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. 2019 Dec 25:10:2042018819895462.
doi: 10.1177/2042018819895462. eCollection 2019.

Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial

Gerald Chen Jie Tan  1 , Suzanne May Quinn Tan  2 , Sonia Chew Wen Phang  2 , Yeek Tat Ng  2 , En Yng Ng  2 , Badariah Ahmad  2 , Uma Devi M Palamisamy  2 , Khalid Abdul Kadir  2
Affiliations

Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial

Gerald Chen Jie Tan et al. Ther Adv Endocrinol Metab. .

Abstract

Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.

Keywords: anti-inflammatory; antioxidant; diabetes; diabetic nephropathy; tocotrienol; vitamin E.

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Conflict of interest statement

Conflict of interest statement: The authors declare no conflict of interest. The sponsors had no role in the design of the study that included data collection, analyses or interpretation, the writing of the manuscript and in the decision to publish the results.

Figures

Figure 1.
Figure 1.
Patient flow diagram.
Figure 2.
Figure 2.
Graph of overall trend in serum creatinine. Error lines represent standard error of mean.
Figure 3.
Figure 3.
Graph of overall trend in estimated glomerular filtration rate (eGFR). Error lines represent standard error of mean.
See this image and copyright information in PMC

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