Life Extension Magazine January 2011
Critical Importance of Gamma E Tocopherol Continues to Be Overlooked
By Kirk Stokel
Neurodegenerative Disease Defense
A particularly dangerous free radical known as reactive nitrogen species has been implicated in Alzheimer’s disease. High intakes of vitamins C and E have been associated with substantially lower risk of age-related neurodegenerative diseases such as Alzheimer’s.31,32 Gamma tocopherol scavenges reactive nitrogen species and may prove beneficial in reducing the impact of the disease.33
Neurodegenerative diseases also have a large inflammatory component. Human trials of supplemental vitamin E in neurodegenerative diseases have almost exclusively used alpha tocopherol, leading many experts to call for new studies using gamma tocopherol because of its more potent anti-inflammatory effects.5 In a mouse model of Parkinson’s disease, gamma tocopherol was more effective than alpha tocopherol at preventing loss of the essential neurotransmitter dopamine, the chemical defect that produces Parkinson’s symptoms.34
Combating Inflammatory Airway Diseases: Allergies and Asthma
Asthma and allergies are closely related conditions that are triggered by our immune system going into red alert in response to substances in the environment. In numerous studies, gamma tocopherol prevents migration of inflammatory cells into the airways at the beginning of an attack of asthma or allergic rhinitis, and also reduces overgrowth of mucous cells in the nose and upper airways.35 Gamma tocopherol supplementation decreases overall oxidative stress and suppresses excessive release of inflammatory cytokines in both normal and asthmatic human subjects.36
Oxidant molecules such as ozone are particularly dangerous for people who suffer from these inflammatory airway conditions.37 Studies of gamma tocopherol have shown broad anti-inflammatory effects in allergic animals experiencing airway inflammation by exposure to ozone.37,38
Vitamin E is one of the earliest-known and best-studied vitamins. Published studies demonstrate that people with higher intakes of gamma tocopherol may achieve a considerable reduction in their risks of common age-related diseases.
Regrettably, most health conscious individuals take only alpha tocopherol and are deprived of the optimal and synergistic benefits provided by the gamma tocopherol form of vitamin E.
Human studies indicate benefits with supplemental doses ranging from 100 mg to 800 mg of gamma tocopherol a day. A review of the scientific literature indicates that most people should supplement with at least 200 mg of gamma tocopherol each day.1,39
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2. 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.
3. Devaraj S, Leonard S, Traber MG, Jialal I. Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome. Free Radic Biol Med. 2008 Mar 15;44(6):1203-8.
4. Brigelius-Flohe R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999 Jul;13(10):1145-55.
5. Usoro OB, Mousa SA. Vitamin E forms in Alzheimer’s disease: a review of controversial and clinical experiences. Crit Rev Food Sci Nutr. 2010 May;50(5):414-9.
6. Galli F, Azzi A. Present trends in vitamin E research. Biofactors. 2010 Jan;36(1):33-42.
7. Devaraj S, Traber MG. Gamma-tocopherol, the new vitamin E? Am J Clin Nutr. 2003 Mar;77(3):530-1.
8. Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11494-9.
9. Jiang Q, Ames BN. Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J. 2003 May;17(8):816-22.
10. Fischer CP, Hiscock NJ, Basu S, et al. Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans. J Appl Physiol. 2006 May;100(5):1679-87.
11. Himmelfarb J, Phinney S, Ikizler TA, Kane J, McMonagle E, Miller G. Gamma-tocopherol and docosahexaenoic acid decrease inflammation in dialysis patients. J Ren Nutr. 2007 Sep;17(5):296-304.
12. Li D, Saldeen T, Romeo F, Mehta JL. Relative effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation and superoxide dismutase and nitric oxide synthase activity and protein expression in rats. J Cardiovasc Pharmacol Ther. 1999 Oct;4(4):219-26.
13. McCarty MF. Gamma-tocopherol may promote effective no synthase function by protecting tetrahydrobiopterin from peroxynitrite. Med Hypotheses. 2007;69(6):1367-70.
14. Saito F, Iwamoto S, Yamauchi R. Reaction products of gamma-tocopherol with (E)-4-oxo-2-nonenal in acidic acetonitrile. Biosci Biotechnol Biochem. 2010;74(1):168-74.
15. Mishima K, Tanaka T, Pu F, et al. Vitamin E isoforms alpha-tocotrienol and gamma-tocopherol prevent cerebral infarction in mice. Neurosci Lett. 2003 Jan 30;337(1):56-60.
16. Singh I, Turner AH, Sinclair AJ, Li D, Hawley JA. Effects of gamma-tocopherol supplementation on thrombotic risk factors. Asia Pac J Clin Nutr. 2007;16(3):422-8.
17. Vucinic L, Singh I, Spargo FJ, Hawley JA, Linden MD. Gamma tocopherol supplementation prevents exercise induced coagulation and platelet aggregation. Thromb Res. 2010 Feb;125(2):196-9.
18. Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN. gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3217-22.
19. Stone WL, Papas AM. Tocopherols and the etiology of colon cancer. J Natl Cancer Inst. 1997 Jul 16;89(14):1006-14.
20. Moyad MA, Brumfield SK, Pienta KJ. Vitamin E, alpha- and gamma-tocopherol, and prostate cancer. Semin Urol Oncol. 1999 May;17(2):85-90.
21. Gysin R, Azzi A, Visarius T. Gamma-tocopherol inhibits human cancer cell cycle progression and cell proliferation by down-regulation of cyclins. FASEB J. 2002 Dec;16(14):1952-4.
22. Campbell SE, Stone WL, Whaley SG, Qui M, Krishnan K. Gamma (gamma) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (gamma) expression in SW 480 human colon cancer cell lines. BMC Cancer. 2003 Oct 1;3:25.
23. Stone WL, Krishnan K, Campbell SE, Qui M, Whaley SG, Yang H. Tocopherols and the treatment of colon cancer. Ann N Y Acad Sci. 2004 Dec;1031:223-33.
24. Campbell SE, Musich PR, Whaley SG, et al. Gamma tocopherol upregulates the expression of 15-S-HETE and induces growth arrest through a PPAR gamma-dependent mechanism in PC-3 human prostate cancer cells. Nutr Cancer. 2009;61(5):649-62.
25. Jiang Q, Wong J, Ames BN. Gamma-tocopherol induces apoptosis in androgen-responsive LNCaP prostate cancer cells via caspase-dependent and independent mechanisms. Ann N Y Acad Sci. 2004 Dec;1031:399-400.
26. Takahashi S, Takeshita K, Seeni A, et al. Suppression of prostate cancer in a transgenic rat model via gamma-tocopherol activation of caspase signaling. Prostate. 2009 May 1;69(6):644-51.
27. Jiang Q, Wong J, Fyrst H, Saba JD, Ames BN. Gamma-tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17825-30.
28. Wells SR, Jennings MH, Rome C, Hadjivassiliou V, Papas KA, Alexander JS. Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells. J Nutr Biochem. 2010 Jul;21(7):589-97.
29. Ju J, Picinich SC, Yang Z, et al. Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis. 2010 Apr;31(4):533-42.
30. Spaccarotella KJ, Kris-Etherton PM, Stone WL, et al. The effect of walnut intake on factors related to prostate and vascular health in older men. Nutr J. 2008;7:13.
31. Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002 Jun 26;287(24):3223-9.
32. Morris MC, Evans DA, Tangney CC, et al. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr. 2005 Feb;81(2):508-14.
33. Williamson KS, Gabbita SP, Mou S, et al. The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain. Nitric Oxide. 2002 Mar;6(2):221-7.
34. Itoh N, Masuo Y, Yoshida Y, Cynshi O, Jishage K, Niki E. gamma-Tocopherol attenuates MPTP-induced dopamine loss more efficiently than alpha-tocopherol in mouse brain. Neurosci Lett. 2006 Jul 31;403(1-2):136-40.
35. Wagner JG, Jiang Q, Harkema JR, et al. Gamma-tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma. Clin Exp Allergy. 2008 Mar;38(3):501-11.
36. Wiser J, Alexis NE, Jiang Q, et al. In vivo gamma-tocopherol supplementation decreases systemic oxidative stress and cytokine responses of human monocytes in normal and asthmatic subjects. Free Radic Biol Med. 2008 Jul 1;45(1):40-9.
37. Wagner JG, Jiang Q, Harkema JR, et al. Ozone enhancement of lower airway allergic inflammation is prevented by gamma-tocopherol. Free Radic Biol Med. 2007 Oct 15;43(8):1176-88.
38. Wagner JG, Harkema JR, Jiang Q, Illek B, Ames BN, Peden DB. Gamma-tocopherol attenuates ozone-induced exacerbation of allergic rhinosinusitis in rats. Toxicol Pathol. 2009;37(4):481-91.
39. Hensley K, Benaksas EJ, Bolli R, et al. New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine. Free Radic Biol Med. 2004 Jan 1;36(1):1-15.