Compendium of the most significant studies with reference to properties, intake, effects.

Traber MG, Leonard SW, Vasu VT, Morrissey BM, Lei HJ, Atkinson J, Cross CE. α-Tocopherol Pharmacokinetics in Adults with Cystic Fibrosis: Benefits of Supplemental Vitamin C Administration. Nutrients. 2022 Sep 9;14(18):3717. doi: 10.3390/nu14183717.

Abstract. Background: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration. Methods: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (n = 6) with moderately advanced respiratory tract (RT) disease consumed a standardized breakfast with 30% fat and a capsule containing 50 mg each hexadeuterium (d6)-α- and dideuterium (d2)-γ-tocopheryl acetates. Blood samples were taken frequently up to 72 h; plasma tocopherol pharmacokinetics were determined. During both trials, d6-α- and d2-γ-tocopherols were similarly absorbed and reached similar maximal plasma concentrations ~18-20 h. As predicted, during vitamin C supplementation, the rates of plasma d6-α-tocopherol decline were significantly slower. Conclusions: The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.

Gohil K, Vasu VT, Cross CE. Dietary alpha-tocopherol and neuromuscular health: search for optimal dose and molecular mechanisms continues! Mol Nutr Food Res. 2010 May;54(5):693-709. doi: 10.1002/mnfr.200900575.

Abstract. Rodents fed alpha-tocopherol (alphaT)-depleted diets develop neuromuscular deficits. Unequivocal role of alphaT in the prevention of these deficits is confounded by possible neurotoxic oxidant products generated, ex vivo in alphaT-depleted diets. The discovery that large doses of alphaT could ameliorate neuromuscular deficits, attributed to very low serum alphaT caused by mutations in either the microsomal triglyceride transfer protein or the alphaT-transfer protein (alphaTTP), underscores the necessity of alphaT for neuromuscular health in humans. The discovery of human alphaTTP provided physiological relevance to biochemical data from rodents documenting alphaT-binding transfer protein, expressed exclusively in liver. The cloning of alphaTTP gene and the creation of alphaTTP-knockout mice allowed to achieve severe systemic alphaT deficiency in brain and muscles, possibly at birth, eliminating the possible confounding effects of ex vivo-generated oxidant products in vitamin E-stripped diets. alphaTTP-knockout mice have proven useful models to discover alphaT-regulated phenotypes and molecular actions of alphaT in vivo. The results suggest that antioxidant and non-antioxidant actions of alphaT in vivo may not be mutually exclusive. These studies also suggest that low levels of dietary alphaT can achieve in excess of nanomolar alphaT levels in tissues and maintain normal neuromuscular functions. This is consistent with biochemical and crystallographic data of alpha-TTP and of other alphaT-binding proteins that have dissociation constants in nanomolar range. Molecular mechanisms that cause a long delay for the development of deficiency symptoms remain enigmatic. It is likely that alphaT is metabolically stable in post-mitotic neurons and myocytes and, if it undergoes redox-cycling in vivo, a large repertoire of alphaT-regenerating systems maintains its biological activity before it is totally depleted.

Reiter E, Jiang Q, Christen S. Anti-inflammatory properties of alpha- and gamma-tocopherol. Mol Aspects Med. 2007 Oct-Dec;28(5-6):668-91. doi: 10.1016/j.mam.2007.01.003.

Abstract. Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (alpha,beta, gamma, delta) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, alpha-tocopherol (alphaT) and gamma-tocopherol (gammaT), and discuss the potential molecular mechanisms involved in these effects. While both tocopherols exhibit anti-inflammatory activity in vitro and in vivo, supplementation with mixed (gammaT-enriched) tocopherols seems to be more potent than supplementation with alphaT alone. This may explain the mostly negative outcomes of the recent large-scale interventional chronic disease prevention trials with alphaT only and thus warrants further investigation.

Engin KN. Alpha-tocopherol: looking beyond an antioxidant. Mol Vis. 2009;15:855-60. Epub 2009 Apr 23.

Abstract. Vitamin E is an important natural antioxidant, and its most common and biologically active form is alpha-tocopherol. In addition to this, specific regulatory effects of vitamin E have been revealing. The body exerts a certain effort to regulate its tissue levels with specific tocopherol transport proteins and membrane receptors. Antiproliferative and protein kinase C-suppressing effects of alpha-tocopherol have been previously demonstrated, which have not been mimicked by beta-tocopherol or probucol. Protein kinase C promises to be an important area of interest in the means of glaucoma and cataractogenesis. It has been shown in different models that retinal vascular dysfunction due to hyperglycemia could be prevented by alpha-tocopherol via the diachylglycerol-protein kinase C pathway. Glutamate transporter activity has been shown to be modulated by protein kinase C. This pathway is also important in intraocular pressure-lowering effects of prostaglandin and its analogs in glaucoma therapy. Filtran surgery became another possible area of usage of alpha-tocopherol since its antiproliferative effect has been demonstrated in human Tenon's capsule fibroblasts. Prevention of posterior capsule opacification is another area for future studies. It is evident that when correct and safe modulation is the objective, alpha-tocopherol merits a concern beyond its mere antioxidant properties.

Kasperczyk S, Dobrakowski M, Kasperczyk A, Nogaj E, Boroń M, Szlacheta Z, Birkner E. α-Tocopherol supplementation and the oxidative stress, homocysteine, and antioxidants in lead exposure. Arch Environ Occup Health. 2017 May 4;72(3):153-158. doi: 10.1080/19338244.2016.1182112.

Abstract. To investigate whether α-tocopherol supplementation in workers exposed to lead would reduce the oxidative stress intensity and decrease homocysteine level, the examined population was randomly divided into two groups. Workers in the first group (n = 49, reference group) were not administered any drugs. Workers in the second group (n = 34) were administered orally α-tocopherol, 200 mg per day for 12 weeks. The level of α-tocopherol significantly increased compared to the baseline and the reference group. The level of thiol groups significantly increased compared to the reference group. However, the levels of malondialdehyde and homocysteine did not significantly change. Animal studies suggest the ability of α-tocopherol administration to reverse adverse health effects of lead exposure, such as oxidative stress; however, the results of this study on humans do not confirm these protective effects.

Singh U, Jialal I. Anti-inflammatory effects of alpha-tocopherol. Ann N Y Acad Sci. 2004 Dec;1031:195-203. doi: 10.1196/annals.1331.019. 

Abstract.  Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the western world. Its incidence has been increasing lately in the developing countries. Much evidence suggests a major role for inflammation in all phases of atherosclerosis. Cell adhesion molecules, cytokines, chemokines, and monocytes-macrophages as well as T lymphocytes play a pivotal role in atherogenesis. C-reactive protein (CRP), a downstream marker of inflammation, in addition to being a risk marker for CVD, could contribute to atherosclerosis. Dietary micronutrients with anti-inflammatory properties, specially alpha-tocopherol, may play an important role with regard to the prevention and treatment of CVD. alpha-Tocopherol has been shown to have anti-inflammatory effects both in vitro and in vivo. alpha-Tocopherol therapy, especially at high doses, has been shown to decrease release of pro-inflammatory cytokines (such as interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) and the chemokine interleukin-8, and to decrease adhesion of monocytes to endothelium. In addition, alpha-tocopherol has been shown to decrease CRP levels in patients with CVD and having related risk factors for CVD (such as diabetes and smoking). Furthermore, pro-inflammatory cytokines and plasminogen activator inhibitor-1 (PAI-1) levels have also been shown to be decreased with alpha-tocopherol supplementation in vivo. In this review, our focus will be on anti-inflammatory effects of alpha-tocopherol reported in in vivo studies.

Azzi A. Molecular mechanism of alpha-tocopherol action. Free Radic Biol Med. 2007 Jul 1;43(1):16-21. doi: 10.1016/j.freeradbiomed.2007.03.013.

Abstract. The inability of other antioxidants to substitute for alpha-tocopherol in a number of cellular reactions, the lack of a compensatory antioxidant response in the gene expression under conditions of alpha-tocopherol deficiency, the unique uptake of alpha-tocopherol relative to the other tocopherols and its slower catabolism, and the striking differences in the molecular function of the different tocopherols and tocotrienols, observed in vitro, unrelated to their antioxidant properties, are all data in support of a nonantioxidant molecular function of alpha-tocopherol. Furthermore, in vivo studies have also shown that alpha-tocopherol is not able, at physiological concentrations, to protect against oxidant-induced damage or prevent disease allegedly caused by oxidative damage. Alpha-tocopherol appears to act as a ligand of not yet identified specific proteins (receptors, transcription factors) capable of regulating signal transduction and gene expression.

Hall KT, Buring JE, Mukamal KJ, Vinayaga Moorthy M, Wayne PM, Kaptchuk TJ, Battinelli EM, Ridker PM, Sesso HD, Weinstein SJ, Albanes D, Cook NR, Chasman DI. COMT and Alpha-Tocopherol Effects in Cancer Prevention: Gene-Supplement Interactions in Two Randomized Clinical Trials. J Natl Cancer Inst. 2019 Jul 1;111(7):684-694. doi: 10.1093/jnci/djy204.

Abstract. Background: Vitamins are among the most frequently used supplements (48% of US adults). However, little is known about contributions of genetic variation to their efficacy and safety. Multiple pathways link catechol-O-methyltransferase (COMT) to the vitamin E supplement, alpha-tocopherol, and cancer. Methods: Here we determined if COMT exerted pharmacogenetic effects on cancer prevention in two randomized trials of alpha-tocopherol supplementation. Pharmacogenetic effects of common COMT rs4680 (val158met), which encodes a nonsynonymous valine-to-methionine substitution, were examined in the trial plus a 10-year post-trial follow-up (overall) period of The Women's Genome Health Study (WGHS, N = 23 294), a 10-year alpha-tocopherol and aspirin trial with 10 years post-trial follow-up. Results were validated in a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC, N = 29 133). The primary outcome was total cancers. Rates of cancer types prevalent in women (colorectal, breast, lung, uterine, and lymphoma/leukemia) were also examined. All statistical tests were two-sided. Results: Random-effects meta-analysis of rs4680 genotype strata, in WGHS and ATBC overall periods, revealed differential alpha-tocopherol effects compared with placebo: met/met (hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.80 to 0.97; P = .01), val/met (HR = 0.99; 95% CI = 0.92 to 1.06; P = .74), and val/val (HR = 1.18; 95% CI = 1.06 to 1.31; P = .002) with a statistically significant COMT by alpha-tocopherol interaction (Pinteraction <.001). Timing of effects differed, with stronger effects in WGHS trial and ATBC post-trial. Conclusion: Pharmacogenetic analysis of COMT and cancer prevention in two large randomized trials revealed statistically significant COMT by alpha-tocopherol interaction, such that alpha-tocopherol was beneficial among rs4680 met-allele (28.0%), but not val-allele (22.8%) homozygotes. These effects indicate the need for additional studies of genetic variation as a determinant of the benefits and possible harms of over-the-counter supplements, like alpha-tocopherol, used for health promotion.

Carpenter KL, Kirkpatrick PJ, Weissberg PL, Challis IR, Dennis IF, Freeman MA, Mitchinson MJ. Oral alpha-tocopherol supplementation inhibits lipid oxidation in established human atherosclerotic lesions. Free Radic Res. 2003 Nov;37(11):1235-44. doi: 10.1080/10715760310001604143.

Abstract. Background: Much experimental evidence suggests that lipid oxidation is important in atherogenesis and in epidemiological studies dietary antioxidants appear protective against cardiovascular events. However, most large clinical trials failed to demonstrate benefit of oral antioxidant vitamin supplementation in high-risk subjects. This paradox questions whether ingestion of antioxidant vitamins significantly affects lipid oxidation within established atherosclerotic lesions. Methods and results: This placebo-controlled, double blind study of 104 carotid endarterectomy patients determined the effects of short-term alpha-tocopherol supplementation (500 IU/day) on lipid oxidation in plasma and advanced atherosclerotic lesions. In the 53 patients who received alpha-tocopherol there was a significant increase in plasma alpha-tocopherol concentrations (from 32.66 +/- 13.11 at baseline to 38.31 +/- 13.87 (mean +/- SD) micromol/l, p < 0.01), a 40% increase (compared with placebo patients) in circulating LDL-associated alpha-tocopherol (p < 0.0001), and their LDL was less susceptible to ex vivo oxidation than that of the placebo group (lag phase 115.3 +/- 28.2 and 104.4 +/- 15.7 min respectively, p < 0.02). Although the mean cholesterol-standardised alpha-tocopherol concentration within lesions did not increase, alpha-tocopherol concentrations in lesions correlated significantly with those in plasma, suggesting that plasma alpha-tocopherol levels can influence lesion levels. There was a significant inverse correlation in lesions between cholesterol-standardised levels of alpha-tocopherol and 7beta-hydroxycholesterol, a free radical oxidation product of cholesterol. Conclusions: These results suggest that within plasma and lesions alpha-tocopherol can act as an antioxidant. They may also explain why studies using < 500 IU alpha-tocopherol/day failed to demonstrate benefit of antioxidant therapy. Better understanding of the pharmacodynamics of oral antioxidants is required to guide future clinical trials.

In 2000, with regard to supplements for human consumption, the SCF (Scientific Committee on Food, dissolved and incorporated into the EFSA European Food Safety Authority in 2001), had expressed an opinion on the maximum tolerable intake level (referred to as the upper level) of Selenium, establishing proportionately, lower levels of intake for children, based on the differences in body weight compared to adults. Based on the results in humans, the SCF noted that a Selenium intake of approximately 850μg/day could be considered as NOAEL for clinical selenosis. Using an uncertainty factor of 3 to consider the remaining uncertainties of the studies, the SCF calculated a higher level for Selenium than 300μg/day (1). The SELECT study (Selenium and Vitamin E Cancer Prevention Trial) started in 2001 on 35,533 men, and provided the following results (2):

2008: In September 2008, researchers found that Selenium (200μg/day) and Vitamin E, taken alone or together for an average of five and a half years, did not prevent prostate cancer.

2011: data from updated studies showed that, in men taking Vitamin E, there was a 17 percent increase in the risk of prostate cancer compared to men taking placebo.

2014: analysis showed that the men who started the process with high levels of Selenium doubled the risk of developing high-grade prostate cancer by taking Selenium supplements, and those who had low Selenium levels at the beginning of the process, doubled the risk of high-grade prostate cancer by taking Vitamin E.

Scientists do not understand how these supplements really work and, above all, the interaction that these supplements have with each other or with foods, drugs or other supplements. There are no clinical studies that show an advantage by taking Vitamin E or Selenium to reduce the risk of prostate cancer or any other cancer or heart disease (3).

References______________________________________________

(1) EFSA-Q-2005-103, EFSA-Q-2006-195, EFSA-Q-2006-196,EFSA-Q-2006-304

(2) http://www.cancer.gov/newscenter/qa/2008/selectqa

(3) http://www.cancer.gov/newscenter/qa/2008/selectqa 
Question 14.

Alpha tocopherol is one of the four isomer components that constitute tocopherol: alpha-tocopherol, beta-tocopherol, delta-tocopherol and/or gamma-tocopherol.

Alpha tocopherol  occurs naturally in cereals, in oils and, in particular in:

• olive oil
• wheat germ oil
• palm oil
• soybean oil
• corn oil
• sunflower oil
• eggs
• butter
• peanuts
• almonds and other dried fruit

It is a fundamental antioxidant and can be created using a chemical process.

Its antioxidant action has effects on the brain (1), when, in the cardiovascular system, there are problems of diabetes caused by LDL cholesterol (2) and in liver diseases (3)

In the medical field it is an adjuvant to treat vascular diseases, as prevention for cellular diseases and for a correct functioning of the immune system.

No positive action, however, was found towards prostate cancer, as demonstrated by this study of very long duration on many samples (4).

What it is used for and where

Medical

Its antioxidant action has effects on the brain (1), when, in the cardiovascular system, there are problems of diabetes caused by LDL cholesterol (2) and in liver diseases (3)

In the medical field it is an adjuvant to treat vascular diseases, as prevention for cellular diseases and for a correct functioning of the immune system.

No positive action, however, was found towards prostate cancer, as demonstrated by this study of very long duration on many samples (4).

Food

Ingredient included in the list of European food additives as E307, antioxidant.

Cosmetics

Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.

Fragrance. It plays a decisive and important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability.  The consumer always expects to find a pleasant or distinctive scent in a cosmetic product.

Skin conditioning agent - Miscellaneous.  This ingredient has the task of modifying the condition of the skin when it is damaged or dry by reducing its flakiness and restoring its elasticity.

Skin conditioning agent - Occlusive. This ingredient has the task of modifying the condition of the skin when it is damaged or dry by reducing flaking and restoring elasticity. It has a strong lipophilic character and is identified as an occlusive ingredient; it is generally composed of oily and fatty materials that remain on the skin surface and reduce trans epidermal water loss.

"Alpha-tocopherol studies"

"Alpha tocopherol vitamin E studies"

• Molecular Formula:    C₂₉H₅₀O2
• Molecular Weight: 430.717 g/mol
• CAS: 59-02-9
• EC Number: 200-201-5    200-412-2
• UNII: N9PR3490H9
• PubChem Substance ID     24899979
• MDL number     MFCD00072045
• Beilstein Registry Number   4712525
• DSSTox ID  DTXSID0026339
• IUPAC  (2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol
• InChl=1S/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1
• InChl Key      GVJHHUAWPYXKBD-IEOSBIPESA-N
• SMILES    CC1=C(C2=C(CCC(O2)(C)CCCC(C)CCCC(C)CCCC(C)C)C(=C1O)C)C
• ChEBI  18145
• NACRES    NA.75
• eCl@ss    34058016
• Nikkaji     J24.260H
• NCI         C68313    C2832    C74960
• RXCUI       237099    1236136    11256
• Metabolomics Workbench    29096
• Pharos Ligand    85BJCGZ83ZT5

Synonyms:

• alpha-Tocopherol
• a-Tocopherol
• D-alpha-Tocopherol
• (2R,4'R,8'R)-alpha-Tocopherol
• 59-02-9
• dl-a-Tocopherol
• 5,7,8-Trimethyltocol
• (+)-alpha-Tocopherol
• (R,R,R)-alpha-Tocopherol
• DL-ALPHA-TOCOPHEROL
• Vitamin Ea
• Mixed tocopherols
• D-alpha tocopherol
• Syntopherol
• Denamone
• Viteolin
• Esorb
• Tocopherol (R,S)
• 2,5,7,8-Tetramethyl-2-(4',8',12'-trimethyltridecyl)-6-chromanol
• Aquasol E
• 10191-41-0
• (+)-|A-Tocopherol
• Tocopherol alpha
• a-Vitamin E
• (2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL
• 2074-53-5
• Profecundin
• Waynecomycin
• Vitamin E alpha
• Vitaplex E
• N9PR3490H9
• Vita E
• EINECS 215-798-8
• Lan-E
• Med-E
• (R)-2,5,7,8-Tetramethyl-2-((4R,8R)-4,8,12-trimethyltridecyl)chroman-6-ol
• Antisterility vitamin
• alpha-Tocopherol acid
• Tenox GT 1
• Endo E
• Eprolin S
• Viterra E
• CHEBI:18145
• E Prolin
• Spavit E
• 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-, (2R)-
• Almefrol
• Emipherol
• Epsilan
• Etamican
• Tokopharm
• Vascuals
• Viprimol
• Vitayonon
• Etavit
• Ilitia
• Verrol
• Evion
• alpha-Tokoferol
• (2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-chromen-6-ol
• 3,4-Dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-ol
• BPBio1_000362
• alpha-Vitamin E

Abstract. Brain-derived neurotrophic factor (BDNF) is involved in the proliferation of neurons, and its expression increases significantly with exercise. We aimed to investigate the effects of chronic exercise (swimming) and sustained hypoxia on cortical BDNF expression in both the presence and absence of vitamin E. Sixty four male Sprague-Dawley rats were divided into two equal groups; a normoxic group and a hypoxic group. Both groups were equally subdivided into four subgroups: sedentary, sedentary with vitamin E, chronic exercise either with or without vitamin E supplementation. Arterial PO(2), and the levels of cortical malondialdehyde (MDA), antioxidants (reduced glutathione GSH, superoxide dismutase (SOD), catalase (CAT) and vitamin E) and BDNF gene expression were investigated. Hypoxia significantly increased MDA production and BDNF gene expression and decreased the antioxidants compared to control rats. Chronic exercise in hypoxic and normoxic rats increased MDA level and BDNF gene expression and decreased the antioxidants. Providing vitamin E supplementation to the hypoxic and normoxic rats significantly reduced MDA and BDNF gene expression and increased antioxidants. We conclude that sustained hypoxia and chronic exercise increased BDNF gene expression and induced oxidative stress. Moreover, vitamin E attenuated the oxidative stress and decreased BDNF gene expression in sustained hypoxia and chronic exercise which confirms the oxidative stress-induced stimulation of BDNF gene expression.

Abstract, Hyperlipidemia and oxidized-low-density lipoproteins (Ox-LDL) are important independent cardiovascular risk factors that have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. The purpose of the present study was to investigate the effect of vitamin E on Ox-LDL, lipid profile, C-reactive protein (CRP), and VSMC proliferation of rat aorta.....Conclusions: These findings strongly support the idea that diabetes induces Ox-LDL-mediated oxidative stress and VSMC proliferation in aorta of rat and imply that vitamin E has a strong protective effect as an antioxidant.

Abstract. Oxidative stress has been investigated in the context of alcoholic liver injury for many years and shown to be a causal factor of chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson's disease, and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays an important role in hepatocarcinogenesis. In cases with persistent hepatitis due to failure of hepatitis C virus eradication, or chronic liver disease, such as NASH, the treatment of which remains unestablished, it is important to reduce serum alanine aminotransferase levels and prevent liver fibrosis and development of hepatocellular carcinoma. This also suggests the importance of antioxidant therapy. Among treatment options where it would be expected that anti-inflammatory activity plays a role in their confirmed efficacy for chronic hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko-To, and vitamin E can all be considered antioxidant therapies. To date, however, the ability of these treatments to prevent cancer has been confirmed only in CHC. Nevertheless, anti-inflammatory and anti-fibrotic effects have been demonstrated in other liver diseases and these therapies may potentially be effective for cancer prevention.

Abstract. Recent studies have reported that remote organs are affected by renal ischemia reperfusion (IR). The present study investigates the role of vitamin E on the liver damage after renal IR. First, male mice were subjected to three groups (n = 9): 1) sham-operated, (2) renal IR (45 min ischemia), (3) renal IR + Vitamin E (150 mg/kg trough feeding tube for 28 d). After 24 h of reperfusion, animal were anesthetized for sample collections. Liver tissues malondialdehyde (MDA) increased and total glutathione (GSH) concentration decreased in the IR group compared to the sham group. Vitamin E consumption diminished the IR-induced increase in plasma AST and ALT. In addition, Vitamin E inhibited the IR-induced decrease in GSH activity and diminished IR-induced increase in MDA concentration. These findings showed that vitamin E consumption partly inhibited the IR-induced liver damage.

Abstract, There are several studies that relate oxidative damage as possible mechanism for many cancers. Many studies have also shown that anti-oxidants like selenium and vitamin E decrease the risk for prostate cancer. The main objective of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) study was to look for the benefits of selenium and vitamin E supplementation on prostate cancer. The study had a large sample size, stringent experimental conditions, very long duration, standardized laboratories for biochemical analyses and other factors that contribute to high external validity. The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations. Because of these conflicting results, many researchers argue about the methods used, supplementations administered (selenium and vitamin E) and indicators used for assessing levels of supplementations. We reviewed many epidemiological studies, clinical trials, and pre-clinical studies. With corroborative evidences we justify that SELECT study has a sound methodology and rationale. In lieu of the contrary results of the select study, researchers should focus on the probable mechanisms for these contrary findings and continue their search for newer and effective agents for prevention of prostate cancer.