Choosing the right vitamin E |
by W.H. Leong
 itamin E supplementation used to be a simple proposition. A recent survey commissioned by the Council for Responsible Nutrition, US (CRN) has concluded that 75 percent of cardiologists recommend vitamin E to their patients and about half of the cardiologists surveyed said they personally use vitamin E.
There are new scientific studies published practically every week about vitamin E. Despite these publications, we have been inundated lately with extensive human studies, questioning the benefits of alpha tocopherol form of vitamin E in preventing cardiovascular diseases. Numerous objections were raised against these trials—most notably the doses used—but the real problem may have been that alpha-tocopherol does not in itself provide the right vitamin E activity and protection for the heart. These studies were carried out with regular commercial vitamin E supplements that did not contain tocotrienols and other forms of tocopherols (i.e. gamma tocopherol), which might explain some of the
inconsistent results in these controlled studies.
Vitamin E research has progressed to the
point where scientists have identified different
forms of natural vitamin E (i.e.: gamma-tocopherol
and tocotrienols) that confer better
protection against the various types of free
radical damages as well as having additional
unique properties in reducing the risk of cardiovascular
disease. Now scientists believe that more
than one type of vitamin E should be a part of a
long-term nutritional or supplement program.
Tocotrienols are fat-soluble vitamins related
to the family of tocopherols. The term vitamin E
is now considered to be the generic name
describing both the tocopherols and tocotrienols.
However, tocopherols and tocotrienols are distinguished
by their side tail. While tocopherol has a
saturated side tail, tocotrienol possesses an unsaturated
side tail. Tocopherols and tocotrienols are
further separated into individual compounds
assigned by the Greek letter prefixes (a, b, d, g)
depending on the number and position of methyl
substitution (-CH3) on the chromanol ring.
In nature, plants, fruits and vegetables
produce both forms of vitamin E—tocopherols
and tocotrienols. While tocopherols are generally
present in common vegetable oils (i.e. soy,
canola, wheat germ, sunflower), tocotrienols, on
the other hand, are concentrated in cereal grains
(i.e. oat, barley, rye, rice bran), with the richest
source found in palm (Elaeis guineensis).
Almost all vitamin E supplements contain
tocopherol (mainly the alpha-tocopherol form)
but not tocotrienols. It doesn’t matter whether
you take natural or synthetic vitamin E, the form
used is almost always tocopherol. There is nothing
wrong with alpha-tocopherol but if a person
expects to obtain the optimal vitamin E antioxidant
protection, s/he should take the full spectrum vitamin E that consists of both the
tocopherols and tocotrienols as produced
in nature.
Scientific Rationale for a Full Spectrum
Vitamin E Complex
Vitamin E products currently available on the
shelves of most health food stores consist mainly
of alpha-tocopherol. In order to produce these
alpha-tocopherol products, the original natural
mixed tocopherol (alpha, beta, gamma and delta
tocopherol—as extracted from soybeans—also
called “non-alpha tocopherol”) is converted to a
single alpha tocopherol isomer by a chemical
process called methylation. What this means to
consumers is that their “natural” vitamin E
formulas may not be so “natural” after all.
Unfortunately we have prematurely pinpointed a
single compound, alpha-tocopherol, as the
“magic” vitamin E. This has caused many of us to
“miss the boat” when shopping for a vitamin E
supplement.
Antioxidant Network—Regeneration Efficiency
The tocotrienols’ unique chemical structures
(unsaturated side tail) allow them to move
around more freely and efficiently in cell
membranes. As a result, tocotrienols can rush in
to intercept and neutralize free radicals more
efficiently than can tocopherols. Tocotrienols’
greater mobility allows them to get
“recharged”/“regenerated” more quickly by
vitamin C or glutathione, in a network of antioxidants
in the cells. The “regeneration effect” as
part of the antioxidant network is vital in
prolonging the vitamin E antioxidant potency. In
fact, when antioxidant recycling fails, vitamin E
molecules can actually become free radicals
themselves, accelerating damage through a
process known as tocopherol-mediated peroxidation
(TMP).
Full Spectrum Vitamin E—“The E Complex”
In nature there are eight forms of vitamin E—4
forms of tocopherols and four forms of
tocotrienols (alpha-, beta-, gamma- and deltatocopherol
and corresponding tocotrienols). All
these forms of vitamin E work synergistically as a
team to confer the maximum antioxidant and
cardiovascular protection. Some other examples
are mixed carotenoids instead of single betacarotene
alone, B complex instead of a single B6
or B12 vitamin alone.
The idea that one single form of vitamin E—
alpha-tocopherol out of eight fractions is the
“magic” vitamin E and assuming that the other
forms are worthless denies the very fact that
nature put seven other tocopherols and
tocotrienols out there for a reason.
Natural Mixed Tocopherols
It is now known that taking too much alpha-tocopherol
both depletes the body of other
vitamin E members, especially gamma-tocopherol
but also tends to reduce the cholesterol reduction
effect of tocotrienols.
A recent study published in the proceedings
of the National Academy of Sciences suggests that
it could be dangerous to take high doses of alpha
tocopherol without also consuming gamma tocopherol.
What made this study interesting was that
it showed that high doses of alpha tocopherol
could displace gamma tocopherol in tissues.
Studies show that vitamin E’s gamma tocopherol
form may be more potent than alpha tocopherol
in suppressing damaging free
radicals. While alpha tocopherol inhibits the
production of free radicals to some degree, it is
gamma tocopherol that is required to trap and
neutralize existing free radicals, as well as key oxidizing
agents that generate free radicals. One dangerous
free radical producing compound that
gamma tocopherol inhibits strongly is peroxynitrite,
which is harmful to cells because of its powerful
oxidizing and nitrating properties. There is a
substantial research documenting the ability of
gamma tocopherol to protect brain cells against
peroxynitrite damage.
Gamma-tocopherol was also reported to be
not only significantly more potent than alphatocopherol
in delaying blood clot formation in
arteries but decreases superoxide free radical
generation in arteries, lipid peroxidation, LDL
oxidation and increases naturally produced superoxide
dismutase activity.
An in vitro study conducted at the University
of Michigan, which compared the effects of alphaand
gamma-tocopherol supplementation on
prostate cancer, found that the gamma form was
superior for inhibiting cancer growth. Similarly, a
recent study published in the Journal of National
Cancer Institute advocated the combined usage of
alpha- and gamma-tocopherol in the prevention
of prostate cancer.
In one of the latest published studies,
researchers at the University of Uppsala, Sweden compared the effect of alpha-tocopherol and
mixed tocopherol in reducing hydrogen peroxideinduced
lipid peroxidation in human
erythrocytes. Interestingly, it was found that the
uptake of gamma and delta-tocopherol by the cells
was much higher than alpha-tocopherol. The
results of the study also indicated that both the
alpha-tocopherol and mixed tocopherol
protected the cells from lipid peroxidation.
However, the mixed tocopherol (alpha, gamma
and delta tocopherol) showed a significantly
stronger inhibitory effect on lipid peroxidation in
human erythrocytes, which could be due to the
higher uptake of gamma and delta-tocopherol by
the cells.
Natural Mixed Tocotrienols
Human studies have shown that palm tocotrienol
complex has the ability to reverse blockage of the
carotid artery and platelet aggregation (i.e. blood
clotting), thereby reducing the risk of stroke,
atherosclerosis, and other heart disease-related
problems. The normal tocopherol vitamin E does
not have this ability.
Palm tocotrienol complex, as demonstrated
by both human and animal studies, can reduce
the production of serum cholesterol. Tocopherol
does not have this effect. The tocotrienol works by
inhibiting cholesterol production in the liver. In
one study (American Journal Clinical Nutrition),
42 milligrams of palm tocotrienols per day
reduced total cholesterol between 5 to 35.9
percent in 4-6 weeks. More good news is that the
HDL level (the “good cholesterol”) was not
affected. The normal tocopherol has no effect on
cholesterol level.
Studies conducted at the University of
Hawaii showed that palm tocotrienol complex,
especially the delta-tocotrienol fraction, inhibits
the production of vascular adhesion molecules.
Hence this suggests that tocotrienols may reduce
the risk of developing plaque, the hallmark of
atherosclerosis.
Six independent research centers in the world
have demonstrated that these particular
tocotrienols potently inhibit both the estrogenpositive
and estrogen-negative breast cancer cells.
The delta and gamma forms of tocotrienol can
inhibit certain types of cancer cell growth, with the
most research carried out on human breast cancer
cells. Alpha-tocopherol, on the other hand,
showed no significant effect.
The protective effect of tocotrienol as an
antioxidant is significantly higher than that of the
common form of vitamin E, alpha-tocopherol.
Studies continue to show that tocotrienols can be
considered as a potent natural antioxidant capable
of protecting cellular membranes against oxidative
damage. Researchers at the University of
California, Berkeley, showed that alphatocotrienol
is 40 to 60 times more powerful than
alpha-tocopherol in the prevention of lipid peroxidation.
Lipid peroxidation leads to free radicals,
the underlying cause of cardiovascular disease.
Research has also shown that tocotrienols
lower apolipoprotein B (apoB) and lipoprotein(a),
two known risk factors for cardiovascular disease.
Studies with test animals showed that palm
tocotrienol complex is a more potent form of
vitamin E than alpha-tocopherol in protecting
brain cells against oxidative damage and thereby
from the ensuing adverse alterations that accompany
aging.
Lipid peroxides in blood vessels and plasma
showed a positive correlation with blood pressure.
The antioxidant ability of tocotrienols may
prevent development of increased blood pressure
and hypertension by reducing lipid peroxides and
enhancing the total antioxidant status, including
superoxide dismutase activity.
Studies conducted at the University of
California showed that tocotrienols preferentially
accumulate at the strata corneum (uppermost 5
microns) of the skin. This is not surprising, given
the fact that being a more potent antioxidant,
tocotrienols may well turn out to be the skin’s first
line of defense against oxidative stress generated by
UV irradiation and other environmental
pollutants. This unique distribution shown by
tocotrienols suggests that given the right ingredients,
the body naturally knows how to protect
itself by distributing them to the right organs in
the body.
The Blood Pressure Regulator
Since the 1960s, researchers have been searching
for the molecule in the body that
regulates the release of excess water held in the
space between its cells, called the body’s pool of
extracellular fluid. Finding this factor is not just a
scientific curiosity because retaining too much of
this extracellular fluid raises blood pressure as well
as increasing the risk of congestive heart failure
and cirrhosis. In 1996, researchers at Loma Linda
University finally identified this molecule as
LLU-alpha, which is made from gamma-tocopherol.
Subsequently, in 2000, researchers at the
University of Tokyo and Linus Pauling Institute
found that LLU-alpha was also produced in the
body from gamma-tocotrienol through in vivo
oxidative metabolism.
LLU-alpha, a metabolite of gamma-tocopherol
and gamma-tocotrienol, is an important
factor in regulating the extracellular fluid volume.
COX-2 Inhibitor
COX-2 is normally kept in check until it is
needed to play its part specifically in the inflammation
process. Hence COX-2, if well regulated,
plays an important role because inflammation is
sometimes needed for the body’s immune
response. However, in people with chronic inflammation
such as rheumatoid arthritis, uncontrolled
COX-2 catalyzes the synthesis of prostaglandin E2
(PGE2), which increases inflammation and its
associated diseases such as cancer and vascular
heart disease.
Researchers have reported that compounds
that inhibit COX-2 also significantly reduce the
risk of having a heart attack and developing
various kind of cancer.
Researchers from the University of
California, Berkeley found that gamma-tocopherol
was a better form of vitamin E in inhibiting COX-2 compared to alpha-tocopherol. In addition,
the metabolite of gamma-tocopherol and
gamma-tocotrienol, LLU-alpha, was also found to
be a potent inhibitor of COX-2 enzyme.
Tocotrienols, through their ability to reduce
the synthesis of an eicosanoid, namely thromboxane
B2 in the cyclo-oxygenase pathway, may
have anti-inflammatory effect. Moreover,
tocotrienols are speculated to inhibit the transcriptional
activation of cyclo-oxygenase gene.
Back to Nature
In nature, almost all plants and oils naturally
contain a mixture of the vitamin E isomers. It
rarely consists of only one single form of vitamin
E. Most of them either contain a mixture of tocopherols
(alpha-, beta-, gamma- and delta-tocopherol)
or a mixture of tocotrienols (alpha, beta-,
gamma-, and delta tocotrienol) or more often, a
mixture of both the tocopherols and tocotrienols.
Similarly, the above reminded us of the betacarotene
debacle in 1996. We have finally realized
the value of other forms of carotenoid such as
alpha-carotene, lycopene, lutein, etc. as naturally
occurring in fruits and vegetables in the prevention
of various free radical-mediated degenerative
diseases. Another example is the vitamin B complex,
which is a family of various compounds—
niacin, riboflavin, thiamine, folic acid, etc.
In light of this new development, scientists
have begun to re-look at their approach towards
supplementation. The best approach is to mimic
nature as nature knows best.
In Summary
Collectively known as vitamin E, tocotrienols are
identical in structure to tocopherols except for the
degree of saturation in their side chain. It is of
particular interest that the slight structural differences
between tocopherol and tocotrienol can account for the greater biological activities found
with tocotrienol. Although most studies have strongly supported vitamin E supplements as an
effective therapeutic agent in the prevention of cardiovascular disease and cancer, not all studies
have found an association. This discrepancy has raised concerns over current formulations and the
vitamin E composition that would be most beneficial in the prevention of these diseases.
The right vitamin E to take is one that provides all the eight forms of vitamin E (d-mixed tocopherols and d-mixed tocotrienols)—“The E Complex,” as the most complete and balanced vitamin E formulation.
For further information on tocotrienols visit the leading educational Web site:
www.tocotrienol.org.
References upon request from totalhealth.
W.H. Leong is vice president of Carotech Inc, USA, the leading supplier of full spectrum tocotrienol complex—Tocomin®. He has extensive knowledge on the production and science of tocotrienols.
Tel: 1-732-906-1901
E-mail:
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