Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Abstract

Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

Comparative effect of vitamin E compounds on HSP70 expression in response to acute redox imbalance in Chang liver cells

“…The tocotrienol-rich-fraction (TRF) of palm oil has been anticipated as an e cient alternative for αtocopherol due to its potent antioxidant properties in vitro (41)(42)(43)(44)(45). Although there was no report on TRF effect on HSP70, the present study ndings are in agreement with a number of studies that suggest a higher antioxidant potency of tocotrienols compared to tocopherols in vitro; as HSP70 reduction has been earlier related in this discussion to vitamin E antioxidant function.…”

Assessing the Impact of Oil Types and Grades on Tocopherol and Tocotrienol Contents in Vegetable Oils with Chemometric Methods

“…Tocols can limit lipid peroxidation in cell membranes and scavenging reactive oxygen species and protect tissues from consequent oxidative damage. Thus, supra-nutritional doses of tocols have been reported for cardiovascular diseases, cancer, chronic inflammation, Alzheimer's disease, and Parkinson's disease [9]. Tocotrienols are reported to be superior to tocopherols in the prevention and treatment of major chronic diseases, as their unsaturated chain facilitating cell penetration is highly antioxidative [10].…”

<p>Pharmacology and Pharmacokinetics of Vitamin E: Nanoformulations to Enhance Bioavailability</p>

“…33 These special properties of tocotrienols have been reported in various in vitro studies using different cell lines (breast, lung, liver, pancreas, skin, and bladder cancers). 34,35 Several in vivo studies have also shown that tocotrienols successfully accumulate in cancer cells but not in normal tissues. 36,37 Previous studies demonstrated that δ-tocotrienol (200 mg/kg) significantly enhanced the efficacy of gemcitabine to inhibit pancreatic cancer growth and survival in vitro and in vivo by suppressing NF-kB activity.…”