October 2012: Letters to the Editor

Dear Editor,
I reviewed WholeFoods Magazine’s recent article, “Tocotrienols: Emerging Science and Innovations of Vitamin E,” (August 2012, p. 52), and found some discrepancies in the information prepared by Drs. Passwater and Tan. Specifically, the following appeared:

Tan: Recently, a clinical study showed that all tocotrienol isomers are actually bioavailable to human tissues (67). Tocotrienols deposited in adipose tissue and the heart, crossed the blood-brain barrier, metabolized in the liver, and were surprisingly low in the blood and skin. My interpretation of the study is that the composition of delta- and gamma-tocotrienol was 1:4—or 20% and 80%, respectively—in the supplement, while tissue distribution in the adipose, blood, skin and brain was reversed at 2:1 or 67% and 33%, respectively. There is strong support that tocotrienols are bioavailable to human tissues, and that delta-tocotrienol’s bioavailability is superior.

The above refers to a paper published in the recent Journal of Nutrition*—the only human clinical tissue distribution study on tocotrienols and it was carried out on Carotech’s Tocomin SupraBio®, a patented and bioenhanced full-spectrum tocotrienols complex. The supplement used in this study was the full-spectrum palm tocotrienol complex, with d-alpha-, d-beta, d-gamma- and d-delta-tocotrienol (Tocomin SupraBio®), and not a gamma-tocotrienol or delta-tocotrienol or any generic tocotrienol oil extract.

Due to different composition and bioequivalence/bioavailability, one cannot claim that data/results from Tocomin SupraBio® would be the same as any generic oil extract (tocotrienol).

In addition, data from the paper indicate that the tissue distribution result was in adipose, brain, heart and liver. It was not in the adipose, blood, skin and brain, as indicated in the WholeFoods article. And, the level of alpha-tocotrienol and gamma-tocotrienol was much higher than delta-tocotrienol in these tissues, contrary to what was indicated in your article. Hence, delta-tocotrienol’s bioavailability is not superior, as indicated.

I also disagree with Dr. Tan’s statement, “My interpretation of the study is that the composition of delta- and gamma-tocotrienol was 1:4—or 20% and 80%, respectively—in the supplement while tissue distribution in the adipose, blood, skin and brain was reversed at 2:1 or 67% and 33%, respectively.”

While the composition of delta and gamma tocotrienol in the supplement (i.e., Tocomin SupraBio®) was right (the actual ratio is 1:4.4), the tissue distribution in the adipose, blood and brain was not reversed. The ratio of d-delta-tocotrienol to d-gamma-tocotrienol was approximately 1:2 in adipose and brain; 1:38 in the heart; and 1:3 in the liver. As such, it is inaccurate to say that in these tissues, the level of delta-tocotrienol is higher than gamma-tocotrienol. It is the opposite.

Based on published papers, the fact is that each tocotrienol has its own unique health benefits and strength within the body. The best way to supplement is to take all the four forms of tocotrienol as they occur in nature/diet.

In addition, the low tocotrienol concentration in the blood is due to tocotrienols’ short half-life of about four to six hours in the plasma. This was proven in published pharmacokinetic studies and, hence, prove that tocotrienols are absorbed and are actively and significantly deposited into the various tissues in the body.

For more information about tocotrienol, please visit the educational Web site: www.tocotrienol.org.

We thank you WholeFoods for sharing the above with your readers.

Bryan See, Regional Product Manager, Carotech Inc.

* Reference 67 is as follows: Patel, V., et al., Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients. J Nutr, 2012. 142(3): p. 513-9.

Dear Mr. See,
Thank you for your letter and your comments on the recently published oral bioavailability study of tocotrienols in humans. It’s good to know that you are a reader. We strive for accuracy in all of our interviews and welcome your input. I respectfully disagree with your opinion that there is a discrepancy in the article, but I totally understand why you may feel that there is one. I would like to reiterate that Dr. Tan’s summary of the study was his interpretation only, as he clearly stated in the interview. As you know, data are meaningful only when correctly interpreted and scientific studies often present difficult or confounding interpretations. Numbers are meaningless without valid interpretations, and sometimes there may be more than one valid interpretation. Thus, I have posed your comments to Dr. Tan for a clarification of the basis for his interpretation. Dr. Tan’s response follows, but first I want to once again thank you for your readership and for bringing this matter up for further discussion. You are certainly welcome to continue the dialogue if you have further questions.

Respectfully,
Richard A. Passwater, Ph.D., Science Editor

Dear Mr. See:
Thank you for commenting on my interview with Dr. Passwater. The points you raise certainly warrant further discussion. In your comment, you address two major categories, including 1) composition and 2) bioavailability/absorption.

1) You are correct in stating that the supplement used in the study was Tocovid SupraBio. This, however, requires some additional qualification. The methods section of the study clearly states that “a single 200-mg Tocovid SupraBio softgel capsule contains 61.52 mg d-alpha-tocotrienol, 112.8 mg d-gamma-tocotrienol, and 25.68 mg d-delta-tocotrienol.” The isomers add up to exactly 200 mg, or 100% of the capsule. This would have been a “tocopherol-free palm tocotrienol” supplement. Is this what you mean? If so, this is not a typical composition of a palm tocotrienol mix or Tocovid SupraBio, as palm-sourced tocotrienols typically contain about 25% alpha-tocopherol. As stated in the study, it can only mean “tocopherol-free palm tocotrienol.”

2 ) As you noted, the supplement used was a bio-enhanced self-emulsifying version of palm tocotrienol (SupraBio). On an empty stomach, self-emulsifying formulations have been shown to be two to three times more bioavailable in the blood as compared to their non-self-emulsifying counterparts (1). Similarly, non-self-emulsifying formulations are about two to three times more bioavailable when taken with a meal rather than on an empty stomach (2). Hence, taking a self-emulsifying formulation on an empty stomach is comparable to taking a natural formulation with a meal. One only needs to take this natural supplement with a meal (a proper thing to do with all lipid-soluble vitamins), thus obviating any emulsifying synthetic excipients.

It is important to realize that blood bioavailability is a measure of convenience, since blood is easily obtained in clinical trials by a phlebotomist. The true measure of bioavailability is in tissues of interest, and much more difficult to obtain, requiring biopsies. Several studies, including the one we are discussing, have shown that tocotrienols are recruited directly to tissues and tumors (3–8), and tocotrienol appearance in the blood is of lesser importance. It would be ironic to talk about bioavailability in the blood when this study expertly highlights the bioavailability of tocotrienols in tissues.

As to the actual tissue distribution of delta:gamma, it is 1:2 for adipose, brain, blood and skin (the latter two available in the supplemental material of the publication). However, this does not account for the fact that delta-tocotrienol had a more than 4-fold lower concentration in the supplement. Therefore, the bioavailability of delta over that of gamma is [1/2 x 4/1] or 2-fold.

I hope that this discussion clarifies my interpretation represented in the interview.

Barrie Tan, Ph.D.

1. S.P. Yap and K.H. Yuen, “Influence of Lipolysis and Droplet Size on Tocotrienol Absorption from Self-Emulsifying Formulations,” Int. J. Pharm. 281 (1-2), 67–78 (2004).
2. S.P. Yap, K.H. Yuen, and J.W. Wong, “Pharmacokinetics and Bioavailability of Alpha-, Gamma- and Delta-Tocotrienols Under Different Food Status,” J. Pharm. Pharmacol. 53 (1), 67–71 (2001).
3. S. Shibata, et al., “alpha-Tocopherol Attenuates The Cytotoxic Effect of Delta-Tocotrienol in Human Colorectal Adenocarcinoma Cells,” Biochem. Biophys. Res. Commun. 397 (2), 214–219 (2010).
4. S. Wada, et al., “Tumor Suppressive Effects of Tocotrienol in vivo and in vitro,” Cancer Lett. 229 (2), 181–191 (2005).
5. L. Brown, “Delta-Tocotrienol from Annatto Oil Ameliorates Metabolic Syndrome Developed In High Carbohydrate, High Fat-Diet Fed rats,” in 2nd International Tocotrienol Symposium, Long Beach, CA, 2012.
6. K. Husain, et al., “Vitamin E Delta-Tocotrienol Levels in Tumor and Pancreatic Tissue of Mice After Oral Administration,” Pharmacol. 83 (3), p. 157–163 (2009).
7. E. Pierpaoli, et al., “Gamma- and Delta-Tocotrienols Exert a More Potent Anticancer Effect than Alpha-Tocopheryl Succinate on Breast Cancer Cell Lines Irrespective of HER-2/Neu Expression,” Life Sci. 86 (17–18), 668–675 (2010).
8. G. Springett, et al., “Delta-Tocotrienol in Subjects With Resectable Pancreatic Exocrine Neoplasia,” in 2nd International Tocotrienol Symposium, Long Beach, CA, 2012.