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A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.
Chilibeck, PD, Candow, DG, Gordon, JJ, Duff, WRD, Mason, R, Shaw, K, Taylor-Gjevre, R, Nair, B, Zello, GA
Medicine and science in sports and exercise. 2023;55(10):1750-1760
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Osteoporosis is a bone disease that gradually develops when bone mineral density (BMD) or bone mass decreases and the quality of bone is impaired. This randomised controlled trial conducted over 2 years wanted to test the effects of creatine monohydrate supplementation on BMD at several bone sites during a supervised resistance training and walking program in post menopausal women. 120 were randomly allocated to creatine and 117 to placebo. All participants received a daily supplement of 500 mg of calcium and 10 μg -400 IU of vitamin D. The researchers were particularly interested in finding out whether the creatine group showed improved (BMD) at the femoral neck, lower spine and upper thigh bone also known as the proximal femur which connects the hip joint. Bone density scans, dual-energy X-ray’s and ultrasounds were used to measure BMD and assess areas of bone. Falls and fractures were recorded for a total of 3 years. Dietary intake and physical activity outside of study requirements was assessed using food frequency and exercise questionnaires. Fasting blood and urine analyses along with 24-h urine analysis were taken. The authors conclude that creatine supplementation during a resistance training and walking program had no effect on BMD at the femoral neck, total hip, or lower spine. They further acknowledge relatively low compliance with the creatine supplements, and exercise protocols, along with a high drop out rate. Further studies of larger sample sizes are needed.
Abstract
PURPOSE Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.
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The relationship between different iodine sources and nutrition in pregnant women and adults.
Sun, R, Fan, L, Du, Y, Liu, L, Qian, T, Zhao, M, Che, W, Liu, P, Sun, D
Frontiers in endocrinology. 2022;13:924990
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Iodine is one of the essential trace elements in human body, which can only be obtained from the diet. Pregnant women are a special population, and their iodine intake needs to not only meet their own health needs but also to supply the growth of the foetus. The main aim of this study was to compare the iodine supplement measures and dietary contribution between pregnant women and adults. This study is based on a multi-stage random sampling method with a total of 2,128 pregnant women and 1,493 adults. Results show that iodine nutrition of pregnant women and adults was adequate in the four provinces included in the study. The largest difference of iodine levels between these provinces was the use of iodine during food preparation and the amount of dietary iodine intake. Additionally, the dietary iodine intake of pregnant women was less than the recommended nutrition intake. Authors conclude that various factors may affect thyroid disease prevalence in pregnant women, such as habitation (urban/rural) and gestation. Furthermore, it is important to coordinate the relationship between iodine nutrition and low sodium diet.
Abstract
BACKGROUND Different iodine supplement measures emerge along with the economy development in China. The article objectives are to compare and explore the relationship between iodine sources and nutrition of pregnant women and adults. METHODS A total of 2,145 pregnant women and 1,660 adults were investigated by multi-stage random method. Questionnaire was used to collect basic information and the consumption of food, water, and iodine preparations. Household salt and individual urine and blood samples were collected, and thyroid function and morphology of pregnant women were measured. RESULTS The median urinary iodine concentration (MUIC) of pregnant women (164.49 μg/L) was lower than adults (187.30 μg/L, p < 0.05). Iodine supplement with IS (iodized salt) was the main measure for pregnant women and adults, and the difference was mainly on the consumption of iodine preparations between pregnant women (5.19%) and adults (0.85%). Moreover, adults' dietary iodine intake from food (100.6 μg/day), IS (140.8 μg/day), and drinking water (6.0 μg/day) was higher than those of pregnant women (86.5, 107.2, and 3.5 μg/day, respectively). Compared with iodine supplement with IS, ISFP (IS + iodine-rich food + iodine preparations) could reduce the risk of iodine deficiency for pregnant women. The MUICs for pregnant women and adults of iodine supplements with IF (iodine-rich food) and ISF (IS + iodine-rich food) were lower. For pregnant women, thyroid nodule (11.90%) and peroxidase antibody (TPOAb) positive (9.32%) were high prevalent thyroid diseases, and habitation (urban/rural), gestation, annual income, and drinking water type would affect them. CONCLUSION Pregnant women and adults had adequate iodine nutrition in four provinces. Their iodine supplement measures were different, the consumption of iodine preparations in pregnant women was higher, and their dietary iodine intake was lower than adults. ISFP was an effect measure for pregnant women to supplement iodine.
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Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth.
Roth, DE, Morris, SK, Zlotkin, S, Gernand, AD, Ahmed, T, Shanta, SS, Papp, E, Korsiak, J, Shi, J, Islam, MM, et al
The New England journal of medicine. 2018;379(6):535-546
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In Bangladesh, 30% of newborns are small for gestational age and 36% of children under 5-years of age have stunted growth. Some previous studies suggest that supplementing mums-to-be with vitamin D during and/or after pregnancy may improve foetal and infant growth. The aim of this trial was to evaluate the dose-dependent effects of vitamin D supplementation on infant growth in Bangladesh. Over 1,100 pregnant women were split into five groups. One group received no vitamin D (placebo group). Three groups received supplementation from mid pregnancy in doses of 4200 IU, 16,800 IU, and 28,000 IU per week. The fifth group received 28,000 IU vitamin D per week during pregnancy, as well as 28,000 IU weekly for 26 weeks after childbirth. At the start of the study, 64% of women were vitamin D deficient (defined as 25(OH)D<30 nmol/L). The vitamin D status of the women was similar across the groups. Among 1,164 infants assessed at 1 year of age, there were no significant differences across groups in the length-for-age scores. Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. The researchers concluded that maternal vitamin D supplementation from mid pregnancy until birth or until 6 months post-partum did not improve foetal or infant growth. The findings of the study do not support routine vitamin D supplementation in pregnancy or lactation to improve birth outcomes or infant growth, even in communities with endemic vitamin D deficiency and foetal-infant growth restriction.
Abstract
BACKGROUND It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).
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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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Long-term effects of provided low and high glycemic load low energy diets on mood and cognition.
Cheatham, RA, Roberts, SB, Das, SK, Gilhooly, CH, Golden, JK, Hyatt, R, Lerner, D, Saltzman, E, Lieberman, HR
Physiology & behavior. 2009;98(3):374-9
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Previous studies have shown a difference between low glycaemic index (GI) and high GI energy restricted diets on mood and cognition. This randomised trial of 46 healthy overweight individuals aimed to assess the long-term effects of LG or HG energy restricted diet on mood and cognition function. Individuals were randomly assigned to a low GI or a high GI diet with caloric restriction for 12 months. The study did not observe any difference in cognitive function of individuals assigned to either the low GI or the high GI diet but it did show a beneficial effect of low GI diet on subclinical depression. The results of this small study were consistent with previous studies where low GI diets may be protective against negative mood change during weight loss whereas negative changes occur if a conventional high GI diet is consumed.
Abstract
Energy-restricted low glycemic load diets are being used increasingly for weight loss. However, the long-term effects of such regimens on mood and cognitive performance are not known. We assessed the effects of low glycemic load (LG) and high glycemic load (HG) energy-restricted diets on mood and cognitive performance during 6 months of a randomized controlled trial when all food was provided. Subjects were 42 healthy overweight adults (age 35+/-5 years; BMI 27.8+/-1.6 kg/m(2)) with a mean weight loss of 8.7+/-5.0% that did not differ significantly by diet randomization. Mood was assessed by using the Profile of Mood States (POMS) questionnaire. Cognitive performance was assessed by using computerized tests of simple reaction time, vigilance, learning, short-term memory and attention, and language-based logical reasoning. Worsening mood outcome over time was observed in the HG diet group compared to the LG for the depression subscale of POMS (p=0.009 after including hunger as a covariate). There was no significant change over time in any cognitive performance values. These findings suggest a negative effect of an HG weight loss diet on sub-clinical depression but, in contrast to a previous suggestion, provide no support for differential effects of LG versus HD diets on cognitive performance.
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Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome.
Zeng, J, Li, YQ, Zuo, XL, Zhen, YB, Yang, J, Liu, CH
Alimentary pharmacology & therapeutics. 2008;28(8):994-1002
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Impaired intestinal mucosal barrier function may be involved in the pathogenesis of diarrhoea-predominant IBS (D-IBS) accompanied by persistent low-grade intestinal inflammation. Attenuating the inflammation and preserving mucosal barrier function may be a potential therapeutic target in D-IBS. This study investigates whether probiotic fermented milk containing multistrain lactic acid bacteria (LAB) can improve intestinal mucosal barrier function in D-IBS. 30 Chinese adults with D-IBS and 12 asymptomatic controls were randomized (1:1 ratio) to consume a probiotic fermented milk (containing Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus acidophilus and Bifidobacterium longum) or a placebo drink twice daily half an hour before meals for 4 weeks. IBS symptoms and intestinal permeability were evaluated at weeks 0 and 4. Before treatment, intestinal permeability of the 30 patients with D-IBS was increased compared to normal controls. After treatment, intestinal permeability in the probiotics group decreased significantly, compared to the placebo group. IBS symptoms score in the probiotics group improved compared with baseline values, but not in the placebo group. This study found that small intestinal permeability was significantly increased in D-IBS patients compared with normal controls. The results indicate that multistrain LAB was associated with the improvement in intestinal barrier function as measured by a reduction in small bowel permeability, in turn accompanied by relief of IBS symptoms, which suggests that increased intestinal permeability may partially contribute to the pathogenesis of IBS symptoms. The mechanisms of increased intestinal permeability involvement in D-IBS were lacking.
Abstract
BACKGROUND The intestinal permeability is increased in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS). AIM: To determine the possible efficacy of lactic acid bacteria on the increased intestinal permeability in D-IBS. METHODS Treatment was employed for 4 weeks in a randomized single blind placebo controlled study with 30 D-IBS patients. Patients were given either probiotic fermented milk (Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus acidophilus and Bifidobacterium Longum) or milk beverage containing no bacteria. The clinical symptoms were scored and intestinal permeability was measured by a triple sugar test before and after treatment. RESULTS Small bowel permeability was measured as the ratio of lactulose and mannitol recovery and colonic permeability was measured as the total mass of sucralose excretion (mg). After probiotics treatment, small bowel permeability decreased significantly from 0.038 (0.024) at baseline to 0.023 (0.020) (P = 0.004), the proportion of patients with increased small bowel permeability was lower than baseline (28.6% vs. 64.3%, P = 0.023). However, colonic permeability improved neither in the probiotics group nor in the placebo group at week 4. Treatment with probiotics significantly decreased the mean global IBS scores compared with the baseline scores (9.62 +/- 1.05 vs. 7.64 +/- 1.24, P < 0.001). CONCLUSION Short-term active lactic acid bacteria treatment for D-IBS improved mucosal barrier function.
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The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study.
Paterson, BM, Lammers, KM, Arrieta, MC, Fasano, A, Meddings, JB
Alimentary pharmacology & therapeutics. 2007;26(5):757-66
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In a healthy gut, intestinal epithelial cells, with their tight junctions, allow controlled passage of gluten and other fragments. When integrity of this system is compromised, as in celiac disease (CD), an inappropriate immune response to environmental antigens (i.e. gluten) develops. This is called hyper-intestinal permeability or 'leaky gut'. AT-1001 is a protein derived from a Gram-negative bacteria called Vibrio cholera. AT-1001 inhibits leaky gut and appears to have an impact on autoimmunity, making it a potential candidate for the treatment of CD. This double-blind, randomised placebo controlled study aims to determine the safety and tolerability of 12 mg doses of AT-1001 in CD subjects challenged with gluten. Intestinal permeability (IP) (measured urinary lactulose-to-mannitol) is used as a measure of drug efficacy. Male and female in-patients (n=20) aged 18-59y with diagnosed CD, on gluten-free diets for 6 months+ were, on days 1 and 3, treated with 12mg AT-1001 or placebo, followed by a sham gluten challenge, followed by the intestinal permeability measure. On day 2 the sham gluten was replaced by gluten. Puddings (containing sham or gluten) were served to all participants by kitchen staff in singe-blind fashion. For day 2 to day 1 IP change, there was a 70% increase in IP in the placebo group (P = 0.041) and no increase in the drug group, confirming the effects of gluten exposure on IP and the protective effects of AT-1001. Adverse events were mild (n=49) or moderate (n=3). Both groups experienced diarrhoea (an expected symptom in CD patients after exposure to gluten) but the AT-1001 treated volunteers reported less diarrhoea than placebo (P=0.017) suggesting a protective effect for AT-1001. This data demonstrate that 12 mg AT-1001 was generally safe, well tolerated and effectively mitigated gluten-induced GI adverse effects in coeliac patients when compared to placebo. Interferon (IFN)-γ (a marker of immune activity after acute dietary gluten) increased on day 3 in both the placebo group and AT-1001 group, but less so in the AT-1001 group though the difference was not statistically significant (likely due to small sample size). AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure. Larger studies are required to further elucidate the effects of AT-1001.
Abstract
BACKGROUND Lifelong adherence to a strict gluten-free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT-1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae. AIM: To determine the safety and tolerability of 12 mg doses of AT-1001 in coeliac disease subjects challenged with gluten. METHODS An in-patient, double-blind, randomized placebo-controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy. RESULTS Compared to placebo, no increase in adverse events occurred in patients exposed to AT-1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group. Interferon-gamma levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT-1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT-1001 group (P = 0.018). CONCLUSIONS AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.