The Science of Midlife Fat Gain: Hormones, Insulin & GLP-1 with Dr. Ben Bikman

Dr. Mindy Pelz  

On this episode of The Resetter Podcast, I am bringing back for the third time one of my favorite guests, Ben Bikman. So Ben and I met when I first started this podcast, and he and I were amongst a handful of people that were out there in the world talking about blood sugar. And what’s really surprising, as I’m reminiscing about that, was that was about five to six years ago, and in that short time, this idea that our blood sugar is contributing to so many chronic disease challenges has become almost mainstream in just five years. But what I love about Ben, and what you’re going to realize as you listen to this, is that he just makes sense. So the fact that he is not just a professor and is actively teaching all aspects of Hormonal Health at the university level, but he’s a scientist. He’s a prolific podcast guest. Man is in high demand, and what you’re about to listen to is a very detailed conversation on glucose, ketones and fat. And what I wanted to do in this conversation for you all is I really wanted to talk a lot about the process of losing weight, because so many of you are struggling with that. How do we simplify this for people? So we started the conversation off there. Then we went to this journey into GLP, one hormone. What were her thoughts? How can we change our behaviors to improve GLP, one hormone, and not have to spend money on the expensive medications? Then we went to keto, and we went to ketones. And how do they affect women differently than men? Why are they necessary for the aging woman. I think this is a lot of what’s happening in the space right now, in the health space, is some of you are getting confused around, should you be doing a ketogenic diet? Should you be fasting? Should you not? And so I really wanted to bring the man himself, the scientist himself, to discuss the power of ketones so you can make your own educated opinion, and then at the end, we had a ton of fun of talking about some hunger hacks. So stay all the way through. It’s a phenomenal conversation. He’s a dear, dear man, and I am so excited for the third time to bring you. Ben Bittman, welcome to the resetter podcast. This podcast is all about empowering you to believe in yourself again, if you have a passion for learning, if you’re looking to be in control of your health and take your power back, this is the podcast for you.

Okay, well, we’re gonna dive in. I want to share with you something that we are really seeing on my YouTube channel, which is, people are now be and I don’t know if it’s because the weight loss drugs, but people are really looking for what’s that thing I can do to lose 2030, pounds, but not change my favorite foods that might not be healthy? Are there things we can do without avoiding these foods that we love that may have gotten us in this place?

Dr. Ben Bikman  

Oh, gosh. Well, that’s a that’s a difficult answer, because usually, the habits that a person’s engaging in, not usually always, are the habits that got them where they are. And so the habits must change in order to have a change in body size or fat mass. You know you want to shrink those fat cells, and so you cannot. You cannot do so meaningfully. Maybe I’ll qualify this a little bit. You cannot do it meaningfully without changing your macronutrients. Now, having said that there are, there are small interventions that can yield smaller changes, like apple cider vinegar or Berberine, or, you know, water extracted cinnamon there are or, you know, yerba mate. There are things that people can take to offset some of the effects, like apple cider vinegar and Berberine, you know, minimizing the glucose and insulin spikes. Then there are other things that they can take that might make managing their macronutrients a little easier, where they don’t feel like they are depriving themselves, because it’s just becomes they have less of an urge or a craving. And that would be something like, say, you know, like yerba mate, where, when the when the bot, when the mouth tastes something a little bitter, that’s a known signal.

To the brain to reduce sweet cravings. There’s good evidence in humans to show this. Bitter tasting things can help, kind of put to bed, the the urge, the beast that’s clamoring for some something sweet. So there can be things that the person may not think they’re changing their habits because they they’re quieting some of the, you know, the noise that’s driving them to want to eat a particular way, but having said that, that may move the needle a bit, and it could even be used as a sort of starting point to start changing habits. But when it’s all said and done, if a person wants to make some meaningful weight loss as shrinking fat cells, they need to make some meaningful changes in their macronutrients.

Dr. Mindy Pelz  

What do we say to the person who’s completely food addicted, and it’s illogical, and they just open up a bag of Doritos, and next thing you know, they are the whole bag’s gone. They tell themselves they’re never going through the fast food drive through again, and then three days later, they’re through the drive through, from the research that I’ve done, a lot of these food additives have people so addicted. And so I think that as silly as the first question might sound, it’s actually the big food has made us really addicted to this stuff. And so the addiction is now a big problem. How do we get over the addiction? Yeah,

Dr. Ben Bikman  

yeah, that’s, I absolutely love that you’ve brought this up because it’s something that I feel so strongly about that as much as I will, like, you know, for example, I will elaborate the the dietary changes in order to, you know, shrink fat cells and reverse insulin resistance. I make great effort to present them in a very simple way. But I don’t want anyone to ever confuse the idea of a simple concept with an ease of application, because while the idea can be simple, the implementation of the idea can be brutal, and that absolutely is because of addiction to the great tragedy of all metabolic health, of all of the three macronutrients, carbohydrates, proteins, fats, the there’s only evidence in humans to show addiction to one of those, right? It is not only the one that humans don’t require. I’m not saying we shouldn’t eat them at all, but it is carbohydrates are not essential. But again, we should, we should enjoy them, but be smart about them. But number two, they’re also the one that has the most negative metabolic impact depending on the nature of the carbohydrate. That’s, of course, an enormous class of foods, but all of the neurobiology of addiction when it comes to food habits comes down to carbohydrates. And so I have nothing but empathy with the person who hears this conversation, in any of our previous conversations, in any of the content you and I’ve created, because it’s easier said than done. It’s easy to think about controlling carbs, just like you said where you elaborated, the sort of cycle of shame. This is actually one of the reasons why, as much as my first rule is always control carbs. You have to replace it like don’t deprive yourself. You need to focus on proteins and fats to at least feel full. But even then, feeling full is not the same as still craving something where the person is prepared to eat themselves sick, even though they’re full, and they know they’re full, their brain tells them they’re full, and yet they still won’t stop. And that’s to be, to be frank, and maybe a little controversial, because you and I have never talked about this, so I could go into a wild direction. This is actually the only so I do think there are interventions, things that can increase. I’m gonna say this, and you already know where I’m going to go with it. Anything that can increase GLP one will help so people who are obese compared them to people who are lean. When you have obese individuals and lean individuals eat fat, they have the exact same amount of GLP one released. And GLP one is a powerful hormone from the guts that tells the brain you’re full. It will quiet your cravings down. However, if you have those same populations consume carbohydrate. In the Lean group, you have a nice, robust GLP one response. In the obese group, you do not, there’s almost no GLP one response whatsoever. This is a human paper from years ago that is so powerful because it suggests that there really might be something about those carbs where the person who’s been struggling with obesity, they eat the same carbs as their lean counterpart, and their brain doesn’t tell them you’re done. They just want to keep going, because they are literally losing out on one of the satiety signals. Whereas the lean person eats that same amount of carbs, they have a bigger. GLP one hit, and the brain is saying, Hey, you’re done. You’re good. Stop. Put that lid back on that ice cream and put it away. So. GLP one, anything a person can do to maybe get a little more. GLP one, whether it’s your bamata, whether it’s AL. Yellows as a sweetener. You know, that is a very powerful GLP one stimulant. But this is where, if there’s any utility to the weight loss drugs in the GLP one family, and I think people have gone way too far with them, personally, that there’s an utter ignorance or totally overlooking the negative side effects which exist as they do with every drug. I think the best use of the GLP one drugs is in confirmed instances of carbohydrate addiction, where they’ve given the best knowledge, the best education, and they still just cannot do it. Okay, then let’s start at the absolute lowest possible dose of a GLP, one agonist micro dosing, or whatever people want to call it, the lowest possible dose, combined with the best information of actually changing your diet, rather than just the same old nonsense of eat less, exercise more. No, it’s actually really manage your macros and really focus on some strength training to help you preserve your muscle mass at the same time, but the lowest possible dose of GLP, one drugs, all for the purpose of helping the person learn how to eat. What it looks like, what it feels like when you’re not constantly craving carbohydrates, yeah,

Dr. Mindy Pelz  

to get in to have a different relationship, that’s Yeah, yeah. And then wean

Dr. Ben Bikman  

them off as you can as soon as it’s viable, that to me. I mean, as complicated and hard as the question is that you posed, I think that’s the best, that’s my best answer for Yeah.

Dr. Mindy Pelz  

Well, I’ve seen some studies that show fats have destroyed the toxic fats, the inflammatory fats, have destroyed the microbes that make GLP one hormone. So there is some belief that actually, if you bring some of these microbes back, then your body starts naturally producing GLP, one on its own. Have you seen that? No,

Dr. Ben Bikman  

so let me, and I’m very curious about what you’ve seen, where just to be, the normal pathway for GLP one release is through cells of the small intestine called L cells, where the microbiome, per se is not the source of the GLP one, but it could be the source of a molecule that’s helping stimulate GLP one from the L cell. So, so what I mean by that is like, for example, I don’t mean to keep mentioning yerba mate. It’s just something my lab is putting a paper together on. But like yerba mate does increase GLP one. However, it appears that one of the main molecules that does so in its native form. It has a modest effect, but the microbiome converts it into a more into a slightly kind of more activated form, if you will. There we go. That molecule actually does stimulate the L cells of the small intestine to create GLP one. So the microbiome isn’t the direct source, but it could certainly contribute to it. Now, having said all of this sounding like I’m so clever, I actually don’t know. I’ve never seen any report that linoleic acid will somehow compromise GLP, one secretion. There is a study that I have seen in humans which do, which had people eat a seed oil rich in linoleic acid and olive oil rich in mono and saturated fatty acid, and then pierce lard, saturated fat, mostly, and the saturated fat had the biggest effect, and then the other two had a more modest effect, but there was still an effect in response to seed oil. So that’s the only paper, and it was an acute bolus. Maybe there’s evidence to suggest that chronic consumption will compromise the L cells, but the one aspect of the gut that I am aware of definitely is that linoleic acid does compromise the tight junctions of the of the cells of the intestine, increasing intestinal permeability, aka leaky gut. Yep,

Dr. Mindy Pelz  

yep. So that leads me to, I mean, I love the way you explain that, and that makes sense, because the microbiome is often performing in this enhancing manner when mixed with our human cells is sort of like the bugs in us go hand in hand. And I will send you that paper, and I’m curious. You have to email me your thoughts on it so but if let’s just go down this hypothesis that linoleic acid, meaning our toxic, inflammatory seed oils, just for everybody, listening is damaging the microbes. Then I have heard, I mean, when we look at things like eat fiber before a high carbohydrate meal, I’m wondering if, yes, it slows down the absorption of blood sugar, but maybe you’re also feeding these microbes, and so you’re also not hunger. You’re killing the hunger quicker, so which makes me wonder, like, well, maybe we should just be eating some leafy greens with everything, and that could really start to bring back the health of those microbes.

Dr. Ben Bikman  

Yeah, yeah, right. I am a big advocate of fiber in the context of. Carbohydrates. So I’m not a, I’m not a kind of universal advocate where, like, for example, if someone finds that a pure carnivore diet has reversed their crushing autoimmune disease, and I’d say, you keep going. Don’t stop You’re doing great. But the more a person eats carbs, then the more important I believe fiber becomes. So yeah, for all the reasons you mentioned in that there are, it has a direct effect at altering and kind of blunting the glycemic and insulinogenic effect, or response to foods, but at the same time, it is a direct food for beneficial bacteria, and the product of its metabolism is beneficial, namely short chain fatty acids that our human diet. Because we don’t eat a lot of fermented foods, we don’t get a lot of short chain fats anymore, like we, like we used to, you know, where we would have a carbohydrate or a dairy and we would ferment it very often. We, especially in the West, we have left fermentation behind entirely. Yeah, it’s and even, even what we do eat as fermented it’s often been so processed that we might not be getting the products of the fermentation, namely, the short chain fats. So short chain fatty acids are not only a fuel for a different sort of microbiome, but they also get absorbed and have tremendous metabolic advantages, like stimulating mitochondrial biogenesis, improving insulin sensitivity, stimulating glucose uptake in muscle cells, thereby helping glycemia. So yeah, short chain fats are really beneficial. And while we don’t metabolize the fiber, various bacteria in our microbiome do, and the product of that metabolism is short chain fats, which we need, yes or we want. So when

Dr. Mindy Pelz  

we look at the carbohydrate, I love the way you said that that there’s really only one macronutrient that gets us in trouble, because that, I think, is a beautiful way to look at it. I really have seen in just coaching so many women, the dysfunctional relationship women specifically have with food. And if we can bring it down to one macronutrient, that makes it a lot easier. But carbs are getting a really bad rap. Women specifically are getting very confused, because some people are saying, Go keto, no carbs. Other people are saying, You need carbs to make serotonin. You need carbs to make hormones. So can we unpack the carb like? I feel like, just like fat was like, we finally figured out there’s good fat and there’s bad fat. I feel like in carbohydrates, we need to have that same carbohydrate, that same that same conversation. Are there good carbs and bad carbs? And maybe that one macronutrient. We just need to take the bad carbs out, but still keeping those good carbs and what are, yeah,

Dr. Ben Bikman  

yeah, yeah. So just, I have to, I have to be careful here, because I don’t want to answer the question in a way that suggests a kind of false sense of authority here. Because the thing I hate the most in academia is people who have an actual area of expertise and pretend they know about everything. And I don’t want to make that claim. What can I claim so in humans, just to sort of make have a common understanding here, humans are capable of living and even thriving in the total absence of carbohydrates. So that is possible. Humans can thrive and reproduce and live on a purely carnivore diet, but we are omnivores, so and so we clearly are adapted and evolved or created in order to eat and consume these and we’ve been doing them since time immemorial. Now I so I very much appreciate that while I point the finger at carbs, I actually don’t want someone to think, Okay, well, then Ben’s solution to everything is just cut carbs. It actually isn’t. It’s a little more nuanced. And I think that different people have different needs. But like, for example, I know someone personally who had absolutely debilitating ulcerative colitis, like, resulting in them having, for years, like, a failure to develop stunted height and just crushing health problems. They went on a carnivore diet and have gotten off all medications and never felt better. It is miraculous. I’ve

Dr. Mindy Pelz  

seen that, by the way, I’ve still, I’ve seen the carnivore diet. Yeah,

Dr. Ben Bikman  

it is incredible. Now, however, there are a lot of people who could eat plenty of carbs, so nd be perfectly well with them. Now, my version of good carbs and bad carbs, it isn’t as clear cut as I wish it could be, which is just the easiest version. If we go kind of first layer down, it would be, just don’t get your carbs from bags and boxes with bar codes, whole fruits and vegetables. Eat them. That would kind of be the first layer down. And for the vast majority of people, that would work. And it would be perfect that eat whole fruits and vegetables liberally, enjoy them. You don’t have to count them. Them. Don’t worry about it. If it’s fruits and vegetables, eat them and then make sure you’re getting lots of good protein and fat all at the same time. Now, however, there could be a kind of another level down, like, let’s say I’m talking to a person with type two diabetes. If I give them carte blanche with fruits and vegetables, they’re going to be eating bananas and apples and the most sugary fruits that are spiking their blood sugar levels. And so in that person, I would say you actually focus more more on the cruciferous vegetables. Eat as much as you want of these cruciferous vegetables, you know, broccoli, cauliflower, the ones that if you put on a plate in front of like an infant, they’re gonna or a toddler, they’re gonna push it away, you know, but that would work. But at the same time, those vegetables may be the worst thing for someone with an autoimmune disease to eat, and they maybe would be better if they were going through some elimination. They may be better with fruits, which generally have far fewer anti nutrients like phytates and oxalates, so they may be more sensitive to those things. And so I actually think there’s kind of a quirky division where it kind of depends on how many layers we have to go down, and then it starts to branch off into different people’s health needs, where the person with insulin resistance diet and diabetes, they’re avoiding these fruits, and yet, those may be the fruits that a person with an autoimmune disease can actually enjoy, because they have fewer extra stuff in them that go beyond the nutrients, you know, like the more of the anti nutrients. So yeah, unfortunately, I wish I could give a simple answer, but that’s the best I can come up with, that there’s no kind of good car, bad carb. I think it really does depend on the person.

Dr. Mindy Pelz  

Yeah, it’s I actually really love the way you you describe that, because my new cry is, stop building your health habits around a 92nd rail like people are getting like they’re fighting with each other on social media about low carb, high carb, no carb, you know. And it’s, it’s personalized, is what I just heard right there. Oh, yeah. Do you think that men and women need a different carb load? Well,

Dr. Ben Bikman  

yeah. Now I can’t speak to the I cannot speak to the hormone differences. I do know that in a short term study, women had an acutel higher cortisol than men, but then it did come back down to normal. That’s the one study I’m aware of that showed a difference, and it wouldn’t surprise me if there are more that show other differences, but I am particularly mindful of the woman who is experiencing frequent ovulation cycles, where when her progesterone is increased, that is an absolute wild card that has both Central and systemic effects. Where, when her progesterone is up, progesterone does have a direct stimulation for hunger, and so if she is trying to fast during her ovulate, during the actual little window of ovulation. Now, of course, I’m a dude, and I appreciate some people may say, you can’t talk about this, so I’m just approaching it as a scientist. Yeah, I would think the evidence would suggest that would be a harder time. And I would say that it would be in her best interest to not even try, but at this and at the same time, progesterone. Would want to be storing more energy during that same phase, resulting in evidenced by higher insulin levels and a little more insulin resistance. So that would be a that’d be a very difficult time. I would think to try to be ketogenic or fasting, and then at another give it, or a week later. And then I would think the the endocrinology would suggest, all right, yep, you can do it. You’re going to be I would think that as much as your male counterparts going to do it now you can too. But I do think that the women’s, I mean, fertility is it is so complicated. When I get to that section in my graduate endocrinology class, I kind of joke where I say, Okay, let’s spend 10 minutes and talk about male fertility, and now we’re gonna spend the next 10 hours talking about female fertility, because it is so much more complicated, so good and in that’s makes sense, right? Like the men’s involvement is, of course, critical. Men matter. Dads matter. If only you know, we need to let men want to be that role. But when it comes to actual reproduction, it’s a brief, glorious moment, right? Women carry the beautiful yet substantial metabolic burden, and so it’s no surprise that she has way more checkpoints and checks and balances than he does, that her body needs to be almost constantly determining the environment and the hormones are a way to determine that it’s essentially her way of having these so many redundancies, of just saying, Okay, are we really okay? Are things really okay for us to reproduce? Are they really okay for us to carry? The baby, are we? Is it okay for us to give birth and then continue to feed the baby? You know, there’s so much that goes into it that anyway, that’s once again, a long winded way of saying, Yes, I do believe there are absolute reasons for the woman to be a little more mindful, particularly with her cycle, because there will be changes that would make it much more difficult for her to adhere to just a simple rule like her male counterpart can adhere to, because he does not have the substantial changes on a regular cycle that she does.

Dr. Mindy Pelz  

Yeah, and I think progesterone is the outlier that progesterone does like glucose to be higher, and I think you’re spot on in ovulation and the week before a woman’s period, when progesterone is at its highest, we actually the cells become more insulin resistant. They want to keep that glucose in the stream, in the bloodstream. So I absolutely agree with you, and that’s what we’ve found in our community. What do you think about the aging woman, the woman who goes into menopause. There’s a lot of experts saying that are, I mean, for both men and women, but especially for women, that our cells in our brain become less sensitive to glucose and more sensitive to ketones. Do you think there should be a carb change as you move into your post menopause years.

Dr. Ben Bikman  

Boy, Mindy, you are pushing the limits of what I know. So, so, which I appreciate. It’s fun for me. I so please. I have to speculate for a little bit great, where estradiol, in particular, kind of being the main of the estrogens, the the kind of poster child of the estrogens. It is such a heavy hitter that I kind of joke when I teach some of these principles that as long as a woman has pre menopausal levels of estrogens, she’s kind of a metabolic superhero, that she’s kind of bulletproof, that her body can handle all kinds of knocks and shots and like, I mean, like external hits with regards to bad lifestyle habits, and she’s immune. Yeah, she may get chubbier, but she’s not gonna have the diabetes that her husband has, or her male counterpart, the hypertension, the migraines, you know, she may be spared all of that. But even beyond the metabolic estradiol is a powerful regulator of neuron health and neuron synthesis, and thus it’s no surprise that of all the chronic diseases, men die more from all of them, except Alzheimer’s disease, right? That is the one of the top killers that is a more female specific one, and I believe it’s because of the loss of the protective effects of estradiol. Now, with regards to the metabolism of the brain, I like the way you framed it, where some of our research supports this idea that as much as the brain is a hybrid relying on glucose and ketones, only, one of those macronutrients, one of those fuel sources, rather, has been shown to be disruptive, disrupted, rather, and that is glucose. That glucose has steps of regulation in its use, that ketones do not have that when we did an analysis of post mortem hypothalamus samples, like actual human samples, every single in the people with confirmed Alzheimer’s disease at the time of death, every gene involved in glycolysis was significantly down in glucose metabolism, whereas the genes involved in ketone metabolism were totally normal. And so my view on the individual, and certainly the woman who has to be more mindful about brain health than her male counterpart. Again, that’s kind of the unique female pathology. All the more reason I would think to make sure that you have some period of time where your brain is getting ketones as a good fuel source, because it will take it in unregulated the moment ketones start coming into the blood. I mean, even just to put a fine point on this, and I feel inclined to be a bit animated, just because my own students, like every student, has been taught such nonsense about brain metabolism that I find like I have this is one of the ideas I have to disabuse from their brains, this false notion everyone hears the brain prefers glue, glucose. Glucose is the preferred fuel for the brain that is so easily falsified, even in even in the whole human so if, if glucose levels are at a normal range of about five millimolar, and and ketones are even at a modest like one millimolar, not to mention up to one and a half or two. But at that point, already, the brain has shifted and is already getting more of its energy from the ketones than it is from the glucose. Yeah. So looking at this, don’t tell me that the brain prefers this one when, even when this one. And is at a fifth of its level. It’s already surpassed right the other so if the brain prefers any it’s just the ketone. There’s no regulation steps the moment the ketones going up, it is literally open doors, not literally. It is figuratively like an open door where the ketones can just come right in. There’s no bouncer, there’s no Usher at the door saying, Okay, you can come in, or you can’t come in because I’m not responding to the signals anymore. You’re knocking on the door insulin, but I’m not listening. Yep, and so that’s to me, both the the relevant variable in the female physiology, with the brain and neurological disorders, but also with the value of ketones, and and the the shift that happens with menopause, and maybe even something to be said for the value of strategic hormone replacement therapy as well.

Dr. Mindy Pelz  

You know, I’m in the process of writing a book on what happens to the female brain after 40, and I stumbled upon so much literature on the ketone not necessarily aimed specifically at women, but both men and women talking about how neuro protective it is, that it actually can protect the neurons from oxidative damage from environmental toxins, how it’s a better fuel source for the mind the mitochondria, like you said, I love the way you said is like they There’s a free pass to come in that you don’t have to and the mitochondria, you actually will get more energy out of the mitochondria from the neurons in the brain, if you’re fueled by ketones. And I mean, the list goes on and on, but those were the two that really struck me. What I find really interesting in this you’re the right guy to ask this question, because you and I have been out in the world, you know, talking about ketones for some time, I do not understand why people keep saying women shouldn’t do the ketogenic diet. Women, menopausal women shouldn’t be doing keto. It makes no sense to me, and I try to prove myself wrong. But the deeper I go into it, the more I realize that that is protective to the brain, if you’re willing to accept the call of either fasting or cut out carb, the refined carbohydrates. I’ve even wondered about exogenous ketones. And if there is a place in which menopausal women can use exogenous ketones for to get all those benefits, but not necessarily have to go into a ketogenic state. What are your thoughts on that I

Dr. Ben Bikman  

well, in addition to just saying stating a hearty Amen, I would I wholeheartedly agree. I don’t know where I think sometimes I think sometimes people are a little too eager to show differences between the sexes. Of course, we are very different, and yet, when it comes to certain metabolic processes and metabolic realities, we’re not we are the same species, and Despite some obvious differences which are real, I don’t know of any reason why a post menopausal woman wouldn’t thrive in a ketogenic diet, especially for the reasons you mentioned where you know, having seen my beloved grandma die with Alzheimer’s disease for 10 years, it is sobering. And if my darling wife ever reported, or ever had any kind of evidence of just boy, I really feel like I’m kind of missing a step here. I’m forgetting things. Oh my gosh. I mean, she already kind of follows a low carb diet. But I wouldn’t hesitate for a second to say, You know what? We’re getting some exogenous ketones. Yep, and let’s start. Let’s make sure you start drinking them every day. Yep, without hesitation. I The nice thing about exogenous ketones is they’re getting better. They’re getting they’re tasting better. They’re different versions out there. Yeah, and as that continues to as the field gets bigger than the prices will start to come down, because they can be a little high, but no, I mean, for every reason you mentioned, in addition to ones we haven’t even gotten into, like our evidence showing higher metabolic rates in fat cells from humans that are in ketosis. There are a lot of reasons, the anti inflammatory effects of the ketones, the reductions in oxidative stress and the enhancement of antioxidant enzymes. So yeah, for all these reasons and more, indeed, these are reasons that play into my own motivation as as a guy who’s knocking on 50, I want to be healthy. I am particularly worried about cancer because of a family history. And then I’m worried about Alzheimer’s disease because it was so terrifying seeing my dear Baba, my grandma, die with this. And I don’t want to touch those. Let me die from anything else, but not those two, or push them off as long as possible. And ketones are therapeutic for both. Good enough for me at the same time, it’s going to help me be lean, yep. All right, good, yeah. It’s yeah.

Dr. Mindy Pelz  

You know, it’s funny, my my dad, my sweet dad, who is very blunt, he’s 88 years old, and when I was going through my perimenopausal years. Studying fasting and really understanding ketones. There was, I don’t know, some point about two years into my fasting journey, my dad looked at me, and I must have been about 47 at the time he goes, You know what? I never realized you were so smart. And I was like, hmm, I’m not really sure how to take that, but I think what now that I’ve thought about it is I learned in the back half of my 40s to get power my brain on ketones, and whenever I needed to learn something, anytime I was giving a talk, anytime I needed maximum brain power, I made sure I switched over into that fuel source. And we’ve seen the same thing in our community. Yet there’s, I don’t know who’s driving the anti keto movement for women, but it really is doing a disservice, because ketones are so from my research as well, so massively important for for both men and women. So

Dr. Ben Bikman  

yeah, they really are. I mean, it’s if, even if a person, like you said a moment ago, even if a person decided, You know what, I don’t want to do low carb for reasons that elude me, I would still say, well, find some way to get some ketones, because your brain and the rest of your body is going to benefit. This is an energy source that our modern diet has made all but gone because we eat 70% of all calories come from carbs, and we eat six or seven times a day, because that’s what we are told to do. We’re told to eat, yeah, all these little snacks all day long, it is just nonsense, and that means all day long we’re we’re sugar burning because our insulin is high and because our insulin is high, we’re not fat burning, and that means we’re never making ketones, because you only make ketones when you’re burning fat, and so most people and what a tragedy. Just one final comment for me on this, like, I think about the person who’s descending into Alzheimer’s disease, one of the most scary and sobering disorders. And throughout this descent. It’s like, it’s like people may be familiar with The Rime of the Ancient Mariner, Water, water everywhere, nor any drop to drink. Is the sailor bemoaning the fact that he’s surrounded by an ocean of water, and yet he can’t drink it as he’s dying from thirst. That’s like the brain saying the body I’m filled with glucose. There’s glucose all over, glucose, glucose everywhere, nor any drop to drink. It. Can’t use it, even if a person’s hyperglycemic, because they’re so insulin resistant, the brain can’t get it, and it’s crying out for some little life preserver in the form of ketones. And yet, because of the hyperglycemia and the associated hyperinsulinemia, they’re not making any ketones, and so the brain is drowning in a sea of energy that it can’t use. Oh, that’s so

Dr. Mindy Pelz  

that was such a good visual description, and I could, I couldn’t, I couldn’t agree more. Let’s move towards this idea of visceral fat and white fat versus brown fat, because I think we also need to unpack that fat. It some fats easier to break down than others. So talk a little bit about what we need to know about visceral fat versus just subcutaneous fat. And in the context of white fat and brown fat, yeah,

Dr. Ben Bikman  

yeah. So let me actually start with the white and brown, and then then the subdivisions of white. So yeah, one of the ways you just presented two ways of classifying adipose of fat tissue. One is the actual color of it because of the composition of the mitochondria. So humans are mostly, most of the fat we have is white fat. Very, very low mitochondrial content. If you look at these fat cells under a microscope, it’s almost entirely made of a big blob of fat, which is why it presents in a kind of whitish color. It’s like little Crisco bubbles, you know, almost in the fat cell. And very, very low mitochondria, like I said, in contrast, brown fat actually does look like a darker brown, and it’s because it has such a high content of mitochondria and the fat droplets. Rather than having one really, really big droplet that dominates the entire thing, it’s tons of little, small ones interspersed amongst all the mitochondria, and mitochondria do have a dark reddish brown color to them, and thus, indeed, so much that the fat actually looks brown. And so brown fat exists to burn fat to make heat. White fat exists primarily to store fat for later energy use. So one is a heat producer, which itself is a kind of inherently inefficient process, but favorable in this case, one is a very low metabolic rate, almost below the point of detection, but even by my instruments in my lab. But we can do it, and we have but very low metabolic rate, because it’s not meant to burn energy. It’s meant to hold on to it. So. Although that just as an aside that is selling the fat cell short, just as an interesting aside, like, for example, the hormone leptin. Leptin is a fat derived hormone, and we leptin has been framed in the context of a signal from fat cells to tell the brain were full. And yet it never should have been known as that, because that effect is kind of modest. Actually. What it is absolutely essential for, I mean, I’m literally essential is reproduction. If you remove someone’s leptin, they are totally in, totally sterile. There is zero reproduction. Yeah, exactly. And yet, there are multiple other hormones that act as a satiety signal. So as much as leptin does have a satiety effect. There are a hand dozen. There’s a dozen other hormones that do the same thing. But if you take out leptin total sterility, they cannot reproduce. And so anyway, that’s just a fascinating effect. So the fat cell, yeah, back to the conversation we had earlier, with regards to reproduction. If a little girl gets too if a girl gets too lean, she doesn’t have enough leptin, and fertility stops. If a younger girl gets too chubby too early, she has too much leptin, and it initiates the process too soon, and now she’s going through puberty at six years old or so. So the fat cell, white fat, is tremendously important in all kinds of things, in addition to just storing energy, and it’s

Dr. Mindy Pelz  

the it’s the white fat that’s making leptin, Yep,

Dr. Ben Bikman  

that’s right, okay, yeah, yeah. And, and women make more leptin than men. If we took out a comparable a little scoop of fat from a man, a little scoop of fat from a woman, her fat cells are making a lot more leptin than his. And that’s just further reflection of the need for the female to have a lot of these checkpoints in assessing her environment, including metabolically, to know, all right, can I commit to the metabolic marathon of pregnancy and then and then lactation? So with regards to white fat, then in brown fat is mostly in humans, it’s mostly sprinkled through this thoracic space and just sort of for fun wondering why. And I joke with my students that a scientist cannot answer why, we can answer how and what, but supposing and philosophizing as to why it could be that as much as we’re shivering to try to warm our body, if we’re cold, you can’t shiver in your head. And so how can you keep the blood in your in your head warm? Maybe by having a lot of little incubators here. It can warm the blood up before it hits the carotid vessels and then keeps the brain warm. Maybe because there’s no shivering here, fast, much as I as much as I wish there were, because I need a little more. Okay, wait, insulation. Wait,

Dr. Mindy Pelz  

I just have this top. I think you just proved why women are smarter than men. Because we have, we have white fat right here on our chest, called breasts. Maybe they were put there so that it could, it could fuel our brains. Maybe that’s what’s going on here. Well,

Dr. Ben Bikman  

I love it, and I won’t go, I won’t say anything too crass, but I’m going to use that line on my wife and see if I can’t get some benefit from

Dr. Mindy Pelz 

Just said, hey, you need to be smarter. We’re going to put two lumps of fat right on the front of your chest so it goes up and fuels the brain.

Dr. Ben Bikman  

So that’s all speculative, but I love it, and I’m going to, when I get home, I’m going to tell my dear Cheryl, I’m going to say, hey, I need to conduct a test and see how warm your chest pad

Dr. Mindy 

This could go this could go dark. Wish me luck.

Dr. Ben Bikman  

Yeah, wish me luck. Report back. I predict it’s going to go very well now, but with white fat in mind. In fact, you know, adipose tissue stored subcutaneously, including breast tissue. It is interesting to note now the differences between men and women, because it is significant that there are two depots of white fat, and you listed them both at the outset of the question, namely, subcutaneous, which is the fat that you can pinch and jiggle if it’s pinchable and jiggable, then it is, it is subcutaneous fat. If it is the fat that is visceral, then it is tucked deep within the muscle of the abdominal cavity. And you can see this on on different men. Let’s imagine two men, two drinking buddies. They go bowling and fishing and drinking together. They’re both the same percent body fat. One of them has fat that spills over his belt, and it is loose and folded and wrinkled, that’s subcutaneous. The other one who’s just as fat, it stands out hard, like he’s almost pregnant. It is this big, hard expansion of his tummy, and it doesn’t drop down over his belt, because it just is protruding straight out rather than hanging down. That’s more visceral. It’s tucked within the organs of his abdominal space, pressing out against the stomach of the third of the of the abdomen. And so so that’s very diff indeed. It is not now. So why is visceral fat so much more problematic? And maybe even before I go to that where a person stores fat is both is genetic, even within sexes, and then very much hormone dependent, where estrogens will more stimulate subcutaneous fat, whereas, whereas androgens will not so androgens do not stimulate as much subcutaneous generally, and thus the man will default to having more stored viscerally. But this is a consequence of the woman who’s going through menopause, in the absence of any hormone intervention, her fat will literally start moving away from the subcutaneous fat storage to the visceral Now, why is that a problem? And why does that make her a metabolic mortal like her male counterpart already is it’s because of the size of the fat cell, and subcutaneous fat has, if you will, an almost limitless site depot like the people who make or the subject of TV shows, my 600 pound life or etc, that is entirely subcutaneous. They may have only a very modest amount of visceral fat, and that’s just genetic largely. In fact, most people could never get that fat because they don’t have the ability to continue to produce that many fat cells, but estrogens enable the production of more fat cells, particularly at the buttocks and the hips. So at those sites, if a woman has a pressure to store more fat because insulin is high and calories are sufficient to fuel the growth that the insulin is signaling, you need both of those signals to tell the body to store fat. In her case, she has a fat cell that gets a little big, and then she’ll make another one. And that one gets a little big, and then she’ll make another one. So her fat cells, even though she has more fat than her male counterpart, her fat cells are smaller. Small fat cells are anti inflammatory and insulin sensitive, so small fat cells are healthy fat cells. In the guy’s case, he’s not growing most of his fat through subcutaneous most of his is visceral. Well, you cannot have unending growth in that visceral space, because if you allowed those fat cells to continue to multiply, you would literally start crushing your intestines, crushing your liver, pressing on your your heart and your lungs, and you would die. And so those fat cells end up self limiting themselves by one not undergoing hyperplasia or multiplication, and thus only growing through hypertrophy. That’s a problem. I mean, on one hand, it keeps the person alive because of those fat cells, like I said, we’re multiplying, it would crush all the internal organs but the fat fat cell, or the fat cell that’s undergone hypertrophy, it has to, it has to take on two adaptations to ensure its own survival, both of which end up creating problems for the body. First one briefly being that has to become insulin resistant to prevent further growth. And then, number two, it has to become very pro inflammatory to stimulate the growth of new blood vessels. Because as it’s getting so big, it’s starting to get pushed they’re pushing each other further and further away from capillaries. They become so far that they start to suffocate, so they start releasing a host of pro inflammatory proteins that kind of act like a trail of bread crumbs for the blood vessel to start growing out to nourish that suffocating fat cell. But the combination of those two adaptations does really spread the insulin resistance throughout the body.

Dr. Mindy Pelz  

Is there a different Yeah, that was beautiful. That was one of the best explanations I’ve heard of the difference, and I’m curious then, is there a different behavior that we need to be able to get rid of brown fat versus white fat? Well,

Dr. Ben Bikman  

yeah, just to make sure you ask that question, the question correctly. So we don’t want to get rid of brown fat, right? We we want. But do you mean the difference of getting rid of visceral versus subcutaneous? Exactly, I was gonna say, okay, visceral to sub, okay, yeah, yeah, good, yeah. Now just to just by way of that first question, ketones actually make white fat behave more like brown fat. So brown fat has a really high metabolic rate that’s roughly comparable to muscle tissue, whereas white fat has an almost negligible metabolic rate in humans, we found that if a human’s in ketosis, their white fat metabolic rate triples, so it goes up three times. So that’s a meaningful change. So just to you know, help people understand that you kind of can blur that line a little bit in a metabolically favorable way. Now, visceral fat and subcutaneous fat do burn differently or break down. They undergo lipolysis at different rates. Specifically, visceral fat is generally considered, I suppose, by the body, so problematic that at any moment, visceral fat is going to respond more to a stimulus to burn more. Better to break down more so especially in response to epinephrine or catecholamines. This is why, one of the reasons, if someone has more visceral fat, I actually think, do whatever you can to get acclimated, or the courage to do some kind of ice bath or some cold there, I was going to ask you, I’ve heard, yeah, because that is a very effective way to spike epinephrine, and epinephrine will induce relatively more lipolysis at the visceral adipose than it will the subcutaneous adipose.

Dr. Mindy Pelz  

Yep, yeah, okay, and so, so it’s it. There’s really what I’m hearing. It’s not like if I go on a long hike versus weight lifting, those two activities aren’t going after visceral or subcutaneous different. They’re there. It’s It’s not like I can target it like that will, rather than make some good ketones,

Dr. Ben Bikman  

you can’t target it, but, but, but the body, if it is any stimulus that increases epinephrine and exercise does visceral is gonna relatively go more now, in the case of the woman, she has so little visceral that that’s not really getting tab right as much, and that’s largely, again, that’s largely estrogens based. If it is a woman who’s going through menopause and sort of diving all in with the with the estrogens coming down, then she will start to store more fat there. And so I would think in that case, all the more reason to take these kind of interventions like cold therapy a little more seriously, because you do not want to force your body to start storing fat more viscerally.

Dr. Mindy Pelz  

Yeah, yeah. That makes sense. Okay. You have to, since you alluded to it in the beginning, you have to tell me what you’re looking into with your bamata, because I think it is. We’ve we’ve used it as a tool to drink in your fasting window. And we have seen people kill their hunger doing

Dr. Ben Bikman

Yeah, we have some right now. Yeah, right. So

Dr. Mindy Pelz  

I’m curious what you’re researching on it and why it does what it does to GLP one hormone, because I may have to sing its praises a little louder in my fasting community.

Dr. Ben Bikman  

Yeah, yeah. So I absolutely I usually take it twice a day. Now I am a scientific advisor for a company that makes it, but I’ll mention it, and then everyone listening can decide I get mine from a company called unicity, and again, I’m an advisor, so I do have not a vested interest in that. I’m an owner, but I’m a scientific advisor for them. But our research, we’ve published a couple papers. One is well, one’s in review right now, and and we actually have published one previous to that. So the first one was just documenting the effects on like fat tissue, and indeed showing an activation which had others had shown too. We just got a little more molecular to the mitochondrial level. This study that we have in review right now, we submitted it to the journal nutrients as a brief report. It’s called so kind of a smaller, tidier study, and we found that the one of the so yerba mate has multiple active ingredients. One of them is a molecule called ferulic acid. And ferulic acid we found so first of all, we found that yerba mate increased GLP one in the blood by about 50% from fasted, which is pretty meaningful from a fasted state. Now, if you eat fats and proteins, you’ll go up higher than that. But for a fasted stimulus, non caloric, that’s pretty good. Yeah. In fact, it’s very good. And so when we treated the L cells with with straight yerba mate, it didn’t result in an like going out of the living organism and right to the cell culture to say, All right, what are the L cells doing that make GLP one. There was only, there was no response at the L cells. If you put on straight yerba mate, it’s not doing anything. And then we got all right, well, let’s just test one of the more active molecules, ferulic acid. It did a little something. But then we were still trying to reconcile this and say, well, then how are we seeing such a big response. And so we we learned that ferulic acid, as I alluded to earlier, will be converted by the microbiome into dihydroferulic acid. And when we incubated the L cells with dihydrofurulic acid, then it went up three times. Wow, huge response. So just a kind of further, a further testament to just how remarkable the interaction is between our bacteria and us, that we have learned to kind of coexist in this sort of beautifully mutually beneficial way where there are some bacteria who can look at this molecule and say, I’m going to take you in, and I’m going to convert you, and I’m going to let this new molecule out, And then it’s that new molecule that we really benefit from. So that’s the paper that’s interview right now. So unpublished evidence,

Dr. Mindy Pelz  

amazing. Wait, and what do we have any idea when it’ll be published? I

Dr. Ben Bikman  

don’t know. In fact, just yesterday, I got an email back from the journal asking for some edits. So it’s the never ending frustration of being an academic where you’re just wanting to throttle the paper. So you just accept it already, right,

Dr. Mindy Pelz  

right, right. So then, if we go back to where we started, which is the micro dosing, GLP, one, could you also decide, okay, I’m gonna go into fasted states every day. Maybe I’m doing a 1315, hour fast, nothing really big. And in that fasted state, I’m going to have some yerba mate mate, and I’m going to have that on a regular basis, hoping maybe 90 days from now that the L cells and the microbes are now more efficiently producing GLP. One could could we look at yerba mate like that?

Dr. Ben Bikman  

Oh yeah, for sure. Yeah. So I definitely think if I do think that there is an opportunity to capitalize on GLP one fervor, that GLP one absolutely is one of the signals that will tell the brain to just calm down. And I cited that human study earlier, I think that is very telling in that it does suggest that there’s value to this. So I don’t want as much as I now have a bit of a reputation of being a naysayer with the GLP one drugs, I actually never intended that to be the case. I just think, as much as there’s such wild enthusiasm for these drugs, I just feel someone has to be the voice of reason to say, Yeah, but at those doses, your risk of depression and anxiety go up, you’re going to start losing muscle mass. You know, there are consequences to these drugs that I just don’t think are being considered. But they are powerful, and thus I think they can be used. So that’s my long winded way of saying. I do believe there’s value in focusing on GLP one your vomit will be a stimulus. Allulose will be a stimulus, even even just the right macros. There’s a human study that showed this was just published months ago. They had humans eat the exact same number of calories, so isocaloric matched for protein, exact same amount of protein. One was low carb, high fat, then the other one was high carb, low fat, and the low carb version of the meal had a GLP one response that was three times higher, wow, than the high carb, low fat version of the meal. So that that that’s important, right? I mean, let’s focus on the macros that are going to give us the best advantage. So all while we are including these natural spikes to endogenously make more of our own like the ones I just mentioned. If that still, if a person is still struggling, then maybe I would say I would maybe it’s like a process of graduating. All right, let’s take the first step first. Let’s see, do these interventions help? Yes, it did help. Great. Let’s keep going. Or we did this intervention and it’s not helping. You’re still just going back to these old habits. Now, let’s take another step, boy, all right, now let’s like, I would say last step with let’s say responsibly. Okay, we’re micro dosing with these GLP one agonists. But you know, Mindy, it’s hard for me to be overly optimistic in that regard, because just like two weeks ago, I think the FDA said that it’s cracking down on these, these compounding pharmacists who have been able to even make the low doses lower dose. Yeah. And so it’s really discouraging to see that, as much as you and I are talking about the strategy, it’s very possible that it might be removed in the foreseeable future. Oh,

Dr. Mindy Pelz  

that is crazy. And I, you know what, I really appreciate your opinion on the GLP one hormone, because my brain was like, why? Where I immediately went to, where is this hormone made? And what in our modern day lifestyle is destroying this hormone? Because people are reacting to it so positively. Then I went to wait, it’s 800 to $1,000 a month. That seems crazy, but I also understand, I’ve sat with so many people struggling to lose weight. I understand how exhausting that fight can be, and if you had the money, you might just do it. But I think we have so many cool new things coming out, like you’re talking about. I’d even heard the order of food, that if you do your vegetables, then your protein, then your carbohydrate, that the order in which you you feed your microbes actually controls how much GLP one will be produced. So if there’s anything good it did is it brought forward. Nobody knew what GLP one hormone was and now everybody does. So we’re having good conversations about it right now, which I think is really important. So,

Dr. Ben Bikman  

yeah, well, and if nothing else, it does allow us to come back to one of the first things you started with, which is we cannot continue to ignore the reality of carbohydrate addiction that the moment we can just sort of generally acknowledge that people really do have addiction, like based on every little metric you want to check, then the sooner we can start. We can get rid of stupid advice like moderation and all things that is something that sounds so nice, it sounds so beautiful, and. Person who says it, it just sounds so clever, and yet, tell that to an addict. Yes, it doesn’t work. If you tell the person you know, would you ever say that to an alcoholic? Well, just drink one glass of wine and stop does? Yeah. And yet they can’t, you know, that’s that’s the problem. You’re giving them more of the thing. You’re encouraging them to indulge in their addiction, whether you know it or not, yeah,

Dr. Mindy Pelz  

yeah. So well said. I just love talking to you. And I talk about glucose and ketones all day long, and your brain is really one of my favorite to to walk these thoughts with. So I really appreciate you. I’m so excited for all the big podcasts you are getting on and going on, and your your teachings getting out there. How do people find you? I know my audience is gonna go if they haven’t, if they didn’t know who you were, they’re gonna go hunt you down.

Dr. Ben Bikman  

Yeah, yes. Well, thanks, Mindy, you’re just so darling. I just love talking with you anytime. Yeah, my the main place for people to find me, the simplest is just going to my website. Ben Bikman.com, so Bikman is just b, i, k, m, A, N, no, C, benBikman.com that’s where I kind of have the that’s the compilation of everything I’m doing.

Dr. Mindy Pelz  

Amazing, amazing. Well, thank you for keeping going. You haven’t lost any steam, and keep up your good work. It’s just really fun to see all the things you’re doing. So appreciate you. Thanks, Mindy, thank you so much for joining me in today’s episode. I love bringing thoughtful discussions about all things health to you. If you enjoyed it, we’d love to know about it, so please leave us a review. Share it with your friends and let me know what your biggest takeaway is.