title: Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.
abstract: BACKGROUND
  Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol.
  
  
  OBJECTIVE
  We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes.
  
  
  METHODS
  Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation.
  
  
  RESULTS
  Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P < 0.001) in the mixed tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation.
  
  
  CONCLUSIONS
  Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol. Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation.
authors.affiliation: Department of Core Clinical Pathology and Biochemistry, Royal Perth Hospital, University of Western Australia, Perth, Australia.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Clarke
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Ward
authors.forename: Jason H Y
authors.initials: JH
authors.lastname: Wu
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hodgson
authors.forename: Ian B
authors.initials: IB
authors.lastname: Puddey
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
mesh_terms: D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism / Q000652:urine; D019587:Dietary Supplements; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D006801:Humans; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D024505:Tocopherols / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D024502:alpha-Tocopherol / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D024504:gamma-Tocopherol / Q000032:analysis* / Q000097:blood / Q000378:metabolism
chemical_list: D002839:Chromans; C483420:carboxyethyl-hydroxychroman; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol; D024505:Tocopherols