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

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

Waist circumference will be measured at baseline, day 30, day 60 and day 90 with a validated metric tape, with the method proposed by ISAK. Values will be expressed in centimeters (cm).

Fasting serum glucose level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

Serum triglycerides level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

Serum HDL-C level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

Systolic blood pressure will be measured at baseline, day 30, day 60 and day 90 with a digital sphygmomanometer. Values will be expressed in millimeters of mercury (mmHg).

Diastolic blood pressure will be measured at baseline, day 30, day 60 and day 90 with a digital sphygmomanometer. Values will be expressed in millimeters of mercury (mmHg).

Changes in Baseline Insulin Sensitivity (Matsuda-DeFronzo insulin sensitivity index) after Intervention.

Insulin sensitivity will be determined at baseline and day 90 with the Matsuda-DeFronzo insulin sensitivity index. Calculated from serum concentrations of insulin (by ELISA) and glucose, obtained during an oral glucose tolerance test (OGTT). A value of <4.3 predict impaired insulin sensitivity. Uses the following formula: Matsuda index = 10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT).

Total insulin secretion will be determined at baseline and day 90 with Insulinogenic index. Insulinogenic index helps to estimate the total insulin secretion. Calculated from serum concentrations of insulin (by ELISA) and glucose, obtained during an oral glucose tolerance test (OGTT). Using the following formula: Insulinogenic Index = δAUCinsulin/δAUCglucose.

First phase of insulin secretion will be calculated at baseline and day 90 with Stumvoll index. Stumvoll index estimate the first phase of insulin secretion using demographic data in addition to plasma glucose (mmol/L) and insulin (pmol/L) levels obtained during an oral glucose tolerance test (OGTT). Calculated with the following formula: Stumvoll index = 1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'.

Body weight will be measured at baseline, day 30, day 60 and day 90 with a bioimpedance scale. Values will be expressed in kilograms (kg).

Body Mass Index will be calculated at baseline, day 30, day 60 and day 90 with with the Quetelet index formula, using a bioimpedance scale. Values will be expressed in kilograms per square meter (km/m2).

Percentage of body fat will be measured at baseline, day 30, day 60 and day 90 with a bioimpedance scale. Values will be expressed in percentages.

Serum total cholesterol level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

Serum LDL-C level will be calculated at baseline and day 90 with the Friedewald formula: LDL-C = TC - (HDL-C + [TG/5]). Values will be expressed in milligrams per deciliter (mg/dL).

Serum VLDL-C level will be calculated at baseline and day 90 with the formula: VLDL-C = TG/5. Values will be expressed in milligrams per deciliter (mg/dL).

Serum alanine aminotransferase level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

Serum aspartate aminotransferase level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

Serum creatinin level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL).

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

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

Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara

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.