Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial

Abstract

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

A Retrospective Study on the Time in Range of Blood Glucose and Type 2 Diabetic Peripheral Neuropathy

“…This experimental study shows that with the increase of Hcy level, the prevalence of DPN gradually increases, and plasma Hcy is related to abnormal nerve conduction velocity. This is consistent with previous studies [ 26 , 27 ]. When Hcy > 15 μ mmo/L, the nerve conduction velocity obviously decreases with the increase of Hcy, and there is a significant correlation between the two [ 21 , 28 ].…”

Association between low birth weight and impaired glucose tolerance in children: a systematic review and meta-analysis

“…The “Fetal Origin hypothesis,” proposed in the 1990s, suggests that the conditions experienced during fetal intrauterine development significantly influence the risk of developing diseases in adulthood. According to this hypothesis, individuals born with LBW are at a considerably higher risk of developing type 2 diabetes later in life ( 34 ). Preterm delivery or intrauterine growth restriction is the most common cause of LBW ( 35 ).…”

Vitamins in neuropathy: pathophysiological and therapeutic roles

“…Progression of the neurological symptoms could be improved by vitamin E supplementation. Vitamin E exerts a key role in CIPN [52] and T2DM [53 ▪ ,54]. Although studies showed controversial results for vitamin E in the incidence of CIPN, the severity of CIPN was greatly reduced and recovery from CIPN was much faster with vitamin E supplementation [55].…”

“…In T2DM patients, tocotrienol-rich vitamin E supplementation significantly improved conduction velocity of tibial motor nerve up to 6 months and that of median and sural sensory nerve up to 12 months. These improvements lasted for 6 months after termination of the tocotrienol-rich vitamin E supplementation [53 ▪ ]. Co-administration of vitamin E and lithium chloride or coenzyme Q10 could ameliorate mechanical allodynia by anti-inflammatory and antioxidant properties in animals with nerve injury [56,57].…”

“…Vitamin K2-7, also known as menaquinone-7 (MK-7), is a form of vitamin K. Vitamin K2-7 has health-beneficial effects in peripheral neuropathy, diabetes, osteoporosis, cardiovascular disease, inflammation, cancer, and Alzheimer's disease. Clinical evidence demonstrates that K2-7 dietary supplementation can ameliorate peripheral neuropathy, reduce bone fracture risk, and improve cardiovascular health [53 ▪ ]. The mechanistic basis for K2-7 might be mediated through signal transduction pathways including PI3K/AKT, MAP kinase, JAK/STAT, NF-κB, and through suppression of proinflammatory mediators IL-1α, IL-1β, and TNF-α [58 ▪ ].…”