Effect of Citrus Flavonoids on Obesity.

Celia Bañuls

Status: Completed

Conditions: Diabetes Mellitus Type 2; Obesity Adult Onset

Treatments: Dietary Supplement: Flavonoid-enriched juice and a low-calorie diet; Dietary Supplement: Food supplement: placebo juice and a low calorie diet

Study type: Interventional

Funder types: Other

Identifiers

NCT06680635

PI21/01160

Details and patient eligibility

About

The aim of this study is to evaluate whether the intake of a functional juice enriched in citrus polymethoxylated flavonoids is able to improve the glycaemic profile and insulin resistance of obese patients by reversing the associated oxidative and inflammatory stress, as well as the differential alteration of the intestinal microbiota. To achieve this, a prospective, randomised, double-blind, placebo- controlled, clinical-baseline intervention study will be conducted in obese patients (BMI=30-40 kg/m2) with type 2 diabetes (DM2) (n=40) and obese patients without alterations in carbohydrate metabolism (n=40). Each of these groups will be randomly divided into 2 subgroups (n=20), one of which will receive polymethoxyflavonoid-enriched orange juice (14%: nobiletin, sinensetin, tangeretin) (200 ml/ day) and the other group will receive the corresponding placebo juice for 8 weeks. In addition, all of them will receive a hypocaloric diet. Anthropometric parameters, body composition and nutritional status will be assessed, cardiovascular risk factors and comorbidities will be studied (HT, SAHS, dyslipidaemia, insulin resistance), oxidative stress parameters will be compared (total and mitochondrial ROS production, mitochondrial membrane potential, glutathione levels by static cytometry and mitochondrial respiration rate by Seahorse flow analyser), antioxidant enzymes (SOD, GPx) and molecular oxidation products (Carbonyl proteins and 8-oxo-dG, LDLox) and LPS by ELISA techniques, inflammatory parameters (IL6, TNFa, IL1b, adiponectin, PAI-1, IL10) by Luminex XMAP technology in serum. Metabolomic analysis will also be performed in plasma (NMR spectroscopy and PLS-DA), and the content and diversity of the gut microbiota (16S rRNA amplicons, and direct metagenomic sequencing, with Illumina MiSeq technology) will be assessed in faeces, before and after the dietary intervention. Individualised dietary follow-up and assessment of subjects' quality of life will be carried out.

Enrollment: 80 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• patients with a BMI of 30 -40 kg/m2, between 18 and 65 years of age.
• Obesity of more than five years' duration
• Patients will maintain a stable weight (±2 kg) during the 3 months prior to the study.

Exclusion criteria

• Patients with acute or chronic inflammatory diseases and established liver and kidney failure (based on transaminase levels ±2 SD of the mean and estimated glomerular filtration rate using the CKD-EPI formula >60), neoplastic diseases and secondary causes of obesity (hypothyroidism, Cushing's syndrome), use of drugs that may influence inflammatory status or insulin sensitivity (NSAIDs, corticosteroids, anti-TNFα), treatment with insulin or GLP1 inhibitors, type 1 diabetes, morbid obesity (BMI>40 kg/m2), hypertriglyceridaemia (> 400 mg/dl), fructose intolerance.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups, including a placebo group

Flavonoid-enriched juice and low-calorie diet for obese patients

Active Comparator group

Description:

Subjects will receive nutritional intervention by a registered dietician and a flavonoid-enriched juice supplement for 8 weeks. The dietary intervention consists of healthy dietary recommendations and hypocaloric diet if necessary (overweight, obesity).

Treatment:

Dietary Supplement: Flavonoid-enriched juice and a low-calorie diet

Pacebo juice and low-calorie diet for obese patients

Placebo Comparator group

Description:

Subjects will receive nutritional intervention by a registered dietitian and a placebo in the form of juice for 8 weeks. The dietary intervention consists of healthy dietary recommendations and hypocaloric diet if necessary (overweight, obesity).

Treatment:

Dietary Supplement: Food supplement: placebo juice and a low calorie diet