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Metabolic syndrome increases dietary ?-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 ?-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 ?-tocopherol catabolites ?-carboxyethyl hydroxychromanol (?-CEHC) and ?-carboxymethylbutyl hydroxychromanol (?-CMBHC) are useful biomarkers of ?-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-labeled RRR-?-tocopherol (d6-?-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured ?-CEHC and ?-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma ?-tocopherol, ?-CEHC, and ?-CMBHC concentrations at various times ?72 h.Results: During the first 24 h, participants with MetS compared with healthy adults excreted 41% less ?-CEHC (all values are least-squares means ± SEMs: 0.6 ± 0.1 compared with 1.0 ± 0.1 ?mol/g creatinine, respectively; P = 0.002), 63% less hexadeuterium-labeled (d6)-?-CEHC (0.04 ± 0.02 compared with 0.13 ± 0.02 ?mol/g creatinine, respectively; P = 0.002), and 58% less d6-?-CMBHC (0.017 ± 0.004 compared with 0.041 ± 0.004 ?mol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d6-?-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-?-CEHC peaked before d6-?-T in 77 of 80 paired plasma concentration curves. Urinary d6-?-CEHC 24-h concentrations were associated with the plasma AUC0-24 h of d6-?-T (r = 0.53, P = 0.02) and d6-?-CEHC (r = 0.72, P = 0.0003), and with urinary d6-?-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 ?-CEHC and ?-CMBHC are useful biomarkers to noninvasively assess ?-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs ?-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.

SUBMITTER: Traber MG

PROVIDER: S-EPMC5320409 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.

Traber Maret G MG Mah Eunice E Leonard Scott W SW Bobe Gerd G Bruno Richard S RS

The American journal of clinical nutrition 20170111 3

<b>Background:</b> 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.<b>Objective:</b> We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol ...[more]

PMID: 28077381

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Project description:Increasing dietary fat intake is expected to improve ?-tocopherol bioavailability, which could be beneficial for improving ?-tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary ?-tocopherol requirements.Our objective was to assess dose-dependent effects of dairy fat and metabolic syndrome (MetS) health status on ?-tocopherol pharmacokinetics in plasma and lipoproteins.A randomized, crossover, double-blind study was conducted in healthy and MetS adults (n = 10/group) who ingested encapsulated hexadeuterium-labeled (d6)-RRR-?-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.Compared with healthy participants, those with MetS had lower (P < 0.05) baseline plasma ?-tocopherol (?mol/mmol lipid) and greater oxidized low-density lipoprotein (LDL), interleukin (IL)-6, IL-10, and C-reactive protein. Regardless of health status, d6-?-tocopherol bioavailability was unaffected by increasing amounts of dairy fat provided by milk beverages, but MetS participants had lower estimated d6-?-tocopherol absorption (±SEM) than did healthy participants (26.1% ± 1.0% compared with 29.5% ± 1.1%). They also had lower plasma d6-?-tocopherol AUC from 0 to 72 h, as well as maximal concentrations (Cmax: 2.04 ± 0.14 compared with 2.73 ± 0.18 ?mol/L) and slower rates of plasma disappearance but similar times to Cmax. MetS participants had lower d6-?-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-?-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.At dietary intakes equivalent to the Recommended Dietary Allowance, ?-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 ?-tocopherol absorption and/or impairs hepatic ?-tocopherol trafficking. These findings support higher dietary ?-tocopherol requirements for MetS adults. This trial was registered at www.clinicaltrials.gov as NCT01787591.

Dataset Information

Metabolic syndrome increases dietary ?-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.

Publications

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.

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