The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial

Nutrients. 2020 May 23;12(5):1522. doi: 10.3390/nu12051522.

Abstract

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

Keywords: diabetic peripheral neuropathy; malondialdehyde (MDA); nerve conduction study; nerve conduction velocity; nerve growth factor (NGF); tocotrienol; tumor necrosis factor receptor 1 (TNFR-1); type 2 diabetes mellitus; vascular cell adhesion molecule 1 (VCAM-1); vitamin E.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antioxidants / therapeutic use
  • Biomarkers / blood
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / drug therapy*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Glycated Hemoglobin / metabolism
  • Humans
  • Male
  • Malondialdehyde / blood
  • Middle Aged
  • Nerve Growth Factor / blood
  • Neural Conduction / drug effects
  • Patient Compliance
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / blood
  • Thromboxane B2 / blood
  • Tocotrienols / pharmacology
  • Tocotrienols / therapeutic use*
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vitamin E / therapeutic use*

Substances

  • Antioxidants
  • Biomarkers
  • Glycated Hemoglobin A
  • NGF protein, human
  • Receptors, Tumor Necrosis Factor
  • Tocotrienols
  • Tocovid
  • Vascular Cell Adhesion Molecule-1
  • Vitamin E
  • Malondialdehyde
  • Thromboxane B2
  • Nerve Growth Factor