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

Abstract

The study aimed to ascertain the effects of delta-tocotrienol (δT3) supplementation on glycemic control, oxidative stress, inflammation and related micro-ribonucleic acid (miRNA) expression in patients with type 2 diabetes mellitus (T2DM). Total 110 patients of T2DM on oral hypoglycemic agents, were randomly divided into tocotrienol and placebo groups and given 250 mg δT3 or cellulose soft gel capsule once daily respectively for 24 weeks. Glycemic control, oxidative stress, inflammatory biomarkers, and miRNAs expression were measured in serum at baseline and end of the intervention by using standard laboratory methods. Compared to the placebo, δT3 supplementation resulted in a significant (p ≤ .05) reduction [mean difference (95% confidence interval)] in plasma glucose [−0.48 (−0.65, −0.30)], insulin [−1.19 (−1.51, −0.87)], homeostatic model assessment of insulin resistance [−0.67 (−0.86, −0.49)], glycosylated hemoglobin [−0.53 (−0.79, −0.28)], malondialdehyde [−0.34 (−0.45, −0.22)], high sensitive-Creactive protein[−0.35 (−0.54, −0.16)], tumor necrosis factor-alpha [−1.22 (−1.62, −0.83)], and interleukin-6[−2.30 (−2.91, −1.68)]. More than twofold downregulation in miRNA expression was observed in the δT3 group compared to the placebo. The study demonstrated that δT3 supplementation in addition to oral hypoglycemic agents, improved glycemic control, inflammation, oxidative stress, and miRNA expression in T2DM without any adverse effect. Thus, δT3 might be considered as an effective dietary supplement to prevent long-term diabetic complications.

Functional role of miR-34a in diabetes and frailty

“…The prolonged exposure of saturated fatty acids to MIN6 β-cells and pancreatic islets increased the expression of miR-34a ( Lovis et al, 2008 ). Furthermore, miR-34a leads to endothelial dysfunction and vascular senescence in diabetes ( Li et al, 2016 ; Carracedo et al, 2019 ; Thounaojam and Bartoli, 2019 ), increasing the overall risk of oxidative stress and inflammation with or without diabetes ( Li et al, 2016 ; Cheleschi et al, 2019 ; Xiong et al, 2019 ; Zimta et al, 2019 ; Li et al, 2021 ; Mahjabeen et al, 2021 ; Zhu et al, 2021 ).…”

Tocotrienol in the Management of Nonalcoholic Fatty Liver Disease: A Systematic Review

“…It is of note that the Homeostatic Model Assessment of Insulin Resistance (HOMA IR), which reflects the extent of insulin resistance, was reduced by 15% from baseline in patients with NAFLD supplemented with annatto T3 after 48 weeks [ 45 ]. This observation has been supported by multiple animal studies and human clinical trials [ 72 , 73 ]. Furthermore, annatto T3 also increased adiponectin levels by 44% and reduced leptin levels by 18% from baseline in patients with NAFLD after 48 weeks [ 45 ].…”

Untargeted muscle tissue metabolites profiling in young, adult, and old rats supplemented with tocotrienol-rich fraction

“…Sarcopenia has been shown to decrease metabolic activities in mitochondria, muscle, kidney, and methylation compared with the declined metabolic activities for antioxidation in frailty (Kameda et al, 2020). There has been growing evidence that tocotrienol, which is a vitamin E isomer, can prevent the onset of age-related chronic illnesses and metabolic disturbances, like obesity (Zhao et al, 2016;Fukui 2019;Pang and Chin 2019), cardiovascular disease (Ramanathan et al, 2018), type-2 diabetes mellitus (Chung et al, 2020;Mahjabeen et al, 2021), arthritis (Haleagrahara et al, 2014;Radhakrishnan et al, 2014;Chin et al, 2019), osteoporosis (Shen et al, 2017) and sarcopenia (Khor et al, 2014;Khor et al, 2016;Chung et al, 2018;Lim et al, 2019).…”