Vitamin E is a lipid-soluble antioxidant that inhibits lipid peroxidation by scavenging reactive oxygen species, and it is thought to protect against the aging process. Indeed, it is one of the most popular supplements in the US. However, recent studies have revealed that vitamin E has dual effects on the aging process. We discovered that α-tocopherol, the major form of vitamin E in the body, stimulates osteoclast fusion and bone resorption as well as induces an osteoporosis-like phenotype in rodents. Clinical intervention trials have also demonstrated that supplementation with vitamin E is neutral or even harmful for preventing age-related diseases in humans. Therefore, the role of vitamin E as an ‘anti-ager' has been called into question. This review outlines the present understanding of the role of vitamin E in age-related disease prevention.

Mocchegiani E, Costarelli L, Giacconi R, Malavolta M, Basso A, Piacenza F, Ostan R, Cevenini E, Gonos ES, Franceschi C, Monti D: Vitamin E-gene interactions in aging and inflammatory age-related diseases: Implications for treatment. A systematic review. Ageing Res Rev 2014;14:81-101.
Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N: The diagnosis of osteoporosis. J Bone Miner Res 1994;9:1137-1141.
Fujita K, Iwasaki M, Ochi H, Fukuda T, Ma C, Miyamoto T, Takitani K, Negishi-Koga T, Sunamura S, Kodama T, Takayanagi H, Tamai H, Kato S, Arai H, Shinomiya K, Itoh H, Okawa A, Takeda S: Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat Med 2012;18:589-594.
Iwaniec UT, Turner RT, Smith BJ, Stoecker BJ, Rust A, Zhang B, Vasu VT, Gohil K, Cross CE, Traber MG: Evaluation of long-term vitamin E insufficiency or excess on bone mass, density, and microarchitecture in rodents. Free Radic Biol Med 2013;65:1209-1214.
Ha H, Lee JH, Kim HN, Lee ZH: α-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity. Biochem Biophys Res Commun 2011;406:546-551.
Lee JH, Kim HN, Yang D, Jung K, Kim HM, Kim HH, Ha H, Lee ZH: Trolox prevents osteoclastogenesis by suppressing RANKL expression and signaling. J Biol Chem 2009;284:13725-13734.
Norazlina M, Chua CW, Ima-Nirwana S: Vitamin E deficiency reduced lumbar bone calcium content in female rats. Med J Malaysia 2004;59:623-630.
Mehat MZ, Shuid AN, Mohamed N, Muhammad N, Soelaiman IN: Beneficial effects of vitamin E isomer supplementation on static and dynamic bone histomorphometry parameters in normal male rats. J Bone Miner Metab 2010;28:503-509.
Shuid AN, Mehat Z, Mohamed N, Muhammad N, Soelaiman IN: Vitamin E exhibits bone anabolic actions in normal male rats. J Bone Miner Metab 2010;28:149-156.
Soeta S, Higuchi M, Yoshimura I, Itoh R, Kimura N, Aamsaki H: Effects of vitamin E on the osteoblast differentiation. J Vet Med Sci 2010;72:951-957.
Urban K, Hohling HJ, Luttenberg B, Szuwart T, Plate U: An in vitro study of osteoblast vitality influenced by the vitamins C and E. Head Face Med 2012;8:25.
Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN: Two different isomers of vitamin E prevent bone loss in postmenopausal osteoporosis rat model. Evid Based Complement Alternat Med 2012;2012:161527.
Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S: Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone. Clin Exp Pharmacol Physiol 2005;32:761-770.
Ima-Nirwana S, Suhaniza S: Effects of tocopherols and tocotrienols on body composition and bone calcium content in adrenalectomized rats replaced with dexamethasone. J Med Food 2004;7:45-51.
Mohamad S, Shuid AN, Mohamed N, Fadzilah FM, Mokhtar SA, Abdullah S, Othman F, Suhaimi F, Muhammad N, Soelaiman IN: The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model. Clinics (Sao Paulo) 2012;67:1077-1085.
Chai SC, Wei CI, Brummel-Smith K, Arjmandi BH: The role of vitamin E in reversing bone loss. Aging Clin Exp Res 2008;20:521-527.
Smith BJ, Lucas EA, Turner RT, Evans GL, Lerner MR, Brackett DJ, Stoecker BJ, Arjmandi BH: Vitamin E provides protection for bone in mature hindlimb unloaded male rats. Calcif Tissue Int 2005;76:272-279.
Tsugawa N, Shiraki M, Suhara Y, Kamao M, Ozaki R, Tanaka K, Okano T: Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Miner Metab 2008;26:79-85.
Frank J, Weiser H, Biesalski HK: Interaction of vitamins E and K: effect of high dietary vitamin E on phylloquinone activity in chicks. Int J Vitam Nutr Res 1997;67:242-247.
Takahashi O, Ichikawa H, Sasaki M: Hemorrhagic toxicity of D-alpha-tocopherol in the rat. Toxicology 1990;63:157-165.
Wheldon GH, Bhatt A, Keller P, Hummler H: D,1-alpha-tocopheryl acetate (vitamin E): a long term toxicity and carcinogenicity study in rats. Int J Vitam Nutr Res 1983;53:287-296.
Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A: Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab 2003;88:1523-1527.
Wolf RL, Cauley JA, Pettinger M, Jackson R, Lacroix A, Leboff MS, Lewis CE, Nevitt MC, Simon JA, Stone KL, Wactawski-Wende J: Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative. Am J Clin Nutr 2005;82:581-588.
Hamidi MS, Corey PN, Cheung AM: Effects of vitamin E on bone turnover markers among us postmenopausal women. J Bone Miner Res 2012;27:1368-1380.
Michaëlsson K, Wolk A, Byberg L, Arnlov J, Melhus H: Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies. Am J Clin Nutr 2014;99:107-114.
Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC: Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-1456.
Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC: Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444-1449.
Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM: Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 1996;334:1156-1162.
Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE: Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005;294:56-65.
Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR: Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-1347.
Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37-46.
Halliwell B: Free radicals and antioxidants: updating a personal view. Nutr Rev 2012;70:257-265.
Vardi M, Blum S, Levy AP: Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus - natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature. Eur J Intern Med 2012;23:628-632.
Song BL, DeBose-Boyd RA: Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. J Biol Chem 2006;281:25054-25061.
Minhajuddin M, Beg ZH, Iqbal J: Hypolipidemic and antioxidant properties of tocotrienol rich fraction isolated from rice bran oil in experimentally induced hyperlipidemic rats. Food Chem Toxicol 2005;43:747-753.
Chin SF, Ibahim J, Makpol S, Abdul Hamid NA, Abdul Latiff A, Zakaria Z, Mazlan M, Mohd Yusof YA, Abdul Karim A, Wan Ngah WZ: Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: a randomized controlled study. Nutr Metab (Lond) 2011;8:42.
Sharma R, Vinayak M: Alpha-tocopherol prevents lymphoma by improving antioxidant defence system of mice. Mol Biol Rep 2013;40:839-849.
Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO: Antioxidants accelerate lung cancer progression in mice. Sci Transl Med 2014;6:221ra15.
Goodman GE, Schaffer S, Omenn GS, Chen C, King I: The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev 2003;12:518-526.
Mahabir S, Schendel K, Dong YQ, Barrera SL, Spitz MR, Forman MR: Dietary alpha-, beta-, gamma- and delta-tocopherols in lung cancer risk. Int J Cancer 2008;123:1173-1180.
Weinstein SJ, Wright ME, Lawson KA, Snyder K, Mannisto S, Taylor PR, Virtamo J, Albanes D: Serum and dietary vitamin e in relation to prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2007;16:1253-1259.
Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Sesso HD, Buring JE: Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 2009;301:52-62.
Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549-1556.
Barve A, Khor TO, Reuhl K, Reddy B, Newmark H, Kong AN: Mixed tocotrienols inhibit prostate carcinogenesis in tramp mice. Nutr Cancer 2010;62:789-794.
Wada S, Satomi Y, Murakoshi M, Noguchi N, Yoshikawa T, Nishino H: Tumor suppressive effects of tocotrienol in vivo and in vitro. Cancer Lett 2005;229:181-191.
Ling MT, Luk SU, Al-Ejeh F, Khanna KK: Tocotrienol as a potential anticancer agent. Carcinogenesis 2012;33:233-239.
Tiwari RV, Parajuli P, Sylvester PW: Gamma-tocotrienol-induced autophagy in malignant mammary cancer cells. Exp Biol Med (Maywood) 2014;239:33-44.
Yatin SM, Varadarajan S, Butterfield DA: Vitamin E prevents Alzheimer's amyloid beta-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimers Dis 2000;2:123-131.
Voronkov M, Braithwaite SP, Stock JB: Phosphoprotein phosphatase 2A: a novel druggable target for Alzheimer's disease. Future Med Chem 2011;3:821-833.
Nishida Y, Yokota T, Takahashi T, Uchihara T, Jishage K, Mizusawa H: Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse. Biochem Biophys Res Commun 2006;350:530-536.
Desrumaux C, Pisoni A, Meunier J, Deckert V, Athias A, Perrier V, Villard V, Lagrost L, Verdier JM, Maurice T: Increased amyloid-beta peptide-induced memory deficits in phospholipid transfer protein (PLTP) gene knockout mice. Neuropsychopharmacology 2013;38:817-825.
Mangialasche F, Westman E, Kivipelto M, Muehlboeck JS, Cecchetti R, Baglioni M, Tarducci R, Gobbi G, Floridi P, Soininen H, Kloszewska I, Tsolaki M, Vellas B, Spenger C, Lovestone S, Wahlund LO, Simmons A, Mecocci P: Classification and prediction of clinical diagnosis of Alzheimer's disease based on MRI and plasma measures of α-/γ-tocotrienols and gamma-tocopherol. J Intern Med 2013;273:602-621.
Mangialasche F, Kivipelto M, Mecocci P, Rizzuto D, Palmer K, Winblad B, Fratiglioni L: High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age. J Alzheimers Dis 2010;20:1029-1037.
Mangialasche F, Solomon A, Kareholt I, Hooshmand B, Cecchetti R, Fratiglioni L, Soininen H, Laatikainen T, Mecocci P, Kivipelto M: Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Exp Gerontol 2013;48:1428-1435.
Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, Scherr PA: Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 2005;81:508-514.
Mangialasche F, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, Cecchetti R, Baglioni M, Simmons A, Soininen H, Tsolaki M, Kloszewska I, Vellas B, Lovestone S, Mecocci P: Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiol Aging 2012;33:2282-2290.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.