Increased susceptibility of post-weaning rats on high-fat diet to metabolic syndrome

The present study aimed to examine the effects of the types of high-calorie diets (high-fat and high-fat-high-sucrose diets) and two different developmental stages (post-weaning and young adult) on the induction of metabolic syndrome. Male, post-weaning and adult (3- and 8-week old, respectively) Sprague Dawley rats were given control, high-fat (60% kcal), and high-fat-high-sucrose (60% kcal fat + 30% sucrose water) diets for eight weeks (n = 6 to 7 per group). Physical, biochemical, and transcriptional changes as well as liver histology were noted. Post-weaning rats had higher weight gain, abdominal fat mass, fasting glucose, high density lipoprotein cholesterol, faster hypertension onset, but lower circulating advanced glycation end products compared to adult rats. This is accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR) α and γ in the liver and receptor for advanced glycation end products (RAGE) in the visceral adipose tissue. Post-weaning rats on high-fat diet manifested all phenotypes of metabolic syndrome and increased hepatic steatosis, which are linked to increased hepatic and adipocyte PPARγ expression. Adult rats on high-fat-high-sucrose diet merely became obese and hypertensive within the same treatment duration. Thus, it is more effective and less time-consuming to induce metabolic syndrome in male post-weaning rats with high-fat diet compared to young adult rats. As male rats were selectively included into the study, the results may not be generalisable to all post-weaning rats and further investigation on female rats is required

The effects of vitamin E on non-proliferative diabetic retinopathy in type 2 diabetes mellitus::Are they sustainable with 12 months of therapy

INTRODUCTION: Prolonged uncontrolled hyperglycaemia has shown to cause oxidative stress, inflammation, thrombosis and upregulation of angiogenesis in diabetics, which all contributes to diabetic retinopathy development and progression. Vitamin E is found to have anti-inflammatory, anti-oxidative, anti-thrombogenic and anti-angiogenesis which could play an important role in early treatment of diabetic retinopathy. This study aims to investigate the effect of Tocotrienol-rich vitamin E (Tocovid) on the progression of retinal microhaemorrhages and diabetic macular oedema in patients with diabetic retinopathy. METHOD: This is a multi-centred, randomized, double-blinded, placebo-controlled trial which involved 55 eligible participants. The participants in the treatment group (n = 22) received Tocovid 200 mg twice daily while those in the placebo group (n = 23) would receive placebo twice daily. Both groups will be on the treatment for a total duration of 12 months. Both retinal signs will be assessed at baseline, 2 months, 6 months and 12 months of treatment to determine the progression of diabetic retinopathy. Serum vascular endothelial growth factor which reflects on the angiogenesis process in the eye was analysed as well at similar time points as the retinal findings. RESULTS: After 12 months of treatment, the placebo group had a significant increase of 23.42% in retinal microhaemorrhages (p < 0.05), but the Tocovid group had no significant changes. Moreover, the Tocovid group showed a significant decrease of 48.38% in area of diabetic macular oedema over the 12 months period (p < 0.05), but the placebo group had no significant changes. Meanwhile, there was no significant difference in serum vascular endothelial growth factor level when comparing between both groups. CONCLUSION: These findings could indicate that Tocovid has an important role in preventing early diabetic retinopathy progression

A phase IIb randomized controlled trial investigating the effects of tocotrienol-rich vitamin e on diabetic kidney disease

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR &gt; 20&ndash;200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: &minus;4.28 &plusmn; 14.92 vs. 9.18 &plusmn; 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 &plusmn; 5.76 vs. &minus;3.29 &plusmn; 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 &plusmn; 6.78 vs. &minus;1.45 &plusmn; 9.18), p = 0.022 and serum creatinine (MD: &minus;7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-&beta;1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR

The effects of tocotrienol-rich vitamin E (Tocovid) on diabetic neuropathy:A phase II randomized controlled trial

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 &lt; 0.001, median nerve; +1.60 m/s, IQR 1.80, p &lt; 0.001, sural nerve; +0.75 m/s, IQR 2.25, p &lt; 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

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

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