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A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics.
Han, K, Nguyen, A, Traba, J, Yao, X, Kaler, M, Huffstutler, RD, Levine, SJ, Sack, MN
Journal of immunology (Baltimore, Md. : 1950). 2018;201(5):1382-1388
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Previous studies have shown that caloric restriction and fasting may modulate immune function and have positive effects in asthmatics. The aim of this pilot study was to evaluate the effects of fasting on specific inflammatory markers that might mediate such benefits. 18 mild asthmatics, 5 of whom were not on steroid inhalers, fasted for 24 hours. Lung function and immune parameters were evaluated at baseline and 2.5 hours after the first meal following the fast. There were significant differences between subjects who were and were not on steroid inhalers. Whilst one day of fasting did not affect lung function, a number of inflammatory parameters were improved by fasting in those not taking steroid inhalers, but not in those who were taking steroids. The authors conclude that caloric restriction might be considered as a strategy to improve systemic and pulmonary inflammation in asthma.
Abstract
A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production and reduced CD4+ T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.
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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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Dose dependent effects of protracted ingestion of small amounts of gliadin in coeliac disease children: a clinical and jejunal morphometric study.
Catassi, C, Rossini, M, Rätsch, IM, Bearzi, I, Santinelli, A, Castagnani, R, Pisani, E, Coppa, GV, Giorgi, PL
Gut. 1993;34(11):1515-9
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Coeliac disease (CD) is an intestinal reaction that is caused by the ingestion of gluten. While this is well established, the relationship between the quantity ingested and the severity of adverse effects, namely for small amounts of gluten, is still unclear. The aim of this study was to assess the effects of chronic ingestion of small amounts of gluten in children with CD. 20 children who had been on a long-term gluten-free diet were given a daily dose of either 100 mg or 500 mg of gliadin for four weeks. Effects were measured through an intestinal biopsy, antibody test and sugar intestinal permeability test. The findings of this study showed that in children with CD, chronic ingestion of gluten causes dose-dependent damage to intestinal mucosa and lymphocyte infiltration.
Abstract
This study aimed to investigate the effects of chronic ingestion of small amounts of gliadin on children with coeliac disease. A four week challenge was performed on 20 children who had been on a gluten free diet for mean (SD) 14 (3) months. They were given a daily dose of either 100 mg (group A, n = 10, mean age 4 (2) years) or 500 mg of gliadin (group B, mean age 5 (3) years). The effects of the gliadin were monitored by morphometric study of the jejunal mucosa, intestinal permeability test with cellobiose/mannitol, and serum antigliadin antibody test. After the challenge, group A patients showed a significant increase in the mean intraepithelial lymphocyte count (before challenge 11 (3), afterwards 19 (6)) and a decrease in the villous height/crypt depth ratio (beforehand 1.5 (0.1), afterwards 1.3 (0.2)), while the intestinal permeability test remained normal and the IgA-antigliadin antibody increased in four of 10 children. After the challenge group B showed more pronounced histological changes, an increase in the mean urinary cellobiose/mannitol % (beforehand 0.028 (0.020), afterwards 0.058 (0.028)), and IgA-antigliadin antibody positivity in six of eight subjects. The discriminant analysis function showed that the pretreatment group, group A after challenge, and group B after challenge were correctly classified in 90% of cases by functions based on the individual intraepithelial lymphocyte count and the villous height/crypt depth ratio. This study shows that chronic ingestion of small amounts of gluten causes dose-dependent damage to the small intestinal mucosa in children with coeliac disease. The predictive value of laboratory tests, such as the antigliadin antibody test and the intestinal permeability test seems to be lower in treated patients than in those with active coeliac disease.