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Background:Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity.Objective:To study the effect of dietary supplementation with PS on cholesterol and glucose metabolism in humans.Methods:Twelve men with the metabolic syndrome (MetS) (according to the International Diabetes Federation (IDF) criteria; age 51±2 years (mean±s.e.m.); body mass index (BMI) 32±1 kg/m2) were randomly assigned to 4 weeks of PS (500 mg twice daily) and 4 weeks of placebo (P) in a double-blind cross-over study, with a 4-week wash-out period between both interventions. At the end of each intervention anthropometric measures and serum lipids were measured and an intravenous glucose tolerance test (IVGTT) was performed.Results:Phytosphingosine did not affect body weight and fat mass compared with P. PS decreased serum total cholesterol (5.1±0.3 (PS) vs 5.4±0.3 (P) mmol/l; P<0.05) and low-density lipoprotein (LDL)-cholesterol levels (3.1±0.3 (PS) vs 3.4±0.3 (P) mmol/l; P<0.05), whereas it did not alter serum triglyceride and high-density lipoprotein (HDL)-cholesterol levels. In addition, PS lowered fasting plasma glucose levels (6.2±0.3 (PS) vs 6.5±0.3 (P) mmol/l; P<0.05). PS increased the glucose disappearance rate (K-value) by 9.9% during the IVGTT (0.91±0.06 (PS) vs 0.82±0.05 (P) %/min; P<0.05) at similar insulin levels, compared with P, thus implying enhanced insulin sensitivity. PS induced only minor gastrointestinal side effects.Conclusion:Dietary supplementation of PS decreases plasma cholesterol levels and enhances insulin sensitivity in men with the MetS. [ABSTRACT FROM AUTHOR]