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

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.

Effects of delta‐tocotrienol supplementation on Glycemic Control, oxidative stress, inflammatory biomarkers and miRNA expression in type 2 diabetes mellitus: A randomized control trial

“…Contrary to these findings, few studies did not find a significant change in levels of TNF between T3 and placebo groups. This can be due to the short duration of the trial or more stable glycemic control of participants as compared to our study (Ng et al, 2020;Tan et al, 2019).…”

Vitamin E for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: A meta-Analysis

“…The results of this study were consistent with most of the RCTs included, indicating a beneficial effect of vitamin E on the incidence of CIPN. This may be explained by the fact that free radical damage caused by chemotherapy plays an important role in the production of CIPN ( Bove et al, 2001 ; Velasco et al, 2016 ; Ahmad Bainmahfouz et al, 2021 ), and supplementation with vitamin E has revealed a potential role in preventing neuropathy in clinical settings ( Rajanandh et al, 2014 ; Ng et al, 2020 ).…”

Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials

“…After screening the title and abstract, 73 studies were retrieved for full-text review. From this, 54 studies were excluded, and the reasons for exclusion are presented in the S2 Table . Out of the 19 studies [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] included in the present systematic review, there were four studies [16,17,22,23] involving subjects from two similar datasets, but these studies were included because each study reported unique biomarkers. For other duplicate publications, Pervez et al [30] was selected due to a larger sample size, while Kooyenga et al [25] was selected due to a longer follow-up duration.…”

“…For other duplicate publications, Pervez et al [30] was selected due to a larger sample size, while Kooyenga et al [25] was selected due to a longer follow-up duration. Thirteen studies [17][18][19][20][21][22][23][24]26,28,30,32,34] reporting CRP or high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), or malondialdehyde (MDA) were included for meta-analyses.…”

“…The characteristics of 19 studies included in the systematic review are presented in Table 1. There were 17 parallel studies [16][17][18][19][21][22][23][24][25][26][28][29][30][31][32][33][34] and two crossover studies [20,27]. Majority of these studies were carried out in Malaysia (n = 12) [16][17][18]20,21,24,[26][27][28]31,33,34], followed by United States of America (n = 3) [19,25,29], Iran (n = 2) [22,23], Pakistan (n = 1) [30] and Australia (n = 1) [32].…”