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

• Published in: Nutrients Vol. 13; no. 1; p. 258
• Main Authors: Koay, Yan Yi, Tan, Gerald Chen Jie, Phang, Sonia Chew Wen, Ho, J-Ian, Chuar, Pei Fen, Ho, Loon Shin, Ahmad, Badariah, Abdul Kadir, Khalid
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-01-2021; MDPI
• Subjects: Adult; Aged; Aged, 80 and over; Albumins; Albuminuria - urine; Analysis; anti-inflammatory; antifibrotic; antioxidant; Antioxidants; Biomarkers; Blood pressure; Chronic illnesses; Clinical trials; Creatinine; Creatinine - blood; Diabetes; Diabetes mellitus; diabetic kidney disease; Diabetic Nephropathies - drug therapy; Diabetic nephropathy; Diet therapy; Double-Blind Method; Drug dosages; Electrocardiography; End-stage renal disease; Epidermal growth factor receptors; Ethylenediaminetetraacetic acid; Fasting; Female; Glomerular Filtration Rate; Glycosylated hemoglobin; Humans; Inflammation; Kidney diseases; Kidney Failure, Chronic - drug therapy; Kidneys; Kinases; Malaysia; Male; Metabolism; Middle Aged; Placebos; Product development; Prospective Studies; Subgroups; Tocopherol; tocotrienols; Tocotrienols - administration & dosage; Transforming Growth Factor beta1 - blood; Transforming growth factor-b1; Transforming growth factors; Treatment Outcome; Urine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Vitamin E; Malaysia; Australia; diabetic kidney disease; tocotrienols; antioxidant; vitamin E; anti-inflammatory; antifibrotic; transforming growth factor-beta 1 (TGF-β1)
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13010258

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 (
= 31) which received tocotrienol-rich vitamin E (Tocovid SupraBio
; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (
= 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),
= 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24),
= 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),
= 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03),
= 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.