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

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-labeled RRR -α-tocopherol (d 6 -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 (d 6 )-α-CEHC (0.04 ± 0.02 compared with 0.13 ± 0.02 μmol/g creatinine, respectively; P = 0.002), and 58% less d 6 -α-CMBHC (0.017 ± 0.004 compared with 0.041 ± 0.004 μmol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d 6 -α-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC 0-24h ): 27.7 ± 7.9 compared with 58.4 ± 7.9 nmol/L × h, respectively; P = 0.01]. d 6 -α-CEHC peaked before d 6 -α-T in 77 of 80 paired plasma concentration curves. Urinary d 6 -α-CEHC 24-h concentrations were associated with the plasma AUC 0-24 h of d 6 -α-T ( r = 0.53, P = 0.02) and d 6 -α-CEHC ( r = 0.72, P = 0.0003), and with urinary d 6 -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.