tumor Necrosis Factor Alpha (TNF-α) (WMD = -1.57, 95% CI: -2.29 to -0.85, P < 0.05), Interleukin 6 levels (IL-6) (WMD = -1.15, 95% CI: -1.58 to -0.72, P < 0.001), and C-reactive protein (CRP) (WMD = -0.31, 95% CI: -0.47 to -0.16, P > 0.001). No effect was detected for ALA on insulin and the homeostatic model assessment of insulin resistance (HOMA-IR). CONCLUSIONS These findings suggest that ALA is a viable supplement to improve some of the glycemic and inflammatory biomarkers.
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Randomized Double-Blind Placebo-Controlled Biomarker Modulation Study of Vitamin D Supplementation in Premenopausal Women at High Risk for Breast Cancer (SWOG S0812).
Crew, KD, Anderson, GL, Hershman, DL, Terry, MB, Tehranifar, P, Lew, DL, Yee, M, Brown, EA, Kairouz, SS, Kuwajerwala, N, et al
Cancer prevention research (Philadelphia, Pa.). 2019;(7):481-490
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Abstract
Observational studies have reported an inverse association between vitamin D intake and breast cancer risk. We examined whether vitamin D supplementation in high-risk premenopausal women reduces mammographic density (MD), an established breast cancer risk factor. We conducted a multicenter randomized double-blind placebo-controlled trial in premenopausal women at high risk for breast cancer [5-year risk ≥ 1.67%, lifetime risk ≥ 20%, lobular carcinoma in situ, prior stage 0-II breast cancer, hereditary breast cancer syndrome, or high MD (heterogeneously/extremely dense)], with a baseline serum 25-hydroxyvitamin D [25(OH)D] ≤ 32 ng/mL. Participants were randomized to 12 months of vitamin D3 20,000 IU/week or matching placebo. The primary endpoint was change in MD from baseline to 12 months using the Cumulus technique. Secondary endpoints included serial blood biomarkers [25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), insulin-like growth factor (IGF)-1, IGF-binding protein-3] and MD change at 24 months. Among 208 women randomized, median age was 44.6 years, 84% were white, 33% had baseline 25(OH)D < 20 ng/mL, and 78% had high baseline MD. Comparing the active and placebo groups at 12 months, MD changes were small and did not significantly differ. Mean MD changes at 12 and 24 months were -0.3% and -1.2%, respectively, in the active arm and +1.5% and +1.6% with placebo (P > 0.05). We observed a mean change in serum 25(OH)D of +18.9 versus +2.8 ng/mL (P < 0.01) and IGF-1 of -9.8 versus -1.8 ng/mL (P = 0.28), respectively. At 12 months, MD was positively correlated with serum IGF-1 and IGF-1/IGFBP-3 (P < 0.01). This trial does not support the use of vitamin D supplementation for breast cancer risk reduction.
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High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes.
Filardi, T, Carnevale, V, Massoud, R, Russo, C, Nieddu, L, Tavaglione, F, Turinese, I, Lenzi, A, Romagnoli, E, Morano, S
Journal of endocrinological investigation. 2019;(3):295-301
Abstract
PURPOSE Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. METHODS Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. RESULTS OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9-31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. CONCLUSIONS In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile.
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Effects of ginseng supplementation on selected markers of inflammation: A systematic review and meta-analysis.
Mohammadi, H, Hadi, A, Kord-Varkaneh, H, Arab, A, Afshari, M, Ferguson, AJR, Ghaedi, E
Phytotherapy research : PTR. 2019;(8):1991-2001
Abstract
The present meta-analysis was performed to evaluate the efficacy of ginseng administration on serum level of inflammatory biomarkers. We performed a systematic search of all available randomized controlled trials (RCTs) conducted up to June 2018 in the following electronic databases: PubMed, Scopus, Cochrane, and Google Scholar. RCTs that investigated the effect ginseng supplementation on high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were included for final analysis. A total of seven RCTs were included in the meta-analysis. Results indicated significant reduction in IL-6 (mean difference [MD]: -0.265 pg/ml, 95% CI [-0.396, -0.135], p < .001) and TNF-α (MD: -2.471 pg/ml, 95% CI [-2.904, -2.039], p < .001) and no significant change in hs-CRP (MD: -0.125 mg/L, 95% CI [-0.597, 0.347], p = .604). Although there was publication bias across studies, trim and fill analysis showed that results from unpublished studies could not change the results for CRP. However, removing one study in sensitivity analysis did reveal a significant reduction in CRP. We conclude that ginseng supplementation significantly lowered IL-6 and TNF-α but did not significantly lower CRP. However, these findings were not robust, because they showed sensitivity for CRP and IL-6, and future long-term well-designed dose-escalating trials are required.
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Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?
Cumpstey, AF, Minnion, M, Fernandez, BO, Mikus-Lelinska, M, Mitchell, K, Martin, DS, Grocott, MPW, Feelisch, M, ,
Redox biology. 2019;:101113
Abstract
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this 'Reactive Species Interactome' (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable 'metabolic signatures' to a defined physiological challenge could potentially offer new avenues for personalised medicine.
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Serum Biomarkers of Iron Status and Risk of Primary Liver Cancer: A Systematic Review and Meta-Analysis.
Tran, KT, Coleman, HG, McCain, RS, Cardwell, CR
Nutrition and cancer. 2019;(8):1365-1373
Abstract
Hereditary hemochromatosis, a disease which causes iron overload, has been shown to increase liver cancer risk but the association between serum iron levels within non-hemochromatosis population and liver cancer risk is unclear. We investigated this association by conducting a systematic review and meta-analysis. Medline, Embase, and Scopus were searched to identify articles published up to January 2019. The search incorporated terms for liver cancer (hepatocellular and cholangiocarcinoma) and for serum iron (iron, ferritin, and transferrin). Briefly, nested case-control or cohort studies were included if they recorded a measure of iron, prior to diagnosis, and contained liver cancer patients and controls. Meta-analysis techniques were used to calculate pooled hazard ratios (HRs) and investigate heterogeneity between studies. Nine relevant studies were identified. There was evidence of an association between high serum ferritin and primary liver cancer risk (six studies, HR 1.49, 95% CI 1.13, 1.96) and high serum iron and primary liver cancer risk (three studies, HR 2.47 95% CI 1.31, 4.63). However, these associations were subject to heterogeneity (I2 = 62%, P = 0.02 and I2=80%, P = 0.007, respectively). In conclusion, we found some evidence that increased iron levels was associated with primary liver cancer. The cause of this association merits additional research.
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A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.
Chashmniam, S, Mirhafez, SR, Dehabeh, M, Hariri, M, Azimi Nezhad, M, Nobakht M Gh, BF
European journal of clinical nutrition. 2019;(9):1224-1235
Abstract
BACKGROUND/OBJECTIVES Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. SUBJECTS/METHODS Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR. RESULTS Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC). CONCLUSIONS Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.
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Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals.
Hang, D, Kværner, AS, Ma, W, Hu, Y, Tabung, FK, Nan, H, Hu, Z, Shen, H, Mucci, LA, Chan, AT, et al
The American journal of clinical nutrition. 2019;(3):635-647
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Abstract
BACKGROUND Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. OBJECTIVES The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. METHODS We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. RESULTS Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. CONCLUSION Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.
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The importance of measurement of plasma fibrinogen level among patients with type- 2 diabetes mellitus.
Abdul Razak, MK, Sultan, AA
Diabetes & metabolic syndrome. 2019;(2):1151-1158
Abstract
BACKGROUND & AIM: Fibrinogen has been implicated as a cause of atherosclerosis and its complications in patients with type 2 DM. We aimed to measure the plasma fibrinogen level in type 2 diabetics and to correlate it with the duration, type of treatment, HbA1c, smoking, lipid profile, diabetic retinopathy, hypertension and ischemic heart disease in comparison to control. METHODS A case control single center study included 50 patients with type 2 DM between the ages of 35-85 y who were randomly selected from the medical units of Baghdad Teaching Hospital compared to 30 non-diabetics as a control. After taking verbal consents; plasma fibrinogen levels were estimated and correlated with aimed variables. Odds ratios with 95% CI were calculated and regression analysis was performed for correlations. P ≤ 0.05 was considered statistically significant. RESULTS There were statistically significant differences regarding total cholesterol, TG, and LDL between cases and control. Mean HbA1c of diabetics was 8.31 ± 1.75% (P < 0.001). Cases showed plasma fibrinogen of (4.01 ± 1.89 g/dL) compared to (2.79 ± 0.55 g/dL) of control (P < 0.001). ROC curve revealed that the AUC was (0.679 ± 0.06, 95%CI = 0.561-0.797, P < 0.008). The sensitivity and specificity of the test at cut off value of 3.05 g/dL were 0.62 and 0.567 respectively. There was a significant correlation between fibrinogen level and each of HbA1c (r = 0.497, P < 0.001) and TG (r = 0.359, P = 0.01). CONCLUSIONS HbA1c has a significant positive effect on plasma fibrinogen and it is important to measure plasma fibrinogen level in patients with type 2 DM.