Tocotrienol-Rich Vitamin E Improves Kidney Function in Diabetic Kidney Disease Patients

by | Mar 23, 2021 | 2021, Diabetes, Kidney Health, Tocotrienols, Vitamin E

Written by Angeline A. De Leon, Staff Writer. This study shows that a three-month supplementation with tocotrienol-rich vitamin E significantly increased estimated glomerular filtration rate (eGFR) and creatinine clearance in participating subjects.

vitamin EDiabetic kidney disease (DKD) is a serious microvascular complication associated with diabetes, resulting from blood vessel damage in the kidneys 1. Progression of DKD culminates in end-stage renal failure, the treatment of which is restricted to hemodialysis and/or renal replacement therapy 2. The research on the benefits of vitamin E supplementation for metabolic disease and diabetes-related complications is mixed: while some work reports a significant improvement in renal function with vitamin E supplementation 3, other research suggests that long-term vitamin E intake (4.5 years) produces no significant reno-protective effects in diabetic patients 4. A potential explanation for current discrepancies in the literature may lie in the distinction between different forms of vitamin E, as the majority of studies reporting non-significant effects seem to primarily rely on the use of vitamin E tocopherols, rather than tocotrienols 5,6, which are noted for their greater antioxidant capacity and higher absorption levels 7. Earlier experimental work has already linked treatment with tocotrienol-rich vitamin E to improved kidney function in diabetic rats 8 and modulation of inflammatory processes in early stage DKD 9. In 2021, a study 10 published in Nutrients evaluated the effects of high-dose tocotrienol-rich vitamin E intake on kidney function in patients with DKD.

A prospective randomized, double-blind, placebo-controlled trial was carried out in a total of 59 DKD patients (median age = 67 years) (qualifying for stage 3 chronic kidney disease or showing a urine to albumin creatinine ratio (UACR) > 20-200 mg/mmol). Subjects were randomized to receive either 400 mg tocotrienol-rich vitamin E or matching placebo daily for 12 months. At baseline and at regular 2-month intervals over the course of a year, fasting blood samples were collected to assess renal parameters (serum creatinine; eGFR; and UACR) and antifibrotic biomarkers (transforming growth factor beta 1, TGF-β1; vascular endothelial growth factor-A, VEGF-A).

After just 2 months, subjects in the vitamin E group, demonstrated a significant reduction in serum creatinine levels (p = 0.003) and a significant improvement in eGFR (p = 0.003), relative to placebo, which remained significant up to Month 8 (p = 0.029 for serum creatinine, p = 0.011 for eGFR). No significant changes were detected for UACR or for any of the serum biomarkers. In a subgroup analysis of patients with stage 3 chronic kidney disease, reno-protective effects were apparent for the vitamin E group vs. placebo up until Month 12 (p = 0.042 for serum creatinine, p = 0.022 for eGFR). However, after a 6-month washout period at the end of the year-long treatment period, any significant improvements in serum creatinine or eGFR were non-existent for all participants.

Results from the trial indicate that supplementation with tocotrienol-rich vitamin E can significantly improve parameters of renal function, based on serum creatinine levels and eGFR, in patients with DKD. However, improvements in kidney function were only observable up until 8 months and were not reflected in any of the other measured indices, including serum biomarkers and UACR. This suggests that vitamin E consumption can effectively improve creatinine clearance and waste filtration rate for a period of time, but does not necessarily impact urine protein extraction. Further research is needed to elucidate the mechanisms associated with these different functional changes in the kidney. Key limitations of the present trial are its limited sample size and failure to include a broader range of DKD biomarkers. In the future, replicating findings using comparative testing to examine the efficacy of tocotrienols vs. that of tocopherols would be valuable.

Source: Koay YY, Tan GCJ, Phang SCW, et al. A phase IIb randomized controlled trial investigating the effects of tocotrienol-rich vitamin E on diabetic kidney disease. Nutrients. 2021; 13: 258. DOI: 10.3390/nu13010258.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0

Click here to read the full text study.

Posted March 23, 2021.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clinical journal of the American Society of Nephrology : CJASN. 2017;12(12):2032-2045.
  2. Luyckx VA, Tonelli M, Stanifer JW. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ. 2018;96(6):414-422d.
  3. Tan SMQ, Chiew Y, Ahmad B, Kadir KA. Tocotrienol-Rich Vitamin E from Palm Oil (Tocovid) and Its Effects in Diabetes and Diabetic Nephropathy: A Pilot Phase II Clinical Trial. Nutrients. 2018;10(9).
  4. Lonn E, Yusuf S, Hoogwerf B, et al. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care. 2002;25(11):1919-1927.
  5. Xu R, Zhang S, Tao A, Chen G, Zhang M. Influence of vitamin E supplementation on glycaemic control: a meta-analysis of randomised controlled trials. PLoS One. 2014;9(4):e95008.
  6. Suksomboon N, Poolsup N, Sinprasert S. Effects of vitamin E supplementation on glycaemic control in type 2 diabetes: systematic review of randomized controlled trials. J Clin Pharm Ther. 2011;36(1):53-63.
  7. Bardhan J, Chakraborty R, Raychaudhuri U. The 21st century form of vitamin E–tocotrienol. Curr Pharm Des. 2011;17(21):2196-2205.
  8. Siddiqui S, Ahsan H, Khan MR, Siddiqui WA. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression. Toxicol Appl Pharmacol. 2013;273(2):314-324.
  9. Cojocel C, Al-Maghrebi M, Thomson MS, Rawoot P, Raghupathy R. Modulation of the transforming growth factor beta1 by vitamin E in early nephropathy. Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2005;14(6):422-429.
  10. Koay YY, Tan GCJ, Phang SCW, et al. A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease. Nutrients. 2021;13(1).