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Clinical Trial
. 2021 Jan 18;13(1):258.
doi: 10.3390/nu13010258.

A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Yan Yi Koay  1 , Gerald Chen Jie Tan  1 , Sonia Chew Wen Phang  1 , J-Ian Ho  1 , Pei Fen Chuar  1 , Loon Shin Ho  1 , Badariah Ahmad  1 , Khalid Abdul Kadir  1
Affiliations
Clinical Trial

A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Yan Yi Koay et al. Nutrients. .

Abstract

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

Keywords: anti-inflammatory; antifibrotic; antioxidant; diabetic kidney disease; tocotrienols; transforming growth factor-beta 1 (TGF-β1); vitamin E.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study that include data collection, analyses or interpretation of data; the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Summary of patient flow diagram. n: number of patients.
Figure 2
Figure 2
Graph of overall trend of estimated glomerular filtration rate (eGFR) for 12 months. Data are presented as mean ± standard deviation. * Significant at p < 0.05, ** p < 0.001.
Figure 3
Figure 3
Changes in serum creatinine in intervention and placebo group throughout the study period of 18 months. Data are presented as mean ± standard deviation. * Significant at p < 0.05.
See this image and copyright information in PMC

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