Therapeutic Intervention of Eriomin Associated with Metformin in the Control of Hyperglycemia in Pre-Diabetic Patients
- Conditions
- Pre-diabetes
- Interventions
- Dietary Supplement: EriominDietary Supplement: WashoutDietary Supplement: Placebo
- Registration Number
- NCT06005142
- Lead Sponsor
- Thais Cesar
- Brief Summary
Citrus bioflavonoids, such as eriocitrin, hesperidin and naringin, have been shown improved hyperglycemia, insulin resistance and systemic inflammation, related to the development of type 2 diabetes. The nutraceutical Eriomin, a lemon flavonoid extract composed mainly by eriocitrin (70%) and other flavonoids (30%), improved the control of moderate hyperglycemia in pre-diabetic and diabetic patients without drug therapy. However, most patients with pre-diabetes are on oral biguanide (metformin) therapy, despite its limited efficacy (30-40%) on glycemic control and its undesirable gastrointestinal effects.
Therefore, in the current study, Eriomin will be administered at a dose of 250 mg/d to adults diagnosed with pre-diabetes and being treated with metformin (1,000 mg/d). This clinical trial was designed as a placebo-control, double-blind, two-arm, crossover design. Clinical characteristics, body composition, food consumption, metabolic and inflammatory biomarkers and the microbiota of all patients will be evaluated before, during and at the end of the 12-week period (arm). Biochemical and metabolic parameters associated with prediabetes are expected to improve or return to normal with Eriomin in combination with metformin. At the same time, an increase in beneficial intestinal bacteria is expected, reducing pre-diabetic dysbiosis, and perhaps a noticeable improvement in body composition.
- Detailed Description
Recent evidence shows that bioflavonoids from citrus fruits and herbs can reduce hyperglycemia, dyslipidemia, insulin resistance and the systemic inflammatory process related to type 2 diabetes (T2D). Although they can be found in fruits and herbs, bioflavonoid supplements and nutraceuticals can provide sufficient and safe amounts of bioactive compounds to prevent the development of metabolic disorders, such as metabolic syndrome, diabetes, obesity and others. Eriocitrin flavanone, present in lemons, limes and oranges, has demonstrated anti-inflammatory, anti-hyperglycemic and antioxidant properties and is an integral part of lemon bioflavonoid supplements that have been widely marketed.
Eriocitrin metabolism, similar to hesperidin, is resistant to pancreatic enzymes and are mostly deglycosylated by intestinal bacteria (Bacteroides distasonis or Bacteroides uniformis) to eriodictyol before absorption. A minimal amount can be absorbed as glycosylated in the upper intestine. Eriodictyol, the aglycon of eriocitrin, can be metabolized by intestinal bacteria (with 3,4-dihydroxycinnamic acid formation) to homoeriodictyol and hesperetin through methoxylation. In the liver, eriodictyol is metabolized into glucuronides and conjugated sulfates of eriodictyol, homoeriodictyol, and hesperitin, through sulfation, glucuronidation and methylation, and later released into the circulation to exert biological activity.
Eriocitrin can increase the total antioxidant capacity, leading to a decrease in inflammatory markers (IL-6, MCP-1 and us-CRP) in the blood and organs of mice supplemented with the flavonoid. Eriocitrin also increased catalase and glutathione enzymes in the liver of diabetic rats, and decreased lipid peroxidation in blood, liver and kidney. Furthermore, oral administration of eriodictyol to diabetic rats improved glucose metabolism in the blood, liver and kidney, and suppressed diabetes by upregulating PPARγ29 mRNA expression.
Based on this experimental evidence, the nutraceutical Eriomin, composed of lemon bioflavonoids, was tested as a dietary supplement to control mild to moderate hyperglycemia in pre-diabetic and diabetic patients. After three months of therapy, there was a decrease in hyperglycemia, improvement in insulin resistance and a decrease in HbA1c.
Thus, the hypothesis of the current study is to use the nutraceutical Eriomin as a co-adjuvant to oral biguanide (metformin) therapy, improving control of hyperglycemia and insulin resistance, while increasing efficacy with a low dosage (250 mg/d) of the nutraceutical. It is expected to improve the quality of the microbiota, the glucose metabolism and body composition, in addition to reducing the side effects associated with the continuous use of metformin.
Therefore, the main objective of this study is to evaluate the effects of Eriomin (250mg/day) associated with metformin on glycemic control, insulin resistance and other metabolic, inflammatory and clinical parameters. Furthermore, it will evaluate changes in the microbiota of pre-diabetic patients.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 80
- Glycemia of 6.1 to 7.0 mmol / L
- Glycated hemoglobin with values between 5.7 and 6.4%
- use of drugs, vitamins and dietary supplements, alcohol consumption (> 20 g alcohol/d), and intense physical activity (> 5 hours/week).
- History of cardiovascular disease, diabetes mellitus, liver, kidney or pancreatic disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo/Eriomin Eriomin Group B will receive placebo (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then Eriomin (250 mg/day) for 12 weeks. Placebo/Eriomin Placebo Group B will receive placebo (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then Eriomin (250 mg/day) for 12 weeks. Placebo/Eriomin Washout Group B will receive placebo (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then Eriomin (250 mg/day) for 12 weeks. Eriomin/Placebo Placebo Group A will receive Eriomin (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then placebo (250 mg/day) for 12 weeks. Eriomin/Placebo Eriomin Group A will receive Eriomin (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then placebo (250 mg/day) for 12 weeks. Eriomin/Placebo Washout Group A will receive Eriomin (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then placebo (250 mg/day) for 12 weeks.
- Primary Outcome Measures
Name Time Method Fasting Glycemia 0-12-18-26 week Dosages of glycemia concentration (mg/dL) before and after intervention with Eriomin/placebo
- Secondary Outcome Measures
Name Time Method Insulin 0-12-18-26 week Dosages of Insulin (µU/mL) in the blood serum/plasma before and after intervention with Eriomin/placebo
Hepatic Enzymes 0-12-18-26 week dosages of alkaline phosphatase (U/L), gamma glutamyl transferase (U/L), aspartate aminotransferase (U/L), and alanine aminotransferase (U/L) in the blood serum/plasma before and after intervention with Eriomin/placebo
HbA1c 0-12-18-26 week Dosages of glycated hemoglobin (%) in the blood serum/plasma before and after intervention with Eriomin/placebo
Microbiota composition by 16S rRNA gene sequencing 0-12-18-26 week Dosages of the main bacteria groups by Operational Taxonomic Units (OTU) and % of relative abundance by group
Blood Lipids profile 0-12-18-26 week Dosages of cholesterol (mg/dL), HDL-cholesterol (mg/dL) and triglycerides (mg/dL) in the blood serum/plasma before and after intervention with Eriomin/placebo
Antioxidant Capacity 0-12-18-26 week Dosages of Trolox equivalent antioxidant capacity (TEAC) (μM) in the blood serum/plasma before and after intervention with Eriomin/placebo
Oral Glucose Tolerance Test (OGTT) 0-12-18-26 week Changes in blood glucose 2 hours after the oral glucose tolerance test (mg/dL) before and after intervention with Eriomin/placebo
Anthropometric Parameters 0-12-18-26 week Measurements of body weight (kg), muscle mass (kg), fat mass (kg) before and after intervention with Eriomin/placebo
Lipid Peroxidation 0-12-18-26 week Dosages of Malondialdehyde (MDA) (mM) the blood serum/plasma before and after intervention with Eriomin/placebo
Glucagon-like peptide-1 (GLP-1) 0-12-18-26 week Dosages of GLP-1 (pmol/L) the blood serum/plasma before and after intervention with Eriomin/placebo
Inflammatory parameters 0-12-18-26 week Dosages of C Reactive Protein (CRP) (mg/dL), TNF-alpha (mg/dL), IL-6 (mg/dL) in the blood serum/plasma before and after intervention with Eriomin/placebo
Kidney Blood Parameters 0-12-18-26 week Dosages of urea (mg/dL) and creatinine (mg/dL) in the blood serum/plasma before and after intervention with Eriomin/placebo
Trial Locations
- Locations (1)
Centro de Estudos e Praticas em Nutrição (CEPRAN)
🇧🇷Botucatú, SP, Brazil