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Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.
Cunha, GM, Guzman, G, Correa De Mello, LL, Trein, B, Spina, L, Bussade, I, Marques Prata, J, Sajoux, I, Countinho, W
Frontiers in endocrinology. 2020;11:607
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Excess fat in the liver, known as non-alcoholic fatty liver disease (NAFLD), has been shown to increase the risk of chronic diseases such as type 2 diabetes. Standard treatment regimens consist of low-calorie (LC) diets and exercise, however these may be ineffective at reversing fat accumulation in the liver. A very low-calorie ketogenic diet (VLCKD) has been proposed as an alternative treatment for NAFLD. This randomised control pilot study of 39 individuals with obesity aimed to compare LC diet and VLCKD on fat accumulation and indicators for NAFLD for two months. The results showed greater weight loss, abdominal fat reduction, liver fat reduction and improvements in liver function with VLCKD compared to the LC diet. Cholesterol was significantly reduced by both diets. However liver stiffness remained unchanged. The authors concluded that VLCKD was more successful at reducing liver fat and abdominal fat accumulation than current standard therapy and has the potential to improve NAFLD. Health care professionals could use this study to improve liver and abdominal fat loss in patients with obesity to improve NAFLD, when standard therapy has been inadequate.
Abstract
Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05. Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.
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Impact of changes in physical activity or BMI on risk of heart failure in women - the prospective population study of women in Gothenburg.
Halldin, AK, Lissner, L, Lernfelt, B, Björkelund, C
Scandinavian journal of primary health care. 2020;38(1):56-65
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Heart failure (HF) is a severe and progressive condition with poor prognosis. Obesity is a risk factor for HF. The aim of this study was to investigate the impact of change in physical activity or change in body mass index on the risk of later developing HF in women without a previous diagnosis of HF. This study is prospective longitudinal study which includes 1749 healthy women from the Prospective Population Study of Women in Gothenburg. Results indicate that gaining weight in early middle age is more harmful than gaining weight later in life, with regard to the risk of developing HF later in life. Furthermore, reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. Authors conclude that the role of physical activity in preventing the development of obesity must be taken into account.
Abstract
Objective: To longitudinally evaluate the impact of change in physical activity or change in body mass index (BMI) over time on the risk of developing heart failure (HF) in women without a previous diagnosis of HF.Design and setting: Longitudinal, observational, prospective study of women in Gothenburg, Sweden. Data on BMI and level of physical activity were collected from examinations 1968-1992 and hospital diagnoses and mortality data were ascertained from 1980 to 2012.Subjects: Data were obtained from 1749 women included in the Prospective Population Study of Women in Gothenburg.Main outcome measures: Hazard ratio (HR) for HF was calculated, using a Cox regression model.Results: Women with stable high physical activity during 1968-1980 and 1980-1992 reduced their risk of subsequent HF compared to the non-active women (for 1968-1980 HR 0.66, 95% Confidence Interval (CI) 0.44-0.99 and for 1980-1992 HR 0.47, 95% CI 0.29-0.74). Women with increasing levels of physical activity during 1980-1992 reduced their risk of HF compared to the non-active women (HR 0.40, 95% CI 0.22-0.72). Increase in BMI from overweight to obesity during 1968-1980 predicted increased risk of developing HF (HR 1.93, 95% CI 1.18-3.14).Conclusions: Reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. This is particularly important for sedentary women in middle age. The role of physical activity in preventing the development of obesity must be taken into account.Key pointsA sedentary lifestyle and obesity are risk factors for developing heart failure (HF) in women.The risk of developing HF may be reduced by increasing the level of activity in sedentary middle-aged women.For younger women, avoiding obesity is most important to reduce the risk of later HF.Primary care has a key role in guiding women towards the most effective lifestyle changes to prevent development of HF.
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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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A randomized controlled study comparing elemental diet and steroid treatment in Crohn's disease.
Zoli, G, Carè, M, Parazza, M, Spanò, C, Biagi, PL, Bernardi, M, Gasbarrini, G
Alimentary pharmacology & therapeutics. 1997;11(4):735-40
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An elemental diet is considered an effective primary treatment for active Crohn's disease, usually given by a feeding tube. This RCT evaluated the affect of elemental diet administered orally on disease activity, intestinal permeability and nutritional status when compared to high-dose corticosteroids. 22 Crohn’s disease patients were enrolled of which 2 withdrew and 20 were randomised to oral elemental diet group (n-10) or corticosteroid plus normal diet group (n=10) for 2 weeks. After 2 weeks clinical disease activity improved significantly in both groups. Crohn’s disease activity and erythrocyte sedimentation rate improved in the diet group. Crohn's disease activity improved in the corticosteroid group. Disease remission rate was higher in the diet group (n=8) compared to the corticosteroid group (n=5). 12 months after the study there was no difference in disease relapse rate between groups. Intestinal permeability was significantly improved in the diet group only. However, at the start of the study, permeability levels were randomly lower in the corticosteroid group than the diet group so it is not possible to say that elemental diet was more effective than corticosteroids in promoting gut mucosal healing. Nutritional status improved in both groups but was more evident in the diet group. The authors conclude that an oral elemental diet is effective in promoting and maintaining remission of Crohn’s disease activity, in restoring intestinal permeability and improving nutritional status, and is generally well tolerated with a high degree of compliance.
Abstract
BACKGROUND Elemental diet is considered an effective primary treatment for active Crohn's disease, but it is usually given by a feeding tube. METHODS Twenty-two patients (12 males, median age 30 years, range 18-60) with moderately active Crohn's disease were enrolled in a randomized study in which the efficacy of an elemental diet administered orally was compared to high-dose corticosteroids in achieving clinical and laboratory remission. Ten patients were treated by oral elemental diet (Peptamen, Clintec, USA) and 10 received corticosteroids. Both treatment regimens lasted 2 weeks. The two groups did not differ with respect to age, sex, body weight, location of disease, treatment or disease activity prior to the study. In all patients studied, simple Crohn's disease activity index, nutritional status (expressed as body mass index), percentage of ideal body weight, fat mass, fat free mass, erythrocyte sedimentation rate, interleukin-6, intestinal permeability (expressed as permeability index), prealbumin, retinol binding protein and multiskin test were evaluated before and after treatment. RESULTS After 2 weeks of treatment, there were significant improvements in simple Crohn's disease activity index, erythrocyte sedimentation rate, permeability index, body mass index, prealbumin, retinol binding protein and multiskin test in the elemental diet group. There were significant improvements in simple Crohn's disease activity index and fat free mass in the corticosteroid group. CONCLUSIONS These data suggest that, in the short term, an oral elemental diet is at least as effective as steroids in inducing remission of mild-moderately active Crohn's disease, but it may be more effective in improving the nutritional status of these patients, probably through a more rapid restoration of normal intestinal permeability.