Effects of delta-tocotrienol supplementation on glycaemic control in individuals with prediabetes: A randomized controlled study

Farhana Suleman, Dilshad Ahmed Khan, Muhammad Amjad Pervez, Mohammad Aamir

J Pak Med Assoc . 2022 Jan;72(1):4-7. doi: 10.47391/JPMA.966.

Abstract

Objective: To study the effects of delta-tocotrienol on glycaemic control parameters in individuals with pre-diabetes.

Methods: The randomised control trial was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 15 to November 15, 2019, and comprised individuals aged 18-60 years having fasting plasma glucose of 5.6 to 6.9 mmol/L or glycosylated haemoglobin of 5.7 to 6.4%. They were randomised into group A receiving 300mg delta-tocotrienol and group B receiving a placebo once daily for 12 weeks. Weight, height, waist circumference, fasting plasma glucose, insulin and glycosylated haemoglobin were measured at the beginning and end of the trial to assess any change. Body mass index and homeostatic model assessment-insulin resistance were also calculated. Data was analysed using SPSS 21.

Results: Of the 77participants, 40(52%) were in group A and 37(48%) in group B. Group A showed significantly greater reduction in terms of fasting plasma glucose, glycosylated haemoglobin, insulin and homeostatic model assessment-insulin resistance index (p≤0.001) post-intervention.

Conclusions: Delta-tocotrienol supplementation was found to have a significant effect in improving glycaemic control parameters in persons with pre-diabetes. Futures larger scale clinical trials are needed to confirm these findings.

Christina Seong, Po-Jung Chen, Zana Kalajzic, Shivam Mehta, Ambika Sharma, Ravindra Nanda, Sumit Yadav, Eliane H Dutra

Am J Orthod Dentofacial Orthop . 2022 Jan 7;S0889-5406(21)00786-1. doi: 10.1016/j.ajodo.2020.10.033. Online ahead of print.

Abstract

Introduction: Vitamin E is a popular antioxidant suggested to affect bone turnover. However, the effects of a vitamin E enriched diet on the rate of tooth movement are unknown. Therefore, this study aimed to evaluate tooth movement in rats receiving a vitamin E enriched diet. In addition, we examined bone remodeling in experimental and control rats.

Methods: Thirty-two 6-week-old male rats were divided into 4 groups: (1) group 1 (n = 8): orthodontic tooth movement (OTM) for 4 days + regular diet; (2) group 2 (n = 8): OTM for 14 days + regular diet; (3) group 3 (n = 8): OTM for 4 days + vitamin E diet; and (4) group 4 (n = 8) – OTM for 14 days + vitamin E diet. Maxillary alveolar bones and femurs of rats were analyzed by microcomputed tomography and histology.

Results: Rats fed a vitamin E diet presented an increased OTM rate at days 4 and 14. We found an increased number of osteoclasts and decreased bone volume in the vitamin E diet group at day 14 of OTM. In addition, there was increased expression of the microphthalmia-associated transcription factor in the alveolar bone of the vitamin E diet group. In contrast, there was no difference in bone remodeling in femurs or alveolar bone at the control side.

Conclusions: We found that an enriched vitamin E diet increases the rate of OTM in rats, suggesting that vitamin E may be useful as an avenue to accelerate OTM.

Riadh Badraoui, Mohd Saeed, Nouha Bouali, Walid S Hamadou, Salem Elkahoui, Mohammad J Alam, Arif J Siddiqui, Mohd Adnan, Mongi Saoudi, Tarek Rebai

Calcif Tissue Int . 2022 Jan 6. doi: 10.1007/s00223-021-00931-3. Online ahead of print.

Abstract

Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 10⁴) in the medullar cavity (W256 group) showed osteolytic damages with marked tumor osteolysis of both cancellous and trabecular bone as assessed by X-ray radiology, micro-computed tomography, and histology. Rats inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW, W256ATA group) presented marked less tumor osteolysis, less disturbance of Tb.Th and Tb.Sp associated with conversion of rods into plates, and increased structure model index and trabecular pattern factor (Tb.Pf). Elsewhere, 3D frequency distributions of Tb.Th and Tb.Sp were highly disturbed in metastatic W256 rats. Overexpression of some genes commonly associated with cancer and metastatic proliferation: COX-2, TNF-α, and pro-inflammatory interleukins 1 and 6 was outlined. ATA alleviated most of the Walker 256/B cells-induced microarchitectural changes in the target parameters without turning back to normal levels. Likewise, it alleviates the BCSM-induced overexpression of COX-2, TNF-α, IL-1, and IL-6. In silico approach showed that ATA bound these proteins with high affinities, which satisfactory explain its beneficial effects. In conclusion, BCBM is associated with bone microarchitectural disorders and an immune response characterized by an overexpression of some key role genes in cancer proliferation and invasion. ATA exerted favorable effects on trabecular bone distribution and morphology, which may involve the COX-2, TNF-α, and ILs pathways.

Qing Jiang, Suji Im, James G Wagner, Michelle L Hernandez, David B Peden

Free Radic Biol Med . 2022 Jan;178:347-359. doi: 10.1016/j.freeradbiomed.2021.12.012. Epub 2021 Dec 9.

Abstract

γ-Tocopherol (γT) is a major form of vitamin E in the US diet and the second most abundant vitamin E in the blood and tissues, while α-tocopherol (αT) is the predominant vitamin E in tissues. During the last >25 years, research has revealed that γT has unique antioxidant and anti-inflammatory activities relevant to disease prevention compared to αT. While both compounds are potent lipophilic antioxidants, γT but not αT can trap reactive nitrogen species by forming 5-nitro-γT, and appears to show superior protection of mitochondrial function. γT inhibits ionophore-stimulated leukotrienes by blocking 5-lipoxygenase (5-LOX) translocation in leukocytes, decreases cyclooxygenase-2 (COX-2)-catalyzed prostaglandins in macrophages and blocks the growth of cancer cells but not healthy cells. For these activities, γT is stronger than αT. Moreover, γT is more extensively metabolized than αT via cytochrome P-450 (CYP4F2)-initiated side-chain oxidation, which leads to formation of metabolites including 13′-carboxychromanol (13′-COOH) and carboxyethyl-hydroxychroman (γ-CEHC). 13′-COOH and γ-CEHC are shown to be the predominant metabolites found in feces and urine, respectively. Interestingly, γ-CEHC has natriuretic activity and 13′-COOH inhibits both COX-1/-2 and 5-LOX activity. Consistent with these mechanistic findings of γT and metabolites, studies show that supplementation of γT mitigates inflammation and disease symptoms in animal models with induced inflammation, asthma and cancer. In addition, supplementation of γT decreased inflammation markers in patients with kidney diseases and mild asthma. These observations support that γT may be useful against inflammation-associated diseases.

Martin Schubert, Stefan Kluge, Elena Brunner, Simona Pace, Marc Birringer, Oliver Werz, Stefan Lorkowski

Free Radic Biol Med . 2022 Jan;178:83-96. doi: 10.1016/j.freeradbiomed.2021.11.032. Epub 2021 Nov 27.

Abstract

Scope: The long-chain metabolites of (LCM) vitamin E are proposed as the active regulatory metabolites of vitamin E providing, with their anti-inflammatory properties, an explanatory approach for the inconsistent effects of vitamin E on inflammatory-driven diseases. We examined the modulation of cytokine expression and release from macrophages, a fundamental process in many diseases, to gain insights into the anti-inflammatory mechanisms of the α-tocopherol-derived LCM α-13′-COOH.

Methods and results: Suppressed gene expression of C-C motif chemokine ligand 2 (Ccl2), tumor necrosis factor (Tnf), and interleukin (Il) 6 in response to lipopolysaccharides by 24 h pre-treatment with α-13′-COOH in RAW264.7 macrophages was revealed using quantitative reverse transcription PCR. Further, reduced secretion of IL1β and CCL2 was found in this setup using flow cytometry. In contrast, 1 h pre-treatment suppressed only CCL2. Consequent gene expression analysis within 24 h of α-13′-COOH treatment revealed the induction of mitogen-activated protein kinases (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) negative feedback regulators including the ‘master regulators’ dual-specificity phosphatase 1 (Dusp1/Mkp1) and tumor necrosis factor induced protein 3 (Tnfaip3/A20). Approaches with immunoblots and chemical antagonists suggest a feedback induction via activation of extracellular-signal regulated kinase (ERK), p38 MAPK and NFκB pathways.

Conclusions: CCL2 is suppressed in murine macrophages by α-13′-COOH and the indirect suppression of MAPK and NFκB pathways is likely a relevant process contributing to anti-inflammatory actions of α-13′-COOH. These results improve the understanding of the effects of α-13′-COOH and provide a basis for new research strategies in the context of inflammatory diseases.

Lixia Gao, Yong Teng

Methods Mol Biol . 2022;2343:241-246. doi: 10.1007/978-1-0716-1558-4_16.

Abstract

Electrochemical biosensors offer a sensitive, specific, and rapid detection platform for in situ real-time monitoring of intracellular and extracellular metabolites. These sensors have been widely used to evaluate the efficacy of preclinical drugs, especially for natural products with antioxidant potency. Ultraviolet (UV) radiation causes oxidative stress in cells and induces cells to release reactive oxygen species. Tocopherol is a fat-soluble vitamin found in vegetable oils as well as in grains, seeds, and nuts, which plays an important protective role as an antioxidant in resisting oxidative stress caused by UV radiation. Here, we describe a protocol using a glass carbon electrode functionalized with nanotube@DNA-Mn₃(PO₄)2 composite to monitor and quantify the production of superoxide ions in UV-irradiated melanoma cells in the presence or absence of tocopherol. This study demonstrates the advantages and potential application of label-free electrochemical sensors in the measurement of natural antioxidants from plant materials.

R Scott Duncan, Daniel T Hurtado, Conner W Hall, Peter Koulen

Front Pharmacol . 2022 Jan 4;12:798938. doi: 10.3389/fphar.2021.798938. eCollection 2021.

Abstract

The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.

Mohadeseh Ahmadi, Akbar Hedayatizadeh-Omran, Reza Alizadeh-Navaei, Majid Saeedi, Ehsan Zaboli, Omolbanin Amjadi, Hamidreza Kelidari, Zahra Besharat

Asian Pac J Cancer Prev . 2022 Jan 1;23(1):201-205. doi: 10.31557/APJCP.2022.23.1.201.

Abstract

Objective: This study aimed to evaluate in vitro synergistic anticancer effect of doxorubicin combined with Vitamin E.

Methods: The MTT assay was utilized to assess the cytotoxicity of Vitamin E and vitamin E combined with doxorubicin and vital activities of SKBR3, MDA-MB-231, and HFF cells over a 24-hour incubation period. In addition, the antioxidant properties of these interventions and the decrease of reactive oxygen species (ROS) content caused by the treatment were evaluated.

Results: The antiproliferative effect of doxorubicin increased significantly in combination with vitamin E (Doxcorobicin 2µM vs. Vitamin E 120µM, P=0.000). Despite reducing cell ROS content due to vitamin E treatment, the combination of vitamin E and doxorubicin showed no significant synergistic effect (Doxcorobicin 2µM vs. Vitamin E 120µM, P=0.998).

Conclusion: This study indicated that the doxorubicin-vitamin E treatment reduced the viability of breast cancer cells with the minimum side effects on normal cells. In addition, the high dosage of vitamin E intensified the cytotoxicity of doxorubicin.

Eka Roina Megawati, Lokot Donna Lubis, Febi Yanti Harahap

Folia Med (Plovdiv) . 2021 Dec 31;63(6):895-900. doi: 10.3897/folmed.63.e57877

Abstract

Introduction: Obesity creates health problems by increasing the risks of chronic diseases such as type 2 diabetes and cardiovascular disorders. Obesity leads to insulin resistance, higher blood glucose and cholesterol levels. Adipose tissues synthesize adiponectin which acts as anti-inflammatory, antidiabetic, and anti-atherogenic agent. Meanwhile, vitamin E is an antioxidant that acts as an anti-inflammation.

Aim: The purpose of this study was to analyze the effects of vitamin E supplementation to metabolic markers on diet-induced obesity in mice.

Materials and methods: Twenty-four mice (Mus musculus, L) aged four weeks were divided into six groups which were fed different diets and given vitamin E in different dosages or methods. The period of treatment was 18 weeks. The mice body weights were measured every week; blood sugar and cholesterol levels were measured every six weeks, and the adiponectin level measurement was done at week 18.

Results: A repeated measures ANOVA showed that body weight and cholesterol level within groups were not significantly different [F(15, 54)=1.417, 0.173 and F(10, 36)=1.391, 0.224 respectively]. The glucose levels were found to be significantly different [F(7.646, 27.526)=2.625, 0.030]. There was no significant difference in the adiponectin levels.

Conclusions: Vitamin E supplementation could not prevent the increase of body weight, the elevation of blood sugar and cholesterol levels, and also could not increase adiponectin level.

Muntaha S Al-Khdour, Omar F Khabour, Laith N Al-Eitan, Karem H Alzoubi

Drug Chem Toxicol . 2021 Dec 29;1-5. doi: 10.1080/01480545.2021.2015369. Online ahead of print.

Abstract

Nedaplatin is a chemotherapeutic agent used widely in cancer therapy. Nedaplatin has been shown to cause DNA damage to cells via the induction of oxidative stress. Vitamin E (Vit E) has an anti-mutagenic activity that can protect cells from DNA damaging agents. The objective of this study is to examine the genotoxic and cytotoxic effects of nedaplatin in human cultured lymphocytes. In addition, modulation of such effects by Vit E was also examined. The frequencies of sister chromatid exchange (SCE) and chromosomal aberrations (CAs) were used as an indicator for genotoxicity. The mitotic and proliferative indices were used to examine the cytotoxic effects of nedaplatin. The results showed that nedaplatin significantly elevated SCE and CA frequencies in human lymphocytes (p ˂ 0.01). The increases in the frequencies of SCE and CA caused by nedaplatin were lowered by pretreatment treatment with Vit E (p < 0.05). Nedaplatin significantly lowered mitotic index but Vit E pretreatment did not modulate this effect. These results suggest that Vit E has the potential to ameliorate the genotoxicity of nedaplatin in cultured lymphocytes.