Tocotrienols

Husband11

What can you tell me about the use of tocotrienols for the prevention of BC recurrance?  What is the best source or supplement?  Are there any dangers or drug interactions to be aware of?

Husband11

Here's some of what I am reading:

Preliminary research by the University of Louisiana and University of Wisconsin in the US, University of Reading in the UK and the University of Western Ontario in Canada, showed tocotrienols can inhibit the growth of both estrogen-positive and estrogen-negative breast cancer cells while protecting healthy cells.

Another set of Canadian scientists at the University of Western Ontario proved tocotrienols are three times more potent than tamoxifen (standard treatment of breast cancer) in inhibiting growth of human breast cancer cells. The inhibitory effect is 45 times more potent when tocotrienol and tamoxifen are used together, suggesting a synergistic mechanism.

A more recent five-year clinical trial at Hospital Kuala Lumpur in 2006, sponsored by MPOB, involving 240 women with early breast cancer, showed a combination treatment of Tamoxifen and Tocovid(R) SupraBio (bio-enhanced tocotrienol capsules provided by Hovid Bhd) resulted in higher survival rate and lower recurrence of breast cancer compared to Tamoxifen alone.

"Since the 2006 clinical trial results, I'm told palm tocotrienols are increasingly being used by doctors to treat breast cancer patients," Dompok said.

Husband11

Some more:

http://www.hovid.com/frame/latestnews_frame.php?catid=&newsid=112

fairy49

Thanks Timothy! Very interesting! I do take this, I started about a month ago.

Husband11

This is the article that someone posted on the Research forum that got me started on this:

A breakthrough breast cancer drug being developed at the University of Louisiana at Monroe's School of Pharmacy could be on the market in less than two years.

Paul Sylvester, ULM pharmacologist, said Monday research is progressing as expected on tocotrienols, a substance naturally found in vitamin E, that could result in a drug that would prevent breast cancer as well as kill cancer cells in people diagnosed with breast cancer. The drug could make it to the commercial market in less than 24 months, he said.

Sylvester's comments came during a news conference with representatives of Beta Pharmaceutical, a research-based biopharmaceutical company that has funded ULM's breast cancer research.

"It looks like we're in a position of getting a product on the market in about a year-and-a-half," said Sylvester, who has been working on breast cancer research for nearly 20 years. "We'd like to start clinical trials about the same time, too."

Scientists at the university have been developing novel cancer chemo-preventive agents using tocotrienols as treatments for breast cancers. The tocotrienols are found in palm oil and have been shown by scientific research to be potent anticancer agents that are able to attack specific pathways associated with certain cancer and kill the cancer cells.

The new drug would not only help prevent breast cancer, but could also be used to treat it through injections to the patient, Sylvester said.

"It would be a prevention pill a woman would take every day," Sylvester said.

The initial product would not have to be approved by the Food and Drug Administration because it is a natural product.

Funding for the research has come from Beta Pharmaceuticals of Perth, Australia and partner First Tech International. Beta recently extended the project's funding period through December 2010. The company's total funding for the project is more than $1 million.

Beta's board Chairman Alan Reid was at the new conference. Reid had been meeting with ULM representatives and the company's Baton Rouge-based patent attorneys about patents on the new drug.

"To date, the results of the work have been outstanding," said Reid. "We're very hopeful and optimistic about the future of the project. It's proceeding in line with our expectations."

The company has already filed provisional patent applications on the drug and is preparing to file several more in anticipation of marketing it.

Greg Leader, ULM School of Pharmacy interim dean, said he's hopeful the collaboration between Beta Pharmaceuticals and the school is a sign of things to come.

"This is typical of the cutting-edge research going on at the university," Leader said. "These are the types of collaboration we would like to bring into the Monroe area to stimulate the economy."

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WHLEONG

HI ALL  

I am pleased to share the following with you vis a vis palm tocotrienol complex and breast cancer :-

About ten years ago, tocotrienols from palm oil was first identified as a potentially novel anti-cancer component. They possess the ability to reduce cancer cell proliferation and cause cell death through stimulating the killing of cancer cells selectively by programmed cell death (apoptosis), while leaving normal cells unaffected [Kline & Sanders, J Nutr 131:161S-163S (2001); McIntyre et al, Exp Biol Med, 224:292:301 (2000)].  

However, tocopherols or alpha-tocopherol (the form of vitamin E used in most commercial preparations) has little or no protective effect against cancer cells. Interestingly, tocotrienols [as pure forms or as components in palm tocotrienol complex ( Palm Tocotrienol Rich Fraction / TRF) are very effective against both estrogen receptor-positive (estrogen responsive) and estrogen receptor-negative (estrogen nonrepsonsive) human breast cancer cells [Guthrie et al, J Nutr 127:544S-548S (1997); Nesaretnam et al, Lipids 22:461-469 (1998); Nesaretnam et al, Int J Food Sci Nutr 51:S95-S103 (2000); Yu et al, Nutr Cancer, 33:26-32 (1999)].  

Since then, scientists have carried out detailed pharmacological studies on the anti-proliferative and apoptotic effects of tocotrienols on breast cancer cells and have generated a significant number of scientific papers published in reputed journals [e.g. Mizushina et al, Biochem Biophys Res Commun 339:949-955 (2005); Nesaretnam et al, Ann N Y Acad Sci 1031:143-157 (2004); Takahashi & Loo, Biochem Pharmacol 67:315-324 (2004)].

When reviewing all the published results, it is evident that palm TRF, and not the alpha-tocopherol, confers a protective effect against breast cancer. Besides in-vitro studies, similar positive results were obtained in animal studies (in vivo) [McIntyre et al, Exp Biol Med 224:292:301 (2000)]. These findings were further supported by mechanistic studies on the anti-proliferative and apoptotic properties of tocotrienols/TRF on breast cancer cells [Nakagawa et al, Biofactors 21:5-10 (2004); Shah et al, Exp Biol Med 229:745-755 (2004); Sylvester et al, Asia Pac J Clin Nutr 14:366-373 (2005); Takahashi & Loo, Biochem Pharmacol 67:315-324(2004)].  

The strong inhibitory effect (anti-angiogenesis) of Palm TRF on breast cancer cell growth and proliferation could explain why they inhibit tumorigenesis [Mizushina et al, Biochem Biophys Res Commun 339:949-955 (2005); Nakagawa et al, Biofactors 21:5-10 (2004)]. In other words, Palm TRF could be used as a safe dietary means to prevent a cancer from becoming metastitic. [Please note that it is the palm oil tocotrienol complex, and not rice bran tocotrienols, that have primarily demonstrated these anticancer effects]

In another study, it is encouraging to know that tocotrienols possess similar cell inhibitory properties as tamoxifen (a commercial anti-breast cancer drug). Furthermore, tocotrienols in combination
with tamoxifen were found to possess more inhibitory effect than either compound alone in estrogen-responsive and -nonresponsive breast cancer cells [Guthrie et al, J Nutr 127:544S-548S (1997); Nesaretnam et al, Int J Food Sci Nutr 51:S95-S103 (2000)]. The authors pointed out that the synergism between tamoxifen and palm tocotrienol complex may allow for the use of lower doses of tamoxifen, and reduce its risk of adverse side effects. Tocotrienols could be a good means as complement to the chemotherapy of breast cancer.

The dosage of tocotrienols for general health and disease prevention is recommended to be 50 mg per day and may increase to 100 mg per day if necessary. However, for best result on treatment, the dosage is suggested to be around 200 mg per day for therapeutic.  

As with any illness / disease, it is best for your customer to also consult her doctor for approval / supervision (since she is a breast cancer patient).

Re : Stage-One Breast Cancer Clinical Trial in Malaysia

This study with stage-one breast cancer patients was conducted in collaboration between Carotech (http://www.carotech.net/) and the Malaysia Palm Oil Board with various hospitals in Malaysia. It was a 5-year study and the patients were given Carotech's Tocomin SupraBio^â natural full spectrum palm tocotrienol complex soft gel capsules. The initial results showed interesting and positive results - in term of survival rate, recurrence rate and the up-regulating of a few other major immune biomarkers - that overall led to the increase in survival and recurrence rate.

Re : Where to Purchase ?

Tocomin SupraBio soft gel capsules can be purchased from the following :-  

i) VITACOST's TOCOMIN SUPRABIO - http://www.vitacost.com/NSI-Tocomin-SupraBio-Palm-Tocotrienol-Complex. You can purchase this product from the website (Tel : 1 800 381 0759).  

ii) TOCO-SORB by Jarrow Formulas - http://www.jarrow.com/product/274/Toco_Sorb_formerly_Toco_Life.This product can be puchased from your local health food stores. Or you can call them at this no : (310) 204-6936  

iii) CAROTEC's Tocomin SupraBio - http://www.carotec.com/product/56/108. You can call this company at 1-800-522-4279   

Thank you

WH Leong

Husband11

Thank you WH Leong.  Do you know where I can get access to the results of the Carotech MPOB 5 year clinical trial?  I'd like to know how positive the results were of Tocomin Suprabio on Stage 1 BC patients.

cp418

WOW - this sounds really really good!!!!  I will certainly add this supplement to my daily 'rock collection'.  Thank you for these posts!

cp418

Found this link on palm oils.

http://books.google.com/books?id=C0_C4-ev-xcC&dq=palm+oil+supplement&printsec=frontcover&source=in&hl=en&ei=wgzZSs7FDsrf8QaKhL23BQ&sa=X&oi=book_result&ct=result&resnum=14&ved=0CDAQ6AEwDQ#v=onepage&q=palm%20oil%20supplement&f=false

cmlai

Met with one of the co-researchers in May who told me that they would probably publish the study on the International Journal of Cancer. If I get further updates, I will post them here.

Merilee

I am looking at the ingredients in Tocomin Suprabio and it says Alpha-tocopherol.

An I reading the research posted by Whleong wrong, or isn't that the form that is not effective?

Husband11

Merilee, alpha tocopheral is the most abundent of the 8 isomers of vitamin E.  In any natural source you will find alpha tocopheral predominating.  The key to benefit is to consume a source that contains also the more obscure tocotrienols.  I wouldn't be worried that it contains alpha tocopheral, so do nuts and healthy oils.  Supplementing with only alpha tocopheral, as is common with vitamin e supplements, has been proven to be of little worth.  The tocomin product contains alpha tocopheral plus 60mg total of alpha, beta, delta and gamma tocotrienols.  It would be hard to natural source the tocotrienols and not capture any tocopheral, esp in its most abundent form.  From my reading, the same concentration process also captures the sitosterols, which may also be of benefit to BC patients.

Let-It-Be

Hi Timothy & Whleong:

Interesting article!  Thanks for bringing this info to my attn.  I glean this means standard good quality vit. E is not that effective as a palm oil tocotrienol complex?  Looks like I need to souce this tocomin suprabio!

Christine

Husband11

Standard vitamin E is close to useless.  It is typically pure a-tocopheral, which has both in large scale clinical trials and subsequent laboratory tests shown itself to be the weakest of the 8 forms of vitamin E.  Its possible they really shot themselves in the foot by focusing on the most abundent form of vitamin E and assuming it was responsible for the benefits of vitamin E rich foods.  Turns out that the other forms that are in lower concentration are the one's that have the most beneficial biological functions for both cancer and heart disease.  It really highlights the weakness of vitamin supplementation.  When you isolate a substance, you'd better be sure you have isolated and supplemented with the right substance.  When you remove it from the whole food, you might be leaving the best part behind.

Merilee

Timothy & WheLong

How do you come to be interested in this topic?

Husband11

My wife, Bev, who also posts on this board, was diagnosed with IDC in November of 2008.  She's had a dbl mastectomy, reconstruction, rads, FEC-T chemo and is now on tamoxifen and in the Zometa trial.  I'm trying to learn everything I can about alternative and complementary therapies that have some reasonable promise of helping prevent a recurrance, and that don't have any downside.  I'm not a Doctor, but I do have a biology degree and its proving helpful in sorting through the myriads of suggestions, books, clinical trial prospectus, journals and studies I've been reading.  I'm pretty much obsessed with this topic.

fairy49

Timothy, I have followed many of your posts, your wife is a lucky lucky woman! You really are a wonderful husband!

Husband11

I'm hoping one of these people who wonderfully popped up and posted on this board about tocotrienols can help provide us with more information.  I have read of the existence of a successful trial at the Malaysian hosptial in Kuala Lumpur of ER+ BC patients and tocotrienols.  I'd like to hear actual facts and figures and it would be wonderful if someone had access and could provide this.  As I mentioned in my earlier post,  I heard about this vitamin E constituent when someone posted on the research forum about a new drug based on tocotrienols.  Never heard of the stuff before, started reading, and it sounds like it has promise.  There's something called the Malasian Palm Oil Board that is funding research on the applications.

 Edit: I don't know Weleong or the other person who posted, but I'm pleased to get any added info on this subject.  Maybe they found this through google or another search engine?

Merilee

Timothy

Sorry to hear about your wife. Also sorry to sound protective but sometimes, believe it or not, people come on here and try to sell things UG! Yes they really stoop that low.

I am interested in this also and just recieved a bottle of eye Vitamins today that have d-aplha tocopheryl succinate in them, which I find an odd coincedence.

Husband11

No problem Merilee.   I'm not selling anything.

 I actually hope someone from Tocomin / MPOB can provide us with all the information we need on their products and the research they've done.  Esp that hospital study.   I'll give them credit for pursuing genuine research and conducting trials on their product.  The breakthroughs have to come from somewhere.

 I'll tell you something I heard from a surgeon.  He used to give out natural vitamin E for patients to use to minimize scarring and speed up healing.  He switched to a synthetic vitamin E because it was cheaper.  Big mistake he said.  He saw more inflamation, scarring and bad skin reactions with it, and ended up switching back to the more expensive natural source.  Lots of trial and error in this world.

Merilee

I'm with you, I give em credit for doing trials too, even on something that cannot be pattented. Did I spell that right? LOL Its Friday and I am pan fried

fairy49

Study Title:

Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells.

Study Abstract:

Numerous dietary phytochemicals have shown anti-breast carcinogenic activities when tested in vitro; however, in most cases, the demonstrated efficacy of individual phytochemicals requires doses not readily achievable in vivo. Therefore, whether diets might exert translational promises and benefits in clinical settings and prevention of breast cancer remain unclear. Since cancer cells are endowed with complex, redundant, converging and diverging pathways spanning both the genetic and metabolic networks that are not merely replicates of those in normal cells, it is of interest to test whether a multicomponent approach involving lower, physiologically relevant doses of natural dietary agents may be developed as a chemopreventive strategy for breast cancer. Herein, we investigated, using the estrogen receptor-positive MCF-7 breast cancer cells as a model, whether the combination of epigallocatechin gallate (EGCG), resveratrol and gamma-tocotrienol at suboptimal doses elicits synergism in suppressing cell proliferation, modulating gene expression, and increasing antioxidant activity, as compared to each of the three phytochemicals added alone. The results showed that there was a approximately 33, 50 and 58% inhibition of cell proliferation by > or =50 microM EGCG, > or =25 microM resveratrol and > or =10 microM gamma-tocotrienol, respectively, added as a single agent. When a suboptimal dose (10 microM) of each phytochemical was used, a significant additive effect in suppression of cell proliferation was observed with the combination of resveratrol and gamma-tocotrienol whereas the three phytochemicals added together did not produce more pronounced inhibition of cell proliferation. A significant additive effect in reducing cyclin D1 and bcl-2 expression was found when gamma-tocotrienol was added with either EGCG or resveratrol. Functional synergism among the three phytochemicals was only observed in the induction of quinone reductase NQO1. These results suggest that diet-based protection against breast cancer may partly derive from synergy amongst dietary phytochemicals directed against specific molecular targets in responsive breast cancer cells, and provide support for the feasibility of the development of a diet-based combinatorial approach in the prevention and treatment of breast cancer.

Study Information:

Hsieh TC, Wu JM. Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells. Int J Oncol.  2009 October  33(4):851-9.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.

fairy49

Tocotrienol's antioxidant function is also associated with lowering DNA damage, tumor formation, and other parameters of cell damage. A study focusing on breast cancer revealed that animals exposed to carcinogens that were fed corn oil- or soybean oil-based diets had significantly more tumors than those fed a tocotrienol-rich palm oil diet. The results clearly noted that the tocotrienol-rich palm oil did not promote chemically induced breast cancer (Sundram et al. 1989).

Tocotrienols possess the ability to stimulate the selective killing of cancer cells through programmed cell death (apoptosis) to reduce cancer cell proliferation while leaving normal cells unaffected (Kline et al. 2001). One of the mechanisms by which tocotrienols are thought to suppress cancer is related to the isoprenoid side chain.

Isoprenoids are plant compounds that have suppressed the initiation, growth, and progression of many types of cancer in experimental studies (Block et al. 1992). They are common in fruits and vegetables, which may explain why diets rich in these foods have consistently been shown to reduce the incidence of cancer.

The antiproliferative effect of isoprenoids is thought to be due to suppression of the mevalonate pathway, through which mutated ras proteins transform healthy cells into cancer cells. Mutated ras is the most common cellular defect found in human cancers. The mevalonate pathway escapes regulatory control in tumor tissue but remains highly sensitive to regulation by toco-trienols. Tocotrienols are at least five times more powerful than farnesol, the body's regulator of the mevalonate pathway ( Elson et al. 1994).

Interestingly, human breast cancer cells have been shown to respond very well to treatment with tocotrienols. Tocotrienols provide growth inhibition of breast cancer cells in culture that is independent of estrogen sensitivity and have great potential to be a significant aid in the prevention and treatment of breast cancer (Nesaretnam et al. 1998).

A number of in vitro studies have demonstrated the effectiveness of tocotrienols as inhibitors of both estrogen-receptor-positive (estrogen-responsive) and estrogen-receptor-negative (nonestrogen-responsive) cell proliferation. Researchers tested the effect of palm tocotrienols on three cell lines of estrogen-responsive and estrogen-nonresponsive human breast cancer cells (MCF7, MDA-MB-231, and ZR-75-1). They found that tocotrienols inhibited cell growth strongly in both the presence and absence of estradiol, the major estrogen in the body. The researchers also demonstrated that tocotrienols enhanced the effect of tamoxifen. The gamma- and delta-fractions of toco-trienols were most effective at inhibiting cell growth, while alpha-tocopherol was ineffective in doing so ( Nesaretnam et al. 2000).

Among the tocotrienols, delta-tocotrienol was shown in another study to be the most potent inducer of apoptosis (programmed cell death) in both estrogen-responsive and estrogen-nonresponsive human breast cancer cells, followed by gamma and alpha-tocotrienol (beta-tocotrienol was not tested). Interestingly, delta-tocotrienol is more plentiful in palm tocotrienols than in tocotrienols derived from rice. Of the natural tocopherols, only delta-tocopherol showed any apoptosis-inducing effect, although it was less than a tenth of the effect of palm and rice delta-tocotrienol (Yu et al. 1999).

Similar results were obtained when mammary cancer cells from mice were studied ( McIntyre et al. 2000). While tocopherols had no inhibitory effect on cancerous cell growth, alpha, gamma, and delta-tocotrienols effectively arrested the cell cycle and triggered cell death. Highly malignant cells were most sensitive to the antiproliferative effects of tocotrienols, whereas less aggressive precancerous cells were the least sensitive.

Tocotrienols were found to be far more effective than alpha-tocopherol in inhibiting breast cancer cell growth ( Guthrie et al. 1997). The tocotrienol concentration needed was less than 1/20 of alpha-tocopherol in estrogen-responsive cells and less than 1/10 in cells unresponsive to estrogen. Tocotrienols in combination with tamoxifen were more inhibitory than either compound alone in both estrogen-responsive and nonresponsive breast cancer cells. The authors pointed out that the synergism between tamoxifen and tocotrienols may allow for the use of lower doses of tamoxifen and reduce its risk of adverse side effects.

While tocotrienols are considered important antioxidants, it may be that they are the most potent of all of the lipid-soluble antioxidants available. From decreasing platelet aggregation (clumping of blood) to anti-inflammatory action to anticancer activity, tocotrienols are a significant nutritional compound. Therefore, a daily dose of 240 mg of tocotrienols should be considered as an adjuvant breast cancer therapy.

fairy49

Interesting......... its WHLEONG!

Despite these big limitations, the news has been welcomed by WH Leong, vice president for Carotech, one of the world' major tocotrienol producers.

"Since angiogenesis is essential for tumour growth, its strong inhibition by tocotrienols but not tocopherols, could very well provide us with a safe dietary means to prevent a cancer from becoming metastatic," said Leong.

Maryiz

Wow, this sounds wonderful.. What is the likelihood of something on the market within 2 years as quoted?  Maryiz

Anonymous

Tocotrienols have been on the market and taken as a breast cancer patient therapy for about 12 years. I think Twin Lab makes one formula --Maxilife Rice Tocotrienols. There was some debate about palm or rice derived formulas being best.

Husband11

Thank you Fairy49!

 Maryiz, we purchased Tocomin Suprabio from Vitacost.  Its reasonably priced, and is a tocotrienol rich fraction made from palm oil.  It's made from Carotech's product, so I'm thinking its the most suitable formulation to tocotrienols.  It also naturally contains other healthful components, such as phytosterols.  I spoke to the pharmacist at the hospital my wife is getting treatment at, and they couldn't find any negative data to suggest problems with it.  I'm cautious to not sabotage the tamoxifen treatment she is on, with anything that could interfere with it.  The tocotrienols appear to in lab studies and lab animals at least, to enhance the effectiveness of tamoxifen.  Sounds very desirable to me.

Merilee

Ok so my suspicious eyebrow up the other day regarding WHLeong was not just paranoia...Ladies, follow your gut, if it looks like a duck, if it quacks like a duck, its probabaly a duck

deni63

But WHLEONG did not start this thread, he (or she) joined in after it was already under way. Has anyone read anything about tocotrienols being effective for cancers other than breast? ie., kidney?

Husband11

I started this thread after reading about it on the Research and Clinical trial forum. 

This is the thread that really started it all:  "2 years from BC Prevention Pill?"

http://community.breastcancer.org/forum/73/topic/742117?page=1#idx_3 

Link to news article:

http://www.thenewsstar.com/apps/pbcs.dll/article?AID=2009910130327

 I found the news of the "new drug" very exciting.  I'm guessing that Carotech's people google the subject and see who's talking  about it.  I've noticed when I research subjects on breast cancer on google, I'm surprised to find my own posts on this site.  I've got nothing against WHLeong coming on here and providing more info on their product.  I take everything with a grain of salt until I've followed the statements with my own research.  Pubmed has lots on tocotrienols.  I'd say its all verifiable.  The only weak link is the absence of clinical trials on women with BC.  So far everything that's published deals with cell lines and lab animal.  Good preliminary stuff, but that's why I'm asking about the hospital trial in Malaysia.  If the results on women with early stage BC were significant, this is a big deal.

fairy49

I think WELEONG was just trying to guide us, Timothy is on to something, there is nothing I have read so far that would discourage me from trying this.

L