Welcome, Empower Nutrition listeners, in our recent episode, we dive deep into one of our favorite topics here at our clinic —the connection between gut health and metabolism, with a special focus on Metabolic Endotoxemia (ME). Listen as we share some exciting insights and practical strategies to help you enhance your overall well-being.
- Frustration with weight loss extremes.
- Passion for natural weight regulation through healed metabolism.
🌐 Understanding Metabolic Endotoxemia (ME):
- ME linked to microbiome insult affecting gut health.
- Factors: antibiotics, c-section, low-fiber diet.
- Vicious cycle: Microbiome issues lead to low fiber, worsening diversity.
- Leaky gut allows lipopolysaccharides (LPS) to trigger systemic inflammation.
- Altered hunger signaling contributes to obesity.
🚨 Impact of Endotoxemia:
- Metabolic syndrome features tied to ME: inflammation, insulin resistance, central fat storage.
📖 Scientific Quotes on Endotoxemia:
- Gut dysbiosis induces oxidative stress and ME.
- Oxidative stress key in type 2 diabetes complications.
- Gut dysbiosis linked to chronic inflammation in coronary artery disease.
🔬 Studies and Interventions:
- Diet High in Fiber, Polyphenols, and Functional Foods:
- Improved metabolic markers in type 2 diabetes.
- Lowered blood sugar, cholesterol, triglycerides, inflammation.
- Flaxseed Intervention:
- Lowered intestinal permeability and LPS in perimenopausal, overweight females.
- Pomegranate Extract:
- Reduced inflammation, improved gut bacteria, and lowered endotoxemia.
- Resistant Dextrin (Prebiotic):
- Lowered endotoxemia, improved sleep, quality of life, and inflammation in type 2 diabetes females.
- Probiotic (Lactobacillus Rosis GG):
- Improved inflammation, lowered endotoxemia, and enhanced metabolic outcomes in coronary artery disease.
- Symbiotic Intervention:
- Significant improvement in endotoxemia, inflammation, and metabolic markers in subjects with obesity.
🛠️ Practical Applications and Recommendations:
- Testing for endotoxemia using LPS antibodies.
- Dietary focus on high polyphenol, unrefined carbs, and nutrient-dense foods.
- Power foods: flax seeds, chia seeds, true fermented yogurt, and pomegranate extract.
- Individualized approach for gut dysbiosis, starting with digestive support.
- Emphasis on the gut-metabolism connection.
- Solutions involve optimizing gut health through diet, supplements, and personalized approaches.
References used in this episode:
1.Medina-Vera I, Sanchez-Tapia M, Noriega-Lopez L, et al. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019;45(2):122-131.
2.Krumbeck JA, Rasmussen HE, Hutkins RW, et al. Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics. Microbiome. 2018;6(1):121.
3.Saleh-Ghadimi S, Dehghan P, Sarmadi B, Maleki P. Improvement of sleep by resistant dextrin prebiotic in type 2 diabetic women coincides with attenuation of metabolic endotoxemia: involvement of gut-brain axis. J Sci Food Agric. 2022;102(12):5229-5237.
4.Fallah F, Mahdavi R. L-Carnitine and synbiotic co-supplementation: beneficial effects on metabolic-endotoxemia, meta-inflammation, and oxidative-stress biomarkers in obese patients: a double blind, randomized, controlled clinical trial. Food Funct. 2023;14(4):2172-2187.
5.Moludi J, Kafil HS, Qaisar SA, Gholizadeh P, Alizadeh M, Vayghyan HJ. Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blindplacebo controlled randomized clinical trial. Nutr J. 2021;20(1):47.
6.Farhangi MA, Dehghan P, Namazi N. Prebiotic supplementation modulates advanced glycation end-products (AGEs), soluble receptor for AGEs (sRAGE), and cardiometabolic risk factors through improving metabolic endotoxemia: a randomized-controlled clinical trial. Eur J Nutr. 2020;59(7):3009-3021.
Gonzalez-Sarrias A, Nunez-Sanchez MA, Avila-Galvez MA, et al. Consumption of pomegranate decreases plasma lipopolysaccharide-binding protein levels, a marker of metabolic endotoxemia, in patients with newly diagnosed colorectal cancer: a randomized controlled clinical trial. Food Funct. 2018;9(5):2617-2622.
8. Gonzalez-Sarrias A, Romo-Vaquero M, Garcia-Villalba R, Cortes-Martin A, Selma MV, Espin JC. The Endotoxemia Marker Lipopolysaccharide-Binding Protein is Reduced in Overweight-Obese Subjects Consuming Pomegranate Extract by Modulating the Gut Microbiota: A Randomized Clinical Trial. Mol Nutr Food Res. 2018;62(11):e1800160.
9. Millischer V, Heinzl M, Faka A, et al. Intravenous administration of LPS activates the kynurenine pathway in healthy male human subjects: a prospective placebo-controlled cross-over trial. J Neuroinflammation. 2021;18(1):158.
10. Iqbal A, Prince LR, Novodvorsky P, et al. Effect of Hypoglycemia on Inflammatory Responses and the Response to Low-Dose Endotoxemia in Humans. J Clin Endocrinol Metab. 2019;104(4):1187-1199.
11. Pei R, DiMarco DM, Putt KK, et al. Premeal Low-Fat Yogurt Consumption Reduces Postprandial Inflammation and Markers of Endotoxin Exposure in Healthy Premenopausal Women in a Randomized Controlled Trial. J Nutr. 2018;148(6):910-916.
12. Madison AA, Belury MA, Andridge R, et al. Afternoon distraction: a high-saturated-fat meal and endotoxemia impact postmeal attention in a randomized crossover trial. Am J Clin Nutr. 2020;111(6):1150-1158.
13. Sant’Ana CT, Amorim AD, Gava AP, et al. Brown and golden flaxseed reduce intestinal permeability and endotoxemia, and improve the lipid profile in perimenopausal overweight women. Int J Food Sci Nutr. 2022;73(6):829-840.
14. Frank J, Gupta A, Osadchiy V, Mayer EA. Brain-Gut-Microbiome Interactions and Intermittent Fasting in Obesity. Nutrients. 2021;13(2).15. Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012;3(4):279-288.
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Well hey there and welcome back to the Empower Nutrition podcast. Erin Skinner here, your host, and I’m excited about this episode. It’s all about unlocking the gut metabolism connection and specifically what we’re gonna be talking about is something called metabolic endotoxemia or me, and I’ll definitely be explaining what that is if you don’t already know.
But the reason why I’m so passionate about this topic is that often we have clients come to our practice who are extremely frustrated with this sort of dichotomy that exists where it’s either you aggressively pursue weight loss and it feels extremely difficult and restrictive and you have to go to extreme measures to achieve it.
Or you just give up on the idea of caring about your weight and your health outcomes related to obesity at all. And that doesn’t feel like it aligns with people’s long-term health goals either. And so people get really frustrated and, and on their behalf, I feel like both are problematic.
And so I, I’ve become very passionate about this topic because really in, in the end what we’re gonna talk about is that for the vast majority of people in the western world, weight and metabolic challenges are related to an underlying dis health and metabolic endotoxemia is a primary driver of that.
So if you can heal your metabolism, then you can, you don’t have to pick between those two bad things I just said. You can just have natural weight regulation the way people maybe did a couple generations ago and before that where you naturally have the right amount of hunger, the right amount of cravings, you don’t have a lot of impulsivity around food. You don’t feel like you have a hard time controlling your portion sizes or your eating, you just kind of naturally eat, want healthy food and it like healthy amounts.
And so like getting, understanding that healing your actual physiological metabolic health allows that to happen I think is just so important because otherwise you kind of get stuck in that place where it’s like you have an unhealthy metabolism.
So you’re pushed into extreme dieting or again, like I already said, you just, which fair, you don’t want to extreme diet so you don’t. But then you have these health ramifications from your weight challenges. So really love to help people with that and that’s what we’re gonna talk about today. So metabolic endotoxemia, if you haven’t heard about this, is basically related to your microbiome.
And so typically the way this plays out is that there’s some, there’s some insult to the microbiome and often this can start from even like preconception and from birth. So things like getting exposed to antibiotics, these kids c-section delivery, lack of breastfeeding, low fiber diet as a child, those things kind of all can set, set the tone for problems with a microbiome down the line or it can be exposure to antibiotics across adulthood that does it. It can just be a lack of knowledge around diet quality and not getting enough fiber, fiber diversity.
But in any case, what happens is that there’s low microbiome diversity and low fiber intake and often the two can cause each other. The way that micro problems with microbiome diversity to cause a low fiber diet is that it’s basically it precipitates these IBS like symptoms when there is a high fiber meal consumed. So, oh, I don’t tolerate all these foods that have like garlic, onion, vegetables, fruits, whole grains, beans.
So I’m just going to eat the foods that I do tolerate. And the vicious cycle kind of sets off from there. So then what happens is there’s this problem where because of this over time degrading of the microbiome, you end up with problems with the mucus layer basically, which is this. It’s like a gelatinous layer that lines your gut and that’s where all the bacteria of your microbiome live when you, you need healthy gut bacteria in order to stimulate the gut lining to release that mucus layer to create it.
So in a way, the bacteria kind of stimulate their own house to get made. And so if you don’t have the healthy bacteria, you don’t have the house for them to live in now without the microbiome and without that mucus layer, you don’t have what’s needed in order to keep the gut lining healthy. And then you have what most of you have heard of which is called leaky gut, but in the scientific literature it’s called intestinal permeability or hyperpermeability.
But in either case you have too much compounds, too much protein from the lumen or from inside the gut, it’s crossing through the gut lining and triggering the immune system in the blood in the bloodstream. And then specifically you have in this scenario of endotoxemia a huge amount of what are called lipopolysaccharides or LPS for short. These are gram-negative or unhealthy gut bacteria pieces.
They also cross through this leaky gut specifically it stimulates receptors in the immune cells in the, of the immune system in the what are called the epithelial cells or the cells that line the gut. And you have this inappropriate activation of the immune system that kicks off these pro-inflammatory mediators.
And here’s the kicker, you guys, these pro inflammatory mediators are pro like inflammation causing immune system like messenger. They go systemic. So they go in the bloodstream that goes all around your whole body impacting multiple organs, including your brain, including other parts of your nervous system such as your vagus nerve that all play a major role in your appetite signaling and your hunger cues. So this is where we start to get to what we’re talking
About with endotoxemia and what it causes. But specifically what we’ve seen from the literature is that there’s a change secretion of satiety hormone. So typically with a healthy metabolism, you eat food and your body releases these hormones that kind of have this negative feedback cycle that tell you to stop eating and it just decouples that. So it’s like I eat a bunch of food, I’m still hungry. Then there’s also reduced actual expression.
So not only do you not sense the hormones as well, but you’ll express less especially of a hormone called leptin. So leptin is one of those important satiety hormones you can just make less of it so you get less full from food basically. And then finally on this vagus nerve, which is the nerve that connects the gut and the brain, you have reduced expression of these receptors for these hunger ho hormones.
So even the hormones that you do release, you don’t sense them as well. And so you don’t get that fed state feeling, meaning you just want seconds or you want larger portions or you want to eat sooner after you eat. So in the end with endotoxemia, because of just to kind of back up problems with the gut health, cause problems with the gut lining allows these LPS or pieces of bacteria to come into the bloodstream and ma and trigger the immune system.
The immune system causes a body-wide inflammation and that inflammation then messes up your hunger and appetite is a primary driver. It’s now believed of the obesity epidemic also causes all the features of metabolic syndrome. So inflammation is a part of metabolic syndrome that drives the insulin resistance. It’s a feature of it. So endotoxemia can is a big driver of even not just pre-diabetes, but even in type two diabetes there’s a high prevalence of endotoxemia, central fat storage, hypertension, dyslipidemia, or high blood cholesterol.
So those are all the features of metabolic syndrome and they’re all associated with this me that we’re talking about. So you might be kind of thinking this sounds like this weird thing that it must be very rare, but actually that is quite the opposite of that. There have been studies where they just get a big group of random people and they study the people who have normal weight versus overweight and they’re, they find a significant higher amount of endotoxemia and the overweight group and the normal weight now that that doesn’t show is cause and effect.
But later in this episode we’re gonna talk about some studies where they do an intervention, they see that that intervention changes the endotoxemia that occurs. And so we do know like the way that the process goes. But the point of what I’m trying to say really is that this is not some weird thing that only applies to a few people.
This literally is something that is generally is is a a main driver of the type two diabetes and the obesity epidemics. And so if you struggle with your weight, your appetite, your insulin sensitivity, if you have metabolic syndrome, chances are you have endotoxemia. Okay, so a few quotes from published peer reviewed studies, this one is from a paper by Fala et al in 2023. They say quote, gut microbiota dysbiosis can induce oxidative stress. So that’s inflammation and metabolic endotoxemia as major drivers of obesity.
So hopefully this sounds kind of freeing if you struggle with your weight because what they’re saying is all these, all the times that people who struggle with their weight have been told they need to eat less food, they need to count their calories, they need to count their points, whatever kind of think their way out of being overweight. This quote is saying, that’s not the problem.
The problem is gut health and until the gut health is addressed, you’re gonna have this, your body promoting obesity. And so you can only fight that for so long. And that’s why energy restriction alone and like old fashioned dieting never works in the long run and actually causes new health problems. The next one is from a 2020 paper and it says oxidative stress plays a key role in the initiation, propagation and development of the complications of type two diabetes.
Now this sounds boring, but it’s actually kind of crazy what they’re saying. And this is this again, the published science that’s current, the kind of old school thinking that is puts shame, I think unfairly on people is that oh, you have some kind of character flaw, you overeat, then you get overweight, then you have type two diabetes, then you have this inflammation that can kill you because it causes heart disease and diabetes, complications and cancer.
What this quote is saying is it’s the opposite of that.
You have inflammation coming from your gut that causes the type two diabetes that causes the weight gain. And so it’s not your fault that this is happening and and the answer to this is not just dieting and cutting back on the amount of food you eat. All right, one more quote from two a paper published in 2020. One says alteration alterations in the gut microbiome or dysbiosis has been associated with increased microbial translocation.
That’s the bacteria coming through the gut lining leading to chronic inflammation in coronary artery disease. So this is published in a cardiology journal and it’s again along the same themes of, okay, you didn’t have inflammation because you got overweight, because you overate, you had inflammation and heart disease because of your gut health and that’s what’s caused the whole thing.
And so the answer to the problem is gut health, not restrictive dieting. Okay? So again, just to reframe or like restate what this is with endotoxemia, you have the low fiber diet and the imbalances in the gut microbiome decreasing the amount of the mucosal lining that exists or that protective barrier. You can think of it as like the shield along the lining of the gut disappears, the gut lining becomes damaged.
Now, unhealthy gut bacteria pieces LPS can cross through the gut lining. They make the immune system triggered, they make it mad and it kicks off inflammation that goes throughout your whole body that changes your metabolic health, your appetite, your insulin sensitivity, and your hunger and cravings. So I’ll just kind of quickly go over a few studies where they look specifically at endotoxemia so that you can kind of get an idea of what even like helps with this. Good news is there’s a lot of common everyday things that help with this so it’s not too fancy.
And then at the end, I’ll kind of tie it all together for you, but one study, this is published in 2018 and we will put the references in the show notes, but it’s Medina vera etal. This was a randomized control trial of 81 subjects with type two diabetes. And they found that sure enough, when we look at the amount of endotoxemia between these two groups, we got, they had healthy controls and the diabetics, the diabetics had significantly more endotoxemia than the healthy controls.
And so then what they did is for three months they gave them this special diet that was high in fiber polyphenols, which are like the important plant chemicals that give plants like color for example, and vegetable protein like, and then some functional foods like noal cactus, chia seeds, soy protein, and a prebiotic called inulin. And then basically they compared it after the three months and they found that there was a significant lowering in the group that got the special diet I described.
They had lower blood sugar, they had lower total cholesterol, LDL cholesterol, triglycerides, free fatty acids, hemoglobin A1C CRP, which is C-reactive protein or inflamma inflammation. Basically all lowered in the group that got the special diet and the diabetics compared to the diabetics that didn’t get the special diet. And yes, there was a lowering of LPS, which is the endotoxemia.
So over and over we see this in studies where if you lower LPS you, you eat a diet that help supports gut health, you’ll see lower LPS, lower LPS or endotoxemia is always gonna correlate with these actual metabolic markers that we know and are used to like blood sugar, A1C cholesterol, another study, this is Santana. And all from 2022 in this study they looked at, it was another RCT or randomized controlled trial that looked at 30 female subjects who were perimenopausal and overweight and they basically gave them 40 grams a day of flaxseed versus none for 12 weeks.
So again, a three month study. And basically they found that in the group that had the flaxseeds, there was a significant lowering of their amount of intestinal permeability tested by using a lactulose or manitol test. So less leaky gut, that’s a critical piece of the endotoxemia. So seeing that lower is huge. And then sure enough, they also had a lowering of their LPS in the groups that had the flax seed.
And then in another study, this was by Gonzales ET all from 2018, they looked at pomegranate extract, which is a polyphenol that we know feeds a keystone gut bacteria called akkermansia. And AKKERMANSIA really is important for encouraging the gut lining to secrete that, that mucus layer, that protective, that protective layer that disappears in endotoxemia. So in this trial what they did is they gave 49 subjects who were overweight or obese with some high cholesterol.
They gave them either pomegranate extract or placebo, so control for three weeks. And they found that in the group that got the pomegranate extract, there was a lowering of high sensitivity CRP and a lowering of the gut bacteria, or excuse me, an improvement of the gut bacteria species. They’re important for gut, your gut lining. They also found that there was a lowering of pro-inflammatory gut bacteria and they found a lowering of endotoxemia as well. So just giving this polyphenol that come that nourishes an important gut bacteria, improved endotoxemia and actually improved inflammation.
So CRP, so that we over and over again see this cause an effect studies where you lower endotoxemia, you see the actual metabolic markers improve in another study. This is by sole ga, how do you say this, GA gmi, I think in 2022, this was a randomized controlled trial of 76 female subjects with type two diabetes.
They were given either one gram of day of a prebiotic called resistant dextrin. So that’s something that targets healthy gut bacteria to feed it kinda like a gut bacteria fertilizer for healthy bacteria, they took that for eight weeks or a placebo. And then the group that actually took the resistant Dion or the prebiotic had a significant lowering of their endotoxemia or the LPS. And guess what, they also had improved sleep, improved quality of life, improved inflammation, improved hemoglobin A1C, so blood sugar across that eight weeks.
So it’s starting to sound like a broken record, I know, but over and over there studies this. So I’ll tell you a couple more and another study by Forgan at all. In 2020, they again gave resistant dextrin or that same prebiotic, either that or placebo to subjects with type two diabetes. And similarly, the prebiotic group that got the resistant dextrin had improvement of their blood sugar triglycerides, the ratio of total to HDL cholesterol, their LDL to HDL cholesterol ratio and their high sensitivity CRP that was statistically significant for all.
This is after only eight weeks only taking a prebiotic. So it’s crazy how simple the intervention is. And for how short to have an improvement of all these things, there was a 23% reduction of LPS or endotoxemia. And so, and then also significant changes in their energy intake and their fat intake. All right.
And then another study that we looked at was malti etal from 2021. And we found that in this study there were 44 subjects with coronary artery disease studied. And they were, this is a double blind placebo controlled trial and they were given a probio. So instead of a prebiotic that feeds bacteria that given the bacteria directly. And in this study they had lactobacillus Rosis gg, which is a very kind of famous probiotic for 12 weeks. And just that probiotic alone improve their inflammation, lower their endotoxemia, and improve their metabolic outcomes as well.
And if you’re thinking food first, there’s also a study on this by pay ET all from 2018 where they just looked at yogurt and they were looking at premenopausal female subjects with obesity and basically found that as compared to the control, which was soy protein pudding, excuse me, soy P pudding, which sounds gross that either that or low fat yogurt. And compared to the soy pudding, the low fat yogurt caused less endotoxemia after meals right out the gate. And then after nine weeks of eating yogurt every day, they had a significant lowered endotoxemia as compared to the control group.
That was less than half. So significant improvement. And then the final study we looked at was bi fol in 2023. And they basically did both. They did the probiotic and the prebiotic together, they gave, and that’s called a symbiotic. So they gave a lacto bifido probiotic with foss, which is an in prebiotic that stands for fructose oligosaccharide.
They gave that or placebo for eight weeks. And you probably by this point know what I’m gonna say.
There was a significant improvement of endotoxemia, there was significant improvement of inflammation. IL six H-S-C-R-P and TNF alpha, if you know those cytokines, those are all inflammatory markers that improved in this group with obesity. So I guess what you can take from this is that there’s a lot of things that can help with endotoxemia, and they’re not super fancy things. It’s things like pomegranate extract, yogurt, pre and probiotics, soy, soy pudding didn’t work. So don’t lean on that chia seeds, inulin is a prebiotic as well, foss.
So starting with those targeted things that improve gut health is obviously helpful. And what we also see in these studies is that when you improve LPS, you always see the improvement of actual metabolic markers tied to it, taking it to actual every day.
Like what do you do about it? We do test for endotoxemia in our clinic. So the two, the two tests we use is are all looking at LPS antibodies. So you can’t really measure LPS directly in a clinical setting only research settings. So the studies that, or the labs that are used in clinical practice look at LPS antibodies.
And so you can get that either from the Cyrex array two or we also use the vibrant wellness wheat zoomer. Both of them have the LPS and some other markers related to intestinal permeability. Other things that we think about when we have a client who, where we suspect or know that there’s endotoxemia. So that would be most people, because that’s the majority of people in the world have this. Things like high polyphenol rich diet, eating unrefined carbohydrates, high fiber diet, focusing on healthy fats, new high nutrient density, minimal processed and refined foods.
The nutrient density is really important because your immune system is needed, is regulated by nutrients that most people have low intake of. So things like zinc, vitamin A are really important for immune system regulation and for quelch inflammation. And most people are low in what they need in order to do that. So high quality diet, high in plants, high in good quality protein.
And I’m talking about animal protein, unrestricted unhealthy fats. Some power foods for this are flax seeds, chia seeds, true fermented yogurt. Some of the studies combine their intervention with some energy restriction, but I don’t think that that’s essential for this because typically did that for the placebo group and the intervention group.
And the intervention group had a significant outcome compared to placebo. So it clearly wasn’t the energy restriction that did it. It was the intervention that improves endotoxemia. So you could say this, this research almost argues against trying to restrict your calories.
It’s more work on optimizing your gut health and from that you’ll want less food. In practice, we do a fair amount of gut testing and optimization. So in these studies, they’re looking at a large cohort of people. They can’t do an individualized plan for everyone, so they just give a simple intervention to everybody. But in practice, we’ll often test the gut and do something that’s a little bit more specific and individualized to that person.
So the full plan aside from that would be thinking about supplements. The the studies that use a probiotic, use a lacto and some lacto bifido or just a lactobacillus probiotic. The prebiotics were inulin resistant, dextrin or phos, or I think you could argue that pomegranate extract is a prebiotic for akkermansia. And then if you’re listening to this and you think I’m nuts because you could never tolerate a prebiotic or a high fiber diet, then I would say that’s something we see a lot because there’s a lot of people in this vicious cycle where they have dysbiosis that prevents them from tolerating the foods that they need in order to get out of dysbiosis.
So we’ll do things like starting with digestive support. So things like, I like to use a specific digestive enzyme called digest from transformation enzymes. Maybe combine that with some bitters, sometimes some betaine HCL, sometimes a pro kinetic. And then being very selective about the probiotic that we start with, usually more of a spore based probiotic.
And then kind of breaking the vicious cycle that way by once you support digestion, fiber tolerance, breaking food down, then you can start to advance on a diet that’s actually the right thing for for gut health without having horrible symptoms when you eat that way. So altogether, I hopefully this episode inspired you.
If nothing else, just to think about gut health and how it connects to metabolic health. I think too few people understand that connection and so too many people are given solutions to metabolic problems that don’t serve them. I think I’ve already explained what I mean by that quite a bit. So again, hope this helps.
Definitely check out the show notes for the references and hit us up if you have any questions or if you have any requests of topics. Always love your suggestions and happy to hear what you guys wanna hear about. All right, have a great rest of your day and talk to you later.
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