Identification of Plasma Lipid Metabolites Associated with Nut Consumption in US Men and Women.

BACKGROUND Intake of nuts has been inversely associated with risk of type 2 diabetes and cardiovascular disease, partly through inducing a healthy lipid profile. How nut intake may affect lipid metabolites remains unclear. OBJECTIVE The aim of this study was to identify the plasma lipid metabolites associated with habitual nut consumption in US men and women. METHODS We analyzed cross-sectional data from 1099 participants in the Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study. Metabolic profiling was conducted on plasma by LC-mass spectrometry. Nut intake was estimated from food-frequency questionnaires. We included 144 known lipid metabolites that had CVs ≤25%. Multivariate linear regression was used to assess the associations of nut consumption with individual plasma lipid metabolites. RESULTS We identified 17 lipid metabolites that were significantly associated with nut intake, based on a 1 serving (28 g)/d increment in multivariate models [false discovery rate (FDR) P value <0.05]. Among these species, 8 were positively associated with nut intake [C24:0 sphingomyelin (SM), C36:3 phosphatidylcholine (PC) plasmalogen-A, C36:2 PC plasmalogen, C24:0 ceramide, C36:1 PC plasmalogen, C22:0 SM, C34:1 PC plasmalogen, and C36:2 phosphatidylethanolamine plasmalogen], with changes in relative metabolite level (expressed in number of SDs on the log scale) ranging from 0.36 to 0.46 for 1 serving/d of nuts. The other 9 metabolites were inversely associated with nut intake with changes in relative metabolite level ranging from -0.34 to -0.44. In stratified analysis, 3 metabolites were positively associated with both peanuts and peanut butter (C24:0 SM, C24:0 ceramide, and C22:0 SM), whereas 6 metabolites were inversely associated with other nuts (FDR P value <0.05). CONCLUSIONS A panel of lipid metabolites was associated with intake of nuts, which may provide insight into biological mechanisms underlying associations between nuts and cardiometabolic health. Metabolites that were positively associated with intake of nuts may be helpful in identifying potential biomarkers of nut intake.

[1]  J. Mataix,et al.  Fatty acid composition of nuts – implications for cardiovascular health , 2006, British Journal of Nutrition.

[2]  An Pan,et al.  Walnut Consumption Is Associated with Lower Risk of Type 2 Diabetes in Women , 2013, The Journal of nutrition.

[3]  E. Ros,et al.  Short-Term Effect of Prebiotics Administration on Stool Characteristics and Serum Cytokines Dynamics in Very Young Children with Acute Diarrhea , 2010, Nutrients.

[4]  Estelle Pujos-Guillot,et al.  Discovery and validation of urinary exposure markers for different plant foods by untargeted metabolomics , 2014, Analytical and Bioanalytical Chemistry.

[5]  E. Riboli,et al.  Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies , 2016, BMC Medicine.

[6]  W. Willett,et al.  Associations between nut consumption and inflammatory biomarkers. , 2016, The American journal of clinical nutrition.

[7]  D. Vance,et al.  Phosphatidylcholine and choline homeostasis. , 2008, Journal of lipid research.

[8]  Walter C Willett,et al.  Understanding nutritional epidemiology and its role in policy. , 2015, Advances in nutrition.

[9]  S. Summers,et al.  Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. , 2008, Endocrine reviews.

[10]  E. Rimm,et al.  Alternative dietary indices both strongly predict risk of chronic disease. , 2012, The Journal of nutrition.

[11]  Kim Ekroos,et al.  Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol , 2016, European heart journal.

[12]  S. Summers,et al.  A ceramide-centric view of insulin resistance. , 2012, Cell metabolism.

[13]  L. Liang,et al.  Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet. , 2017, The American journal of clinical nutrition.

[14]  E. Rimm,et al.  Plasma leptin concentrations and four-year weight gain among US men , 2001, International Journal of Obesity.

[15]  Peter Kraft,et al.  Elevated circulating branched chain amino acids are an early event in pancreatic adenocarcinoma development , 2014, Nature Medicine.

[16]  E. Ros,et al.  Other relevant components of nuts: phytosterols, folate and minerals , 2006, British Journal of Nutrition.

[17]  G A Colditz,et al.  Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. , 1989, International journal of epidemiology.

[18]  Cristina Andres-Lacueva,et al.  Plasma metabolomic biomarkers of mixed nuts exposure inversely correlate with severity of metabolic syndrome. , 2015, Molecular nutrition & food research.

[19]  Dolores Corella,et al.  Primary prevention of cardiovascular disease with a Mediterranean diet. , 2013, The New England journal of medicine.

[20]  J. Manson,et al.  Nut Consumption and Risk of Cardiovascular Disease. , 2017, Journal of the American College of Cardiology.

[21]  Scott A Summers,et al.  Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. , 2003, Archives of biochemistry and biophysics.

[22]  J. Kirwan.  Plasma Ceramides Target Skeletal Muscle in Type 2 Diabetes , 2013, Diabetes.

[23]  M. Hartmann.  Plant sterols and the membrane environment , 1998 .

[24]  Cristina Andrés-Lacueva,et al.  Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. , 2011, Journal of proteome research.

[25]  D. Mozaffarian,et al.  Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials. , 2015, The American journal of clinical nutrition.

[26]  F. Hu,et al.  Use of Metabolomics in Improving Assessment of Dietary Intake. , 2018, Clinical chemistry.

[27]  J. Manson,et al.  Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. , 1998, Journal of the National Cancer Institute.

[28]  D. Corella,et al.  Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population: the PREDIMED study. , 2014, Journal of proteome research.

[29]  J. Manson,et al.  A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. , 1997, Carcinogenesis.

[30]  W. Willett,et al.  Reproducibility and validity of a semiquantitative food frequency questionnaire. , 1985, American journal of epidemiology.

[31]  D. Mozaffarian,et al.  Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women , 2015, Circulation.