Impact of Vitamin E supplementation on vascular function in haptoglobin genotype stratified diabetes patients (EVAS Trial): a randomised controlled trial
What this study found
Vitamin E did not improve the primary vascular outcomes overall and showed no evidence of an interaction with haptoglobin genotype. RHI-EndoPAT and AI@75bpm did not change significantly with supplementation (p > 0.05), and the genotype interaction was also not significant (p > 0.05). In the non-Hp2-2 group, vitamin E was associated with higher EndoPAT-derived AIx along with higher LDL and ox-LDL concentrations (p < 0.05). An exploratory analysis found increased EndoPAT-derived AIx when baseline haptoglobin was > 119 mg/dl, but not when haptoglobin was ≤ 119 mg/dl; minor adverse effects such…
- Study & population
- Randomized controlled trial in adults with type 2 diabetes in Singapore, stratified by haptoglobin genotype (Hp2-2 vs non-Hp2-2).
- Intervention
- Vitamin E was given as natural alpha-tocopherol, 200 IU per tablet, two tablets daily for a total oral dose of 400 IU/day for 24 weeks.
- Key limitation
- The trial was relatively small within genotype strata and lasted only 24 weeks.
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Open PDFOriginal abstract
Aims Vitamin E (Vit-E) may preferentially improve cardiovascular risk in haptoglobin 2-2 (Hp2-2) genotype diabetes individuals. We studied the impact of Vit-E supplementation on vascular function in diabetes individuals stratified by haptoglobin genotype in Singapore. Methods In this 24-week, double blind, placebo-controlled RCT, we recruited 187 subjects (101 Hp2-2, 86 non-Hp2-2). Intervention: alpha-tocopherol-400 IU. Primary Outcome: Change in EndoPAT-derived reactive-hyperaemia index (RHI) and augmentation index (AIx); Secondary Outcomes: Pulse-Wave velocity (Sphygmocor-PWV), carotid intima media thickness (CIMT), inflammation (hsCRP), derivatives of reactive-oxygen metabolites (dROMs), biological antioxidant-potential (BAPs), HbA1c, LDL-C, HDL-C and oxidised LDL-C (ox-LDL). Results Overall, with Vit-E supplementation no significant change in RHI, PWV, CIMT, hsCRP, dROMS, BAPs, HDL-C and HbA1c was observed ( p > 0.05); an increase in LDL-C with concomitant decrease in ox-LDL, and incidentally increase in eGFR was observed ( p < 0.05). No interaction effect with haptoglobin genotype was seen for all outcomes ( p > 0.05). Subgroup analysis: In the non-Hp-2-2 group, Vit-E supplementation led to a higher EndoPAT-derived AIx, accompanied by higher LDL and ox-LDL concentrations ( p < 0.05); Hp2-2 group: Vit-E supplementation led to higher eGFR when compared to the non-Hp2-2 group (exploratory) ( p < 0.05). We observed an interaction effect for baseline haptoglobin concentration (threshold > 119 mg/dl) with intervention in terms of increased EndoPAT-derived AIx in the Hp > 119 mg/dl group whereas no change in the group with Hp ≤ 119 mg/dl. Conclusion Vit-E supplementation did not show any preferential benefit or deleterious effect on vascular function in Hp2-2 diabetes subjects in Singapore. A possible deleterious effect of an increase in arterial stiffness in individuals with Hp > 119 mg/dl was observed. Future studies should consider personalisation based on baseline Hp concentrations in patients with T2DM rather than just Hp2-2 genotype to evaluate impact on the detailed lipid pathways, cardiac and renal physiology. The impact of ethnic differences needs to be explored in greater details.