Increases in Plasma Tryptophan Are Inversely Associated with Incident Cardiovascular Disease in the Prevención con Dieta Mediterránea (PREDIMED) Study.
Background:During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective:We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern.Methods:We used a case-cohort design nested in the Prevención con Dieta Mediterránea randomized controlled trial. There were 231 CVD cases (stroke, myocardial infarction, cardiovascular death) among 985 participants over a median of 4.7 y of follow-up [mean ± SD age: 67.6 ± 6.1 y; 53.7% women; mean ± SD body mass index (in kg/m2): 29.7 ± 3.7]. We assessed plasma tryptophan, kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid concentrations at baseline and after 1 y of intervention with a MedDiet. We combined these metabolites in a kynurenine risk score (KRS) by weighting each metabolite by the adjusted coefficient of its associations with CVD. Cox models were used in the primary analysis.Results:Increases in tryptophan after 1 y were associated with a lower risk of composite CVD (HR per SD: 0.79; 95% CI: 0.63, 0.98). The baseline kynurenic acid concentration was associated with a higher risk of myocardial infarction and coronary artery disease death but not stroke. A higher KRS was more strongly associated with CVD in the control group than in the 2 intervention groups (P-interaction = 0.003). Adjustment for changes in plasma tryptophan attenuated the inverse association between MedDiet+EVOO and CVD.Conclusions:An increase in the plasma tryptophan concentration was significantly associated with a decreased risk of CVD. A MedDiet may counteract the deleterious effects of a high kynurenine risk score.
Departments of Nutrition.
Edward
E
Yu
Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.|Navarra Institute for Health Research, Pamplona, Spain.|Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Miguel
M
Ruiz-Canela
Departments of Nutrition.|Navarra Institute for Health Research, Pamplona, Spain.|Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Marta
M
Guasch-Ferré
Departments of Nutrition.
Yan
Y
Zheng
Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.|Navarra Institute for Health Research, Pamplona, Spain.|Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Estefania
E
Toledo
Broad Institute of MIT and Harvard University, Cambridge, MA.
Clary B
CB
Clish
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
Jordi
J
Salas-Salvadó
Biostatistics, and.
Liming
L
Liang
Departments of Nutrition.
Dong D
DD
Wang
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Department of Preventive Medicine, University of Valencia, Valencia, Spain.
Dolores
D
Corella
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain.
Montse
M
Fitó
Department of Preventive Medicine, University of Málaga, Málaga, Spain.
Enrique
E
Gómez-Gracia
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Department of Family Medicine, Unit Research, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain.
José
J
Lapetra
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Department of Internal Medicine Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clinic, and.
Ramón
R
Estruch
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Lipid Clinic, Department of Endocrinology and Nutrition and University of Barcelona, Barcelona, Spain.
Emilio
E
Ros
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Lipid Clinic, Department of Endocrinology and Nutrition and University of Barcelona, Barcelona, Spain.
Montserrat
M
Cofán
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Department of Cardiology, University Hospital of Álava, Vitoria, Spain.
Fernando
F
Arós
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Health Research Institute of Palma, University Hospital Son Espases, Palma de Mallorca, Spain.
Dora
D
Romaguera
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain; and.
Lluis
L
Serra-Majem
Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.|Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain.
Jose V
JV
Sorlí
Departments of Nutrition.|Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Frank B
FB
Hu
Departments of Nutrition, mamartinez@unav.es.|Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.|Navarra Institute for Health Research, Pamplona, Spain.|Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Miguel A
MA
Martinez-Gonzalez
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D038441:Diet, Mediterranean; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014364:Tryptophan / Q000097:blood*
D014364:Tryptophan
Mediterranean diet; cardiovascular disease; epidemiology; metabolomics; nutrition; tryptophan