the present study demonstrate that the two isomers of tocotrie- nols, alpha and gamma, render the hypercholesterolemic hearts resistant to ischemic reperfu- sion injury by lowering several hypercholesterolemic proteins and upregulating TGF-beta.” (Transforming growth factor beta is a protein that controls proliferation and cellular differ- entiation, as well as providing inflammation control.)33


Finally, tocotrienols regulate NF-kappaB, a protein complex that controls the transcription of DNA regulating genes that are critical for inflammation and immunity. NF-kappaB is particularly relevant to both chronic inflammation and can- cer. This may have relevance not only to any disease involv- ing inflammation, but also to aging, according to scientists Mary Kaileh, PhD and Ranjan Sen, PhD, of the Laboratory of Cellular and Molecular Biolo- gy at National Institute on Ag- ing, Baltimore, Maryland. “It is widely hypothesized that NF-kappaB dysregulation ac- companies human aging,” they note. “It is possible that regulat- ed consumption of tocotrienols may counter this form of chron- ic NF-kB dysregulation with- out seriously impacting acute NF-kB responses that are essen- tial for immune responses and thereby improve the quality of life of the elderly.”34


8 Focus April 2013


Tocotrienols are the Future of Vitamin E Research


Before soybean oil is refined to obtain alpha-tocopherol, gam- ma-tocopherol is plentiful in the raw material, but in concentrat- ing alpha-tocopherol, gamma-to- copherol was largely discarded. Recent research shows the criti- cal importance of balancing in- gestion of alpha-tocopherol with gamma-tocopherol, and gam- ma-balanced tocopherol formu- las are now favored.35


Likewise, tocotrienols obtained from fresh palm oil provide a rich balance of alpha-, beta-, gamma-, and delta-tocotrienols, along with a modest amount of tocopherols. As this newsletter shows, alpha-tocopherol does not interfere with the absorp- tion of tocotrienols, as long as alpha-tocopherol is not artifi- cially concentrated at excessive levels. In this particular case, nature offers a balanced combi- nation of various vitamin E frac- tions that can offer therapeutic potential without interfering with each other.


We know now that meaningful research on vitamin E must de- fine the isomer or isomers being studied. Studies that only look at alpha-tocopherol should not be titled as having researched “vita- min E”. And it is time for tocot- rienols to take their place in the forefront of vitamin E research. From the heart to the brain, from the liver to life itself, tocotrienols are proving to truly be the next generation Vitamin E.


References:


1. Personal interview with Chandan Sen, PhD, Jan- uary 27, 2013.


2. Sen CK, Khanna S, Sashwati R. Tocotrienol Neu- roprotection: The Most Potent Biological Function of All Natural Forms of Vitamin E. Micronutrient & Brain Health. CRC Press, 2009.


3. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK and Sethi G. Inflammation and cancer: How hot is the link? Biochem Pharmacol 72(11):1605–1621.


4. Aggarwal B, Nesaretnam K. Genes Nutr DOI 10.1007/s12263-0`1-0234 Springer Verlag


5. Prasad S, Sung B, Srivedi P, Gupta SC, Aggarwal BB, Tocotrienols, Inflammation and Cancer, How Are They Linked? Tocotrienols: Vitamin E Beyond Tocopherols, Second Edition. CRC Press 2012.


6. Kannappan R, Ravindran J, Prasad S et al (2010a) Gamma-tocotrienol promotes TRAIL-induced apoptosis through reactive oxygen species/ex- tracellular signal-regulated kinase/p53-mediated upregulation of death receptors. Mol Cancer Ther 9:2196–2207


7. Kannappan R, Yadav VR, Aggarwal BB (2010b) {Gamma}-tocotrienol but not {gamma}-tocopherol blocks STAT3 cell signaling pathway through in- duction of protein-tyrosine phosphatase SHP-1 and sensitizes tumor cells to chemotherapeutic agents. J Biol Chem 285:33520–33528


8. Personal Interview with Bharat B. Aggarwal, PhD, January 24, 2013


9. Sen CK, Khanna S, Roy S, Packer L. Molecular basis of vitamin E action. Tocotrienol potently inhib- its glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells. J Biol Chem. 2000 Apr 28;275(17):13049-55. PMID: 10777609


10. Khanna S, Roy S, Slivka A, Craft TK, Chaki S, Rink C, Notestine MA, DeVries AC, Parinandi NL, Sen CK. Neuroprotective properties of the natural vitamin E alpha-tocotrienol Stroke. 2005 Oct;36(10):2258-64.


11. Rink C, Christoforidis G, Abduljalil A, Kontzialis M, Bergdall V, Roy S, Khanna S, Slivka A, Knopp M, Sen CK. Minimally invasive neuroradiologic model of preclinical transient middle cerebral artery occlu- sion in canines. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14100-5. doi: 10.1073/pnas.0806678105.


12. Rink C, Christoforidis G, Khanna S, Peterson L, Patel Y, Khanna S, Abduljalil A, Irfanoglu O, Machi- raju R, Bergdall VK, Sen CK. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis. J Cereb Blood Flow Metab. 2011 Nov;31(11):2218-30. doi: 10.1038/jcb- fm.2011.85.


13. Rubin BY, Anderson SL, Kapás L. Can the thera- peutic efficacy of tocotrienols in neurodegenerative familial dysautonomia patients be measured clini- cally? Antioxid Redox Signal. 2008 Apr;10(4):837-41. doi: 10.1089/ars.2007.1874.


14. Anderson SL, Rubin BY Tocotrienols reverse IKAP and monoamine oxidase deficiencies in famil- ial dysautonomia.Biochem Biophys Res Commun. 2005 Oct 14;336(1):150-6.


15. Anderson SL, Qiu J, Rubin BY Tocotrienols in- duce IKBKAP expression: a possible therapy for familial dysautonomia.Biochem Biophys Res Com- mun. 2003 Jun 20;306(1):303-9.


16.http://www.fordham.edu/academics/pro- grams_at_fordham_/biological_sciences/faculty/ berish_y_rubin_27245.asp


17. Email interviews with Enrico Magosso PhD, Jan- uary 23-31, 2013


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