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

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.

Hypoxia and chronic kidney disease

“…Although the role of vitamin E (a traditional antioxidant) for kidney diseases is unlikely to help much, 98 , 99 a recent phase IIb randomized controlled trial found that 400 mg tocotrienol-rich vitamin E supplementation for 12 months could ameliorate the progression of diabetic kidney disease (assessed by serum creatinine and eGFR). 100 Therefore, these results indicated that oxidative stress is a promising therapeutic target in the context of CKD.…”

Vitamin E beyond Its Antioxidant Label

“…Additionally, a pilot randomized, double-blind, placebo-controlled trial investigated the effects of 400 mg of a TT-rich vitamin E product for 12 months on the renal function of the supplementation of patients with stage 3 chronic kidney disease (CKD). Vitamin E improved kidney function, as revealed by serum creatinine, as well as estimated glomerular filtration rate [ 185 ].…”

"Comparative Efficacy of Tocotrienol and Tocopherol for their Anti Diabetic Effects"

“…The same is supported by available literature that ideal dose range should vary between 200-400mg. 11 The different finding was observed where duration of study was 24 weeks and 430mg olive oil extract as a source of totoctrienol was used and significant effects were observed to improve quality of life for diabetic patients [11,12].…”

“…Despite having similar structure and antioxidant properties, these isoforms differ in their bioavailability and metabolism [1]. The other difference is the amount of saturation tails whereas tocotrienols have unsaturated isoprenoid side chain with three double bonds [2].…”