Linus Pauling Institute

BACKGROUND: Increasing dietary fat intake is expected to improve α-tocopherol bioavailability, which could be beneficial for improving α-tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary α-tocopherol requirements.

OBJECTIVE: Our objective was to assess dose-dependent effects of dairy fat and metabolic syndrome (MetS) health status on α-tocopherol pharmacokinetics in plasma and lipoproteins.

DESIGN: A randomized, crossover, double-blind study was conducted in healthy and MetS adults (n = 10/group) who ingested encapsulated hexadeuterium-labeled (d6)-RRR-α-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.

RESULTS: Compared with healthy participants, those with MetS had lower (P < 0.05) baseline plasma α-tocopherol (μmol/mmol lipid) and greater oxidized low-density lipoprotein (LDL), interleukin (IL)-6, IL-10, and C-reactive protein. Regardless of health status, d6-α-tocopherol bioavailability was unaffected by increasing amounts of dairy fat provided by milk beverages, but MetS participants had lower estimated d6-α-tocopherol absorption (±SEM) than did healthy participants (26.1% ± 1.0% compared with 29.5% ± 1.1%). They also had lower plasma d6-α-tocopherol AUC from 0 to 72 h, as well as maximal concentrations (Cmax: 2.04 ± 0.14 compared with 2.73 ± 0.18 μmol/L) and slower rates of plasma disappearance but similar times to Cmax. MetS participants had lower d6-α-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-α-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.

CONCLUSIONS: At dietary intakes equivalent to the Recommended Dietary Allowance, α-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 α-tocopherol absorption and/or impairs hepatic α-tocopherol trafficking. These findings support higher dietary α-tocopherol requirements for MetS adults. This trial was registered at www.clinicaltrials.gov as NCT01787591.