say it would definitely work in a human until a human clinical tri- al is done and published.
Focus: So, on to humans. Where are you at with human studies?
Sen: The human study started the same year as dog study end- ed. First we proved that the dos- ages we were studying were safe. Then we did a study on over 80 patients who were in end stage organ failure and needed heart, lung, or liver transplants, or pa- tients who suffered from severe epilepsy that required a surgi- cal procedure where nearly a gram of their brain was removed. We gave full-spectrum palm tocotrienols to all these patients, and we studied the organs that were removed, and the brain tis- sue that was removed. To make a long story short, the tocotrienols were efficiently absorbed into all the organs including the brain. We also found something com- pletely unexpected. We found that people with end stage liver disease and awaiting liver trans- plantation, began to improve. They experienced a reduction in their MELD (model for end stage liver disease) score. MELD is scored according to the sever- ity of chronic liver disease, and determines the priority and need for liver transplant allocation. So it looks based on these experi-
12 Focus April 2013
ences as if tocotrienols may have a valuable and effective hepa- toprotective function. We pub- lished this in the Journal of Nutri- tion last year.5
We are now in a Phase II clin- ical trial, where we are testing different dosages and regimens to determine what is optimal. And finally we will go to a full- blown Phase III clinical human trial in stroke.
Focus: That’s great. Can we address a few technical aspects of tocotrienols? For instance,
ol absorption.
Focus: What about the fact that tocotrienols are irregularly present in the diet globally? For instance, they are prevalent in palm oil, which is popular in Ma- laysia, but there is very little in the American diet. They are pres- ent in trace amounts in grains.
We found that fifty percent of people with end-stage liver disease, awaiting liver transplantation, began to improve when given an oral mixed tocotrienol supplement.
one concern among research- ers is that alpha-tocopherol, the most famous fraction of Vitamin E, is preferentially ab- sorbed over tocotrienols.
Sen: This is only partly true. When researchers mention that, they are referring to Alpha-to- copherol Transfer Protein, TTP. But we have shown that in TTP knockout mice, tocotrienol transport is not hindered. Thus, TTP-independent mechanisms of tocotrienol transport also exist. It is true however, that alpha-to- copherol in high amounts (over 400 mg/day) taken concurrently may be detrimental to tocotrien-
Sen: If you take an average American off the street and mea- sure the amount of tocotrienols in his or her blood, you’d find very little. Whereas in Malay- sia and Singapore they use red palm oil in cooking and so their diet has a rich source, but even so, the amounts uti- lized in clinical trials are higher than the amount available in
red palm oil consumed as food. These amounts are not achiev- able clinically in the normal diet. For the effects we are claiming, tocotrienols have to be provided through oral supplementation.
Focus: What about the fact that alpha-tocopherol functions as an antioxidant? Do tocotrienols function as antioxidants?
Sen: They certainly do. All Vi- tamin E forms have antioxidant properties. But interestingly, what we are reporting in stroke, we believe is an antioxidant-in- dependent mechanism. We have published four different targets or pathways by which tocotrie-
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