Dario Tuccinardi1,2, Olivia M Farr1, Jagriti Upadhyay1, Sabrina M Oussaada1, Maria I Klapa3, Marco Candela4, Simone Rampelli4, Sylvain Lehoux5,6, Iolanda Lázaro7,8, Aleix Sala-Vila7,8, Patrizia Brigidi4, Richard D Cummings4, Christos S Mantzoros1,9. 1. Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Centre/Harvard Medical School, Boston, Massachusetts. 2. Unit of Endocrinology and Diabetes, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy. 3. Department of Chemical & Biomolecular Engineering & Bioengineering, Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas, Patras, Greece. 4. Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. 5. Department of Surgery, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, Massachusetts. 6. Department of Surgery, Beth Israel Deaconess Medical Centre Glycomics Core, Boston, Massachusetts. 7. CIBERde Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. 8. Lipid Clinic, Department of Endocrinology and Nutrition, Institut d'Investigacions Biomediques August PiSunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain. 9. Section of Endocrinology, Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts.
Abstract
AIMS: To assess the effects of walnuts on cardiometabolic outcomes in obese people and to explore the underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic and microbiome analysis, integrated with lipid particle fractionation, appetite-regulating hormones and haemodynamic measurements. MATERIALS AND METHODS: A total of 10 obese individuals were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. The participants had two 5-day inpatient stays, during which they consumed asmoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts, with a 1-month washout period between the two visits. RESULTS:Walnut consumption improved aspects of the lipid profile; it reduced fasting small and dense LDL particles (P < 0.02) and increased postprandial large HDL particles (P < 0.01). Lipoprotein insulin resistance score, glucose and the insulin area under the curve (AUC) decreased significantly after walnut consumption (P < 0.01, P < 0.02 and P < 0.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with eight of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. The peptide YY AUC significantly increased after walnut consumption (P < 0.03). No major significant changes in haemodynamic or metabolomic analysis or in microbiome host health-promoting bacteria such as Faecalibacterium were found. CONCLUSIONS: These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic variables. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption, which may explain the longer-term benefits of walnuts or other nuts on insulin resistance, cardiovascular risk and mortality. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
RCT Entities:
AIMS: To assess the effects of walnuts on cardiometabolic outcomes in obese people and to explore the underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic and microbiome analysis, integrated with lipid particle fractionation, appetite-regulating hormones and haemodynamic measurements. MATERIALS AND METHODS: A total of 10 obese individuals were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. The participants had two 5-day inpatient stays, during which they consumed a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts, with a 1-month washout period between the two visits. RESULTS: Walnut consumption improved aspects of the lipid profile; it reduced fasting small and dense LDL particles (P < 0.02) and increased postprandial large HDL particles (P < 0.01). Lipoprotein insulin resistance score, glucose and the insulin area under the curve (AUC) decreased significantly after walnut consumption (P < 0.01, P < 0.02 and P < 0.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with eight of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. The peptide YY AUC significantly increased after walnut consumption (P < 0.03). No major significant changes in haemodynamic or metabolomic analysis or in microbiome host health-promoting bacteria such as Faecalibacterium were found. CONCLUSIONS: These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic variables. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption, which may explain the longer-term benefits of walnuts or other nuts on insulin resistance, cardiovascular risk and mortality. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
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