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 alpha-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 alpha-tocopherol catabolites alpha-carboxyethyl hydroxychromanol (alpha-CEHC) and alpha-carboxymethylbutyl hydroxychromanol (alpha-CMBHC) are useful biomarkers of alpha-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-alpha-tocopherol (d(6)-alpha-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured alpha-CEHC and alpha-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma alpha-tocopherol, alpha-CEHC, and alpha-CMBHC concentrations at various times <= 72 h. Results: During the first 24 h, participants with MetS compared with healthy adults excreted 41% less alpha-CEHC (all values are least-squares means +/- SEMs: 0.6 +/- 0.1 compared with 1.0 +/- 0.1 mu mol/g creatinine, respectively; P = 0.002), 63% less hexadeuterium-labeled (d(6))-alpha-CEHC (0.04 +/- 0.02 compared with 0.13 +/- 0.02 mu mol/g creatinine, respectively; P = 0.002), and 58% less d(6)-alpha-CMBHC (0.017 +/- 0.004 compared with 0.041 +/- 0.004 mu mol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d(6)-alpha-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 3 h, respectively; P = 0.01]. d(6)-alpha-CEHC peaked before d(6)-alpha-T in 77 of 80 paired plasma concentration curves. Urinary d(6)-alpha-CEHC 24-h concentrations were associated with the plasma AUC(0-24)h of d(6)-alpha-T (r = 0.53, P = 0.02) and d(6)-alpha-CEHC (r = 0.72, P = 0.0003), and with urinary d(6)-alpha-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 alpha-CEHC and alpha-CMBHC are useful biomarkers to noninvasively assess alpha-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs alpha-tocopherol trafficking.