Tocotrienols - Twenty Years of Dazzling Cardiovascular and Cancer Research

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Tocotrienols -

Twenty Years of Dazzling Cardiovascular and Cancer Research

http://www.wellnessresources.com/health/articles/tocotrienols_twenty_years_of_dazzling_cardiovascular_and_cancer_research/

by Byron s, Board Certified Clinical Nutritionist

Numerous studies over the past two decades have clearly

proven that the tocotrienol form of vitamin E is a top

choice for cardiovascular protection and heart health. A recent review of

tocotrienol science1

points out that they are also being researched for benefits to bone health, blood sugar metabolism, brain health, and cancer. Tocotrienols offer a safe and effective way to

help achieve or maintain healthy cholesterol, while simultaneously protecting

your arteries. It is worthwhile understanding more about them and how they can

improve your health.

The vitamin E family consists of 4 tocotrienols and 4

tocopherols. D alpha tocopherol is the commonly understood form of vitamin E

and has been extensively researched and has its own value to human

health. The difference between tocotrienols and tocopherols is the “tailâ€

on the vitamin E molecule. Tocopherols have a long saturated tail. Tocotrienols

have a short unsaturated tail. The unique structure of tocotrienols enables

them to do many things that tocopherols cannot do. This includes easier access

to cells, better antioxidant function in cells, a better ability to move around

in cells, and the activation of a wide variety of gene signals including

cholesterol regulation.

The first recognition of tocotrienols as regulators of

cholesterol occurred in a 1986 study2 in which tocotrienols were

isolated from barley and fed to chickens. Tocotrienols reduced the rate of

synthesis of cholesterol by the liver, in turn reducing total and LDL cholesterol. In April of 1991 the American

Journal of Clinical Nutrition published an animal study and two human

studies, triggering an explosion in scientific interest in tocotrienols which

continues to this day. The animal study involved pigs with inherited high

cholesterol3. Tocotrienols reduced their total cholesterol by

44% and LDL by 60%. They also reduced factors in the blood associated

with sticky platelets, suggesting an additional cardiovascular protective

mechanism was in play.

The same University

of Wisconsin research

team that did the pig study also conducted an 8-wk double-blind crossover study

with 15 humans. During the 4 weeks on 50 mg per day of tocotrienols the

total cholesterol was lowered 15%, LDL by 8%, and factors affecting platelet

stickiness were also improved. Another preliminary human study with 42 mgs of tocotrienols per day5

found that many participants lowered their cholesterol, in some cases up to 35%

for both total and LDL cholesterol. The dose of

tocotrienols used in these early studies was relatively small, yet it still

showed a positive influence on cholesterol levels.

Researchers next documented that it was gamma tocotrienol6

responsible for inhibiting cholesterol synthesis in the liver. As the research

progressed, scientists showed that gamma tocotrienol

was reducing the HMG CoA reductase enzyme7 which

is the starting point in the production line for cholesterol synthesis within

your liver. It should be pointed out that statins—especially in high doses—take

a sledgehammer to this same enzyme, essentially clogging up its receptors so

that no communication can get through. By comparison, tocotrienols work more on

a consulting basis, gently down-regulating the enzyme as part of a

communication strategy. Big Pharma invariably likes the sledgehammer approach,

as they produce forced behavior on human systems. They can change numbers, even

if a person continues to eat excessively. Maximizing the benefits of

tocotrienols would require a person actually eat better. Of course,

tocotrienols have none of the toxic side effects8 that statins

have.

While your liver uses this HMG CoA reductase

cholesterol-synthesis pathway (melvalonate pathway) to produce LDL cholesterol for your entire body, every cell in your body

also uses the same pathway to produce small pieces of cholesterol that are

vital for maintaining the health and survival of any cell. In cancer

situations, this pathway is hijacked and used by cancer cells to foster their

own survival at the expense of your body. Researchers quickly realized that the

“consulting style†of tocotrienols within your liver and healthy cells would be

very different inside cancer cells9

and would not place any brakes on tocotrienols stopping HMG CoA reductase

activity. In other words, tocotrienols had a unique ability to differentiate

between healthy cells and cancer cells and in the case of cancer they could cripple a

primary defense system of the cancer. I should point out that statins can also

kill cancer in a test tube but the dose required to kill cancer in humans kills

the human first. On the other hand, tocotrienols have demonstrated excellent

tumor killing ability, even helping chemo drugs work much

better10 on resistant forms of cancer. Tocotrienols do not

injure the human body.

As the benefits of tocotrienols became apparent,so did the

commercial interests in potentially different sources of them. Palm oil was

high in gamma tocotrienol but not as high in alpha tocotrienol, which was turning out to be relevant to

antioxidant protection of the arteries and brain. Palm oil is more difficult to

put into capsules and requires the addition of other oils to make it flow

easily. Rice bran oil is a rich source of both gamma and alpha tocotrienol and with some additional attention to quality can

be produced without any filler oils. This allows for the production of a highly

purified end product with no additive oils should a manufacturer chose to go

the extra mile.

Rice bran oil11 was known for some time to

help cholesterol reduction. The recognition that tocotrienols were a main

component of the oil in combination with all the emerging tocotrienol

research, led scientists to study tocotrienols isolated from rice bran oil.

Leading the pack was the University

of Wisconsin research

team that a decade earlier had done the pioneering work with palm tocotrienols,

hypercholesterolemic pigs, and the first human studies. They tested 50 mgs per

day of rice bran oil tocotrienols12

in the genetically high-cholesterol pigs. After 6 weeks total, cholesterol was

reduced 32-38%, LDL cholesterol was reduced 35-43%,

glucose was reduced 22-25%, triglycerides were reduced 15-19%, and various

factors influencing sticky platelets were also reduced.

Next the Wisconsin researchers placed 28 people with high cholesterol13

on a restricted diet for a month and then gave them either 50 mg of rice bran

oil tocotrienols, 10 mg of the statin drug Mevacor (a

relatively low dose which is generally not toxic), or 50 mg tocotrienols, or a

combination of 50 mg tocotrienols and 10 mg Mevacor. In the 50 mg tocotrienol group total cholesterol was lowered by 14% and

LDL by 18%. In the Mevacor group total cholesterol was lowered by 13% and

LDL by 15%. In the combination group, total cholesterol was lowered by

20% and LDL by 25%. Several months later the researchers tested various doses

of rice bran oil tocotrienols (25 mg, 50 mg, 100 mg, 200 mg). After being

put on a restricted diet for a month 90 people were then divided into various

groups. The 100 mg per day dose14 worked best,

lowering total cholesterol by 20%, LDL by 25%, and triglycerides by 12%.

This is excellent human data to support the use of tocotrienols from rice bran

oil in combination with eating well in the management of cholesterol.

In addition to the cholesterol-lowering properties of

tocotrienols scientists were becoming interested in the ability of tocotrienols

to positively benefit the health of arteries. In this case the focus turned

primarily to alpha tocotrienol, which demonstrated a

high level of antioxidant function. It was first recognized that alpha tocotrienol could prevent free radical damage to LDL cholesterol15

in humans with high cholesterol. Only damaged (oxidized LDL) can form

plaque in the arteries.

Scientists then tested tocotrienols in mice16

who are genetically programmed to develop high cholesterol and hardening of the

arteries when eating a high fat diet. When given tocotrienols and a high fat

diet these mice did not develop high cholesterol and the hardening of their

arteries was almost completely stopped (98% reduction). Other researchers found

similar results when they placed rabbits on a diet designed to produce hardening of the arteries17.

Free radical damage in the blood was significantly reduced and the rabbits fed

tocotrienols along with the bad diet had much less thickening of their arteries

as well as retaining more elastic properties in their arteries.

In order for damaged cholesterol to stick to the lining of

your arteries it is engulfed by macrophages (immune cells) that then stick to

the endothelial cells that line your arteries. When endothelial cells become inflamed they project a Velcro-like

piece of fly paper on the surface of their cells (adhesion molecules) which

then enable the cholesterol-laden macrophages to lock on and start the

plaque-forming process. A study with inflamed human endothelial

cells18 shows that alpha tocotrienol

powerfully inhibits this sticking process, turning off the sticky adhesion

molecules by turning down the inflammatory gene regulator within the

endothelial cell (NF-kappaB ).

The ability of alpha tocotrienol to

regulate the core inflammatory gene signal is highly relevant to human health,

since it is now recognized that chronic low-grade activation of NF-kappaB is a primary factor in nearly every disease of

aging. Indeed, researchers soon discovered that alpha tocotrienol,

but not d alpha tocopherol, could completely inhibit excitotoxic injury to brain cells19

(a key feature to most aspects of cognitive decline and memory loss).

This article highlights some of the key tocotrienol

cardiovascular and cancer research going on around the world which continues in

full swing today. Human studies continue to show cholesterol-lowering benefits20,

even in difficult problems like type 2 diabetes21. Numerous review articles22 tout the broad range

of benefits, including the prevention of disease23, offered

by the unique form of vitamin E known as tocotrienols – which truly is the vitamin E for the 21st Century24.

Referenced Studies:

^

Tocotrienols,

the Vitamin E of the 21st Century Biochem Pharmacol. Aggarwal

BB, Sundaram C, Prasad S, Kannappan R. ^

The

Discovery of Tocotrienols as Cholesterol Regulators J Biol

Chem. Qureshi AA, Burger WC, DM, Elson CE. ^

Tocotrineols

Lower Cholesterol in Pigs Am J Clin Nutr.

Qureshi AA, Qureshi N, Hasler-Rapacz JO, Weber FE, Chaudhary

V, Crenshaw TD, Gapor A, Ong AS, Chong YH, D, et al. ^

Totcotrienols

Lower Cholesterol - Early Human Study #1 American Journal

of Clinical Nutrition Qureshi AA, Qureshi N, JJ, Shen Z,

Kramer G, Gapor A, Chong YH, DeWitt G, Ong A, DM, et al. ^

Totcotrienols

Lower Cholesterol - Early Human Study #2 American Journal

of Clinical Nutrition Tan DT, Khor HT, Low WH, Ali A, Gapor A. ^

Gamma

Tocotrienol Inhibits Cholesterol Synthesis J Med Chem.

Pearce BC, RA, Deason ME, Qureshi AA, JJ. ^

Gamma

Tocotrienol Regulates HMG-CoA Reductase J Biol Chem.

RA, Pearce

BC, RW, Gordon DA,

JJ. ^

The

Statin Scam Marches On ^

How

Tocotrienols Help Kill Cancer J Nutr. Elson CE. ^

Gamma

Tocotrienol and Pancreatic Cancer Cancer

Res. Kunnumakkara AB, Sung B, Ravindran J, Diagaradjane P,

Deorukhkar A, Dey S, Koca C, Yadav VR, Tong Z, Gelovani JG, Guha S,

Krishnan S, Aggarwal BB. ^

Rice

Bran Oil and Cholesterol Metabolism Journal of

Nutrition Sugano M, Tsuji E. ^

Rice

Bran Oil Tocotrienols Lower Cholesterol in Pigs J

Nutr. Qureshi AA, DM, Hasler-Rapacz JO, Rapacz J. ^

Rice

Bran Oil Tocotrienols Lower Cholesterol - Study #1 J Nutr

Biochem. Qureshi AA, Sami SA, Salser WA,

Khan FA. ^

Rice

Bran Oil Tocotrienols Lower Cholesterol - Study #2 Atherosclerosis.

Qureshi AA, Sami SA, Salser

WA, Khan FA. ^

Alpha

Tocotrienol Reduces Oxidized LDL Cholesterol in Humans Free

Radic Biol Med O’Byrne D, Grundy S, Packer L, Devaraj S,

Baldenius K, Hoppe PP, Kraemer K, Jialal I, Traber MG. ^

Tocotrienols

Prevent Hardening of Arteries in Mouse Model of Atherosclerosis J

Nutr. Black TM, Wang P, Maeda N, RA. ^

Tocotrienols

Reduce Athersclerosis Formation in Rabbits Malays J Pathol.

Nafeeza MI, Norzana AG, Jalaluddin HL, Gapor MT. ^

Tocotrienols

Help Prevent Atherosclerosis Atherosclerosis.

Theriault A, Chao JT, Gapor A. ^

Alpha

Tocotrienol Inhibits Excitotoxic Brain Cell Injury Ann N Y

Acad Sci. Sen CK, Khanna S, Roy S. ^

Tocotrienols

and Citrus Flavonoids Lower Cholesterol Altern Ther Health

Med. Roza JM, Xian-Liu Z, Guthrie N. ^

Tocotrienols

Lower Cholesterol Atherosclerosis. Baliarsingh

S, Beg ZH, Ahmad J. ^

Reviewing

the Power of Tocotrienols J Nutr. Schaffer S,

Müller WE, Eckert GP. ^

Tocotrienols

in Health and Disease ^

Tocotrienols,

the Vitamin E of the 21st Century Biochem

Pharmacol. Aggarwal BB, Sundaram C, Prasad S, Kannappan R.