The Best Approach to Keto Diets for Women

Intro:

Welcome to Dr. Ruscio Radio, providing practical and science-based solutions to feeling your best. To stay up to date on the latest topics, as well as all of our prior episodes, make sure to subscribe in your podcast player. For weekly updates, visit DrRuscio.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking with your doctor. Now let’s head to the show.

DrMichaelRuscio:

Hey everyone. Today I spoke again with Dr. Sara Gottfried. We discussed her coming book, Women, Food, and Hormones, which helps women use the ketogenic diet almost as a reset, the appropriate way, a way in which you can reap the metabolic rewards, but also not fall into some of the pitfalls which I definitely see in the clinic of extended or over-use of the ketogenic diet, which can lead to things like fatigue, hair loss, and insomnia. So we go into some detail about the book, the approach, and again, how to use the ketogenic diet the right way in women avoiding some of the pitfalls.

DrMR:

One of the potential pitfalls or areas of concern when mentioning ketogenic dieting used in a population of women is potential thyroid problems, so we discussed that. We also had a very interesting sidebar conversation on cortisol, how to look at cortisol, how to think about it, and I think most importantly, what to do about aberrants in cortisol.

DrMR:

That all took us about an hour to get through. There was a lot there. One of the things I have always appreciated about Sara is she’s not only progressive and open-minded, but evidence-based and skeptical. So we both have a similar way we filter information so as to bring you the best information and not get swept away in theory or speculation, but also be open-minded in searching for things that may help people.

DrMR:

So with that, we will go to the conversation here with Dr. Sara Gottfried and her new book, Women, Food, and Hormones. And remember if you’re enjoying this podcast, please take a moment and leave us a review on iTunes. Okay, here we go.

DrMR:

Hey everyone. Welcome back to Dr. Ruscio Radio. This is Dr. Ruscio back again with my good friend, Dr. Sara Gottfried to discuss female hormones, thyroid, and maybe genetics if we have time. Sara, welcome back to the show.

DrSaraGottfried:

Hey, Michael. So happy to be here.

DrMR:

It’s always great chatting with you. We had a chance maybe two years ago now to meet in person and to record a few things in person. So it’s always nice to have had that one-to-one in person connection to be able to build from. We had done a short “Q and A” about thyroid. And another thing is because we both used to be located in Northern California and we were about one town away from each other. You’re in Moraga, I’m in Walnut Creek.

DrSG:

Yeah, we were neighbors. I remember this was pre-pandemic that you came over. We recorded a podcast and my dog fell absolutely in love with you.

DrMR:

I’m on that level, you know. Dogs tend to just…

DrSG:

They know what’s up.

DrMR:

So we have a nice backstory in doing some work together and also seeing eye to eye on a lot of things. But just in case people didn’t catch that podcast or your last time on this podcast, give us the brief primer on who you are, what you’ve been up to, and then we can talk about this book that you have coming up. And I’m actually really excited because it touches on female hormones and how this plugs into a ketogenic diet, which I think if done the right way, as you said, offline, can be quite helpful. So I want to set the stage for our audience that’s coming, but let’s give people your brief background before we do.

Background Information.

DrSG:

Absolutely. So I am a physician, a medical doctor. I went to Harvard Medical School at MIT. I am the director of precision medicine at Thomas Jefferson University in Philadelphia. I’m an assistant professor in the Department of Integrative Medicine and Nutritional Sciences at the Sidney Kimmel Medical College. I live in Northern California and commute to Philly where I see patients about once a quarter.

DrSG:

And what else? I’m a wife and a mom and a dog owner, obviously. We were just talking about mold and SIRS and that whole rabbit hole. I really love in our conversations how you are the voice of reason. And I appreciate so much that you take some of these complex, meaty topics and really simplify them without oversimplifying. And I think it just offers us tremendous service for those of us who are trying to change the healthcare paradigm.

The Hierarchical Process

DrMR:

And that’s where I think we’ve always seen eye to eye, which is being curious and wanting to learn more, but then having a good filter system for saying, “Okay, here’s stuff that’s irrelevant but, interesting academic bells and whistles. Here’s what’s actually clinically relevant.” And then I think we both go even a step further for how do we take all this information, this smattering of data testing, viable treatments, and try to organize them — so that we have a system to work through, so that we know this is what someone should be looking like when they’re responding appropriately. And this is what it looks like when they’re not responding appropriately. And we have this hierarchical process that we can work people through so that we’re not doing what I think sometimes patients like to think, which is creating a unique care plan for every individual.

DrMR:

I mean to some extent, there’s always going to be personalization, but I’ve said on the podcast many a time that what you want your provider to say is, “Oh yeah, I’ve seen this before many times. It typically responds to ‘XYZ,’” and not say, “Hmm, I’ve never seen this before. This is going to be new.” So yeah, these are a few reasons why I think we see so eye to eye, because I guess we’re trying to have some logic out of the chaos that is this emerging field of integrative medicine.

DrSG:

Yeah. Right on. I feel like that healthy skepticism is really called for right now. I practice precision medicine. I’ve gone through most of the training in integrative medicine and functional medicine and I think you and I do have a meeting of the minds about the thousands and thousands of dollars that you could drop in testing. And is that really going to serve the patient that’s in front of you the best, or do you want to really be thoughtful and methodical and skeptical about what you’re going to do with each test result, how is this meaningful, how is this going to advance us forward in terms of improving health? And always circling back to health as the focus, not health as the absence of disease, but really health for health’s sake. What does that look like for the individual?

Female Hormone Imbalances

DrMR:

Absolutely, and one of the realms of symptoms that I think is overlooked is female hormone imbalance symptoms. I’ve noticed that an alarming number of patients, at least in the clinic, and now we’re a clinic five doctors strong. This observation has been carried across the other providers in the clinic which gives me even more confidence in it, is someone will have female hormone symptoms that are being falsely labeled as thyroid symptoms. And this is why I’m glad that you’re doing the work that you’re doing, including this new book, because we want to make sure that we’re treating the cause. I was just saying the other day to a patient, “We want to avoid treating not the cause.” So in my vantage, the female hormones are often overlooked.

DrMR:

Now I’m sure in your vantage, since you’re someone who’s talked about it so much, you’re probably helping women make sure to get there moreso out of the gate. But tell us a little bit about the book, and then I’m really curious to explore, as you said earlier, one of the main items discussed in the book is how to use the ketogenic diet, which can have many health benefits. But how to apply it the right way for a woman because I’m sure people have heard these stories of women who’ve gone keto and it’s helped them.

DrMR:

This is something I definitely see in the clinic also, but then after months or years their hair is thinning, they have no libido, they’re going into what looks like a premature menopause, and are expressing clear symptoms of fatigue and low vitality. You get them back on some carbohydrate and they feel a lot better. And it’s because they used the keto intervention for too long. So I’m really glad to see you helping to bring some parameters to people for successful application. But, tell us a little bit about the book and then maybe we can explore some of the different topics you cover.

DrSG:

Sure. So the new book is Women, Food, and Hormones. I’ve got a few books that I’ve published in the past, mostly about women’s hormones, including The Hormone Cure, The Hormone Reset Diet, and Younger. And what I realized was exactly what you just described. I suddenly, over the past five plus years, was seeing keto refugees.

DrSG:

I think you painted the picture so beautifully. These are women that often go on a ketogenic diet because of one reason or another, usually weight loss, or they’re over the age of 35 and they’re trying to deal with a slower metabolism, and they’ve got all the problems you mentioned — the hair loss, no libido, fatigue. They often have food stress because they’re just not getting the prebiotic fibers that we need to feed the benevolent microbes in the gut. Their microbiome has probably taken a hit.

DrSG:

And what I see is that often that classic ketogenic diet, the 70/20/10 rule with macronutrients, with fat, protein, and carbs, it just often doesn’t suit women because in some ways I think women benefit from more diverse and nutrient-rich carbohydrates. And so to just give up a whole class of micronutrients often is not a long-term solution.

DrSG:

So the book is about a four week protocol designed for women to address many of these issues. As an example, some of the studies that have been done on the ketogenic diet, most of which has been done in men and assumed to apply to women and then that application doesn’t necessarily work, we see that about 45% of women have thyroid issues. Now it may not be from Hashimoto’s, it may not be a primary thyroid problem but, more secondary to other causes. And the other thing that we see is menstrual irregularity. We can see that in about half of women that go on a ketogenic diet that are still cycling.

DrSG:

So the idea with this program and the reason why I wrote the book was I wanted to help these keto refugees. I wanted to help them with metabolism. I’d love to talk a little bit together about what is metabolism, how do you address it, and what are some of the proven ways to do that; to do a ketogenic diet that’s well-formulated, really clean, still has those prebiotic carbohydrates that we need and also includes detoxification. I think this is so important for female hormone balance. Also, intermittent fasting – not so aggressively that you’re raising cortisol and leading to hypothalamic pituitary adrenal access dysregulation – but, a gentler version of intermittent fasting to support some of these hormones that tend to change as we get older, such as insulin, growth hormone, and even testosterone.

DrMR:

There are so many directions I want to go there, but one fundamental that I think connects all of these is finding the optimum balance point for some of these hermetic or healthy stressors. And these are things that I struggle with, too. Some fasting helps me regulate appetite, helps me with energy, but then if I go too far, I notice libido goes down, sleep gets poor, and exercise performance suffers. So maybe just to put some of my own experience on the table, it’s not always easy to find the optimum balance of some of these stressors, including exercise. I’ve sometimes flirted with probably exercising too much, and again, definitely for women, keto too long or too intense. And also I’m glad you said fasting, and that’s another thing that seems to be problematic.

Hormetic Stressors

DrMR:

So, I do think there’s a lot of value in helping give people a system that provides guard rails to prevent going too far in either direction so that we don’t hit some of these low points. And then I guess even worse, maybe hitting a low point. I don’t want to promise too much from your book, but if you’re given a warning like, “Hey, this is a sign that you’ve gone too far, too long,” people can recognize that and course correct quickly. Whereas, if people are just going to the “ketofan.org” website, and they’re just being told “Keto, keto, keto. Forever, forever, forever,” they may suffer needlessly for months or sometimes even years with those symptoms. They had no forewarning that this symptom is an indicator that we’ve gone past the “Goldilocks zone” and now we need to roll things back a little bit.

DrSG:

I love that “Goldilocks zone.” I agree with you that hormesis is really where it’s at here. I think of hormesis as this positive stress, as you described with exercise, with fasting, and with some of these different stressors that can potentially bounce you into a new state of health. But for those of us, and I’m going to put myself in this group, who maybe don’t tune into themselves quite the way that maybe we could be, you can take hormesis too far. And I think that’s what you’re describing with the ketogenic diet with some of the folks that you see in your practice. It’s certainly what I see as well.

DrSG:

In some ways I would say a ketogenic diet is a medical intervention and it needs to be treated like a medical intervention where we want to test to make sure that it’s the right fit for you. I have some patients who come to see me after being on keto for six weeks or six months and we find, for instance, that their cardio-metabolic function has declined. So I think being able to monitor can be very helpful when it comes to these different hormetic stressors.

Assessments for Ketogenic Diets

DrMR:

When you say cardio-metabolic, are you meaning something like a lipid panel is going to start to skew or does something like their mile run time start to tank?

DrSG:

Yeah, I would say exercise performance. I would also say a metabolic risk panel looking at hemoglobin A1C, fasting insulin, even continuous glucose monitoring, which is something I do for a lot of my patients and I’d love to talk about further with you. But also, in terms of the testing I like to do – since we know that cardiovascular disease is the number one killer of people – I run an advanced lipid panel on pretty much all of my patients looking at least once at Lipoprotein little a; not the old-school lipid panel of total cholesterol, HDL, LDL, and triglycerides, but the more advanced markers that we have with lipoprotein fractionation, NMR, LDLP, and the fractionation of lipoproteins to see whether someone is at risk.

DrSG:

I often find that there are some people who can go on a well-formulated ketogenic diet and their lipid panel looks fantastic and their cardio-metabolic function is excellent. But then there are others who go down this path of more classic keto and really end up having problems with their lipids. Even just looking at LDL as an example, LDL can increase on a ketogenic diet, especially in people who are vulnerable to it. So those are some of the medical assessments that I like to do on patients who are on a ketogenic diet.

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Metabolism and Ketogenic Diets

DrMR:

You were saying a moment ago that this is a shorter term. I believe it was four weeks. So can we see this kind of like a reset? That’s how I often look at fasting, but also lower-carb, as a way to help exercise some of that physiology – whether it be fasting physiology or just fat-burning physiology – and then that can be carried forward into a more balanced diet.

DrMR:

Just to refer back to a prior podcast with Mike T. Nelson, I’m not sure if he was the first one to describe this or if he’s quoting someone else, but he describes this as metabolic flexibility. Meaning, we should be able to train metabolism to thrive under different conditions. I’m curious if you are looking at this as a healthy, hormetic, reparative resetting intervention? One that then allows you to go into a more balanced diet with healthier metabolic machinery, if you will?

DrSG:

Exactly right. So the way I look at a ketogenic pulse is that it’s a four-week reset. For instance, I have patients who I describe in the book who have a fair amount of weight to lose. So one woman, for instance, ended up losing about 40 pounds over about a six month period. She did the four-week pulse. We tested her to make sure that it was a good fit. She then went to a more balanced diet, increasing her carbohydrates. During that time we were able to define what her carbohydrate threshold was, and this allowed her to improve her metabolic flexibility.

DrSG:

So I would say it’s all about metabolic flexibility. I really love that term. We can think about metabolism as being the sum total of all of the biochemical reactions in your body, including those related to your hormones that dictate how fast or slow you burn calories. We know that metabolic flexibility is that capacity to flip a switch between burning carbs or burning glucose versus burning fat and being able to flip back and forth; flip that switch depending on what’s available.

DrSG:

Most of us, for instance, have limited carbs available. We’ve got our glycogen stores. My husband loves to ride centuries; he does a hundred miles and more. He needs to be able to have that metabolic flexibility to burn his glycogen but, then to also go to his fat reserves. And some people, such as this woman who lost 40 pounds, became more carb intolerant. She did not have metabolic flexibility and she knew it because her insulin was elevated and her fasting glucose was elevated. She was able to use this four-week ketogenic pulse to start to unravel that and to create metabolic flexibility.

DrMR:

And what do you think is happening in those who see their metabolic markers deteriorate when they’re on keto for too long? This might not be something that’s been sussed out. The one hypothesis I’ve always kicked around in my head is that some people are just very efficient at the ketogenic metabolism, if you will. If they stay there, they end up paradoxically having blood sugar that creeps up even though they’re eating almost no glucose. Or they’re showing signs of metabolic excess even though they’re really restricting some of the metabolic fuel of carbohydrates. Or maybe this is a skewed response because it’s overly stressing the system. How are you interpreting that?

DrSG:

Yeah, it’s a good question. I would say from a research perspective, I don’t know that the mechanism is really clearly defined. As you’re describing, there are some people who go on a ketogenic diet and they paradoxically become more insulin-resistant. So why is that? Is it genomics interacting with the environment? Is it related to their microbiome? We don’t really know. I would say animal models are the best that we have at this point. But I definitely see that.

DrSG:

In the patients that I’ve seen over the past 25 or 30 years, what I know is that there are some people who are super responders to a ketogenic diet. This is even described in the epilepsy literature for which a ketogenic diet was first defined in the 1930s. There are some people who are able to get off of their epilepsy medications because they respond so well to a ketogenic diet. And then there are other people, and I put myself in this camp too, who need to do cyclic ketosis. They need to bounce back and forth to create that metabolic flexibility so that they’re not just stuck in nutritional ketosis 24/7, but they can flip back and forth as needed depending on what kind of fuel is available.

Length of Keto Diets

DrMR:

You’re noticing that women can’t be in keto for too long. We’ve established this concept. What else do you think women need to know? Are there guidelines for what they do after keto? Is this something that’s highly individual? Is there a standard range where most women do okay when their carbs clock in somewhere, I’m assuming, between 125 and 200 grams per day? Or is it not that simple?

DrSG:

It’s a good question. I remember when I was first studying nutrition and looking at women’s health and how many carbs do we really need. I remember there was this endocrinologist down in Santa Barbara, Diana Schwarzbein. Do you remember Diana?

DrMR:

Oh yeah. Yeah.

DrSG:

She used to talk about how women really need this minimal threshold of somewhere around 50 to 100 grams of carbs a day. And if women are not getting that level of carbohydrates, then there’s more thyroid and also adrenal dysfunction or HPA dysregulation. So I think that was maybe her opinion and also her empiric evidence that she came up with after seeing patients for a long time. I haven’t seen a lot of research on this particular topic.

DrSG:

But I think when you do keto too long, what I see is that the volume of stool dramatically decreases. Some people have constipation because they’re just not feeding those good microbes the way that they could be. I think it can also lead to some food stress. So we know that restricting carbohydrates, for instance, can lead to higher cortisol levels. Some of us can tolerate that pretty well. People who are quite resilient can go low-carb and extract a lot of the benefits and don’t really have these downstream consequences like issues with their thyroid, issues with their microbiome, or with HPA regulation. But then some of us just really need to be getting a threshold of carbohydrates that just helps keep things working the way that we want, especially with the gut, and how the gut talks to the control system for your hormones.

DrMR:

It totally maps on and fits with my clinical observation, which is some people are eating too restrictive. Sometimes it’s purely total carbohydrate load, sometimes it’s their following unnecessary restrictions. I’ve even poked fun on the podcast. I read about low-histamine, low FODMAP, low-oxide, low-salicylate. They’re doing all these things and then someone in a position of authority tells them to relax the diet a little bit and it’s like, wow, it opens up all this improvement for them very, very easily.

Overly-Restrictive Diets

DrMR:

It could be the carbs or the FODMAPs or both. Maybe the primary driver for some people, as I think you’re kind of intonating, is this psychological stressor where people just feel like they can’t do anything or go anywhere because they can’t eat food. I think it all boils down to this same sort of cadence, if you will, of a shorter intervention of being restrictive followed by a broadening. There’s almost this oscillation.

DrMR:

Some of this does map onto an ancestral principle which is food stuff availability changes as the seasons shift. So maybe some of this is just programmed into our DNA where planned change might be something that’s really healthy. Is that something that you would agree with or disagree with? Maybe it’s not that keto is the best and this moderate carb is the best, but maybe some change and therefore some exercising of that metabolic flexibility, is really perhaps a unifying principle that underlies all this?

DrSG:

This is why I love talking to you, Michael, because I feel like this is a very advanced concept and it’s what I’ve arrived at in my own medical practice. I think when I first met you I was on low-FODMAP and low-oxalates. I was eating like six or seven foods and I was no fun to be around.

DrMR:

I never said that.

DrSG:

You did not say that, but you and I couldn’t meet at a restaurant. Let me put it that way. My life was so restrictive and I feel like people with the best intentions end up becoming these professional patients and really restricting their food plan in a way that doesn’t serve them. If we look at some of the data of Rob Knight at the University of California, San Diego — What he tells us from the human gut project is that the more food diversity you have, especially with fruits and vegetables, (ideally somewhere around 25 to 35 species per week), that’s associated with the greatest diversity and the healthiest microbiome. So it’s very hard to do that on a classic ketogenic diet, but often when you provide that kind of food diversity, it really gets people to perk up. I think the connection to hormones is a little bit more speculative, but in terms of what we know with diversity and with just the level of dysbiosis, we think that species diversity is really important.

DrMR:

Yes. Another concept I am predicting people listening to this are saying to themselves is, “Oh my goodness. Maybe I should either stop fasting or stop my low-FODMAP protocol.” Firstly, remember that there’s this shorter-term intervention followed by broadening. So just because we’re pointing to the fact that a broader diet long-term is better doesn’t mean that if you’re still on your journey of healing, you should throw all that out. So don’t forget that. I’m not saying that you’re insinuating that, Sara. I’m just trying to contextualize for people.

DrMR:

The other thing of this hopeful, underlying theme that we’re agreeing on is change. I think of when David Jockers was on the podcast and he referenced some of the literature that found increased mucus production, and I believe it was Akkermansia muciniphila, was actually facilitated by fasting. Again, if you fast too much, you’re likely going to hit some problems with too many hermetic stressors. So this planned change where we can have these periods of perhaps lower-carb or fasting are going to give us healthy stress. Then, if we shift out of that, we unload and we can recover. This push and pull – or oscillation – seems to be the best.

DrMR:

Maybe using exercise is just one more way of trying to paint this scenario. A degree of exercise is health-promoting, but too much can lead to osteoporosis, chronic joint pain, problems with sleep, and increased risk of upper respiratory tract infections. So I’ll just offer that for people. Don’t latch onto one thing as the best thing and just lock into that and stay there. I think this theme hopefully that’s emerging is some planned change and oscillation over time.

DrSG:

Yeah, I totally love that. I’m looking for ways that I could disagree with you because I think that makes for a better podcast, but I’m having trouble. I’ll have to go back and listen to your podcast with David Jockers. I agree that Akkermansia is one of the most important keystone species in the gut. We know that it’s involved in helping to repair the gut lining. We also know that it plays a key role in the glucose insulin pathways. That’s something that I do a lot of clinical research on so I have tremendous interest in that.

DrSG:

I remember I had a course of antibiotics in 2017 and I tested my gut before and after this course of antibiotics. Akkermansia were just gone after this course of antibiotics. One of the ways that you can feed Akkermansia is through fasting. Akkermansia love cranberries and pomegranates. At this time – this was right around the time that I met you – I don’t think I had had a pomegranate or a cranberry for years. It’s just an example of what you’re describing – oscillation.

Interoception – Listening to Yourself

DrSG:

I do think that the more gray hair that I have and the more that I see patients, I think about this idea of pulsing and really getting a sense of what fits with your body. Never mind what is right for your friend that’s talking to you about what they’re doing for their gut or thyroid or weight loss. What’s true for you? One of the things that I’ve been paying attention to is this concept of really tuning into what’s true for you. It is called interoception and I kind of suck at it. I think just from going through medical training, you just learn to ignore the messages from your body. You just can’t pee and go to the bathroom when you should or sleep when you should, so you just learn to tune out that interoception.

DrSG:

I remember at the time I was fasting. I was doing like a 16/8 protocol with an eight hour eating window, even going to 18/6 with a six-hour eating window. I started wearing a Garmin and I noticed that I had really high stress levels when I would do these 18 hour fasts. It was just too much cortisol running through my system and so I had to back off. What I learned was that a 14 hour overnight fast is a much better fit for me. It doesn’t stress my matrix out as much as those longer fasts. That’s the kind of data that I hope our listeners can start to pay attention to and collect. I think that kind of personalization really can make a difference.

DrMR:

One hundred percent in agreement with you. There are many options on offer. I think one of the primary utilities that a clinician provides to a patient is just helping them to navigate those options and helping them listen to their body and be okay with what they get. Sometimes patients feel almost guilty. I’m not sure if you’ve seen this, Sara. Let’s say they come from a community – maybe they’re a CrossFitter and their husband is die-hard keto. We then together help her discover she feels better on a moderate carb approach. She almost feels guilty because it cuts against so much of the cultural norms, if you will. But that’s what I think a good clinician should help someone discover.

DrMR:

We’re getting a fairly clear biofeedback signal that this is what’s right for you. Even though there are evidence points that show a low-carb diet can be helpful for various conditions, it doesn’t mean that it’s best for everyone everywhere all the time and in perpetuity.

DrSG:

Yeah, totally right. What you just described is something that I have seen hundreds of times in my practice where people have carb fear. They have fear of taking carbohydrates. The truth is that the data we have on the ketogenic diet is pretty limited. If you look at the best evidence that we have, it’s with the Mediterranean diet. That’s really the archetype of the most proven diet that we have. The way that I like to work with patients is just to assume a Mediterranean diet that we can adjust up and down – maybe a lower carb version of it after I’m taking a patient off of a ketogenic diet.

N of 1 Experiments

DrSG:

The tool that I use in precision medicine is the N of 1 experiment where each person serves as their own control. I was taught at Harvard medical school that the N of 1 experiment is the best quality of evidence that you can possibly get. It’s even superior to a randomized trial because so much of the work that you and I do, Michael, is this kind of complex, lifestyle-diet-supplement-medication management. It’s very rare that you’re just having one intervention, like let’s give Metformin to you and not change anything else. Usually we’re changing diet, we’re adjusting these other things. Maybe we’re addressing some hormonal imbalances. In that situation with this complex intervention, N of 1 experiments can be so helpful.

DrMR:

I think that’s another way of saying personalized medicine. I would add to that we can have a framework of a series of N of 1 experiments that we run to personalize the available therapeutics to an individual. Do we start with someone with some mild GI symptomatology? Do we go right to Rifaximin or Alinia or a two-week course of an elemental diet? Maybe we start with something more general like a run-of-the-mill elimination diet and then reevaluate. Perhaps step two is another N of 1 experiment – this time with a low FODMAP diet. We’re working our way toward these interventions that are either more expensive or higher risk like antibiotics, but we’re using the evidence base to help guide us through how to run these N of 1 experiments for the individual.

DrSG:

That’s exactly right. I think this brings us back to the Mediterranean diet and just the bulk of data that we have. I had a patient today who has a family history of Alzheimer’s disease. She was embarrassed to admit to me that she felt like she had failed at a ketogenic diet. She was so motivated after reading Dale Bredesen’s book to go on a ketogenic diet and felt like that was so important for preventing the risk of Alzheimer’s disease. The truth is when it comes to cognitive health, we’ve got so much more data on a Mediterranean diet. I consider that archetype to be the place from which we then make these changes in an N of 1 framework such as you described with an elimination diet. I gained weight on a traditional Mediterranean diet, so I have to do a more low-carb version, but it’s not strictly low-carb.

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Hi everyone, just a few fairly important updates. I’ve been working diligently behind the scenes tweaking and updating our paperwork, our clinical systems, our treatments, our data gathering, data organization, reporting, and patient monitoring. I’ve refined the algorithm to be even better than it was before. How confident am I in our clinical team? Well, my mother is working with our health coach and my father just started working with one of our doctors. So about as confident as you can get. Collectively, we are moving towards our goal of reforming functional medicine. We are gathering data on our patients and working toward publishing our data. We have taken big steps in this direction. So, you are part of something big here. You’re not only a patient we aim to serve and help, but also as one of our patients, you become an example of how people can improve their health in less time and for less money compared to what appears to be commonplace in the functional medicine field. So, I encourage you to look forward not only to potentially working with me, but also with any of our tremendously skilled, attentive, and empathetic clinicians. Thank you for being a part of it or thank you for waiting to be a part of it if you’re about to be seen soon. If you have not yet reached out and you’re in need of help, we would be pleased and honored to work with you.

Thyroid Hormones

DrMR:

Circling back to the low-carb concept, I’m curious to get your thoughts on this. When someone is doing the appropriate application of a low-carb diet and seeing whatever improvements they’re experiencing – oftentimes weight loss, reduced cravings, improved sleep, improved energy – you may see a skewing of thyroid hormones. The patient’s reverse T3 may go up a little bit, their free T3 may go down a little bit, but that’s occurring in the context of someone clearly getting healthier.

DrMR:

I interpret that as a healthy metabolic stressor and stressors will skew hormones. It doesn’t mean that this is primarily any damage to the thyroid hormone. I’m glad you made the comment earlier that what you’d see would be secondary, not primary. Also, as long as this healthy stress load isn’t left for too long, then we should be able to unload you or bring you to a more balanced diet and reap all of the rewards with little or no repercussions. Tell us a little bit more about how you’re thinking about thyroid hormones skewing short-term, long-term. Is it relevant? What do you do about it?

DrSG:

Great question. I feel like so many people go on a low-carb diet and they just assume that the reason why it’s working and the reason why it helps them with fat loss is related to lower insulin levels and increased fat burning. That certainly happens for a lot of people, but there are a lot of other steps along the way. You described with the skewing with reverse T3 and free T3 and even conversion. I think that in many ways is just another example of hormesis and it’s not something that you have to jump on or treat. I think it can be helpful to look at if there’s some food stress here. Are you getting sufficient carbohydrates to be detoxifying, to be pooping every morning, to feel like you’re completely evacuating? I think we also want to look at some of the other measures, not just laboratory values, but symptoms of thyroid dysfunction as you described.

DrSG:

The thing that is so tricky with women who are affected much more by thyropause and thyroid changes is that it’s often in the context of a woman who’s over age 35 or 40. These women have changes happening with progesterone, estrogen, testosterone, and DHEA. There’s an overlap with a lot of these symptoms. I don’t get too excited when I see a free T3 that’s gone down a little bit or a reverse T3 that’s gone up on a low-carb diet. I think sometimes that can just be a call for finishing this four week pulse of a ketogenic diet. Then, let’s bring some more carbs in. More often than not, it resolves that skewing issue that you described with T3.

DrMR:

Great point. I’m also glad you reminded our audience that what you’ll see in women as they get into their late 30s or 40s potentially is some of these female hormone imbalances manifesting. They can look similar to thyroid hormone imbalances. I just want to again sound the alarm bell for our audience that it’s becoming increasingly disturbing how often people are being forced into this hypothyroid diagnosis without anywhere near ample laboratory evidence to make that diagnosis and put on thyroid hormones.

DrMR:

Sara, you and I were discussing this recent meta-analysis that piggybacks on the Livadas paper that was published in the journal Thyroid in 2018. This article found that 60% of patients with an ambiguous thyroid diagnosis were able to stop thyroid hormone and remain normal thyroid. This meta-analysis of 17 studies and 1,100 patients found that 34% of people could stop thyroid hormone and remain normal thyroid afterwards.

DrMR:

So that’s just one data point to put out there that you may have about a one in three chance of being misdiagnosed. Now be careful and don’t just take yourself off thyroid hormone. Follow up with your doctor. If you feel like your doctor is a bit dogmatic, get a second opinion. Don’t just stop something willy nilly, but be armed with that knowledge that there could be as much as a one in three chance that there’s been a misdiagnosis. Perhaps this was something that was being done or should have been done in a short-term trial application and your doctor didn’t really explain that very well. Maybe to put a little bit of onus on the patient, maybe you didn’t listen very well and forgot about it. Whatever the rationale or the reasoning is, there’s that potential one in three chance.

DrMR:

I think it’s important to say that it’s not to suggest there is no cause of your symptoms. I don’t want to just say, “Well, it’s not thyroid and it’s all in your head.” There’s definitely a subset of people for whom there are these female hormone imbalances that are really the driver of the symptoms. Sara, I think if anyone is dealing with that clinically here the most, it’s definitely you, obviously, because of all your background there. What else should women know in terms of these female hormone driving symptoms that look similar to thyroid hormone imbalances?

DrSG:

This is a really good point. I haven’t read the meta-analysis. I’ve got to look it up because it sounds super interesting. That fits with what I see clinically. I would say with probably about a third of the patients that come to me that are taking thyroid medication, I’m asking them, “Okay, why did you get started on this medication?” They have a TSH of like 2.5 or they have a slightly low total T3 or a slightly low free T3. I think the problem is more conversion and maybe some genomic drivers like DIO2 and not that they should be started on thyroid medication. Then it ends up being like a game of telephone where the patient then tells every future doctor “I’ve got hypothyroidism and this is my medication.” I think with root cause analysis, we always have to ask, “Ok, what’s the reason?”

DrMR:

Great reminder for the clinicians listening to this. Start checking and verifying the diagnosis of patients because you will probably be shocked. Just like you said Sara – a very good analogy of telephone. The diagnosis was vectored four years ago and they’ve changed doctors a few times. It’s almost like the more doctors they change, the more you’re thinking it’s a legit diagnosis because it’s a diagnosis that’s been in the chart longer. I think it’s a good reminder for all of us to be re-checking this.

DrSG:

Yeah, really important. So many things that I think we could say about that. Going back to root cause analysis, I like to look at the age of a woman, the context, and how much stress they’re managing. I do look at levels. I look at serum levels because I work in an academic medical center and it’s the universal language of communication about hormones. I also really like to do dried urine testing. I do cortisol awakening response to look at what’s happening with the HPA. What we know is that there’s so much interdependence between these hormone systems.

DrSG:

Estrogen, progesterone, and testosterone are intimately related to your cortisol levels. If you just look at estrogen, progesterone, and testosterone, but don’t look at cortisol, you’re going to miss the fuller story. Same thing with thyroid. I think you have to look at all of these in context; look at these hormones as this bigger family and you want to manage the family. You don’t want to just manage one person in the family. You want to get the whole family dynamic working again.

Cortisol Testing

DrMR:

What are your thoughts on testing cortisol? This is something I’ve admittedly been critical of. I was questioning how helpful these tests were in practice maybe five years ago now. I’ve since stopped using them. A few years ago, there was that systematic review with meta-analysis that found over 50% of the time, the adrenal tests didn’t really correlate with the peer-reviewed fatigue questionnaires that these researchers were issuing. There was a various array of different adrenal tests that were included in this meta-analysis. I think there were 55 studies, perhaps. There’s a couple of newer tests that are purported to be better. I’m wondering how you’re using the adrenal test, what tests you’re using, and what you would say in response to some of the criticisms of cortisol testing.

DrSG:

I think the criticisms are valid. I remember a paper a couple of years ago published about how adrenal fatigue does not exist – like it’s not a diagnosis. I agree with that. I think in some ways alternative medicine, functional medicine, has maybe shot us in the foot in terms of some of the testing that’s been done and what has been done based on that. I see a lot of patients with autoimmune disease and I do find that looking at a diurnal cortisol pattern and a cortisol awakening response is helpful in that context. We know that the greatest immunological activity occurs in people who have a flat diurnal pattern. I think a flat diurnal pattern is very helpful. I don’t think a one-off blood test at eight o’clock in the morning with your cortisol is that helpful.

DrSG:

What you’re describing with the systematic review makes sense to me and it fits with some of what I’ve seen. The patients that I’m dealing with are of a certain ilk. For instance, I had a patient today who’s got multiple sclerosis, celiac, and also Hashimoto’s, so measuring her cortisol levels is very helpful. She takes these treatments for her MS that include high-dose steroids. Understanding what kind of HPA regulation she has is very helpful.

DrSG:

I spent probably my first 10 to 15 years in practice chasing after these salivary cortisol tests and trying every adaptation under the sun. I felt like “God, am I really helping these patients? I’m not sure I am.” Occasionally you’ll get a patient who says, “Oh ashwagandha changed my life.” For the most part, I just wonder if I’m just making the urine more expensive. For me, looking at the control system for your hormones and understanding at least the cortisol levels in the cortisol awakening response as well as the diurnal cortisol – I find that to be helpful. Not in all patients, but in some patients.

DrMR:

There was a gentleman – I want to say his name may have been Thomas Myers – although I may be totally mis-recalling his name. He did a review that did seem to substantiate that the cortisol awakening response was the most accurate way of measuring cortisol. From what I’ve seen, that is agreed upon. I didn’t know the diurnal rhythm was a window into immune system health. What does that tie in?

DrSG:

Well, it tells you about hypothalamic pituitary adrenal access regulation. So for people who have a flat pattern, I generally feel like those are the people that I’m more likely to see with mood issues, anxiety, and autoimmune conditions. We also know from a study that was done at Stanford that women with breast cancer who have a flat diurnal pattern have lower survival. So, I’m a fan of trying to recreate the type of circadian rhythm that our bodies are meant to have. When you lose that circadian rhythm, such as with a flat diurnal pattern, that’s one thing that I think we can address. I that’s the way I hold cortisol testing.

DrSG:

The other place where I think it can be helpful is with the test that I do I like to measure a total cortisol load. That tells me a lot about a patient’s perceived stress. I’ll use my husband again as an example here because he’s my favorite athlete. He deals with a lot of stress and he just rolls with the punches. He’s so good at it. We both wear Garmins. His Garmin is always better than mine. His stress level is always barely measurable and his body battery that Garmin provides is always really high. He’s just a very stress resilient person. I don’t have many people like him in my practice other than some NBA players. These folks that come to see me that are peri-menopausal women who are trying to lose weight or are struggling with one thing or another related to their hormones are often the people who do have dysregulation of the control system.

DrSG:

I keep talking about the HPA. I think a better way to think of it is this larger envelope – this larger umbrella of the hypothalamic pituitary adrenal thyroid gonadal gut access. That’s really the control system that we’re interested in; trying to tune it with hormesis and with some of these other methods that we’re talking about so that people really have that feeling of vibrant health.

Lifestyle Adjustments

DrMR:

That was my follow-up question. Let’s say you see an inversion or a flattening of the cortisol rhythm. Some will say, “You need pregnenolone and DHEA in the morning and you need phosphatidylserine at night.” I think that’s just a good example of what natural and integrative medicine should not be, which is treating the labs. What I’m hoping you’re going to say is let’s look at someone’s bedtime, when they’re getting outside, their exposure to the sun, their total level of stress, and really trying to just get their life into a better order so that the rhythm can rectify itself — rather than looking at supplements as being the primary way of changing the rhythm.

DrSG:

I appreciate you leading the witness, but the truth is that’s what I like to do. I would say I was more heavy-handed with the supplements that you mentioned like pregnenolone, phosphatidylserine, adaptogens, and DHEA in the past.

DrMR:

As was I, admittedly.

DrSG:

I was really underwhelmed with the effect long-term. I had a patient last week who had a flat pattern and she’s someone who’s figured out that she’s got to exercise every morning within 30 minutes of waking up in order to feel human; to feel like she’s got the cortisol to meet the day. I would say that is one of the best interventions that you can have.

DrSG:

We know that she happens to like to spin. She’s got a Peloton. Doing power zone training and the exercises that she’s doing in the morning is a really good way for her to raise her cortisol in the morning and get that diurnal pattern. What we also talked about was if it was possible for her to do some sort of meditation before climbing into bed that didn’t involve a glass of red wine – because that also raises cortisol. So, I think these lifestyle interventions can be very powerful. I prefer reaching for those before supplements.

Sleep Adjustments

DrMR:

Yes. That’s so well said. This reminds me of something that I’ve learned and experienced my way through over maybe the past year. If I exercise too late, I sauna too late, I eat too late, and then I either go to bed too late or I eat too close to bedtime. The main metric I’m using to track this is my Oura Ring. What I would notice is that I’d be a C- sleep score most of the time. There was a correlation between my sleep score and subjective well-being or energy the next day. So over time, I’m assuming I learned how to get the best cortisol output or rhythm, if you will.

DrMR:

Now I wasn’t testing it, but I’m assuming if I had been doing serial cortisol testing – paralleling your patient case study from a moment ago – I would have seen that when I exercise too late, sauna too late, and eat too late, my sleep is deterred or my sleep quality is sacrificed to some extent. That then manifests the next day by not having the optimum output of stress hormones. I feel that subjectively, as when it is where it should be, I have consistent focus, energy, and none of those lulls where I’m reaching for coffee or I find myself mindlessly scrolling on Facebook because I can’t focus. When I’m doing all those things right, I’m just sharp and focused the entire day.

DrSG:

Amen brother. I think that’s a beautiful example of an N of 1 experiment. I think you really learned what’s the timing of exercise, and then you have this cascade of events with the sauna too late, eating too late, and then a C- on your sleep score. Through a similar process, I went through with my Oura Ring and figured out that I really do best when I exercise in the morning. It helps me with my dopamine issues. It helps me with focus throughout the day. I feel like the glass is half full. My mood is better and my deep sleep is longer.

DrSG:

I know for me I need two hours plus of deep sleep every night for my gut to really function at its best. I want to architect the day to make that happen. It’s all about the sleep. Sleep is as close to a panacea as we have. And heart rate variability. I think that’s another thing that Oura does so well. You said you weren’t looking at your cortisol levels, but I think in some ways HRV is a really good measure or proxy of your stress load.

DrMR:

I agree. I’ll do the Oura Ring every morning and then I’ll do a chest strap HRV and use the app ithlete to track that. Thank you and credit to Mike T. Nelson for getting me on that. I do notice that what seems to track most closely with how I feel is the HRV. The sleep data is also helpful, but I think you get a more complete how stressed or unstressed is my body picture from the HRV. I think they can be used together to give you the best complete picture. There are some times when my sleep won’t be that good and I want to see that register on my Oura data, but I’ll be able to buffer that stress and it won’t really hit my HRV unless maybe that sleep disruption continues for two or three nights consecutively. I think together they really give you the most complete picture.

DrSG:

I agree with that. I was in Carmel last week and my sleep wasn’t great because I was staying with a friend of mine. But I was walking on the beach every single morning for an hour and walking in the waves and my HRV was fantastic. That’s an example of being able to make up for sleep issues. As you said, you don’t want that to be prolonged and to build up a sleep debt, but there are other ways that we can manage lifestyle and architect lifestyle so that we can make up for some of those deficits.

DrMR:

This is why I’m so excited about some of the work that we’re just kind of foraying into at the clinic. We’re running these home sleep tests that essentially look for sleep disordered breathing, apnea, upper airway resistance syndrome, and we’re using that to refer people either for myofunctional therapy or perhaps mandibular advancement devices.

DrMR:

As I’ve examined this body of literature progressively, there is some pretty impressive data out there. For example, a meta-analysis showing that myofunctional therapy, which essentially is like physical therapy for the mouth and tongue, can reduce 50% of cases of apnea. Other data has shown that mandibular advancement devices – just a mouth guard you wear while you sleep – is as effective as a C-PAP. So it’s really exciting.

DrMR:

It’s early, so I want to bridle my enthusiasm and not make too much of a promise to our audience because I haven’t seen the patients who we’ve referred for these things post yet. Of course the myofunctional therapy will be four to six weeks, and then from there, sleep quality improves and that’ll take at least a few weeks to manifest. So we’re early on in that process. To your earlier comment about sleep being the most important factor – the king or the queen – that’s what’s so exciting about the work that we’re doing.

DrMR:

I have a suspicion that there are some people out there who are having to live such a perfect lifestyle because their baseline sleep isn’t where it should be due to some oral airway resistance issue. I’m really hopeful at the prospect of being able to open up improvements for these people who are doing everything right, but they still have fatigue, brain fog, and daytime sleepiness It’s early to report on that yet, but I’m very excited with the potential that may hold.

DrSG:

I’m thrilled that you’re doing that. I might have to come to your clinic in Austin and get tested. Are you doing O2 SAT at night with the home testing?

DrMR:

Yeah, we’re using the WatchPAT ONE by Itamar. It’s essentially a pulse oximeter and a watch device that gives you positions and a chest microphone sensor that will detect snoring sounds. What’s really novel about this is you’ll get snoring sounds and the incidents of respiratory distress events total, but also positionally. This can be really helpful, especially to know if someone’s a chronic back sleeper. You then see from the data that they’re having 70% of their apneic events while sleeping on their back. There are things that you can do. Firstly, just disclosing to them that they can sleep more on their side. There are even these little magnet-like ball devices that you can put on the upper back of your shirt that discourage you from sleeping on your back. So some of these things are actually really simple and low-cost, but yeah, we’re using a pulse-oximeter oxygen saturation device called the WatchPAT ONE.

DrMR:

What’s nice about this is it’s a take home, disposable test and it costs about $200 to run one of these data points. So it’s not a big deal, and it’s certainly much easier than going to a sleep clinic and doing an overnight study, which is usually going to cost about $700 if not more. I haven’t heard good things about people trying to go through insurance on that. It seems like people have to be really fairly severe in terms of their symptoms to get insurance coverage on that. So that’s one whole battle with the insurance company we can save people by using these at home tests.

DrSG:

I love it. Sign me up. I feel like for a lot of the folks that are drawn to keto, they’re struggling with fat deposition. They want to do something about visceral fat which maybe they’ve noticed is increasing. I feel like sleep apnea and disrupted sleep is such a major cause of increased visceral fat and just that downstream metabolic badness that we want to avoid.

DrMR:

One hundred percent. That’s one of the reasons why I’m so excited about this.

RuscioResources:

Hi everyone, this is Dr. Ruscio. In case you need help, I wanted to quickly make you aware of what resources are available to you. If you go to DrRuscio.com/resources, you will see a few links you can click through for more. Firstly, there is the clinic, which I’m immensely proud of the fact that we deliver cost-effective, simple, but highly-efficacious functional medicine. There’s also my book, Healthy Gut, Healthy You, which has been proven to allow those who’ve been unable to improve their health, even after seeing numerous doctors, to be able to help them finally feel better. There’s also our store where there’s a number of products like our Elemental Heal line, our Probiotic line, and other gut-supportive and health-supportive supplements. We also now offer health coaching. So, if you’ve read the book or listened to a podcast like this one, or are reading about a product and you need some help with how or when to use or how to integrate with diet, we now offer health coaching to help you along your way. Finally, if you’re a clinician, there is our clinician’s newsletter – The Future of Functional Medicine Review. I’m very proud to say we’ve now had doctors who’ve read that newsletter find challenging cases in their practices, apply what we teach in the newsletter, and be able to help these patients who were otherwise considered challenging cases. Everything for these resources can be accessed through DrRuscio.com/resources. Alrighty, back to the show.

DrMR:

I think we should do another podcast and talk about genetics for performance and continuous glucose monitoring because I made a note about both of those. I feel like that’s a good 45 minutes right there and I don’t want to shortchange those. So why don’t we plan on doing a part two and just squarely tackling those? Actually what we can do, since I’m in California for the summer and we are neighbors, I had this fun mobile setup where we can go to a coffee shop somewhere and actually do another one in person.

DrSG:

I’d love it. Sign me up. Sign me up for all of it, Michael.

DrMR:

I really want to actually selfishly pick your brain on the performance bit because that’s something I’m trying to goose my performance as much as I can.

DrSG:

Well your performance is already at a high level, but happy to help in any way I can.

Episode Wrap-Up

DrMR:

I need all the help I can get. Tell people where they can track you down online and then again about your book please.

DrSG:

Sure. So the book is Women, Food, and Hormones. You can pre-order it now. It comes out September 21st. You can get it anywhere books are sold – Amazon, Barnes & Noble, etc. To learn more about the work that I do, the mothership is saragottfriedmd.com.

DrMR:

Awesome. Well, Sara, thank you for coming on the show again. And folks, there’ll be a follow-up really soon for you on genetics, continuous glucose monitoring, and I will again selfishly be picking your brain on that topic. For the women out there, Sara and I obviously have a lot of similarities in how we think in terms of being pragmatic, evidence-based, putting patients first, and not getting caught up in the dogma. So I just want to make sure if it isn’t obvious yet that I really appreciate her work and would highly recommend checking out her book.

DrSG:

Thank you. Michael, it was so fun to be with you. I always learn so much.

DrMR:

Always a pleasure. Thank you.

Outro:

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