How to Improve Your Metabolic Flexibility & Why It Matters (Minisode #57)

Our bodies produce energy thanks to a process called metabolism. It sounds simple, but in the modern world this process has become difficult. For many individuals, a declining metabolism is an early indicator of poor health. In this mini-episode of the Dhru Purohit Podcast, Dhru speaks with Dr. Casey Means, Chief Medical Officer and Co-founder of metabolic health company Levels, and Dr. Sara Gottfried, Clinical Assistant Professor in the Department of Integrative Medicine and Nutritional Sciences at Thomas Jefferson University. Dr. Means shares what metabolism is, and how it impacts overall health.

03:55 – Metabolism is how we produce energy

Dr. Means explained that when metabolism works well, our body works well as a whole.

Fundamentally, our metabolism is how we produce energy from our food and the environment. We make energy by converting sugar and fat into something we can actually use, namely things like ATP. This metabolic process of energy production is this core, fundamental pathway of every single cell in the body. When it doesn’t work well, we see diseases and symptoms emerge. When it does work well, we thrive and we see stable energy, we see vigor, we see mental clarity, athletic endurance, stable mood, good skin, good memory, really all the things we want.

04:33 – How food is converted to glucose

Excess carbs result in our bodies producing too much insulin. That’s when the issue of insulin resistance can develop.

The way this works is that when we eat carbohydrates, it’s converted to glucose and our bodies have to then release a lot of insulin to get that glucose to be taken up into the cells. Over time, if we’re eating lots and lots of carbohydrates, especially refined carbohydrates and sugars, we’re going to have our bodies required to release lots and lots of insulin. Over time, our cells actually get numb to that insulin. They see so much of it that they actually put up the block. This is a process called insulin resistance.

05:05 – The problem with insulin resistance

When there is too much insulin present, over time our cells can’t get the energy they need, and begin to deteriorate.

When [insulin resistance] happens, our body has to release even more insulin to get the same amount of glucose into the cells. It becomes harder over time to even get that glucose into the cells to be converted to energy, so we end up getting this deficit of energy inside our cells. And you can imagine, when our tissues aren’t getting the energy they need, they’re going to start falling apart.

05:26 – When stored fat cannot be used

Another downside to insulin resistance is that our bodies are not able to use stored fat as an energy source.

The secondary issue with insulin being elevated is that because it is a signal that there’s enough glucose in the blood, it says to the body, “We don’t actually need fat for energy, so stop breaking that down.” So it’s going to cause you to not be able to use fat as an energy source. In two ways, it’s actually creating an energy deficit in the body when insulin is high and we’re insulin resistant. We’re not able to process glucose effectively and we’re not tapping into fat usage.

05:50 – The many faces of metabolic dysfunction

Dr. Means said that a poor metabolism can manifest in many ways, from chronic pain to infertility.

You can imagine, well, anywhere this is happening in the body, you might see dysfunction. This is why metabolic dysfunction has so many different faces clinically. If this is happening in the brain where the brain’s not able to process energy effectively, it could look like poor memory, it could look like Alzheimer’s, it could look like chronic pain, it could look like fatigue, it could look like depression and anxiety. If this is happening in the ovaries, it could look like infertility, which is why polycystic ovarian syndrome, the leading cause of infertility in our country, is fundamentally a metabolic condition.

06:41 – Greater glucose insight is needed

Prior to Levels, the only way to understand your blood sugar health was to get it checked annually at the doctor’s office.

How we produce energy in the body, it’s just such a core fundamental pathway. We unfortunately right now don’t have a lot of insight into how this is working in our bodies. We may get our glucose, our blood sugar, checked once a year at the doctor’s office, but that’s about it. It’s really hard to currently track this, measure it, and know how to improve it.

Dhru Purohit (00:00):

Coming up on this week’s mini episode of the Dhru Purohit Podcast.

Dr. Casey Means (00:03):

This is why metabolic dysfunction has so many different faces clinically. If this is happening in the brain where the brain’s not able to process energy effectively, it could look like poor memory, it could look like Alzheimer’s, it could look like chronic pain, it could look like fatigue, it could look like depression and anxiety. If this is happening in the ovaries, it could look like infertility, which is why polycystic ovarian syndrome, the leading cause of infertility in our country, is fundamentally a metabolic condition.

Dhru Purohit (00:32):

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Dhru Purohit (02:05):

Hi, everyone. Dhru Purohit here. Most of us hear the term metabolic health and think that it only applies to our ability to burn food and manage our weight. And while those are certainly big pieces of metabolic health, it also impacts everything from our cardiovascular health to cognition, mood, infertility, and so much more. That’s because our metabolism is actually our body’s ability to create energy and this happens all over the body.

Dhru Purohit (02:32):

If our energy production in the brain is hindered, we could have memory loss. If it’s not functioning properly in muscle cells, we may see chronic pain, and the list goes on and on. In today’s mini episode, I speak with my friends, Dr. Casey Means and Dr. Sara Gottfried, about how our metabolic health impacts our overall health, indicators of poor metabolic health and what they are, and how to improve our metabolic flexibility.

Dhru Purohit (02:57):

Let’s listen in starting with Dr. Casey Means, a Stanford trained physician, chief medical officer and co-founder of the metabolic health company, Levels, an associate editor of the International Journal of Disease Reversal and Prevention, and a lecturer at Stanford University. Dr. Means has been featured in the New York Times, Wall Street Journal, Men’s Health, Forbes, and much more.

Dhru Purohit (03:18):

I always wish that we had come up with a different term than metabolic health because I almost feel like in one way, the term, it makes people feel like they think they know what it is, “Oh, that’s just metabolism, I guess.” But it doesn’t address the seriousness of really everything included. Let’s even start there. What is metabolic health and maybe even what would you call it if you were going to give it a different name?

Dr. Casey Means (03:48):

That’s such a great question. I mean, it really does need a rebrand, I think. But let’s just start from the beginning. What is it? Fundamentally, our metabolism is how we produce energy from our food and the environment. We make energy by converting sugar and fat into something we can actually use, namely things like ATP. This metabolic process of energy production is this core, fundamental pathway of every single cell in the body. When it doesn’t work well, we see diseases and symptoms emerge.

Dr. Casey Means (04:22):

When it does work well, we thrive and we see stable energy, we see vigor, we see mental clarity, athletic endurance, stable mood, good skin, good memory, really all the things we want. The way this works is that when we eat carbohydrates, it’s converted to glucose and our bodies have to then release a lot of insulin to get that glucose to be taken up into the cells. Over time, if we’re eating lots and lots of carbohydrates, especially refined carbohydrates and sugars, we’re going to have our bodies required to release lots and lots of insulin.

Dr. Casey Means (04:57):

Over time, our cells actually get numb to that insulin. They see so much of it that they actually put up the block. This is a process called insulin resistance. When that happens, our body has to release even more insulin to get the same amount of glucose into the cells. It becomes harder over time to even get that glucose into the cells to be converted to energy, so we end up getting this deficit of energy inside our cells. And you can imagine, when our tissues aren’t getting the energy they need, they’re going to start falling apart.

Dr. Casey Means (05:26):

The secondary issue with insulin being elevated is that because it is a signal that there’s enough glucose in the blood, it says to the body, “We don’t actually need fat for energy, so stop breaking that down.” So it’s going to cause you to not be able to use fat as an energy source. In two ways, it’s actually creating an energy deficit in the body when insulin is high and we’re insulin resistance. We’re not able to process glucose effectively and we’re not tapping into fat usage.

Dr. Casey Means (05:50):

So you can imagine, well, anywhere this is happening in the body, you might see dysfunction. This is why metabolic dysfunction has so many different faces clinically. If this is happening in the brain where the brain’s not able to process energy effectively, it could look like poor memory, it could look like Alzheimer’s, it could look like chronic pain, it could look like fatigue, it could look like depression and anxiety.

Dr. Casey Means (06:15):

If this is happening in the ovaries, it could look like infertility, which is why polycystic ovarian syndrome, the leading cause of infertility in our country, is fundamentally a metabolic condition. If it’s happening in the blood vessels, it could look like high blood pressure or heart disease. If it’s happening in the liver, it could look like fatty liver disease. If it’s happening in the skin, it can look like acne. These are all conditions that are related to underlying metabolic health.

Dr. Casey Means (06:39):

So, fundamentally, it comes down to how we produce energy in the body and it’s just such a core fundamental pathway. We unfortunately right now don’t have a lot of insight into how this is working in our bodies. We may get our glucose, our blood sugar, checked once a year at the doctor’s office, but that’s about it. It’s really hard to currently track this, measure it, and know how to improve it.

Dhru Purohit (07:05):

My next guest, Dr. Sara Gottfried, is a board-certified physician who graduated from Harvard and MIT. She practices evidence-based integrative precision and functional medicine. She’s a clinical assistant professor in the Department of Integrative Medicine and Nutritional Sciences at Thomas Jefferson University and a director of precision medicine at the Marcus Institute of Integrative Health.

Dhru Purohit (07:27):

Her three New York Times bestselling books include The Hormone Cure, The Hormone Reset Diet, and Younger. Her latest book is Women, Food, and Hormones. Dr. Gottfried and I dive into how to use a ketogenic diet to improve our metabolic health, why classic keto works better for men than women, and what can be done to adapt it for a women’s unique biology. Let’s listen in.

Dhru Purohit (07:50):

I think we should absolutely go into metabolic flexibility because this is really the sophistication of the wellness movement, the culmination. And we’ll grow every year and we’ll learn more. But this is a term that a lot more people are getting familiar with because there’s been all sorts of diets that have steered us in one direction or another. Like the Buddha used to say, “There’s something to say about the middle path.” So talk to us about metabolic flexibility and how it’s understanding when we incorporate it into not only our body, but our mindset, can be a better way to navigate life and also a little bit more of an enjoyable way to navigate life.

Dr. Sara Gottfried (08:33):

It’s definitely more fun than I think the alternative, which is metabolic and flexibility. The definition of metabolic flexibility is the ability to switch between burning carbs and burning fat depending on what type of fuel is available. You can think of it like a hybrid car that can switch between electricity and gas depending on the type of fuel that’s available. What happens is that a lot of folks become less metabolically flexible over time because they’re snacking all the time or they’ve got too much stress or maybe they’ve got some of those genetic variations that are associated with insulin resistance.

Dr. Sara Gottfried (09:14):

They become metabolically inflexible and they often get stuck in burning glucose, burning carbs. That was my own story. When I first tried the ketogenic diet, I remember going on Atkins before I got married. My husband lost about 20 pounds in a short amount of time and I maybe lost two pounds. What I realized was that now I know in retrospect I was carbon tolerant and I was also metabolically inflexible. A few years ago, in 2016, I tried the ketogenic diet a couple of times. I had a lot of patients who were coming to me on keto and I wanted to learn more about it myself.

Dr. Sara Gottfried (09:53):

I tried keto a couple times and I just couldn’t get it to work. Part of what was the problem for me was that I was metabolically inflexible. So for instance, to get into ketosis, it would take me about 10 to 14 days just to start to make ketones because my body was so used to burning carbs. So, metabolic flexibility is really the goal. It’s not that I recommend that people go on a ketogenic diet and stay on a ketogenic diet for long periods of time. What I recommend is using a ketogenic diet as a therapeutic pulse.

Dr. Sara Gottfried (10:31):

So, typically four weeks, which is what I cover in my book, and then to start to bring more carbohydrates in while you’re tracking metabolic flexibility. You can track it as your ketones, you can use a breath meter like Lumen, you can use a continuous glucose monitor, you can use glucose ketone index. There’s many different ways to track this. But what we’re looking for is that ease with which you can flip the switch between burning glucose and burning fat depending on the type of fuel that’s available.

Dhru Purohit (11:05):

It’s a powerful way to really see that metabolic flexibility as a human being, as an organism. The human species has been probably a big part of what has allowed us to become the species that we are, travel all around the world, be able to think of advanced technologies, be able to expand our brain size because we had that flexibility, especially at times of major changes in the climate that could affect food sources and other aspects.

Dhru Purohit (11:37):

It’s also great because diet sometimes can get so tribal. Using these tools, as you mentioned, the continuous glucose monitor, using things like Lumen or other breathometers that are there, you can really dial into what works well for you. On a personal anecdote, if I could add in, a few years ago when I started going to keto… And a big part of keto in the more traditional sense is making sure you get a higher amount of saturated fat inside of your diet, the clean sources of saturated fat that are there. I noticed that my health journey originally started because I had really bad acne.

Dhru Purohit (12:17):

I noticed that, because I’ve dealt with so many gut issues from being on antibiotics as a child, that the saturated fat would trigger almost like an endotoxemia effect inside and I started getting a lot of flare up of almost acne-like symptoms. My face would be red all the time. Then on top of that, as I would track my blood results on a pretty regular basis, getting blood work every month, I noticed again for myself personally, and the big part of this is genetics coming from a south Asian background, even though I was not worried about cholesterol, I was paying attention to my NMR particle size and I was noticing that my lipoprotein (a) was getting quite high up there.

Dhru Purohit (12:59):

And I just saw that my body, genetically, for who knows what all the different reasons are, was not as efficient as somebody else’s body at utilizing that saturated fat and putting it to work. So just another reminder of how you can try things, see the actual difference that it makes for you, get your blood work done, use things like continuous glucose monitors, and then you can personalize it to what makes sense for you, in cases sometimes biological sex, which you write a lot about inside of your book, your ethnic background, which plays a role into it, and your personal lifestyle choices and goals that are there.

Dhru Purohit (13:40):

So I think it’s the combination of all of that, that just like you personalized it, we can all take a lesson from that and look at how we can personalize all these things that broad strokes seem to work for a lot of people, but might need to be tweaked to work for us uniquely.

Dr. Sara Gottfried (13:54):

That was such a helpful illustration of how keto can increase inflammation in some people, especially the dose of saturated fat. So I really appreciate how you shared that story with acne. Thank you so much. Your skin looks amazing by the way, Dhru, I must say.

Dhru Purohit (14:10):

Oh, thank you.

Dr. Sara Gottfried (14:13):

But I think this brings up some really important points which include… When I put someone on a ketogenic diet or when people follow the four-week pulse that’s in my book, what we know is that it’s pretty significantly changing hormones, signaling pathways, and there’s genomic drivers. So for instance, part of the genetics that you inherited from your parents determine the way that you respond to saturated fat and the way that it affects the glucose and insulin pathways.

Dr. Sara Gottfried (14:46):

So sometimes knowing that information can be very helpful, or you can track some of these biomarkers such as the NMR lipofraction assessment that you were describing. We know for a lot of people that LDL goes up. If we just look at low density lipoprotein, LDL goes up in about 10%… Well, about one in four people that are on the ketogenic diet. Sometimes it’s not clinically significant, but it’s something that we want to track and understand, especially if people are staying on it for a longer period of time, such as they do in the Virta study, which enrolled type two diabetics and put them on a ketogenic diet.

Dr. Sara Gottfried (15:28):

Overall, they had about a 10% increase in LDL. So I think this individualization is so important. You said something else that I really liked, which is the tribalism that occurs around food. What I really hope that people hear from us in our conversation today is that I’m food agnostic. So I really believe that even though a lot of my friends are keto or they’re paleo or they’re vegan or vegetarian, I think it’s important to understand what works the best for you.

Dr. Sara Gottfried (16:06):

I learned, for instance, in medical school, when I went vegan, low fat, that was not a good fit for me. I needed more fat, I needed more protein for my hormone balance. So being able to understand that feedback loop, I think, is such an essential part of this empowerment conversation we want to be having with our body, our health, our hormones.

Dhru Purohit (16:27):

Let’s come back to the Gottfried Protocol while we have a little bit of time here or towards the end of our interview. What is it? Who is it designed for? And can you walk us through what are the key pillars that are part of it?

Dr. Sara Gottfried (16:42):

The key pillars start first with detoxification. Maybe I’ll give an overview and then we’ll circle back to why I designed it in this particular sequence. Step one is detoxification, opening up your detox pathways. That includes methylation, it includes cruciferous vegetables, it includes paying attention to antioxidants. The second part is the ketogenic diet, so really following a ketogenic diet in a particular way, using net carbs. I was told when I first started on keto not to use net carbs, but I think we have to, especially for women.

Dr. Sara Gottfried (17:21):

Then the third part is to layer in intermittent fasting, but to do it in a particular way that doesn’t cause hormone imbalances like disrupted cortisol. So if I take a step back now, what I found, Dhru, was that about seven or so years ago, I suddenly had all of these patients who came to me who were struggling with a ketogenic diet. They were early adopters, they were following different thought leaders. They were trying keto, they were doing the macronutrients, they were eating the fat bombs and the bacon, and they just weren’t getting the results that they were hoping for.

Dr. Sara Gottfried (18:02):

Often, they would do it, they’d do keto with a colleague from work, like a male colleague, and the male colleague would get all benefits and they were struggling. These were mostly women. So I saw this sex difference. I saw that my male patients were doing a lot better on keto, they were becoming metabolically flexible, and the women were really struggling. I called them my keto refugees because they were so frustrated and they felt like, “I’m doing everything right. What is wrong? Why is this not happening?”

Dr. Sara Gottfried (18:31):

So as I was struggling on my own with the ketogenic diet, I realized one of the first pieces that’s so important for women is to make sure that those detox pathways are open. I see a lot of women who struggle with constipation, who are not pooping every single morning with feeling of utter relief like you have evacuated completely and you are ready to start your day. So we need that in place before you can really be successful on a ketogenic diet. You have to be eliminating. That is priority number one when it comes to many of these metabolic hormones, especially the estrogens, because the gut is so involved in estrogen balance, especially estradiol.

Dr. Sara Gottfried (19:15):

So detox, getting that dialed in is so essential that I put it first, and also getting the vegetables that you need, the allium vegetables that raise glutathione, the dark green leafies that help you with the B vitamins, that help you with methylation, really important to have that in place. Then the ketogenic diet itself. Again, I said before that I use net carbs because I find that women who restrict total carbs too much often end up having menstrual irregularity. We see that in up to 45% of people on classic keto.

Dr. Sara Gottfried (19:50):

They often have thyroid issues because reverse T3 can be raised by restricting carbohydrates successively. I also see that they have issues with cortisol, so too much food stress. So if you adapt the ketogenic diet, you focus on net carbs… I have people begin with 20 to 25 net carbs each day. I find that that is so much better in terms of keeping the gut component of the control system for your hormones really working. Then I like to layer in intermittent fasting. There’s a lot of different people giving conflicting information about intermittent fasting.

Dr. Sara Gottfried (20:30):

My review of the literature is that 14 hours is probably the right number in terms of an overnight fast for women that’s not associated with too much cortisol or other hormone disruption. This comes from UCSD, the work of Barbara Patterson. She’s done some work looking at breast cancer risk and a few other hormonal factors. I think 14 hours is probably the best way to go. I recommend that people ramp up slowly to intermittent fasting. I like to combine it with the well reformulated ketogenic diet because it’s a back door to ketosis.

Dr. Sara Gottfried (21:12):

Most people can get into ketosis after some period of an overnight fast, typically 14 to 18 hours. That’s basically the protocol. Then when you come off the protocol, it’s really important, almost like an elimination diet, to very gradually add those net carbs back in. Five grams of net carbs per day is what I recommend where you’re tracking metabolic flexibility. So you’re looking at glucose, you’re looking at your weight, you’re looking at inflammatory fluid. If you want to test a little further, you’re looking at glucose ketone index. That’s a quick overview of the four-week protocol.

Dhru Purohit (21:52):

That’s great. What are some signs, especially for somebody who comes from this background, of pretty major hormonal imbalances? What are some of the leading indicators that they should notice during the program and especially afterwards that they’re headed in the right direction? What should they pay attention to?

Dr. Sara Gottfried (22:11):

Well, the first reaction is satiety, which is a very lovely reaction where you just don’t feel as hungry. If I take a step back, if you look at the literature on glucose and insulin, probably the most proven diet is a whole foods diet with no animal protein or fat. This is very well proven to help with glucose control. My problem is, when I eat that way, I actually gain weight. So it doesn’t work for me personally, and so I have to find a way to eat clean, but to follow a ketogenic diet.

Dr. Sara Gottfried (22:54):

The main issue when I eat a whole foods, plant-based, 100% plant-based diet is that I’m hungry, I’m really hungry. So I end up eating excessive calories. So for me, the satiety that you get from producing ketones as a result of burning fat really helps me with creating that metabolic flexibility that I’m after. Of course, it’s not about me. It’s about other people. When they follow a low carbohydrate, high fat food plan, moderate protein, they have this feeling of satiety that comes from the ketones that are produced, mostly beta-hydroxybutyrate.

Dr. Sara Gottfried (23:38):

That’s one example, the feeling of being satisfied, not being hungry. I haven’t eaten yet today because my ketones are relatively high. I cycle in and out of ketosis as needed. Another benefit is there should be some weight loss. Especially for people who are overweight or obese, we expect as you start to burn more fat, we expect that you’re going to have some fat loss. So technically, it’s fat loss. I don’t want people to lose muscle. I want them to lose fat, and if you have fat to lose, that’s one of the benefits that you should see from this type of program.

Dr. Sara Gottfried (24:17):

Another one is relationship health. Since we talked about this earlier, I think this is a really key concept. I was filling out a functional medicine matrix, and under relationship and community, which is something we pay a lot of attention to at the Institute for Functional Medicine, I was thinking about how relationships are affected by someone becoming metabolically flexible. When you’re metabolically flexible, your blood sugar is where it should be and not spiking high after you have, I don’t know, an acai bowl, and then crashing down low right afterwards.

Dr. Sara Gottfried (24:59):

That’s the kind of situation where you are just a setup for a fight with the people that you love. So I think another benefit is that you feel more even, your mood is better, you might find that anxiety is improved, and that the quality of your relationships gets better. So those are a few examples. There’s a long list in the book, but those are the three that I’m thinking about right now.

Dhru Purohit (25:21):

Thankfully, many of the factors that impact your metabolism are within your control and they can be changed to improve your body’s metabolic flexibility. The food you eat and how often you eat holds a lot of power over your metabolism. While everyone is different and your exact diet is going to look different than someone else’s, in general, focusing on eating clean, whole food sources, eating fewer sugars and carbs, and eating more healthy fats are going to radically do wonders for achieving metabolic flexibility.

Dhru Purohit (25:54):

Thanks for tuning into this week’s mini episode of the Dhru Purohit Podcast. I hope you enjoyed it. And if you do, send it to a friend who might be interested in this topic.