title: Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.
abstract: Background:Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements.Objective:We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status.Design:Adults (healthy or with MetS;n= 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeledRRR-α-tocopherol (d6-α-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured α-CEHC and α-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma α-tocopherol, α-CEHC, and α-CMBHC concentrations at various times ≤72 h.Results:During the first 24 h, participants with MetS compared with healthy adults excreted 41% less α-CEHC (all values are least-squares means ± SEMs: 0.6 ± 0.1 compared with 1.0 ± 0.1 μmol/g creatinine, respectively;P= 0.002), 63% less hexadeuterium-labeled (d6)-α-CEHC (0.04 ± 0.02 compared with 0.13 ± 0.02 μmol/g creatinine, respectively;P= 0.002), and 58% less d6-α-CMBHC (0.017 ± 0.004 compared with 0.041 ± 0.004 μmol/g creatinine, respectively;P= 0.0009) and had 52% lower plasma d6-α-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC0-24h): 27.7 ± 7.9 compared with 58.4 ± 7.9 nmol/L × h, respectively;P= 0.01]. d6-α-CEHC peaked before d6-α-T in 77 of 80 paired plasma concentration curves. Urinary d6-α-CEHC 24-h concentrations were associated with the plasma AUC0-24 hof d6-α-T (r= 0.53,P= 0.02) and d6-α-CEHC (r= 0.72,P= 0.0003), and with urinary d6-α-CMBHC (r= 0.88,P< 0.0001), and inversely with the plasma inflammation biomarkers C-reactive protein (r= -0.70,P= 0.0006), interleukin-10 (r= -0.59,P= 0.007), and interleukin-6 (r= -0.54,P= 0.01).Conclusion:Urinary α-CEHC and α-CMBHC are useful biomarkers to noninvasively assess α-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs α-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR; and maret.traber@oregonstate.edu.
authors.forename: Maret G
authors.identifier: 0000-0002-2892-4024
authors.initials: MG
authors.lastname: Traber
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH.
authors.forename: Eunice
authors.initials: E
authors.lastname: Mah
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR; and.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Leonard
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR; and.
authors.forename: Gerd
authors.initials: G
authors.lastname: Bobe
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Bruno
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000378:metabolism; D002839:Chromans / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D009751:Nutritional Requirements; D009752:Nutritional Status; D010421:Pentanoic Acids / Q000097:blood / Q000378:metabolism* / Q000652:urine; D055815:Young Adult; D024502:alpha-Tocopherol / Q000378:metabolism*
chemical_list: C434334:5-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)-2-methyl-pentanoic acid; D015415:Biomarkers; D002839:Chromans; D015850:Interleukin-6; D010421:Pentanoic Acids; C483420:carboxyethyl-hydroxychroman; D016753:Interleukin-10; D002097:C-Reactive Protein; D003404:Creatinine; D024502:alpha-Tocopherol
keywords: bioavailability; metabolic syndrome; nutrient requirements; vitamin E; α-CEHC; α-carboxyethyl hydroxychromanol; α-carboxymethylbutyl hydroxychromanol