Fruit and Vegetable Intervention Lowers Circulating Ceramide Levels and Improves Estimated Insulin Sensitivity in Young Adults at Risk of Developing Metabolic Syndrome: A FRUVEDomic Pilot Study
Authors: Mathews Alice T. , Famodu Oluremi A. , Olfert Melissa D. , Murray Pamela J. , Cuff Chris F. , Downes Marianne T. , Haughey Norman J. , Colby Sarah E. , Olfert I. Mark , McFadden Joseph W. 
Published: November 2023

Sphingolipid ceramide (Cer) is a biomarker for the progression of metabolic disease, such as metabolic syndrome (MetS) and type 2 diabetes. Nutritional interventions aimed at lowering circulating Cer may be a preventative means to improve health in young adults. Therefore, our objective was to identify improvements in serum sphingolipid profiles of young adults at risk for MetS throughout an 8‐week nutritional intervention. Subjects (n = 37; 23 ± 2 y; −0.54 ± 0.7 MetS score) were randomized into one of three nutritional intervention groups: 1) daily intake included 50% fruit and vegetables (FRUVED; USDA Dietary Guidelines for Americans, 2010), 2) FRUVED + low intake of refined carbohydrates (LRC), or 3) FRUVED + low intake of fat (LF). Blood was collected at regular intervals. LC/MS was used to profile Cer, monohexosylceramide (GlcCer), and lactosylceramide (LacCer) in serum. Data were analyzed using a mixed model with repeated measures including nonparametric correlations and linear regression. Overall, subjects consumed more fruit and vegetables during intervention (FRUVED or FRUVED + LRC, P < 0.05; FRUVED + LF, P = 0.08), as compared with pre‐intervention. Intervention increased the intake of calories from fat (FRUVED + LRC, P < 0.05), protein (FRUVED + LRC, P = 0.05), and fiber (FRUVED or FRUVED + LRC, P < 0.05) without modifying total sugar intake (all groups, P > 0.05), relative to pre‐intervention. Increasing fruit and vegetable intake improved insulin sensitivity, as measured by HOMA‐IR (FRUVED or FRUVED + LRC, P < 0.05); however, MetS score remain unchanged. Predominant serum sphingolipids included C24:0 Cer, C24:0 GlcCer, and C16:0 LacCer. Total serum Cer and GlcCer levels decreased following FRUVED with LRC or LF (P < 0.05), relative to FRUVED; however, LacCer levels were not modified. Intervention lowered many Cer and GlcCer in serum (P < 0.05), relative to pre‐intervention. Serum C22:0 and C24:0 Cer were lower in FRUVED with LRC or LF (P < 0.05), as compared with FRUVED. Serum C16:0 LacCer levels were unaffected by intervention. Serum C22:0 Cer levels were positively correlated with waist circumference (P < 0.05), and multiple Cer were positively associated with BMI (P = 0.05). Total serum Cer as well as abundant C24:0 Cer were positively correlated with systolic pressure (P < 0.05), but not diastolic pressure. Multiple serum Cer and GlcCer were positively correlated with aspartate aminotransferase (e.g. C24:0 Cer and GlcCer; P ≤ 0.05). Unsaturated Cer were positively correlated with serum triacylglycerol and VLDL (P < 0.05). Serum total Cer as well as C22:0 and C24:0 Cer were positively correlated with MetS score (P ≤ 0.05), and C24:1 and C22:1 Cer were positively associated with insulin resistance (P ≤ 0.05). Interestingly, C16:0 Cer levels were not correlated with any recorded measures of health. Employing a fruit and vegetable intervention with the purpose of lowering circulating ceramide may be a preventative means to reduce metabolic disease.Support or Funding InformationFunding by NIH/NIGMS U54GM104942