Table 4.

Principal clinical studies investigating the effect of brown seaweeds in MS comorbidities.

Brown Seaweeds	Bioactive Compound	Study Design and Population	Observed Effect	Refs.
A. nodosum and F. vesiculosus	Polyphenols, fibers, minerals	Double-blind, placebo-controlled, cross-over randomized trial with 23 men and women (18–60 years) with BMI 20–30 Kg/m2.	Decrease in insulin iAUC. Increase in the Cederholm index of insulin sensitivity.	[112]
A. nodosum and F. vesiculosus	Phlorotannins	60 men and women (18–65 years).	Improvement of postprandial cognitive performance and drowsiness.	[170]
A. nodosum and F. vesiculosus	Polyphenol extract (titrated to 20%)	65 dysglycemic patients.	Reduction in HbA1c, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, high sensitivity C-reactive protein, and HOMA-IR. Improve insulin sensitivity and glycemic status.	[171]
A. nodosum and F. vesiculosus	Polyphenol extract (titrated to 20%)	50 men and women (18–60 years), 44 overweight and 6 obese.	Reduction in waist circumference, plasma glucose, and insulin and HOMA index.	[172]
A. nodosum	Polyphenols (phlorotannins)	Double-blind, randomized, placebo-controlled crossover trial with 80 subjects (30–65 years) with BMI ≥ 25 Kg/m2.	Decrease in DNA damage in obese subjects. No significant changes in CRP, inflammatory cytokines, and antioxidant status.	[157]
F. vesiculosus	Polyphenols	Double-blind, placebo-controlled, randomized, cross-over trial with 38 volunteers (26 non-Asian, 12 Asian, 19–56 years).	No lowering effect on postprandial glucose or insulin responses in healthy subjects. Different insulin sensitivity in Asian subjects.	[173]
E. cava	Dieckol	Double-blind, placebo-controlled, randomized trial with 80 men and women (20–65 years) with a fasting glucose between 100 and 180 mg/dL.	Decrease in postprandial glucose, insulin, and C-peptide levels.	[174]
E. cava	Polyphenols. Including dieckol, 8,8’-bieckol, 6,6’-bieckol, and phlorofurofucoeckol A	Double-blind, placebo-controlled, randomized trial with 97 men and women (19–55 years) with BMI 24–29 Kg/m2.	Decrease in BMI, body fat ratio, waist circumference, waist/hip ratio, total cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol/high-density lipoprotein (HDL), cholesterol, and atherogenic index. High dosage showed also significant decreases in serum glucose and systolic blood pressure.	[175]
E. cava	Polyphenols (dieckol)	Double-blind, placebo-controlled, randomized trial with 80 healthy subjects (19–80 years) with total cholesterol > 200 mg/dL or of LDL cholesterol > 110 mg/dL.	Decrease in total cholesterol and LDL cholesterol levels.	[176]
U. pinnatifida and L. japonica	Indigestible polysaccharides dietary fiber	20 T2D patients (men and women, 40–70 years).	Improvement of blood glucose levels, serum TG decrease. Increase in HDL cholesterol and activity of CAT and glutathione peroxidase.	[102]
U. pinnatifida	Fresh Wakame or Mekabu	Randomized, crossover study with 12 healthy adults (men and women).	Reduction in plasma glucose levels, due to the improvement of glycemic index of foods.	[177]
U. pinnatifida	Dried Wakame powder	36 elderly outpatients with hypertension.	Decrease in systolic and diastolic blood pressure. Improvement of hypercholesterolemia.	[178]
U. pinnatifida	Dried algal powder	27 patients (men and women) with at least one symptom of MS.	Decrease in systolic blood pressure and waist circumference.	[179]
U. pinnatifida	Fucoxanthin	Double-blind, randomized, placebo-controlled study of 115 obese, premenopausal, non-diabetic women with and without NAFLD.	Decrease in body weight, waist circumference, body and liver fat content. Improvement in liver function tests and resting energy expenditure.	[180]
Kelp Laminaria	Fucoxanthin	Randomized, double-blind, placebo-controlled crossover trial with 50 men and women (20–59 years) with a BMI of > 26–30 Kg/m2 and waist circumference of ≥90 cm (women) and ≥85 cm (men).	Decrease in body weight, BMI, and visceral fat.	[181]
L. japonica	Fucoidan	Double-blind, placebo-controlled, randomized trial with 25 overweight or obese adults (30–60 years).	Decrease in diastolic blood pressure and LDL-C. Increase in insulin levels, HOMA β-cell, and HOMA IR.	[182]
Fermented L. japonica	5.56%-aminobutyric acid (GABA)	Randomized, controlled trial with healthy subjects with high levels of γ-GT (< 132 U/L).	Decrease in serum γ-GT and malondialdehyde. Reduction in oxidative stress. Increases antioxidant activity of CAT and SOD.	[183]
S. horneri	Fucoxanthin	Single-blinded and randomized study with 60 normal-weight and obese Japanese adults with a BMI > 22 Kg/m2.	Decrease in HbA1c levels.	[184]