Non Alcoholic Fatty Liver, Obesity
Conditions
Keywords
NAFL; obesity; probiotics; berberine; microbiota;
Brief summary
Effect of oral selected Probiotics (PRO) and/or Berberine (BBR) supplementation on hepatic steatosis markers, cardiometabolic profile, and gut microbiota profile in the non-alcoholic fatty liver (NAFL) - a randomized double-blind clinical study.
Detailed description
Probiotics (PRO) and bioactive natural substances such as Berberine (BBR) can improve metabolic parameters in patients with obesity and metabolic disorders. In addition, they significantly affect the composition and function of gut microbiota (GM) and support anti-inflammation and antioxidant defense. These data have become the starting point for the proposed multidirectional approach, aimed at assessing the effect of PRO and/or BBR supplementation on: * hepatic-related outcomes, * changes in anthropometric measurements (body mass, BMI, body mass composition and fat mass % content), * cardiometabolic profile (e.g. blood pressure, noninvasive markers of endothelial function, cardiometabolic biochemical parameters) * microbiotic profile (gut microbiota composition, endotoxemia) * the content of the minerals, in overweight/obese patients with nonalcoholic fatty liver (NAFL).
Interventions
DIETARY_SUPPLEMENTProbiotic
The probiotic group will receive one capsule of the probiotic mixture (dose:1x109 colony forming units (CFU) per day in one dose (before breakfast). The PRO preparation will contain the following bacterial strains: 50% Lactococcus lactis Rosell® - 1058, 25% Lactobacillus casei Rosell® - 215, 12,5% Lactobacillus helveticus Rosell® - 52, 12,5% Bifidobacterium bifidum Rosell® - 71). Probiotics will be administered orally.
DIETARY_SUPPLEMENTBerberine
The berberine group will receive 1500 mg of Berberine (Berberine hydrochloride 97% extract of Berberis aristata) per day in 3 doses. Berberine will be administered orally, before breakfast, dinner, and before supper.
DIETARY_SUPPLEMENTPlacebo
The placebo group will receive a placebo. Placebo will contain only the excipients and will be administered orally for 24 weeks. Placebo in no way: color, taste, smell, form of taking, the dosage will not differ from the preparations tested. However, it will not contain probiotcs or berberine. Placebo will be orally administered three times a day: before breakfast, dinner, and supper (6.00-7.00 p.m.). To meet the GCP conditions, subjects from all groups will receive the same number of capsules (six) per day.
DIETARY_SUPPLEMENTProbiotc and Berberine
Probiotics and Berberine groupwill receive both: a probiotics mixture (as in PRO group: 1x109 CFU/day; in one dose) and 1500 mg/day of Berberine (Berberine hydrochloride 97% extract of Berberis aristata; in 3 doses). Probiotcs and berberine will be administered orally before breakfast, before dinner, and before supper.
Sponsors
Poznan University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* age 40 to 60 years; * women ≥1 year since last menstruation; * body mass index (BMI): 27.0 kg/m2 to 34.9 kg/m2; * abdominal obesity-related waist circumference \> 80 cm (women) and \>94 cm (men) (in accordance to International Diabetes Federation); * stable body weight in the 3 months prior to the trial (permissible deviation is ± 3 kg); * NAFL - diagnosed based on USG in accordance with PGE-NAFLD recommendation
Exclusion criteria
* history of following alternative diets within 3 months before the study; * history of use of any dietary supplements in the 3 months before the study; * history of intake of antibiotics, probiotics, prebiotics within 3 months before the study; * secondary form of obesity, pharmacological treatment for obesity (in the 3 months before the study), history of bariatric surgery; * another liver diseases: high risk of NASH (assessed on the FIB-4, according to the PGE-NAFLD recommendation), autoimmune hepatitis, hepatitis B and C, toxic hepatitis, cirrhosis, Wilson's disease, hemochromatosis; * other gastrointestinal disorders, especially: IBD, celiac disease, gastritis and duodenitis, pancreatic disorders, gastrointestinal symptoms suggestive of IBS; * clinically significant acute inflammatory process (elevated hsCRP); * abnormal kidney function (GFR \<60mL/min/1,73m2); * T2D; * dyslipidemia or hypertension - requiring the introduction and/or change of pharmacological treatment in the 6 months before the trial or during intervention; * pump inhibitors, anticoagulants, drugs causing metabolic alteration, e.g., SFAs (second-generation antipsychotics); * diseases requiring nutritional requirement and chronic supplementation; * alcohol (\>30g/d for men and \>20g/d for women), nicotine or drug abuse; * mental disorders, including eating disorders; * cancer, autoimmune diseases; * any other condition which may influence on final results of the study or pose a risk for subjects health.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Fibrosis-4 (FIB-4) - Index for Liver Fibrosis. | At the baseline and 12 weeks of treatment | FIB-4 will be estimated using a medical calculator (based on parameters as: age, ALT, AST, and platelet count). |
| Changes in HSI - Hepatic Steatosis Index. | At the baseline and 12 weeks of treatment | HSI will be estimated using a medical calculator (based on parameters as: gender, ALT, AST, BMI, and type 2 diabetes). |
| Changes in NAFLD-LFS (liver fat score). | At the baseline and 12 weeks of treatment | NAFLD-LFS will be estimated using a medical calculator (based on serum aspartate transaminase/alanine transaminase (AST/ALT) ratio, fasting serum aspartate transaminase (AST) level, fasting serum insulin level, presence of metabolic syndrome and diabetes mellitus). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in waist circumference, hip circumference. | At the baseline and 12 weeks of treatment | WC will be measured between the iliac crest and the lower rib at the end of a normal expiration, and HC will be measured around the widest portion of the buttocks. Both HC and WC will be measured using stretch-resistant medical tape (Seco) to the nearest 0.5 cm. The measurement of WC and HC will be performed according to the World Health Organization (WHO) protocol. |
| Changes in waist to hip ratio. | At the baseline and 12 weeks of treatment | WHR will be calculated as WC to HC quotient. |
| Changes in BMI. | At the baseline and 12 weeks of treatment | BMI will be calculated according to the formula: BMI = kg/m2 where kg is a person's weight in kilograms and m2 is their height in meters squared. |
| Changes in pulse wave velocity (PWV). | At the baseline and 12 weeks of treatment | The pulse wave velocity (PWV) will be measured using the SphygmoCor Px (Atcor Medical Blood Pressure Analysis System, Sydney, Australia) in a temperature-controlled room before making anthropometric measurements and blood collection. |
| Changes in pulse wave analysis (PWA). | At the baseline and 12 weeks of treatment | The pulse wave analysis (PWA)will be measured using the SphygmoCor Px (Atcor Medical Blood Pressure Analysis System, Sydney, Australia) in a temperature-controlled room before making anthropometric measurements and blood collection. |
| Gut (taxonomic and functional) microbiota analysis in stool. | At the baseline and 12 weeks of treatment | Analyzed by the NGS method. |
| Short-chain fatty acids (SCFAs) concentration in stool. | At the baseline and 12 weeks of treatment | Analyzed using gas chromatography (Agilent Technologies 1260 A GC system with a flame ionization detector (FID)) |
| Measurement of hair minerals (Fe, Mg, Ca, Cu, Zn) concentration. | At the baseline and 12 weeks of treatment | Performed using atomic absorption spectrometry (Atomic Absorption Spectrophotometer ZA3000, Hitachi, Tokyo, Japan) |
| Changes in ALT, AST, GGT | At the baseline and 12 weeks of treatment | The ALT, AST, GGT will be measured using standard methods. |
| Changes in non-esterified free fatty acids. | At the baseline and 12 weeks of treatment | The NEFA will be measured using standard methods. |
| Changes in lipids profile (TC, HDL, TG). | At the baseline and 12 weeks of treatment | The TC, HDL, TG will be measured using standard methods. |
| Changes in low-density lipoprotein (LDL). | At the baseline and 12 weeks of treatment | The low-density lipoprotein cholesterol (LDL) will be calculated according to the Friedwald equation. |
| Changes in fat mass content in the body. | At the baseline and 12 weeks of treatment | The fat mass content \[in kg\] in the body will be estimated using BIA methods (InBody 270 and Bioscan 920-2), |
| Changes in fasting insulin level. | At the baseline and 12 weeks of treatment | The ELISA will be used in the estimation. |
| Changes in insulin resistance index (HOMA-IR) | At the baseline and 12 weeks of treatment | The HOMA-IR will be calculated according to formula: HOMA-IR = (insulin \* glucose) / 22.5 for the glucose concentration in mmol/L, or: HOMA-IR = (insulin \* glucose ) / 405 for glycemia in mg/dL. In both cases, the insulin is in mU/L. |
| Changes in parameter of liver damage: cytokeratin 18. | At the baseline and 12 weeks of treatment | The ELISA will be used in the estimation cytokeratin 18 (ccK18). |
| Changes in parameter of liver damage: Glutathione S-transferase (GST). | At the baseline and 12 weeks of treatment | The ELISA will be used in the estimation GST. |
| Changes in parameter of liver damage: collagen IV. | At the baseline and 12 weeks of treatment | The ELISA will be used in the estimation collagen IV. |
| Changes in parameter of liver damage: hyaluronic acid. | At the baseline and 12 weeks of treatment | The ELISA will be used in the estimation hyaluronic acid. |
| Changes in hsCRP. | At the baseline and 12 weeks of treatment | The hsCRP will be measured using ELISA. |
| Changes in pentraxin 3. | At the baseline and 12 weeks of treatment | The pentraxin 3 (PTX3) will be measured using ELISA. |
| Gut barrier integrity parameter: calprotectin. | At the baseline and 12 weeks of treatment | The ELISA, will be used in the estimation. |
| Gut barrier integrity parameters: liver fatty acid-binding protein (L-FABP), intestinal fatty acid-binding protein (I-FABP). | At the baseline and 12 weeks of treatment | The ELISA, will be used in the estimation. |
| Gut barrier integrity parameters: lipopolysaccharide (LPS). | At the baseline and 12 weeks of treatment | The ELISA, will be used in the estimation. |
| Cardiometabolic risk. | At the baseline and 12 weeks of treatment | Cardiometabolic risk will be estimated at baseline and after 3 months of treatment using the SCORE scale. SCORE scale summarize 5 risk factors (sex, age, systolic blood pressure, total cholesterol and smoking). |
| Changes in fasting glucose level. | At the baseline and 12 weeks of treatment | The fasting glucose level will be measured using standard methods. |
| Changes in blood pressure. | At the baseline and 12 weeks of treatment | Resting seated BP (both systolic and diastolic) will be measured using a brachial cuff (Omron Healthcare, Kyoto, Japan) three times at 2-min intervals, and the average value will be calculated. |
| Changes in weight. | At the baseline and 12 weeks of treatment | Weight will be measured in light clothing and without metal objects (i.e., belt, jewelry). Weight will be measured to the nearest 0.1 kg. |
Countries
Poland
Contacts
Primary ContactMałgorzata Moszak, PhD
Backup ContactMonika Szulińska, DSc
Outcome results
None listed