Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals

Clin Nutr. 2021 Jun;40(6):4192-4200. doi: 10.1016/j.clnu.2021.01.039. Epub 2021 Feb 3.


Background & aims: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population.

Methods: This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of α-TOH metabolites and measures of glucose homeostasis.

Results: We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-TLHQ-SO3 was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH.

Conclusion: Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.

Keywords: Alpha-tocopherol; Glucose homeostasis; Insulin resistance; Vitamin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Chromans / blood
  • Chromans / urine
  • Cross-Sectional Studies
  • Female
  • Healthy Volunteers
  • Homeostasis / physiology*
  • Humans
  • Insulin Resistance / physiology
  • Linear Models
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Netherlands
  • Oxidation-Reduction
  • Propionates / blood
  • Propionates / urine
  • Prospective Studies
  • Urine / chemistry*
  • Vitamin E / analogs & derivatives*
  • alpha-Tocopherol / analogs & derivatives*


  • Blood Glucose
  • Chromans
  • Propionates
  • Vitamin E
  • 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman
  • alpha-Tocopherol