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Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer.
Demark-Wahnefried, W, Rais-Bahrami, S, Desmond, RA, Gordetsky, JB, Hunter, GR, Yang, ES, Azrad, M, Frugé, AD, Tsuruta, Y, Norian, LA, et al
British journal of cancer. 2017;117(9):1303-1313
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Obesity is a risk factor for 13 different cancers and a recent meta-analysis has shown increased weight to be associated with biochemical recurrence in men with prostate cancer. However, few studies have explored whether presurgical intentional weight loss results in improved prostate cancer outcomes. The aim of this trial was to explore the efficacy of weight loss among overweight and obese men with prostate cancer. Forty participants were randomised to either the presurgical weight loss intervention group or control arm, and changes in weight, body composition, quality of life, tumour biology and biomarkers were recorded. This study found that intentional weight loss caused mixed effects on tumour proliferation and gene expression. Based on these results, the authors recommend that more research is needed before effectively recommending presurgical weight loss among overweight men with prostate cancer.
Abstract
BACKGROUND Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. METHODS This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. RESULTS The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P=0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs -1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P=0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. CONCLUSIONS Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.
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Adipose Tissue Meal-Derived Fatty Acid Uptake Before and After Diet-Induced Weight Loss in Adults with Overweight and Obesity.
Vink, RG, Roumans, NJ, van der Kolk, BW, Fazelzadeh, P, Boekschoten, MV, Mariman, EC, van Baak, MA
Obesity (Silver Spring, Md.). 2017;25(8):1391-1399
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Weight loss among the obese population is difficult to sustain and there is substantial evidence arising that biological and metabolic mechanisms are a crucial factor. In obese people, the ability of adipose tissue to remove fatty acids from circulation is impaired, and it is hypothesised that reducing the size of adipose cells through weight loss will increase the storage capacity in adipose tissue, leading to greater uptake for circulating fatty acids. Therefore the aim of this study was to investigate whether diet-induced weight loss alters fat uptake in adipose tissue. In this randomised controlled trial, 16 individuals were assigned to either a low-calorie diet for 12-weeks or very low calorie diet for 5-weeks, both followed by a 4-week weight stable period and a 9-month follow up. Blood samples, adipose tissue biopsies and anthropometric measurements were taken at baseline, after weight loss, after weight stable period and at follow-up. Contrary to hypothesis, this study found that fatty acid uptake dynamics and expression of genes involved in fat metabolism were not significantly changed during the intervention period. Based on these results, the authors did not detect dietary weight loss-induced changes in gene expression involved in fat metabolism.
Abstract
OBJECTIVE This study investigated whether diet-induced weight loss alters indices of in vivo postprandial fat uptake in adipose tissue (AT) and whether these changes are associated with weight regain in adults with overweight and obesity. METHODS In this randomized controlled trial, 16 (6 male) individuals (BMI: 28-35 kg/m2 ) were randomized to either a low-calorie diet (1,250 kcal/d) for 12 weeks or a very-low-calorie diet (500 kcal/d) for 5 weeks (weight loss [WL] period) followed by a 4-week weight-stable (WS) period (together, the dietary intervention [DI] period) and a 9-month follow-up period. Arteriovenous difference measurements combined with stable isotope labeling ([U-13 C] palmitate) of a mixed meal were used to determine postprandial fatty acid uptake in AT. RESULTS Body weight was significantly reduced during the WL period (-8.2 ± 0.6 kg, P < 0.001), remained stable during the WS period (0.4 ± 0.3 kg, P = 0.150), and increased during follow-up (3.5 ± 0.8 kg, P = 0.001). Meal-derived in vivo fatty acid uptake dynamics across AT and expression of genes important for fatty acid uptake, storage, and release were not significantly changed during the DI period. CONCLUSIONS Subcutaneous AT does not appear prone to enhanced meal-derived fatty acid uptake after weight loss, nor were fatty acid uptake dynamics detected as related to weight regain.
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Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial.
de Courten, B, Mousa, A, Naderpoor, N, Teede, H, de Courten, MP, Scragg, R
Trials. 2015;16:335
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With the rising rates of vitamin D deficiency, identifying cost-effective, preventative strategies are imperative. Vitamin D plays a well-known role in bone mineralisation, however its protective role against chronic diseases is not very well understood. The aim of this trial is to investigate whether vitamin D supplementation will increase insulin sensitivity and secretion, as well as to determine whether vitamin D deficiency underlies the inflammatory properties associated with obesity. 50 overweight adults between 18 and 60 years old were recruited and assigned to receive either 4,000 IU vitamin D daily or identical placebo capsules for 16 weeks. This study elucidates the potential role vitamin D supplementation could have on preventing diabetes and its associated co-morbidities. It also provides comprehensive insight into the potential mechanisms of action. The authors conclude that this trial can corroborate existing knowledge while expanding the understanding on the role of vitamin D in the inflammatory response and subsequent development of disease.
Abstract
BACKGROUND Despite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity. METHODS/DESIGN Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers. DISCUSSION The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes. TRIAL REGISTRATION Clinicaltrials.gov ID: NCT02112721 .
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Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.
Salden, BN, Monserrat, V, Troost, FJ, Bruins, MJ, Edens, L, Bartholomé, R, Haenen, GR, Winkens, B, Koning, F, Masclee, AA
Alimentary pharmacology & therapeutics. 2015;42(3):273-85
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Gluten is high in proline, an amino acid that is not naturally broken down in the human gastrointestinal tract. In patients with coeliac disease, proline-rich gluten reaches the small intestine and triggers an abnormal immune response, causing inflammation and microvilli damage. The aim of this randomised study was to test the efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) on gluten degradation. AN-PEP belongs to a family of enzymes that has been previously known to break down proline in vitro. The study included 12 healthy volunteers aged 18-45 who were administered a low or high calorie meal containing 4.0g of gluten protein, with AN-PEP or placebo into the stomach. The findings of this study showed that AN-PEP significantly enhanced gluten digestion in the stomach before entering the duodenum of healthy volunteers. Based on this study, the authors conclude that AN-PEP is a promising option for degrading inadvertent dietary gluten consumption, and should be evaluated in target populations.
Abstract
BACKGROUND Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. AIM: To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. METHODS In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. Via a triple-lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240-min area under the curve (AUC0-240 min ) of ?-gliadin concentrations. Absolute ?-gliadin AUC0-240 min was calculated using duodenal PEG-3350 concentrations. RESULTS AN-PEP lowered α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 μg × min/mL; P = 0.001). CONCLUSIONS AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN-PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.
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Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth): a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study.
Bohl, M, Bjørnshave, A, Rasmussen, KV, Schioldan, AG, Amer, B, Larsen, MK, Dalsgaard, TK, Holst, JJ, Herrmann, A, O'Neill, S, et al
The American journal of clinical nutrition. 2015;101(4):870-8
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The health effects of dairy products on cardiovascular disease (CVD), diabetes, obesity and total mortality may depend on their varying composition. This study aims to examine the long-term effects of milk proteins (whey and casein) and milk with a high or low content of medium-chain saturated fatty acids (MC-SFAs) on postprandial lipid metabolism. In this randomised, parallel-controlled, double-blinded, 12-week intervention study, 63 abdominally obese individuals were randomised to one of four diets, containing different compositions of whey, casein and MC-SFAs. Results showed that whey compared to casein significantly decreased postprandial apoB-48, independently of the fatty acid composition. Fasting and postprandial triacylglycerol and FFA responses were independent of protein or fatty acids composition. Authors conclude that 12-week supplementation with whey protein reduces postprandial apoB-48 compared to casein, indicating a beneficial effect on CVD risk.
Abstract
BACKGROUND Abdominal obesity and exaggerated postprandial lipemia are independent risk factors for cardiovascular disease (CVD) and mortality, and both are affected by dietary behavior. OBJECTIVE We investigated whether dietary supplementation with whey protein and medium-chain saturated fatty acids (MC-SFAs) improved postprandial lipid metabolism in humans with abdominal obesity. DESIGN We conducted a 12-wk, randomized, double-blinded, diet intervention study. Sixty-three adults were randomly allocated to one of 4 diets in a 2 × 2 factorial design. Participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (with high or low MC-SFA content) daily. Before and after the intervention, a high-fat meal test was performed. We measured changes from baseline in fasting and postprandial triacylglycerol, apolipoprotein B-48 (apoB-48; reflecting chylomicrons of intestinal origin), free fatty acids (FFAs), insulin, glucose, glucagon, glucagon-like peptide 1 (GLP-1), and gastric inhibitory polypeptide (GIP). Furthermore, changes in the expression of adipose tissue genes involved in lipid metabolism were investigated. Two-factor ANOVA was used to examine the difference between protein types and fatty acid compositions, as well as any interaction between the two. RESULTS Fifty-two participants completed the study. We found that the postprandial apoB-48 response decreased significantly after whey compared with casein (P = 0.025) independently of fatty acid composition. Furthermore, supplementation with casein resulted in a significant increase in the postprandial GLP-1 response compared with whey (P = 0.003). We found no difference in postprandial triacylglycerol, FFA, insulin, glucose, glucagon, or GIP related to protein type or MC-SFA content. We observed no interaction between milk protein and milk fat on postprandial lipemia. CONCLUSION We found that a whey protein supplement decreased the postprandial chylomicron response compared with casein in persons with abdominal obesity, thereby indicating a beneficial impact on CVD risk. This trial was registered at clinicaltrials.gov as NCT01472666.
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A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.
Vazquez-Roque, MI, Camilleri, M, Smyrk, T, Murray, JA, Marietta, E, O'Neill, J, Carlson, P, Lamsam, J, Janzow, D, Eckert, D, et al
Gastroenterology. 2013;144(5):903-911.e3
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The relationship between gluten exposure and diarrhoea-predominant irritable bowel syndrome (IBS-D) is not well understood. Non-celiac IBS-D patients who are positive for HLA-DQ2/8 genes associated with CD can show symptom improvement on a gluten-free diet (GFD). The aim of this 4-week parallel randomized controlled clinical trial in HLA-DQ2/8 positive and negative patients with IBS-D was to assess the effects of a gluten-containing diet (GCD) compared to a GFD on bowel function, gut transit, small bowel (SB) and colonic barrier functions as measured by two-sugar excretion permeability test and mRNA expression of TJ proteins in mucosa of the small bowel (SB) and rectosigmoid (RS) derived by biopsy. Immune response to diets was also measured as cytokine production from peripheral blood mononuclear cells (PBMCs). Patient were recruited from the Mayo clinic’s database of IBS suffers, and invited to participate. Patients with diagnosed CD were excluded. Genotype analysis was performed for HLA-DQ2 and HLA-DQ8. 22 patients were placed on the GCD (11 HLA-DQ2/8–negative and 11 HLA-DQ2/8–positive) and 23 on the GFD (12 HLA-DQ2/8−negative and 11 HLA-DQ2/8–positive. All meals and snacks were ingested or prepared in the Mayo Clinic. Patients were advised to eat only the foods provided by the study dieticians. Gluten-free and gluten-containing meals were prepared using the same macronutrient content (20% protein, 30% fat, 50% carb). Compliance to the diet was assessed by direct questioning by the dietitians and reported to be excellent. All patients were ingesting gluten in their diet prior to starting the study. At 4-weeks, a statistically significant decrease in stool frequency of subjects on GFD compared to subjects on GCD (p=0.04) was seen. This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (p=0.019) There was no significant diet effect (GFD vs. GCD) on, daily stool form, ease of passage or gastric emptying. The GCD was associated with higher small bowel (SB) permeability (based on 0–2 hr levels of mannitol (p=0.028) and lactulose:mannitol ratio (P=0.0012)). SB permeability was greater in HLA-DQ2/8–positive than −negative patients (P=.018). No significant differences in colonic permeability were observed. Significant diet-associated changes in occludin expression in SB mucosa in the HLA-DQ2 or 8 positive group were seen (p=0.017). Expressions of tight junction proteins (zonulin (ZO-1), occludin, and claudin-1 mRNA) in colonic mucosa were significantly lower in GCD relative to GFD in the overall groups, particularly in subjects with HLA-DQ2 or 8 positive status. Cytokine response was higher (interleukin-10) in response to GCD than GFD (unrelated to HLA genotype). A limitation in the quantification of TJ protein expression is that it was solely based on PCR (mRNA expression). In future, other methods should be included to directly identify these proteins and their distribution. The inability to document alterations in colonic permeability using the 2-sugar excretion profile from 8 to 24 hours is a limitation. This may be due to lack of sensitivity of the lactulose and mannitol excretion test, for example, due to the metabolism of both sugars by colonic bacteria. Another limitation is that the mechanism for improvement in stool frequency on a GFD in the absence of changes in colonic transit was not elucidated by our studies. This study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed. The author concludes that this study provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS. The data also partially explains that the biological effects of gluten were associated with HLA-DQ2 or 8 genotype. The relationship of dietary factors, innate and adaptive immune responses and mucosal interactions in IBS-D deserve further study. Further clinical studies evaluating the effects of gluten withdrawal in patients with IBS-D are needed.
Abstract
BACKGROUND & AIMS Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). METHODS We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. RESULTS Subjects on the GCD had more bowel movements per day (P = .04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). CONCLUSIONS Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.govNCT01094041.
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Reintroduction of gluten following flour transamidation in adult celiac patients: a randomized, controlled clinical study.
Mazzarella, G, Salvati, VM, Iaquinto, G, Stefanile, R, Capobianco, F, Luongo, D, Bergamo, P, Maurano, F, Giardullo, N, Malamisura, B, et al
Clinical & developmental immunology. 2012;2012:329150
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A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying new strategies. Chemically altering the protein in wheat flour (transamidation of gliadin) reduces the reaction experienced in vitro in intestinal cells of CD patients. This randomized single blinded, controlled 90-day trial in 47 CD patients examines the safety of transamidated wheat flour compared to control. 35 patients received 50g a day of transamidated flour bread and 12 received 3.7g of non-transamidated flour bread. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse whereas intestinal permeability was mainly altered in the control group. On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no change to the autoantibody found in CD (Ttg) and other markers of CD. This study demonstrated that a protracted intake of gluten from chemically treated wheat flour was associated with a reduced number of relapses in challenged patients. Nevertheless, the enzyme reaction did not eradicate gluten activity in all CD patients examined. Whether an upgrade of the transamidation reaction might be instrumental in blocking other immune components involved in the mucosal lesion is under investigation.
Abstract
A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (P = 0.04) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, P = 0.06). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (P = 0.63), Marsh-Oberhuber grading (P = 0.08), or intestinal IFN-γ mRNA (P > 0.05). Creatinine clearance did not vary after 90 days of treatment (P = 0.46). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.
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Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial.
Itariu, BK, Zeyda, M, Hochbrugger, EE, Neuhofer, A, Prager, G, Schindler, K, Bohdjalian, A, Mascher, D, Vangala, S, Schranz, M, et al
The American journal of clinical nutrition. 2012;96(5):1137-49
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Adipose tissue inflammation is the basis of obesity-related systemic inflammation, which predisposes patients to the development of metabolic and cardiovascular disease. Previous studies show that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduce cardiovascular events and exert anti-inflammatory effects but their effects on human adipose tissue inflammation have so far been unknown. This randomized open-label controlled clinical trial evaluated the effect of an 8-week treatment with n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on adipose tissue and systemic inflammation and on metabolic control. Fifty-five severely obese non-diabetic patients, scheduled for bariatric surgery, were allocated to receive either n-3 PUFAs (n=27) or an equivalent amount of butterfat as control (n=28). Systemic inflammatory markers and metabolic variables were measured at baseline and at the end of the intervention before the participants underwent bariatric surgery. Adipose tissue samples were collected during surgery for the assessment of inflammatory gene expression and lipid mediator production. Treatment with n-3 PUFAs for 8 weeks favourably affected adipose tissue and systemic inflammation. In adipose tissue, the expression of most inflammatory genes was reduced and the concentrations of lipid mediators, responsible for the resolution of inflammation (resolving lipid mediators), were increased. Systemically, the results showed a shift to a more anti-inflammatory plasma fatty acid profile and a decrease in circulating triglyceride levels. The authors concluded that the observed beneficial effects of n-3 PUFAs may be useful in the long-term treatment of obesity.
Abstract
BACKGROUND Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. OBJECTIVE We investigated whether n-3 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. DESIGN We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n-3 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n-3 PUFA-derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. RESULTS Treatment with n-3 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P < 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P < 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. CONCLUSIONS Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760.
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An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach.
Bakker, GC, van Erk, MJ, Pellis, L, Wopereis, S, Rubingh, CM, Cnubben, NH, Kooistra, T, van Ommen, B, Hendriks, HF
The American journal of clinical nutrition. 2010;91(4):1044-59
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Increasing numbers of the population are overweight or obese, which increases the risk of metabolic diseases such as diabetes and heart disease. Overweight/obese individuals have increased low grade inflammation, which is thought to be an underlying process in disease development. This double blinded randomised controlled trial (RCT) aimed to investigate if dietary supplements could reduce inflammation and oxidative stress. Dietary supplements contained six nutrients (fish oil, green tea extract, resveratrol, vitamin E, vitamin C, and tomato extract) that had evidence of anti-inflammatory properties. Supplements were taken by thirty-six overweight male subjects for five weeks, following a crossover study design. Blood, urine and fat tissue samples were taken as markers of inflammation, oxidative stress and nutrigenomics. Although the main inflammatory marker was unchanged, the study did show a decrease in other inflammatory and oxidative markers, and increase in antiinflammatory markers. The highly sensitive nutrigenomnic measures were able to detect an overall metabolic change. The authors suggested that greater changes might be seen with a longer intervention period. The study showed that supplementation with antiinflammatory food extracts had a beneficial effect on inflammatory and metabolic processes in overweight individuals.
Abstract
BACKGROUND Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. OBJECTIVE It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. DESIGN Dietary products [resveratrol, green tea extract, alpha-tocopherol, vitamin C, n-3 (omega-3) polyunsaturated fatty acids, and tomato extract] selected for their evidence-based antiinflammatory properties were combined and given as supplements to 36 healthy overweight men with mildly elevated plasma C-reactive protein concentrations in a double-blind, placebo-controlled, crossover study with treatment periods of 5 wk. Inflammatory and oxidative stress defense markers were quantified in plasma and urine. Furthermore, 120 plasma proteins, 274 plasma metabolites (lipids, free fatty acids, and polar compounds), and the transcriptomes of peripheral blood mononuclear cells and adipose tissue were quantified. RESULTS Plasma adiponectin concentrations increased by 7%, whereas C-reactive protein (principal inflammation marker) was unchanged. However, a multitude of subtle changes were detected by an integrated analysis of the "omics" data, which indicated modulated inflammation of adipose tissue, improved endothelial function, affected oxidative stress, and increased liver fatty acid oxidation. CONCLUSION An intervention with selected dietary products affected inflammatory processes, oxidative stress, and metabolism in humans, as shown by large-scale profiling of genes, proteins, and metabolites in plasma, urine, and adipose tissue. This trial was registered at clinical trials.gov as NCT00655798.
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Fish consumption and markers of colorectal cancer risk: a multicenter randomized controlled trial.
Pot, GK, Majsak-Newman, G, Geelen, A, Harvey, LJ, Nagengast, FM, Witteman, BJ, van de Meeberg, PC, Timmer, R, Tan, A, Wahab, PJ, et al
The American journal of clinical nutrition. 2009;90(2):354-61
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Colorectal cancer (CC) risk is strongly related to dietary habits, with 65–75% of the incidence of CC attributed to dietary factors. This RCT studied the effects of fish consumption on markers of CC risk. 242 patients, either at high risk of developing CC or with a healthy bowel, were randomly assigned to 3 groups - 2 portions of oily fish per week, 2 portions of lean fish per week, or a control group who received dietary advice only for 6 months. 216 patients completed the trail. No statistically significant effect on CC risk markers was found between the fish groups and controls at 6 months. These results did not support the hypothesis that additional fish consumption over a 6-month period changes the number of colonic precancerous cells. The authors call for further studies to include non-fish eaters to further test their hypothesis.
Abstract
BACKGROUND Diet is a major factor in the etiology of colorectal cancer, with high fish consumption possibly decreasing colorectal cancer risk, as was shown in several observational studies. To date, no intervention trials have examined the possible beneficial effects of fish intake on colorectal cancer risk. OBJECTIVE The objective was to investigate the effects of a 6-mo intervention with oil-rich or lean fish on apoptosis and mitosis within the colonic crypt. DESIGN In a multicenter, randomized, controlled intervention trial, patients with colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease were recruited (n = 242) and randomly allocated to receive dietary advice plus either 300 g oil-rich fish (salmon) per week (n = 82), 300 g lean fish (cod) per week (n = 78), or only dietary advice (DA) (n = 82). Apoptosis and mitosis were measured in colonic biopsy samples collected before and after intervention (n = 213). RESULTS The total number of apoptotic cells per crypt did not increase in the salmon or cod group: -0.10 (95% CI: -0.36, 0.16) and -0.06 (95% CI: -0.32, 0.20), respectively, compared with the DA group. The total number of mitotic cells per crypt decreased nonsignificantly in the salmon group (-0.87; 95% CI: -2.41, 0.68) and in the cod group (-1.04; 95% CI: -2.62, 0.53) compared with the DA group. Furthermore, the distribution of mitosis within the crypt did not significantly change in either group. CONCLUSION An increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6 mo does not markedly change apoptotic and mitotic rates in the colonic mucosa. This trial was registered at www.clinicaltrials.gov as NCT00145015.