Serum Vitamin E and Oxidative Protein Modification in Hemodialysis: A Randomized Clinical Trial

Background

Patients with end-stage renal disease have increased circulating concentrations of oxidatively modified circulating proteins. Therefore, we examined the ability of vitamin E α (α-tocopherol) to alter levels of these modified proteins.

Study Design

Randomized clinical trial.

Setting & Participants

27 clinically stable patients treated by means of hemodialysis in 4 freestanding outpatient dialysis units.

Intervention

Oral administration of 800 IU of vitamin E α or placebo daily.

Outcomes & Measurements

Plasma levels of α- and γ-tocopherol and oxidative protein modifications reflecting 2 pathways for protein-oxidant damage. The advanced glycation end product pentosidine reflects glycoxidation. The lipid peroxidation products iso[4]-levuglandin E₂, (E)-4-hydroxy-2-nonenal, and (E)-4-oxo-2-nonenal are formed through covalent adduction.

Results

Circulating levels of all oxidative protein modifications were increased in patients with end-stage renal disease. Supplementation with α-tocopherol caused α-tocopherol levels to rise (13.2 ± 3.7 to 27.3 ± 14 μg/mL), but γ-tocopherol levels to decrease (4.1 ± 1.6 to 3.5 ± 1.1 μg/mL). Control values were unchanged. There was no effect on oxidative protein modifications (placebo versus treatment; mean for pentosidine, 15.6 ± 11.4 (SD): 95% confidence interval (CI), 8.2 to 23.1 versus 21.3 ± 9.0 pg/mg protein; 95% CI, 16.1 to 26.6; iso[4]-levuglandin E₂, 8.31 ± 2.55; 95% CI, 6.77 to 9.85 versus 8.46 ± 2.37 nmol/mL; 95% CI, 7.09 to 9.84; (E)-4-hydroxy-2-nonenal, 0.51 ± 0.11; 95% CI, 0.45 to 0.57 versus 0.51 ± 0.08 nmol/mL; 95% CI, 0.46 to 0.56; (E)-4-oxo-2-nonenal, 189 ± 44; 95% CI, 162 to 215 vs 227 ± 72 pmol/mL; 95% CI, 183 to 271).

Limitations

Sample size was adequate to show changes in α- and γ-tocopherol levels in response to treatment. However, power was insufficient to show an effect on oxidative protein modifications.

Conclusions

Intervention of oral supplementation with α-tocopherol did not result in changes in circulating oxidative protein modifications. A larger study may be required to show an effect in this clinical setting.

Index Words: Vitamin E, α-tocopherol, γ-tocopherol, pentosidine, isolevuglandin, hydroxynonenal, oxononenal, hemodialysis, end-stage renal disease