Background/objective: Lipid peroxidation has been indicated to be associated with glucose homeostasis. Vitamin E (mainly α-tocopherol), a well-known lipid radical scavenger, might mitigate the damage induced by lipid peroxidation. Here, we aimed to investigate the association between α-tocopherol metabolites and measures of glucose homeostasis at middle age.

Methods: In this cross-sectional study, 526 participants (mean age: 56 ± 6 years, 54% women) without glucose lower medication were analyzed. Alpha-tocopherol metabolites in blood (α-tocopherol and α-CEHC-SO₃) and urine (α-TLHQ and α-CEHC, presented as their sulfate and glucuronide conjugates) were quantified by untargeted metabolon platform and LC/MS-MS, respectively. Glucose homeostasis measures were also measured. Multivariable linear regression models were performed to assess the associations between metabolites with measures of glucose homeostasis (HOMA-IR, HOMA-β, insulinogenic index and Matsuda index), adjusted for age, sex, educational level, lifestyle factors, and total body fat.

Results: In blood, a one-SD higher α-tocopherol was associated with 0.1 SD (95% CI -0.18, -0.02) lower HOMA-β, but not for other measures. In urine, α-TLHQ-to-α-CEHC ratio was calculated as a conversion between none-enzymatic (i.e. anti-lipid oxidative) and enzymatic metabolism, representing functional capacity. A one-SD higher in α-TLHQ-to-α-CEHC ratio was related to 0.09 SD (-0.17, -0.02) lower HOMA-IR and 0.1 SD (0.02, 0.19) higher Matsuda index. Similar associations were also observed for both glucuronide and sulfate conjugate ratios.

Discussion: The current study showed that none-enzymatic α-tocopherol metabolites were associated with glucose homeostasis measures. Though the associations contradict to what was hypothesized, our results might suggest that functional capacity, rather than circulatory level, should provide more insight.