Antioxidant

Human Studies/ Cohort Studies 
Article Study objective/ findings
Comparing Palm Oil, Tocotrienol-Rich Fraction and α-Tocopherol Supplementation on the Antioxidant Levels of Older Adults

Nor Azman, N. H. E., et.al (2018). Antioxidants

 This study compared the effects of tocotrienol-rich-fraction (TRF) with α-tocopherol (α-TF) on the antioxidant status of healthy individuals aged between 50-55 years old. The study found that both TRF and α-TF exhibited similar effects to the antioxidant levels with TRF showed more significant effects in the females subjects.
Validation of HPLC/FLD Method for Quantification of Tocotrienols in Human Plasma

Che, H. L., et.al (2015). Int J Anal Chem.

 A simple and practical normal-phase high performance liquid chromatography method is developed to quantify the amount of four tocotrienol homologues in human plasma. The four tocotrienol homologues were well separated within 30 minutes. A large interindividual variation between subjects was observed as the absorption of tocotrienols is dependent on food matrix and gut lipolysis. The accuracies of lower and upper limit of quantification ranged between 92% and 109% for intraday assays and 90% and 112% for interday assays. This method was successfully applied to quantify the total amount of four tocotrienol homologues in human plasma. 
Reduction of DNA damage in older healthy adults by Tri E tocotrienol supplementation

Chin, S. F., et al (2008). Nutrition.

 

 To evaluate the effects of tocotrienol on DNA damage in humans.Tocotrienol supplementation may be beneficial by reducing DNA damage as indicated by a reduction in DNA damage, SCE frequency, and urinary 8-OHdG.

In vivo / Animal Studies
Article Study objectives/ findings
Tocotrienol rich palm oil extract is more effective than pure tocotrienols at improving endothelium-dependent relaxation in the presence of oxidative stress

Ali, S. F. & Woodman, O.L (2015). Oxid Med Cell Longev.

 

 This study investigated whether tocotrienols, when compared to tocopherols, might be more effective at preserving endothelial function. Tocotrienol rich tocomin is more effective than α-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and although α-, δ-, and γ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function.
Tocotrienols delays onset and progression of galactose-induced cataract in rat

Abdul Nasir, N.A., et.al (2013). Acta Pharmacologica Sinica.

 

 The effect of tocotrienol eye drop in delaying onset and progression of galactose-induced cataract. Tocotrienol delayed cataract progression at low doses but enhanced cataract progression at higher doses.
Antioxidant Activity of Tocotrienol Rich Fraction Prevents Fenitrothion-induced Renal Damage in Rats

Budin, S.B., et.al (2013). J Toxicol Pathol.

 

 Fenitrothion (FNT) is an organophosphate compound widely used as pesticide in Malaysia. The present study aims to investigate effects of palm oil tocotrienol rich fraction (TRF) on the renal damage of FNT-treated rats. In conclusion, palm oil TRF was able to reduce oxidative stress and renal damage in FNT-treated rats.
Tocotrienol rich fraction (TRF) supplementation protects against oxidative DNA damage and improves cognitive functions in Wistar rats.

Taridi, N.M., et.al (2011). Clin Ter.

 

 This study was undertaken to elucidate the effect of TRF on oxidative DNA damage and cognitive functions in experimental rats. Continuous supplementation of TRF for 8 months reduced DNA damage and exhibited positive influence in spatial learning and memory.
Comparison of antioxidative and antifibrotic effects of alpha-tocopherol with those of tocotrienol-rich fraction in a rat model of chronic pancreatitis.

Jiang, F., et.al (2011). Pancreas.

 

 This study aimed to compare the antioxidative and antifibrotic effects of α-tocopherol and TFR in dibutylin dichloride (DBTC)-induced chronic pancreatitis (CP) rats. Oral administration of α-tocopherol and TRF improves pancreatic inflammation and fibrosis in DBTC-induced CP rats, with TRF being more effective than α-tocopherol. Therefore, TRF may be a novel option for alleviating inflammation and, particularly, the fibrotic process in CP.
Protective effect of dietary tocotrienols against infection and inflammation-induced hyperlipidemia: An in vivo and silico study

Salman, K.M., et.al (2011). Phytother Res.

 To explore the therapeutic potentials of naturally occurring Tocomin (mixture of dietary α-, β-, γ- and δ-tocotrienols). Tocotrienols was orally administered daily for 10 days before and 12 h after bacterial lipopolysaccharide (200 μg) or 24 h after zymosan (20 mg) or turpentine (0.5 mL) to Syrian hamsters. The results favor the daily intake of naturally occurring tocotrienols as dietary supplement in the prevention and treatment of infection/inflammation induced dyslipidemia compared with the hypolipidemic drugs.
Increased antioxidant capacity in the plasma of dogs after a single oral dosage of tocotrienols.

Raila, J, et.al (2011). Br J Nutr

 The intestinal absorption of tocotrienols (TCT) in dogs is, to our knowledge, so far unknown. Adult Beagle dogs (n 8) were administered a single oral dosage of a TCT-rich fraction (TRF; 40 mg/kg body weight) containing 32 % α-TCT, 2 % β-TCT, 27 % γ-TCT, 14 % δ-TCT and 25 % α-tocopherol (α-TCP). Blood was sampled at baseline (fasted), 1, 2, 3, 4, 5, 6, 8 and 12 h after supplementation. The results show that TCT are detected in postprandial plasma of dogs. The increase in antioxidant capacity suggests a potential beneficial role of TCT supplementation in the prevention or treatment of several diseases in dogs.
An in vivo and in silico approach to elucidate the tocotrienol-mediated fortification against infection and inflammation induced alterations in antioxidant defense system.

Khan, M. S. et.al (2011). Eur Rev Med Pharmacol Sci.

 

 Tocotrienol are naturally occurring analogues of vitamin E family and has been reported to possess a potent free radical scavenging activity. In the present study we have initially investigated protective role of tocotrienol against infection and inflammation induced alterations in tissues antioxidant defense system, as well as speculated, via in silico docking studies, that tocotrienol can act by directly binding to antioxidant enzymes.
Effects of tocotrienol-rich fraction on exercise endurance capacity and oxidative stress in forced swimming rats.

Lee, S.P., et.al (2009). Eur J Appl Physiol.

 The effects of tocotrienol-rich fraction (TRF) on exercise endurance and oxidative stress in forced swimming rats are examined. Rats fed on isocaloric diet were orally given 25 (TRF-25) and 50 (TRF-50) mg/kg of TRF, or 25 mg/kg D-alpha-tocopherol (T-25) whilst the control group received only the vehicle for 28 days, followed by being forced to undergo swimming endurance tests, with measurements taken of various biochemical parameters, including blood glucose, lactate and urea nitrogen, glycogen, total antioxidant capacity, antioxidant enzymes, thiobarbituric acid-reactive substances (TBARS), and protein carbonyl.  The results suggest that TRF is able to improve the physiological condition and reduce the exercise-induced oxidative stress in forced swimming rats.
Palm tocotrienol exerted better antioxidant activities in bone than alpha-tocopherol.

Maniam, S., et.al (2008). Basic Clin Pharmacol Toxicol.

 The aim of this study was to investigate the effects of vitamin E on the levels of lipid peroxidation and antioxidant enzymes in rat bones. Palm tocotrienol showed better protective effect against free radical damage in the femur compared to alpha-tocopherol. This study suggests that palm tocotrienol plays an important role in preventing imbalance in bone metabolism due to free radicals.
A comparison between tocopherol and tocotrienol effects on gastric parameters in rats exposed to stress.

Azlina, M. F., et.al (2005). Asia Pac J Clin Nutr.

 This study was designed to compare the impact of tocopherol and tocotrienol on changes that influence gastric and hormonal parameters important in maintaining gastric mucosal integrity in rats exposed to restrain stress. Both tocopherol and tocotrienol are comparable in their gastro-protective ability against damage by free radicals generated in stress conditions, but only tocotrienol has the ability to block the stress-induced changes in the gastric acidity and gastrin level.
Effect of dietary tocopherols and tocotrienols on the antioxidant status and lipid stability of chicken.

Lenari, M.C., et.al (2004). Meat Sci.

 

 The effect of dietary tocopherols and tocotrienols on the lipid stability of pre-cooked chicken breast and thigh. Lipid stability of pre-cooked chicken was not enhanced by adding tocotrienols to a tocopherol supplement.
Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR).

Newaz, M.A., et.al (1999). Clin Exp Hypertens.

 The aim of this study was to determine the effects of gamma tocotrienol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar Kyoto (WKY) rats. All the three treated groups showed improve total antioxidant status significantly. Correlation studies showed that, total antioxidant status (TAS) and SOD were significantly negatively correlated with blood pressure in normal rats but not in SHR control. This correlation regained in all three groups SHR’s after treatment with tocotrienol.. In conclusion it was found that antioxidant supplement of gamma-tocotrienol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels and enhanced total antioxidant status including SOD activity.
Protection by tocotrienols against hypercholesterolaemia and atheroma

Teoh, M.K. et.al (1994). Med J Malaysia.

 The effects of tocotrienols on serum cholesterol, lipid peroxides, and aorta atheroma were assessed in rabbits fed an atherogenic diet for 12 weeks. Tocotrienols were more effective than tocopherols in preventing increases in serum LDL and total cholesterol levels in the cholesterol-fed rabbits. Elevation of serum lipid peroxides was effectively suppressed by tocotrienols (p = 0.01). Both tocopherols and tocotrienols offered significant protection against atheroma in the rabbit aorta, but tocotrienols had a stronger hypolipidaemic effect.
Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogues of the tocotrienols.

Pearce, B.C., et.al (1994). J Med Chem.

 Tocotrienols exhibit antioxidant and cholesterol-biosynthesis-inhibitory activities and may be of value as antiatherosclerotic agents. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase (HMGR) in a manner mimicking the action of putative non-sterol feedback inhibitors. The in vitro cholesterol-biosynthesis-inhibitory and HMGR-suppressive activities in HepG2 cells of an expanded series of benzopyran and tetrahydronaphthalene isosteres and the hypocholesterolemic activity of selected compounds assessed in orally dosed chickens are presented. Preliminary antioxidant data of these compounds have been obtained using cyclic voltammetry and Cu-induced LDL oxidation assays. The farnesyl side chain and the methyl/hydroxy substitution pattern of gamma-tocotrienol deliver a high level of HMGR suppression, unsurpassed by synthetic analogues of the present study. In orally dosed chickens, 8-bromotocotrienol (4o), 2-desmethyltocotrienol (4t), and the tetrahydronaphthalene derivative 35 exhibit a greater degree of LDL cholesterol lowering than the natural tocotrienols.
Gamma-tocotrienol as a hypocholesterolemic and antioxidant agent in rats fed atherogenic diets

Watkins, T., et.al (1993). Lipids.

 This study was designed to determine whether incorporation of gamma-tocotrienol or alpha-tocopherol in an atherogenic diet would reduce the concentration of plasma cholesterol, triglycerides and fatty acid peroxides, and attenuate platelet aggregability in rats. Supplementation with gamma-tocotrienol resulted in similar, though quantitatively smaller, decrements in these plasma values.

In vitro Studies
Article Study objectives/ findings
The Modulation of NMDA and AMPA/Kainate Receptors by Tocotrienol-Rich Fraction and Α-Tocopherol in Glutamate-Induced Injury of Primary Astrocytes.

 

Abedi, Z., et al., (2017).  Biomedicines

 The aim of the current study was to elucidate the potential of vitamin E in protecting glutamate-injured primary astrocytes. The IC20 and IC50 values of glutamate, as well as the cell viability of primary astrocytes, were assessed with 100 ng/mL, 200 ng/mL, and 300 ng/mL of tocotrienol-rich fraction (TRF) and alpha-tocopherol (α-TCP), as determined by an MTT assay. Both TRF and α-TCP (at the lowest and highest concentrations, respectively) were able to increase the MMP to 88.46% and 93.31% pre-treatment, and 78.43% and 81.22% post-treatment, respectively.
The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts.

Khor, S. C., et.al (2016).  PLoS One.

 This study aimed to determine the effects of the tocotrienol-rich fraction (TRF) and α-tocopherol (ATF) in protecting myoblasts from replicative senescence and promoting myogenic differentiation.  Tocotrienol-rich fraction is superior to α-tocopherol in ameliorating replicative senescence-related aberration and promoting differentiation via modulation of MRFs expression, indicating vitamin E potential in modulating replicative senescence of myoblasts.
Pleiotropic Effects of Tocotrienols and Quercetin on Cellular Senescence: Introducing the Perspective of Senolytic Effects of Phytochemicals.

Malavolta, M, et.al (2016). Curr Drug Targets.

 The possibility to target cellular senescence with natural bioactive substances open interesting therapeutic perspective in cancer and aging. Engaging senescence response is suggested as a key component for therapeutic intervention in the eradication of cancer. The rejuvenating effects of tocotrienol (T3) and QUE (quercetin) on pre-senescent and senescent primary cells might be the net results of a senolytic activity on senescent cells and a selective survival of a sub-population of non-senescent cells in the culture.
Location of α-tocopherol (α-T) and α-tocotrienol (α-T3) to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts

Nakamura, T., et.al (2014). Sringerplus.

 

 The distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts was investigated. These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.
Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts

Makpol, S., et.al (2013). Complementary & Alternative Medicine.

 

 To evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs (Human Diploid Fibroblasts).
Effect of the tocotrienol-rich fraction on the lifespan and oxidative biomarkers in Caenorhabditis elegans under oxidative stress

Goon, J.A., et.al (2013). Clinics (Sap Paulo).

 

 This study was performed to determine the effect of the tocotrienol-rich fraction on the lifespan and oxidative status of C. elegans under oxidative stress. The tocotrienol-rich fraction restored the lifespan of oxidative stress-induced C. elegans and reduced the accumulation of lipofuscin but did not affect protein damage. In addition, DNA oxidation was increased.
A tocotrienol-rich faction (TRF) from grape seeds inhibits oxidative stress induced by tert-butyl hydroperoxide in HepG2 cells

Choi, Y, et.al (2010). J Med Food.

 

 The protective effect of TRF from grape seeds on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. TRF has significant protective ability against TBHP-induced oxidative insult and that the modulation of antioxidant enzymes by TRF may have an important antioxidant effect on HepG2 cells.
γ-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals

Makpol, S., et.al (2010). Oxid Med Cell Longev.

 

 The effects of palm γ-tocotrienol (GGT) on oxidative stress-induced cellular ageing was investigated in normal human skin fibroblast cell lines derived from different age groups; young, middle and old. γ-tocotrienol protects against oxidative stress-induced cellular ageing by modulating the telomere length possibly via telomerase.
Comparative antioxidant activity of tocotrienols and the novel chromanyl-polysioprenyl molecule FeAox-6 in isolated membrane and intact cells.

Palozza, P, et.al (2006). Mol Cell Biochem.

 The antioxidant efficiency of different tocotrienol isoforms (alpha-, delta-, gamma-tocotrienols), and that of FeAox-6, a novel synthetic compound which combines, by a stable covalent bond, the chroman head of vitamin E and a polyisoprenyl sequence of four conjugated double bonds into a single molecule. FeAox-6 showed an antioxidant potency greater than that of delta-tocotrienol. Such an efficiency seems to depend on the concomitant presence of a chromane ring and a phytyl chain in the molecule, which because of four conjugated double bonds, may induce a greater mobility and a more uniform distribution within cell membrane. In view of these results, FeAox-6 represents a new potential preventive agent in chronic diseases in which oxidative stress plays a pathogenic role.
Evidence for the preventive effect of the polyunsaturated phytol side chain in tocotrienols on 17beta-estradiol expoxidation.

Yu, F.L., et.al (2005). Cancer Detect Prev.

 17beta-estradiol (E2) could be activated by epoxidation to bind DNA and to inhibit nuclear RNA synthesis. Vitamin E compounds are powerful antioxidants and chain-breaking free radical scavengers. The chromanol ring in Vitamin E is believed to be involved in these reactions. The polyunsaturated phytol group in tocotrienols plays a key preventive role in E2 epoxidation. This is the first report showing that the polyunsaturated phytol side chain in tocotrienols is involved in an antioxidative activity and it may also have a preventive effect against the E2 epoxide induced breast cancer carcinogenesis at the initiation.
Lack of oxidative stress in a selenium deficient area in Ivory Coast-potential nutritional antioxidant role of crude palm oil.

Tianhou, G., et.al (2004). Eur J Nutr.

 

 To assess the antioxidant capacity of subjects from a selenium deficient area in Ivory Coast (Glanle region). The long–term consumption of crude palm oil could be considered as an effective protective factor against oxidative stress.
Inhibition of THP-1 cell adhesion to endothelial cells by alpha-tocopherol and alpha-tocotrienol is dependent on intracellular concentration of antioxidants.

Noguchi, N., et.al (2003). Free Radic Biol Med.

 The reactivity of alpha-tocopherol and alpha-tocotrienol in inhibiting lipid peroxidation in vitro was essentially identical but the inhibition of adhesion of THP-1 cells, a monocytic-“like” cell line, to endothelial cells differs substantially. To determine the mechanism underlying this response, human umbilical vein endothelial cells (HUVECs) were assessed for their ability to accumulate vitamin E analogs. Alpha-Tocotrienol accumulated in HUVECs to levels approximately 10-fold greater than that of alpha-tocopherol. Both alpha-tocopherol and alpha-tocotrienol suppressed VCAM-1 expression and adhesion of THP-1 cells to HUVECs in a concentration-dependent manner. The efficacy of tocotrienol for reduction of VCAM-1 expression and adhesion of THP-1 cells to HUVECs was also 10-fold higher than that of tocopherol.
Comparative study on the action of tocopherols and tocotrienols as antioxidant: chemical and physical effects.

Yoshida, Y, et.al (2003). Chem Phys Lipids.

 Alpha-Tocopherol is known as the most abundant and active form of vitamin E homologues in vivo, but recently the role of other forms of vitamin E has received renewed attention. The antioxidant properties were compared for alpha-, beta-, gamma- and delta-tocopherols and tocotrienols. The following results were obtained: (1). the corresponding tocopherols and tocotrienols exerted the same reactivities toward radicals and the same antioxidant activities against lipid peroxidation in solution and liposomal membranes; (2). tocopherols gave more significant physical effect than tocotrienols on the increase in rigidity at the membrane interior; (3). tocopherols and tocotrienols showed similar mobilities within the membranes, but tocotrienols were more readily transferred between the membranes and incorporated into the membranes than tocopherols; (4). alpha-tocopherol and alpha-tocotrienol, but not the other forms, reduced Cu(II) to give Cu(I) together with alpha-tocopheryl and alpha-tocotrienyl quinones, respectively and exerted prooxidant effect in the oxidation of methyl linoleate in SDS micelles.
Molecular aspects of alpha-tocotrienol antioxidant action and cell signaling.

Packer, L, et.al (2001). J Nutr.

 Vitamin E, the most important lipid-soluble antioxidant, was discovered at the University of California at Berkeley in 1922 in the laboratory of Herbert M. Evans (Science 1922, 55: 650). At least eight vitamin E isoforms with biological activity have been isolated from plant sources. Since its discovery, mainly antioxidant and recently also cell signaling aspects of tocopherols and tocotrienols have been studied. Tocopherols and tocotrienols are part of an interlinking set of antioxidant cycles, which has been termed the antioxidant network. Although the antioxidant activity of tocotrienols is higher than that of tocopherols, tocotrienols have a lower bioavailability after oral ingestion. Tocotrienols penetrate rapidly through skin and efficiently combat oxidative stress induced by UV or ozone. Tocotrienols have beneficial effects in cardiovascular diseases both by inhibiting LDL oxidation and by down-regulating 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG CoA) reductase, a key enzyme of the mevalonate pathway. Important novel antiproliferative and neuroprotective effects of tocotrienols, which may be independent of their antioxidant activity, have also been described.
Structural and dynamic membrane properties of alpha-tocopherol and alpha-tocotrienol: Implication to the molecular mechanism of their antioxidant potency.

Suzuki, Y.J., et.al (1993). Biochemistry.

 Simple models of phospholipid membrane systems were used to investigate the mechanism of the antioxidant potency of alpha-tocotrienol in terms of its effects on membrane order and reorientation dynamics. When alpha-tocopherol and alpha-tocotrienol were examined for their effects on phospholipid molecular order using conventional ESR spin labeling with 5- and 16-position-labeled doxylstearic acid, although both vitamin E constituents disordered the gel phase and stabilized the liquid-crystalline phase, no differences were observed between the effects of the two compounds. A slightly greater increase (19% vs 15%) in ordering of the liquid-crystalline state due to alpha-tocopherol, however, was discerned in noninvasive 2H NMR experiments. The difference is most noticeable near C10-C13 positions of the phospholipid chain, possibly suggesting alpha-tocotrienol is located closer to the membrane surface. Saturation-transfer ESR, furthermore, revealed that on the time scale tau c = 10(-7)-10(-3) s the rates of rotation about the long molecular axis and of the wobbling motion of the axis are modified to differing extents by the two forms of the vitamin E.
Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogenous system, and in rat and human lipoprotein.

Suarna, C., et.al (1993). Biochim Biophys Acta.

 

 The antioxidant activity of tocotrienols toward peroxyl radicals was compared with that of other natural lipid-soluble antioxidants in three different systems by measuring the temporal disappearance of antioxidants and the formation of lipid hydroperoxides.  Our results show that dietary tocotrienols become incorporated into circulating human lipoproteins where they react with peroxyl radicals as efficiently as the corresponding tocopherol isomers.
Free radical recycling and intermembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol.

Serbinova, E., et.al (1991). Free Radic Biol Med.

 d-Alpha-tocotrienol possesses 40-60 times higher antioxidant activity against (Fe2+ + ascorbate)- and (Fe2+ + NADPH)-induced lipid peroxidation in rat liver microsomal membranes and 6.5 times better protection of cytochrome P-450 against oxidative damage than d-alpha-tocopherol. Higher antioxidant potency of d-alpha-tocotrienol is due to the combined effects of three properties exhibited by d-alpha-tocotrienol as compared to d-alpha-tocopherol: (i) its higher recycling efficiency from chromanoxyl radicals, (ii) its more uniform distribution in membrane bilayer, and (iii) its stronger disordering of membrane lipids which makes interaction of chromanols with lipid radicals more efficient.

Review Article
Article Study objectives/ Findings
Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics.

Kanchi, M.M., et.al (2017). Drug Discov Today. 

 Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials. This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases.

 
Focus on Pivotal Role of Dietary Intake (Diet and Supplement) and Blood Levels of Tocopherols and Tocotrienols in Obtaining Successful Aging.

Rondanelli, M., et.al (2015). Int Mol Sci.

 Numerous specific age-related morbidities have been correlated with low intake and serum levels of tocopherols and tocotrienols. We performed a review in order to evaluate the extant evidence regarding: (1) the association between intake and serum levels of tocopherols and tocotrienols and age-related pathologies (osteoporosis, sarcopenia and cognitive impairment); and (2) the optimum diet therapy or supplementation with tocopherols and tocotrienols for the treatment of these abnormalities. This review included 51 eligible studies. The recent literature underlines that, given the detrimental effect of low intake and serum levels of tocopherols and tocotrienols on bone, muscle mass, and cognitive function, a change in the lifestyle must be the cornerstone in the prevention of these specific age-related pathologies related to vitamin E-deficient status. The optimum diet therapy in the elderly for avoiding vitamin E deficiency and its negative correlates, such as high inflammation and oxidation, must aim at achieving specific nutritional goals. These goals must be reached through: accession of the elderly subjects to specific personalized dietary programs aimed at achieving and/or maintaining body weight (avoid malnutrition); increase their intake of food rich in vitamin E, such as derivatives of oily seeds (in particular wheat germ oil), olive oil, hazelnuts, walnuts, almonds, and cereals rich in vitamin E (such as specific rice cultivar rich in tocotrienols) or take vitamin E supplements. In this case, vitamin E can be correctly used in a personalized way either for the outcome from the pathology or to achieve healthy aging and longevity without any adverse effects.
Tocotrienols, health and ageing: A systematic review.

Georgouspoulou, E. N., et.al (2017). Maturitas.

 

 A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage. Research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects.
Tocochromanol functions in plants: Antioxidation and beyond.

Falk, J & Munne-Bosch, (2010). J Exp Bot.

 Tocopherols and tocotrienols, collectively known as tocochromanols, are lipid-soluble molecules that belong to the group of vitamin E compounds and are essential in the human diet. Not surprisingly, most of what is known about the biological functions of tocochromanols comes from studies of mammalian systems, yet they have been shown to be synthesized only by photosynthetic organisms. The last decade has seen a radical change in the appreciation of the biological role of tocochromanols in plants thanks to a detailed characterization of mutant and transgenic plants, including several Arabidopsis thaliana mutants, the sucrose export defective1 (sxd1) maize mutant, and some transgenic potato and tobacco lines altered in tocochromanol biosynthesis. Recent findings indicate that tocopherols may play important roles in plants beyond their antioxidant function in photosynthetic membranes. Plants deficient in tocopherols show alterations in germination and export of photoassimilates, and growth, leaf senescence, and plant responses to abiotic stresses, thus suggesting that tocopherols may influence a number of physiological processes in plants. Thus, in this review not only the antioxidant function of tocochromanols in plants, but also these new emerging possible roles will be considered. Particular attention will be paid to specific roles attributed to different tocopherol homologues (particularly alpha- and gamma-tocopherol) and the possible functions of tocotrienols, which in contrast to tocopherols are only present in a range of unrelated plant groups and are almost exclusively found in seeds and fruits.
The chemistry and antioxidant properties of tocopherols and tocotrienols.

Kamal-Eldin A, & Appelqvist, L.A., (1996). Lipids.

 This article is a review of the fundamental chemistry of the tocopherols and tocotrienols relevant to their antioxidant action. Despite the general agreement that alpha-tocopherol is the most efficient antioxidant and vitamin E homologue in vivo, there was always a considerable discrepancy in its “absolute” and “relative” antioxidant effectiveness in vitro, especially when compared to gamma-tocopherol. Many chemical, physical, biochemical, physicochemical, and other factors seem responsible for the observed discrepancy between the relative antioxidant potencies of the tocopherols in vivo and in vitro. This paper aims at highlighting some possible reasons for the observed differences between the tocopherols (alpha-, beta-, gamma-, and delta-) in relation to their interactions with the important chemical species involved in lipid peroxidation, specifically trace metal ions, singlet oxygen, nitrogen oxides, and antioxidant synergists. Although literature reports related to the chemistry of the tocotrienols are quite meager, they also were included in the discussion in virtue of their structural and functional resemblance to the tocopherols.

Others
Article Study Objectives/ Findings
Antioxidant activities of tocopherols/tocotrienols and lipophilic antioxidant capacity of wheat, vegetable oils, milk and milk cream by using photochemiluminescence.

Karmowski, J., et.al (2015). Food Chem

 

 The purpose of this study was to measure the antioxidant activity (AOA) of tocopherols and tocotrienols by using photochemiluminescence (PCL). This method enables to detect total lipophilic antioxidants. The second aim was to analyse different kinds of wheat, vegetable oils, milk and milk cream on their antioxidant capacity (AOC) by using PCL and α-TEAC. The contents of vitamin E and carotenoids were analysed by HPLC. Correlations between the sum of carotenoids and vitamin E and the AOC were detected. Based on high vitamin E contents, the oils had the highest and in contrast, the product macaroni showed the lowest AOC. A concentration-dependent effect was observed in both assays, PCL and α-TEAC.
Alpha-tocotrienol quinone modulates oxidative stress response and the biochemistry of aging.

Shrader, W.D., et.al (2011). Bioorg Med CHem Lett.

 It is that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function.
Molecular mechanism of antioxidant synergism of tocotrienols and carotenoids in palm oil.

Schroeder, M.T., et.al (2006). J Agric Food Chem.

 During repeated deep-fat frying of potato slices at 163 degrees C in yellow or red palm olein of comparable fatty acid profiles, the oxidative stability (peroxide value and anisidine value) of the palm oleins was similar, and in yellow palm olein, the rate of antioxidant depletion decreased in the order gamma-T3 > alpha-T3 > delta-T3 (T3, tocotrienol). In red palm olein, which had a total tocopherol/tocotrienol content of 1260 vs 940 ppm in yellow palm olein and a corresponding longer induction period in the Rancimat stability test at 120 degrees C, only depletion of gamma-T3 was significant among the phenols during frying and slower as compared to that in yellow palm olein. The carotenes in the red palm olein were depleted linearly with the number of fryings, apparently yielding an overall protection of the phenols. In antioxidant-depleted palm olein and in phospholipid liposomes with added increasing concentrations of phenols, gamma-T3 was found to be a better antioxidant than alpha-T3. alpha-T3 and alpha-T (T, tocopherol) had a similar antioxidant effect in antioxidant-depleted palm olein in the Rancimat stability test, while in the liposomes the ordering as determined by induction period for the formation of conjugated dienes was gamma-T3 > alpha-T3 > alpha-T. The addition of 100-1000 ppm beta-carotene to antioxidant-depleted palm olein or liposomes (lycopene also tested) did not provide any protection against oxidation. In the liposomes, synergistic interactions were observed between beta-carotene or lycopene and alpha-T, alpha-T3, or gamma-T3 for carotene/phenol ratios of 1:10 and 1:2 but not for 1:1. In chloroform, carotenes were regenerated by tocopherols/tocotrienols from carotene radicals generated by laser flash photolysis as shown by transient absorption spectroscopy, suggesting that carotenes rather than phenols are the primary substrate for lipid-derived radicals in red palm olein, in effect depleting carotenes prior to phenols during frying. Regeneration of carotenes by the phenols also explains the synergism in liposomes. In the laser flash photolysis experiments, gamma-T3 was also found to be faster in regenerating carotenes than alpha-T3 and alpha-T.