Tocotrienols : vitamin E beyond tocopherols

392 Pages·2013·20.224 MB·English

by  Barrie Tan, Ronald R Watson, Victor R Preedy

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Cover: Design & photography by Thong Vo of annatto seed pod with thanks to Harrison Tan for his assistance. Annatto (Bixa
orellana) is a plant from which tocopherol-free tocotrienol is obtained.
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Contents
Preface...............................................................................................................................................ix
Acknowledgments ..........................................................................................................................xiii
Editors ..............................................................................................................................................xv
Contributors ...................................................................................................................................xvii
Chapter 1 Tocotrienols in Plants: Occurrence, Biosynthesis, and Function .................................1
Maren Müller, Jana Cela, María A. Asensi-Fabado, and Sergi Munné-Bosch
Chapter 2 Safety of Unsaturated Vitamin E Tocotrienols and Their Isomers ............................17
Alexander G. Schauss, John R. Endres, and Amy Clewell
Chapter 3 Bioavailability and Metabolism of Tocotrienols ........................................................37
Zhihong Yang, Mao-Jung Lee, Shengmin Sang, and Chung S. Yang
Chapter 4 Bioavailability of Tocotrienols and Interference of Their Bioavailability
by α-Tocopherol Supplementation .............................................................................53
Saiko Ikeda, Tomono Uchida, and Chisato Abe
Chapter 5 Alpha-Tocopherol: A Detriment to Tocotrienol Benefits ...........................................61
Anne M. Trias and Barrie Tan
Chapter 6 Antiangiogenic Effects of Tocotrienol .......................................................................79
Takahiro Eitsuka, Kiyotaka Nakagawa, and Teruo Miyazawa
Chapter 7 Mechanism of Delta-Tocotrienol on Colorectal Cancer .............................................89
Sayori Wada and Yuji Naito
Chapter 8 Targeted Prostate Cancer Chemoprevention Trial with Tocotrienols ......................101
William L. Stone, Victoria P. Ramsauer, Sharon E. Campbell,
and Koymangalath Krishnan
Chapter 9 δ-Tocotrienol: Demethylated Vitamin E with Hormetic Function
and Therapeutic Application in Breast Cancer ........................................................117
Francesca Pilolli, Marta Piroddi, Elisa Pierpaoli, Silvia Ciffolilli,
Mauro Provinciali, and Francesco Galli
v
vi Contents
Chapter 10 Mevalonate-Suppressive Tocotrienols for Cancer Chemoprevention
and Adjuvant Therapy ..............................................................................................135
Huanbiao Mo, Manal Elfakhani, Anureet Shah, and Hoda Yeganehjoo
Chapter 11 Potential of Tocotrienols in Lung Cancer ................................................................151
Xiangming Ji, Arvind Goja, and Smiti V. Gupta
Chapter 12 Tocotrienols and Atherosclerosis: Potential in Cardioprotection .............................163
Hapizah Mohd Nawawi
Chapter 13 Tocotrienols: Viable Options for Managing Metabolic Diseases.............................185
Chi-Wai Wong
Chapter 14 Tocotrienols as Possible Treatments for Obesity ......................................................195
Wong Weng-Yew and Lindsay Brown
Chapter 15 Tocotrienols, Inflammation, and Cancer: How Are They Linked?..........................209
Sahdeo Prasad, Bokyung Sung, Sridevi Patchva, Subash C. Gupta,
and Bharat B. Aggarwal
Chapter 16 1-Modulating NF-κB Activity by Tocotrienols ........................................................225
Mary Kaileh and Ranjan Sen
Chapter 17 Antioxidant Action of Tocotrienols ..........................................................................233
Etsuo Niki
Chapter 18 Tocotrienol in Human Pancreatic Cancer ................................................................241
Mokenge P. Malafa and Kazim Husain
Chapter 19 Tocotrienols in the Treatment of Dyslipidemia ........................................................259
Mark Houston
Chapter 20 Tocotrienols and Vascular Effects ............................................................................267
Aida Hanum Ghulam Rasool
Chapter 21 Prolongevity Effects of Tocotrienols: Trials in Caenorhabditis elegans .................279
Noriko Kashima, Yukiko Fujikura, Tomomi Komura, Keiji Terao, Barrie Tan,
and Yoshikazu Nishikawa
Contents vii
Chapter 22 Anti-Tyrosinase Activity of Tocotrienol in Skin Blemishes .....................................291
Daniel Yee Leng Yap
Chapter 23 Tocotrienols and Bone Health ..................................................................................305
Ima Nirwana Soelaiman, Norazlina Mohamed, Ahmad Nazrun Shuid,
and Norliza Muhammad
Chapter 24 Tocotrienol and Physiology of Reproduction ...........................................................323
M.H. Rajikin, N. Mokhtar, A. Chatterjee, and Y.S. Kamsani
Chapter 25 Tocotrienol and Tocopherol in Stress-Induced Gastric Mucosal Injury ..................333
Nafeeza Mohd Ismail and Ibrahim Abdel Aziz Ibrahim
Chapter 26 Structural Modification of Tocotrienols to Improve Bioavailability ........................359
Awantika Singh, Philip J. Breen, Sanchita Ghosh,
K. Sree Kumar, Kottayil I. Varughese, Peter A. Crooks, Martin Hauer-Jensen,
and Cesar M. Compadre

Preface
For 90 years, vitamin E research has produced prolific and notable discoveries, including
isolation from plants, chemical identifications, and total syntheses. Until the last few decades,
however, attention has been given mostly to the biological activities and underlying mechanisms
of alpha-tocopherol, which we now know is only one of more than eight vitamin E isomers.
Beginning in 1922 with the announcement by Herbert Evans and Katherine Bishop that “the mys-
terious substance X” would henceforth be known as vitamin E, “a hitherto unrecognized dietary
factor essential for reproduction” [1], there have been many good days for the science of this
“birth vitamin.” Following the discovery of vitamin E’s antioxidant function [2], the preponder-
ant research in subsequent decades (1965–1985) focused on food protection, an activity offered
particularly by, once again, alpha-tocopherol [3].
Tocotrienol discovery came much later, in 1965 [4,5], but existed for almost 20 years as an
obscure vitamin E [6]. Vitamin E was erroneously named tocopherol, an error that remained uncor-
rected [7] for 30 years—appearing as such in the Merck Index as recently as 1996—until eventu-
ally changed in 2001 [8]. Recognition for tocotrienol began to emerge in the early 1980s at the
University of Wisconsin, Madison, through the efforts of Asaf Qureshi and Charles Elson. They
were the first to delineate the function of tocotrienol to lower cholesterol [9,10]. The mechanism,
initially shown by a group at Bristol-Myers Squibb (1992) [11], was validated nearly 15 years later at
the University of Texas, Dallas (2006) [12], by studies on the regulation of HMG CoA reductase by
delta-tocotrienol and gamma-tocotrienol, but not alpha-tocopherol. This 2006 study was endorsed
by Joseph Goldstein and Michael Brown, the 1985 Nobel Prize recipients for the discovery of the
LDL receptor [13]. Another noteworthy development took place in 1985 when the ability of tocotri-
enol, but not alpha-tocopherol, to inhibit tumors was first shown [14,15] by the research group with
Kanki Komiyama of Kitasato Institute, Tokyo, Japan.
I personally became very excited about tocotrienols back in 1982. I remember meeting A. Kato
who was working on vitamin E and cancer inhibition when almost everyone was talking about
“rich vitamin E” in palm oil. I became curious to figure out more about this vitamin E. In 1983,
I met Asaf Qureshi and Charles Elson at an annual Palm Oil Research Institute of Malaysia grant
update meeting, and even then they had a hunch that alpha-tocotrienol may not be the strongest
tocotrienol for cholesterol reduction. Subsequently, I continued to follow the flow of research and
clinical trials while developing patents for extracting tocotrienols from natural sources—initially
palm, and then rice and annatto.
Tocotrienols have now stepped into the limelight of vitamin E research and have proven
to contain some exceptional benefits that are not shared by their “older” tocopherol siblings.
Today, the brightest spot for tocotrienol research is in cancer and CVD (Figure F.1). Tocopherols
and tocotrienols are powerful antioxidants—known as early as 1937 [2]—for improving food
protection and are shown today [16] to potentially protect from cognitive decline. This anti-
oxidant vitamin E function never gets old! Emergent fields of tocotrienol research are promis-
ing—with many covered in this volume—including angiogenesis, bioavailability, bone health,
gastric injury, inflammation, life extension, obesity, radiation protection, skin health, tocopherol
interference, and, recently, cognitive impairment.
The availability of tocotrienol samples and standards has helped to catalyze the research for-
ward. The three major sources of tocotrienols are rice, palm, and annatto. The ratio of tocopherol-
to-tocotrienol in each is 50:50, 25:75, and 0.1:99.9, respectively [17]. Tocotrienol’s natural abundance
is important as alpha-tocopherol has repeatedly been shown to be ineffective, or worse, to interfere
with the function of tocotrienols.
ix
x Preface
Cancer
e)
v CVD and
elati diabetes
r
s (
n
o
ati Antioxidant
c
bli
u
P
Other
1980–1990 1990–2000 2000–2010 2010–2020
Time line (decades)
FIGURE F.1 Progress in tocotrienol research.
Research published in the last decade warranted the publication of the first-ever tocotrienol book,
forwarded by Chandan Sen, indicating a wealth of vitamin E literature (greater than 95%) focused
on alpha-tocopherol. Currently, tocotrienols have reached a new measure of research height: more
than one-third of all vitamin E tocotrienol research of the last 30 years was published in the last
3 years (2009–2011). The thriving field of tocotrienol research gives ground for this second edi-
tion, launched in conjunction with the 103rd Annual AOCS Meeting (April 29, 2012, Long Beach,
California). It is an excellent time to continue the vitamin E research with a new focus on tocotri-
enols, the late arrival in the vitamin E family.
Barrie Tan
American River Nutrition
Hadley, Massachusetts
REFERENCES
1. Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduc-
tion. Science 1922 (December 8); LVI: 650–651.
2. Olcott HS, Emerson OH. Antioxidants and autoxidation of fats: The antioxidant properties of tocopher-
ols. J Am Chem Soc 1937; 59: 1008–1009.
3. Eitenmillar R, Lee J. Vitamin E: Food Chemistry, Composition and Analysis, Marcel Dekker, New York, 2004.
4. Pennock JF et al., Reassessment of tocopherol chemistry. BBRC 1964; 17: 542–548.
5. Whittle KJ et al., The isolation and properties of delta-tocotrienol from Hevea latex. Biochem J 1966;
100: 138–145.
6. Tan B, Appropriate spectrum vitamin E and new perspectives on desmethyl tocopherols and tocotrienols.
J Am Nutr Assoc 2005; 8: 35–42.
7. Merck Index, Tocols: 9631 through 9638, 12th edn. Merck Publishing Group, Rahway, NJ, 1996,
pp. 1620–1621.
8. Merck Index, Tocols: 9570 through 9577, 13th edn. Merck Publishing Group, Rahway, NJ, 2001,
pp. 1693–1694.
9. Burger WC et al., Effects of different fractions of the barley kernel on the hepatic lipid metabolism of
chickens. Lipids 1982; 17: 956–963.
10. Qureshi AA et al., The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol
Chem 1986; 261: 10544–10550.
11. Pearce BC et al., Hypercholesterolemic activity of synthetic and natural tocotrienols. J Med Chem 1992;
35: 3595–3606.