Effect of inulin supplementation on clinical symptoms, inflammatory and oxidative stress markers in women with migraine: study protocol for a randomized clinical trial.

BACKGROUND: Migraine is a complex, chronic, and debilitating multifactorial disorder characterized by recurrent episodes of headache and related symptoms. It typically begins in early ages and is more prevalent in women than in men. Recently, the gut-brain axis has emerged as a new candidate that may be linked to neurological diseases. We hypothesize that selective modulation of the intestinal microbiota, oxidative stress, and inflammation through inulin supplementation may improve clinical outcomes in these patients. Therefore, this study aims to examine the effects of high-performance inulin supplementation on clinical symptoms, mental health, quality of life (QOL), intestinal permeability, and inflammatory and oxidative stress factors in women with migraine. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial involving 80 women with migraine who meet the inclusion criteria (aged between 20 and 50 years with a diagnosis of migraine by a neurologist based on the ICDH-3). Participants will be assigned to receive a daily dose of 10 g of inulin for 12 weeks (intervention group, n = 40) or 10 g of maltodextrin as a placebo for the same duration (control group, n = 40). The primary outcome will measure the variations in the frequency of headache experienced by the patients. Secondary outcomes will encompass serum levels of zonulin, high-sensitive C-reactive protein, total antioxidant capacity, total oxidant status, nitric oxide, mental status, QOL, duration, and severity of migraine attacks. DISCUSSION: This clinical trial aims to evaluate the effect of inulin supplementation on inflammatory status, oxidative stress, intestinal permeability, clinical symptoms, mental health, and QOL in women with migraine. The findings of this trial could contribute to the identification of mechanistic action and evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in the management of clinical outcomes in migraine patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20121216011763N58). Registration date: 23 April 2023. TRIAL STATUS: The protocol is version 3.0, September 17, 2023. Recruitment began August 21, 2023, and is anticipated to be completed by March 22, 2024.

Effects of enriched seafood sticks (heat-inactivated B. animalis subsp. lactis CECT 8145, inulin, omega-3) on cardiometabolic risk factors and gut microbiota in abdominally obese subjects: randomized controlled trial.

PURPOSE: To assess the effects of enriched seafood sticks with postbiotic and bioactive compounds on CMD risk factors and the gut microbiota in abdominally obese individuals. METHODS: Randomized, double-blind, parallel, placebo-controlled trial with abdominally obese individuals. Participants (n = 120) consumed 50 g/day of enriched seafood sticks containing SIAP: (1010 colony forming units (CFUs) of heat-inactivated B. animalis subsp. lactis CECT8145, 370 mg/day omega 3 and 1.7 g/day inulin), or 50 g/day of placebo seafood sticks for 12 weeks. At 12 weeks, an acute single-dose study of 4 h was performed. RESULTS: Sustained SIAP2 consumption significantly decreased the insulin by - 5.25 mg/dL and HOMA-IR (homeostatic Model Assessment of Insulin Resistance) by - 1.33. In women, SIAP2 consumption significantly decreased the pulse pressure (PP) by - 4.69 mmHg. Gut microbiota analysis showed a negative association between glycemic parameter reduction and Alistipes finegoldii and Ruminococcaceae, and between PP reduction and Prevotella 9-ASV0283 and Christensenellaceae. In the acute single dose-study 4-h, SIAP2 consumption produced a lower increase in the postprandial circulating triglyceride levels [23.9 (7.03) mg/dL (mean [standard error])] than the observed with placebo [49.0 (9.52)] mg/dL. CONCLUSION: In abdominally obese individuals, enriched seafood sticks induce a potential protection against type 2 diabetes development by the reduction in the insulin and HOMA-IR; and in cardiovascular disease, in women, by the PP reduction. These effects are accompanied by partial changes in the gut microbiota composition. The enriched seafood sticks reduce the atherogenic triglyceride postprandial concentrations. Our results support the use of enriched seafood sticks as a complementary strategy in the management of CMD risk factors. REGISTRATION NUMBER OF CLINICAL TRIAL: ( www. CLINICALTRIALS: gov ): NCT03630588 (August 15, 2018).

Intervention with inulin prior to and during sanative therapy to further support periodontal health: study protocol for a randomized controlled trial.

BACKGROUND: Periodontal disease is a chronic state of inflammation that can destroy the supporting tissues around the teeth, leading to the resorption of alveolar bone. The initial strategy for treating periodontal disease is non-surgical sanative therapy (ST). Periodontal disease can also induce dysbiosis in the gut microbiota and contribute to low-grade systemic inflammation. Prebiotic fibers such as inulin can selectively alter the intestinal microbiota and support homeostasis by improving gut barrier functions and preventing inflammation. Providing an inulin supplement prior to and post-ST may influence periodontal health while providing insight into the complex relationship between periodontal disease and the gut microbiota. The primary objective is to determine if inulin is more effective than the placebo at improving clinical periodontal outcomes including probing depth (PD) and bleeding on probing (BOP). Secondary objectives include determining the effects of inulin supplementation pre- and post-ST on salivary markers of inflammation and periodontal-associated pathogens, as these outcomes reflect more rapid changes that can occur. METHODS: We will employ a single-center, randomized, double-blind, placebo-controlled study design and recruit and randomize 170 participants who are receiving ST to manage the periodontal disease to the intervention (inulin) or placebo (maltodextrin) group. A pilot study will be embedded within the randomized controlled trial using the first 48 participants to test the feasibility for the larger, powered trial. The intervention period will begin 4 weeks before ST through to their follow-up appointment at 10 weeks post-ST. Clinical outcomes of periodontal disease including the number of sites with PD ≥ 4 mm and the presence of BOP will be measured at baseline and post-ST. Salivary markers of inflammation, periodontal-associated pathogens, body mass index, and diet will be measured at baseline, pre-ST (after 4 weeks of intervention), and post-ST (after 14 weeks of intervention). DISCUSSION: We expect that inulin will enhance the positive effect of ST on the management of periodontal disease. The results of the study will provide guidance regarding the use of prebiotics prior to and as a supportive adjunct to ST for periodontal health. TRIAL REGISTRATION: ClinicalTrials.gov NCT04670133 . Registered on 17 December 2020.

Inulin Supplementation Disturbs Hepatic Cholesterol and Bile Acid Metabolism Independent from Housing Temperature.

Dietary fibers are fermented by gut bacteria into the major short chain fatty acids (SCFAs) acetate, propionate, and butyrate. Generally, fiber-rich diets are believed to improve metabolic health. However, recent studies suggest that long-term supplementation with fibers causes changes in hepatic bile acid metabolism, hepatocyte damage, and hepatocellular cancer in dysbiotic mice. Alterations in hepatic bile acid metabolism have also been reported after cold-induced activation of brown adipose tissue. Here, we aim to investigate the effects of short-term dietary inulin supplementation on liver cholesterol and bile acid metabolism in control and cold housed specific pathogen free wild type (WT) mice. We found that short-term inulin feeding lowered plasma cholesterol levels and provoked cholestasis and mild liver damage in WT mice. Of note, inulin feeding caused marked perturbations in bile acid metabolism, which were aggravated by cold treatment. Our studies indicate that even relatively short periods of inulin consumption in mice with an intact gut microbiome have detrimental effects on liver metabolism and function.

Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

SCOPE: The objective of the present study is to evaluate the effects of milk powder co-supplemented with inulin and resistant dextrin (MPCIR) on elderly patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A randomized, double-blind, placebo-controlled clinical trial is carried out among elderly T2DM patients. The subjects recruited from the community are randomly assigned to either the MPCIR group or placebo group for 12 weeks intervention. Each group receives 45 g milk powder with or without inulin and resistant dextrin. Anthropometric and metabolic variables are measured. For the MPCIR group, systolic blood pressure (BP) and diastolic BP are reduced significantly by 5.45 and 4.56 mm Hg (p < 0.001, vs placebo group), respectively. Compared with the placebo group, the fasting and 2-h postprandial plasma glucose levels, glycosylated serum protein, and insulin resistance index of the MPCIR group are significantly decreased by 0.96 mmol L-1 , 1.47 mmol L-1 , 16.33 µmol L-1 , and 0.65 respectively (p < 0.001). The MPCIR group shows an increase by 7.09 µIU mL-1 and 20.43 in 2-h postprandial insulin (p = 0.016) and ß-cell function index (p < 0.001), respectively. CONCLUSION: MPCIR supplementation helps to improve glycemic control, insulin resistance, and blood pressure.

The effect of enriched chicory inulin on liver enzymes, calcium homeostasis and hematological parameters in patients with type 2 diabetes mellitus: A randomized placebo-controlled trial.

BACKGROUNDS AND AIMS: Type 2 diabetic mellitus (T2DM) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes, serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM. METHODS: Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of chicory and subjects in control group received a placebo for two months. Anthropometric variables, glucose homeostasis, hematological parameters and metabolic indices including serum alanine aminotransfersae (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium and phosphorous as well as creatinine concentrations, glomerular filtration rate (GFR) and blood pressure were assessed at the beginning and end of the trial. RESULTS: Significant reductions in fasting serum glucose (FSG), Hb A1C, AST and ALP concentrations were observed in chicory-treated group. Systolic and diastolic blood pressures were also reduced in chicory-treated group. Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred (P=0.014). Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume (MCV) values (P<0.05). Changes in serum insulin, creatinine and GFR were not significant. CONCLUSION: The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis, liver function tests, blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM. Further studies in both genders are needed to generalize these findings to total population.

Effects of prebiotic supplementation on the expression of proteins regulating iron absorption in anaemic growing rats.

Prebiotics may increase intestinal Fe absorption in anaemic growing rats. The present study evaluated the effects of high-performance (HP) inulin and oligofructose on factors that regulate Fe absorption in anaemic rats during the growth phase. Male Wistar rats aged 21 d of age were fed AIN-93G ration without Fe for 2 weeks to induce Fe-deficiency anaemia. The rats were fed on day 35 a control diet, or a diet with 10 % HP inulin, or a diet with 10 % oligofructose, without Fe supplementation. The animals were euthanised after 2 weeks, and segments of the duodenum, caecum, colon and liver were removed. The expression levels of proteins in the intestinal segments were assessed using Western blotting. The levels of serum, urine and liver hepcidin and the concentrations of IL-10, IL-6 and TNF-α in the caecum, colon and liver were measured using the ELISA test. HP inulin increased the expression of the divalent metal transporter 1 protein in the caecum by 162 % (P= 0·04), and the expression of duodenal cytochrome b reductase in the colon by 136 % (P= 0·02). Oligofructose decreased the expression of the protein ferroportin in the duodenum (P= 0·02), the concentrations of IL-10 (P= 0·044), IL-6 (P= 0·036) and TNF-α (P= 0·004) in the caecum, as well as the level of urinary hepcidin (P< 0·001). These results indicate that prebiotics may interfere with the expression of various intestinal proteins and systemic factors involved in the regulation of intestinal Fe absorption in anaemic rats during the growth phase.

Effect of a Natural Supplement Containing Curcuma Longa, Guggul, and Chlorogenic Acid in Patients With Metabolic Syndrome.

The impact of a natural supplement (Kepar; Rikrea, Italy), containing several plant extracts such as curcuma longa, silymarin, guggul, chlorogenic acid, and inulin, was evaluated in 78 patients with metabolic syndrome (MetS; 45 men; age: 62 ± 9 years). Kepar at a dose of 2 pills/d was given for 4 months as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study. Anthropometric variables, plasma lipids, glucose parameters, and oxidative stress were measured at baseline and after 4 months. We found significant reductions in body weight (from 81.1 ± 13.5 to 79.4 ± 12.5 kg, P < .0001), body mass index (from 29.6 [23.7] to 29.3 [21.9] kg/m(2), P = .001), and waist circumference (from 105 ± 11 to 102 ± 10 cm, P = .0004) as well as in fasting glucose (from 6.5 [11.7] to 6.4 [7.6] mmol/L, P = .014) and total cholesterol (from 4.8 ± 1.4 to 4.5 ± 1.0 mmol/L, P = .03). No significant changes were found in the other appraised parameters, including oxidative stress. In conclusion, after few months of treatment Kepar seems to exert beneficial effects in patients with MetS. Larger studies with a longer follow-up period are needed to confirm these preliminary findings.

Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial.

BACKGROUND & AIMS: The sterile newborn digestive tract is rapidly colonized after birth and feeding type could influence this process. Infant formulas try to mimic the bifidogenic effect of human milk using prebiotic supplementation. The aim of this study was to demonstrate the efficacy, safety and tolerance of a 0.8 g/dL Orafti(®)Synergy1 (oligofructose-enriched inulin) supplemented infant formula during the first 4 months of life. METHODS: In a double-blind, randomized, placebo-controlled and parallel trial, formula fed healthy term newborns were randomized to receive a control (controls) or SYN1 supplemented infant formula (SYN1). Breastfed newborns (BF) were also followed for comparison. Anthropometry, water balance, blood parameters, adverse events, stool frequency and characteristics and faecal microbiota were assessed. RESULTS: A total of 252 formula fed infants were randomized at birth (n = 124 controls, n = 128 SYN1) and 131 BF infants were recruited; after 4 months 68 controls, 63 SYN1 and 57 BF completed the study. SYN1 infants showed a microbiota composition closer to that of BF infants, with a trend towards higher Bifidobacterium cell counts, softer stools and a higher deposition frequency compared to controls. There were no differences between formulas in anthropometry and relevant adverse events, water balance or blood parameters. CONCLUSION: A 0.8 g/dL SYN1-supplemented infant formula during the first 4 months of life is safe and effective, promoting a gut microbiota closer to that of breastfeeding. This clinical trial was registered at Clinicaltrials.gov as Study on Fermentable Carbohydrates in Healthy Infants (number NCT00808756).