title: α-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial.
abstract: BACKGROUND
  Increasing dietary fat intake is expected to improve α-tocopherol bioavailability, which could be beneficial for improving α-tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary α-tocopherol requirements.
  
  
  OBJECTIVE
  Our objective was to assess dose-dependent effects of dairy fat and metabolic syndrome (MetS) health status on α-tocopherol pharmacokinetics in plasma and lipoproteins.
  
  
  METHODS
  A randomized, crossover, double-blind study was conducted in healthy and MetS adults (n = 10/group) who ingested encapsulated hexadeuterium-labeled (d6)-RRR-α-tocopherol (15 mg) with 240 mL nonfat (0.2 g fat), reduced-fat (4.8 g fat), or whole (7.9 g fat) milk before blood collection at regular intervals for 72 h.
  
  
  RESULTS
  Compared with healthy participants, those with MetS had lower (P < 0.05) baseline plasma α-tocopherol (μmol/mmol lipid) and greater oxidized low-density lipoprotein (LDL), interleukin (IL)-6, IL-10, and C-reactive protein. Regardless of health status, d6-α-tocopherol bioavailability was unaffected by increasing amounts of dairy fat provided by milk beverages, but MetS participants had lower estimated d6-α-tocopherol absorption (±SEM) than did healthy participants (26.1% ± 1.0% compared with 29.5% ± 1.1%). They also had lower plasma d6-α-tocopherol AUC from 0 to 72 h, as well as maximal concentrations (Cmax: 2.04 ± 0.14 compared with 2.73 ± 0.18 μmol/L) and slower rates of plasma disappearance but similar times to Cmax. MetS participants had lower d6-α-tocopherol AUC from t = 0-12 h (AUC0- t final) in lipoprotein fractions [chylomicron, very-low-density lipoprotein (VLDL), LDL, high-density lipoprotein]. Percentages of d6-α-tocopherol AUC0- t final in both the chylomicron (r = -0.46 to -0.52) and VLDL (r = -0.49 to -0.68) fractions were inversely correlated with oxidized LDL, IL-10, IL-6, and C-reactive protein.
  
  
  CONCLUSIONS
  At dietary intakes equivalent to the Recommended Dietary Allowance, α-tocopherol bioavailability is unaffected by dairy fat quantity but is lower in MetS adults, potentially because of greater inflammation and oxidative stress that limits small intestinal α-tocopherol absorption and/or impairs hepatic α-tocopherol trafficking. These findings support higher dietary α-tocopherol requirements for MetS adults. This trial was registered at www.clinicaltrials.gov as NCT01787591.
authors.affiliation: Human Nutrition Program, Department of Human Sciences and.
authors.forename: Eunice
authors.initials: E
authors.lastname: Mah
authors.affiliation: Human Nutrition Program, Department of Human Sciences and.
authors.forename: Teryn N
authors.initials: TN
authors.lastname: Sapper
authors.affiliation: Human Nutrition Program, Department of Human Sciences and.
authors.forename: Chureeporn
authors.initials: C
authors.lastname: Chitchumroonchokchai
authors.affiliation: Human Nutrition Program, Department of Human Sciences and.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Failla
authors.affiliation: Human Nutrition Program, Department of Human Sciences and.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Schill
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, and.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR.
authors.forename: Gerd
authors.identifier: http://orcid.org/0000-0002-3129-5628
authors.initials: G
authors.lastname: Bobe
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR.
authors.forename: Maret G
authors.identifier: http://orcid.org/0000-0002-2892-4024
authors.initials: MG
authors.lastname: Traber
authors.affiliation: Human Nutrition Program, Department of Human Sciences and bruno.27@osu.edu.
authors.forename: Richard S
authors.identifier: http://orcid.org/0000-0002-6772-2038
authors.initials: RS
authors.lastname: Bruno
mesh_terms: D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003903:Deuterium; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007408:Intestinal Absorption; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008892:Milk / Q000737:chemistry; D018384:Oxidative Stress; D014811:Vitamin E Deficiency / Q000178:diet therapy* / Q000209:etiology; D055815:Young Adult; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D004041:Dietary Fats; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003903:Deuterium; D024502:alpha-Tocopherol
keywords: bioavailability; metabolic syndrome; nonalcoholic steatohepatitis; pharmacokinetics; α-tocopherol