Therapeutic potential of palm oil vitamin E-derived tocotrienols in inflammation and chronic diseases: Evidence from preclinical and clinical studies

Zaida Zainal, Huzwah Khaza'ai, Ammu Kutty Radhakrishnan, Sui Kiat Chang

Food Res Int . 2022 Jun;156:111175. doi: 10.1016/j.foodres.2022.111175. Epub 2022 Mar 21

Abstract

Palm oil is rich in tocotrienols (T3s), a type of vitamin E that has garnered considerable research interest as it exhibits anti-inflammatory as well as antioxidant characteristics that are comparable to or exceed those of tocopherols (Toc). Notably, T3 must be consumed as it cannot be produced by the human body. Here, we reviewed the anti-inflammatory activities of T3s in the prevention and treatment of various inflammatory disorders; focusing on recent preclinical and clinical studies. There is compelling data from experimental models and human studies that shows that T3 administration can inhibit the release of various inflammatory mediators that contribute to age-related disease by enhancing oxidative stress, reducing melanin production and skin damage, and preventing cardiovascular disease and stroke. There is evidence to show that T3s possess neuroprotective, anticancer, and anti-osteoporosis properties. In addition, T3s also protect the gastrointestinal tract, facilitate blood glucose control in people with diabetes, and prevent fatty liver disease. Furthermore, results from some clinical studies suggest that T3s are beneficial nutritional supplements with no evident side-effects when administered to patients with neurological or cardiovascular disorders. There is growing evidence from clinical trials that shows that T3s can help prevent dementia and Alzheimer’s disease. More well-designed clinical trials, as well as human intervention studies, are required to confirm the health benefits of palm T3.

Ying Zhang, Wei Gao, Xia Li

Exp Ther Med . 2022 Jun 1;24(1):480. doi: 10.3892/etm.2022.11407. eCollection 2022 Jul.

Abstract

Patients with end-stage renal disease (ESRD) are characterized by augmented oxidative stress (OS) due to the imbalance between the generation of increased concentrations of oxidative molecules and decreased antioxidant capacity. Vitamin E-coated dialyzer membranes (VEMs) have previously been reported to alleviate the imbalance of redox metabolism in patients with ESRD undergoing hemodialysis (HD); however, their effect on the deformability of red blood cells (RBCs) remains unknown. In the present study, 48 patients with ESRD undergoing HD were enrolled and randomly assigned into two groups: HD with VEMs (VEM group; n=24) and HD with polysulfone dialyzer membranes (PM group; n=24), and another 24 healthy volunteers served as the control group. The present study investigated the morphological changes and deformability of RBCs in patients with ESRD and healthy volunteers. The concentration of serum vitamin E, the parameters of antioxidant stress and OS, and the degree of oxidative phosphorylation and clustering of anion exchanger 1 (Band 3) in RBCs were measured. The results obtained suggested that VEM treatment markedly ameliorated the abnormalities of RBC morphology and deformability in patients with ESRD undergoing HD. Mechanistic studies showed that VEM treatment led to a marked improvement in the concentration of serum vitamin E, which was positively associated with the restored antioxidant capacity, and decreased oxidative phosphorylation and clustering of Band 3 in RBCs of patients with ESRD undergoing HD. Taken together, the results of the present study have demonstrated that VEM treatment effectively restored the imbalance of redox metabolism, and improved the oxidative phosphorylation and clustering of Band 3 in RBCs of patients with ESRD undergoing HD via delivering vitamin E, which may alleviate the abnormal morphological and mechanical properties of RBCs. These findings are anticipated to be useful with respect to improving the nursing care and cure rate of patients with ESRD.

J-Ian Ho, En Yng Ng, Yilynn Chiew, Yan Yi Koay, Pei Fen Chuar, Sonia Chew Wen Phang, Badariah Ahmad, Khalid Abdul Kadir

SAGE Open Med . 2022 May 26;10:20503121221095324. doi: 10.1177/20503121221095324. eCollection 2022.

Abstract

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.

Genea Edwards, Caroline G Olson, Carlyn P Euritt, Peter Koulen

Front Neurosci . 2022 May 4;16:890021. doi: 10.3389/fnins.2022.890021. eCollection 2022.

Abstract

The eye is particularly susceptible to oxidative stress and disruption of the delicate balance between oxygen-derived free radicals and antioxidants leading to many degenerative diseases. Attention has been called to all isoforms of vitamin E, with α-tocopherol being the most common form. Though similar in structure, each is diverse in antioxidant activity. Preclinical reports highlight vitamin E’s influence on cell physiology and survival through several signaling pathways by activating kinases and transcription factors relevant for uptake, transport, metabolism, and cellular action to promote neuroprotective effects. In the clinical setting, population-based studies on vitamin E supplementation have been inconsistent at times and follow-up studies are needed. Nonetheless, vitamin E’s health benefits outweigh the controversies. The goal of this review is to recognize the importance of vitamin E’s role in guarding against gradual central vision loss observed in age-related macular degeneration (AMD). The therapeutic role and molecular mechanisms of vitamin E’s function in the retina, clinical implications, and possible toxicity are collectively described in the present review.

G W Burton, A Joyce, K U Ingold

Arch Biochem Biophys . 2022 Mar 28;109195. doi: 10.1016/j.abb.2022.109195. Online ahead of print.

Abstract

Application of a time-tested quantitative method of measuring peroxyl radical production in conjunction with the determination of the stoichiometry of the reaction of peroxyl radicals with α-tocopherol has permitted the conclusion that α-tocopherol is the major lipid-soluble chain-breaking antioxidant in human plasma and red cell membranes.

Shitao Lv, Haiyan Yang, Pengcheng Jing, Haiying Song

CNS Neurosci Ther . 2022 Mar 18. doi: 10.1111/cns.13814. Online ahead of print.

Abstract

α-tocopherol showed antioxidant, anti-inflammatory and anti-apoptotic abilities in rat brain tissue, thus alleviating cerebral ischemia-reperfusion injury-induced nerve damage.

Karem H Alzoubi, Abdulsalam M Halboup, Omar F Khabour, Mahmoud M Alomari

CNS Neurol Disord Drug Targets . 2022 Mar 18. doi: 10.2174/1871527321666220318113635. Online ahead of print.

Abstract

Background: Waterpipe smoking (WP) exposure has a negative health impact including memory deficit which was attributed to elevation of oxidative stress. Vitamin E (VitE) or swimming exercise have protective effects that prevent memory impairment. In the current study, the modulation of WP-induced memory impairment by the combined effect of VitE and swimming exercise (SE) was investigated.

Method: Animals were exposed to WP one hour/day, five days per week for four weeks. Simultaneously, VitE (100mg/kg, six days/week for four weeks) was administered via oral gavage, and the rats were given swim exercise one hour/day, five days/week for four weeks. Changes in memory were evaluated using Radial Arm Water Maze (RAWM) and Oxidative stress biomarkers were examined in the hippocampus.

Results: WP exposure induced short-term/long-term memory impairment (p <0.05). This impairment was prevented by a combination of VitE with SE (p <0.05). Additionally, this combination normalized the hippocampal catalase, GPx, GSH/GSSG ratios that were modulated by WP (p <0.05). The combination further reduced TBARs levels below the control group (p <0.05).

Conclusion: WP induced memory impairments were prevented by the combination of VitE with SE. This could be attributed to preserving the hippocampal oxidative mechanism by the combination of VitE and SE during WP exposure.

Anahita Garg, Jetty Chung-Yung Lee

Life (Basel) . 2022 Feb 18;12(2):310. doi: 10.3390/life12020310.

Abstract

Vitamin E is one of the most popular fat-soluble vitamins in pathological research and has been under scrutiny since the 1980s as a vital dietary component of food. The antioxidant effect of vitamin E has been widely studied due to its benefits in the prevention of various cardiovascular diseases. In recent years, alternative effects of vitamin E, in terms of anti-inflammatory pathways and gene regulation, have also been of interest to researchers. This review examines the role of dietary vitamin E (α-tocopherol) as an antioxidant and bioactive molecule in promoting vascular health. While the antioxidant effect of vitamin E is well established, knowledge about its capacity as a promising regulatory molecule in the control of the vascular system is limited. The aim of this review is to discuss some of these mechanisms and summarize their role in the prevention of cardiovascular diseases (CVD). Here, we also briefly discuss foods rich in vitamin E, and deliberate some potential toxicological effects of excessive supplemental vitamin E in the body.

Farah Zaaboul, YuanFa Liu

Compr Rev Food Sci Food Saf . 2022 Feb 18. doi: 10.1111/1541-4337.12924. Online ahead of print.

Abstract

Vitamin E is a group of isoprenoid chromanols with different biological activities. It comprises eight oil-soluble compounds: four tocopherols, namely, α-, β-, γ-, and δ-tocopherols; and four tocotrienols, namely, α-, β-, γ, and δ-tocotrienols. Vitamin E isomers are well-known for their antioxidant activity, gene-regulation effects, and anti-inflammatory and nephroprotective properties. Considering that vitamin E is exclusively synthesized by photosynthetic organisms, animals can only acquire it through their diet. Plant-based food is the primary source of vitamin E; hence, oils, nuts, fruits, and vegetables with high contents of vitamin E are mostly consumed after processing, including industrial processes and home-cooking, which involve vitamin E profile and content alteration during their preparation. Accordingly, it is essential to identify the vitamin E content and profile in foodstuff to match daily intake requirements. This review summarizes recent advances in vitamin E chemistry, metabolism and metabolites, current knowledge on their contents and profiles in raw and processed plant foods, and finally, their modern developments in analytical methods.

Zaleha Abdullah Mahdy, Kok-Yong Chin, Nik Lah Nik-Ahmad-Zuky, Aida Kalok, Rahana Abdul Rahman

Cells . 2022 Feb 10;11(4):614. doi: 10.3390/cells11040614.

Abstract

The pathophysiology of pre-eclampsia involves two major pathways, namely systemic oxidative stress and subsequent generalised inflammatory response, which eventually culminates in endothelial cell injury and the syndrome of pre-eclampsia with multi-organ dysfunction. Aspirin has been used to reduce the risk of pre-eclampsia, but it only possesses anti-inflammatory properties without any antioxidant effect. Hence, it can only partially alleviate the problem. Tocotrienols are a unique form of vitamin E with strong antioxidant and anti-inflammatory properties that can be exploited as a preventive agent for pre-eclampsia. Many preclinical models showed that tocotrienol can also prevent hypertension and ischaemic/reperfusion injury, which are the two main features in pre-eclampsia. This review explores the mechanism of action of tocotrienol in relation to the pathophysiology of pre-eclampsia. In conclusion, the study provides sufficient justification for the establishment of a large clinical trial to thoroughly assess the capability of tocotrienol in preventing pre-eclampsia.