Vitamin E and Cancer

 

and3).

3). Tocotrienols are found in certain cereals and vegetables such as palm oil, rice bran oil, coconut oil, barley germ, wheat germ and annatto [34, 35]. Palm oil and rice bran oil contain particularly higher amounts of tocotrienols (940 and 465 mg/kg, respectively) [36]. Other sources of tocotrienols include grape fruit seed oil, oats, hazelnuts, maize, olive oil, Buckthorn berry, rye, flax seed oil, poppy seed oil and sunflower oil (Fig. 2) [37].

Table 2

Back to August 2014

The Little-Known Benefits Of Tocotrienols

August 2014

By Thomas Rosenthal

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and3).

3). Tocotrienols are found in certain cereals and vegetables such as palm oil, rice bran oil, coconut oil, barley germ, wheat germ and annatto [34, 35]. Palm oil and rice bran oil contain particularly higher amounts of tocotrienols (940 and 465 mg/kg, respectively) [36]. Other sources of tocotrienols include grape fruit seed oil, oats, hazelnuts, maize, olive oil, Buckthorn berry, rye, flax seed oil, poppy seed oil and sunflower oil (Fig. 2) [37].

Table 2

If your vitamin E supplement contains only tocopherol forms, you may not be getting all of the benefits this nutrient has to offer. While tocopherols are very important, they lack many of the synergistic benefits offered by their cousins, the tocotrienols.

Few people realize that vitamin E is composed of eight different compounds. Half of these are called tocopherols, which is the most common form of vitamin E. The other half are known as tocotrienols.

Scientists are discovering that tocotrienols provide valuable therapeutic and preventive options for the diseases of aging that tocopherols alone may not provide.

For example, researchers found that tocotrienols given to mice with pancreatic cancer significantly improved their survival. Only 10% of animals in the control group survived for the study period while 70% of those taking tocotrienols survived!1 Pancreatic cancer is a particularly fast-moving and lethal form of cancer, and this study presents a promising new treatment option.

Beyond cancer, research is showing that tocotrienols have a place in reducing important risk factors for some of the most lethal chronic diseases. For example, tocotrienols have been found to promote new artery formation after a stroke, lower homocysteine levels, improve insulin sensitivity, protect vital brain circuitry, and even prevent bone loss.2-5

In addition, tocotrienols have powerful lipid-lowering, anticancer, and neuroprotective properties that tocopherols lack.6,7

These recent investigations into this overlooked form of vitamin E are providing new strategies to fend off multiple risk factors to ensure optimal health.

Tocotrienols And Cancer

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For many years, studies of vitamin E produced inconsistent results regarding its effect on cancer. It is now thought that this inconsistency was likely due to the widespread use of alpha-tocopherol alone in such studies.8 We now know that alpha-tocopherol has weak anticancer activity, while tocotrienols are more potent cancer-preventive agents.8-10

In a recent finding that stunned researchers, tocotrienol supplementation was found to dramatically extend the life span of mice with pancreatic cancer.8 Pancreatic cancer is among the most aggressive and deadly human cancers, with survival times typically counted only in months.11,12 The 2013 study showed that after 16 weeks of treatment, just 10% of placebo-treated mice remained alive, while 30% survived in a group treated with gemcitabine, a standard chemotherapy drug. However, a remarkable 70% of mice had survived in the tocotrienol group. Combination treatment with gemcitabine and tocotrienols produced a remarkable 90% survival rate.1

Tocotrienols are the ultimate multi-targeting nutrient when it comes to cancer. Their actions affect virtually every step in the progression of cancer.13 They share antioxidant effects with tocopherols, but there seems to be a considerable amount of anticancer action that is unrelated to antioxidant actions.13,14

PROPOSED MECHANISMS OF TOCOTRIENOLS IN CANCER PREVENTION13

Effect Result
Apoptosis (programmed cell death) Tumor-cell death
Cell cycle arrest Slows tumor growth
Inhibit new blood vessel growth (angiogenesis) Starves tumor of nutrients and oxygen
Inhibit HMG-CoA reductase enzyme Inhibits metastasis65
Decreases expression of cancer causing genes Prevents initiation of cancer
Increases the expression of genes that suppress cancer Prevents initiation and progression of cancer

Proposed Mechanisms Of Tocotrienols In Cancer Prevention

Tocotrienols impact several factors that tumors need for their development and growth.

Tocotrienols have been shown to inhibit the growth of new blood vessels to rapidly growing tumors and inhibit growth and proliferation of cancer cells.9,15 Tocotrienols also sensitize cancer cells to the effects of standard chemotherapy, and astonishingly, appear capable of combating cancer stem cells, which are highly resistant to standard chemotherapy and contribute to cancer recurrences.9 They also blunt the impact of chemical carcinogens in animal studies.16

Tocotrienols also trigger apoptosis, which is the programmed cancer cell death that can prevent a tumor from ever getting a toe-hold in the body. Apoptosis is also vital in shrinking existing tumors, a factor that may account for the growing use of tocotrienols (alone or with conventional chemotherapy drugs) in patients with existing cancers.14,17

Tocotrienols have another rather unusual mechanism for fighting cancer. They appear to block an enzyme that cancer cells need for invasion and metastasis. This enzyme, called HMG-CoA reductase, is the same enzyme blocked by statin drugs.2 In fact, the combination of tocotrienols with the statin drug atorvastatin (Lipitor®) was recently shown to greatly increase inhibition of cancer cell growth.18

Summary

Tocotrienols are potent gene regulators and modulators of many enzymes involved in human health, helping to quash the inflammation, glycation, and other processes that contribute to age-related diseases.

Tocotrienols are increasingly being recognized for their potential roles in protecting against cancer, heart disease, stroke, diabetes, liver disease, neurodegenerative diseases, and even osteoporosis.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Husain K, Centeno BA, Chen DT, Hingorani SR, Sebti SM, Malafa MP. Vitamin E delta-tocotrienol prolongs survival in the LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) transgenic mouse model of pancreatic cancer. Cancer Prev Res (Phila). 2013 Oct;6(10):1074-83.
  2. Norsidah KZ, Asmadi AY, Azizi A, Faizah O, Kamisah Y. Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet. J Physiol Biochem. 2013 Sep;69(3):441-9.
  3. Park HA, Kubicki N, Gnyawali S, et al. Natural vitamin E alpha-tocotrienol protects against ischemic stroke by induction of multidrug resistance-associated protein 1. Stroke. 2011 Aug;42(8):2308-14.
  4. Rink C, Christoforidis G, Khanna S, et al. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis. J Cereb Blood Flow Metab. 2011 Nov;31(11):2218-30.
  5. Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN. Tocotrienol supplementation in postmenopausal osteoporosis: evidence from a laboratory study. Clinics (Sao Paulo). 2013 Oct;68(10):1338-43.
  6. Sen CK, Khanna S, Roy S. Tocotrienols in health and disease: the other half of the natural vitamin E family. Mol Aspects Med. 2007 Oct-Dec;28(5-6):692-728.
  7. Sen CK, Khanna S, Roy S. Tocotrienols: Vitamin E beyond tocopherols. Life Sci. 2006 Mar 27;78(18):2088-98.
  8. Wada S. Cancer preventive effects of vitamin E. Curr Pharm Biotechnol. 2012 Jan;13(1):156-64.
  9. Ling MT, Luk SU, Al-Ejeh F, Khanna KK. Tocotrienol as a potential anticancer agent. Carcinogenesis. 2012 Feb;33(2):233-9.
  10. Sylvester PW, Akl MR, Malaviya A, et al. Potential role of tocotrienols in the treatment and prevention of breast cancer. Biofactors. 2013 Jan-Feb;40(1):49-58.
  11. Malafa MP. New insights and gains in pancreatic cancer. Cancer Control. 2008 Oct;15(4):276-7.
  12. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16920426. Accessed April 2, 2014.
  13. Nesaretnam K. Multitargeted therapy of cancer by tocotrienols. Cancer Lett. 2008 Oct 8;269(2):388-95.
  14. Sylvester PW, Wali VB, Bachawal SV, Shirode AB, Ayoub NM, Akl MR. Tocotrienol combination therapy results in synergistic anticancer response. Front Biosci (Landmark Ed). 2011;16:3183-95.
  15. Miyazawa T, Shibata A, Sookwong P, et al. Antiangiogenic and anticancer potential of unsaturated vitamin E (tocotrienol). J Nutr Biochem. 2009 Feb;20(2):79-86.
  16. Rahmat A, Ngah WZ, Shamaan NA, Gapor A, Abdul Kadir K. Long-term administration of tocotrienols and tumor-marker enzyme activities during hepatocarcinogenesis in rats. Nutrition. 1993 May-Jun;9(3):229-32.
  17. Viola V, Pilolli F, Piroddi M, et al. Why tocotrienols work better: insights into the in vitro anticancer mechanism of vitamin E. Genes Nutr. 2012 Jan;7(1):29-41.
  18. Yang Z, Lee MJ, Zhao Y, Yang CS. Metabolism of tocotrienols in animals and synergistic inhibitory actions of tocotrienols with atorvastatin in cancer cells. Genes Nutr. 2012 Jan;7(1):11-8.

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In nature, tocotrienols are present in many plants and fruits. The palm fruit (Elaeis guineensis) is particularly high in tocotrienols, primarily gamma-tocotrienol, alpha-tocotrienol and delta-tocotrienol. Other cultivated plants high in tocotrienols includes rice, wheat, barley, rye and oat.[31] In anatto, tocotrienols are relatively abundant (only delta- and gamma-tocotrienol however) and it contains no tocopherols.[32]

  1. ^ Tocopherol and tocotrienol contents of raw and processed fruits and vegetables in the United States diet p.199
  2. ^ Identification and estimation of tocotrienols in the annatto lipid fraction by gas chromatography-mass spectrometry

Annatto Seeds are a Natural Source of Tocotrienols with No Tocopherols

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Achiote, known by its botanical name, Bixa orellana, is a shrub or small tree originating from the tropical region of the Americas.  The Achiote tree is sometimes called the lipstick tree due to the fact that people would use the seeds to make red body paint and lipstick.

The bright red seeds of the Achiote tree is called annatto.  Annatto seeds impart a slight peppery taste with a hint of nutmeg.  They have been used in cooking methods in Latin America and to color cheeses.

Annatto seeds are a rich source of tocotrienols.  Tocotrienols are members of the vitamin E family.  Vitamin E is actually made up of two families:

  • Tocotrienols
  • Tocopherols

Tocotrienols are made up of four fractions:

  • alpha
  • beta
  • gamma
  • delta

Tocopherols are made up of four fractions:

  • alpha
  • beta
  • gamma
  • delta

The difference between tocotrienols and tocopherols lies in the unsaturated side chain of tocotrienols, having three double bonds in its farnesyl isoprenoid tail.

Supplemental tocotrienols are derived primarily from three sources:

  • Palm oil
  • Rice bran
  • Annatto seeds

Annatto seeds are a superior source of tocotrienols since it is the only natural source that contains only tocotrienols and no tocopherols.  Palm oil and Rice bran have a mixture of tocopherols and tocotrienols.  The Table below illustrates the percentages of tocotrienols and tocopherols of palm oil, rice bran and annatto seeds:

Content of Tocotrienols and Tocopherols of Palm oil, Rice bran and Annatto seeds

A common method to obtain the tocotrienols from annatto seeds is to steep them in a healthy oil, also known as Annatto oil.   Oils that are often used are:

  • Extra Virgin Olive oil
  • Mustard oil
  • Walnut oil

Most recommendations on creating Annatto oil advise that you heat the oil in a frying pan and then add the annatto seeds.  The inherent problem with this approach is that when you heat any oil, especially extra virgin olive oil, it becomes oxidized and therefore rancid.  Consuming this rancid (heated) oil is detrimental to your health.

Instead of heating the oil, simply place the annatto seeds into the oil bottle and let it steep in the oil for as long you use the oil.  It is also advisable to not place the oil bottle in direct sunlight as this may also oxidize the oil.


Informational References:

DeltaGOLD™ is supplemental tocotrienols derived exclusively from Annatto developed by American River Nutrition


Resources:

Annatto Seeds  (Spice Jungle)

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Nature’s Best Kept Secret – Vitamin E Tocotrienols

Tocotrienol, a member of vitamin E family. The natural vitamin E family comprises four tocopherol and four tocotrienol isomers, namely alpha (α), beta (β), gamma (γ) and delta (δ). Throughout the past 30 years, very few vitamin E studies focused on tocotrienols although tocotrienols constitute half of the entire vitamin E family. In recent years, tocotrienol research has gained much prominence due to its potential health attributes. Tocotrienols are not only structurally different from tocopherols (see Figure 1), but also possess biological functions which are not shared by the tocopherol isomers.Tocotrienols are only available from selected plant sources.

Tocotrienols are minor components in plants, mainly concentrated in cereals like rice bran, barley, rye and wheat germ. Unlike tocopherols that occur naturally in most common vegetable oils, tocotrienols are found only in selected oils such as palm oil and rice bran oil (see Table 1).
Palm oil is the richest natural source of tocotrienols. Palm oil extracted from the fruits of Elaeis guineensis, is known to be one of the most abundant natural sources of vitamin E, with composition of approximately 30% tocopherols and the remaining as tocotrienols1. Palm and rice bran oils are the highest known source of tocotrienols in the plant kingdom2. Crude palm oil, contains tocotrienols as high as up to 550 mg/kg with mostly γ and α-tocotrienols.

Tocotrienols have unique biological activities not shared with tocopherols.
Tocotrienols have an unsaturated side tail which differs from tocopherols and this may account for significant difference in the biological activities of these isomers (see Figure 1).

Tocotrienol is a more superior antioxidant.
Due to the presence of a unique side chain, tocotrienol is able to penetrate into tissues with saturated fatty layers more efficiently3. This means that it can attach itself to the inside of cell membranes and hence exert its antioxidant activity. Studies also report that α-tocotrienol is 40-60 times more potent than α-tocopherol in preventing lipid peroxidation4. With such potent antioxidant properties, it makes tocotrienol an effective antioxidant in protecting against free radical-induced oxidative stress.

The science behind tocotrienols.
Research conducted all over the world to demonstrate the various health attributes of palm tocotrienols.

(i) Cardioprotective Effects
Tocotrienols particularly palm tocotrienols have demonstrated promising cardioprotective properties. Amongst the published studies that reported an ability of palm tocotrienols to reverse arterial blockage by decreasing the amount of cholesterol deposits in the carotid artery5. Tocotrienols also help reduce the production of endothelial adhesion molecules thus reducing the risk of developing atherosclerotic plaque6. In addition, they possess cholesterol lowering activity by inhibiting the HMG-CoA reductase that regulates cholesterol biosynthesis7.

(ii) Skin Health
Due to the higher antioxidant activity, tocotrienols can be absorbed quickly and penetrate through the deep layers of skin. It was found that tocotrienols could accumulate at the stratum corneum of the skin with highest concentrations found in the uppermost of 5 microns8. Tocotrienols will promote healthy skin barrier in reducing oxidative effects for prevention of UV induced cancer like melanoma, and other related photo-aging effects when consumed orally or applied topically. Due to its significant antioxidant properties, tocotrienols are now widely being used in many formulations for cosmetic and dermatological applications.

(iii) Anti-cancer and cancer suppression properties
Tocotrienols portray an anti-cancer properties that are not demonstrated by other antioxidants. It may not only help to prevent cancer but has an ability to block cancer cell growth and initiate apoptosis – a process whereby cancerous cells commit suicide. Interestingly, tocotrienols only induce programmed death in certain cancer cells while sparing other healthy cells. This ability is not found in tocopherols. The efficacy of palm tocotrienols in suppressing cancer cell growth has been widely studied in various cancer cells such as breast9,10 , prostate11,12, and pancreas13.

(iv) Tocotrienols is a natural neuroprotective vitamin
Tocotrienol, particularly α-tocotrienol is the most potent neuroprotective form of vitamin E. It protects neuron death at an extremely low level (nanomolar concentrations)14. At such low doses, tocotrienol was reported to be able to reach the brain and to provide protection against stroke15. It is interesting to note that, only α-tocotrienol but not α-tocopherol, protects neural cells from neurodegenerative diseases by virtue of its more superior antioxidant property.

Tocotrienol is indeed one of the most fascinating members of the vitamin E family. Abundantly available from palm oil, tocotrienols are regarded as the millennium’s most promising natural resource in influencing human health and disease prevention.

Palm oil has a history of food use of over 5000 years and has emerged as a preferred oil of this millennium by billions all over the world. More than 150 countries worldwide favour it for its natural, versatile and excellent properties. To those who wish to reap the benefits of this oil and its products, the Malaysian Palm Oil Council (MPOC) will be your trusted information provider. Please visit MPOC website at www.mpoc.org.my for more information.

Source:
1. Sundram K. et al. (2003). Asia Pacific J. Clin. Nutr. 12 (3): 355–62
2. Theriault A. et al. (1999). Clin. Biochem. 32: 309-319
3. Suzuki Y.J. et al. (1993). Biochemistry. 32 (40): 10692–9
4. Serbinova E. et al. (1991). Free Radic. Biol. Med. 10: 263-275
5. Tomeo A.C. et al. (1995). Lipids. 30 (12): 1179–83
6. Theriault A. et al. (2002). Atherosclerosis. 160 (1): 21-30
7. Qureishi A. et al. (1995). Lipids. 30 (12): 1171 1177
8. Traber M.G. et al. (1998). Lipids. 33 (1): 87–91
9. Guthrie N. et al. (1997). J. Nutr. 127: 544S-548S
10. Nesaretnam K. et al. (1998). Lipids. 33 (5): 461–9
11. Srivastava J.K. et al. (2006). Biochem Biophys Res Commun.346 (2): 447-53
12. Yap W.N. et al. (2008). Br. J.Cancer. 99 (11): 1832–41
13. http://clinicaltrials.gov/ct2/show/NCT00985777
14. Sen C.K. et al. (2000). J. Biol. Chem. 275 (17): 13049–55 15Khanna S. et al. (2005). Stroke. 36 (10): 2258–6

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