Dr Tan: Yes. There were a lot of studies at the beginning that were extracted…wheat germ was because it had a huge abundant source. It’s original discovery of vitamin E itself was from spinach, because of two pediatrician. It’s not a lot in spinach, but these two pediatricians were studying it in rats to bring the fetus to full-term. And that’s why vitamin E is a birth vitamin. Most people may or may not know, they may know them as an antioxidant, but not as a birth vitamin. But it became a vitamin because of the ability to bring it to full-term. And then also for the beginning, I’m not exactly the person that discovered tocotrienol, instead, I discovered a pure source of tocotrienol directly from a plant, and the plant is called annatto. If I tilt my head a little bit… I’ll come back to the same place, so don’t get… If I tilt my head for a little bit, you see in the back here? See here?

Andrew: Yeah.

Dr Tan: That is from the annatto plant. I also discovered this special vitamin E from palm and also from rice. So that’s my, really, claim to fame. But tocotrienol was known in 1960s, I was a mere 10-year-old then, but its utility and its abundance in nature was not known until at least 20 to 30 years later. And then another 20 to 30 years later before we now know what tocotrienol vitamin E is even beneficial. Hopefully, we will uncover some of these in the interview today.

Andrew: Right. Gotcha. Okay, because like, you know, in the old days when I knew vitamin E, my history of it was that the major exponents of it were the Shute brothers, Wilfrid and, can’t remember his brother, cardiologists. And they were basically laughed out of cardiology for suggesting that vitamin E had any beneficial effect in cardiovascular disease. Dr Lady Cilento, an Australian GP, used to also tout its uses, not just for cardiovascular disease, but for many other uses as well. But then it fell into ill-favour, and there was quite a few negative trials, there was the chaos study, and it sort of while seemingly positive, there were certainly its detractors. But there was many others. So it’s sort of gone through this whole lifecycle. So, when did they know about tocotrienols and when did they think maybe it’s not the tocopherols that are the important part?

Dr Tan: Okay. Let me see if I can paint a broad paintbrush on the timing. Tocopherol was discovered about 40, 45 years before tocotrienol. So the discovery of tocopherol was 1922 by 2 pediatrician from UC Berkeley, like that. And tocotrienol was not discovered until the 1960s, like that. And when tocotrienol was first discovered, it actually was as early in 1962, 1963, but it was so close in structure to… I have a structure here, I know this is only an audio thing, this is for your concept. If you see here, where my finger is pointing, there is a double-bond here, here, and double-bond here again, and the last double-bond is here. So because of these three-double bond, the tail is called triene. It just means three double-bond. A tocopherol would have the same tail, but the three double-bonds would not be there.

The antioxidant head will be in here. A tocopherol and tocotrienol would have the same head, and this would be the antioxidant head, that’s it. So because of the structure that’s so similar between tocopherol and tocotrienol, even in the early 10 year, 20 years of tocotrienol discovery, they have other Greek letters. The four common one is alpha, beta, delta, gamma-tocopherol. You will also see epsilon, nu, zeta, and phi tocopherol. Those tocopherol are actually tocotrienol. It was not until 2002 or 2003, they fix it. So, not only is the identification 40 years later, the nomenclature was also been delayed. So, that means, it’s almost as if that if we wait any longer, tocotrienol would have never been known. So, I persisted with tocotrienol in my earlier career, and then have stayed on in the last 30, 40 years to study it. And surprisingly and happily, it have differentiated properties from tocopherol, very different property. Today, we know, and 30 years ago, 40 years ago, when I started, I did not know. I just knew that the compound had different structure, slightly different structure, but the slightly different structure bear enormous difference in functions.

Andrew: Right, okay. So, just going back, that’s really interesting about the evolution about the naming of it, the nomenclature. So, it’s basically like how tuberculosis used to be called consumption. So if you look for tuberculosis in the early medical papers it’s not there because it was called something different. But can you take us through that evolution of vitamin E with the concentration of alpha-tocopherol? And whenever there was a negative trial, the defendants used to come back and say, “You used the synthetic form the dl-alpha- tocopheryl,” or, “You’re concentrating on alpha-tocopherol, not gamma-tocopherol.” You know, was there the, forgive me, tocotrienols, hiding in the background doing its work, but we were concentrating on these other molecules, because that’s all we knew?

Dr Tan: Not so much hiding in the background. It’s just that from the delay in terms of its 40 years after on its discovery, and then misnomenclature, that’s the timing of the tocotrienol. But for the tocopherol side, is very simple. About 15 years after the discovery of tocopherol, tocopherol is known to be a very powerful antioxidant. It is known to protect lipids and fat in the plant. It’s not a substance for people. It’s a substance known in the plant. And they’re found in nuts, anything that is rich in oil and fat. So it’s known to protect the vegetable oil from going rancid, so it’s known as a potent antioxidant for the fat.

Now, since then, people study animal cell line study throughout the ’60s and ’70, a lot of study with tocopherol. Forget the tocotrienol for the time being. So when they did those studies, it looked like the more tocopherol they add on to the animal or the cell, the better the protection would be. And somewhere in the 1950s and ’60s, you mentioned about the Shute brothers in Toronto, they begin to give to patient, apparently it helped the patient a lot. So, now, you fast forward a little bit to the 1990. So there were huge clinical trials that use 400 milligrams, sometime they use synthetic vitamin E. And initially they all use synthetic vitamin E. And after another 5, 10 years, it didn’t quite work. So they change it to natural vitamin E. And then another 5, 10 years passed, and still it didn’t work.

So, if you sum up all the clinical trials from synthetic to natural vitamin E, they were all about alpha-tocopherol. And that was when they found out that, at best, it didn’t work. At worst, it may do some harm. So then people begin to raise the question, could it be the gamma-tocopherol did work, but nobody was making gamma-tocopherol. Gamma-tocopherol is abundant in the plant, but nobody synthesized to make it for consumption purposes. Not them. So now, in the middle of all this happening, I show up with others at early 1980s, and discovered this first from barley, a source that nobody cares about, and then from palm oil. And then we decided to do studies on it. So we were actually doing studies on it, almost like in the shadow of tocopherol. And it’s almost as if, in the mid-90s, right when we were finding some interesting findings on tocotrienol, and all these tocopherol studies came crashing down. I thought our days of tocotrienol research is going to crush with the tocopherol. But I persisted. The tocopherol went down. I continued to do research on tocotrienol. And then we found out that it worked on many chronic conditions. The tocotrienol does, but not tocopherol.

Andrew: Gotcha. And I also have to ask about the antioxidant theory, because I’ve sort of…I waver with the antioxidant theory. So, you know, electron transfer happens. Oxidation is an essential part of life in the electron transfer chain. And then we talk about these antioxidants, but is it more of just a biochemical or an atomic-level action that might even happen with [inaudible 00:12:09]? But the real action, or the real important thing is does it help Mrs Jones’s condition? So, how much do we concentrate on the antioxidant theory and how much should we now be really concentrating on endpoints on, not just markers, but actual human benefits?

Dr Tan: Yeah. Let me answer the first part on the antioxidant theory. The benefits to human life, I will touch on that. It’s a very insightful question you have. The initial part about the antioxidant work was, it was very elegant. You have this tocotrienol tocopherol molecule. It’s part of a ring, and is able to satisfy itself to capture the free radical of fat that is easily oxidizable. It’s very neat. It’s very clear chemistry. They did that. And it showed up in fat oxidation, they did it on butter. They stress the animal, and is able to capture the free radical, so it fits the mechanism. And so, I as a young chemist and biochemist in the 1980s, I bought into that. So, no shame in doing that. We just bought into that. And then later on, when the clinical trials fail, it’s just like a domino one after another with alpha-tocopherol. They were positing that the alpha-tocopherols must be the end game in capturing the free radical. It didn’t do that. And when it didn’t do that, it raised a lot of doubt in people’s mind. Could it be the free radical understanding the antioxidant thing not working, or it’s just simply not able to bring it to pass in, I call it phenomenon. When it happened to people, it didn’t work like that.

I think that the free radical and the antioxidant theory hasn’t gone away. I think that we were over-enthused to say that the antioxidant theory is explaining everything. But it just did not explain everything. So when we conduct clinical trials now, of course, hindsight is 2020, like that. We would do antioxidant study of fat, of lipids, that are in the blood, the MVA, mevalonaldehyde drop, the antioxidant, I know you gave up some ROM and ROS thing, we sometime measure that. But we limit it, because if you do this, then the comments that you can make, Andrew, would be phrase that you say proxy.

So, words that people use would be a proxy to predictors, biomarkers, indicators, or even blood enzyme. None of this is necessarily bad. So, we decided that, when we start to do clinical trials on chronic conditions, right now, of course, we are talking about 20, 30 years after, so I’m not talking in any boastful manner. It just that we learn from the past, and I don’t want to repeat things that people do. And still harping on the antioxidant thing, this is not to say that tocotrienol is not. We have so many study. If you ask me, I can tell you

later how tocotrienol is superior as an antioxidant to tocopherol. There’re actually hundreds of studies. They’re superior, but I don’t want to posture that to you.

When we study it, we study chronic condition people, clinical trial of type-two diabetes, pre-diabetes, people with fatty liver disease, metabolic syndrome, we study all this. And now, we’re conducting study on obese men and obese women study, severely under stress. So when we study, let’s pick up one. Type-two diabetes. The patient is gonna ask, “Dr Tan, does it work, or does it not work on my sugar?” They’re not going to ask, how does it work as an antioxidant? Don’t say anything, yes or no to sugar? They’re going like that. And then, for the fatty liver people, they’re gonna say, “Do I have fibrosis of the liver or not? Is my liver enzyme increasing or not?” So we study that dramatically. And we found that they’re still a proxy, but they are closer to the problem organ area. And right now, we are doing a third clinical trial on fatty liver. We already done all the other ones. The third one, we’re gonna have a CAT scan or MRI on the liver. So those are not giving you proxy. You either see fat deposit, or you don’t see fat deposit. So we do that. But we still measure a C-reactive protein, for example, to inflammation. We study mevalonaldehyde for measuring fat, and then we measure oxidized LDL to see if it just LDL, which is a potential atherogenic. But oxidized LDL is definitely atherogenic. To see if the oxidized LDL has increase or not. You follow what I mean?

Andrew: I do.

Dr Tan: So, we still do some of those, but they’re not our endgame anymore.

Andrew: Gotcha. Okay. So, with those papers, when I was doing the research for our podcast, you know, whatever the total file levels and things like that, they’re just a proxy, and we may as well use ALT, AST, GGT, you know, your liver enzymes. We may as well use CRP, more orthodox method. One that I’m not familiar with, was the, forgive me, the mevalonaldehyde, is that right? Mevalonic…I’m used to mevalonic acid.

Dr Tan: Mevalonaldehyde. Mevalonaldehyde is fatty acid, the final breakdown product of fat.

Andrew: Right.

Dr Tan: So the final breakdown product of fat, they are stable, and they’re measurable. And then there are some intermediate one, it just slipped my mind, is oxidized, they’re kind of like a fatty acid, but they’re stable enough that when you measure them, it’s reliable. Lipoxide, something like that. We measure that occasionally. We also measure deoxy guanidine base, which is a DNA base that is stable to do this. We have those, Andrew, we measure them. I know time doesn’t permit us because we only have a short time. We measure these, and they consistently drop. Why? Because tocotrienol is a powerful antioxidant. They’re working. But if it is were to be a college professor, if I would publish a paper, would do this. I’ll get something to publish clearly differentiated from the control. But we are trying to make a product that is useful to people.

So, we have to figure out a way to study does it work on improving the insulin? Does it work on managing the sugar? Does it work on reducing the triglyceride? Those parameters, on pre-diabetes and diabetes. Does it reduce scarring tissues on the liver, or fatty liver? Those are the thing. And then, in the current obesity study, we actually going to get biopsies of the adipose tissue, because they are obese people. And then we’re going to study the leptin and adiponectin. These are not the marker, these are the actual reagent that helps the protein that help it to burn the fat or store the fat. So we’re directly studying something like that. And they are not necessarily easy to do. And you have to get institutional approval to do. It’s easy to do this with animal study. It’s not easy when you come to human being. If it were to be, we would have biopsies on all the organ tissue. We can’t do that. We can only get biopsies tissue when people is clearly sick in that area like people who have liver cancer, then you can get the biopsies done. But otherwise, is that huge desire to know, but we cannot access it. And by the way, when we do the adipose tissue, we know for example from animal study, the tocotrienol is deposited into the adipose tissue. So, now with that adipose tissue, we’ll be able to see how much of the tocotrienol is stored when people take it. So that’s a true bioavailability measurement, as opposed to an emotional one on the blood.

Andrew: Yes. Oh, my goodness, I could go so many ways here with so many other supplements that speak about bioavailability when they’re not, they’re talking about absorption. Thank you for covering that. But just a last question, and I hate to be the sort of devil’s advocate here but I’m really curious, and that is, why not give the alpha-tocopherol or beta-gamma-tocopherol with tocotrienols? I was looking at the molecular structures of them and how they sort of bend apart, if you like the fatty acids in the cell wall, is that part of how they work? Do we need to blend them together, or should we just forget the tocopherols and use tocotrienols from now on?

Dr Tan: Okay. I’ll answer the second one first. The tail of a tocopherol, tocopherol here, they do not have the three double-bond here. The tocopherol tail is longer. The tocotrienol, because of the three double-bond, the tail is shorter. So, therefore, the tocotrienol is able to circle the cell membrane much faster, fifty time faster than tocopherol, it’s basically spinning around the cell. The tocopherol still move around the cell, but it’s moving 50 times slower. So, therefore, this is a metaphor, works in the U.S. I’m not sure if it works in Australia. We have local police. The local police are confined in the area of the town, they do not cross to the next town. The people that cross to the whole state, they are state troopers in the U.S. And the people that cover the whole country, they’re FBI agent. So FBI agent covers the whole country. State trooper covers each state, and the police cover this town. So, I think of a tocopherol, because it’s moving slowly, it capture the free radical in the town, because it’s not moving very fast. Well, so tocotrienol, the tail is shorter. It’s able to spin around the cell fast, 50 times faster, therefore, is able to capture the free radical of the entire state, essentially covering a much larger surface area. So, in that way, that’s why it is a more potent antioxidant.

Now, let me answer your second question. Do we need tocopherol? We do not need tocopherol only in this sense. Only in the sense that alpha-tocopherol blocks or interferes with the function of tocotrienol. This is repeatedly shown in the last 20 years in cancer, in diabetes, in lowering cholesterol, so I just gave you some example. And also, high amount of alpha-tocopherol seems to be negative, some of them you mentioned, on a clinical trial. But I care mostly on the first one, because tocopherol interferes with the function of tocotrienol. So if you wish tocotrienol to have cardiovascular benefit, metabolic syndrome benefits, diabetes and cancer, then it is best not to put in tocopherol that interferes with the function.

So now, I’m sure the audience is wanting to know, like, why alpha-tocopherol interferes with the function of tocotrienol. There are several mechanism that people propose. The simplest one it is. Of the four tocopherols and four tocotrienols, only alpha-tocopherol has a transport protein. Meaning that, it has a right of passage that a protein will hold onto the alpha-tocopherol, it goes right in. All the remaining seven tocopherols and tocotrienol, they will go to what we call passive diffusion. Engineering term. A difference in concentration to put over, but alpha-tocopherol has a transport protein, it has a rite of passage, just like vitamin D, just like retinol, vitamin A. So alpha-tocopherol is the only one. So if you consume food with alpha-tocopherol, all the alpha-tocopherol will go in without any assistance because of the transport protein.

Andrew: Okay. So, that answers so many questions in itself. But also, what about the different tocotrienols? Do they interfere with each other? Should we be favouring certain ones over others?

Dr Tan: So far that we have tested, only the alpha-tocopherol interferes, but so far it’s clearly tested. Alpha-tocopherol interferes with the absorption of gamma-tocopherol. If you Google, you’ll find lots of study, one. And two, alpha-tocopherol interferes with the functions of all the tocotrienol.

Andrew: Of all of them? Okay. So, now going on to the tocotrienols, should we be favouring certain tocotrienols over others? Do they have varying actions?

Dr Tan: That’s a good question. In the late 1990s, early 2000, at the time, researchers and scientists were curious. You have four tocotrienols, alpha, beta, delta and gamma. So, they compared them individually. And when they did, the rank order of efficacy is, delta is more active than gamma, in turn more active than alpha, and beta-tocotrienol is almost not active at all for most of the time. So once again, delta is equal to or twice as active as gamma, typically. And then in turn, gamma-tocotrienol is about anywhere from 2 to 10 times more active than alpha-tocotrienol, with very few exceptions, like that.

So, now having said that, the unique finding of annatto tocotrienol is this. When I first took annatto tocotrienol to analyze, the annatto…if I just move my head, you see the red colours in here, those are carotene. And carotenes are very unstable. I expected that something is protecting the carotene. At the time I didn’t know what it was, and thinking that it’s probably a polyphenol. And when I analyzed it using high-pressure liquid chromatograph a while back, long time back, and I was surprised I only saw two peaks, and I thought it must be alpha-tocopherol somehow, because plant makes alpha-tocopherol or gamma-tocopherol. I found neither alpha-tocopherol nor gamma-tocopherol. I only found delta-tocotrienol and gamma-tocotrienol. And I remember, that was about the year 2000, and I thought, “Wait a minute, delta-tocotrienol in all the other animals study is the most potent and gamma-tocotrienol is a close second.” And now, when I analyze it from annatto tocotrienol, it’s got 90% delta, and 10% gamma. So, it has 90% of the most potent vitamin E, and 10% of the second most potent. Then I immediately called my colleague at the time in University of Wisconsin. And I remember Dr Qureshi said, “Barrie, if tocotrienol is ever going to work on human being, your annatto tocotrienol better do. If it doesn’t, then all cause tocotrienol work is useless.”

So from then on, I committed my life to continue to purify the tocotrienol. So now you fast-forward 25 years, we have lots and lots of clinical study, and really grateful to report, in everything that we have done clinical trials it worked. This annatto tocotrienol is supposed to be a drug. But we are not making it a drug, we just do this study and publish it, and so you see that. If you go on our website, we cite all the papers that we’ve been studying, and they’re continuing to come. So, I’m eternally grateful. And this is something I just stumbled on when I was in South America looking for totally something else in that part of the Amazonia. Remember, Andrew, there are 50 million chemicals on earth. And I happen to stumble onto a plant that happened to give me two of the most potent thing. I’m really grateful if I can pass this thing on to be of use

to other people. That would be such a fantastic way to finish my career. So I’m still working on this until the studies come through, so there you have it.

Andrew: Well, you know what, it’s one of the things that impressed me about you when I was reading your book, and it was your love of plants. And I remember the story, you’re in South America looking at some plant and there was one annatto plant. And you found that, and you were just drawn to it. And you said something very interesting there as well, which I’ll get back to a little bit later. But before we do that, when we’re talking about annatto versus palm, you know, like the palm oil, you know, has huge ethnobotanical issues. What about annatto? Is it grown ethically? Is it causing the destruction of, you know, virgin forests like we’re seeing in Indonesia and things like that?

Dr Tan: Thank you for asking that question. I don’t get asked that question often enough. When you think about palm oil, it is a global vegetable oil, much less expensive than soya oil. And remember, soya oil is already dirt-cheap. Because in the U.S., we use soya oil as a byproduct of soy protein and corn to feed the animal. So the vegetable oil coming from soy is already cheap. And against that, palm oil is even cheaper than soya oil. So for the part of Southeast Asia, particularly Indonesia and Malaysia, there’s huge amount of it. And then, you and I read the same thing, deforestation, and an ethnobotanical problem, and all of this, like that. Now, if you stop there for a moment, you flip to annatto, annatto is a drop in the bucket. Because annatto is grown for the benefit of the colour. If you go to your Australian supermarket to buy a hunk of cheese, that beautiful orangey-yellow colour is annatto colour, if they do not put synthetic colour. If it’s synthetic colour, that is worse. But if it’s normal colour, it will be cheese. Sometimes they use that for colouring ice cream, meat to systematize the colour, but it’s famously used for colouring cheeses, like that.

So for colouring cheeses, compared to a vegetable oil like palm oil for human consumption, and palm oil is also used as a biodiesel. So that means annatto usage will pale compared to, it’s really literally a drop of water in the ocean compared to palm oil. So, it almost have… And also, there are no massive annatto plantation. There’re no such thing. They are small sharecropper, subsistent farmer that they sell the annatto seeds to the processor, the processor process that bixin we use, the remaining of the annatto oil, and then we purified it further to make…it is almost as if that if it is not, then after they process the annatto colour, it will be thrown to waste. So we’re actually saving what is not used to get the tocotrienol. So it’s hardly disrupting anything in nature.

Andrew: Thank you for answering that. That eases my mind. Barrie, we have to get deeper into the trials that you’ve done, because they’re really important. Now, you were talking about liver enzymes, and you were talking about diabetes. You know, we’ve got a huge issue of nonalcoholic fatty liver disease, you know, it’s estimated to be 30% of the Australian population, and we are a lot of drinkers. So tell us a little bit about the work that you’re doing with nonalcoholic fatty liver disease, and indeed other liver diseases, cirrhosis, things like that, but also diabetes, these are very important.

Dr Tan: Okay. The liver disease thing has a story in and of itself. It was a fame, Ohio State University professor, and he was needing to do tocotrienol in head trauma stroke patient. But the National Institute of Health said that to give him money, which they were going to give him the grant for, he need to give human subjects to know that these tocotrienol is found in different organs in the body without him…so he had to figure how to do that. And the university happened to say to him that, “Well, we have a liver failure patient.” Remember, he’s studying trauma of the brain, but the only patient that they have is end-stage liver failure patient. You probably know where I’m going with this, and then they are not expected to live. So, they give them the tocotrienol, and then they would not be expected to live. I don’t remember the time. Let’s say three months after, they are no more. Surprisingly, for the one that did die, they were able to show the tocotrienols were found in different organs on the cadaver tissues. Surprisingly, half or so of the patient didn’t die. So they have an accidental finding that the tocotrienol, help to improve the liver. So, it was an accident finding.

I did not find it. Somebody else found it with the palm tocotrienol, which is about 25% tocopherol and 75% tocotrienol, in the palm. So, I surmised that if I gave them annatto tocotrienol that is free of tocopherol, it ought and should work better than palm tocotrienol. That’s where my opportunistic entry into this is. So, I didn’t sort of…so when we started on that, and sure enough, the first study was for three months, the liver enzymes dropped. And then we found out that they dropped about 10 pound, nothing to sneeze at for people who have fatty liver, because they’re overweight. So, we did a six-month trial, they continue to drop their weight. This is not a weight-loss product, but their weight dropped, nothing to sneeze at, and the liver enzymes continue to drop, the C-reactive protein dropped. And so we then did a liver scarring tissue and then a liver fibrosis, they also reduced on the scan that we have. So now, we finally did a 12-month study to do this. And with the 12-month study, we’re gonna have a CAT scan or MRI. And with that, I’m done. I’m going to bury the hatchet. I’ve done everything that I could.

Remember we’re not making a drug. We wanted to show this would work. That’s on a fatty liver thing. And we did not study people with cirrhosis, but we did do in the…you asked me other liver disease, when we did do the study, we excluded people who have hepatitis C, which is a virus cause of a liver condition, which clearly can bring cirrhosis if the liver succumb. And so about 9 to 12 patient were excluded from the study. Unbeknown to me, the investigator gave them tocotrienol. They’re not part of this study. They were excluded from this study. And then some years later, they published the work. I said, “Hey, what’s this about?” So they told me after the paper was there, and they found that even for people who have hepatitis C, the tocotrienol would still work to reduce the damage on the liver. So if you ask me what tocotrienol can do for the liver, it is a liver hepato-tonic thing. We did not study, we hope someday we can do a liver cancer study. All the cancer study in Denmark currently are colon, lung, breast, and ovary cancer, but not on liver cancer. So that’s on that part.

I want to address the second one because you asked me to, on type-two diabetes. So we gave to people about 250 milligrams, not very high dosage. The fatty liver was on 600 milligram, the type-two diabetes we studied for 6 months, which is long enough. The sugar dropped, the insulin sensitivity increased, and then there’s a measurement that the American Diabetes Association support is HOMA-IR. That stands for homeostasis… It basically is a measurement of the sugar and the insulin together. So when you map this resistance, and HOMA-IR also would drop. So I know the HOMA-IR dropped, insulin sensitivity increased, and A1C, which is measurement of sugar over three months also dropped, and the emotional glucose overnight fasting also dropped. And then we thought, “Well, I am a happy puppy,” because all these are direct measurement of it. Of course, we also study the mevalonaldehyde, we also study the C-reactive protein, we also measure the weight drop, we also measure the triglyceride, all these secondary markers also drop, but the main primary markers as it pertain to diabetes drop.

So right now, we are studying pre-diabetes. So, in other words, they’re short of being diabetic. So that study, we were indicated that it’s promising, but the study has not been public. So pretty much in the entire spectrum on metabolic syndrome, it helps. In other words, pre-diabetes, and then diabetes, and then fatty liver, and then NASH. Fatty liver is NAFLD and NASH. So, we have not gone all the way to study cirrhosis. We are hoping to do a cirrhosis study in Argentina. As you know, Andrew, it’s easy to say what study need to be done, but it’s hard to design and even longer to wait. So we are thinking to do liver cirrhosis or NAFLD study in Argentina. So we don’t know if that’s gonna to pan out, but as far as I’m concerned, it works on liver, it works on diabetes, and now we are doing it on obesity, because obesity is also an epidemic in the U.S. now.

Andrew: Right. And then obviously, following on from there would be cardiovascular disease. Something that really interests me, and I only recently found this out, was another compound in annatto. And I am going to read this out, because I will murder this word if I don’t. But that is geranylgeraniol.

Dr Tan: Yes. It is geranylgeraniol. Yeah?

Andrew: So, what I was really interested in here was that it’s an isoprenoid. And what interests me there is its association with CoQ10, which is used commonly for cardiovascular disease. So where do we go here with annatto and cardiovascular disease?

Dr Tan: Yes. Let’s say this would be a CoQ10. So, the CoQ10 ring is here, and the CoQ10 tail is exceedingly long, you can see here. And then about here, where my finger is pointing here to here, that is GG. So, two GG will be here, two and a half GG would be here. So, the entire 2.5 length of the tail of CoQ10 is GG. That’s how the body use a GG to make CoQ10. I’m wrapping it here, this is a pure cartoon. If this is tocotrienol here, and this is the ring of the antioxidant of a tocotrienol, the entire tail of tocotrienol is GG. Human being cannot use GG to make tocotrienol, but the plant use GG to make the tocotrienol. So, GG is using the plant to make tocotrienol. In the human body, GG is used in the body to make four things to the best of my knowledge. One is to make CoQ10 that you mentioned. Skeletal muscle protein is used GG to make. Menaquinone-4 (MK4) is made directly from GG. And the last one is to promote the production of testosterone, particularly of the elderly. I think we should leave the last one out. And MK4, if you read about that, is for cardiovascular health, it’s for anti-arteriosclerosis and bone health. And CoQ10 is for energy. So you can see that. But the main thing would be for skeletal muscle protein synthesis.

So, let’s take the skeletal muscle protein synthesis. When people take statin drug, it’s supposed to inhibit the isoprenoid so that it does not make cholesterol. A good thing. But about several steps down, it is obligatory when you inhibit the cholesterol synthesis, it also inhibit GG that the body makes. So, because it inhibit GG, therefore, the body also saw reduction of CoQ10. So if you see CoQ10 reduction for people who take statin, it’s because statin inhibited the GG. That’s it. That’s the reason why CoQ10 dropped. But the main reason the cardiologist is worried about with the patient is really not CoQ10. CoQ10 is what you and I are worried about, because we’re alternative and we are holistic.

The doctor, the cardiologist is concerned that the patient would have back pain, trunk muscle pain, and muscle pain. Why is that? Because trunk muscle pain and back pain, they are skeletal muscle protein. And GG is required for the synthesis of skeletal muscle. So, when you inhibit cholesterol synthesis by statin, it inhibit GG, and thereby also reduce the ability of GG to make skeletal muscle. So, therefore, if you add GG back to statin, it’s fantastic, because it makes CoQ10 reverse that and also reverse the damage cause of myopathy by statin. This is very exciting.

Andrew: This is very exciting to me as well because what you’re talking about there, skeletal muscle protein, you’re talking about supporting at least and hopefully reversing sarcopenia. And it answers also something that happens with statins and that is weight gain. So, Barrie, I could talk to you for hours. I’m learning so much. Would you be happy…? You go.

Dr Tan: I want to say something, right? It is an Australian scientist. And if you hear this, she’s probably tickled pink. She’s based in Queensland. Her name is Doctor or Professor Jordon Irwin. And she did four groups of animal study. A control group, that means just normal rat. Rats with statin, second group, rats with statin and GG, and rats with just GG. So if you compare rats with GG and the control group, she saw that the muscle power of the rat increased. So that would work on exercise people, exercise signs, or on the elderly to prevent sarcopenia. When she did the statin group, the second one, the statin reduced the ability of the force production. And when she compared the statin group and a statin and GG, she found that the statin and GG is able to reverse the damage caused by the statin. That study was only published last year by an Australian scientist, in your neck of the woods. So, it’s amazing. And if any of interest to you, my folks here can send you those papers. If you want another time to do another interview, I would love to do that to follow up on this.

Andrew: Oh, please. I would love that. I would love… And I’m definitely going to get in touch with, is it her, Jordon Irwin?

Dr Tan: Jordon, yeah, J-O-R-D-O-N Irwin, is a she. Jordon Irwin. And I think she’s based in Queensland, somewhere. I don’t know the precise address at the university.

Andrew: I will find her out.

Dr Tan: And she was on…

Andrew: Because I live in Queensland.

Dr Tan: Yeah. What did you say?

Andrew: I live in Queensland. I’m in Queensland.

Dr Tan: Oh, okay. So, you will be…and we were wanting her to see if she could continue to study with us, but she has moved on to other studies. Otherwise, we would love her to continue to study. But we’re highly grateful for the seminal work she did. And we are having other people in Texas and elsewhere to continue to follow up on that study and to do some clinical trials on exercise signs, on people that take a statin, on the elderly population. So more to come. But the tocotrienol, because we did that earlier stage, so we’ve lots of study on tocotrienol, much less study on GG at this point.

Andrew: Right. Well, I look forward to so many more studies coming out with GG, but also, we’re going to put up all of the show notes. And I’d love to put up as much research as we can on the tocotrienols, the delta, gamma especially. Dr Barrie Tan, thank you so much for taking me and us through, not just vitamin E, but also the benefits of tocotrienols. It’s cleared up so many aspects in myself that I was unsure of about vitamin E and its history, and it answers why we need to, you know, bend and just leave tocopherols behind and concentrate on the tocotrienols. But thank you so much for joining us today on “Wellness by Designs.”

Dr Tan: Thank you so much. Blessings.

Andrew: And thank you, of course, for joining us today and listening to Barrie Tan. Remember that you can catch up on all the show notes on the Designs for Health website, as well as the other podcasts on your favourite podcast app. Thanks so much for joining us on “Wellness by Designs.” I’m Andrew Whitfield-Cook.