Vitamin E (Tocopherols/Tocotrienol)

The value of tocotrienols in the prevention and treatment of cancer.
Sylvester PW, Kaddoumi A, Nazzal S, El Sayed KA.
J Am Coll Nutr. 2010 Jun 29

 Tocopherols and tocotrienols represent the 2 subgroups that make up the vitamin E family of compounds, but only tocotrienols display potent anticancer activity. Although in vitro experimental evidence has been very promising, oral supplementation of tocotrienols in animal and human studies has produced inconsistent results. However, recent studies have now clarified the reasons for these discrepancies observed between in vitro and in vivo studies. Oral absorption of tocotrienols into the circulation is mediated in large part by carrier transporter systems that display saturation and apparently down-regulation when exposed to high concentrations of tocotrienols. To circumvent these limitations in oral absorption of tocotrienols, investigators have developed novel prodrug derivatives and nanoparticle delivery systems that greatly enhance tocotrienol bioavailability and therapeutic responsiveness. Additional studies have also demonstrated that combined treatment of tocotrienols with other traditional chemotherapeutic agents results in a synergistic anticancer response, and this synergistic response was further enhanced when these agents were encapsulated in a nanoparticle delivery system. Taken together, these findings clarify the limitations of oral tocotrienol administration and provide novel alternative drug-delivery systems that circumvent these limitations and greatly enhance the therapeutic effectiveness of tocotrienols in the prevention and treatment of cancer. PMID: 20823492

  Do tocotrienols have potential as neuroprotective dietary factors?
Frank J, Chin XW, Schrader C, Eckert GP, Rimbach G.
Ageing Res Rev. 2011 Jul 7

 Tocotrienols (T(3)) belong to the family of vitamin E compounds (α-, β-, γ-, δ-tocopherols and -tocotrienols) and have unique biological properties that make them potential neuroprotective dietary factors. In addition to their antioxidant activity, T(3) at micromolar concentrations exert cholesterol-lowering activities in cells, animal models and some, but not all, human studies by means of inhibition of the activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. At lower concentrations (∼10nmol/L), T(3) modulate signalling pathways involved in neuronal cell death in cell culture experiments. Targets of T(3) include prenyl transferases, non-receptor tyrosine kinase, phospholipase A(2), 12-lipoxygenase, cyclooxygenase-2, and nuclear factor κB. The low bioavailability and rapid excretion of T(3) represents a major hurdle in their preventive use. Fasting plasma concentrations, even after supplementation with high doses, are below 1μmol/L. T(3) bioavailability may be enhanced by ingestion with a high-fat meal, self-emulsifying drug delivery systems, or phytochemicals that inhibit T(3) metabolism and excretion. T(3) have no known adverse effects when consumed as part of a normal diet and the studies reviewed here support the notion that they may have potential as neuroprotective agents. However, experiments in relevant animal models and randomised human intervention trials addressing the neuroprotection mediated by T(3) are scarce and, thus, highly warranted.
PMID: 21763788 Copyright © 2011 Elsevier B.V. All rights reserved

  Vitamin E and immunity.
Pekmezci D.
Vitam Horm. 2011;86:179-215.

 Vitamin E is the most important chain-breaking, lipid-soluble antioxidant present in body tissues of all cells and is considered the first line of defense against lipid peroxidation and it is important for normal function of the immune cells. However, vitamin E deficiency is rare in well-nourished healthy subjects and is not a problem, even among people living on relatively poor diets, both T- and B-cell functions are impaired by vitamin E deficiency. While immune cells are particularly enriched in vitamin E because of their high polyunsaturated fatty acid content, this point puts them at especially high risk for oxidative damage. Besides its immunomodulatory effects, vitamin E also plays an important role in carcinogenesis with its antioxidant properties against cancer, and ischemic heart disease with limiting the progression of atherosclerosis. Supplementation of vitamin E significantly enhances both cell mediated and humoral immune functions in humans, especially in the elderly and animals. PMID: 21419272
Copyright © 2011 Elsevier Inc. All rights reserved.

  Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases.
Aggarwal BB, Sundaram C, Prasad S, Kannappan R.
Biochem Pharmacol. 2010 Dec 1;80(11):1613-31

 Initially discovered in 1938 as a “fertility factor,” vitamin E now refers to eight different isoforms that belong to two categories, four saturated analogues (α, β, γ, and δ) called tocopherols and four unsaturated analogues referred to as tocotrienols. While the tocopherols have been investigated extensively, little is known about the tocotrienols. Very limited studies suggest that both the molecular and therapeutic targets of the tocotrienols are distinct from those of the tocopherols. For instance, suppression of inflammatory transcription factor NF-κB, which is closely linked to tumorigenesis and inhibition of HMG-CoA reductase, mammalian DNA polymerases and certain protein tyrosine kinases, is unique to the tocotrienols. This review examines in detail the molecular targets of the tocotrienols and their roles in cancer, bone resorption, diabetes, and cardiovascular and neurological diseases at both preclinical and clinical levels. As disappointment with the therapeutic value of the tocopherols grows, the potential of these novel vitamin E analogues awaits further investigation. PMID: 20696139
Copyright © 2010 Elsevier Inc. All rights reserved.

  Vitamin E supplementation and mammalian lifespan.
Banks R, Speakman JR, Selman C.
Mol Nutr Food Res. 2010 May;54(5):719-25.

 Vitamin E refers to a family of several compounds that possess a similar chemical structure comprising a chromanol ring with a 16-carbon side chain. The degree of saturation of the side chain, and positions and nature of methyl groups designate the compounds as tocopherols or tocotrienols. Vitamin E compounds have antioxidant properties due to a hydroxyl group on the chromanol ring. Recently, it has been suggested that vitamin E may also regulate signal transduction and gene expression. We previously reported that lifelong dietary vitamin E (alpha-tocopherol) supplementation significantly increased median lifespan in C57BL/6 mice by 15%. This lifespan extension appeared to be independent of any antioxidant effect. Employing a transcriptional approach, we suggest that this increase in lifespan may reflect an anti-cancer effect via induction of the P21 signalling pathway, since cancer is the major cause of death in small rodents. We suggest that the role of this pathway in life span extension following supplementation of vitamin E now requires further investigation. PMID: 20205192

  Antioxidant properties of palm fruit extracts.
Balasundram N, Ai TY, Sambanthamurthi R, Sundram K, Samman S.
Asia Pac J Clin Nutr. 2005;14(4):319-24.

 Phenolic compounds have been shown to exhibit bioactive properties, and in particular antioxidant effects. A phenolic-rich fraction has been isolated from the aqueous by-product obtained during the milling of oil palm fruits. The objectives of the study were to determine the phenolic content of the crude and ethanolic extracts of oil palm fruits and to evaluate the antioxidant properties of these extracts. The total phenolics content of the crude and ethanol extracts as determined by the Folin-Ciocalteu method were found to be 40.3 +/- 0.5 and 49.6 +/- 0.6 mg GAE/g extract (dry basis), respectively. The radical scavenging activity of the extracts determined using 2,2 diphenyl-1-picrylhydrazyl radical (DPPH.) indicated that both crude and ethanol extracts exhibit hydrogen-donating capacity, and have antiradical power (ARP) comparable to ascorbic acid. The DPPH radical scavenging activity of the extracts were less than that of gallic acid, but the time-course variations of the scavenging curves suggest that the extracts acted by a mechanism similar to that of gallic acid. The electron-donating potentials of the extracts were inferred from the hydrogen peroxide scavenging and reducing power assays. The reducing power of crude and ethanol extracts at 1 mM GAE were found to be comparable to that of 0.3 mM gallic acid. The extracts indicated complete scavenging of hydrogen peroxide at concentrations above 0.4 mM GAE. These findings suggest that the crude and ethanol extracts are able to scavenge free radicals, by either hydrogen or electron donating mechanisms, and can therefore act as primary antioxidants. PMID: 16326638

  Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease.
Sen CK, Rink C, Khanna S.
J Am Coll Nutr. 2010 Jun 29

 A growing body of research supports that members of the vitamin E family are not redundant with respect to their biological function. Palm oil derived from Elaeis guineensis represents the richest source of the lesser characterized vitamin E, alpha-tocotrienol. One of 8 naturally occurring and chemically distinct vitamin E analogs, alpha-tocotrienol possesses unique biological activity that is independent of its potent antioxidant capacity. Current developments in alpha-tocotrienol research demonstrate neuroprotective properties for the lipid-soluble vitamin in brain tissue rich in polyunsaturated fatty acids (PUFAs). Arachidonic acid (AA), one of the most abundant PUFAs of the central nervous system, is highly susceptible to oxidative metabolism under pathologic conditions. Cleaved from the membrane phospholipid bilayer by cytosolic phospholipase A(2), AA is metabolized by both enzymatic and nonenzymatic pathways. A number of neurodegenerative conditions in the human brain are associated with disturbed PUFA metabolism of AA, including acute ischemic stroke. Palm oil-derived alpha-tocotrienol at nanomolar concentrations has been shown to attenuate both enzymatic and nonenzymatic mediators of AA metabolism and neurodegeneration. On a concentration basis, this represents the most potent of all biological functions exhibited by any natural vitamin E molecule. Despite such therapeutic potential, the scientific literature on tocotrienols accounts for roughly 1% of the total literature on vitamin E, thus warranting further investment and investigation. PMID: 20823491

  Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cell
Wu SJ, Liu PL, Ng LT.
Mol Nutr Food Res. 2008 Aug;52(8):921-9.

 Tocotrienol-rich fraction (TRF) of palm oil has been shown to possess potent antioxidant, anticancer, and cholesterol lowering activities. In this study, our aim was to examine the effects of TRF on LPS-induced inflammatory response through measuring the production of inflammatory mediators, namely nitric oxide (NO), prostaglandin E(2) (PGE(2)), inducible nitric oxide synthase (iNOS), cytokines (TNF-alpha, IL-4, and IL-8), cyclooxygenase-1 and -2 (COX-1 and COX-2), and nuclear factor-kappaB (NF-kappaB) in human monocytic (THP-1) cells. At concentrations 0.5-5.0 microg/mL, TRF dose-dependently protected against LPS-induced cell death. At same concentrations, TRF also showed potent anti-inflammatory activity as demonstrated by a dose-dependent inhibition of LPS (1 microg/mL)-induced release of NO and PGE(2), and a significant decrease in the transcription of proinflammatory cytokines. TRF at 1.0 microg/mL significantly blocked the LPS induction of iNOS and COX-2 expression, but not COX-1. This anti-inflammatory activity was further supported by the inhibition of NF-kappaB expression. These results conclude that TRF possesses potent anti-inflammatory activity, and its mechanism of action could be through the inhibition of iNOS and COX-2 production, as well as NF-kappaB expression. PMID: 18481320