Effect of Fucoxanthin on the Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion

The Metabolic Syndrome (MS) is a cluster of cardiometabolic risk factors, which include abdominal obesity, hyperglycemia, dyslipidemia, and high blood pressure. MS is considered a serious problem to health systems due to a current inability on implementing an effective prevention and treatment program. In Mexico 73% of adult population suffers obesity or overweight, this condition triggers the best studied pathophysiological mechanism; insulin resistance, which in turn precedes the diagnosis of diabetes and cardiovascular disease, that are the main cause of general mortality in Mexico, thus the prevention and timely treatment of this condition are now a priority.

Actual pharmacological therapy is designed to control its components individually, however, there are great interest in developing new therapeutic lines that improve more than one component simultaneously and thereby increase the cost-benefit and effectiveness of the therapy. Fucoxanthin is a functional element present in seaweed species. Several studies have offered certain perspectives on its action mechanism and safety. The information available is favorable for weight control in overweight subjects, but its activity in glucose levels, lipid metabolism and blood pressure is inconsistent. It represents a natural option with great interest in this research, since it could be a new, safe and effective therapy in the MS.

The aim of this study is to evaluate the effect of fucoxanthin on the components of the MS, insulin sensitivity and insulin secretion. The investigators hypothesis is that Fucoxanthin modifies the components of the MS, insulin sensitivity and insulin secretion

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: Fucoxanthin; Drug: Placebo

Detailed Description

A randomized, double-blind, placebo-controlled, clinical trial will be conducted in 28 patients with MS according to the International Diabetes Federation (IDF) criteria, men and women, ages 30 to 60. Participants will be assigned randomly into two groups of 14 individuals each. Patients will receive a capsule with Fucoxanthin 12 mg or homologated placebo once a day during 90 days.

Waist circumference, fasting blood glucose, serum triglycerides, serum HDL cholesterol and blood pressure will be evaluated before and after intervention in both groups. First phase of insulin secretion (Stumvoll index), total insulin secretion (Insulinogenic index) and Insulin sensitivity (Matsuda index) will be calculated from the concentration of glucose and insulin obtained from an Oral Glucose Tolerance Test.

Data from statistical analysis will be presented through measures of central tendency and dispersion( mean and standard deviation) for quantitative variables and frequencies and percentages for qualitative variables. The qualitative variables will be analyzed through the X2 or Fisher's exact test. The intra-group analysis of the quantitative variables will be carried out by means of the Wilcoxon rank test, while the inter-group analysis with the U test of Mann Whitney and Kruskal-Wallis. Statistical significance will be considered with a p<0.05.

This protocol was approved by a local ethics committee and written informed consent will be obtained from all volunteers

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed MS according to the IDF criteria:
• - - Waist circumference: ≥80 cm (women) ≥90 cm (men), plus two or more of the following:
• - - - - Fasting glucose ≥ 100 mg/dL
• - - - - Triglycerides ≥150 mg/dL
• - - - - HDL-C: Men ≤40 mg/dL, women ≤50 mg/dL
• - - - - Blood pressure ≥130/85 mmHg
• Body Mass Index between 25 and 34.9 kg/m²
• No pharmacological treatment for MS
• Stable weight during the last 3 months

Exclusion Criteria:

• Pregnancy or breast-feeding
• History of kidney or liver disease
• Drugs or supplements consumption with proven properties that modify the behavior of the MS
• Total cholesterol >240 mg/dL
• Triglycerides >500mg/dL
• Glucose ≥126 mg/dL or HbA1C ≥6.5%.
• Hypersensitivity to Fucoxanthin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fucoxanthin; 12 mg Fucoxanthin capsule, once a day before breakfast during 90 days.	Drug: Fucoxanthin; Intervention will be administered 30 minutes before breakfast.
Placebo Comparator: Placebo; Homologated magnesium sterate capsule, once a day before breakfast during 90 days.	Drug: Placebo; Intervention will be administered 30 minutes before breakfast.; Other Names: Magnesium Sterate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist Circumference (WC)	WC was measured with a flexible tape at the midline between the highest point of the iliac crest and the lowest rib in the midaxillary line.	12 weeks.
Fasting Serum Glucose	Fasting serum glucose concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.
Triglycerides (TG)	TG concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.
High-Density Lipoprotein (HDL-C)	Serum HDL-C concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.
Systolic Blood Pressure	Blood pressure was evaluated using a digital sphygmomanometer after a resting period of 15 min with the subject sitting; the bracelet was adjusted 3.0 cm above the fold of the elbow of the left arm.	12 weeks.
Diastolic Blood Pressure	Blood pressure was evaluated using a digital sphygmomanometer after a resting period of 15 min with the subject sitting; the bracelet was adjusted 3.0 cm above the fold of the elbow of the left arm.	12 weeks.
Matsuda-DeFronzo Insulin Sensitivity Index	The Matsuda-DeFronzo index measures whole-body insulin sensitivity from serum insulin and glucose levels during an oral glucose tolerance test (OGTT). The index is calculated with the formula: 10,000 / sqrt([fasting glucose (mg/dL) × fasting insulin (µU/mL)] × [mean glucose × mean insulin during OGTT]). The scale ranges from 0 to infinity, with higher values indicating greater insulin sensitivity. Typical values for healthy individuals range between 2 and 10, while lower values suggest insulin resistance.	12 weeks.
Total Insulin Secretion	The Total Insulin Secretion is calculated as the ratio of the area under the curve (AUC) for insulin to the AUC for glucose during a 120-minute oral glucose tolerance test (OGTT). The formula is: AUC insulin / AUC glucose. AUC values are derived from concentrations measured at 0, 30, 60, 90, and 120 minutes post-ingestion of a glucose solution at week 12. Interpretation of the AUC insulin/AUC glucose ratio is as follows: values <0.5 indicate insulin resistance, values between 0.5 and 1.0 suggest moderate insulin secretion, and values >1.0 reflect optimal insulin secretion.	12 weeks.
Stumvoll Index	The Stumvoll index measures the first phase of insulin secretion, incorporates demographic data along with plasma glucose (mmol/L) and insulin (pmol/L) levels measured during an oral glucose tolerance test (OGTT). There is no universally standardized ranges, values ranges from 0 to infinity; higher values indicate a better early insulin response to glucose (first 30 minutes), reflecting more effective beta-cell function.	12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	Body weight was measured at baseline a bioimpedance scale.	12 weeks.
Body Mass Index (BMI)	BMI was calculated with the Quetelet index formula.	12 weeks.
Body Fat	Percentage of body fat was measured using a bioimpedance scale.	12 weeks.
Total Cholesterol (TC)	Serum Total Cholesterol concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.
Low-Density Lipoprotein (LDL-C)	Serum LDL-C concentration was calculated using the Friedewald formula (LDL-C = TC - (HDL-C + [TG/5])	12 weeks.
Very-Low-Density Lipoprotein (VLDL)	Serum VLDL concentration was calculated with the formula: VLDL-C = TG/5.	12 weeks.
Alanine Aminotransferase (ALT)	Serum ALT concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.
Aspartate Aminotransferase (AST)	Serum AST concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.
Creatinin	Serum creatinin concentration was measured with enzymatic/colorimetric techniques by spectrophotometry.	12 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of treatment-related adverse events during the intervention.	Number of participants presenting treatment-related adverse events will be determined with oral questionnaires to the participants and with the records in a treatment-adherence diary (provided to the participant) at day 30, day 60 and day 90, as assessed by the common terminology criteria for adverse events (CTCAE) v5.0	Day 30, Day 60 and Day 90.

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: Manuel Gonzalez Ortiz, MD MSc Phd, University of Guadalajara

Publications and helpful links

General Publications

• Yang M, Xuan Z, Wang Q, Yan S, Zhou D, Naman CB, Zhang J, He S, Yan X, Cui W. Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets. Nutr Neurosci. 2022 Oct;25(10):2167-2180. doi: 10.1080/1028415X.2021.1926140. Epub 2021 May 15.
• Lopez-Ramos A, Gonzalez-Ortiz M, Martinez-Abundis E, Perez-Rubio KG. Effect of Fucoxanthin on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion. J Med Food. 2023 Jul;26(7):521-527. doi: 10.1089/jmf.2022.0103. Epub 2023 Jul 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): January 30, 2022
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: September 25, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Metabolic Syndrome; Insulin Sensitivity; Fucoxanthin; Insulin Secretion
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Immune System Diseases; Disease; Glucose Metabolism Disorders; Hyperinsulinism; Syndrome; Hypersensitivity; Metabolic Syndrome; Insulin Resistance
• Other Study ID Numbers: Fucoxanthin-MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No