title: A nutrient-wide association study on blood pressure.
abstract: BACKGROUND
  A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner.
  
  
  RESULTS
  Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate <5% in training, P<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP.
  
  
  CONCLUSIONS
  We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tzoulaki
authors.forename: Chirag J
authors.initials: CJ
authors.lastname: Patel
authors.forename: Tomonori
authors.initials: T
authors.lastname: Okamura
authors.forename: Queenie
authors.initials: Q
authors.lastname: Chan
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Brown
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueshima
authors.forename: Liancheng
authors.initials: L
authors.lastname: Zhao
authors.forename: Linda
authors.initials: L
authors.lastname: Van Horn
authors.forename: Martha L
authors.initials: ML
authors.lastname: Daviglus
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000097:blood / Q000453:epidemiology; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D002149:Energy Intake / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage* / Q000097:blood*; D008875:Middle Aged; D009749:Nutrition Surveys / Q000379:methods*; D009752:Nutritional Status; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000097:blood; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000097:blood; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood
chemical_list: D015415:Biomarkers; D018977:Micronutrients; D017419:Potassium, Dietary; D012982:Sodium, Dietary; D014803:Vitamin B Complex