Lipid-Soluble Nutrients in Metabolic Syndrome: The Supportive Roles of Tocotrienols, Resveratrol, and Vitamin D Full Webinar

Tyler: All right. We’re gonna wait for a few people to come back in and then we’ll get started. All right. Perfect. People are flooding. I think we’ll go ahead and get started. All right. Well, welcome, everyone, to the Tuesday webinar series. My name is Tyler Mikon with Chiropractic Economics. And in today’s webinar, Lipid-Soluble Nutrients in Metabolic Syndrome: The Supportive Roles for Tocotrienol, Resveratrol, and Vitamin D” is brought to you by Designs for Health. Our speaker for today is Dr. Barrie Tan. Dr. Tan is a renowned scientist with a Ph.D. in chemistry and biochemistry and a former assistant professor at the University of Massachusetts in Amherst. Over the past 35 years, he’s become a leading expert in vitamin E, having commercialized tocotrienol in palm, rice, and annatto. Dr. Tan discovered the best-in-class tocotrienol in the annatto plant, which he has extensively researched over the past 20 years, along with its discovery of geranylgeraniol or GG, a vital nutrient for healthy aging.

His current research focuses on lipid-soluble nutrients that have the potential to slow chronic conditions. And before I pass this off to Dr. Tan, I would just like to remind everyone that this webinar is being recorded and will be available to watch shortly after the conclusion of this webinar. Should be posted within about 24 hours, and it will be professionally transcribed as well. And we would also love to hear from our great chiropractic audience. So, questions are encouraged. So, at any moment if you’d like to ask any questions, feel free to either use the Q&A button or the chat icon. We’ll be sure to ask or answer as many questions as possible. And with that being said, Dr. Tan, I will pass it over to you.

Dr. Tan: Thank you. Thank you, Tyler. I know some of the audience this is a busy time for you and thank you for making the time to come to the talk. And some of you have heard me speak before. So, this particular one is on lipid nutrients, and we’re not covering all the lipids, but certain lipid nutrients as they pertain to metabolic syndrome cluster. And so, this should be very interesting and important topic as I would go along like that. In terms of the slide, the progression would be this, at the high level. So, if you miss something, I’m sure Designs for Health would let you have the slide. You can see how it would go. In terms of the flow, there will be a story I’ll be telling of the anchor ingredient, which I believe is tocotrienol, this particular vitamin E. And I’ll describe some story about this. Some of you may have heard this before.

You’ll see as the slide goes on, people interested in protocol are usually listed somewhere and is in green color or something in the bottom so you know whether it’s animal study translated dose to a 70 kg person or a clinical study. And the dose is a dose itself like that. And the reason I chose metabolic syndrome, I didn’t do the study because of Designs for Health’s product. I do this kind of study all the time throughout the 40 years of my career. So, Designs for Health is rapidly responding to why a product like that should be made and it should be obvious. So, I do the study. I went after metabolic syndrome because… I went after fatty liver disease as a very important cluster of the metabolic syndrome. And it should be obvious and it’s the widest reach of people who are not well on this chronic condition.

So, the abstract that I would say for this talk would be delta-tocotrienol or annatto tocotrienol. Our trade name is Deltagold. So, delta-tocotrienol plus resveratrol plus vitamin D and K. And, of course, all of these ingredients are lipid-soluble. So, that’s pretty much what I would say. And I have pictures of annatto throughout that you can see, this beautiful plant that I stumbled on in South America some 25 years ago. So, this is a required disclaimer on this. It’s not a prescription. You should talk to your doctors, not FDA-approved for curing or treating diseases. The roadmap, pretty much what I had discussed before, our focus initially largely on tocotrienol, how I develop and came up with the milligram that is needed, and then talk about the clinical trials on other aspects as well, like resveratrol and then conclusions to be made.

My discovery, you can actually see the age of mine when I had more hair, and then I progressively lost all my hair as I went on. I discovered palm tocotrienol in the 1980s when I was visiting a palm plantation, and Malaysia produces a lot of palm oil. And we usually think of palm oil as a saturated fat because of the palmitic acid. Then you fast forward another 10 years. Then I discovered rice tocotrienol from rice from the browning skin of the rice, the fiber, rice fiber. And that was a Thailand project. And then fast forward another 10 years while I was visiting Peru, looking for lutein, you can see the picture on top right, giant Marigold flower, I was looking for lutein for macular degeneration. This is 1994 when this was… At the time, people did not hear about lutein and macular degeneration, filtering blue light, and all this. Today, people know about it, but not then.

So, I was there. You can see a younger me looking for this. That was what I went to South America for. So, this is my fate, but about 30 feet away from me, I saw the annatto plant in the bottom picture, but that’s a much later picture, of course. I saw the annatto plant. And then I noticed that when the parts open, they had this red color, which I know that is a carotene like lutein, like zeaxanthin, like lycopene, like beta-carotene. These are carotene. And they’re highly unstable. So, I suspected that is some antioxidant that would protect it. So, one thing led to another. I discovered the fantastically strong potent antioxidant, and that was a delta-tocotrienol. You’ll see that when I give you a description of picture. So, therefore, if you fast forward to 2010, I was hunkering down to know…figuring how to extract the tocotrienol.

I discovered geranylgeraniol, GG, as well. So, we did production right here in Massachusetts. We are the only facility in United States making tocotrienol. And we are the only company in the world making GG. So, this is very special to me and very important. So, I commit a lot of my life and energy towards this kind of a study. So, none of this is overnight stuff. It take a long time to do. So, proud that this has happened this way like that. And sometime people have asked me, you know, “Dr. Tan, are you like a medicine hunter?” I wish I could say that. You know, if I were to be in the jungle of Amazonia, I’m so lame, I probably get bitten by a mosquito and a malaria and die or something. So, I’m no medicine hunter. I was just in the right place at the right time. And then I saw this plant, made some assumption, and sure enough, it did not end up in some ended cul-de-sac. It actually worked out, and it was…enhanced the discovery.

So, I consider this plant, this beautiful flower, lots of stigma and pollen like that, it’s native to Tropical and Central America, is a shrub. And indigenous people use it to mark their… You can see me in my picture. You can see the indigenous people marking on their body like that. And soon after my discovery, this is a picture of me when I was in South America. And a more beautiful plant would look like this. See that? If I get closer, you can see the part is very red. The British nickname this the lipstick plant. And to show that it is from Amazonia, you can see this picture, the frog is about the…inside the whole fruit, which is about… The whole fruit is about the size of a fig. So, the frog is only like a dime. So, it’s tiny. So, this to show you the Amazonian tree. The tree frog, which is small, was discovered in Amazonia on the top of the canopy of the plant.

So, here’s a picture for me to show you from them. So, that’s all from that piece there. The bixin is the carotene color. The tocotrienol is a protectant to protect the bixin from degradation. Keep in mind, the plant never makes things for you and I. So, we just got it into our head. We are lucky that we have plant to live with. The plant always makes things for themselves, never for human being. So, they make the tocotrienol to protect the color from degradation. That’s it. That’s what the plant does. And the terpenoid, which is GG, they use it to repel mosquito and pestilence that land on them like that. So, this would be a quick snapshot for vitamin E. About a hundred years ago, it is…alpha-tocopherol was known as a vitamin E because it helped the fetus to full term.

I don’t know everybody knows that. It is not known as a vitamin E because it’s antioxidant, though it is, but it is known as a vitamin because it helped the fetus to full term. So, it’s a burst vitamin. And in 1937, about 15 years later, its antioxidant property is known. So, the antioxidant property of vitamin E is known a long time ago. And tocotrienol, another 25 years later, it was discovered. So, clearly, this is a younger brother, like a runt to the vitamin E from alpha-tocopherol. Today is almost 40, 50 years after, before it was discovered. And hence we heard a lot less about tocotrienol and tocopherol. And then in 2003, we start commercializing and extracting this. When did I come into play in the vitamin E research? Somewhere here. In 1984, I started my career at UMass in Amherst. And that’s when I started to study this sort of vitamin E. And if you look at…look at the bottom here, the kind of research on antioxidant, a peak, and then they start to go down. It never went away. So, the people study all kinds of antioxidant. But if you look at the two slopes that are going up, they are on chronic conditions like cancer, like cardiovascular disease, and diabetes. I’ve talked about cancer many times, but it’s not this talk. So, if you send me email, I’ll be happy to send you some of the papers that we did. We have about six clinical trials in Denmark on cancer like that. But today, mostly on a cluster of these diseases here and metabolic syndrome to be expect. And then there are some unusual one others that I put here as well that people study.

This is the only picture slide that I have of a structure. On the left is the structure of tocopherol. You see that. And on the right is a structure of tocotrienol. Now, see, a tocopherol, this is an antioxidant, OH, same thing with Tocotrienol, exactly the same. And the difference being a tocopherol, the tail is saturated. The tail is completely saturated. In the tocotrienol, the tail is not saturated. See, 1, 2, 3, double bond, and hence trien, three double bond like that. Otherwise, they’re both antioxidant. Because this tail is shorter, it flies around the cell membrane. Another time I can explain better. If you want a potent antioxidant for membrane protection, why membrane? Because membrane is where all the fats are in your love handle. Half of those fat are in your love handle, but the other half is on the cell membrane. You cannot feel and touch because we have 38 trillion cells and all of them have cell membrane. And the cell membrane must have a water-soluble group sticking out here.

And the other part is lipid-soluble sticking into the cell membrane. That is a lipid membrane antioxidant. So, there are many other good antioxidant such as resveratrol, but resveratrol is not a good antioxidant for membrane because it’s got OH group everywhere. So, if it got OH group everywhere, it cannot stick into the cell membrane. So, this is just that piece. Not to say resveratrol is no good. In fact, we’re talking about resveratrol into this GlucoSupreme thing, but it is not a cell membrane antioxidant for which tocotrienol is best. So, all these eight isomers, four tocopherol, four tocotrienol, I used to produce every paper when it’s published. But now, there are so many hundreds of them. I don’t collate them. So, lucky for us, we have Google search PubMed. If you just type delta and gamma-tocotrienol, there’ll be a huge amount of study on all kinds of different thing that you will be able to find.

So, over time, why is alpha-tocopherol so well known? Because it was the first vitamin E to be discovered. And in fact, if you look at plant, most plant have delta-tocopherol and gamma-tocopherol, not alpha. But then why they convert to alpha-tocopherol? Because at the time, alpha-tocopherol was a currency of vitamin E. So, therefore any vitamin E you have, you just convert to alpha-tocopherol. It’s a bad direction, but it was a great marketing idea, but it was a bad direction. And it’ll be obvious in the next few slide. And then similarly on the tocotrienol side is delta and gamma-tocotrienol. Having said this, when I show you the next slide, when my discovery…is my whole life was arrested. Remember, I just explained to you, if you search [inaudible 00:15:01] is delta and gamma-tocotrienol.

Typically, from plant, you have a mix of different vitamin E like that. They don’t make it one or two. But in the annatto plant, it is an exception. So, this is HPLC chart. If you look at this chart here, 90% is delta-tocotrienol, 10% is gamma-tocotrienol. I just show you the previous slide. The two most potent vitamin E is delta and gamma-tocotrienol. And then this plant is undoctored, unmanipulated, nothing. I did nothing to it. The plant just make these two and mostly delta secondarily gamma. If there were to be tocopherol, it’ll be somewhere here. Nothing, nothing showed. So, therefore, it is the only plant that I know that simply make tocotrienol. End of story. They don’t make anything, no tocopherol. If you look at the chart, these are the only three sources of natural tocotrienol. All of them I discovered over the span of 35 years. If you look at the teal color, 25% to 30%, under 25% to 50% of the vitamin E are tocopherol. See that? Tocopherol in palm and rice. And then in annatto, 100% is delta and gamma. See, from the maroon color, delta and gamma like that. So, there you have. If you look at the bottom, you can read that faster than I can.

So, I have spent some time to enunciate and focus on why not alpha-tocopherol. So, here you have a reason. So, why not? Alpha-tocopherol interferes with the function of tocotrienol. In essence, if you read this faster than I could here, you’ll come to the conclusion the alpha-tocopherol put breaks on the function of tocotrienol. Over here, not related to tocotrienol, alpha-tocopherol have problems in physiologic function. If you read this yourself, you’ll find that alpha-tocopherol has too many landmine to be important. You just look at those studies yourself and you’ll come to the same conclusion.

There is a meta-analysis somebody have done that clearly show that tocotrienol from annatto is the best. We did not do anything with this. So, other people did. So, people have also asked me, “What about when you eat food? It naturally contains alpha-tocopherol.” No problem. If you typically eat food, you may get about 10 to 15 milligram of alpha-tocopherol. That’s fine, and that would be good. The RDA is about 15 milligrams, but you do not need to supplement vitamin E as in alpha-tocopherol. If you did, then you have risk on all these things alpha-tocopherol could do. And if you take alpha-tocopherol with tocotrienol, then the alpha-tocopherol would put brakes on the tocotrienol. So, now, I have give you some introduction of vitamin E. And these are basically four of them. Annatto is most potent. Alpha-tocopherol interferes and is too laden with other landmines.

So, now, comes to the part we talk about metabolic syndrome and its cluster. This is a good slide to remember like that, that metabolic syndrome is a cluster…the pressure is somewhat high but not hypertensive yet. The triglyceride is somewhat high, but not too high to be off the chart. And then HDL is reduced like that. And then the waist circumference is very obvious to know. And then the glucose is elevated, but not too high to be diabetic. So, this is the cluster of metabolic syndrome. I don’t have a time just now. If the audience wish to ask, I would love to explain that later. Initially, when there was this…they’re figuring out this cluster. If you’ve been around 25, 30 years ago, it’s called syndrome X. So, they didn’t know what the syndrome was. They called it X. But once they figure out what X was, and it’s these five things, and then they change it. This is metabolic syndrome because these simply are the metabolites in the body. And therefore it’s a dysfunction of the metabolites that cause this syndrome, and therefore it’s a metabolic syndrome.

Fifteen years ago, we did not go straight after fatty liver disease. We didn’t know enough to go straight after. So, as I tell this story of clinical trial after clinical trial, you’ll see, I don’t have all the roadmap. I am fumbling myself trying to figure out how to go about getting what to study, how much to give to people. So, therefore, among the first study we did was healthy elderly. So, they have no disease of any kind other than they are 60 to 70 years old, did a four-week study, short study like that. And in this short four-week study… And we didn’t know to just give them tocotrienol or what. So, we give them a mixture of antioxidant. So, you can look at the bottom, the combo, 200 milligram tocotrienol, annatto tocotrienol, which is our delta goal, quercetin 300, resveratrol 100 milligram.

We just did it to see how it might help the elderly. And interestingly, the C-reactive protein drop a good sign and then the total antioxidant would go up. And then the GGT, which is the marker of oxidative stress, sometimes people use it for heart failure marker, drop. And say, “Okay, there’s something about this that can help the elderly.” So, I kept this in the back of my mind and think that someday I’ll probably come back to it. Then about seven years ago, I decided, I took a major risk. At the time people know about hypercholesterolemia. About 40 million people have high cholesterol. The people know that. But then as I read and I read the literature, I say, “Wow, this fatty liver disease thing, it is going to explode.” So, like this, you can google the website, the government will give you this number. Globally, 20% to 30% people have fatty liver. And in America another 5% more, 30%, that means 90 million American have fatty liver disease. Who would have guessed that the liver of person who inundate themselves with high carbohydrate and fat, the liver looked like cerotic liver of somebody who abused with alcohol? Nobody would have guessed that. And sure enough, this is happening. We will never have enough liver for transplant if this many people are getting to the list of transplant. So, here you have it, and the complication will be these four. I will try to cover the first two. By the time you get the infection like hep C like that preponderance to do that or cancer, then it’s too far gone to the right. I’m not expecting my tocotrienol to be able to do that. We don’t have a clinical trial on liver cancer. Other cancer, yes, but not that.

So, in terms of safety, a relatively safe would be a subcutaneous fat, but in the visceral fat like omentum, in other words, this is your love handle here. Inside your love handle, that will be the omentum then is less safe in the visceral. Then the least safe will be fat in the muscle, in the liver, and in the pancreas. They’re not good places. So, this is a big summary sheet, but I put this thing out. You don’t have to memorize anything. I have three or four other slide that have a picture on a graph, how to exemplify this. These are three randomized double-blind placebo control trial. So, I’m gonna put a little bit of effort in here. The subject for each study is about 80 to 100, 300 milligram twice a day on the higher end of the dose.

We chose the higher end of the dose because people have fatty liver disease. So, we did a 3-month study, 6-month study, 12-month study. Often time the audience and I would hear about dose-dependent, which means you give this amount dose and this amount dose and higher amount dose. This is not a dose-dependent study, this is a dose-consistent study. You see that? A 600 milligram in 3 month, 6 month, and 12 month, no change. I was confident that that is supposed to work on NAFLD. Instead, I did a time-dependent study. I did it a three-month finish. This is not the same group of people. The three-month finish, the study’s over, published. And then six-month study, six months over, finish. The study’s over. The 12-month study, the same, the longest study we did. But at 6 months in the 12-month study, we did all the markers and then 12 months again so that I have a chance to compare the 6 month in the 12-month study to the 6-month study that was separate.

I chose all these different markers here so that in the first three markers, the patient themself know if something is going to happen or not. They do not even need to talk to the health professional. They know. But if they go to see the health professional or doctor, they would want to measure these things, triglyceride, liver enzyme, liver enzyme, C-reactive protein, like that. For the 3, 6, and 12, we did that. I did this one further. Beyond the health professional and the internist doctor, their specialist, I’m trying to figure out how to study fatty liver so that hepatologists and gastroenterologists will also buy in. They would want to see if there’s fibrosis, cirrhosis, steatosis, and HOMA-IR. So, we did further on this study.

Those you saw in red color here, there is time dependence. Some of them are not all time-dependent, in other words they drop, but they don’t have a time dependence on it. You’ll see in the next three slides how this is so. The first one, the delta-tocotrienol at three months, six months, and nine months, the BMI drop, the waist circumference drop, and the weight drop. I was surprised that they have dropped weight. So, it is not a weight loss product per se, but when the inflammation and the body come back to balance because it’s so out of kilter, and when they come back to balance, not surprisingly, the weight would also respond to the loss of weight. And hence we saw the weight loss. Delta-tocotrienol reduces these elevated parameters.

So, you can see that, AST/ALT, I call this liver stress enzyme. You can see the liver is de-stress. And so, it dropped by the tocotrienol 600 milligram at this time-dependent. By the way, if I go back again, you notice that the weight loss is consistent even though it came back up here. So, they lose about 12 pounds consistently. If a person is overweight and a fatty liver, losing 12 pounds is nothing to sneeze at. So, now, the second one, ALP-GGT also drop. And clearly, the inflammation drop under high-sensitivity C-reactive protein. And I think this is the last one of that study from the table. See the steatosis drop and apoptosis, meaning that the liver cells is not dying, that also drop. That’s fantastic. And the fibrosis marker also dropped.

HOMA-IR Is a measurement of insulin resistance. But this is supported by American Diabetes Association. When you see this hemostasis… I forgot…is hemostasis of model of insulin-resistant. That means that you not only measure the sugar, you want the sugar to drop. You also measure the sensitivity of the insulin. So, if the sensitivity of the insulin increase and the sugar drop, the translation of these two factor that is in this HOMA-IR equation, then it will drop. So, the HOMA-IR drop, means the sugar drop, and the insulin is beginning to be functional. This is as sweet and as good as it’s going to get. I was just really happily surprised by this finding.

So, I’ve done the fatty liver thing. So, then we move on to another cluster of metabolic syndrome hypercholesterolemia. We did this quite earlier on. We did not know at what dose it would work. So, we have 125, 250, 500, 750. We give them all at one time like that. We did not know like that. And when we did, you notice that for cholesterol, 250 works well, 500 work, but begin to work less. And then 750 work even less is because when we give them all at one slug, the body can absorb it. So, therefore most of them is pooped off. So, then from there, we level up and set that at any one time, the dosage of the tocotrienol should not be more than 300 milligram, otherwise, it’s not absorbed as well. But for what is worth here, you noticed at 125 milligram, the C-reactive protein dropped, oxidized, fat dropped, the total antioxidant would increase.

You can see, the total antioxidant increase in this teal color. At 250, it works better. And 500 also work better. So, we submit to help in this lipidemia, somewhere between 250 and 500 would work. In the back of your mind, don’t ask, “Oh, does Designs for Health have 250, 500?” I did this before I even partner with Designs for Health. I did this to know what would be the dosage that would be. So, you can see, I’m trying to be as honest as I can to figure out what works. So, I’m trying to find that dosage, so sometime at this level, sometime at that level. So, on here, I summarize this as somewhere between 250 and 500 milligram would help people with dyslipidemia. So, now, I move on to another kind in people with pre-diabetes. See how I randomized them.

The sugar, fasting sugar, is 100 to 124, moderately high, but not diabetic, and A1C is 5.7. These are all classified by the American Diabetes Association. I didn’t do anything to it. And then if you look at this three-month study, randomized double-blind placebo control, if you look, the fasting glucose compared to placebo drop, somewhat modest, but it drop. It’s only a three-month study, and the insulin drop, which means that there’s improvement in the sensitivity of the insulin so that the insulin secreted by the pancreas is reduced. And HOMA-IR drop and I explained that, compared to placebo, definitely functional. Remember, this is a pre-diabetic study. The next slide is diabetic. I think of it this way, pardon me for using this metaphor. I think of it like a floodgate. In pre-diabetes, the floodgate is being contained, so, therefore, the sugar is leaking, but not serious, but leaking. You can still change it.

In diabetes, the floodgate is burst open and the sugar is spewing forth, and the sugar is high. So, in pre-diabetes, it’s a contained floodgate. So, you can…easy to see what’s happening. So, in the next one, this is type 2 diabetes. Randomized, again. Here we did the study for longer, six months. I wasn’t confident that in three months, I might see something. So, we look at it longer and we have two dose here. So, this is a dose-dependent, one at 250, one at 500. So, you can see the 500 by not double, by a little more, but not a whole lot more like that. So, whole lot more means that if this is 7%, then this glucose would’ve dropped 14%. We didn’t see that. If you look at A1C, 6.328 like that. So, by some more, but not a whole lot more like that. And HOMA-IR, I explained that to you. But if you look at the second one, clearly, the triglyceride drop. Interleukin is another measurement for inflammation and tumor necrosis factor also. And then this is oxidized fat here in the bottom. So, clearly, the subset of metabolic syndrome is partly addressed, the sugar, the triglyceride, and then the… Oh, we didn’t do HDL. But then we chose inflammation markers for this one here.

So, now, I’m done on the tocotrienol. I want to move on to other study where we use combination that have resveratrol and vitamin D. So, summary here, maybe you can…rather than me repeat the reading, you can read this. So, it summarizes the six, seven slides that I mentioned earlier. So, like that, and I wrote the recommended dosage for people on tocotrienol on related conditions. I was presented a chance to look at resveratrol vitamin K and vitamin D. So, I decided to search the literature. First, I searched the literature on resveratrol. We do not conduct a lot of studies on resveratrol because we don’t make resveratrol to do that. But we did one. Remember the healthy elderly, we did that, right? And so, when I did the literature search on metabolic syndrome with this, if you look carefully on this table, I summarized that, just too many studies out there.

If you look, generally, they’re done on obese men and patient. If you look on the conclusion on the right-hand side, some things are significant, other things are not. And for it to work, they typically…in the bottom I wrote there about 250 to 500 milligram per day. And you have to wait for three months or more to see any significance like that. I can point to you that it’s not as good as tocotrienols, not significant. Liver enzyme didn’t drop. I show you several slide that the tocotrienol drop liver enzyme like that. And some of this thing here, the lipids improve, but the anthropometric improve also, but the glycemic did not improve. So, you can see, it doesn’t equate as well as a tocotrienol, but it does have some benefit. As you can see some of this thing here, like here, there are some benefit, however…but this is kind of wild. They gave people 2 gram. It’s just too much, you know, like that. So, I would say that 250 to 500 milligram would be good.

So, the next slide is on vitamin D. So, if you look at the vitamin D thing, you can also see sometime no clear conclusion, not significant and significant. So, I put it down here. You can get it from Designs for Health on this slide that I summarize clearly here. And my conclusion here would be 4,000 IU per day would be about right. And I also found that if you just titrate this slide with the one before, resveratrol probably is a little bit better than vitamin D in metabolic syndrome. Eventually, I’m trying to have an integration of this that will eventually come up with what is our GlucoSupreme. I don’t have magic to make this happen. I’m trying to have an understanding how this… And people do all kinds of clinical study.

But if I look at just between resveratrol and vitamin D, resveratrol appeared to work better than vitamin D, but not that vitamin D did not work, just resveratrol works better. So, that’s the vitamin D thing. The next one, vitamin K1 and K2. On this one here, if you look at this one here, you’ll see that the metabolic syndrome…see, older people, again, metabolic syndrome prevalence drop when the vitamin K in the blood is high. So, this is more progressive progression study. They did not intervene them. And then not significant in the meta-analysis K1 and K2 toward improving insulin sensitivity. Tocotrienol did, but not this one. The glycemic, they did not. I was a little bit disappointed that the glycemic HOMA-IR glucose did not work. And the cytokines, leptin, and adiponectin didn’t, and this one also didn’t. So, this was somewhat of a depressing study.

Then this next one, which is later review, it looked like the menaquinone intake does show as the higher intake compared to lower intake shows that the metabolic syndrome drop, and then also work on people with reduced body fat. Okay, there’s something there. Generally, when I read this study that for the bone health, it is indicated by MK-4, for vascular calcification, MK-7, for metabolic syndrome seems to be indicated by vitamin K. So, if I try to package the vitamin K together, my conclusion will be 1 milligram of K1 plus vitamin K2. And in the GlucoSupreme, it’s essentially 1 milligram of vitamin K1 and 1 milligram of vitamin K2. And the K2 is 1 milligram, is entirely MK-4. Hopefully, I’m in a [inaudible 00:38:27] later. So, that’s pretty much that.

Then comes this study we done. We did this study somewhat prophetically, meaning to say I didn’t do this study because of metabolic product. We’re trying to make it… We did this study because there were a lot of animal study we did this way, that way, every way, and all kinds of combination. So, finally we came up with a thing to do a combination of delta-tocotrienol, which is annatto tocotrienol resveratrol vitamin D. And then if it’s all combined with this, this just mean nutritional supplement three, three nutritional supplement, which is this three. So, this is four clinical trials, ladies and gentlemen. So, this is this study as a group, second group, third group, and then this is fourth group. This is a monstrous study. It’s just so huge like that. So, when we did this, the one that have NS3, which means all the combo, the glycemic or this… The study was so large. I cannot even put all the thing to plot graph for you. If I did, then this would be like 10 different graph. It’s just too much. So, the glucose A1C insulin, HOMA-IR, they generally drop 10% to 20%. The lipid drop 8% to 10%, not dramatic, somewhat drop. And inflammation, C-reactive protein, tumor necrosis factor, interleukins drop beautifully. So, the summary that the authors made was that the combo, all the three together, is better than delta-tocotrienol in turn better than resveratrol, in turn better than vitamin D in type 2 diabetic, which means that for a standalone, delta T3 is top. If it’s combo, the best. So, therefore I learned from this. So, if we were to make a GlucoSupreme, I should have it all three. If I were to have a standalone, I’ll go for delta-tocotrienol. So, if I were to be someone with metabolic syndrome, what would I do? I will take GlucoSupreme and I separately in addition would take the Annatto-E tocotrienol, which Designs for Health have. So, therefore, my conclusion, delta-tocotrienol resveratrol would be best for people with metabolic syndrome with obesity because this type 2 diabetic have obesity. I’m making my conclusion here. The study was for type 2 diabetic for [inaudible 00:40:55]. So, there you can see how I’m trying to summarize this. I don’t have a clinical study on arteriosclerosis.

So, therefore we can only have animal study. So, an animal study, what I saw in tocotrienol, it reduces the Velcro effect. When you have inflammatory particle, you don’t want them to cling onto the artery. You want the artery to be smooth. If they cling onto the artery like oxidized LDL, then there’ll be the starting point for the formation of arteriosclerosis and making a plaque. If the plaque already exists, you want the inflammation to be contained. You don’t want the plaque to rupture and then, therefore, attract more platelets and clog the plaque even more. That’s no good. So, what we found with tocotrienol, the anti-Velcro effect, I just call it like that, would be the inflammation is reduced, as you can see, inflammation marker here reduced.

The adhesion molecule, this is the one that attracted the wall, is reduced, like we can see that, we can reduce vascular cellular adhesion molecule as it is. Like, adhesion molecule is reduced. Proteolytic enzyme would be enzyme that just chew up the protein and make the plaque unstable. You want them to be reduced as it did here. This would be a cross-section of a rat artery, aortic artery control lots of plaques. See that here. With alpha-tocopherol, essentially no reduction. With annatto tocotrienol, the reduction you can see here with so little amount of to tocotrienol in the food, 24% reduction. And when you look at the whole aorta, 36% reduction translated to a human is about 340 milligram. That’s it.

So, now comes our study. No, this is not even our study yet. This is still not our GlucoSupreme, but it leads to how we formulate this GlucoSupreme, gives us a last study. So, if you look at this study carefully, we study people with metabolic syndrome… And I think they’re overweight people, metabolic syndrome, for six months. So, based on other study, we have to come up with one because they’re very expensive study. So, we use 500-milligram tocotrienol and 300-milligram resveratrol, primary, secondary endpoint primary. You can see that. The blood pressure drop. The waist circumference for men and women drop, drop better in women, weight loss about 9 pounds or so, triglycerides 16, HDL 4% and 5% increase. If you look at the slide that I have for metabolic syndrome, all of them are covered. People with metabolic syndrome have high blood pressure…moderately high pressure. The waist circumference is high, triglyceride is high, and HDL is low.

So, therefore this is doing the opposite, which is what you want, that the blood pressure drop, the waist circumference drop, triglyceride drop, and HDL you want increase. Beautiful. And then in the secondary endpoint, we study this. So, mostly we marked a secondary endpoint for inflammation. You can see that. Adiponectin is a hormone of the fat that help people to control the amount of body weight and appetite. So, you want adiponectin to increase, which it did. And we just talk about weak and adhesion molecule and that drop. So, it also prevent arteriosclerosis. Oxidized fat drop and total antioxidant increase. All is to say the combination is best when they contain delta-tocotrienol and resveratrol, most important to must have these two. Any benefits I wrote down here, dramatic vascular function improvement.

Even though we don’t look at the vascular function of a metabolic syndrome, it clearly is important to people with metabolic syndrome. So, I decided to put this here. Now, come to third product. If you look at the nutritional panel of Designs for Health, they put this thing in a different manner because this is what the government expect them to put, no change in that. The only thing that I have changed is just to put emphasis. Whatever I put on top, I consider the anchor ingredient. And then the next important one, the third important one to last like that, it go decreasing important. Otherwise, the amount is the same. So, when we make this product, I believe based on all the studies being published, it’s good for people about 18 to 45 years old. Not only older people, even younger people.

Increasingly, we have people who are overweight and pre-diabetic or diabetic earlier in age like that. Then it would be 20, 30 years ago. And then useful for early stages of metabolic syndrome to avert the pre-diabetic to become diabetes. So, I consider the vitamin E tocotrienol to be about 250 in two soft gels, resveratrol 250 milligram, and then vitamin D 5,000. If you look at the study that we did, we put 10,000. I was not comfortable with 10,000. I used a little bit too much. So, I think that 5,000 and therefore Designs for Health did this. Even though the study teaches 10,000, I was not comfortable because many supplement already contain vitamin D. So, I’m not comfortable with it going to 10,000 IU. It’s not a cost consideration, it is a dosage consideration. And for vitamin K, it had 1 milligram of K1 and essentially 1 milligram of MK-4 adding to 2 milligram of this.

And then for GG, the… The GG, typically, I would have people take as an anti-aging amount for muscle health and other would be about 150 milligram. So, this is not added for that reason. This GG here, 5 milligram is to potentiate the synthesis of vitamin MK-4. Another time, if you email me, I can show you a GG is required for the synthesis of MK-4 biologically in your body. So, this is a support to the MK-4 case. So, I don’t know if happened now. So, this is your GlucoSupreme that is about to come out or Designs for Health have already had it out. So, anyhow, if you would like a copy of my vitamin e-book, you can download this. And it’s free of charge. Just put GlucoSupreme and you can download this book. If you want a handwritten a copy, if you happen to be in Designs for Health at A4 next month, I believe, I’m gonna do book signing, would like to run into you and say hi to you. I want to thank you so much for your patiently listening day. So, we probably have about 10, 15 minutes to fill out question. So, Tyler, I’m gonna pass it back on to you.

Tyler: Yep. Thank you, Dr. Tan, for that. We have a few questions. I have four to ask you. So, the first one that I have is, why is MetS a disease cluster and not a single-bullet entity disease?

Dr. Tan: Yes, great question. If you remember the slide that I had earlier, I don’t know how to go back to that slide, it had a heart and then have that five thing. That was considered a syndrome X because somehow the sugar was moderately high, somehow the triglyceride was moderately high, somehow the lipid was moderately high. So, people could not fathom what exactly is happening. Usually, if you think of a disease, it’s an organ disease, a liver disease, a heart disease, an eye that, or gut that. But this metabolic syndrome is a cluster because it doesn’t go to just only one place like that. And hence in essence, it is a metabolic disease. It is a disease of dysfunction of the metabolites in our body, particularly triglyceride and sugar. So, therefore we have to figure out way to study this different metabolite. However, truth be told, I chose the liver. See, liver is an organ, I chose the liver because metabolic syndrome especially infirmed the liver. And when they become fatty, that fat is high stuck in the liver and can’t go any place and then the liver suffers. And then all kinds of condition happen. So, metabolic syndrome will not be a singular single-bullet disease. It’s a cluster of everything. Many things.

Tyler: Cool. Thank you so much. Next question would be, what form of vitamin K2 is more important and why, MK-4 or MK-7?

Dr. Tan: Okay. This may be new to the audience, and the audience may be surprised. For the last 10 years, you’ll hear on the news and people pump literature that the most important menaquinone MK-7. I will let you know. MK is the long chain menaquinone, MK-7 to 13. They are produced in the gut. So, MK-7 is important when you talk about gut health. There are small traces of menaquinones in the body that is not four MK-7, 8, 9, like that. The preponderant menaquinone in the human body is MK-4. The body makes MK-4 using GG that the body also makes like that. So, that begs the question. And the audience should take note of this. Why does the body make MK-4? The body does not make MK-7. MK-7 is made by bacteria in the gut.

So, for good gut health, MK-7, but for good body health, you need MK-4. I’ll give you the shorthand. MK-4 is synthesized in the human body for two simple reason. It put the calcium where it should be in the bone, 95% or more of calcium in the bone, 5% are in soft tissue. The moment soft tissue exceeds 5%, you’ll have calcium loaded everywhere in the human body that you don’t want. That would be gall as in gallstone, kidney as in kidney stone, and plaque as in arteriosclerosis. You don’t want that. So, therefore MK-4 does this. It sweeps the calcium from everywhere in the body to the bone. That’s why we need MK-4.

Tyler: All right. Thank you. We have another question. What form of vitamin E is more important and why, tocopherol or tocotrienol?

Dr. Tan: For the longest time, people have been studying tocopherol is not gonna go away. Unfortunately, our industry greater than 90% of the vitamin E out there is alpha-tocopherol. I strongly discourage people to take alpha-tocopherol. I think that the food which will provide you 10, 15 milligram is good enough. Instead, people should take tocotrienol. For 35 years, I’ve been studying this, I show you lots of example. And in clinical study, in animal study will be 20 times more study. They consistently point to the fact that tocotrienol helps to reverse chronic conditions unshed by tocopherol. It’s amazing like that. Hopefully, if you download my book, you can see many of these studies that point to tocotrienol but not tocopherol.

Tyler: All right. Awesome. And we have one more question. You have five major ingredients in GlucoSupreme. How would you rank them in descending priority for metabolic health support?

Dr. Tan: Okay, I sort of answered this question, which is this slide here. I don’t know if the audience can still see that. There are five of them. So, if you look at it… Now, keep in mind, the way the nutritional label is made by GlucoSupreme by Designs for Health is not in this order. I place it in this order to put priority. So, I would say the priority would be vitamin E delta and gamma-tocotrienol. And after that, resveratrol, and after that vitamin D. I kind of like go back and forth. Should I put vitamin D first or vitamin K first? In here I put vitamin D first because of the amount of study vitamin D have been produced. That doesn’t mean that it’s going to be the most active, but close enough. So, I put vitamin D first. In time, I put more study on vitamin K1 and K2. So, the D and K are about same. And the GG I put last only because of the amount 5 milligram. But for having a strong muscle and strong bone, I would recommend people to take 150 milligram for which Designs for Health have this product. It’s called Annatto-GG. You can look for it in other place. So, if you want more GG, Annatto-GG Designs for Health have. If you want more tocotrienol Designs for Health Annatto-E. And then if you want specifically for metabolic syndrome, this is it. It’s hot from Designs for Health to just come up with this.

Tyler: All right. Awesome. Well, I believe that will finish up the questions. I would just like to let everyone, or thank you, Dr. Tan, for the incredible presentation. And I also wanna thank everyone for joining us today. There will be an email that’ll come out through Zoom, usually within a day. And that’ll include information where you can reach out to Designs for Health or Dr. Tan for any more questions. Dr. Tan, do you have anything else you’d like to say?

Dr. Tan: No, hoping that all of us will be in good health, do well. And if I run into you and show, come up and say hi to me. Have a wonderful week, everybody. Thank you.

Tyler: Thank you, guys.