Cracking the Leptin Code

by Deanna Mutzel, DC

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Mike Mutzel: Thanks again for joining us everyone. I know we had some scheduling glitches. I wanted to apologize to all of you about that. I did send an email to most of you regarding those issues. We have a lot more people helping out. Thanks for your support and participation every week here. Quite a few huge interest in the webinars. We’re getting 5 to 18,000 people signing every week, and so we’ve had more stuff involved. This webinar, for example, was scheduled when I was traveling doing some other talks in different areas in the country and then Dr. Carnahan couldn’t make it to… She’s actually doing a lecture tonight in Denver, so we just had some scheduling glitches and changes and so forth. Really, we’re grateful that you are so interested and we want to return that to you in the form of better and better education. So, the last couple two webinars had some issues, so we want to apologize for that. We want you guys to know that that wouldn’t happen again. So Bettina, what do you say?

Bettina Newman: I say take it away, Mike.

Mike Mutzel: Take it away… Get this thing rock and rolling. Some of you may have heard this before. We’ve done webinars on this topic. What we’re going to talk about tonight is leptin and belly fat in the gut. We know that the gut is so important in many aspects of metabolism, immunity, and weight loss, and so many different components. So, we’re going to talk about how the gut is really an instigator of leptin resistance, but first, I want to talk about fat and just make sure we’re all in the same page because I don’t know if you’ve seen this or not, so I just want to make sure we covered the nuts and bolts.

So, we know that excess fat or excess fat – excess adipose tissue is linked with many inflammatory disorders, from depression, neurologic disorders, autoimmunity, diabetes and much more. What the research is showing is that balancing the immune system really helps to ameliorate seemingly non-immune diseases, such as diabetes. There was a paper published in Nature Reviews Endocrinology and Metabolism, one of the leading endocrinology journals. So, just saying that clinicians should be looking at balancing the immune system for type-2 diabetes, whereas historically, we’ve been focusing on just the metabolic component, restoring insulin sensitivity and so on, but the research is clearly pointing this metabolic immune overlap and leptin is a critical hormone at the epicenter of this system. But I don’t just want to pick on too much fat – overweight individuals/obese individuals – because there are many skinny individuals running around or seemingly thin on the outside, fat in the inside, the so-called “TOFI,” or “MONWI,” which is metabolically obese normal-weight individuals). This is an MRI scan – metabolically obese individual on the left and lean metabolically normal individual on the right. As you see, this ectopic lipid deposition is found in the liver; it’s found in the pancreas; it’s found in various tissues throughout the body. And so, just because someone presents with a so-called lean phenotype, they may be metabolically obese. So, it’s very important to run body fat percentage and not just look at someone on the outside. Roughly one in five individuals is so-called “TOFI” or “thin on the outside, fat on the inside,” so keep that on your radar.

MI – we’ve talked about this many times. Body mass index is not really suggestive of all the metabolic deteriorations that link with obesity. So, we need to look at body fat percentage.

What are we talking about when we talk about fat? Well, this was a recent article that shows that really, we need to talk about the immune system when we talk about excess fat because as you will soon see, the fat tissue is as much an immune organ as it is a metabolic tissue. So, adipose tissue is not just involved in storing lipids; it plays a very critical immune role and releases immune signaling molecules, and leptin, as you will soon learn, is one of them, and it’s very problematic as individual’s body fat percentage increases above 20%. So, it’s much more than you think. In fact, if you grab or pinch your abdomen, it’s only about 50% fat on the cellular level. Now, on a volume basis, when you pinch fat, it’s about 95% lipid droplets, but if you want to partition that out on a cellular level and look at all the different cell types in there, it’s less than 50% fat. So, it’s very important that if you have visible fat and you can pinch, you’re pinching a lot of immune cells, and those immune cells get in there via leptin. Leptin is a powerful immune modulator; it downregulates a critical immune hormone signaling molecule cell type called the “T-regulatory cell.” The T-regulatory cell prevents immune cells from flooding tissues such as the thyroid, such as the joints in autoimmune joint disorders, and such as fat in the context of overweight and obesity. So, leptin is critical for allowing these immune cells to cause a really inflammatory environment inside fat, and that is really at the core of weight loss resistance. This is why people can’t burn fat – because their fat is inflamed.

Here is a breakdown of the fat tissue – what it looks like. Again, on the volume basis, it’s largely adipose, lipid droplets and so on. But on a cellular basis, it’s much more than just lipid droplets.

Now, here’s a picture of that. There are many non-fat cells in adipose tissue. Let me say that one more time because that is so important. There are many non-fat cells in adipose tissue. From a medical standpoint, I know it’s easier just to say “fat” and talk about fat, but we should really be referring to increased body mass and refer to that medically using terminology to adipose tissue because what adipose tissue describes is all the non-fat cells – the T-helper cells, the inflammatory Th1 type T-helper cells, Th17, different types of macrophages and mass cells, and pretty much any inflammatory immune cell that you can think of is found at high levels as individual’s body fat get above 20%. It doesn’t take a lifetime to get these immune cells to start flooding into the tissue. This has been shown in short-term overfeeding studies in just two months, just two months of eating excess calories and I know I talked about how the calorie myth – there’s a book on it (Jonathan Bailor, who lives in Seattle – he’s been really discussing calories) – but we know that eating a lot of bad food will make you fat, and that is linked with inflammation. So, the more fat tissue you have, the more inflamed you’re going to be at the fat-cell level, and so there’s a correlation between rising body fat percentage and rising inflammation, and leptin is at the core as you will soon learn.

This has been shown or demonstrated. This is the earliest study that I could find in obese 11-year-olds. This is happening to our children. This chronic inflammation in and around adipose tissue occurs early on, and why does it happen (as you’ll soon see)? Leptin and of course, the gut, is at the core of this. Many studies have shown chronic inflammation in and around the adipose tissue of children. This is just one of many studies.

What you’re going to see here is leptin correlates with all these different metabolic markers and with the inflammatory markers, as does insulin and triglycerides, but leptin is what we want to focus in on because this is a pleiotropic adipocytokines that’s really involved in allowing this inflammation to ensue. Now, what happens when individuals gain weight, as many of you know, particularly for people that workout – when a man or woman go to the gym and want to put on muscle; that’s called hypertrophy or expansion. Now, what’s unique about adipocytes or fat cells is they can undergo hypertrophy just like muscle tissue does, but they also undergo hyperplasia, which means that they form new fat cells from stem cells. So, that’s the challenge, and that’s why individuals tend to gain more and more weight, and that’s why individuals that are working out don’t tend to put on more and more muscle, because muscle can only hurt hypertrophy so much. Lifting weights does not cause muscle tissue hyperplasia; it just causes hypertrophy. But overfeeding and eating bad food – processed, standard, American diet food – causes both expansion and the formation of new fat cells. This is very interesting. It doesn’t take much increase in body weight to create new fat cells. For example, around a 4-pound gain in body fat leads to the creation of 2.6 billion new fat cells – 2.6 billion. Each one of those fat cells, keep in mind, releases leptin, visfatin, resistin, TNF-alpha, interleukin-6, interleukin-1, interferon gamma – all these pro-inflammatory cytokines. So, you can see now how as individuals who have gained 10 or 15 or 20 pounds over a decade of life are more inflamed, because each one of those new fat cells is releasing hormones. So, we’ll talk about one of the strategies to reduce the inflammation that’s linked with adiposity by suppressing the body’s ability to make new fat cells. There are some new strategies from researchers in Spain that have published research on this, and we can actually prevent this formation of new adipocytes through the use of hyaluronic acid. It’s really unique. So, we’ll talk about that.

As individuals gain weight, there’s a four to five fold increase in macrophages, which are very pro-inflammatory immune cells. There’s a downregulation in the protective T-regulatory cells and pretty much every immune cell type that you can think of is found in high levels in and around fat tissue. Now, this fat tissue that we’re speaking of is around the visceral omental area near the intestine, where the problem is coming from. But subcutaneous adipose tissue to a lesser level does have this immune shift, but this immune shift is more characteristic of the visceral adipose tissue.

It wouldn’t be a problem if fat tissue is just inert and individuals just kind of gained weight and didn’t look so good in bathing suit, but the challenge is, as we’ve just learned, is as individuals put on the pounds, there’s a huge shift in the type of immune cells that are found in and around there, and these adipocytes are releasing pleiotropic adipocytokines that cause major problems.

Here’s another confounding effect that I don’t always get into. I talked about it in my book, “Belly Fat Effect” a lot, but adipose tissue hypoxia – this is very critical to understand. Just know that oxygen as a nutrient just like glucose or lipids and so on. When oxygen becomes deprived on a cellular level, no matter the tissue (brain, heart, gut, pancreas, fat cells), there’s a dramatic shift in the cellular metabolism and also in the inflammatory load when oxygen becomes diminished. As you can imagine, the more fat you have particularly in your abdomen, the less oxygen will be there just based on volume and so forth. Now, studies have shown that body fat percentage above 20% is linked with increased hypoxia in and around adipose tissue. As I just mentioned, there are two problems with that – adipose tissue hypoxia or hypoxia in general is linked with inflammation, number one; and number two, hypoxia is linked with the dramatic shift in cellular metabolism (this shift is characteristic of cancer cells; it’s characteristic of autoimmune disease, and so forth). Hypoxia is a critical signaling event in both the metabolic and the immune system. When you’re hypoxic, you can’t burn fat, you burn sugar; you need oxygen to burn fat. When you go on a run, that’s where you breathe heavily because your cellular respiration and oxidative phosphorylation and all these mitochondrial pathways are turned on. So again, oxygen is critical for burning fat. Fat tissue is hypoxic that triggers the shift of pivot in the cellular metabolism to burn sugar instead of fat, which is problematic; it makes fat burning challenging, and it also creates inflammation – the same inflammation that we’ve been talking about. Remember, inflammation is linked with insulin resistance; insulin resistance means you’re not burning fat. So, this is another compounding effect. I have a whole chapter in my book dedicated on this event, but this is why regular daily exercise and movement and possibly hyperbaric oxygen therapy is so critical, and deep yoga, chronic breathing, and so on is very critical. I’m a huge fan of oxygen, and I think you should be, too.

Here’s a snapshot of adipose tissue hypoxia. There’s a key transcription factor called “hypoxia inducible factor 1 alpha (HIF-1α).” The name is a little complex, but this is like a cellular switch that is able to turn on all the pro-inflammatory signaling molecules that we’ve been discussing – CD40 helper, Th17 cells, different types of macrophages that are inflammatory and so on. So, just understand that when you become oxygen-deprived, whether it’s through sleep apnea, for example, in the night or excess adipose tissue, you’re triggering cellular inflammation. This is why exercise, yoga, and walking and movement is so, so critical. Now, short-term hypoxia, as in doing CrossFit or extraneous exercise, is beneficial, but it’s just chronic tissue hypoxia that triggers these salutary changes. I do want to highlight here FOXP3 and T-regulatory cells – this same cellular shift is linked with leptin as well. So, we see hypoxia and inflammation, and so on – the downregulation of the policemen, the upregulation of the bad guys – is induced by HIF1-alpha, but also leptin. So, these things go hand in hand. The more fat you have, the more leptin release; the more leptin release, the less abundant T-regulatory cells you have and more Th17 cells. Also, the more fat you have, the less oxygen is available, and so, you see that same shift. You can see why individuals gain, it becomes very, very challenging to lose it; there are so many things going against weight loss with all these different cellular changes and metabolism, and so on. We did a whole webinar on this autoimmune disease component; out of the five defining criteria of the autoimmune disease, obesity meets four of the five. So, we really need to change our clinical approach to how we help people – facilitate people’s weight loss – and focus on the immune system. Because leptin is a critical metabolic immune hormone, I think that’s a great clinical point to address.

Here are the defining criteria of an autoimmune disease, and again, obesity meets four of the five. The only criterion that obesity does not meet is circulating auto-antibodies that react against the adipocytes themselves. Otherwise, obesity would be studied by rheumatologists in the field of immunology, and so on. Anyway, very unique to think about.

Fat cells are not inert. We’ve discussed this. Fat cells actually recognize they have antigenic receptors on their cell surface. Before, we would categorize adipocyte as just storage tissues and organs, but these  MHC class-II receptors sends different antigens from the gut, from food sources, from damage tissues, and so on. So, adipocytes do respond to antigenic stimuli just like immune cells do, so they’re sensing and receiving immune stimulus in much the same way the immune system is. That’s why when we eat these processed diets, take antibiotics, and have leaky gut from alcohol and non-steroidal anti-inflammatories and proton-pump inhibitors, they’re linked with increased fat cell size and increase fat cell number because the immune system is responding – the immune system inside the adipocytes, I should say, is responding as well.

Now, why is this? In more primitive animals and such, the immune system in these animals is the fat tissue, and so these tissues have evolved through hundreds of years and so forth throughout humankind and the animal kingdom in particular. And so, this cross-talk between these storage depots that contain energy in the immune system, at one time was very beneficial. It just turns out that now, when we’re faced with all kinds of antibiotics and we’re not born via the vagina anymore (a lot of children are born through the C-section and exposed to toxic skin, bacteria, and so on), our immune systems are much more hypervigilant and that’s bringing these different challenges. But beforehand, it was considered beneficial because life is predicated on the ability to stand starvation and chronic infection, and so that ability to communicate between starvation and infection was critical. So, that’s where leptin comes in. Leptin has two personalities for this very reason – to be a metabolic hormone, which all defines leptin’s role as a metabolic hormone; and also immune hormone as well. We’ve already kind of mention this.

Suffice it to say, leptin correlates directly with body fat percentage. As individuals get more and more overweight, fat cells enlarge, they release even more leptin. Also, as individuals age, the fat cells tend to release more and more leptins. So, a couple of things we need to understand here. Women compared to men age matched, women will have, I think it’s like 20 to 30% general – this is generally speaking; not every single female is going to have high leptin. But comparatively, women tend to run higher leptin levels than men, and that may be why in addition to estrogen and other components, why there’s a higher prevalence of autoimmunity in women. The other thing is as individuals age, fat cells enlarge, fat cells release more leptin, and so forth. That’s what’s going on here at the adipocyte level in terms of leptin. It was discovered by Dr. Proenca back in 1994. He’s a researcher out of New York. He figured out in animals that animals somehow are able to respond to their diet and there is some sort of anti-obesity factor. That’s what leptin was really known as. It’s sort of like a fuel gauge on your car when the gas gauge is full, you’re not going to go eat or go to the gas station and fill it up, but when the gas gauges low on empty, you’re going to refill. That’s what leptin does. Throughout the day, leptin’s lowest levels run around 11 a.m. to 12 p.m. depending on the individual. Leptin is going to be at its lowest level, and that’s just like the gas gauge on your car being empty, suggesting or telling the body to go refill, to eat, that’s why we really should be eating breakfast and a big lunch and a very small supper supporting the day with calories. What happens is throughout the day then, after about 11 a.m. to 1 p.m., leptin starts to rise, and what you see then is leptin will be at its highest state around 2 to 3 in the morning (something along those lines). The reason it’s high while you’re sleeping is that you don’t wake up and eat. It’s designed to be an anti-obesity factor. So, it’s designed to tell the brain that there’s plenty of energy on board; you don’t need to go and raid the refrigerator and have cookies, cupcakes, and crackers; you can sleep soundly. That’s what leptin’s designed to do.

As many of you know, there’s a thing called “leptin resistance,” just like insulin resistance. Leptin becomes resistant at the cellular level much like insulin does, but the caveat, unlike insulin, pretty much every cell in the body becomes leptin-resistant except for the immune cells. That’s very, very critical because that means that high levels of leptin just amplify leptin’s message in the immune system. That’s why it’s so problematic. I think when individuals talk about leptin resistance, the appetite and satiety component is not a big deal. Yeah sure, it’s not a big deal. But I think the immune component is much more profound, and links excess fat tissue with many chronic inflammatory diseases, and makes weight loss challenging.

Here’s a picture of the leptin resistance and insulin. You have insulin and leptin and whatever. So, as individuals gain more body fat, they then release more leptin from their fat tissue. That’s going to be received at the hypothalamic level. The 1990s way to think about it is that what causes leptin resistance, but that’s not really the full story. What really causes leptin resistance is gut inflammation, endotoxin, which we’ll talk about so many times in this webinar, but I’m going to review it.

So, the T-regulatory cells, as we’ve mentioned, very protective. They’re the policemen of the immune system; they’re responsible for downregulating inflammation, for controlling autoimmunity, and so on. What leptin does is leptin perturbs the activity and number of these Treg cells and causes a pivot in the phenotype of the team lymphocyte that individuals have, pretty more Th1 cells, more Th17, Th23, very pro-inflammatory cells, which is very problematic. So, that’s the main way that leptin drives inflammation. How leptin is linked with autoimmunity, how leptin is linked with weight loss resistance, is this component right here – this T-regulatory cell component. This is why it’s so critical. Now, keep in mind – though I’ll mention it later – some things that can increase your regulatory cells are mindful based meditation, curcumin, resveratrol, vitamin D, vitamin A, saccharomyces boulardii, bifido bacterium probiotics, alpha lipoic acid; these are all things that increase T-regulatory cells, and some research shows that those nutrients also affect leptin signaling. But if leptin is really the bad guy, if we had a tool that can address leptin as that bad guy and prevent fat cells from being so numerous and enlarged, we can go higher order, and I’ll show you how we do that.

Here is an illustration; one in 23 different illustrations that I have in the book. Pretty much, these T-regulatory cells are the policemen, and here’s your fat tissue. What the policemen do is prevent unrestrained inflammation, prevent bad guys from being where they’re not supposed to be. So, imagine your adipose tissue’s kind of a vault. What happens is leptin comes in and wipes up T-regulatory cells and allows a bunch of pro-inflammatory mean cells to hangout and have a big party. Again, that’s problematic because inflammation is linked with insulin resistance; if you’re insulin-resistant, you’re not burning fat. So, that’s the critical take-home. That’s why leptin is so problematic in terms of weight loss.

Leptin correlates directly with fat tissue. So, this is around 20% body fat, maybe 23 to 25% in women. This is where leptin starts to rise, and it correlates directly with the amount of fat you have and the number of fat cells you have.

Here’s how you really become leptin-resistant. A lot of people talk about the hypothalamic leptin resistance – I think that’s the 1990s way of thinking about it. There’s this thing called “endotoxin” or “lipopolysaccharide;” we all have five grams of this material inside our intestines of this endotoxin from gram-negative bacteria, such as Yersinia, such as E. Coli, and so on. When we eat a Western diet – high fat, high sugar, high carb (you name it – just processed food) – this endotoxin crosses the gut through the two mechanisms, from paracellular and transcellular intestinal permeability, and latches on to the immune cells, latches on the fat tissues, and drives inflammation. As you will soon see on the next several slides, endotoxin is linked with leptin resistance, and in my opinion, based upon the number of studies that have linked endotoxin with obesity, I truly believe, based on the science, that endotoxin is the root cause of leptin resistance. And so again, we need to address the gut first, and of course work on the systemic stuff at the same time, but this is the real nasty guy. Let me show you the study that proves that. This is a group in Diabetes Care in 2010, about four years ago, but this group has able to show that eating high-fat meal, and this is the cream, and they compare high sugar versus high fat and then high sugar with polyphenols. What they found was that the high-fat meal out, the beverage thing of the high-sugar meal increases endotoxin absorption in the intestine, and that also is associated with inflammation. But increased expression of a protein called “SOCS-3,” and this, everyone, is the cellular signaling molecule that causes leptin resistance. It’s very, very important that you understand this because this is how leaky gut is connected with the big belly; this is how dysbiosis is connected with the big belly, in cravings for food, is this guy right here. SOCS-3 is very, very powerful; it not only downregulates leptin, but it also affects insulin. So, this is a problem. Now, if you want to learn more about endotoxin and lipopolysaccharide, the book, “Belly Fat Effect” is loaded; every chapter I’ve cited studies that talk about endotoxin and how you can increase endotoxin breakdown, prevent leaky gut, and certain foods that you can take. Endotoxin is the big deal, and I really think we should call obesity and obesity after endotoxin and obesity.

Here’s the thing that you need to understand here is that high-sugar and high-fat meals increase SOCS-3. And so here’s the cream, after three hours, you’re seeing this molecule increase. I’ll show you the picture later, but a dramatic increase in the expression of this protein. I know fat is really in right now. Everyone’s talking about butter, coconut oil, and NC2 oil, and that’s great. But I want you to understand the implications of this study. This is heavy cream, just like you might find or use in your coffee. High-fat diet on opposed with polyphenols is linked with inflammation. So, there’s a caveat to this high-fat diet thing that’s really going on right now in the paleo world and on the blogosphere, and so on. I’m not a fan of fat; believe me. I’m not saying, “Don’t eat butter,” but I am not saying that when you eat butter, make sure you’re also eating polyphenols alongside with it because those polyphenols will help you offset these chronic challenges, and so the proof is on the pudding, or this orange juice here, right here in the triangle, has the same amount of sugar as this glucose. But what does the orange juice also have? Well, it’s full-pulp orange juice, so it had polyphenols and a little bit of fiber, and as you see here, even though the sugar is the same, the macronutrient composition is the same, the micronutrient or polyphenolic component is totally different between orange juice and sugar, and that’s offsetting SOCS-3; that’s offsetting endotoxin-induced leptin resistance. So, hopefully that makes sense to you. Feel free to email me if you want to talk more about it.

Here is the SOCS-3 guy. It’s very problematic. It downregulates leptin and insulin at the cellular level, so these two are key to balancing, and how do you balance this? Well, you have to work on the gut – immunoglobulins, bovine serum-derived immunoglobulins, and bovine colostrum or something that Xymogen, we’ve recommended for a very, very long time for not only improving gut immunity, but also working on preventing this endotoxemia. And so, that’s why it’s in i5 and ProbioMax Plus, and all these beneficial products to help to restore the gut immune function to offset some of these bacterial antigens.

Now, we’re going to dive into some of the products. Again, if you have some questions, feel free to start typing them in. What we discussed up to now is my opinions only, not the opinions of Xymogen. They don’t endorse what I’m saying. I’m just basing this off research. Here’s a study of a product that has published research on it; it’s not really common in the nutraceutical industry to have a finished product that also has been clinically studied. Often times, there are ingredients or components of products that are studied and then that research is piggy-banked and so on, but this is a product that’s been clinically studied to lower serum and synovial fluid leptin levels. This is known as the “Leptin Manager.” This was a clinical study that has been recently published, and what is it? It’s hyaluronic acid and glycosaminoglycans. This product – ORALVISC – here is the ingredient right here. Significantly, for known research and especially for what we’re seeing clinically so far, has been shown with lower leptin levels. I’ll show you how it does this very shortly. But really a unique product – great and inexpensive – we have excellent feedback for this. So far, we’ve had it – it’s a very similar – it has the same ingredient as SynovX Metabolic. So, you have two good options here – SynovX Metabolic and Leptin Manager. Again, it’s proprietary, glycosaminoglycans and hyaluronic acid – a really unique product. I’ve been taking that personally for quite some time and noticed nice changes in exercise performance actually for myself and cravings in the evening. So, really unique product. And what the research has found is how this product tissue works is by downregulating some of the transcription factors that promote fat cell adipogenesis. And so, here are some of the studies that they’ve found. So, what this compound has been shown to do – here’s the ore of this compound; here’s the transcription factors actually make fat cells; PPAR gamma and there’s quite a few other ones. Anyway, this hyaluronic acid product; this is an animal’s, mind you, has been shown to downregulate the fat cells. As we mentioned earlier, a four-pound gain in fat mass is linked with the formation of 2.6 billion new fat cells. So, what’s happening is that as individuals gain weight, they’re making more and more mature adipocytes from stem cells. According to this Spanish research team, what this hyaluronic acid product is able to do is actually inhibit the adipogenesis away from making new adipocytes, and in turn favor the formation of chondrocytes. The chondrocytes are a huge component of cartilage, tendons, and ligaments, and synovial fluid. So indirectly, not only are we affecting offsetting some of the formation of new fat cells, but we’re also improving joint mobility and fluidity, and so forth. So, very unique way to manage dysfunctional metabolic signaling in overweight individuals, and has a nice research there to support it.

Again, we always have to talk about the gut. We can’t not talk about the gut because this is so important. We’re outnumbered by bacteria 10 to 1; our DNA’s outnumbered 350 times a 1, and so forth. Another area of control is polyphenolic compounds and prebiotic fiber, and also the type of proteins. I’ll mention here, just in case you don’t know, one reason why Xymogen has shifted away from soy protein and rice protein is there’s no satiety-inducing effect with those proteins, and if we’re trying to help people get off junk food and get them on a more friendly real-food-based diet, we want them to feel satiated. That’s why we’ve moved to pea protein-based products. Those pea proteins, if you look here on the left side (hopefully, you can see my mouse.) – pea protein has been shown to increase the levels of these satiety-inducing hormones released from the small intestine (GLP-1, CCK, GLP-2, PYY – there’s a bunch of them). Researchers at Duke have shown that pea protein, compared to other proteins, is wonderful for increasing the levels of these incretin hormones, which by the way, this is the huge area where the drug companies are going after now. There are quite a few drugs out there that work on this category. So, polyphenolic rich foods, pea protein, and inulin, also work on this level, so very nice to have that additional advantage to just your macronutrient drink.

Let’s talk about some specific fibers that have been shown to benefit the GI tract, and in turn affect this whole metabolic community wind up. Chitan Glucan – this is a very unique product. Inulin is as well. Inulin has been shown, in clinical studies, to increase bifidobacterium and faecalibacterium prausnitzii. These two genres and the genre species of probiotics are very metabolically protected. So, when looking at a probiotic (This is based on ample research; I go through this a lot in the book, “Belly Fat Effect.”), bifidobacterium is very, very beneficial. It’s by far the most beneficial healthy genre that you can name. I’ll just cite a recent study that was published in Japan. Diabetic patients had higher levels of lactobacillus in their GI tract compared to healthy controls. So, overweight individuals have been shown with higher levels of lactobacillus inside their GI tract, and this may be that lactobacilli, a faculty of anaerobe, can live in higher levels in the small intestine and ferment bad foods and so forth, so it may be linked with diet and so on, but the bottom line is bifidobacterium is consistent, study after study, is inversely correlated with endotoxin, is inversely correlated with gut inflammation and belly fat. So, inulin is one very beneficial way to increase the levels of bifidobacterium in your patients. Now, this is why if you look at all the different Xymogen shakes, inulin is found in pretty much every single one of them in therapeutic dose levels, between 4 and 9 grams. So, these are human clinical studies that I just mentioned here for looking at endotoxin, which is that bad guy that induces both insulin and leptin resistance; inulin has been able to offset endotoxin reduction and different biomarkers, and so forth. So, very protective, and it does this by increasing healthy levels of bifidobacterium in the GI tract.

This product right here is one of my favorite ones. OptiMetaboliX has 10 grams of inulin in there, and this is a really nice inulin from a European group – very clean, it has some data on it. So, this is one of the reasons that I do recommend this.

Here’s a new product – Chitan Glucan. It’s another similar fiber. It’s very complex like inulin, and it facilitates and fosters the growth of good bacteria, and prevents the growth of bad bacteria, “clostridia.” We know clostridia to be pro-inflammatory and bad and so forth. It’s been shown to reduce, in humans, the production of LDL particles and also reduce the oxidation effect of those LDL particles. So, this is a really unique product. It’s a new ingredient that we picked up here at Xymogen.

And, a new product. Some of you may be familiar with this one. Maybe we’re repeating this if you’ve heard it before, but this new formula, “Fit Food Vegan Complete,” under $16 price point, and it has these two different fibers in there, so you get both the inulin in therapeutic levels, and the Chitan Glucan, and you get 15 grams of the pea protein. Remember, Duke University has shown many studies that pea protein induces those satiety receptors in the gut that help the brain and help individuals not eat as much food and so forth, and this also has activated folate, activated B12, micronutrient complex – a really unique product, great price point. Practitioners and patients have been loving this so far. So, that is now available to you.

Lastly, I want to talk to you about gut antibody support, and IgG 2000 has recently changed slightly. It’s now a whey protein-derived immunoglobulin. It has a great formula. We’ve had actually a lot better feedback on this formula compared to the serum-derived material. The way that I look at it is this is designed to work on the gut; it mimics the composition of breast milk. We’ve had a really good feedback with this. I use this myself. And how do these immunoglobulins work? Sure, it surely gets immunity, of course, but if we think about this new model, this metabolic immune wind up with gut inflammation and translocation of gut antigens into systemic circulation, which trigger leptin and insulin resistance, a key way in addition to improving the composition of healthy bacteria here through probiotics and saccharomyces boulardii and prebiotics that I just mentioned, increasing the immunoglobulin support here will help to neutralize these different antigenic bacteria before they can cross and cause systemic challenges. So, I recommend this for anyone that is embarking weight management, metabolic restoration program because it’s core support. Many studies show that individuals that are insulin-resistant have gut permeability, individuals that have belly fat (guess what?), they have gut permeability. So, by improving the immune support at the gut level, we can help all these different systemic challenges.

Now, there’s one more different thing I do want to mention. Fish oil is critical. Many of you have probably used for a variety for a variety of different things, but enteric-coated fish oil, in particular, is really good for keeping the gut nice and sturdy. There are a couple of different studies that have shown this, and that is something about Xymogen that we’ve done different from the start, is enteric-coated fish oil. It’s better absorbed; there’s no burping; there’s no belching. And guess what? It has an additional benefit in being more protective for the GI tract. The reason why I love fish oil, in the context of leptin resistance or weight management and so on, is fish oil has some unique properties in that it increases adiponectin. If you think about leptin is kind of bad, adiponectin is very good; it increases insulin sensitivity; it helps to improve the activity of the T-regulatory cells; it does so many beneficial things. Many studies have shown that just fish oil use and enteric-coated fish oil use is linked with elevated levels of adiponectin. So, very protective.

Now, we do have a special offer on a lot of different things. If you like what you’re hearing, this is available now on Amazon on the Kindle or on the Nook. Some of you probably read this or have it. I would love your feedback if you have read it. Feel free to go on Amazon and type in any beneficial things or comments that may help other people, but if you do purchases in the future, I have created a membership site, BellyFatEffect.com, and a few go-to advanced course, and I have all the medical illustrations on the course. So, if you want more information, you want more detailed stuff to give the patients or help teach other people, maybe it’s your colleagues or whatever, that’s available to you. I spent close to 8 grand getting all these illustrations flashed out. There are over 20 of them on the site, so all you have to do is just email your receipt to [email protected]. Our staff will make sure that you get those illustrations if you want them. There are also comments and support on there, so if you do have questions, there’s a lot of people in the group now – over 150 – and you can interact with them and so forth on the group. Of course, I want to thank Xymogen, and first of all, thank you for attending this webinar. Xymogen has offered a really nice special here of the Fit Food Vegan Complete; there’s already a great price point on that, but you can save up to 25% off, and the Leptin Manager, which is a really unique product. Before you try it on your patients, try it on yourself. I think you’d be very pleased with that particularly if you’re one that exercises and do yoga, you’ll really notice that quite profoundly. And the new IgG 2000 material, we’ve had just amazing feedback on that material, and you’ll see that in pretty much in all the new products, ProBiomax Plus and i5. It’s really unique. Some really great savings. Here’s the code here; it’s SPWEB070914.

Lastly, for those of you that have already sent me the receipt for the leptin blueprint, which I know we did cover some of that here, I will update you on the website, so you have the membership there, too. Some of you have sent me receipts in before we’ve updated that, but if by chance, we missed you or you haven’t heard back or something like that, or there’s one or two people there, feel free to send another email – [email protected]. We’ll make sure to get you that access you have the membership site and so forth.

With that, I’m going to open up to questions here. Just give me a few seconds. So, there are some people… Let me see here. Hopefully, you guys can see me. I don’t know this webcam thing. First time.

Anyway, thanks again for joining the webinar. If you do have some live questions, I would like to unmute you here. So Yvonne, are you there?

Hello? Yvonne Duffy, did you have a question? I can’t hear you. Sorry.

Karen Koffler, did you have a question?

Karen Koffler: Yeah, do you mind going a little bit over when patient’s food would be restrained and it’s difficult losing weight. Does that have anything to do with the hypoxia that you were talking about?

Mike Mutzel: The food restriction component?

Karen Koffler: Yeah, when they aggressively calorie restrict and then find it is more even difficult to lose.

Mike Mutzel: Yeah, I do have an answer for that. Just give me a quick second here. I’m going to zoom out and go to… Give me a second. I’m going to this picture. I want to show you this picture because it will explain this a little bit better. I do cite the specific studies in the book, “Belly Fat Effect,” but I’ll explain it really quickly here. That’s a great question, by the way. So, your GI tract releases a bunch of hormones. We talked about how polyphenols and fibers and nutrients like pea protein increase the release of these hormones. But here’s the challenge when individuals embark on this low-calorie diets, and they restrict themselves and do yo-yo dieting, these hormones get suppressed. These hormones are very critical because up to 50% of insulin’s activity is contingent upon the release of these different hormones from the GI tract. So, that’s the big challenge with yo-yo dieting. There are many challenges with that in terms of weight loss resistance and so forth, but a low-calorie dieting leads to suppression of these hormones for up to one year. There are two studies that have shown this; I talked about this in the book quite a bit. That’s why I don’t recommend doing these calorie-restriction diets because they really lead to challenges long term.

Karen Koffler: Great. Thank you. I’ve got another quick question.

Mike Mutzel: Yeah, go ahead.

Karen Koffler: If we’ve got patients who we are treating for yeast overgrowth, when we’re figuring that it’s playing a role on their metabolic picture. Can we use saccharomyces for restricting their yeast exposure for taking out sugars and so forth? Is the saccharomyces in that setting?

Mike Mutzel: Yeah, really a good probiotic – probiotic yeast in that case. But it does outcompete candida and even pathogenic bacteria. I’m working on a blog on saccharomyces boulardii. A recent study has shown it to be very metabolically protected, too, and neutralizes endotoxin that we’re speaking about. That answers your question very specifically. Absolutely, it can be used alongside yeast overgrowth conditions – candida and so on.

Karen Koffler: Great. Thank you.

Mike Mutzel: Yeah, thank you for your participation.

Let me see here. Dr. Fine, how are you doing?

Jeffrey, you there? Hello?

Renee Stout, did you have a question? Renee? Guess not.

Let’s see here. If you do have a question and you want me to answer it, feel free. If not, I’ll just go down the list here.

“Is there anything that I can do to supplement those with the gallbladder?” Yeah, a great question. Xymogen does make the formula called “LipotropiX.” It has a lot of choline, taurine and different things that are very beneficial for improving the formation of bios and so forth. That would be something that I would highly recommend. Bios are so critical. I’m really glad you asked that question there, Patty, because bios antimicrobial – there are studies linking reduce bios signaling with dysbiosis and inflammation in the gut, so it’s very critical to improve bio flow and function. I will mention that improving upstream digestive processes, such as hypochloric acid and making sure that individuals are eating mindfully and chewing their food, will increase the production and release of bio. I talked about digestion is so critical and it’s iterative – one thing builds upon the other. And so with that, individuals are not digesting the food properly, chewing poorly, then they will have a poor bio release. So, that’s going to be a challenge for individuals that do have a gallbladder.

“Should the Fit Food Vegan be taken prior to or after individual training workout?” Renee, I’m so glad you asked that question. It would be better to  take before. Now, here is why. It’s very low glycemic. The product does have fiber, does have 15 grams of protein, but it’s designed to be a low-glycemic meal and after exercise, we actually want to spike insulin. Insulin is one of the most anabolic hormones in the body and as such, after workout, you want anabolism, you want to build stuff, you want to put glycogen and glucose into tissues, you want to put amino acids in the tissues, and that’s why causing mild spike in insulin via high-glycemic meal is beneficial. Many fitness competitors, bodybuilders, athletes I like spike insulin after exercise because of that very reason. I highly recommend something a little bit more high-glycemic. I recommend Fit Food Whey with a berry shake. What I do is I take half a zucchini just because the alkalinizing effect of the zucchini, and I take berries and the Fit Food Whey. I like the banana even though it’s going to be unavailable soon because no one else likes it apparently. I put that – half a cup of berries – in my VitaMix. Great post workout – because you’re going to create an insulin spike that’s going to help recolonize, if you will, the glycogen that you broke down during your workout. Spike insulin – you’re going to shuttle amino acids into your tissues and cells. So, very, very protective in terms of rebuilding, recovering from your workout, and helping to increase lean muscle mass, and lean muscle mass is so critical for this whole thing. So, great question. Awesome. Dr. Fine, thanks so much, and if you still have a question, I’ll unmute you again maybe when you’re around.

Jeff, are you there? Guess not.

Exercise is very critical. Weight lifting is very critical. We’ve seen excellent feedback with the leptin manager up to now, so I recommend using it alongside. Nothing is going to replace exercise or calorie balance and all that, no pill or supplement. Supplements are just that – they’re supplementing; they’re helping to get these results faster. But still, the exercise and the diet changes are critical.

“What’s your opinion on intermittent fasting?” Oh, man. Michael Carns, I’m so glad you asked that question. I talked about intermittent fasting a lot in Belly Fat Effect. I think it’s very, very protective, but the time that you intermittent fast is very critical. There’s a lot of buzz right now on the internet and individuals are saying to skip breakfast, which is totally not want you want to do. If you’re going to intermittent fast, you want to skip dinner. Eat a very, very light dinner, and fast for 12 to 14 hours.  This is something that Mark Houston’s been talking about forever. He’s been an early mentor to me. He lifts weight. For some of you that have seen him speak, he’s very physically fit and very lean. This is based on research in Europe in cancer individuals. So, if you’re going to do calorie or intermittent fasting, I think it’s very beneficial, but don’t skip breakfast. That’s the worst thing you can do that you’re going to be catabolic; you’re going to lose your lean muscle mass; you’re going to eat more throughout the day, crave more; you’re going to be insulin-resistant throughout the day and so on. So, if you’re going to do this intermittent fasting protocol, skip dinner; that’s the biggest thing that I can say. My wife and I have been experimenting with this, either eating a very light dinner at around 5:30, which is I’m a little beyond that right now, but eat light dinner or no dinner at all. And getting up around 5:30 or 6, doing a little bit of exercise and then eating a huge breakfast and a big lunch. You’re going to get the best results doing it that way. We’ve talked about this in another webinar. Shoot me an email if you want it on circadian clocks, but your biology is such that in the morning and middle part of the day, your gut is on fire. That’s when your GI tract is really active. The thermostat for GI function is turned on really high, and that’s when you’re going to absorb through the best; that’s when you’re going to break down through most efficiently; and that’s when you’re most insulin sensitive. We want to eat when we’re insulin-sensitive so that the things that we absorb and flood around into our bloodstream get put into tissues, as opposed to get stored in the pancreas or the liver or muscle tissue, what have you. So, you become more insulin-resistant as the day goes on. So, you don’t want to do this intermittent fasting thing and skip breakfast. That’s going to lead to diminishing returns. So, thanks Michael for that great question.

Jim asked a question on krill oil versus fish oil. Krill oil is really great. It’s phospholipid-bound. It’s delivered a little bit differently.  There are some different changes in the lipid parameters and HDL particles and so forth. We’ve had really good feedback on LipiChol – really nice feedback there with the krill-based delivery system. I’m personally a fan of the cholesterol-based fish oil. I mean, enteric-coated delivery system because the research shows that’s what’s the best, but the krill oil components are really nice because you have that lipid astaxanthin component to it, which is a lipid-soluble antioxidant and it’s great for cell membrane damage and so forth. So, from that perspective, I think there is some added benefit with the oxidative stress component, so if there are individuals that have cell membrane damage, heavy metal exposure, what have you, they may benefit more from having the polyphenolic astaxanthin really wrapped in the phospholipid of the krill. There’s kind of some different applications there. Okay, so great question.

Brenda Spencer on the IgG 2000 material: “Is that going to be safe for individuals that are dairy-sensitive? Is sensitivity not an over allergy?” We’ve had actually great feedback with that, Brenda. It hasn’t been an issue. Cheryl Burdette, she’s on our board. She runs the laboratory, “Dunwoody Labs.” What they found out is actually individuals that had a dairy sensitivity – those sensitivities actually improved through the use of this material. These were IgG antibody levels towards casein and metroglobulin and beta-2-metroglobulin and so on. We’ve actually seen the opposite that this helps to restore GI function and helps you improve immune tolerance. So, that could be something to consider there.

“At the end of the webinar, would you please repeat the process you have mentioned?” So, we talked about Fit Food Vegan Complete. It has that new Chitan Glucan fiber that has a really beneficial research on it, good clinical feedback, and it also has inulin. Inulin increases bifido bacterium. It’s a pea protein-based; pea protein increases satiety in the gut. So, all these different components, and it’s very cost-effective. We talked about OptiMetaboliX, which is a little bit more of a Cadillac, if you will, type of product, much higher fiber content, much higher protein content, and some different bells and whistles in terms of blood sugar support.

We talked about Leptin Manager; that’s the hyaluronic acid-based product that’s very effective for modulating adipogenesis and helping to modulate leptin signaling, so that’s a really unique product. We’ve got great feedback with that so far. So, I’d like to recommend that for anyone that is embarking on a weight management program.

We talked about the benefits of enteric-coated fish, OmegaPure 900. This is an IFOS-certified; one of the cleanest fish oils that you can find out there. It’s enteric-coated. Price point’s great. It delivers 900 mg of EPA/DHA per capsule. So, phenomenal product; hard to beat on price and quality and cleanliness. It’s just hands down – one of our top formulas.

And then we talked about gut immune support and the whey protein-derived immunoglobulins, excellent gut immune support with ancillary components to it, lactoferrin, transferrin, and all these proteins that were not present in the former material. So, those are things that I recommend across the board when we’re talking about this immune metabolic lined up, and so on.

“What’s the best timing on the Leptin Manager?” Dr. Morris, great question. The study, by the way – they didn’t tell people to take it at any particular time. But I would recommend taking it at night. The reason is we don’t want people eat a lot of food at night, so if we can help to improve leptin sensitivity in the hypothalamus, hopefully, people won’t eat as much for dinner and they won’t have this food fermenting in their stomach while they’re sleeping and creating the formation of the bad guy bacteria. So, that’s just my two cents. I personally take two a day – one in the morning; one at night. Not that I have leptin issues, but the research is so phenomenal here and how it’s working on the immune system level is really great. So, I love the product. That’s when I take it. What I would just recommend – tell your patients just to take it. I’ll tell you, remember, wherever they’re more compliant. If they’re more compliant in the morning, take it in the morning; if they’re more compliant at night, take it at night. I don’t know that makes that big of difference, but ideally, maybe in the afternoon or evening. But great question.

“I miss the beginning of the webinar. Thanks for sending up the link.” Stephanie, thanks for your comments, and we’ll make the webinar available to you with the replay.

“A couple of more questions… How can you test leptin to ensure you are leptin-resistant?” That’s a really good question. I’m glad you asked that, Robin. The thing about leptin is it oscillates dietarily. We talked about how it’s really a bit lowest around between 10:30 a.m. and 1 p.m., about early to mid-day. And it’s going to progress – it should progressively increase to a peak around 2 to 3 a.m. So, just be consistent with yourself and with your patients when you’re testing that because if you tested someone at 8 a.m. and then the next time they came in for repeat, it was 3 p.m., you’re comparing apples to oranges. Be very consistent when you test your labs. If the only time you can do it is in the afternoon, fine, but make sure when you retest it, it’s in the afternoon. But I think for leptin, even though it may be very convincing for some people to know their leptin levels and may help them to get on this dietary change, I don’t think it’s that important to test as long as you know your body fat percentage. Remember, leptin is only really released in high quantities from one cell, and that’s fat tissue. The more fat tissue you have, the more leptin you’re going to be releasing. So, if individuals have a body fat percentage of about 20 to 23%, we know based on research that their leptin levels are going to be high. Now, just as I mentioned earlier, the skinny fat people, the TOFIs (the thin on the outside, fat on the inside people), which is about 15 to 20% of the population, they, too, may have high levels of leptin, but I think by measuring body fat, you’re going to get a nice kind of baseline there. So, hopefully that helps. Feel free to email me.

“Patients who have diabetes with hemoglobin A1c about 8.5 can’t miss dinner or go intermittent fasting.” Rita, good point. I’m not a clinician. In a sense, I’m not training diabetics, so you know more than that about me. I would say for dinner for diabetic individuals that they can’t miss dinner, so they’re going to bounce around blood sugar and hypoglycemic crash and say make sure it’s vegetables and lean protein. Try and minimize the amount of carbohydrates that people are having at dinner. That said, a practitioner in Eastern Washington sent me some papers showing that eating carbohydrates in the evening actually reduce leptin levels, and I haven’t fully analyzed this paper so I can’t say, “Go and start eating all these carbs in the evening,” but there is apparently conflicting research emerging. This one, I would say, just stick to what has worked. Ayurveda can change this medicine for a long time. Eat larger, eat like a king, then a prince, and then a helper later in the day. So, supper is really to support what you’ve already eaten, not to be the main meal.

“Take Leptin Manager away from food.” Great question. You can take it with food. Studies conducted in humans that it’s great with meals. So, no problem.

“How do you test body fat percentage?” Bioimpedance testing. We work with a lab – you can touch your wrap and so forth. We have some units. There’s a bunch of different units that we can help you with. But it’s a great in-office test that’s been validated and so forth. It looks at intracellular water and body fat percentage and all that. So, great question, Dr. Morris.

I think that is going to be it. I want to thank you for… Let me just see if I have any more questions. So, that’s it. Thanks so much, everyone, for joining us tonight. I’ll make this available to you tomorrow, so if you want to relisten to it, you’re welcome to. We have that up to 25% off discount for 24 hours, so you can take advantage of that. If you have any questions, feel free to email me. Hope you have a great evening. Thanks so much.