Ep. 234 Metabolic Longevity and Vitamin E with Dr. Barrie Tan

Cynthia: Welcome to Everyday Wellness Podcast. I’m your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent, is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.

Today, I had the honor of connecting with the delightful Dr. Barrie Tan. He has a PhD in biochemistry and he is a vitamin E expert with a focus on lipid soluble nutrients and impact chronic disease. Today, we dove deep into vitamin E, how it plays a role in the antioxidant protection of lipids and fats, what are tocotrienols, his discovery of annatto, the benefits of delta and gamma tocotrienols, why we can’t get sufficient tocotrienol in our diets and why supplementation is so beneficial, the impact of tocotrienols in cholesterol and metabolic health, bone health, and also cancer, along with recommendations and a brief discussion about GG. I hope you will love this podcast as much as I did. It has certainly changed my entire perspective on metabolic and bone health needs relevant to this particular variation of vitamin E.

Dr. Tan, it’s such a pleasure to connect with you, today. Thank you for carving time out of your busy schedule.

Barrie: Well, I’m glad to be on your show and hopefully, this will be a blessing to all the people following you and listening to you. So, I’ve been excited to talk about this lesser known type of vitamin E.

Cynthia: I was actually saying before we started recording that as I was doing research for this podcast, I started to realize that this is applicable to nearly every person that is listening to this podcast. Now, you’re trained as a biochemist and a chemist. How did your background prepare you for the discovery of annatto, which is how you came into this vitamin E expert space?

Barrie: I think I got into that broadly because of my interest in keeping fat stable and so is antioxidant. And on this, I know you didn’t specifically ask this, but I like to give this an illustration and then the audience will quickly grasp this. Many people talk about antioxidant that they should be taking. And so, it seemed there’s a lot of noise in the background. But I think I can help the audience to skim away the grass, so that you can clearly see what stands out. The antioxidant I care about most would be the thing that protect the lipids and the fat. It is true we need to protect the protein, the sugar, and the nucleic acid. Anything oxidized like that is no good. And at the same time, oxidizing just means too much oxygen. We need oxygen to live. But of all the protein, the fat, the nucleic acid, and the sugar, the one that is easiest to oxidize would be the lipid. If you just put a stick of butter out on a summer day, you’ll know exactly what I mean, an hour or two later or you drive past a roadkill that smell, that stench would be clearly that of fat. Now, having said that, now you go back. That means fat is the easiest thing to get oxidized.

In each human body, we have about 38 trillion cells. That’s a big number. It’s about 5,000 times the population of the Earth and each cell has a cell membrane and lining all the cell membrane are fat. It’s hard to imagine. Less than half the fat in our body is where you hold on to your love handle or our butt, for example. I know that sounds crude, but more than half of our fat is actually in the cell wall throughout our entire body and that is what I’m concerned about most because the cell is a gated community. In other words, what goes in and what goes out is very important. If that is compromised, a lot of bad things happen to us and that cell wall is actually fat, which is why you would ask your audience and I would do the same to take high amount of omega-3, everybody knows, good and eventually, the omega-3 would land into the cell wall to make the cell wall more pliable and omega-3 is very unstable.

Of all the antioxidant out there, a vitamin E type of antioxidant perfectly fits into the cell wall because it looks like a sperm or a tadpole, where the hydroxyl group sticks out in the water and inside the water, the tail would be saturated like vitamin E here. The black and white are the very lipid soluble. It sticks into the cell membrane where the fat is and then we go the other side, see the oxygen group, that’s an antioxidant. Now, there are many good antioxidants. I’m sure your audience know this, like lycopene, resveratrol, green tea extract, but they have two heads, or three or four heads. They can have a tail that sticks into the lipid. They are all sticking out. So, it doesn’t really fit. Every time I gave this example, I know it’s very simplistic. It is actually true. It was discovered by a professor in Austria in the 1980s. He was just curious what protects the cell wall and he found nearly more than 90% of the antioxidant in the cell wall. They are either a tocopherol or tocotrienol and if they’re not that it would be CoQ10. And CoQ10 by the way, in the back you’ll see, I have a huge molecule. There you see how much longer antioxidation is right over there. That our body makes. It’s made actually in situ in the cell and it’s just stays there, which is why a huge molecule, so lipid soluble. If you take exogenous supplemental CoQ10, which we should as we grow older and everybody said about how necessary it is to be bioavailable.

The reason they do that is because this molecule is like an albatross. It is very difficult to absorb in a body and that’s why we want to encourage our body to make this because then it’s made in place. Just like we become elderly, someday I would become elderly, to have what they call a room or a home in place. To encourage the CoQ10 to be made in place it’s beautiful but still we don’t have enough, so we supplement and a fraction of them go in. The reason the fraction of them go in is because of the long, long tail. And the tocotrienol is approximately about two and a half, three times shorter. Sorry, it took them too long to explain that, but I think that’s a very important understanding of antioxidant and why I care about the kind of antioxidant that would protect fat and lipid from easily going bad, going rancid.

Cynthia: It’s such an important point and you’re bringing me back to my organic chemistry days, as I’m looking at those very long lot and one on the table behind you one that you were carrying a few minutes ago and probably equally important is understanding that the cellular membrane, the phospholipid bilayer that this is what holds our mitochondria, other organelles within the cell. We know that our mitochondria as we are getting older become dysfunctional and so these are really important and listeners understand that dysfunctional mitochondria occur with nearly all chronic disease states. I think a lot of the connecting the dots for you is talking about the role of vitamin E and its impact on some of these chronic health issues that so many, not just Americans, many westernized countries are now dealing with.

Barrie: Correct.

Cynthia: And so, there are different types of vitamin E. I think this was an important distinction as I was getting prepped for this interview was having people understand that there are different types of vitamin E. You’re speaking specifically toward the tocotrienols but there are other types of vitamin E as well that do not penetrate that cell layer in the same way.

Barrie: Yes, and there are eight of them, four tocopherols and four tocotrienol. Simplistically, the best-known vitamin E is alpha-tocopherol on the tocopherol side and that was why it was called vitamin E to begin with. And it is very interesting about the misstep and the sites that– This vitamin E was discovered because I know many of your listeners are women and this alpha-tocopherol was discovered as a vitamin E because it helped the fetus to go to full term. That is actually what the– But most people understand vitamin E as an antioxidant. They’re both correct, but the original vitamin E is to bring the fetus to full term, which is why you’ll find alpha-tocopherol in a prenatal, for example.

Then over time, people had studied again, if you have a cell that look like this shape, like a mouse here and then when you have tocopherol, the tocopherol spin around like a kidney bean, so to speak like this relative speed. Why? And then a tocotrienol also the same, except it’s been 50 times faster. Why is the reason that is spent 50 times faster? Here is an example. If this tail were to be a tocopherol, it would be about 20% to 30% longer. If I rotate it, you see that there’s a double bond here. A tocotrienol, three double bonds. Tocopherol doesn’t have that. So, it’s longer. All that to say, a tocopherol inserts itself deep into the membrane. So, therefore it anchors deeply and moves around slower and tocotrienol anchors less deeply, perfectly, molecularly less deeply and spin around much faster. I simplify this for people to understand a tocopherol and tocotrienol, they do the same thing. A tocopherol would be more like a local policeman to catch the bad guy and a tocotrienol would be like a state trooper. You’re able to scan a much broader space and for that reason alone, the tocotrienol is able to cover a much larger space to protect oxidation. It is consistently shown and this is 1997 in UC Berkeley when the professor last did this work.

Cynthia: So, my understanding is that you actually found this tocotrienol in a plant. In annatto, when you were in South America and you identify that it was not bound to anything else, it actually stained your hands. So, I think this is really interesting when I was diving into your background and your research discovering annatto was a type of tocotrienol plant based.

Barrie: Yes, and here would be a younger me with a lot more hair. So, you could see that.

Cynthia: [laughs]

Barrie: I discovered this when I was in South America in Peru. I’ll show you some pictures. And this is a plant. It is really a very beautiful looking plant. This is a picture of annatto. We use it for coloring cheeses. You see, if I scratch this, I notice [unintelligible [00:11:47], it would stain. So, that is the carotene color. And if you look at this fruit carefully, there’s something very unusual about it. If you think of a fruit that you like, it will be the texture, the tartness, and the sweetness and that part that we eat is called a mesocarp. There is no mesocarp. There’re lots of seeds and where the mesocarp is it’s just when you open it. So, therefore, the plant uses to conserve the making of the mesocarp, the fleshy part and make the color, and the color is to deceive the birds up the air and the Amazonian tree frogs thinking it is the food and swallow it and then they’ll spit out the seeds to procreate. That’s it. [unintelligible [00:12:31] smell.

If any of your audience is somewhere near a botanical garden, you ask the botanist, “Where can I find a lipstick plant?” The British discovered it. I still haven’t figured out where it is. I think the original coloration of the lipstick of women being red comes from what the British called it the lipstick plant and today Aveda that make many wonderful natural products. They use this annatto color and they specifically buy tocotrienol to protect the lipstick from discoloration. So, this is one and this is an example of an Amazonian tree frog. The frog is about the size of a dime and the seed is about the size of grapeseed. It’s very tiny and this is to show you that this plant is truly from the Amazonia, where the Amazonian tree frog was first discovered. Here, you can see it’s used since time immemorial. The Inca Indians used to color the markings in their society and the young Inca boys put it on their head. You can see in the bottom the annatto seeds there and then they put it on their head because there are certain components in there that is insect repellent. Anyway, I described all of these in my book. You can download free later or you can find out from here. It’s a labor of love. I wrote this for people. No charge. You can download it.

I went to South America because there was a famous ophthalmologist, Professor Johanna Seddon in Harvard and she said that, in the back of the retina of the eye is lined with lutein and zeaxanthin, so that it filters the blue light. When the blue lights come and then they will be able to protect the retina while we see the image. Today, everybody knows to take lutein and zeaxanthin for macular degeneration. Now, I’m talking about 1994, it is quite some time earlier. I did find a giant miracle. I saw that and I described it in this book. I’ll show it quickly. Sorry, I’m taking my time. This is a picture. You can see me.

Cynthia: Yeah.

Barrie: I did find a giant marigold plant, but fate has it literally 20, 30 feet away from me. I saw the annatto plant. And then that color is also a carotene but unlike every other carotene that I’m familiar with and you are familiar with. For example, beta-carotene. You can touch a cut carrot, it is very difficult to stain beta-carotene in your hand or tomato, which is lycopene. Or if you live in New England, if you cook [unintelligible [00:15:02] from yucky green to suddenly a flamboyant astaxanthin color, they are protonated and protected, not so with that of the annatto. So, I surmise that there must be a very powerful antioxidant protected, but it was just a hypothesis. I was expecting that it would be a polyphenol but it was not a polyphenol. So, surprisingly it was a vitamin E molecule and more surprisingly it doesn’t contain tocopherol, and most surprisingly, it only contained the two most active tocotrienol.

I’m really blessed. I did not even go to South America to look for this plant. For the last 25 years and for better or for worse, my life had been arrested to focus on studying this and I’m thrilled that I’m sharing this more of passion and enthusiasm because of its benefit to people and it was entirely not what I went to South America for. So, I was given this on a plate. I owe it to let people know what it’s supposed to do and I stumbled on one in 50 million, it’s like a lottery ticket. The people sometimes get bitten by mosquitoes, snake, this and that when they go to Amazonia. I wasn’t. I just happened to see a tree 20, 30 feet away from me. So, that would be a medicine man as simple as it gets it. Not deep in the jungle, not like that.

Cynthia: I think it was serendipitous that you were there, and you were curious, and you were paying attention and my understanding that the two types of tocotrienols, it’s the delta and gamma that are part of the annatto plant and are attributable to most of the benefits.

Barrie: Yeah. Of the eight vitamin E and I already mentioned that alpha-tocopherol is best known and then of the eight, only two stands out to be the most potent, this is before my discovery and they are delta and gamma tocotrienol. If you were to run an analysis, you would have about 90% delta and you probably have 10% gamma like this. Now, when people did studies, if you rank the order, the most potent one is delta, and then the half potent one is gamma, and then everything else is head and shoulder below that of delta and gamma and now if you do an analysis of annatto, it is 90% delta and 10% gamma. So, I immediately called my friend in Wisconsin. He was the father of modern day tocotrienol. And then I distinctly remember what he said. He said, “Barrie, if tocotrienol would mitigate human conditions, this annatto tocotrienol. If not, all our work and life in doing tocotrienol research will be waste.” And I said, “Well, in that case, let’s start to do some clinical trials and see.” That was in 1997, 1998, sometime during that, about four years after Johanna Seddon discovered the lutein and zeaxanthin. It is because of that I went to South America. So, even that it is quite some years ago now, some 25 or more years ago.

Cynthia: It’s really fascinating and before we get into the benefits of the tocotrienols without question, one of the questions I’ve been asked is, can we get this from our diet? And I know the answer to this, but I would love to have you explain why we can’t get enough of this in our diets.

Barrie: Yeah, thank you for asking. This is important, Cynthia, because people ask, “Can I–?” If you don’t [unintelligible [00:18:36] I could get it and buy annatto seeds like this. I did do a study one time. Tocotrienol, I discovered all from the three sources, from rice bran, from palm, and from annatto. Rice bran would be if in Thailand or Japan or China, they eat a lot of rice and you need to eat brown rice to get it, because it’s in a bran. And then palm oil, most Americans don’t take a lot of palm oil because of the saturated fat, but many other countries in the world, they do and palm oil has–

Now, I want to make a distinction. Palm and rice contain 25% to 50% tocopherol. And these high amounts of tocopherol will put brakes on the function of tocotrienol. Later, I may get to explain this, but with annatto, it is completely free of tocopherol. So, that itself should clear the path that nothing is putting brakes on it. Annatto is used throughout South America. If you are in a country that consumes palm oil or rice bran oil, you potentially can get to probably three to five milligrams of tocotrienol. If you were to live in South America taking annatto because of pound tortilla chip and then they put it in many other South American foods, perhaps five to 10 milligram a day from your diet.

And then if you eat American diet, that is generally– This is all gone. For example, you have to eat a tortilla chip that people put this thing in or cheese. It is not in a normal food. It is in a processed food of some kind or animal that we eat meat from that consumes corn, because corn has a small amount. Indirectly you can get from the meat. Then in a typical American diet, I’ve seen them still about three to five milligrams seldom above. In comparison, we consume about 10 to 15 milligrams alpha-tocopherol from the diet. Then the small amount of tocotrienol probably is subsume and overcome by the two, three times more tocopherol. And for the better of all our studies, you need about 100 to 200 milligrams on the low side of tocotrienol. Therefore, three to five or 10 milligrams are not going to cut it for the dietary concern.

And of course, furthermore, it will supplement the popular vitamin E, which is alpha-tocopherol, something like 200, 400, or 1000 IU, which approximate to milligrams. 200, 400, 1000, that is huge amount of alpha-tocopherol, so huge. The tocotrienol, even if you take from food or from supplements, you have no [unintelligible [00:21:25] for that to be absorbed, because the alpha-tocopherol, it has a transport protein, right of passage, it is immediately absorbed and everything have to wait in the way. If you want to know what the right of passage is, it’s like, if you were to go to an Oscar party, if you were to be like Nicole Kidman, you don’t have to wait in line. [laughs]

Cynthia: [laughs]

Barrie: If you were to be anybody else, you had to wait there all night for a chance to get in. That’s what I mean. The tocopherol has a right to passage. It goes straight in. And tocotrienol goes through by passive diffusion like other fats. So, if you take so much tocopherol and everything else on the vitamin E series, they wouldn’t have a [unintelligible [00:22:12] to go in. So, I hope that’s useful.

Cynthia: No, no, the analogies are very, very helpful. And so, to reiterate you need to supplement. You can’t get enough in your diet of the right types of tocotrienols. Now, what I found particularly interesting was the benefits of tocotrienols. So much so that I started taking supplementation immediately after reading your book and prepping for this interview because I think it is that important specifically for metabolic health, inflammation, bone health in particular, which how many women are struggling with bone health, because we don’t realize that we are really at peak bone and muscle mass in our 20s and 30s. So, if you’re not ahead of the curve as you transition into middle age, you can put yourself at risk for developing osteoporosis.

Barrie: Wow. Yeah, thank you. Now, we’re slowly segueing into the clinical studies side. Just that the audience know that even though I am in business to make this, I want the audience to know this. This is a slow train coming from it. It is not as I told you from the story. And even before I discovered annatto, I was already studying tocotrienol for some 15 years before that. So, it is a very slow train. In the earlier years, we were doing a lot of animal studies, because we can’t be doing clinical study when we don’t even know what it does. In the animal study, consistently it works in this chronic condition. You have a chronic condition like metabolic syndrome, insulin resistance, and you mentioned osteopenia. We even have a study now on middle-aged men and women who are obese because I surmise of the huge inflammation burden on this– No judgement. Simply just doing the study to see what benefit to people.

And then also in the animal study, just before we start doing clinical work, we just thought, “Wow.” Initially, it was like 90% on chronic condition and 10% on cancer. Now, cancer is also a chronic condition thing with exception of glioblastoma, hematologic cancer, which is very common in juvenile thing. But just for simplicity, so, 90% chronic, 10% cancer. And in the last 10 years, if you look at the published work, you can go online to do this. Then you’ll be like, half on chronic condition and 50% on cancer. I was so troubled. I talked to my director of research, Ann [unintelligible [00:24:42] for many years. I said, “Ann, there’re so many studies on cancer thing and everybody keep publishing it. So, I’m just pent up on it.” I said, “We should be doing some clinical trials on cancer.”

And the reason people are not doing that, Cynthia is because even if you did and it is a big C word. It is a horrible C word. If you do this, you’re never going to get the FDA approval done. I said, “It doesn’t matter to me. Let’s do this and see if it works on people or not. Right now, I’ll pass it back to you on a clinical study like we’ve done about 20, 30 different study on chronic conditions including cancer.” We cannot do 20, 30. We have done 20 to 30 clinical trials to some ongoing, but we only choose a narrower thing. Of all the clinical studies that we have done, I’ll name them and I’ll let you decide which one we’ll talk about. It would be lipidemia. prediabetes, diabetes, fatty liver disease, osteopenia, obesity, and then cancer. And in the cancer area, we specifically studied for cancer. We studied ovarian cancer, breast cancer in women, both men and women, colon cancer and lung cancer. So, you can pick whatever [unintelligible [00:26:07] you want and then I’ll tell you what we have done on it. [laughs]

Cynthia: Yeah. No, no, I would say all of the above, but I want to be respectful of your time. When I think about metabolic health, I think that is the biggest bucket. And I know from preparing for the interview that NAFLD, this nonalcoholic fatty liver disease, and insulin resistance, and inflammation, all play a role with one another. So, I think we might be able to weave in the lipids and the insulin resistance altogether because they are so interplayed with one another. They don’t exist in a vacuum. Let me be very clear.

Barrie: That’s true. That is true. Yeah, maybe then I start this way. Initially, when we first found in animal, it was to lower lipids in the early 1980s just at the advent of statin drugs coming for lowering cholesterol. And then fortunately, that student who was a PhD in University of Wisconsin, he became the vice president of research and development in Bristol-Myers Squibb. Therefore, he continued to fund a professor on it. Later, they abandoned the tocotrienol study not because it didn’t work, but because as most of the audience know, the water-soluble statin in the Bristol-Myers Squibb that is still in use today is pravastatin or Pravachol, is not the most active one but when people have muscle problem, then they will take the Pravachol, because it’s something rather than nothing. So, they abandoned the tocotrienol research and then go on the statin thing but not until all the mechanism, the understanding why lower cholesterol was done. That was in the early 80s and I just became an assistant professor at the University of Massachusetts then. I jumped on this, I studied, and then since 1982 to today, you can calculate how long I’ve been studying on this.

In lipidemia, it would lower the cholesterol probably about 15%, 20%, not as dramatic as statin at 30% to 50% but still is nothing to sneeze at. But when we first did that, we were pleasantly surprised. Not only it lowered cholesterol, but it lowered triglycerides. And I said, “Wait a minute, triglyceride is particularly important in people with metabolic syndrome.” So, it’s not an overnight thing, Cynthia. I learned as I went along. When we checked carefully, it even lowered triglyceride little bit better and more consistently than cholesterol more like 20% to 30%. Then I said, “Wait a minute, people who have metabolic syndrome, prediabetes, diabetes, this is the problem.”

For the audience, take home message on metabolic syndrome and insulin resistance when you mentioned, it is interesting here. I remember the professor in Stanford University, he has since retired and passed away now, he came up with this idea called syndrome X before it was metabolic syndrome because it was just a cluster of things. The cholesterol is high, the triglycerides are high, the sugar is high. It’s actually metabolites in the body. He didn’t know what is kicking in to do what. He called this a metabolic syndrome, metabolic X, because the metabolites, there’s something he needed to unravel. And by the time he was near retirement, he gave a speech in American Diabetes Association. There were so many people wanting to talk with him.

I never got to poke my head. I’m a short guy and everybody’s going up but I waited until he left the stage and about to go back and to leave for the plane, then I caught him. You can see he was not very happy that I stopped him but I just said to him, “Hey, can you just–” I asked him a question. I forgot the precise question. He said, “Look, I don’t have time to answer your question, but I give you this one line and then if you got it, you’ll understand much of my work is published.” I never forgot the one thing he said. I will say exactly what he said and then I’ll simplify. He said that, “Hypertriglyceridemia always precedes hyperglycemia.” That means high triglyceride always precedes high sugar. So, therefore, somebody does not get to be diabetic. They have high triglycerides and high triglycerides is certainly a hallmark of metabolic syndrome. I never forgot it.

To this day, I consistently ask, if you see a doctor, you have your lipid panel, just look at the triglyceride. Your doctor may be reading about the cholesterol, the bad cholesterol, the good cholesterol, all good but also look at the triglycerides to see if you have hypertriglyceridemia. If you do then you can do things that control that before the triglyceride gets so high, and the floodgates would open, and then your sugar will burst. You don’t want that. When we study people with prediabetes that’s a real blessing I saw. I saw that the triglyceride is being controlled and as the triglyceride is being controlled, I took courage to know that this prediabetic people are not going in the direction of being diabetic. They’re going the opposite direction. And then I noticed that as the triglyceride dropped, the sugar dropped slightly. Then I said, “Wow, that’s a very good sign.” We did work on the prediabetes and the diabetes.

And then later, the reason we segued to do the fatty liver thing was, the fatty liver is a very silent disease about 25%, 30% Americans have that and it’s about 90 million have fatty liver. It is not possible. If this fatty liver ever becomes NASH, which is the worst case that get to be a liver transplant, we will never have enough– Basically, we’ve consumed so much fat and carbohydrate to convert to fat, such that our liver looks cirrhotic of people who consume way too much alcohol and disrupt the liver. Can you imagine that? Who would have guessed 30 years ago, we can get a liver to be like that of alcoholic destruction? But this is simply due to fat destruction. I’m still stumped by that. Enough that this description of diseases is so awkward. It is actually called NAFLD standing for nonalcoholic fatty liver disease. It is clear, but it’s very awkward. Don’t you think that they explicitly say that it is nonalcohol related and of course, if one were to have fatty liver and furthermore you continue to consume a lot of alcohol. Well, then that is clearly a double whammy. This is not saying more than that, but still this condition is devoid of alcohol.

We did this and we have three studies, one for three months, six months, and 12 months. This is over eight years, Cynthia. The reason we did three times is because the liver is a single largest organ in our body. I was not confident that if I do it three months that will be satisfactory. We stopped, we published the three months, and then we got the six months, we got the data, and we published in the 12 months. After we had done that in this three-month study, we measured stress enzyme like ALT, AST. Many doctors, PA would do this kind of thing. They don’t poke a needle and get a sample. You do that only if you’re looking for hepatitis, or serious liver damage, or liver cancer. But otherwise, you do this. So, we did that and then noticed something and she told me, “I’m not sure. I’ll keep that for you and let you know at the end and I’m not sure you’d do that.” I said, “Let’s see what the six-month study shows.” We committed a six-month study and this time, we studied the liver enzyme. We studied also C-reactive protein, and sugar, and triglycerides. They all dropped. In other words, the metabolites are coming back to kilter, the balance. I like it. Then Anne nudged me and said, “Barrie, remember I told you that. It is happening again in the six-month study.” So, right now, intellectually, I cannot disagree with my director. Then, I said, “Let me do a 12-month study and if it still does then I’m going to budge and do something about it, okay?”

We did the 12-month study. This time we had ultrasound and CAT scan to make sure that we can actually see the fat egress from the liver. We did all the earlier things as well, consistent still there, it’s sustainable and then the ultrasound saw the fat egress such that they would not have fibrosis of the liver. When you have too much fat in the liver and then the liver becomes scarring tissue, and is beginning to have sign of irreversibility, but instead we saw the fat egress. So, I like that. Now, I did not have Ann telling me this. I’m seeing it on the paper and that is consistently in the three, six, and 12-month study, the patients with fatty liver on tocotrienol, they lost weight. I’m very skittish to mention about weight loss because weight loss program is usually two weeks and four weeks and the shortest study we had was three months, but they lost weight and they consistently lost about 12 to 15 pounds.

Then I said, “Wait a minute, if people are overweight and they have fatty liver disease, losing 12 to 15 pounds is nothing to sneeze at.” That means even the body is reacting positively and they come back. I told Ann, “All right, I’m willing to say that now” [laughs] and this is consistent in a three, six, and 12 months. I just said, “Wow.” And I don’t think it is a weight loss product as it brings your body back into balance and the inflammation reduces and eventually your body adjusts, and then your body begins to lose weight. I don’t know what that is called but I think weight loss has other connotation and then it may come across misleading. However, I now undoubtedly can say it is statistically significant in these fatty liver patient loss rates. I’m actually thrilled to see this happening. So, if you have your audience who have fatty liver condition, how would you guess that.

When you see your lipid profile, when your doctor does it just see if your triglyceride is high. And then also see if your sugar is high and moderately high, it doesn’t have to be diabetic level sugar. If your triglyceride is a little bit high and your sugar is a little bit high, it’s time to take your life back in order to attend to this and if you’re on the overweight list, your BMI is on the overweight side and you would notice, you can go online and find out where your BMI is, then you can take your life back and attend to some of these necessary things. Of course, I always want to include a moderate amount of exercise with it as well.

Cynthia: I think that’s really amazing and for the benefits of listeners, my whole background is in cardiology. I looked at a lot of lipid panels and we used to define high triglycerides were 150 and above and looking at your HDL, wanting if you’re a female greater than 55, male greater than 45 and those were generally the areas that we spent a lot of focus on. I think that for the context of the conversation, when you were looking at defining those values for the study participants, was there an average or was there a benchmark for their triglycerides need to be higher than x or these people who had significant familial distributions of high triglycerides or this is something over 150 and also fasting glucose maybe over 100, 110 that they were included in the studies?

Barrie: They were exactly as you said. The triglyceride is above 150 and then the fasting glucose is 100, but not more than 110 on fasting because that would be diabetic, so we did that. A long time ago, this is my [unintelligible [00:38:25] exactly as you said. This is from Sanofi and this is [unintelligible [00:38:28] If I go closer, look at the metabolic thing. The very top is a high trigly– Exactly as what you said. These have not gone away after 15 years and right now, there is not much of a medication that can help people with lower triglycerides and also the HDL is also very low. It is very difficult to increase the HDL except for exercise but surprisingly, people that have metabolic syndrome, the LDL does not necessarily increase, but it’s usually the triglycerides, and then the measurement of the central obesity, and then your lipid panels. So, those are the few guys that we have.

We only study new ones of blood work of AST, ALT, because that’s a common stressor of the liver enzyme, so we do that and then I was already suspecting that this patient probably under inflammation. We have C-reactive protein, and interleukin, and it has become more sophisticated following through the study, we start to look at fibrosis score and then steatosis. Steatosis is the amount of fat stashed in the liver. The 12-month study was particularly designed in such a way that is not really to convince patient or to convince a health professional necessarily. I set the bar really high because it just cost me so much time, and energy, and money to do this kind of work. I decided in a 12-month study, “Please design the study in such a way,” I set the bar really high, so that even hepatologist and endocrinologist will buy in on that. So, they’re specialists. That’s why they did CAT scan and when they did that, I told design for health, we partnered with them. I said, “Look, I’ve done this.” He said, “Don’t ask me to do any more study. If I should do, I should do something else. I’m done with this. I have three months and six months.” And most people have, what they call dose dependent. You have x dose, and double the dose, triple the dose and then you see where it goes. But this one, I didn’t do it. I already decided that the active dose is 600 milligrams. In the three, six, and 12-month, this is in essence is a gamble of a sort because we can do all the studies in the world that is to do, but I decided that they are seriously under stress and the body is under inflammation. So, I decided under 600 milligram in the three, six, and 12 months. I consider this not a dose-dependent study, but a time-dependent study. So, they systematically got better.

I now nailed on this. People who have fatty liver disease should consider taking 600 milligrams, 300 milligram each pill with two meals. You got to take it with the meal to absorb better. Lunch and dinner will be ideal and then take this and then we consistently see the benefits, and some of the benefits I had mentioned. And by the way, if the audience are scientifically curious, you need to know the study. Let Cynthia know, I would be happy to pass those three studies to you. We already put press releases out like that and so, this is what I’m hoping to do. If the audience are listening, I may fail, but better that I tried and failed and never tried it all.

Now that I have three studies and they are controlled really well, and then they are placebo controlled, which means where we have a dummy group as well to show that it didn’t do anything. So, we’re going to seek a law firm that can help us to package this together, and then write it, and we will then make a presentation to the FDA, and see if the FDA would allow a condition claim. They will probably never allow that. If you take this tocotrienol it would help you to treat NAFLD. That’s too strong a word, but maybe allow for those who have something more bland, for those who have fatty liver condition among exercise and good diet, and they may benefit from having toco– something like that. But even like that, we still need the FDA.

But as far as the studies are concerned, you are smart listeners and you are smart people who know how to read the literature. If you read the conclusion of the cardiologists who did the study, then it will be explained. We have no impact on the study and by the way, it’s a double blind, placebo control. You know what that means? That means that neither the patient nor the physician knows who is getting the Real McCoy and the dummy pill. And I’m providing the tocotrienol. How would I know? I’m not even involved in anything. This study is what this study is. For me, this is very thrilling to see that we subject ourselves to the same scrutiny of study and it’s coming out. So, I don’t know, this is probably as good as it’s going to get. [laughs]

Cynthia: No, it’s very exciting. And this is the gold standard of research. This is high-quality research. We talk about improving insulin sensitivity, reducing inflammation, improving NAFLD, which is a terrible byproduct of metabolic disease and more efficiently burning fat. Now, I’d love to shift our focus, because of particular interest to my listeners is bone health. Unfortunately, a lot of us don’t realize that we’re heading into middle age with– Maybe we’re at greater risk due to genetics, maybe we’re at greater risk because we weren’t doing a bone-bearing exercise when we were younger. Let’s talk about bone health and the impact of tocotrienols because I think this is of particular interest along with the metabolic disease that we just talked about.

Barrie: Yeah, on the bone health thing, let me quickly disclose what the audience, and you, and I already know. As we grow older, we’re able to retain calcium less in the bone, which is mostly protein, but have calcium maintained there, it would be to take vitamin D and calcium. We all know about that. And more recently, we know about vitamin K, particularly menaquinone. You probably read about that, however, the audience may or may not know. The activity to retain bone strength, bone mineralization in the bone is actually MK-4, menaquinone 4, not the popularly proposing MK-7. I will get to that. But just make a note as MK-4 in the bone. Now, in the bone, we have the bone that grows the bone called osteoblast and then the bone that breaks down the bone called osteoclasts. We need this because I know it’s a little bit sci-fi-ish and zombie-ish. Every two years, our entire bone system is replaced. You need to have the growing bone and to breaking down bone. You cannot just have growing bone like that. That means we’re like the Hulk. And you can’t do this, because our body have to replenish itself. The skin and other place will be much faster turnover, but the bone is slower, so you need a balance to it.

Now, if you were to be a young boy or girl going into puberty, you can imagine the osteoblast will be super high and the osteoclast will be low. And before puberty, they are equal. The first 10 years, perhaps slowly like that and then suddenly, osteoblasts go high when the hormone is surging and osteoclasts go down. Now, if you try to remember for all women going through menopause then the opposite happens because she’s closing down on her hormone production, then the osteoblasts come down and osteoclasts go up. Then if on balance that is out of kilter and then the bone loss will drop. Men also have this but it’s androgenic. Meaning, when they both reach 80 years old, if the men live long enough to be in their 80s, then the bone loss will be comparable. But during the menopause, let’s say 50, 55, it drops quite suddenly for the reason I just explained.

We designed the study to take advantage of this. Of course, we did not do the study on puberty girls and boys because it just doesn’t make sense and then we would not do a study prepuberty, because there are a lot of questions that the professor would ask, “Why would you give this to a–?” And then doing most of their life and maybe from 18 to 35, 40 years, it’s pretty stable balance. We chose people who are 55 to 65 years old. We did not choose women above 65, because we fear that they may be osteoporotic. That stage is hard to call back. So, it is on osteopenic area and we measure the amount of bone growing to the bone– The bone growing osteoblast would be say here, but over the three months that we gave to them the indicator on the bone growing increase and then on a bone loss one, let’s say, it would drop. The bone loss would be this amount and then when we gave them the tocotrienol, the bone loss thing would also drop and the bone growth would increase and that’s the ratio doctors want, the bone growth against the bone loss and we saw that to be increased approximately 100%.

The reason we measured like that and not actually measure the DEXA thing is because if you physically measure the DEXA thing, you will need about three to five years and our study cannot be so long. It is going to fail on us because the woman will get disenchanted. They don’t want to do the study more unfortunately if they pass away or they move out of town. There are many things you have to think about when it comes to clinical study. We measure the cytokines, the measurement on what grows and not grow the bone and that’s what we did. do.

Now, the other measurement we did, we are very excited about the scientists and– This was done in Texas was that I surmise that women who are going to menopause have high degree of oxidative stress and the reason I came to that conclusion is, the estrogen E2 is actually an antioxidant. I heard very few doctors telling me that. I saw the molecule of the feminine estrogen. It actually has a phenyl ring and OH group that’s an antioxidant. When that drops, I said, “Wow, her systemic ability to protect her body by making the estrogen drop.” But most people only think about that as loss of bone, but also increased oxidative stress because of the estrogen being an antioxidant. I decided that, because it’s like, let’s measure her oxidative stress marker. We did that specifically because the estrogen dropped and we saw that when they took the tocotrienol, that oxidative stress is reduced by no less than 100%. This was also published, I think, in the year 2017 or 2018. So, we did that.

After that, the same professor came to me, he said, “Barrie, I think that it’s very difficult for a long-term study to measure the DEXA thing on women with osteopenia.” I asked Professor [unintelligible [00:50:03], “What do you have in mind?” He said, “Barrie, I think that when men and women are carrying a lot of weight, they have sarco-osteopenia, which means that they put on weight, and they mask their muscle drop, and then the bone loss. I think that we should study people who have obesity. Then I said, “Okay.” This study started two years ago right in the middle of COVID. It’s been delayed a year, but it’s still ongoing. I’m actually not wanting to say thrilled because it just means funny. This is the first time we’re going to have biopsies of the obese patients’ fatty tissue, just where the grab is in front of their abdomen here.

As you know, the inflammatory cytokine is actually on the fat itself. When we sample it out, now we can decisively look at the cytokines at the fat. Not the cytokine subsequent to the fat and in the blood. Not that that is no good, but it’s after– A lot of time even when we study AST and ALT, which is produced in the liver but we actually measure them in the blood. But of course, we are not simply allowed to poke into the liver. That is easy to say and easy to do in an animal, but you can’t do it in a human, unless somebody showed that they have hepatitis C or liver cancer, then the doctor would perform something like that. We don’t know the study result, because its blinded again. Probably in a year, we would know that. So, I’m very confident that the tocotrienol will reduce severe inflammation and stress whether the stress is based on huge amount of fat, or huge amount of bone loss, or the liver.

But on the bone thing, let me segue into something that I believe will be very useful to your audience. I mentioned MK-4, menaquinone 4 and you will read some study MK-7. MK-7 is made by bacteria fermentation in the gut, so that if you take cheese, or kimchi, or kefir, or anything that is done by fermentation, you get this MK-7 and there are many menaquinone, MK-7. MK-9, MK-11, and MK-13. Basically, the tail is long. MK-7 come from a compound called vitamin K. Let’s say, you have a ring like this. You have a head, so that is phylloquinone and a tail– The dark green vegetable, you have this. Nobody asked this question. If you were to be a vegan, you would consume a lot of green leafy vegetable or what I call eating more like a rabbit food, then they would be consuming a huge amount of phylloquinone. Were they to consume a huge amount of phylloquinone and they were all absorbed, they would clot to death, [chuckles] because vitamin K is known for clotting, to seal the tear but healthy vegan and vegan do not clot to death.

The reason is because only a fixed amount of phylloquinone when it gets to the gut is absorbed to do exactly what we said. But for the one [unintelligible [00:53:33] actually at the gut, it crops it up. See? The tail is flushed out. Now, the ring goes in and when the ring goes in, I know I’ve got a terrible example here. The ring is going to look for another tail and then stitch this on like this. That is MK-4. It starts with this phylloquinone and some amount going for clotting and then it becomes MK-4 and the yellow one that makes MK-4, not MK-7 the tail, that is GG. That is a compound called geranylgeraniol and geranylgeraniol among many thing it does is to make MK-4. And then now, I’ve taken the time to explain this. Why is this important to bone health? MK-4 helps in a biochemical pathway for the carboxylation to make protein that is cross lattice in the bone to trap and keep the calcium in place in the bone and that is MK-4.

To this day, if you google MK-4, at 45 milligram is a pharmaceutical drug in Japan for anti-osteoporosis. All this to say, I will segue now to this, in the background here, see, that is a molecule of GG. That molecule of GG in the plant is used to make tocotrienol. Our body doesn’t know to do that. And this compound is made in a body since time immemorial. Whether we know it or not, we make this. So, I will tell you this. I know of at least three reasons why our body makes GG. A body makes GG to make MK-4 and I took the time to explain to you. Not phylloquinone, but MK-4 after a fixed amount goes in. Our body also uses GG to make CoQ10. In the background, you see the other long molecule. Look at the black and white thing. Two and a half length of the tail is GG and people know to take CoQ10 because it’s good for energy and also good for the muscle. And the last thing is, this compound GG that I mentioned to you, it is critical in the body to make, I’ll say very carefully and slowly for skeletal muscle protein synthesis. So, therefore, of the 40% of the muscle protein our body makes as we are younger and of course, we lost much of this as we grow older is dependent on GG for the skeletal muscle protein to be made.

If we lost this as we grow older, therefore GG is an anti-aging supplement. Therefore, when people say that as we grow older, we don’t have enough energy, CoQ10, because we don’t have enough GG. And we take statin drug, everybody knows it lowers CoQ10. It lowers CoQ10 because statin drug is on the same pathway that inhibits GG synthesis. GG is the reason why CoQ10 drops. CoQ10 is called ubiquinone, it’s ubiquitous. Wow. Happy to let you know. Probably, CoQ10 is ubiquitous because GG is ubiquitous. It explains there. Why do we lose muscle mass? Because we don’t make enough GG. Just think of your elderly parent and why do we have osteopenia and osteoporosis as we grow older? Because we don’t have enough GG.

Now, I know I elaborated on women, but this one I must let you know. There are two drugs that affect GG. One is statin and people take statin drugs because they lower cholesterol. Everybody knows that. And the same pathway lowers GG. Your doctor does not really care if you take statin drug if it’s lower CoQ10, unless it’s a holistic doctor. However, that doctor as well as your holistic doctor do care when you take statin drug, if you have muscle problems, everybody cares. The muscle problem is because that inhibits GG also as it inhibits cholesterol, but it inhibits the ability to make skeletal muscle protein and that’s why they have myopathy. That’s it. Very simple. But if you don’t take statin drug, then you have sarcopenia.

The other one, if I were to be a woman, my ears will be perked up. Women at menopause, when they have osteoporosis, the doctor prescribes bisphosphonate. Bisphosphonate is clearly a drug to help in the maintenance of mineralization in the bone. A good thing. After my talk you google this phrase, BRONJ. It simply stands for bisphosphonate-related osteonecrosis of the jaw. It is a terrible phrase. If I could explain it, your jaw like fall apart and dies. Bisphosphonate-related osteonecrosis of the jaw, this is not a normal dental problem. The dentist discovered this because– I’ve asked many dentists. They said, “Barrie, I have never seen this in a normal person who had bacterial action, blah, blah, blah.” So, this is clearly a drug associated thing.

The dentists were the first to found this thing out and then they found out systematically it would be 50 something to 60 something women and they are taking antiosteoporosis drug. The answer is very simple when they take this drug to strengthen the bone in the bone elsewhere but somehow in the jaw, it does the exact opposite. In the jaw, it helped to destroy the gum, which is a soft tissue bone and then the jaw bone where the extraction is particularly when the woman has an extraction, and then the wound would not heal, and the bone would not seal, and then they found out this, and then now they found out that bisphosphonate uniquely and surgically inhibit the osteoblast of the gums and of the jaw bone, GG, such that it cannot make enough of the gums and the bone. So, there you have it.

Right now, we are trying to find a dental department that if they take extraction of people they put in a small drop of GG. I have to wait to see this. Until then, if I were to be a person of older age and particularly of a woman, and if a person is taking a bisphosphonate drug, then minimally they should consider supplementing GG.

Cynthia: No, my mind is completely blown. One of the things that I read about last night is, as it pertains to GG that some Japanese scientists determined that actually increases testosterone and progesterone, which I found fascinating. These compounds that we may not have been familiarized with prior to this discussion can have a significant impact on our health, our longevity, our metabolic health, our bone health. I could probably talk to you for hours because you have so much amazing research. I would love for you to share with listeners how to connect with you, how to get your book, how to learn more about you and your research. And we will be putting links to all these research articles that you have discussed so that people can take this information, take it to their providers, perhaps, start integrating some of these concepts and supplements into their lifestyle. What’s the easiest way to connect with you?

Barrie: I guess the easiest way would be, if you were to type my name and my name is spelt a little bit affectatious, I had this thing for a long time or you can go to barrietan.com/book and then you can download the book. That will be a best way to do it. If not, you can go to our– We don’t sell finished product. The company is American River Nutrition. We are based here in Massachusetts, [unintelligible [01:02:08] buying tocotrienol and then we’ll list all the companies selling it. When you come to our website, because we don’t sell products to consumer, but you can download our white paper on GG on tocotrienol. Oh, we also make CoQ10 because people who takes statin drug drop. So, we have a particular CoQ10 ubiquinol and GG together because I don’t know now yet if people would take a powerful drug like satin. If they just take GG, it is enough to fix mixing all the CoQ10. So, I thought to just combine the two and the absorption is much better. So, we’re happy with that. You can download the three studies. And if you have questions, you can send us an email and then we can answer. We’ll be happy. By the way, in the book here, it has lots of references and you can download the paper to read more so.

Well, thank you so much for having me, I hope that the audience has learned something from this and seek applications to see. And also, we are now conducting two studies out there, it will be more on GG. At least from the conducting of the study, you know what direction we’re going to. In Florida, we’re doing a study on people taking GG to see if their testosterone and progesterone would increase per what you just mentioned earlier. We should know that by the end of this year. The other one is a more complex study. It won’t be done until next year. It would be people who have hypercholesterolemia under a cardiologist care, who are currently taking statin, who have confirmed myopathy and is running on a medical treadmill to see if the myopathy would reduce when they take a GG compared to the one who’s taking statin and not taking GG. If that were to work, that would be great.

And the last two, we don’t know when we’re going to do that. It would be for a young person 20 something college students not taking statin or anything, if they will increase muscle mass force. That will be more athletic type thing. And then hopefully, on the other section of life on the elderly population to see if this would mitigate sarcopenia per se. Nothing to do with drug. If I can do that, it’s probably time for me to retire. But that will be the last two things I would like to do and then I’ll put my print on this and I’m sure there will be many other people that would follow this. This is exceedingly exciting. I’m not talking about a supplement that you just give to people. This is something our body produces. We’re just thinking, “Hey, if our body produces, let’s listen to what our body is supposed to do with this compound in our body.” So, I’m just simply answering very simple questions.

Cynthia: Well, I’m so grateful for your research and the opportunity to connect with you. Your enthusiasm is infectious. I love that you included analogies to make it much more accessible to listeners. Thank you so much for your time today. I’ll definitely have to have you back and hear more about your research going forward.

Barrie: Thank you so much.

Cynthia: If you love this podcast episode, please leave a rating and review, subscribe, and tell a friend.