Decode and Defend: Unlocking Genetic Secrets to Metabolic Health

What’s Inside This Episode?

• Genetics as a Predictive Tool: How understanding certain SNPs can reveal hidden metabolic risks and be used to personalize plans.
• Practical Applications: How to integrate genetic insights with lab testing for personalized dietary and lifestyle strategies.
• The Sweet Tooth Gene and Beyond: Explore key SNPs affecting blood sugar, insulin resistance, and weight management.
• Fasting Protocols: The role of fasting mimicking diets in optimizing metabolic health safely and effectively.

Actionable Lab Testing Tips: What markers to test for a comprehensive metabolic health assessment.

Resources and Links:

• See the Full Transcript here
• Download our FREE Guide to Using Genetic Testing to Optimize Patient Outcomes
• References to GLUT2 gene?
• Video for Adiponectin?
• Find out more about our Insulin Resistance Mastery Program for Practitioners here.
• Join the Next-Level Health Practitioner Facebook Group for free resources and community support.
• Get the replay and slides from our most recent summit for practitioners, ReInvent 2025 here, a deep dive into the impact of the microbiome, lab 
• Visit INEMethod.com for advanced practitioner training and tools to elevate your clinical skills.
• Learn more about The Lab Testing Gaps That Are Sabotaging Your Client’s Health found in this episode.

Dr. Ritamarie Loscalzo’s Bio

Dr. Ritamarie Loscalzo is a pioneer in functional nutrition and nutritional endocrinology. With over 33 years of clinical experience, she’s helped thousands uncover the root causes of their health challenges through a unique, data-driven approach. As the founder of the Institute of Nutritional Endocrinology and author of Unstoppable Health, Dr. Ritamarie trains practitioners worldwide to think beyond symptoms and connect the dots to true healing.

Transcript

Dr Ritamarie  

Welcome back to the podcast. I’m super excited about the episode that I have planned for you. So what if you could predict metabolic health risks before they become chronic diseases? That would certainly save lots of people from the impact of metabolic imbalances, the deadly impact in many cases of metabolic imbalances. So genes can be like a crystal ball for metabolic health.

When you understand how to determine which specific genetic SNPs contribute to imbalances in blood sugar, insulin, and to people’s more sensitivity to carbohydrate intake, you will have the ability to better guide a person to optimal health. 

Dr Ritamarie (01:06)

So today we’re going to talk about some key genetic metabolic health markers. I’m not going to talk about all of them. I have a document, I think it’s 16 pages that lists them all and has little descriptions. It’s something that I share with people in my practitioner trainings and also in my public trainings to empower them to figure out some of their imbalances. But I’ve chosen nine of them. I was going to choose five, but I just couldn’t narrow it down to five.

So the ones that I chose were IGFR-1, insulin-like growth factor 1, FTO, fat mass and obesity associated gene, but people call it the fatso gene or the obesity gene. PPARgamma which is Peroxisome proliferator activated receptor gamma. 

I’ll talk to you about what each of these does and how you know what to do when people have these. MTHFR, we have heard about, there’s tons of research and literature. It is related to metabolic imbalance, this is the C677T version.

We have GLUT2, which is related to the glucose receptors on each cell. We have TCF7L2, which shows how we handle carbohydrates basically, the hunter gatherer versus the person that stores everything away. 

Dr Ritamarie (02:19)

We have ADiPO Q which is related to adiponectin receptors. We have SLC3A2, which is a sweet tooth gene, and then LEPR, which is leptin receptor. Lots there. I’ll go through each one. I will tell you that in the show notes, you should see a document that I’ve put together that you can review these in. And there’s also ways to get access to some of the recordings and presentations I’ve done on this that go into more detail. 

Dr Ritamarie (02:47)

Let’s start with IGF1R, insulin-like growth factor one receptor. It’s a polypeptide protein hormone that’s similar in structure to insulin, and it can bind to the insulin receptor, and it can cause insulin resistance as a result of binding to the insulin receptor. So basically it blocks insulin from the receptor. 

FTO, the fatso gene, the obesity gene, and it’s related to not feeling satisfied after eating. People with FTO SNPs, they just never get satisfied. And of course that can be related to leptin and leptin signaling, but FTO genes relate to that.

The other thing is it is associated with obesity and decreases insulin sensitivity. And people who don’t tend to do well on a ketogenic diet. They tend not to do so well with extra fats, the extra fats will stimulate the binding and the lack of receptivity. So that’s one to keep in mind that you have somebody who’s, I’ve been on a keto diet for a long time and nothing’s happening. Well, they may have that FTO tendency, and you’ve got to guide them differently than you would if they did not. 

Dr Ritamarie (03:33)

We have PPARG, Peroxisome proliferator activated receptor gamma. That is such a big mouthful. And it regulates adipocyte differentiation, adipocytes being fat cells. It’s been identified as an important mediator for maintaining whole body insulin sensitivity. 

We know that fat cells generally don’t become insulin resistant. They are always insulin sensitive, which is why when we can’t get the insulin to take the glucose into a cell to make ATP and all, we just have this buildup of fat, because the extra sugar has to get stored and the fat cells aren’t resistant. So it’s going to take the sugar wherever the cells are not resistant. So this SNP is associated with decreased insulin sensitivity and weight gain that happens, especially in people who have diabetes.

Dr Ritamarie (04:51)

So let’s look at the good old MTHFR, C677T. It helps convert homocysteine to methionine. know that, most people know that. It can lead to high homocysteine. Homocysteine is an inflammatory marker that affects the cardiovascular system in the brain. And insulin signaling becomes impaired when we have extra homocysteine in the mix.

 So they’ve done cultures in cells and seen that you can’t be  sensitive to insulin when there’s elevated homocysteine and this SNP in particular can create that situation where somebody is prone to have an elevated homocysteine. It increases the risk of obesity, and it’s associated with metabolic syndrome and insulin resistance. So it’s one that we really need to be looking at. And about 40% of the population has at least one single SNP, heterozygous for it, MTHFR C677T. 

So we really need to be looking for it. And there’s a lot of things you can do to help balance the person’s physiology, balance their diet, and balance their folate intake, so that they don’t have the associated problems.

Dr Ritamarie (05:59)

So the TCF7L2 is not one you’re going to hear talked about a lot like MTHFR or COMT even, but it is a very important gene to be looking at in people to see if they have the tendency towards insulin resistance and metabolic syndrome. It influences the transcriptions of several genes, just the TCF. 

There’s several of these genes that affect transcription of genes, but it affects insulin secretion, and it affects glucose production. So how sensitive a person is to insulin and to getting sugar into the cells with the use of insulin can be predicted by their TCF7L2 status. 

So the hunter gatherer variant is one that causes people to spike blood sugar when they take in starches. So we’re not talking about eating Wonder Bread and your sugar goes up. That’s kind of common, but somebody eats a little bite of a sweet potato or plantain or squash and their sugar goes up. These people most likely have a TCF7L2. I have that one. 

The farmer variant can handle more of that. So really looking at this, overexpression of the TCF7L2 stimulates insulin secretion.

And people with this have more of a tendency to type 2 diabetes. So something to be looking at, and you can use knowledge of these genes to help inform the kind of diet you’re going to recommend to that person. You may not be telling them to have, you know, starch with every meal or something if they have this variant, or you’re going to know they have this variant and have them test what happens when they have starch with their meals, even whole food starches that are vegetable based starches.

So let’s look at ADIPO-Q. You’ve heard of adiponectin, a really important hormone to keep control of our metabolic health, to keep control of our insulin and glucose. And it’s expressed exclusively in adipose tissue. So the SNPs are associated with adiponectin deficiency. And we know adiponectin deficiency is related to gaining weight, to having insulin resistance.

Dr Ritamarie (08:09)

So adiponectin stimulates glucose uptake by the muscle, and it inhibits glucose production. So that’s a good thing, right? But when they have this SNP, they’re not going to produce as much adiponectin. Highly recommend that you go study adiponectin. Really important, most people aren’t talking about this. Most people aren’t studying it.

It gives us some really good clues and insights on how we can help people to be efficient in their digestion and in their blood sugar management. 

Adiponectin provides a link between visceral fat accumulation, right, that stuff that’s under the surface around the middle, and insulin resistance. And there’s a higher risk of obesity in type 2 diabetes and people who have this. So this is going to help you to predict. All of these are, they’re going to help you to predict.

So there’s SLC2A2 in the solute carrier family, and there’s a bunch of different SNPs in that family. This particular one codes for the sugar transporter receptor GLUT2. So when we have a particular SNP here, especially the F295Y, it induces beta cell differentiation even in the absence of glucose. 

So we’re going to have a lot more of the insulin being produced and that’s going to lead to a lot more insulin resistance. They often call this the sweet tooth gene. And I’ve got some references that we’ll include in the notes in case you want to go deeper with this. 

LEPR is our last one we’re going to look at, and it’s really important for leptin resistance. So it’s the leptin receptor gene. And when people aren’t getting the leptin into the cells, the fat cells produce the leptin, and it has to go to the hypothalamus and has to go to the pancreas. We don’t get the message that you’re full. And what happens is they’re snacking behavior. People are grabbing food in between meals. So for a person who has this LEPR, it’s not as simple as saying, don’t eat between meals, only three meals a day.

Dr Ritamarie (10:05)

They’re going to have to exert a lot more willpower with that, because this pathway is overpowering them. So in a person with leptin resistance, it’s even more important to recommend that they don’t eat between meals, fill up at the previous meal, drink tea or drink some things that are going to satisfy the mouth craving and turn that off and eventually it could get better. So those are the kinds of things that I would recommend. 

It’s one thing to look at genes, but genes are not our destiny. The genes predict the specific things that could happen. It increases the risk factor, but there have to be other things in place. And that’s why it’s so important that we learn what’s going on with their genes, so we can inform them of healthy lifestyle choices based on their genes. What I find is that people respond when you show them a gene and then you give them a lifestyle choice that’s related to that gene. 

So what we want to do in terms of testing. It’s not just about genes. You look at the genes, yes, but you want to look at the early signs. You want to look at somebody. You want to get to the point where as a practitioner, you’re looking at somebody and go, that person has insulin resistance. Waist-hip ratio, waist-height ratio, right? You want to be looking at that stuff, and you can predict that, because it’s a very early predictor, and most people don’t pay any attention to it. It’s that stubborn weight gain.

If you’re doing testing, I highly recommend you do comprehensive blood sugar testing on these people and look at fasting insulin, fasting glucose, of course, postprandial glucose, either with a CGM or finger prick, and a hemoglobin A1C, and in some cases fructosamine and C-peptide. But doing those tests are really important.

Dr Ritamarie (11:47)

And also looking at some of the downstream results of having imbalanced blood sugar and insulin resistance, and that would be lipid panels. You really want to look at their lipid panels and their inflammation panels. 

So how do you optimize a person’s diet and lifestyle based on what you find? So say you find a handful of these particular SNPs, and you know they’re predisposed and you know they’re having trouble with their weight, and their waist is a little bit bigger than it should be. Well, we want to put them on a low glycemic diet, right?

There’s a lot of attention on carnivore diets and keto diets and paleo diets, it’s finding the right balance for each person. I’m not a fan of butter and bacon diets. I just don’t think it provides enough nutrition. I’m not a fan of carnivore diets. I just don’t think they pay attention enough to the nutrients. But a low glycemic diet. And it could be a plant-based low glycemic diet, which is what I follow with more of the whole foods, plant-based fats, but helping them get them on a CGM. 

Watch what happens while they’re eating and then see what you can do to optimize their diet, their glycemic load based on what’s going on. I would say that you want them to be moving, of course, and stress management and sleeping enough. 

All of those things are more important in a person who has the genetic tendency. They’re important for everybody, right? But for somebody who has this genetic tendency, it’s being able to explain to them that you need to do these things or you’re going to end up with full-blown metabolic syndrome or full-blown diabetes. And that’s going to affect your cardiovascular system. And it’s a death sentence. So let’s get this under control now. 

There are certain supplements. We talk about that in another episode, the B vitamins and omega-3s and magnesium and other herbs and stuff. 

And then of course, my favorite is fasting mimicking protocols. I have my own version of fasting mimicking diet, which is fasting while feasting or fasting, but fasting is a little trickier, right? Because you can’t guide a person through a fast unless you really are on top of them. So I don’t recommend extended fasts unless somebody’s supervised. Extended fasting saved my life, and I’m all for it, but I think people need to be supervised to do that. 

Dr Ritamarie (14:05)

That’s why I created the fasting while feasting program, so that people can eat in a certain way that has been scientifically proven to have the effects of fasting on lowering insulin levels, lowering glucose levels, increasing ketone levels, decreasing inflammatory markers. 

So that’s the kind of stuff that you can incorporate and work with people. And you’ll see in the notes, you’ll see a link to a program that we have, which is a practitioner insulin resistance reversal program that you can go through and learn how to do that and get access to all of my handouts and my charts and all that. 

If you’re a practitioner, here’s what to do to start integrating Nutrigenomics into your practice, right? Explore the options for genetic testing. And it’s a lot harder today than it was like 5, 6, 10 years ago. There’s a lot more choices. They’re not all very excellent choices, let’s just say. And the jury’s out for me as to is there any one best one, but explore those and any of you, if you’ve been to any of my events, we have a long list of sample reports and all that.

And just a little shameless plug, we are doing an event in January 2025, if you’re listening to this before that, you can come live, and if you’re not, you can come and get the recordings of it, but we’ll be talking about the connection between microbiome and metabolic health hormones and brain chemistry and genetics. And so we’re going to be going through labs and genetics, and we’re going to give you resource sheets so that you can look into our favorite labs to do that. 

You’ve  got to educate your clients. The correlation between their genes, their metabolic health, and their long-term health outcomes and then dive deeper. Dive deeper. Keep learning about this. It’s a relatively new science. The genomics project started in the 90s. So we’re only less than 25 years in that this has been around and science is evolving. So educate yourself, check out our resources in the show notes and the description page. 

So today we explored how genetic insights can transform our understanding of metabolic health. What’s the takeaway?

Dr Ritamarie (16:11)

Genetics is a tool for identifying people at risk by combining genetic data with looking at the body, doing some of our typical physical assessments, our lab test assessments, and looking at their lifestyle. It’s really easy to predict by looking at a person eating an ice cream cone with a belly hanging over their pants that they are in metabolic crisis at this point. So learning to use this. Don’t just rely on lab tests. And we really want to be looking at this,

 so that we can create personalized health strategies. 

If you want to learn more, download my free resource guide, which is a guide to using genetic testing to optimize patient outcomes. The link will be in the show notes. And you can also find a link on our page, on our Reinvent Healthcare page, which houses all of our podcasts.

Dr Ritamarie (17:02)

We are the future of healthcare. Our system needs to change. We need to move away from the symptom focus, the this for that approach to healthcare. And we want to put the care back into healthcare. We want to put personalization back into healthcare. I’ve dedicated my life to empowering people to take back control of their health and supporting health practitioners in getting to the root causes of chronic health conditions. And I love that you’re on this mission with me.

So if you’re ready to take your practice to the next level, visit my website, inemethod.com and see if you want to learn more about insulin and metabolic health and genetics and lab testing. And be sure to visit the show notes for lots of great resources. And until next time, shine on.