This week’s podcast guest is Jonathan Jones, PhD, a plant polyphenols researcher and the Chief Scientific Officer at Monteloeder, a company that provides innovative, scientifically researched botanical ingredients by assessing the botanicals’ components, antioxidant and anti-inflammatory capacities, and mechanisms of action.
They developed a product called metabolaid®, which contains a standardized ratio of Hibiscus sabdariffa extract and lemon verbena extract to deliver active compounds, primarily anthocyanins and verbascoside, respectively. This product reduces triglyceride buildup in fat cells in the liver and adipose tissue.
We learned from Dr. Jones about how metabolaid® activates AMPK, which can switch on fat burning and block fat storage. There are numerous other cardiovascular and weight-loss benefits linked to this product, including improved microbiome diversity and others discussed by Dr. Jones in this episode.
Please listen to the full conversation to learn the following about this powerful botanical:
- Its cardiovascular and fat-loss benefits
- The plant components and mechanisms of action
- The research and extraction process
- How this product differs from incretin agonists and increases GLP-1 expression
- And much, much more!
Dr. Jonathan Jones: And so specifically, what we observed with participants that were taking metabolaid® and following an isocaloric diet because that’s what we did in our first initial clinical trials with metabolaid® was to give a nutritionist-led diet together with the ingredient and compare this to placebo. But what we observed was that those that were taking metabolaid® lost twice as much weight than the placebo group. So, of course, the placebo group, since they were on a diet, lost some weight, but we saw the metabolaid® contribute to losing twice as much.
At the same time, this was related to a smaller waistline, they had less abdominal fat, and abdominal fat is the one most related to cardiovascular disease or type 2 diabetes. And of course, when you combine a dietary supplement, such as metabolaid®, with diet and exercise, you’re going to have the most impressive results. Though we did perform studies in absence of diets where you do see a smaller but still significant improvements in all these conditions.
James Maskell: Welcome to the Evolution of Medicine podcast, the place health professionals come to hear from innovators and agitators leading the charge. We cover the latest clinical breakthroughs and health technology, as well as practical tools to help you transform your practice and the health of your community.
This podcast is brought to you by the Lifestyle Matrix Resource Center, who provide a range of options to help you deliver successful, effective functional and integrative medicine. To find out more and to get started, go to goevomed.com/lmrc. That’s goevomed.com/lmrc.
Hello and welcome to the podcast. This week we are going to speak to a research expert on the cutting edge of some of the most innovative dietary supplements in our space. If you’ve been interested in weight loss, if you’ve been interested in GLP-1 agonists, if you’ve been interested in AMPK activation in patients, then definitely tune in to this podcast. We’re with PhD scientist, he’s the Chief Scientific Officer, and he is called Jonathan Jones. And just a wealth of information, over 25 years of clinical research into different plant polyphenols. And yeah, we’re going to learn about how certain plant polyphenols and certain combinations can facilitate weight loss, can mimic some of the effects of GLP-1 agonists, but with a very different side effect profile. And we’re going to talk about AMPK activation. All topics that come up at conferences and leading-edge clinical discussions. I think you’ll get a lot of value out of it. Enjoy.
So, a warm welcome to the podcast, Dr. Jonathan Jones. Great to have you here, doc, and to share a little bit more about your work. And I think what we’re going to get into today is plant polyphenols. I think this is relevant to clinicians on the front line. It’s relevant to previous conversations we’ve had about weight loss drugs. So, let’s just jump into it. How did you start working with plant polyphenols as your PhD work? And so, tell us a little bit more about that journey.
Dr. Jonathan Jones: All right. Well, first of all, James, thanks for having me here. It’s a great pleasure. My journey started over 25 years ago when I began working in Monteloeder exporting botanicals originating from the Mediterranean region to other parts of the world. And back then, the industry wasn’t as advanced as you can see now. The extracts were mainly standardized by ratio, and there was very little known regarding the active compounds that were present in the plants. However, at the research level, there were studies that were demonstrating the health benefits of specific plant polyphenols. And as this knowledge grew and the technology advanced, the demand for standardized extracts with identifiable actives began to grow.
So, in the sense, a vital part of our work has been researching to identify plant polyphenols that are present in the botanicals that we commercialize and assess their potential health benefits. So, to this end, we’ve been collaborating with several laboratories for almost two decades, working on identifying the different polyphenols, assessing their antioxidant, their anti-inflammatory properties, as well as their potential mechanisms of action.
And also, another aspect that we’ve been working a lot has been assessing the potential complimentary or synergistic effects when you combine different polyphenols from different plants, allowing you to develop innovative, more potent formulas than with just single extracts. So, this would be the case scenario of what we’ve done with our ingredient metabolaid®.
So, metabolaid® is a result of over seven years of research where we tested 300 different botanical extracts, either alone or in combination. And our results indicated that the combination of the Hibiscus sabdariffaextract, standardized and anthocyanins, and lemon verbena extract, standardized and verbascoside, at the proper ratio of each was the best combination for the effect we were looking for. And very special interest in lemon verbena part because we actually had to develop our own extraction process, which is very unique, in order to purify one of those active compounds, verbascoside, to the levels that was needed for metabolaid®.
James Maskell: Interesting.
Dr. Jonathan Jones: It’s currently one of the highest quantities of verbascoside you can find in market.
James Maskell: That’s so cool. Yeah, I remember listening to doctors in our field like Bob Rountree, who was doing this kind of clinical work in the eighties. And at that point, he said that he was really, he had all of these herbs up on his shelf, and he was actually having to take handfuls of them and combine them in some ratio and do his own testing. And that was the very beginning of the sort of professionally delivered plant medicine in that way. And obviously, it’s come a long way both on the doctor side, on the clinical side, but also on the research side with all the time that you spent in really understanding what those properties are. So, let me ask you, what is the process that you use to determine the correct ratio of lemon verbena and hibiscus to make your product?
Dr. Jonathan Jones: Yeah. Well, once we identified that lemon verbena and hibiscus were the candidate plants, the extracts we were going to work with for our final formula, then we had to test different combinations of each at different ratios, different purities of certain active compounds. And we did this in the lab. So, what we did is we knew that verbascoside was, in the case of lemon verbena, the major active compound that we were interested in. So, that’s why we had to develop a new extraction process because, at the market, there was very low levels of verbascoside we were looking for, so we had to develop that internally. And actually, it was a lot of work. It was almost 10, 15 years of work, and we had to gain a lot of deep knowledge on not only the extraction process, but also the locations of where to find the raw materials, when is the best moment to collect the leaves. And this way, we could increase as much as possible the highest verbascoside content in the raw material, allowing us through a simple extraction process, obtain the percentages that we were looking for.
And regarding the hibiscus, it was quite similar. Not as challenging as it was with lemon verbena, but still, it was a challenge as well. We identified a couple of anthocyanins as the adequate ones that we had to look for. And then what we had to do was, besides working them in isolation, was work with these active compounds, combining them in different ratios. And we tested this actually in cell models for adipose-derived tissue cells. So, what we did here, this is a model of fat storage, and what we were analyzing was the fat storage in those cells, the triglyceride accumulation and the lipid droplets. So, what we wanted to see was that the combination would reduce as much as possible that triglyceride accumulation in the fat cells.
And the negative action that we identified in order to reduce this triglyceride accumulation was through AMPK activation. So, the rationale behind the study that we did in vitro in the cell model was that the ingredient would block that lipogenesis in the adipose tissue. And also we were looking at that moment in the liver because you know that there’s nonalcoholic fatty liver disease, which is a consequence of obesity as well. So, we were looking for in general how to reduce those fatty deposits both in the adipose tissue as well as in the liver. And this was a therapeutic target to promote weight loss. So, once we tried different combination and we worked them in these adipose-derived cells, we identified the combination that decreased the most the triglyceride accumulation and increased also at the same time AMP activation, which was what was chosen for metabolaid®.
James Maskell: Yeah, that’s really interesting. That’s kind of become, I think, a bit of a buzzword recently, that topic of AMPK activation. I guess, for people who aren’t familiar with that topic, can you just share a little bit more about how it’s activated generally with diet, exercise and herbal products, and what effect it has in the body?
Dr. Jonathan Jones: Yeah. So, AMPK is an enzyme you can find in all the cells of the body. And basically, it acts as a metabolic switch. So, when you activate it, basically what you’re doing is you’re activating your body to burn off the energy because you got to move or you’re hungry or you got to use that glycogen storage that you have or your fat tissue, they got to release triglycerides in order to give energy to the muscles and so forth. So, basically, the concept here is that if you’re activating AMPK, especially in the adipose tissue, at one side, you’re blocking the formation of new fatty deposits, and you’re also promoting your body to burn off that fat storage that you have and break it down, take it to the muscles to be used as energy. So, like I said, it’s also related to glycogen storage, so it also increases glucose sensitivity and activates the mitochondria to create ATP, to create energy for the cells.
So, AMPK is activated naturally when we exercise or our body’s hungry, like I said. So, if it doesn’t have the energy to continue moving, whether it activates AMPK to induce all these processes. And overall, whenever our body needs energy. Right? So, what happens is that when someone is suffering from obesity, their AMPK activation overall is very low. So, it makes it very difficult for them to lose weight because their body, their metabolic rate is very low. And even though if they’re doing exercise or they’re on a diet, they can’t really reach those levels necessary to promote weight loss. So, what we observed in the preclinical setting is that metabolaid® can increase AMPK activation up to 12 fold compared to the obese situation, and even more so compared to the lemon verbena or hibiscus by themselves.
Now, this is very relevant when someone is on a diet. So, someone, let’s say they’re overweight or they’re obese, and they undergo a weight loss or low calorie, hypercaloric diet. So, our body fights back that diet. So, basically, it decreases further your metabolism and at the same time, it increases your hunger state. And this is an effect that’s called energy gap. So, when we quit the diet and you’re in that situation of the energy gap, as soon as you start eating again what you normally eat and the high levels of calories that usually take, well, you quickly regain that lost weight and many times you gain a couple more pounds because of this. And that’s the reason why the majority of the weight loss programs fail. So, what we observe with metabolaid® is that it decreases this energy gap effect. So, it naturally increases your metabolic rate while also promoting satiety, which would benefit a lot those people that are going on a diet and be more successful in losing that weight that they’re looking to lose.
James Maskell: Interesting. Yeah. Well, I’d love to just bring it back to a topic that we had actually last month on the podcast, which was we spoke to a doctor who was recommending a lot of GLP-1 agonists. And this is definitely obviously a hot topic in medicine. A lot of the practitioners that listen to this have patients coming in asking about GLP-1 agonists and are trying to work out: Is it a net benefit to the person in front of them given the side effect profile? And given what we don’t know as well as what we do know about its effect in curbing hunger and affecting weight loss. So, I guess can you, I guess, share from your perspective? I know that you have done some research with the same kind of endpoints, right, as those GLP-1 agonists. So, I guess, can you share a little bit more about how you see it from your perspective?
Dr. Jonathan Jones: Yeah, sure. I think right now at a consumer level, there’s a lot of confusion as to what is GLP-1, what semaglutide does and how this relates to weight loss. Right? So, actually GLP-1, which its long name is glucagon-like peptide-1, is mainly involved in lowering blood sugar levels. And semaglutide was initially developed to treat type 2 diabetes. However, the researchers working with semaglutide observed a significant weight loss in the patients that were both either obese and/or had type 2 diabetes as a sort of side effect.
So, we know that obesity, excess body weight and hyperglycemia usually go hand in hand. And there’s a very high prevalence of both diseases in the US. So, it’s logical to consider this craze right now that’s behind semaglutide, especially at the consumer level. And this has also caused a steer in the nutraceutical industry where we see certain companies that have been quick to classify their ingredient as a natural semaglutide.
Now, I prefer to base my claims on science and not on hype. And I think it’s important to state that metabolaid® is not a natural semaglutide. Okay? It’s not a natural drug. And its major mechanism of action is different. Like I mentioned before, it’s based on the AMPK activation. However, we do have results, which I’ll explain now, as to this effect on GLP-1.
So, GLP-1, as with any hormone, has more than one effect in our body. And besides glucose control, it’s also implicated in satiety at the gut level. So, it’s actually one of those intermediates that’s involved in the gut-brain axis. It is released from intestines whenever there’s food there, it travels to the various parts of the body for different effects, like in the pancreas to release insulin and so forth. And it also travels to the brain to activate the signaling cascades to tell your body that you’re full and you should stop eating.
So, we analyzed GLP-1 expression in a couple of our clinical trials with metabolaid®, and we did observe an increased expression of this hormone when taking the ingredient extract. So, in one of the studies, we compared two groups of individuals that were both on a nutritionist-controlled diet where one was also taking a placebo and the other one was taking metabolaid®. So, this is what we’re talking about, that energy gap effect.
And what we observed was that the placebo group presented lower GLP-1 levels in blood while also reporting to feel hungrier throughout the day, which is an expected outcome. This is something that’s normal. Right? And as for those that were taking metabolaid®, we actually observed the opposite. They had higher GLP-1 expression, and they also reported to feel less hungry throughout the day. So, this suggested initially for us that there is a certain correlation between the decreased appetite sensation that the consumers, the participants of the study were perceiving when they were taking metabolaid® and the increased GLP-1 expression.
We also analyzed other satiety related hormones, but we did not observe such a significant effect. So, we saw the GLP-1 was the main culprit here. So, we did an additional study here where there was no diet involved. And what we did is they were taking metabolaid® for two months, and we compared this to a placebo. All our studies are always double-blind, placebo controlled. And we conducted a meal challenge to both study groups.
So, the volunteers, they were brought to the clinic, they were in fasting conditions, they were provided a set breakfast and then four hours later they were given a buffet lunch. And throughout that whole time, from before breakfast to after their lunch, blood samples were taken from them at different regular intervals to later analyze various hunger- and satiety-related hormones while the participants were also filling out questionnaires regarding their appetite levels.
So, the result of this study demonstrated metabolaid® increased GLP-1 expression compared to the placebo immediately after breakfast, and it maintained these levels higher compared to the placebo throughout the whole timeframe up to the lunch. At the same time, these same participants were prone to feel less hungry compared to the placebo group, and with a special relevance in the first two, three hours after the meal. Then when lunch came, while both groups, they felt that they were hungry and they wanted to have their lunch, at the end, those that consumed metabolaid® for two months ate less and consumed about 10% fewer calories and reported to feel fuller faster than the control group. And therefore, we could identify this correlation between metabolaid® consumption, lower appetite and increased GLP-1 expression.
James Maskell: Yeah, that’s really interesting. As I was looking at the ingredients there, I could see ingredients, I guess, I’m familiar with, that can help with weight loss, blood pressure, inflammation, cholesterol. What are some of the mechanisms of action for how that works in the body?
Dr. Jonathan Jones: Yeah. Well, based on our studies with our ingredient, we have a total of nine scientific papers published with metabolaid®. Some of them are clinical trials. And we’ve analyzed various aspects regarding excess body weight and its secondary complications. So, basically, when you have excess body weight, you have excess body fat storage in your abdominal region, you have certain secondary complications that appear throughout time. So, you can start having increased blood pressure, you have a low level of chronic inflammation, you have high cholesterol, high triglycerides, high blood glucose, and altogether this comprises the condition called metabolic syndrome. So, when a person out of these five conditions meet at least three of these criteria, they’re considered that they have metabolic syndrome.
And so specifically, what we observed with participants that were taking metabolaid® and following an isocaloric diet because that’s what we did in our first initial clinical trials with metabolaid® was to give a nutritionist-led diet together with the ingredient and compare this to placebo. But what we observed was that those that were taking metabolaid® lost twice as much weight than the placebo group. So, of course, the placebo group, since they were on a diet, lost some weight, but we saw the metabolaid® contribute to losing twice as much.
At the same time, this was related to a smaller waistline, they had less abdominal fat, and abdominal fat is the one most related to cardiovascular disease or type 2 diabetes. And of course, when you combine a dietary supplement, such as metabolaid®, with diet and exercise, you’re going to have the most impressive results. Though we did perform studies in absence of diets where you do see a smaller but still significant improvements in all these conditions.
At the same time, we also observed in more recent studies that metabolaid® seems to have performed changes in the gut microbiome. So, you know that right now there’s increasing evidence that the gut microbiota plays a very important role in our health. It could go from weight management to immunity or even our state of mood. So, what we observed with our results of metabolaid® was that its intake increases microbiome diversity as well as the production of short-chain fatty acids. So, these are all markers concerning what is a healthy gut. That’s what, for example, when people are taking probiotics are looking for. And this is part of the reasons of the benefits of taking metabolaid®, this improved microbiome diversity, this short-chain fatty acid, especially butyric acid, production. And also, there were other hormones besides GLP-1 where we observed very notable changes when taking metabolaid®.
So, one of these hormones is leptin. So, leptin is involved in several metabolic processes. This includes appetite control, it includes fat storage, it’s released from the adipose tissue. And there’s an interesting thing about leptin is that leptin induces satiety, yet people with obesity have high levels of leptin. And the reason behind this is because there is a leptin resistance similar to what you observe with the insulin resistance in type 2 diabetes. So, people with obesity have very high levels of leptin. And what we observed with our clinical trials with metabolaid® was that leptin levels dropped dramatically. So, what we saw was that there was increased leptin sensitivity when taking metabolaid®.
James Maskell: Interesting.
Dr. Jonathan Jones: And this coincides as well with another hormone called adiponectin. Okay, so this is another hormone, it’s released from our fat tissues, and it’s implicated in the lipid metabolism, in the triglyceride accumulation and so forth. So, those that have obesity or with metabolic syndrome, adiponectin is generally, its expression is very low. So, what we observed is that when taking metabolaid®—this was analyzed both in a preclinical and clinical setting, so with animal models as well as in people—we observed that the adiponectin increased its expression. And it’s also one of the reasons when those mechanisms of actions in that lower triglyceride accumulation that we observed in the preclinical tests.
James Maskell: Interesting. I’ve been doing this podcast for almost 10 years, and I never heard of adiponectin in that whole time, no one ever mentioned that, but that’s really interesting. Well, it’s really interesting to see what’s possible when you sort of apply rigorous science and lots of testing into plant polyphenols to come up with something that is having such a significant effect on the physiology. What do you see moving forward? What seems promising, and what is sort of coming next in the research?
Dr. Jonathan Jones: Yeah. Well, right now, we’re trying to reach out to more a broader audience with our ingredients. Because like I said before, we have nine studies performed, seven clinical trials, and we’re still doing a few. We’re thinking about adding a few new ones in the next coming months or years. But one of the things that we’re really working on, especially throughout this past year, was you know that from a consumer level, there’s an increased pill fatigue effect. Okay, people are getting a bit tired of taking the capsules, the tablets, and looking for alternatives to the traditional delivery formats.
And the past year or so to a couple of years ago, the fastest growing format in recent years are the gummies, which is very easy. It’s fun. It’s a go-to solution. You can take it whenever you want. And the problem with this is that while everyone wants to have their product in a gummy, there’s many challenges with this format, especially when we’re talking about botanical extracts. So, for example, the botanicals usually have a bit of a higher dose compared to what you find in, for example, in the case of vitamins and minerals. It requires mainly to have to take several gummies in order to reach that daily dose that you need.
And then of course, being natural extracts, well, they can give a certain color or taste or smell or even the texture can change a bit, and that might not be the most appealing for the consumers. And lastly, from a more technical point of view, it’s like, okay, we have to prove that not only can we put those botanical extracts in those gummies, but they maintain stabilized, especially those active compounds that we want throughout the time. They can withstand the fabrication process, the manufacturing process of the gummies and are stable throughout the whole time. So, while initially the gummies might sound very appealing for the consumers, from a technical point of view, in many cases, for many ingredients out in the market, it’s not possible or very difficult to achieve, especially when we’re talking about botanical extracts.
So, in this sense, we’ve been working very hard in improving the ingredient to try to be compatible with the gummies. We’ve already had success with other formats, and you can find in the market final products in a powder form that you mix with water or already ready to drink or in gels and jellies and sachets. The anthocyanins present in hibiscus extract give it a natural red to bluish color. So, in that case, it’s very easy and compatible to use. In fact, hibiscus is usually used as a food coloring agent. The only thing is that it has that very bitter taste. So, that’s something that we have to use masking techniques and so forth to try and improve the compatibility in products like the gummies. So, we’re testing those kinds of different possibilities to try to improve the taste and the texture. And we work together also with our clients that they wish to commercialize this kind of products and in order to find that optimal flavor and color and texture and so forth for their end product.
James Maskell: All right. Yeah, that’s really interesting. Well, look, I really appreciate you coming to share a little bit about it. This topic came up off the back of the podcast that we did with Dr. Christina Robins on GLP-1 agonists and how it’s being used in clinical practice. I’ve seen more and more practitioners using plant polyphenols as a sort of first line therapy for weight loss to see if they can get the sort of outcomes that you are talking about with patients without the same side effect profile as GLP-1. I think what you’ve shared today is exciting and promising and speaks to the power of natural medicine, basically. I mean, that’s as far as I see it and that’s really what we’re involved in here and what we’re looking to move forward. I guess one last question. This is called the Evolution of Medicine Podcast. When I say the words the evolution of medicine, what does it bring up in you?
Dr. Jonathan Jones: Well, for me, the first thing that comes to mind is personalization, is trying to find what’s right for the right patient at the right moment, the right dosage, the right ingredient and so forth. And that’s really where I think medicine is going forward. And in that sense, from the nutraceutical industry, I think it is also working in a similar fashion. You’re already seeing in the market certain companies that are offering more personalized solutions for their consumers, both maybe through questionnaires, through blood tests, urine tests, genetic testing and so forth. And I believe really that’s the way going forward.
And more and more, I think there’s a blend of what is medicine and what is dietary supplements and how we can try to drive medicine away from the treatment towards prevention. Try to avoid, prevent them from getting the disease before you have to give them some kind of treatment, drugs and so forth with all the side effects and complications that you have afterwards.
James Maskell: Beautiful. Well, that’s what we’ve been doing and that’s what we’ll continue to do. And really appreciate your expertise and all the work that you’ve been doing over the last 25 years to bring us products that can really make an impact to patients. So, thank you so much for being part of the Evolution of Medicine Podcast. I’ve been here with Dr. Jonathan Jones and he’s been talking all about the work that they’ve been doing in understanding plant polyphenols. This is the Evolution of Medicine Podcast, I’m your host, James Maskell, and we’ll see you next time.
Thanks for listening to the Evolution of Medicine podcast. Please share this with colleagues who need to hear it. Thanks so much to our sponsors, the Lifestyle Matrix Resource Center. This podcast is really possible because of them. Please visit goevomed.com/lmrc to find out more about their clinical tools, like the Group Visit Toolkit. That’s goevomed.com/lmrc. Thanks so much for listening, and we’ll see you next time.
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