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Sustained Diet-Induced Remission in Pediatric Crohn's Disease Is Associated With Kynurenine and Serotonin Pathways.
Ghiboub, M, Boneh, RS, Sovran, B, Wine, E, Lefèvre, A, Emond, P, Verburgt, CM, Benninga, MA, de Jonge, WJ, Van Limbergen, JE
Inflammatory bowel diseases. 2023;29(5):684-694
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Crohn’s disease (CD) is an inflammatory bowel disease associated with alterations in intestinal tryptophan metabolism, in particular with increases in metabolites of the kynurenine pathway and decreased metabolites of the serotonin pathway. The aim of this 12-week randomised clinical study was to evaluate the effect of CD exclusion diet with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) on intestinal tryptophan metabolism (as measured in faeces) in 43 children with mild-to-moderate CD. 13 of 15 patients on CDED+PEN and 9/13 on EEN achieved remission at week 6, and 8/9 and 6/9 patients, respectively, maintained remission at 12 weeks. Some kynurenine pathway metabolites decreased and some serotonin metabolites increased, in patients who achieved induction and maintenance of remission. These changes were similar in both intervention groups. On the other hand, in patients on EEN who did not go into remission, these changes were not observed. The authors concluded that further studies are warranted to inform whether there is a causal link and to refine nutritional interventions.
Abstract
BACKGROUND Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission. METHODS A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn's disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission. RESULTS Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission. CONCLUSIONS The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission. We show that fecal tryptophan metabolites are associated with remission following dietary therapy in a prospective clinical trial of pediatric Crohn’s disease patients. Our study shows that reduction in some kynurenine pathway metabolites and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. These compounds may play a role in mediating the mechanism of action of dietary therapy.
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The effect of melatonin on irritable bowel syndrome patients with and without sleep disorders: a randomized double-blinded placebo-controlled trial study.
Faghih Dinevari, M, Jafarzadeh, F, Jabbaripour Sarmadian, A, Abbasian, S, Nikniaz, Z, Riazi, A
BMC gastroenterology. 2023;23(1):135
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Previous research has shown that the use of melatonin by individuals with irritable bowel syndrome (IBS) has improved symptoms and quality of life (QoL) but did not affect sleep. This research has been shown to have some limitations in that it has been conducted in a small number of individuals and did not use the latest IBS diagnostic criteria. This randomised control trial aimed to determine in 136 individuals with IBS with and without sleep disorders the effects of melatonin on IBS score, gastrointestinal (GI) symptoms, QoL, and sleep. The results showed that compared to placebo, the use of melatonin for 8 weeks resulted in improved IBS score and GI symptoms in individuals with and without sleep disorders. Severity and frequency of abdominal pain, satisfaction with bowel habits, disease impacts on life, and stool consistency were all improved, however frequency of defecations was unaffected. Sleep was improved in those with sleep disorders, but not those without. It was concluded that melatonin can be used to improve IBS and QoL in individuals with or without sleep disorders and may also improve sleep in those with sleep disorders and IBS. This study could be used by healthcare professionals to recommend the use of melatonin to individuals with IBS to improve symptoms and QoL.
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is one of the world's most common gastrointestinal (GI) disorders, and current treatments do not meet patients' demands. This study aimed to investigate melatonin's therapeutic effects on IBS score, GI symptoms, quality of life, and sleep parameters in both groups of IBS patients with and without sleep disorders. METHODS In this randomized double-blinded placebo-controlled trial study, 136 patients with a diagnosis of IBS based on ROME IV criteria were enrolled and then divided into two groups respecting having sleep disorders or not. Patients of each group were randomized in a 1:1 ratio to receive melatonin 6 mg daily (3 mg fasting and 3 mg at bedtime) for 2 months (8 weeks). Blocked randomization was used in this process. All patients were evaluated both at the beginning and the end of the trial regarding IBS score, GI symptoms, quality of life, and sleep parameters through valid questionnaires. RESULTS In both groups of patients with and without sleep disorders, a significant improvement was observed in IBS score and GI symptoms, including the severity and the frequency of abdominal pain, the severity of abdominal bloating, satisfaction with bowel habits, disease's impact on patient's life, and stool consistency; however, there was no significant improvement in the frequency of defecations per week. In patients with sleep disorders, significant improvement in sleep parameters, including subjective sleep quality, sleep latency, sleep duration, sleep efficiency, and daytime dysfunction, was observed, while in patients without sleep disorders, there was no significant improvement in sleep parameters. In addition, quality-of-life improvement was observed in a significant number of melatonin recipients compared to placebo in both groups of patients. CONCLUSION Melatonin can be considered an effective treatment for improving IBS score, GI symptoms, and quality of life in IBS patients with and without sleep disorders. It is also effective to improve sleep parameters in IBS patients with sleep disorders. TRIAL REGISTRATION This study has been registered to the Iranian Registry of Clinical Trials (IRCT) with the approval number IRCT20220104053626N2 on the date of 13/02/2022.
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Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial.
Bahramrezaie, M, Amidi, F, Aleyasin, A, Saremi, A, Aghahoseini, M, Brenjian, S, Khodarahmian, M, Pooladi, A
Journal of assisted reproduction and genetics. 2019;36(8):1701-1712
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Polycystic ovary syndrome (PCOS) is a condition in women characterised by disruptions in the ovulation cycle and hormonal imbalances causing infertility. There are several biological mechanisms involved in the development of PCOS, including hormonal imbalance. Recently, high levels of a protein known as VEGF, which stimulates the formation of new blood vessels, has been detected in the ovaries of women with PCOS and is thought to be involved in its development. Resveratrol is a herbal supplement, which has been shown in animal studies to reduce VEGF. This randomised control trial of 61 women with PCOS aimed to determine if there was a similar effect in humans. The results showed that VEGF was decreased following the supplementation of resveratrol, and that it also helped to achieve a more normal hormonal balance. As a result, this improved the quality of embryos, but did not increase the rate of fertility. It was concluded that resveratrol may be of benefit to women with PCOS by decreasing the production of VEGF and helping to achieve a better hormonal balance in women with PCOS.
Abstract
OBJECTIVES Management options for PCOS, as the most prevalent endocrine disorder in women of reproductive age, using natural supplements have a high priority for physicians, especially based on the etiological pathways. Therefore, this study was conducted to describe the effect of resveratrol on the angiogenesis pathway, for management of PCOS through assessing VEGF, HIF1 gene expression, and laboratory parameters. METHODS In this triple-blind RCT, PCOS was confirmed in ICSI candidates based on the Rotterdam criteria. Sixty-two patients that met the inclusion criteria were randomly assigned to two groups. All patients took resveratrol 800 mg/day or placebo for 40 days orally from the beginning of their previous menstruation cycle until the oocyte retrieval day. The serum levels of different hormones were measured, and the expression of HIF1 & VEGF genes was quantified by real-time PCR. RESULTS As for the laboratory hormone assay in 61 PCOS patients, a significant mean difference was seen in the FSH, LH, TSH, and testosterone between the two groups (P < 0.05). The results showed a reduction in the expression of VEGF & HIF1 genes under the effect of resveratrol in the granulosa cells (P = 0.0001). The number of mature oocytes, cleavage rate, fertilization rate, and fertility rate were not significantly different between the two groups (P > 0.05), but the high-quality oocyte rate and high-quality embryo rate were higher in the resveratrol group (P < 0.05). CONCLUSIONS Based on the results, resveratrol may improve some outcomes of PCOS patients, probably through changing the serum levels of some sex hormones and expression of VEGF & HIF1 genes in the angiogenesis pathway of granulosa cells.
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Effects of Different Types of Front-of-Pack Labelling Information on the Healthiness of Food Purchases-A Randomised Controlled Trial.
Neal, B, Crino, M, Dunford, E, Gao, A, Greenland, R, Li, N, Ngai, J, Ni Mhurchu, C, Pettigrew, S, Sacks, G, et al
Nutrients. 2017;9(12)
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Nutrition labelling on the front of packaged food is a policy tool to help promote healthier food choices. Current research on the effectiveness of package labelling food-purchasing behaviour is both limited and mixed in results. The aim of this large-scale randomised trial was to compare Australia's new Health Star Rating (HSR) with five other front-of-pack labelling schemes with a focus on usability and impact on food choices. The 1578 participants were randomised to one of six experimental groups or the control group and food purchases were tracked by a smartphone application for four weeks. This study demonstrated that the HSR system was as good as other front-of-pack labelling schemes in many outcomes, and superior in terms of usefulness, however there was no evidence to show HSR improved food purchasing behaviour. Based on these results, the authors conclude that various package labelling systems are effective and HSR is one they would recommend.
Abstract
BACKGROUND Front-of-pack nutrition labelling may support healthier packaged food purchases. Australia has adopted a novel Health Star Rating (HSR) system, but the legitimacy of this choice is unknown. OBJECTIVE To define the effects of different formats of front-of-pack labelling on the healthiness of food purchases and consumer perceptions. DESIGN Individuals were assigned at random to access one of four different formats of nutrition labelling-HSR, multiple traffic light labels (MTL), daily intake guides (DIG), recommendations/warnings (WARN)-or control (the nutrition information panel, NIP). Participants accessed nutrition information by using a smartphone application to scan the bar-codes of packaged foods, while shopping. The primary outcome was healthiness defined by the mean transformed nutrient profile score of packaged foods that were purchased over four weeks. RESULTS The 1578 participants, mean age 38 years, 84% female recorded purchases of 148,727 evaluable food items. The mean healthiness of the purchases in the HSR group was non-inferior to MTL, DIG, or WARN (all p < 0.001 at 2% non-inferiority margin). When compared to the NIP control, there was no difference in the mean healthiness of purchases for HSR, MTL, or DIG (all p > 0.07), but WARN resulted in healthier packaged food purchases (mean difference 0.87; 95% confidence interval 0.03 to 1.72; p = 0.04). HSR was perceived by participants as more useful than DIG, and easier to understand than MTL or DIG (all p < 0.05). Participants also reported the HSR to be easier to understand, and the HSR and MTL to be more useful, than NIP (all p < 0.03). CONCLUSIONS These real-world data align with experimental findings and provide support for the policy choice of HSR. Recommendation/warning labels warrant further exploration, as they may be a stronger driver of healthy food purchases.
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Randomized placebo control study of insulin sensitizers (Metformin and Pioglitazone) in psoriasis patients with metabolic syndrome (Topical Treatment Cohort).
Singh, S, Bhansali, A
BMC dermatology. 2016;16(1):12
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As an immune-mediated chronic inflammatory skin condition, psoriasis is associated with obesity, metabolic syndrome, diabetes, and cardiovascular disease. Medications capable of sensitising insulin, such as Metformin and Pioglitazone, have also shown benefits in improving factors associated with metabolic syndrome and psoriasis. This single-centre, parallel-group, randomised, open-label with blinded endpoint evaluated the effects of Metformin with Pioglitazone and placebo in psoriatic patients. Patients with mild-to-moderate psoriasis were randomised to a topical treatment cohort to take 1000 mg metformin daily or 30 mg pioglitazone or placebo groups for 12 weeks. Each participant received a topical ointment containing 5% coal tar during the treatment period. The Metformin and Pioglitazone groups showed significant improvements in psoriasis and metabolic syndrome parameters, such as fasting plasma glucose, total cholesterol, and triglyceride levels, after 12 weeks of treatment. The treatment with metformin resulted in significant improvements in weight, BMI, waist circumference, FPG, triglycerides, and total cholesterol, while the treatment with pioglitazone resulted in significant improvements in FPG, triglycerides, systolic and diastolic blood pressure, cholesterol levels, and LDL cholesterol levels. There was no significant improvement in inflammatory cytokine levels in any group. For further evaluation of the beneficial effects of insulin-sensitising drugs in patients suffering from psoriasis and metabolic syndrome, more robust studies are needed. The study results can be used by healthcare professionals to better understand how insulin-sensitising drugs may decrease the risk of diabetes, cardiovascular disease, and psoriasis in psoriasis patients with metabolic syndrome.
Abstract
BACKGROUND Increased prevalence of metabolic syndrome (MS) is observed in psoriasis. Metformin has shown improvement in cardiovascular risk factors while pioglitazone demonstrated anti proliferative, anti-inflammatory and anti angiogenic effects. Study objective is to evaluate the efficacy and safety of Insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome (MS). METHODS Single centre, parallel group, randomized, study of metformin, pioglitazone and placebo in psoriasis patients with MS. RESULTS Statistically significant improvement was observed in Psoriasis Area and Severity Index (PASI), Erythema, Scaling and Induration (ESI) and Physician global assessment (PGA) scores in pioglitazone (p values - PASI = 0.001, ESI = 0.002, PGA = 0.008) and metformin groups (p values - PASI = 0.001, ESI = 0.016, PGA = 0.012) as compared to placebo. There was statistically significant difference in percentage of patients achieving 75 % reduction in PASI and ESI scores in metformin (p value - PASI = 0.001, ESI = 0.001) and pioglitazone groups (p vaue - PASI = 0.001, ESI = 0.001). Significant improvement was observed in fasting plasma glucose (FPG) and triglycerides levels in metformin and pioglitazone arms. Significant improvement was noted in weight, BMI, waist circumference, FPG, triglycerides and total cholesterol after 12 weeks of treatment with metformin while pioglitazone showed improvement in FPG, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and LDL cholesterol levels. There was no difference in pattern of adverse drug reaction in three groups. CONCLUSION Insulin sensitizers have shown improvement in the parameters of MS as well as disease severity in psoriasis patients. TRIAL REGISTRATION CTRI Registration Number: CTRI/2011/12/002252 . Registered on 19/12/2011.