Vitamin E beyond Its Antioxidant Label

Abstract

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting

“…As such, the administration of antioxidant supplements can increase the defense capacity of islet cells to cope with oxidative stress [ 127 ]. Vitamin E is a redox-active natural compound that downregulates levels of ROS under different experimental conditions [ 128 , 129 , 130 , 131 ]. Interestingly, vitamin E reduces the uptake of OX-LDL by inhibiting CD36 expression via the PPARγ signaling pathway [ 132 , 133 , 134 ].…”

Physical Activity and Nutritional Influence on Immune Function: An Important Strategy to Improve Immunity and Health Status

“…Reports also purported about the side effects of intake of high dose single type of antioxidant. A high doses of vitamin E potentially acts as modulator proinflammatory agents, oxidative stress and NF-κB pathway having role in neuroprotection and cancer (Ungurianu et al, 2021). However, a high dose of antioxidant seems to be favorable to individuals at high risk of URTI to enhance the immunity to reduce URTI risk (Davison et al, 2014).…”

“…• High doses of antioxidant vitamins (i.e., 10× RDA, recommended dietary allowance) effectively minimized the chances of infection in ultra-endurance athletes (Salehi et al, 2018); high dose of antioxidant decreased risk of URTI (Davison et al, 2016). • Vitamins C and E in combination reduce oxidative stress in athletes (De Oliveira et al, 2019) • Vitamin C inversely related to phagocytosis (Fantacone et al, 2020) • Vitamin E before exercise under hypoxic condition at high altitude restores interleukin (IL)-6, TNF-α, IL-1ra, and IL-10 to normal level (Santos et al, 2016); decreases systemic inflammatory biomarkers in elite endurance athletes at altitude (Koivisto et al, 2019); in high dose acts as modulator proinflammatory agents, oxidative stress and NF-κB pathway having role in neuroprotection and cancer (Ungurianu et al, 2021). • An association exists between vitamin D content and Acute Respiratory Tract Infection risk (Pham et al, 2019).…”

Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation

“…Vitamin E, comprising eight vitamers (four tocopherols and four tocotrienols), is the most abundant liposoluble antioxidant compound in the human body. Among them, α-tocopherol accounts for 90% of vitamin E activity in human tissues [ 30 ]. During pregnancy, the recommended intake is 15 mg/day, which can be easily covered with a regular diet.…”