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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.
Chuar, PF, Ng, YT, Phang, SCW, Koay, YY, Ho, JI, Ho, LS, Botross Henien, NP, Ahmad, B, Abdul Kadir, K
Nutrients. 2021;(11)
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.
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The Effect of Oral Vitamin E on Semen Parameters and IVF Outcome: A Double-Blinded Randomized Placebo-Controlled Clinical Trial.
Sabetian, S, Jahromi, BN, Vakili, S, Forouhari, S, Alipour, S
BioMed research international. 2021;:5588275
Abstract
BACKGROUND Male infertility is a main clinical problem that affects about 7% of all men worldwide. Many patients with male infertility are caused by a reduced antioxidant capacity of semen. Several antioxidant supplements, especially vitamin E, are proposed to help male infertility treatment. This project was goaled to study the effects of oral synthetic vitamin E (400 IU/day) for eight weeks on betterment of semen parameters and pregnancy rate. METHODS After dropping the cases, 124 infertile couples with a male factor who were admitted to the IVF program were included. The male patients with idiopathic abnormal motility and/or morphology were randomized into two groups: 61 receiving vitamin E and 63 as the control group receiving placebo for eight weeks. The pretreatment semen parameters of both groups were compared with those of posttreatment. The pregnancy outcomes were considered between the two groups. RESULTS There were no significant differences statistically between before and after treatment in the term of sperm volume, count, motility, and morphology. Furthermore, the IVF outcomes of the two groups were not different significantly, either. Interestingly, the percent of normal sperm in the placebo group was significantly decreased after eight weeks. CONCLUSION Vitamin E supplementation might neutralize free radical activity to keep sperm from more oxidative damages. Further studies regarding the influence of higher acceptable doses of vitamin E on semen characteristics and fertility rates are needed. This study was registered as a two-arm, blinded, randomized, placebo-controlled clinical trial (IRCTID IRCT2014020616506N1, 2014-03-18).
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The use of vitamin E in preventing taxane-induced peripheral neuropathy.
Heiba, MA, Ismail, SS, Sabry, M, Bayoumy, WAE, Kamal, KA
Cancer chemotherapy and pharmacology. 2021;(6):931-939
Abstract
PURPOSE Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy. Several trials have evaluated the protective effect of vitamin E in preventing CIPN with controversial results. This study aims to outline the role of vitamin E in preventing CIPN. METHODS A prospective phase II, open-label randomized controlled study was conducted in patients receiving taxane-based chemotherapy in Ain Shams University Hospitals, using vitamin E at a dose of 400 mg twice daily. The primary endpoint was the incidence of grade ≥ 2 sensory neuropathy according to CTCAE v 5.0 in each treatment arm. Secondary endpoints include time to onset and the duration of grade ≥ 2 sensory neuropathy. RESULTS A total of 140 patients were randomized between the control and vitamin E arms. There was no difference in the incidence of grade ≥ 2 sensory neuropathy between the two arms (25.7% in each arm; P = 1.0), as well as the time to onset of neuropathy (P = 0.24). However, there was a statistically significant difference between the 2 arms as regards the duration of neuropathy. The median duration was 12.5 vs. 5 weeks in the control and vitamin E arms respectively (P = 0.01). CONCLUSION Our study did not demonstrate a protective role of vitamin E in decreasing the incidence of CIPN in patients receiving taxane-based chemotherapy. However, the recovery from CIPN was much better as compared to the control arm, which may indicate a role for vitamin E in decreasing the duration and severity of CIPN.
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The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial.
Ng, YT, Phang, SCW, Tan, GCJ, Ng, EY, Botross Henien, NP, M Palanisamy, UD, Ahmad, B, Abdul Kadir, K
Nutrients. 2020;(5)
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.
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Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial.
Jafari, T, Fallah, AA, Reyhanian, A, Sarmast, E
Food & function. 2020;(9):7987-7993
Abstract
Inflammation and endothelial dysfunction are major problems in hemodialysis (HD) patients. This study assessed the effects of an 8 week administration of pomegranate peel extract (PPE) and vitamin E (Vit E) alone or in combination on the biomarkers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the biomarkers of endothelial function, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, in HD patients. In a randomized, double-blind, parallel, placebo-controlled trial, 100 HD patients were randomly divided into 4 equal groups: (a) PPE + Vit E, received 2 pomegranate tablets (each tablet contained 225 mg PPE, equal to 90 mg ellagic acid) + 1 Vit E soft gel (400 IU) daily, (b) PPE, received 2 pomegranate tablets + 1 Vit E placebo soft gel daily, (c) Vit E, received 1 Vit E soft gel + 2 pomegranate placebo tablets daily, and (d) placebo, received 2 pomegranate placebo tablets + 1 Vit E placebo soft gel daily. For group allocation, a stratified block randomization procedure based on sex, age, and HD duration was used. Each intervention product and its placebo had identical shape, color, size, and packaging. Consumption of PPE + Vit E significantly reduced the serum CRP level (mean change: -7.12 ± 4.59 mg l-1, P < 0.001) compared to other groups, while reduced levels of IL-6 (mean change: -2.19 ± 2.33 pg ml-1, P < 0.001), TNF-α (mean change: -2.41 ± 3.21 pg ml-1, P = 0.008), ICAM-1 (mean change: -64.2 ± 111.0 ng ml-1, P = 0.017), and VCAM-1 (mean change: -117.7 ± 177.1 ng ml-1, P = 0.002) were observed compared to the control. There was no significant difference in the P-selectin level among the groups. Consumption of PPE or Vit E alone significantly reduced the CRP level (mean change for PPE: -3.58 ± 5.41 mg l-1, P < 0.001; mean change for Vit E: -3.25 ± 8.29 mg l-1, P = 0.002) compared to the control. As a result, consumption of PPE in combination with Vit E enhanced the inflammatory status and endothelial function in HD patients.
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Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design.
Traber, MG, Leonard, SW, Ebenuwa, I, Violet, PC, Wang, Y, Niyyati, M, Padayatty, S, Tu, H, Courville, A, Bernstein, S, et al
The American journal of clinical nutrition. 2019;(5):1148-1167
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Abstract
BACKGROUND Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed. OBJECTIVE We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport. METHODS A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted). RESULTS Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role. CONCLUSIONS Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.
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Differentially expressed plasma proteins of β-thalassemia/hemoglobin E patients in response to curcuminoids/vitamin E antioxidant cocktails.
Panachan, J, Chokchaichamnankit, D, Weeraphan, C, Srisomsap, C, Masaratana, P, Hatairaktham, S, Panichkul, N, Svasti, J, Kalpravidh, RW
Hematology (Amsterdam, Netherlands). 2019;(1):300-307
Abstract
OBJECTIVE Iron overload and oxidative stress are the major causes of serious complications and mortality in thalassemic patients. Our previous work supports the synergistic effects of antioxidant cocktails (curcuminoids or vitamin E, N-acetylcysteine, and deferiprone) in treatment of β-thalassemia/Hb E patients. This further 2-DE-based proteomic study aimed to identify the plasma proteins that expressed differentially in response to antioxidant cocktails. METHODS Frozen plasma samples of ten normal subjects and ten β-thalassemia/Hb E patients at three-time points (baseline, month 6, and month 12) were reduced the dynamic range of proteome using ProteoMiner kit and separated proteins by two-dimensional gel electrophoresis. Differentially expressed proteins were identified using tandem mass spectrometry. Several plasma proteins were validated by ELISA and Western blot analysis. RESULTS Thirteen and 11 proteins were identified with altered expression levels in the curcuminoids- and vitamin E cocktail groups, respectively. The associations between vitronectin (VTN) expression and total bilirubin levels, as well as between serum paraoxonase/arylesterase 1 (PON1) expression and blood reactive oxygen species were observed. Validation results were consistent with proteomics results. DISCUSSION AND CONCLUSIONS These plasma proteins may provide better understanding of the mechanisms underlying the therapeutic effects of antioxidant cocktails in thalassemic patients.
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Effect of Vitamins C and E on Endothelial Function in Type 1 Diabetes Mellitus.
Cazeau, RM, Huang, H, Bauer, JA, Hoffman, RP
Journal of diabetes research. 2016;:3271293
Abstract
BACKGROUND/OBJECTIVES Endothelial dysfunction due to hyperglycemia-induced oxidative damage is an important predictor of future cardiovascular risk in patients with type 1 diabetes mellitus (T1DM) and is present in adolescent T1DM. We hypothesized that combined treatment with the antioxidant vitamins C and E might improve endothelial function (EF) and other biochemical risk factors in adolescents with T1DM. SUBJECTS/METHODS Open-label antioxidant supplementation was given for six weeks with endpoint measurements collected at baseline and study completion. Endpoints measured included EF and plasma measurements of biochemical endothelial risk. RESULTS Two males and 7 females were studied. Mean age was 12.9 ± 0.9 yrs; mean T1DM duration was 5.5 ± 2.5 yrs; mean BMI was 22.1 ± 3.8 kg/m(2); and mean hemoglobin A1c was 9.3 ± 1.1%. No differences were found for EF, high sensitivity CRP, total antioxidant capacity, adiponectin, or endothelial progenitor cells (EPCs) between before and after combined vitamin C and E therapy. CONCLUSIONS Our negative study results do not support previous findings of decreased oxidative damage, improved endothelial function, and increased vascular repair capacity with antioxidant therapy. Longer term studies may be needed to determine the effects, if any, of combined antioxidant therapy on EPCs, EF, and markers of micro- and macrovascular complications in T1DM.
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A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer.
Kyriakopoulos, CE, Heath, EI, Eickhoff, JC, Kolesar, J, Yayehyirad, M, Moll, T, Wilding, G, Liu, G
Investigational new drugs. 2016;(2):225-30
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Abstract
BACKGROUND A phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC). METHODS This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days. RESULTS Twenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1-3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1-8). CONCLUSIONS APC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted.
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The Effect of LDL-Apheresis and Rheohaemapheresis Treatment on Vitamin E.
Solichová, D, Bláha, M, Aufartová, J, Krcmová, LK, Plíšek, J, Honegrová, B, Kasalová, E, Lánská, M, Urbánek, L, Sobotka, L
Journal of nutritional science and vitaminology. 2015;(2):105-12
Abstract
Lipid apheresis (extracorporeal lipoprotein elimination) is administered to patients with familial hypercholesterolemia who fail to respond to standard therapy. The nature of the treatment process raises the suspicion that it decreases not only cholesterol but also antioxidants. A group of 12 patients (average age 47±17 y, 4 homozygous and 8 heterozygous individuals) with familial hypercholesterolemia treated by LDL-apheresis or rheohaemapheresis for 3-12 y was included in the study. In addition to cholesterol and triacylglycerol levels, vitamin E and vitamin A and also other markers of antioxidant activity were investigated. Nevertheless, the most important determined parameter was the vitamin E/cholesterol ratio in serum and lipoproteins. The results indicate that both extracorporeal elimination methods are effective and suitable ways to treat severe familial hypercholesterolemia, as the LDL fraction of cholesterol decreased by approximately 77% and 66% following LDL-apheresis and rheohaemapheresis, respectively. In addition, the serum vitamin E decreased by 54% and 57% and the decrease of the serum vitamin A was approximately 20%. However, the main marker of antioxidant capacity, vitamin E/cholesterol ratio, in the serum, VLDL and LDL significantly increased. The increase of vitamin E levels in the erythrocyte membranes of 2% following LDL-apheresis and a significant increase of 4% following rheohaemapheresis were confirmed. The presented results indicate that LDL-apheresis and rheohaemapheresis can be considered to be safe procedures according to the antioxidant capacity of the serum, VLDL and LDL lipoprotein fractions and the erythrocyte membrane.