Keto for Women: Insights on Hormones, PCOS, Menopause, and more from the SHE IS Lab with Dr. Madison Kackley

Madison: 
But really those who have tried it, even from not being in our studies, just listening to us talk on our pedestal, they do come back and say that was the best diet they’ve ever had, a best lifestyle change that they’ve had. And they feel so much better, especially women in either perimenopause or menopause.

Bret: 
Welcome to the Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a non-profit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only and we aren’t giving medical advice, we hope you will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health.

Dr. Madison Kackley, a research scientist at the Ohio State University, is specifically studying ketogenic interventions in women. Why? Because women aren’t the same as everybody else, right? They’re not the same as men. We shouldn’t expect that whatever intervention we have for men is going to work for women.

There are different hormones, different cycle changes. So, she and her lab at the SHE IS Lab at Ohio State are specifically studying what is unique about women, and what can we learn from that and what is that change in terms of using ketogenic interventions. So here’s the interview with Madison Kackley.

All right. Dr. Madison Kackley, thank you so much for joining me today at Metabolic Mind. 

Madison: 
Bret, thanks for having me. Excited to be here. 

Bret: 
Yeah. It’s my pleasure to have you here. And as we were talking offline, we just, we don’t talk enough about ketosis in women and what’s different about it and what we need to consider.

And I think that’s what’s a great thing that we can talk about here today. But first, tell us a little bit about you and tell us what the SHE IS Lab is and why we’re here. 

Madison: 
Yeah, absolutely. So I have, I think everybody on this channel can, is a fan, but I have worked very closely with Dr. Jeff Volek for I think we’re going on eight years now.

And I was actually his grad students, and one of his grad students, and then a research scientist now. And one of the studies that we did pre-COVID was a weight loss study where we worked with Metagenics. They were a ketone supplement company, a pharmaceutical ketone supplement company, and they used ketone salts.

So it was a weight loss study. And, we had, I would think, seven papers out of that now and still some still pending. But one of the interesting facts that we had, it was just an anecdotal question for the women who were in the study, did your menstrual cycle change? And so after getting five of these publications out, I was interested just to see, as we’re going through the survey questions, that so many of these women actually had a menstrual cycle change.

There was a few of them that actually hadn’t had a cycle in almost over a year, and they were pretty perturbed about it, although we are now seeing how healthy that is, they were pretty perturbed about it. But they were, they’re very confused, and that was actually pretty insightful for us. It wasn’t something that we were originally looking into. Again, it’s just one of the run of the mill questions that we asked in terms of how the diet’s going. And so then, we decided to do a little bit of background of just looking at the women.

When we saw that there was a significant change in the women who were on the ketogenic diets versus the low fat diet, everybody was hypocaloric so everybody lost weight. And essentially when somebody gains their menses back, we’re going to usually attribute it to weight loss. But we had three different groups and only the ketogenic diet groups were the only ones to see the menstrual change.

So, when that happened, like there has to be more to this. I also have a personal background. My sister has PCOS and trying to look into things that were useful for her, the background obviously shows there’s so much targeted towards or influenced by insulin sensitivity, insulin resistance.

And so this challenge just defined all of the science that we had done before, but targeted towards women, we really needed to step up our game. So even though we’ve scratched the surface on quite a bit of ketogenic interventions, women derivatives, that’s pretty new to the game. So the SHE IS Lab essentially started.

On one of our first studies was not looking necessarily at ketogenic interventions, but just finding trackers essentially that would follow women over their cycle and which ones were the most applicable to different hormones. And that would give us the, basically the consensus of which non-invasive tracker we would use.

It would be great to do studies on women and bring them in for blood draws every single time, but we know that can be a little aggressive for women who are just trying to find answers. So, we started with the non-intervention study. And now we’re opening up to all of our interventions now that we’ve used so many cycle trackers to pinpoint which ones would be the most useful.

Bret: 
Yeah, and I’m so glad you mentioned Dr. Jeff Volek. We’re a big fan of his here. We’ve had him on the channel a number of times, and he’s doing his research study at Ohio State on ketogenic interventions for college age students with depression. So, you can see how when you’re dealing with a population that has their menses on a regular basis, you can’t just treat the men and the women the same.

You have to treat them differently depending on what’s happening in their cycle. So, I’m curious to ask him when I get to talk to him more about that study if he saw a difference. But I’m sure that speaks to exactly what you are doing. And so you’re talking about how women can regain their cycle, but also how everything else is impacting their health.

How the ketogenic diet impacts their health in so many other ways, depending on where they are in their cycle. So have you seen changes with that as well? I know maybe you haven’t studied it specifically, but anecdotally, have you seen changes about how it impacts people in other ways? 

Madison: 
Yeah, actually, because of, because of that finding. It started with the menses because it’s the most obvious and most potent change. But then we have branched out to specific studies in postpartum depression. Just looking at mental health in general and women that across the phases, even in the study that we’re looking at now that doesn’t actually have a intervention associated with it.

We do take surveys during each phase of their cycle. So, we have found quite a few interesting markers that have popped up. And again, we’ve just started these studies the last two years so we don’t have necessarily enough to validate anything, but that’s essentially why we’re doing it.

These studies are ongoing. So, we have a study that is in postpartum depression. A study looking into perimenopause. Obviously, the study looking into PCOS. We’re also looking at the correlation between polycystic kidney disease and PCOS because women who have polycystic kidney disease tend to have quite a bit of hormonal issues, hormonal imbalances. And honestly, their physicians and we’re working one, she’s very lovely, Rima Kang, who is actually seeing these things, but they aren’t getting noticed by other physicians.

So, essentially, we’re utilizing this SHE IS Laboratory to add this insight and add this perspective to their typical care or what would be standard of care. 

Bret: 
Yeah, I think that’s fantastic. I love how you’re expanding, and studying so many different aspects of how this makes a difference and how we have to think of it differently now.

To go back to the menstrual cycle for a second though, I think we can look at this in two different ways, right? If somebody has obesity or has PCOS and they have irregular menses, and then they go on a ketogenic diet, we often hear, and there are studies showing that they can improve their menstrual cycle or resume their menstrual cycle.

But on the other hand, if somebody, we hear these reports all the time in on social media or whatever, keto wrecked my hormones and keto destroyed my menstrual cycle and wrecked my hormones. So, I think we, we’ve heard it from both sides of the equation.

So, I’m curious how you make sense of that one intervention has been reported to have differing results basically. 

Madison: 
it’s going to be very dependent on when they’re actually checking their hormones as well, and that’s why women’s research is so hard.

One of the studies that we have has some coming in every week for their phase because what hormones that you see in your follicular phase are going to be different than what you’re seeing in your luteal phase and vice versa. And so if there is an ebb and a flow to their hormones, and they’re saying that the intervention itself is wrecking it, they may not actually be hitting it at the correct time or checking it at the correct time.

This is where we look at, we don’t just look at the hormone panel, but we’ll have metabolic lipid panels as well, which it’s a typical routine in our lab to measure those. So, we’re looking at the full picture where we don’t want to be, have reductionist view of the menstrual cycle because it is so complex that it is very hard to follow.

So, ideally, and I think that’s why these studies are going so slow, is because we have to put all of the information in at once. But for the naysayers, essentially, especially since I have been a mentee of Jeff Volek for so long, I know what it takes to have a very well-formulated ketogenic diet.

If you’re following the fad of the keto diet that is online, finding Google and not necessarily looking at the specialist in the area, then you’re going to have some not great information in regards to a ketogenic diet. They’re not going to pay attention to micronutrients. They’re not going to pay attention to minerals and all of these other things that may be a cause for why they’re seeing this random change in their hormones.

What we do at our lab, it’s very individualized. I think Jeff had said this when they were, when he was talking with you about the the KIND study, but it’s very individualized. We have dieticians on deck, specifically Teryn Bedell who has been wonderful. She obviously works integrated into the SHE IS Lab, but has been Jeff’s main research dietician for 10 years, I think, she’s going on.

She’s very meticulous about what we’re looking for. If we see a plummet in ketones or if we see that somebody isn’t feeling well with PHQ-9, we’re going to check in and see what they’ve been eating for the last couple days so we can prioritize what nutrients they would be needing or they’re missing.

Sometimes it’s just sleep. And especially in regards to mental health, you have too much stress in your life, that throws off your cycle as well. So are they starting an intervention at a time that’s probably the inopportune to see regulated hormones? There’s a whole bunch of things that go into play.

Bret: 
Yeah, that’s such an important perspective because the intervention might be the ketogenic diet, but first, as you’re, as you referenced, there’s not just one ketogenic diet. So, as Dr. Volek says, a ketogenic diet because are they getting enough calories, are they getting enough fat? And like you said, the micronutrients, are they getting enough micronutrients?

Any of those factors could impact menses and hormones and how you’re sleeping and how you’re feeling. All those get rolled into it. So, it might not be the state of ketosis. But interestingly, when we talk about interventions for mental health, it appears the key is, what are the ketones?

How high can you get the ketones? Can you get them in that 2 range? Emerging evidence is coming out, but that’s where the direction seems to be. But we can’t ignore all the other factors of the well-formulated diet, the micronutrients, getting enough calories and what else is going on with your life.

Do you try to control for those things? Do you advise people about sleep hygiene and about physical activity and about the type of foods to eat? You get to that level of discussion when you’re teaching them in the beginning about a ketogenic diet? 

Madison: 
Yeah, their dietary consult in the beginning of each of our dietary interventions, and we’ll talk about supplements here in a second because we’ve been brushing into that as well, but their dietary consults are about an hour to an hour and a half long just due to the intricacies in what we walk through with them.

We have tried adapting this, providing them with food for the first two weeks before we actually let them free rein and figure out the diet, essentially on their own but with lots of education.

And there are so many barriers out in the world, essentially that are, that could pseudo villainize the ketogenic diet. So, they need that support system from us as well. So, it’s a continual conversation back and forth. We had a participant once who had familial issues on a, somebody who had read something online that said that keto was bad for them.

And so they were concerned about the guy. And basically talking to them off of that cliff was actually pretty easy. It was a person who was very excited about the diet. but this won’t stop. This will be a continual battle until we basically change some of these dietary guidelines and get some of this information out there.

I did want to loop back into supplements though. And for those who maybe aren’t interested or don’t have the capacity to change into a ketogenic diet specifically, we have four more of the signaling mechanisms. We have moved over also into some of our studies utilizing ketone esters or a ketone salt.

And essentially like that postpartum depression study that I was mentioning earlier, you don’t really want to change a diet on a woman who’s breastfeeding or lactating after she’s just given birth, essentially. Some of them are interested in it, like I stayed low carb-keto during my pregnancy, but some of them are not.

And so utilizing supplementation like that just for the signaling effects of the ketones that are so very needed are even most applicable. 

Bret: 
Yeah, that’s a great point that they, the ketones themselves, it’s like a two-way street. You can have the metabolic benefits and the nutrition, changing your nutrition, but also the ketones themselves as individual signalers, like you said.

We’re learning so much about that. What does the diet do? What does the metabolic changes do and what do the ketones themselves do? So I’m glad to hear that you’re doing that research.

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But now you’ve also done some research on BDNF, which I thought was really interesting. Brain derived brain derive, neurotrophic neurotropic factor. I can do this, brain derive neurotropic factor, which is fascinating because when we start talking about mental health, when we start talking about cognitive function, any brain-based functioning, it’s a pretty important factor. So, what have you found with BDNF and ketogenic interventions? 

Madison: 
The time at which we’re looking at BDNF, and the interventions that we’ve done.

So this is actually my dissertation study, and I took three different studies. One of them was a long-term ketogenic diet with resistance training. Next was an acute supplement study with a quick physical performance, albeit aggressive, physical performance. The other was the weight loss study.

So, we saw in the weight loss study, which was really interesting, that BDNF actually dropped from baseline. But the concern with that is, and maybe not concern, but the interesting fact of that would be BDNF almost acts or essentially the central nervous system wants to counteract when insulin it, when you’re insulin resistant.

When the metabolic cycle isn’t doing exactly what it’s supposed to do, your body tries to reprogram and say, hey, let me help you out. And so, essentially, that’s where we’re assuming that spike in BDNF came because it actually dropped after the diet and after people lost weight. It was a shock for a minute. We looked at it, we’re like, oh, did we just decrease brain plasticity?

Or what are we actually looking at here? But then in another study, we saw that BDNF had an increase with ketones, supplementation, and exercise. So, it all depends on where that person started essentially, and basically what stage of, oh no, we have to fix ourselves is the body in? But in all of the, we haven’t published this data yet, but some of the current studies that we have going on are pilot, our pilot evidence of BDNF is that utilizing the ketogenic interventions have helped increase, especially in more of a mental health population, whether it be the the KIND study or PPD. 

Bret: 
Yeah, I think that’s such an interesting perspective that it’s not so just basic as, up as good, down as bad. It depends on what baseline you started with and why.

And so I think that’s a really interesting perspective and interesting finding. All right, so let’s get back to physical activity because you brought that up. So, you know, you are a certified strength. conditioning coach and so physical activity is really important to you. So what do you find when you’re working with women with ketogenic interventions?

Does their ability to exercise change in any way when they’re in ketosis? And does it change during their cycle that they have to be aware of? 

Madison: 
It’s not that their ability to exercise changes, but their immediate needs for recovery tend to be the things that ebb and flow. So, the caloric need at the end of it in, somebody who is high carb is going to be a little bit more than somebody who’s in ketosis.

Ketosis have seen that they can go a little bit longer without needing food or something along the lines of, but those who are trying to keep their, keep their muscle mass, essentially, they’re going to basically almost force themselves to eat the protein. But their body is so used to making that energy without food essentially because they’ve switched into a lipolytic system, that they’re trying to meander through those waters.

I don’t necessarily train people differently if they’re in certain diets, and they will follow that effect in regards to their phase. So, some people are more affected by their luteal phase, and want more carbs than others.

And actually there is relatively minimal, but there’s an increase in basal metabolic rate during your luteal phase. So you might be able to have a little bit more carbs and still stay ketosis on that time, too. So, you’re going to want to change essentially, your performance in regards to that.

Maybe a little bit more explosive because you want to that readily available carbs and to get rid of it because you’re trying to stay in ketosis. There’s also body water composition as well. I would say that women that are in ketosis ebb and flow on holding water less than somebody who is on a higher carb diet.

That’s to be expected essentially. But other than that, if they are holding a little bit more water, we’ll probably transition away from the intensity plyometric exercises because we want the form to be correct. We don’t want to hurt any joints. We don’t want any extra added risk.

So, that’ll be about the only things that we essentially target changing. Otherwise, it’s very individual to the person. It’s very individual to the athlete, the type of athlete, what they’re used to doing. 

Bret: 
Yeah, that’s so interesting that depending on the phase that someone is in may dictate which exercises they can do better or maybe struggle with a little bit more.

And I am really interested in what you said about increasing carb intake during the luteal phase and still be able to stay in ketosis, and that some women are just going to feel better that way and perform better. But now I want to put that into perspective. Does that apply to the woman who’s trying to get 30 minutes of cardio in or the woman who’s trying to do more extreme intense training or everywhere in between?

Does it apply to both ends of the spectrum? 

Madison: 
It’s dependent on the person, so unfortunately, that’s the worst part about a lot of the guidelines for things is because it should be so individualized and it really takes a full metabolic comprehensive test, athletic test to be able to associate what is the best for this athlete.

But that is why being, for somebody who wants to be in ketosis. the marker of adherence, just being able to measure your ketones and seeing, okay, at this day, I had this amount of ketones and I felt great. Or I didn’t feel great, and I added some carbs and I realized I felt worse or I felt better.

Now when we say add carbs, it would be like maybe 10 more grams of carbs per that day or day. So, not essentially ,here’s your a hundred grams of carbs, eat a piece of bread. That would not work out very well. But so the study that we’re running that is very, we look at basal metabolic rate throughout the phases.

We look at water holding during the phases. We start with a DEXA so we can basically correlate what their changes are to that DEXA, which is obviously our gold standard. We look at strength and component and fatigue ability. We actually put an EMG on the leg to see if what the muscle activation is.

Obviously, checking hydration in blood levels including metabolic lipid and hormonal panels at the same time, just to get this full picture. So, unfortunately, it’s going to be very particular, very individualized but I am, I’m a advocate for try it out, see how it feels, if you feel and be honest with yourself, if you feel better as you do that, great work with that.

If you don’t, let’s try going back to the, to where we started essentially. But that’s for athletes, essentially, who really know what they’re doing in the gym. If we’re looking at lay or general pop, we want to stick closer to the guidelines until they’re more comfortable with their bodies to be able to de deduce what feels better or when they have more energy. 

Bret: 
Yeah, and I’m glad you brought up DEXA scans as well and body composition measurements because I think that is so important. And I heard a podcast recently where they tried to normalize losing 40% of your weight from lean mass that like ozempic, you lose 40% from muscle. That’s okay, that’s what studies show.

And they tried to normalize that. And my jaw hit the floor when I heard that. And so what do you think about weight loss and fat mass versus lean mass and how do you try and target weight loss interventions? 

Madison: 
Yeah, we try very hard to explain that all weight loss isn’t good. That we need to be very particular about what we’re losing. So, this calories and calories out, I don’t really live by that, obviously. We want to be very specific about how we’re losing weight and why we’re losing weight. In our Spark study, the PCOS study, we’re very closely monitoring their body composition.

So, they actually get DEXAs pretty frequently every two weeks because we want to make sure that they’re not losing the amount of lean mass that could be really detrimental to them, especially since they already have insulin resistance and metabolic ailments. And hormonal concerns, we don’t want to add anymore to that.

The ketogenic diet, especially for those who are trying to lose weight, since it’s so protein sparing, muscle sparing, is so effective in that way. But we have women who come in, not even from our studies, but just from the public looking for a DEXA scan. because they’re very interested in it. And they’ve lost weight, but they feel worse about their bodies.

They’ve lost weight, but they feel squishier and they feel weaker. And, unfortunately, to get their doctors to prescribe a DEXA and insurance to pay for it, it’s crazy expensive. They come to Ohio State, essentially, to get that scan and have us talk through with them like what we should be looking for.

And, obviously, they ask for dietary recommendations most of the time. And I always preface that we are the ketogenic diet labs so we’re probably going to be biased. But really those who have tried it, even from not being in our studies, just start listening to us talk on our pedestal. They do come back and say that was the best diet they’ve ever had, a best lifestyle change that they’ve had. And they feel so much better, especially women in either perimenopause or menopause who, the preventative care that’s out there now or the preventative awareness that’s out there now was not there when they felt that they could have used that preventative explanation.

The diet explanations, the exercise prescriptions. They’re like, I feel like I’m at a loss. So, I’m at the end of my game here and I’m just looking for something to pick me back up. And so a lot of those women come into our lab and basically get very excited about the evidence that we have to offer.

Bret: 
Yeah. Yeah, so important. Yeah, i’m glad that you’re really focusing on the body composition and helping people lose weight in the healthiest manner possible, especially as people age, as we know, strength, bone health. So important, not just for metabolic health, but for frailty and for thriving as we age.

So well, I am thrilled to meet you and have this discussion and learn every about what you’re doing at the SHE IS Lab at Ohio State, to focus on ketogenic interventions in women so we can learn so much more about it. So if someone wants to learn more about you and all your work, where could you direct them to go?

Madison: 
Yeah, you can find us at u.osu.edu/SHEISLABORATORIES.. We’re also on Instagram. SHEISLABS.OSU. we’re also on Twitter with the same exact tag name. \But otherwise we filter all over the OSU website as well. You can find the low carb OSU website between Jeff’s lab, has ours integrated in with it if you’re interested in some of his stuff as well.

Bret: 
Fantastic. And you have so many studies going on, so many irons in the fire right now. We’ll have to have you back when when these studies get published to hear about all the exciting work you’ve done. So, thank you so much and keep up the great work. 

Madison: 
Thanks Bret. Can’t wait. 

Bret: 
Thanks for listening to the Metabolic Mind Podcast.

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