Ep. 316 The Impact of Age, Gender and Lifestyle on Metabolic Health with Dr. Ben Bikman

I am delighted to have the privilege of reconnecting with Dr. Ben Bikman today. (He was with me previously on episodes 114 and 168.) 

Dr. Bikman has a Ph.D. in Bio-energetics and also served as a postdoctoral fellow at the Duke-National University of Singapore, specializing in metabolic diseases. His current professional focus, as a scientist and Associate Professor at Brigham Young University, is on understanding the effects of elevated insulin, obesity regulation, diabetes management, the relevance of ketones, and the workings of mitochondrial function. He is also the author of a book I love and often recommend called Why We Get Sick. 

In today’s conversation, Dr. Bikman and I delve into a wide range of topics, including age-related changes in fat cells, gender-specific differences, the contrasting dynamics of hyperplasic and hypertrophic fat cells, and the impact of hormone replacement therapy and a metabolic buffer. We explore the changes in insulin sensitivity occurring during perimenopause and menopause and discuss the role of muscle, explaining how it can utilize either carbohydrates or fat for fuel. We also highlight the importance of strength training, discuss the impact of GLP-1 agonists- focusing specifically on Wegovy, and get into the effects of lifestyle factors like sleep and stress, the repercussions of endocrine-mimicking chemicals, and the significant impact of statin use with its associated diabetes risk. Lastly, we dive into the complex question of what poses more of a threat to our health- seed oils, high-fructose corn syrup, refined starches, or sugars? 

“I believe sleep is the most likely cause of stress induced insulin resistance.”

– Dr. Benjamin Bikman

IN THIS EPISODE YOU WILL LEARN:

• How our fat cells change with age 
• How lifestyle factors impact insulin sensitivity
• The hormonal changes that occur during perimenopause and menopause
• Why it makes sense for women to have more fat cells than men
• The importance of resistance training for building muscle
• Risks associated with relying on GLP-1 agonists for weight loss
• How immobility activates inflammatory pathways in muscles, leading to insulin resistance
• How stress and poor sleep impact insulin resistance
• Why is it essential to avoid high-carbohydrate or high-fat foods before bedtime?
• How alcohol, plastics, and pesticides impact insulin resistance and fat cell biology
• The potential risks of statin use
• How seed oils, refined starches, and refined sugars contribute to health problems

Connect with Cynthia Thurlow

• Follow on Twitter, Instagram & LinkedIn
• Check out Cynthia’s website
• Submit your questions to support@cynthiathurlow.com

Connect with Dr. Ben Bikman

• On his website
• On social media: @benbikmanphd

Previous Episodes Featuring Dr. Ben Bikman

Ep. 114 – Why Obesity Matters When It Comes to Coronavirus – with Dr. Benjamin Bikman

Ep. 168 – What To Do About Insulin Resistance Disorders (and the Role that Digestion Plays) with Dr. Benjamin Bikman

Transcript:

Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness Podcast. I’m your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. 

[00:00:29] Today, I had the honor of reconnecting with Dr. Ben Bikman, who has previously joined me on Episodes 114 and 168. He earned his PhD in Bioenergetics, and was a postdoctoral fellow with the Duke National University of Singapore in Metabolic Diseases. Currently, his professional focus is as a scientist and associate professor at Brigham Young. And he focuses on the role of understanding the impact of elevated insulin in regulating obesity, diabetes, the relevance of ketones and mitochondrial function, and he is also the author of one of my favorite books to recommend, Why We Get Sick. 

[00:01:05] Today, we dove deep into the changes to fat cells with age, gender differences, hyperplasic versus hypertrophic fat cells, the impact of HRT and a metabolic buffer, changes to insulin sensitivity in perimenopause and menopause, the role of muscle, the impact of how muscle utilizes either carbohydrates or fat for fuel, the importance of strength training, the impact of GLP-1 agonists; specifically Wegovy, the role of lifestyle including sleep and stress, endocrine-mimicking chemicals, the impact of utilizing statins and diabetes risk, which is quite significant, and lastly, what is worse, seed oils or high fructose corn syrup, refined starches and sugars. I know you will love this conversation as much as I did recording it. Dr. Bikman is a true pleasure to connect with. 

[00:02:02] Welcome back, Dr. Bikman. It’s always a pleasure to have you on the podcast. 

Dr. Ben Bikman: [00:02:05] Oh, my pleasure. Cynthia, thank you so much for inviting me back on.  

Cynthia Thurlow: [00:02:08] Of course. Of course, you’re definitely a fan favorite. I would love to start the conversation today talking about how fat cells change with age. I think this is really interesting. And I know for many of my listeners, we acknowledge that we might be more prone to visceral fat distribution and less subcutaneous fat. But what is actually changing to our fat cells as we’re getting older? 

Dr. Ben Bikman: [00:02:33] Mm-hmm. Well, in fact, the scenario that you just described is very much the case with women where there is this shift– But that’s because of how fat cells will grow and shrink and die and the various stimuli that dictate those processes. If we just take humans in general, that would be across both sexes. The general trend is that the number of fat cells we have during infancy, childhood, and adolescence is steadily increasing. So we’re literally making new fat cells during this time of our life. And then as we transition out of adolescence, things start to change. And of course, that happens at different times in men and women. Women will transition into adulthood in their mid to late teens on average, and then men, in contrast, will be late teens or even early 20s in some boys. This is why you know, if a boy goes off to freshman year of college and comes home, he’s six inches taller. He clearly wasn’t done puberty, because adulthood is when we’re set.

[00:03:31] Now, typically, again, at that point, just like our height, so too it is with our fat cells, the number of fat cells we have is typically set. That’s mostly the case in men. With some of course genetic variation, some people just genetically have the ability to continue to make fat cells, and maybe that’s something we can revisit. But in women, it’s largely an effect of the estrogens, where the sex hormones allow her subcutaneous fat to continue to expand with number, which is a process called hyperplasia. And so her fat cells will continue to proliferate as needed. This is most pronounced at the buttocks and hip areas. That’s the general area of the woman’s body that is more sensitive to the ability of the fat cells to continue to proliferate.

[00:04:23] But it’s not just a given. It’s important to note that this does not mean a woman’s going to have this limitless fat cell growth. There must be a stimulus, independent of the sex hormones that is signaling to the fat cells that they need to store more. And that stimulus is, of course, insulin. In the absence of insulin, a woman can be swimming in a sea of estrogens, and it will not be inducing the synthesis or the multiplication of new fat cells. That’s not the way it works. There has to be this additional stimulus. 

[00:04:52] Now, however, as you’d mentioned, with age, let’s continue this story along. So the average individual is generally going to be set in the number of fat cells they have through adulthood. Again, of course, with women with a little bit of capacity to expand that number. So all of this so far has been a description up to the early stage of adulthood. And then, as we continue to age through adulthood, the number of fat cells we have is generally pretty static, which is not to say that the fat cells are immortal. That is absolutely not true, even though it is something that is still taught on college campuses to this day. It’s one of these principles I’m trying to disabuse my students of these false ideas. A fat cell is very long lived, relatively. It has a lifespan of about 10 years. But during this time, wherein fat cell number is generally pretty static. For every fat cell that dies, it’s simply replaced by another one. 

[00:05:48] However, once we get to about 60 or so years old, then the number of fat cells we have starts to drop in men and women. And this means, particularly in women, there is this potential to shift how she’s storing her fat, or rather where she’s storing her fat. But once again, this is completely contingent on the hormone insulin being elevated. If insulin isn’t elevated, then as she is losing fat cell number, then all the remaining fat cells are still shrinking if insulin is down. So this is an opportunity in the life of the woman in particular where if she’s able to change her lifestyle or she’s already following a lifestyle that is more inclined to be burning fat rather than storing it, namely, insulin is low and calories are generally under control, because calorie number matters, of course. 

[00:06:41] But in this state of life, if she is continuing to eat away the same way that wanted her body to store that much fat in the first place, then that means all of the remaining fat cells are left to carry a larger metabolic burden, where any remaining fat cells will start to get bigger and undergo a process called hypertrophy rather than the hyperplasia that I mentioned earlier. And that matters, because far more important than the actual mass of fat that a person has on their body is the size of every individual fat cell. So fat cell size matters much more than the amount of fat that a person has on their body. 

[00:07:20] So let’s imagine two women who were roommates in college, and they get together a few years later, and they’ve both gained 20 pounds of fat. Whereas one woman is still generally healthy. Her blood pressure is normal, she doesn’t have diabetes, no other [unintelligible [00:07:38] evidence of fatty liver disease. The other woman, who’s also gained 20 pounds of fat, has diabetes, and hypertension, and fatty liver disease, and maybe she has PCOS, polycystic ovary syndrome. She has all of these cardiometabolic complications that are, in fact, a consequence of how she’s storing her fat. And the difference between them is clearly not in how much fat they’ve gained, but rather how they gained it. Because if the first woman I described has this greater genetic potential for hyperplasia, then all of her fat cells are actually quite modest in size, there are just more of them. It’s not the number of fat cells that matters, it’s the size of them. But however because she can make more, the moment a fat cell starts to get a little big, a new fat cell simply starts to help carry that burden. And so no fat cell is particularly overburdened, if you will. 

[00:08:30] However, in the other woman, in her case, it could be that her few number of fat cells means that each individual fat cell has to get significantly larger. Now the hypertrophic or enlarged fat cell bearing the brunt of the burden becomes insulin resistant. This is actually as a survival mechanism. It becomes insulin resistant in order to prevent further growth. But in the process, it starts to induce insulin resistance throughout the rest of the body. That is the first domino to fall in this row of dominoes, if you will. And once the body, of course, starts to become insulin resistant, now you have all of these, what I like to call, plagues of prosperity that I’d mentioned earlier, these cardiometabolic complications that stem from disrupted metabolism. 

Cynthia Thurlow: [00:09:17] I find it really fascinating because when I was a younger woman, I didn’t fully appreciate some of the physiologic changes for women as they’re navigating perimenopause and menopause. When all of a sudden, women who’ve never been insulin resistant, as they start having fluctuations in estrogen towards the tail end of perimenopause and then navigating menopause, this is when I would assume some of these hypertrophic cells will start to grow and they are more prone. It’s like you mentioned the domino effect. But how many women don’t realize that loss of estrogen can be a hallmark of this prelude to developing insulin resistance? 

[00:09:56] And so with the Women’s Health Initiative, which I know was not the focus of our conversation, and many, many years of physicians and clinicians being fearful to talk about hormone replacement therapy. In your research, are you finding that women that are on hormonal replacement therapy are more likely to have less visceral fat, and perhaps stable subcutaneous fat vis-à-vis, this modest hyperplasic fat versus hypertrophic fat. I’m hoping that’s clear, but I’m trying to follow physiologically what’s happening in our bodies and trying to put it together, so that listeners can understand what’s happening in their bodies at this stage of life. 

Dr. Ben Bikman: [00:10:40] Right. Yeah. In fact, the way you framed that question causes me to realize a description or a part of my answer that I should have elaborated on, which is that, in men and women, around 60, we start to lose fat cell number. The fact that in women, this has been preceded by a drop in estrogens means not only has she already started to stop storing more subcutaneous fat. So there’s this prelude to this, which is she’s already started shifting where she’s storing her fat, because it’s estrogens that are generally dictating the storage and subcutaneous fat depots, which is a very healthy place to store fat. And then the absence of that high estrogens level, now she’s starting to shift into what is a general fat pattern more similar to men storing it more centrally. And then that gets compounded when she starts to go through around 60s reduction in fat cell number. 

[00:11:31]] So yes, in women who are on a hormone replacement therapy– I don’t want anyone to take this as me being an advocate of one thing or the other. I’m not. Just simply observing research. There’s complications that need to be considered in both sides of this on hormone replacement therapy or not. And that’s not my purview. However, because estrogens do offer a metabolic buffer in large part by telling the body how to store fat, the woman does lose that buffer. And so she’s more subject to the consequences of fat gain at that point in the absence of those high levels of estrogens. And of course, hormone replacement therapy continues that buffer. It allows her body to continue to enjoy that metabolic benefit. But the metabolic benefits are even more relevant than where she stores her fat. In other words, there’s more to estrogens than just telling the body to store fat in the subcutaneous space beneath the skin, particularly in the butt and hips. 

[00:12:25] Estrogens also stimulate a high turnover of fat. Most ladies don’t appreciate this, but if we were to measure the metabolic rate of fat tissue from women, that’s about 50% or double the metabolic rate of fat tissue from men. So not only does the woman’s metabolic rate in fat is significantly higher, but it’s also reflected in an almost twofold increase in the amount of lipolysis from her fat cells at any moment. So women are fat burning machines compared to men. Any moment, she’s burning more fat and breaking down more fat than her male counterpart is. 

[00:13:01] Now, of course, I appreciate that any of the ladies in the audience are thinking, “Well, why do I have more fat than my male counterpart?” which is absolutely normal because of estrogens. Paradoxically, I just said how estrogens help the body burn fat, but they also tell the body to store fat. Those are not mutually exclusive ideas. It’s simply– You look at the fat cell and in a fat cell in a man with a more androgen dominant scenario, endocrinology, the fat cell is more static. It’s just sitting there storing energy and then involved in endocrinology and other things, of course. But the fat cell in the woman is sort of this soccer mom scenario where it is very, very busy. There’s something coming in, there’s something going out all the time. And it’s much more than a trickle like it is in perhaps the case of the men. A man’s fat cell is pulling in less fat and it’s breaking down less fat. It’s just much slower. Not so in the woman, where it’s almost twice as active in this regard, breaking down fat and yes, storing fat, but that is by design of course, the reason being the female carries the metabolic responsibility of reproduction. And so she must have this check, a way of ensuring a metabolic status before committing. 

[00:14:15] Because of course, the male’s involvement in reproduction is very brief, of course, wonderful, but brief, [Cynthia laughs] but nevertheless– And very important later in life. I’m a huge, huge advocate of fathers being involved in children’s lives, enormous advocate. I think that’s part of what’s wrong with the world is that there aren’t enough involvement of fathers. But nevertheless, during gestation, that’s the mother’s burden. I hope it’s a wonderful burden, but nevertheless, her body is the one that has to cope with this. And so if she doesn’t have enough fat tissue, she doesn’t have enough leptin, and then the brain will stop menstruation, or more importantly, ovulation, to be a little more precise. 

[00:14:52] I think your audience is more informed, most people only think of leptin as satiety signal. And long before it was ever known to have any influence on satiety, we knew that this hormone that we didn’t call it leptin that there was this signal that prevented ovulation or allowed ovulation. And so that fat tissue, lest we be inclined to curse this intelligent design of the female body having more fat, it makes sense in light of reproduction, which of course is the purpose largely of every organism on the planet. 

Cynthia Thurlow: [00:15:27] Absolutely. I love that you wove in that reproductive piece because it is ultimately why women have different types of fat distribution in our bodies that makes sense. Now before we pivot and talk about lifestyle, because I know you’ve been doing a lot of content around this, and I love that you’ve got your finger on the research and it makes it so much easier when I’m trying to decide what directions to go down for our conversations, I’d love to at least talk about a little bit of muscle physiology. I know that your undergraduate degree, if I recall properly. This is an area of interest of yours. And so as we’re looking at individuals, men and women, that are navigating post 40, so people who are more prone to muscle loss as they’re getting older and how that impacts insulin sensitivity, I find this interrelationship really interesting, because I think for a very long time, I, myself included used to think about muscle as muscle, and then not really understanding that it is this very metabolically active and rich tissue. But as individuals are losing muscle mass with age, unless they’re actively working against it, that can impact their insulin sensitivity or lack thereof. 

Dr. Ben Bikman: [00:16:41] Yes. So you’ve framed this very well and brought up a lot of interesting points that I’m going to try touch on in my answer. But I am an enormous advocate of muscle to make that very clear, because I am such a scientist with regards to insulin resistance. Because I respect insulin resistance, not only how prevalent it is but also how relevant it is, namely prevalent to the point that it’s potentially affecting up to 9 in 10 American adults. And in fact, later this week, as we record this, I will be in Vietnam giving a talk on this very topic. So this is very much a global problem where we– Within the US, we need to realize that we’re not even the worst, we’re not even in the top 10 when it comes to the most diabetic with type-2 diabetes, insulin resistant countries on the planet. There are a handful, a dozen, at least, countries that have it worse than we do, statistically speaking, and the world is waking up to it, thankfully. So this is a very relevant problem in that regard and because of the diseases that come from it. 

[00:17:38] So with regards to muscle then, muscle is the great glucose consumer. If someone’s wearing a continuous glucose monitor and they eat something that is starchy or sugary, when you look at that curve starting to climb and then wait patiently for it to start to come back down, 80% of why it’s coming down is because of what’s being pulled into the muscle. Muscle is just the big, hungry tissue. This isn’t necessarily because muscle itself has such a high metabolic rate, every individual muscle cell, but rather there’s just so much of it. If you look at the net, the sum of all mass within the body or what makes us who we are, most of us are made of muscle. That is the largest single tissue within the body. And so it’s no surprise that it has the largest single demand. It will use what’s there. 

[00:18:27] Muscle is an indiscriminate metabolizer. It doesn’t care what’s available. It will use it. But if you’ve just gone through some big hyperglycemic bout because of some starchy, sugary indulgence, muscle naturally will pivot, adjust its metabolic demands and use glucose. This is dictated by the hormone insulin. If insulin is elevated, the body is in glucose burning mode or sugar burning mode. If insulin is low, the body is in fat burning mode. And this is very much reflected at a whole-body level, including in the muscle. With low insulin, the muscle shifts to primarily using fat. 

[00:19:01] Now, unless I get distracted, that to me, this ability of the muscle to chew through glucose thereby lowering blood glucose, thereby helping insulin come down, that really is where the rubber meets the road. If you have a body that is able to bring insulin down quickly and keep it down for significant periods of time, that is a body that is insulin sensitive. And if the body’s insulin resistant, that is the strategy to reverse that and to make the body more insulin sensitive. Thus, I am an enormous advocate, not only of muscle being appreciated as part of the solution, but also strategies that are explicitly intended to build up muscle. I believe, minute for minute, a man or a woman would better served metabolically by engaging in resistance training of any kind than aerobic training, I think both are fine, both are wonderful. And if there’s time and means to do both, then excellent, do them. However, if there’s insufficient time or means to do both, engage in resistance training. 

[00:20:02] Now, of course, at the end of the day, the most important exercise is the one you will do. So I don’t want to prevent someone from just doing whatever they know they can and will do. Regardless though, resistance training of any kind, body weight based even go to failure or near failure as often as you can. Even if that is doing a very lightweight and you do 20 or 30 or so repetitions, that is fine. It will still be sufficient to build muscle. There’s nothing magic about failing your repetitions at 8 to 10 reps. No. What matters is that you actually are going to exhaustion. So whatever it may be, air squats or pushups or chair dips, these are things that really matter. And women should not shy away from that. 

[00:20:46] This is in fact, one of the things that worries me about Wegovy in particular, and I’m being very deliberate with which medication I’m mentioning, the one that has the high dose of GLP-1drug, the semaglutide, at the very high dose for weight loss, the evidence showing that it results in that almost half of the weight loss is coming from lean mass. That, to me, is a catastrophic concern and should give anyone pause before they start injecting themselves with that drug. But I don’t mean to shift us off topic. Anyway, suffice it to say, I’m an enormous advocate of muscle. We need muscle. It helps resolve hyperglycemic bursts. It helps keep the body more insulin sensitive, and thus reducing risk of chronic disease. 

Cynthia Thurlow: [00:21:28] Yeah. I think that it’s certainly over the past 25 years, I’ve watched this metabolic health crisis evolve as a clinician. And to me, what I found really interesting is over the past three years, dealing with the pandemic and the stress of the pandemic and what has come out of that. And in many ways, I think instead of being focused on the lifestyle measures, which I think most people can do, whether it’s focusing on sleep, helping to manage stress, doing body weight exercise, being physically active. We’re now again with the focus on polypharmacy, encouraging patients in many ways to lean into taking medications to lose weight. I keep reminding people that maybe that helps with a quick win. Maybe for some individuals, being on a GLP-1 is very helpful to allow them to get to the point where they’re more satiated. They can get to a point where they can eat more reasonable sized meals. They’re not having those cravings. 

[00:22:27] But the loss of muscle mass is catastrophic because I would imagine the individuals that are probably using things like Wegovy as you appropriately mentioned, that’s a specific GLP-1 that’s used in larger doses. If they’re losing muscle mass in an effort to lose weight, muscle is very hard to rebuild depending on where someone is in their life stage. I know for the stage of life I’m in, it is an uphill battle unless I’m taking a good amount of testosterone and lifting heavy and eating enough protein. So when you lose muscle mass, you don’t get the muscle mass back on automatically. It’s quite a bit of effort to do so. 

Dr. Ben Bikman: [00:23:04] Yeah. So Cynthia, I don’t even mean to hijack the conversation, but just to–. 

Cynthia Thurlow: [00:23:07] No, it’s totally fine. 

Dr. Ben Bikman: [00:23:08] –Just to elaborate on that. I’ve kept my finger on the pulse of GLP-1 agonists quite well and thoroughly because of the interest and the work done during my PhD lab, where we were one of the initially funded labs to study these incretins, these class of hormones from the gut that had just been discovered. At their lower doses, even semaglutide, for example, and it’s cousin analogues were first being used, I looked at them, and to a degree even still do with a very hearty dose of appreciation. When they were originally used for antidiabetic purposes because of their inhibition of the hormone glucagon, if you could lower glucagon, then you could correct blood glucose levels very, very well. I looked at them and thought, “That is generally– It’s probably a net benefit.” Any of the weight loss was very modest, the so-called cravings control, which is really just a nice way of saying you feel a little nauseous. If we were being honest, that’s how we would describe it. But it sounds better to say, “I’m controlling my cravings.” 

[00:24:07] In that case, I could understand. I could nod my head along to someone who says, “I’m on a low dose GLP-1 agonist and I’ve coupled this with intense workouts or frequent workouts just to be more diplomatic, and a generally low carb diet where I’m controlling my insulin. I would give that person a high five and say, “That’s probably a really winning combination.” But that’s not how most people do it. Indeed, they look at it as an excuse not to control their diet. And that higher dose induces such a “cravings control” to say it nicely, or to say it more accurately, such a severe nausea that they just stop eating. And then you get into the starvation induced weight loss, not to mention nutrient deprivation, where they’re eating so little and their stomachs are so paralyzed that they’re just not moving food anymore through their intestines that they start to truly develop nutrient deficiencies, and that worries me. 

[00:25:02] So at the high dose that it’s being used currently, I do not believe. I believe it’s a net negative. I don’t mean to scare anyone and I don’t mind anyone saying, “To get the hell with you Ben.” I love how I feel. I’m thrilled if that’s the way people are experiencing this. But my general advice as a metabolic scientist or my view is that the better combination is use the lowest possible dose coupled with generally a low-carb diet, high in protein, and I would say, even high in fat to help the body use the protein better, and then make sure that you are engaging in some degree of resistance exercise frequently going to exhaustion. 

Cynthia Thurlow: [00:25:37] Yeah, I think that it’s insightful that you were actually looking at the research initially when these drugs were being considered for coming to market, and have been able to watch this explosion of GLP-1 agonists and their popularity in a lot of different ways. I’d love touch on some research that you were talking about on Instagram about movement and insulin sensitivity. And you were talking about how one week of being sedentary, and specifically nine days, took four weeks to undo. Meaning, that being sedentary for even a short period of time has a significant net impact on our insulin sensitivity. When you were expounding upon that research, what was the specific reason for why that was occurring? 

Dr. Ben Bikman: [00:26:22] Mm-hmm. Oh, I’m thrilled that you’re highlighting that work. That’s work done from a colleague of mine, and I was involved in some of his earliest publications on this. But what he found was that bedrest or sedentary, when the muscle stopped moving, this immobility actually activated inflammatory pathways within the muscle. And this is why I was involved with his work on the very early end of it, because my fellowship research with Duke into diabetes explored the role of inflammatory pathways and inflammation in causing insulin resistance. And that’s what he found too. He found that those same pathways were turned on when the muscle was immobilized. And that if you blunted the inflammation within the muscle, you mitigated the insulin resistance. In other words, the muscle preserved its insulin sensitivity despite the immobility. 

[00:27:07] Now, just for a point of clarity, when I say inflammation, a little part of me worries at how people hear that. Inflammation itself is a term that is more broad than most people realize. There are better terms that I could probably use, like, maybe it would have been better off if I would have said immune pathway, but that just gets a little too confusing. It is these inflammatory pathways, but just like we do have inflammation involved in an immune response, or we typically think of– When we think of angry, red scratch that gets infected, we would look at it and say, “That’s inflamed.” That isn’t necessarily what we mean by inflammation when we talk about it. In other contexts, that’s certainly not the case when we invoke inflammation in the context of metabolism. 

[00:27:52] There’s nothing swollen about those immobilized muscle cells. It’s just those same immune pathways in the muscle are turned on that are the same pathways that would be turned on in a macrophage or a white blood cell at an angry, oozing wound. And so these pathways have much more involvement than just prototypical immune processes or inflammation, per se. This is just reflective of the fact that the immune and metabolic systems within the body have an enormous amount of overlap that these are two fundamental systems to the survival of the organism. It’s no surprise that there’s a deep level of interconnection between the two. Improper metabolism leads to improper immunity. Improper immunity leads to improper metabolism. So it goes both ways. And in this case, we’re leveraging, we’re taking advantage of an immune pathway, which then has a metabolic consequence. But again, just to state it clearly, the immobilized muscle has an increased inflammation or an activation of inflammatory pathways, and that causes the insulin resistance. And as you noted, it is not as easy as just get up and do one day of exercise and you undo it all. No, it takes a multiple length of time in order to really recover fully from that. 

[00:29:12] Now, I would hate the idea of anyone listening to this thinking, “I’ve been sedentary for 20 years. So is that going to take me now 60 years to reverse?” No, of course not. Not even close. It just means it’ll take some time. And so be patient. But anything you start to do will better than where you started. So just doing anything, any intervention, will start to elicit positive benefits. And then my suggestion and hope is that that develops a momentum that makes the next things easier than the last things were. 

Cynthia Thurlow: [00:29:40] Yeah, thank you for that, because I’m sure there are probably a few people listening that are thinking to themselves, “Oh, my gosh, now, because it takes so long, I might as well do nothing.” That’s not the point you’re trying to make. Anything is better than doing nothing, for sure. How does stress and poor quality sleep impact insulin resistance substantially? This is something that I’ve started to talk more openly about. I will oftentimes say, “If I cannot get you to sleep through the night, I cannot get you to lose weight.” That is how critically important sleep is. 

Dr. Ben Bikman: [00:30:12] Right. Yeah, that’s a good sentiment, actually. I appreciate you saying that and I’m glad you’re sharing that message to your group. Stress is one of the three cardinal causes of insulin resistance. I look at most of human health through the lens of endocrinology. I confess. In fact, this upcoming winter semester, that’s my class load that I’ll be teaching at my university. I’ll be teaching graduate endocrinology classes, and I love it. It’s a fascinating topic. Now my reason in mentioning this is that’s how I see stress. People may have various definitions when it comes to stress. It is one of those words that has almost taken on a life of its own. For me, stress is an elevation in the two prototypical stress hormones, namely cortisol and epinephrine, AKA adrenaline. These two hormones are each reflective of a stress state within the body. 

[00:31:01] What’s interesting about them is that these hormones have nothing in common. They are made from different cells. Someone may say, “Well, Bikman, they’re both coming from the adrenal gland.” Yeah, but they’re both coming from very different parts of the adrenal gland. Namely, cortisol is coming from the adrenal cortex, which is a totally distinct section of the– It might as well not even be considered the same gland, truly. Whereas epinephrine is coming from the adrenal medulla. These are very different cells and these two hormones are produced in very different ways. They move through the blood in very different ways. They signal on different cells throughout the body in very different ways. And their general response, nothing they do is in common, except one thing, which is that they both want to increase blood glucose, and they do it very, very well and very quickly. 

[00:31:49] Now, they each have other distinct effects. Cortisol does a host of other things, epinephrine does a host of other things, but the one thing they have in common is that they both increase blood glucose and, again, do so very well. This means anytime the stress hormones are elevated, and sleep deprivation is absolutely the main cause of this. In fact, I’ll elaborate on that for just a moment. Sleep deprivation elicits an increase in cortisol, and then cortisol is causing this elevated glucose. Caffeine is a stressor because caffeine will increase epinephrine. 

[00:32:21] Now, I don’t mean to say no one should ever take caffeine, but I do think there is prudence in wondering how much you’re taking that if you are perhaps consuming too much and your body is a poor or slow metabolizer of caffeine, or that caffeine is really lingering in the body for a long time, that could cause insulin resistance by chronically increasing epinephrine, the other of the two stress hormones. But regardless of how it happens, if one or both of these hormones are elevated– You could see how it becomes a vicious cycle of sleep deprivation, caffeine consumption, sleep deprivation, caffeine consumption. When they’re elevated, they’re pushing glucose up, which means the other hormone, namely insulin, has to work harder to push the glucose down. The more insulin has to work, the more the body’s becoming resistant to insulin. So there’s this battle over blood glucose levels and there are consequences that go beyond just blood glucose control as the battle is between insulin constantly trying to push the glucose down, and then these other antagonists, in this case, stress and epinephrine or cortisol and epinephrine that are trying to push the glucose up. 

[00:33:29] So when it comes to stress, when I talk about stress as a cardinal cause of insulin resistance, I always invoke sleep. I believe sleep is the most likely cause of stress-induced insulin resistance. And so I think it is very prudent for us to focus on it. But maybe with that thought in mind– I’ll finish my rant here. As much as we have historically focused on blue light exposure, that probably matters, probably. But I think the much more important variable when it comes to getting a good night of sleep is do not go to bed with hyperglycemia. Unfortunately, most people find that in the evening is when they want to indulge the most. And of course, what we crave is always going to be something that spikes our glucose. I know of no exception to that. We crave something that is sweet and gooey or salty and crunchy, and that is going to spike our blood sugar levels. Would to God that we all craved a plate of bacon and eggs in the evening, and thus we could fill our stomachs and not spike our glucose, but nobody craves proteins and fats. It’s either pure carb or carbon fat, and that’s going to spike either of those. It is going to spike glucose considerably. 

[00:34:35] When we go to bed in a hyperglycemic state, we activate the sympathetic nervous system, which is the so-called fight or flight response. It means that the body temperature spikes, it means our heart starts beating harder and faster and our blood pressure goes up. So you have an individual who’s lying down and always cursing their poor sleep thinking, “I wish I weren’t so anxious because I’m laying here and I’m hot and I’m bothered. My heart is pounding, and I’m wondering, what am I anxious about?” In reality, you’re not anxious about anything. You just activated your sympathetic nervous system because you spiked your glucose levels, because you indulged in something you shouldn’t have.

[00:35:14] So as much as everyone focuses on blue light and whatever else they may talk about, I want to just pound the drum of, don’t indulge in something that will spike your glucose levels within about– I would say, four hours before you go to bed, give yourself that buffer to allow your glucose levels to have evened out before you go to bed. I guarantee you will sleep better. 

Cynthia Thurlow: [00:35:35] What are your thoughts on the impact of alcohol with sleep? 

Dr. Ben Bikman: [00:35:38] I don’t know enough about it, unfortunately. I wish I did. I don’t know. Mind you, Cynthia, this could because you’re talking to a guy who’s literally never had a drop of alcohol in his life. So I’ve never made it a focus of research for me. I’m afraid. 

Cynthia Thurlow: [00:35:52] Yeah. The reason why I asked was, it seems to me that it is absolutely those hyperpalatable foods before bedtime. But I’m starting to notice in a lot of my patients and clients that it’s the alcohol that in the evening for them will disrupt secretion of melatonin, it will dysregulate their blood sugar, they’ll eat those hyperpalatable foods we don’t want to be eating and can disrupt REM and deep sleep. And so this has now become something that I talk about more frequently on the podcast because I’m finding how interesting it is that maybe someone was capable in their 20s and 30s of being able to drink alcohol, and then as their findings are getting older, it no longer serves them. 

[00:36:33] Now, when I’m thinking about other things that impact insulin resistance, I think one area in particular that probably doesn’t get enough discussion is talking about endocrine-mimicking chemicals and how plastics and pesticides impact metabolic health. I know this is an area that I’m noticing you have more content around. Let’s talk about this, because I feel like this is something that many people think is very intangible. They can’t see these chemicals. Therefore, they’re not concerned about them. 

Dr. Ben Bikman: [00:37:01] Mm-hmm. Right. Yeah, I’m very glad you’re bringing attention to this. It’s something that is very overlooked and potentially very impactful. By way of preface to this answer, lest someone leave our discussion and feel overwhelmed with the sheer number of things they need to scrutinize, I would say that macros matter most. So if someone is looking to correct their insulin resistance, focus on just the macronutrients. And my advice is control carbs, prioritize protein, don’t fear fat, and then frequently fast as you are able. So that to me, is absolute biggest bang for the buck. If you’re going to leave this conversation with any action items, let that be the action item. 

[00:37:38] Now, having said that, if someone has the bandwidth or now has progressed to such a point having already managed macros and is ready for more, then it is absolutely valuable to scrutinize the chemicals that you may be inadvertently getting into your body because they will have an impact, albeit smaller than just overall macronutrients will. And these are, as you noted, generally the two biggest offenders are plasticizers and pesticides. It isn’t as hard as people think to avoid the plasticizers. Well, it’s a little harder because they can come in a lot of detergents. But generally, if you’re avoiding soft plastic bottles, then generally, you’re avoiding the worst of the offenders. And anything else you may get, even from detergent, if there’s a little bit on your clothes and so little of it actually is getting through your skin. I’m not saying it’s irrelevant, but I think that gets to the point where you don’t need to be so worried about it. 

[00:38:32] But if you’re avoiding the squishy plastics, especially never heating them up, then generally you’re okay. Mind you, if you’re buying plastic water bottles from a grocery store, you don’t know how hot those have ever been and how long it’s been in there. So it’s difficult to know that. But generally, I’m an advocate of drinking from glass and steel and metal largely, actually exclusively for that reason, certainly for cooking and baking and putting hot things in those kinds of plastic containers. But then with regards to the pesticides, generally, if you are buying organic, you are avoiding, not all of them, but most of the pesticides. But this is something that– Of course, there are other people that are much more informed on that topic than I am. Just the ubiquitous nature of these pesticides and the true consequences of them. 

[00:39:21] From just a fat cell scientist’s perspective, these are all chemicals that will in fact get integrated into fat cells, affecting the fat cell. In fact, even potentially affecting the ability of the fat cells to multiply, which, lest we think that’s a good thing, that means that the fat cell is forced to undergo hypertrophy, which of course, in the earlier part of our conversation, we described as a pathogenic way for fat tissue to grow. So it forces the fat cell into this more pathogenic pattern of growth. But at the same time, it’s like, there’s a kick on the way in and a kick on the way out. Because as you start to shrink the fat cell, in addition to the fats that are leaking out, you do start to leak and leach out these pesticides and even plasticizers, and they can then have other systemic effects. Now, inevitably, you need to get rid of them. And so I wouldn’t want someone to think, I don’t want to lose weight because I don’t want to have toxins in my blood. No, they’re there and you need to get rid of them. The only way to get rid of them is to, at least in this case, allow the fat cells to shrink and release these chemicals. 

[00:40:22] These chemicals do have a pattern for clearing from the body, namely through the liver, sometimes through the kidneys depending on exactly how the chemical is metabolized. So I would say it’s certainly a reason to stay very well hydrated during weight loss, just to help clear these out. But yeah, these are chemicals that will alter insulin resistance. They do influence fat cell biology and other tissues too. I just don’t focus on other tissues as much. My lab, in fact, has published a few papers looking at inhaled particles that go beyond the plasticizers and pesticides, which is generally considered persistent organic pollutants or POPs. And we’ve looked at inhaled pollution particles from combusted diesel exhaust or Wood Burning[?], that’s a new paper we have coming out, or cigarette smoke. These are molecules that will activate inflammation pathways within the body. No surprise there. These are very harmful molecules as we inhale them, and the fine particles get through the lung and start circulating in the blood. There’s evidence to even suggest that diesel particles accumulate in fat cells, just like these POPs that I just mentioned. 

[00:41:28] And our work actually, now with my collaborator, Dr. Paul Reynolds, and anyone can find his– He has a social media channel too, Paul Reynolds, PhD, where he talks more about the inflammation and these inhaled pollutants more than do. But yeah, our own work has contributed to this and we’ve implicated these same inflammation pathways, actually, that are activated with immobilization of the muscle. 

Cynthia Thurlow: [00:41:50] That’s really interesting. Now, I got quite a few questions and I’m going to give you the opportunity to say, “Yes, I’m comfortable talking about this,” or “No, this is not my area of expertise.” But there were many people, when they knew that we were connecting, they were curious to get your take on statins. So this is a class of medications, cholesterol lowering medications, certainly drugs that I prescribe quite a bit while I was working in cardiology. Can we talk about how statins and specific ones– I know Crestor is more likely to cause insulin resistance than something like Pravachol. How statins actually work mechanistically to decrease insulin sensitivity? 

[00:42:29] Because I know there was a study that came out around 2016, and I think every single patient of mine in cardiology that was taking a statin brought this information and said, “Am I going to end up developing diabetes because I’m on Lipitor at the time.” As a group, having to have a conversation, how are we going to discuss the research with patients, so they feel comfortable in the context of having cardiovascular disease? So lots of questions came in about statins. People concerned about taking statins, is it going to increase their likelihood of developing insulin resistance? 

Dr. Ben Bikman: [00:43:00] Right. Well, the very clear answer is yes. Yes, It probably will, especially for women. That’s where the strongest evidence is. The evidence in men suggesting that statins cause insulin resistance and increase the risk of type-2 diabetes is much smaller. Not to say it’s irrelevant, but the average woman will have a 50%, at least greater risk of developing type-2 diabetes with her use of statins. The irony is that a recently published paper confirmed, and this has been known for decades, that the leading cause of heart disease is diabetes. And so again, ironically, sure, the statin is controlling your ability to produce cholesterol, which very likely has no effect on heart disease risk. I’ll revisit that perhaps in a moment. But it is increasing your risk of diabetes, which is a far more relevant risk factor to heart disease than any cholesterol number is. So that’s what the study found. 

[00:43:55] Maybe I’ll frame the conversation this way. This paper that was published, very large paper, looking at the primary risk factors for heart disease and type 2 diabetes, nothing was even close to how relevant this risk factor was. And the least relevant of the risk factors was cholesterol. And so if you’re taking a drug that lowers your cholesterol, well, based on this evidence, cholesterol has almost no influence on your heart disease risk. So it is, in fact, possible to consider that you’re increasing your risk by taking the statin. But I’m not going to stick to that comment because I don’t have any evidence to that effect. However, working with two collaborators, Dr. David Diamond and Dr. Paul Mason, I published a paper last year that found that, if LDL levels were used as the marker to dictate the use of statins, it had no influence on the person’s survival. However, if a person had a high triglyceride to HDL ratio, statins did appear to have some benefit. 

[00:44:55] Now, I’m still not advocating the use of statins. I think statins are drugs where overwhelmingly the negative effects out offset any potential positive effect. I think any lifestyle gain that might be realized or any mortality benefit that might be realized by someone with a high triglyceride to HDL ratio, taking a statin would be much, much greater if they were just to change their diet, and reduce the triglyceride to HDL ratio, which is itself a much better predictor of heart disease risk than LDL. Unfortunately, statins don’t affect the triglyceride to HDL ratio in any meaningful degree. But they do affect LDL. 

[00:45:37] Maybe I’ll finish with this thought. There is significant evidence worldwide now, particularly in women, the lower cholesterol levels get, including LDL, the higher the risk of overall mortality. In other words, the more you push LDL down, the more likely you are to die. Whether it’s through an increased risk of diabetes, whether it’s an increased risk of cancer, whether it’s an increased risk of Alzheimer’s disease, all of these risks go up with statin use, all for the sake of trying to reduce the risk of heart disease. I think that statins are one of the most over prescribed medications on the planet that the number of people who would actually benefit from taking a statin are vanishingly small. It’s difficult to even know who would really benefit. But at the very least, basing a prescription of statin on someone’s LDL level is a horrible way to leverage that drug. 

Cynthia Thurlow: [00:46:32] Thank you for that. It’s interesting. Probably 10 years ago, I had an NIH researcher who was a patient of mine, and her cardiologist who I worked with, would always say, “She’s non-compliant. She won’t take the statin. Her LDL is terrible.” And I’ll never forget, she looked at me and she said, “This person has never asked me why I won’t take a statin. They just keep labeling me non-compliant.” But she said, “Do you realize what my research is in?” And so she started to explain her research. For purposes of anonymity, I will not say more than that. But when she explained mechanistically what statins were doing cognitively to many of the patients she was following, she explained, she was like, “My brain is something I’m not willing to run the risk of not being able to or to have any neurocognitive deficits, because this is how I make my living.” And so that was the very first time that I started to find this reframe about statins.

[00:47:22] And to your point about total cholesterol, in many instances, when I saw patients total cholesterol starting to fall underneath 150 and 125, and I would start backing down on doses of statins, I would get admonished. There were a group of a couple of cardiologists who would admonish me and I would tell them like, “Let’s look at the literature that’s showing the prognostic indicators on longevity for these patients if we get their total cholesterol under 100, and they can’t make any steroid hormones. Just the things that are happening. Nerve transmission in their brain and everything else, not to mention the fact that increased likelihood of developing diabetes. So thank you for that, because I probably get asked this question multiple times a week, and in many ways, I just keep referring them to other people’s work, so they can look at the research, so they can have that conversation with their physician. 

[00:48:09] I would love to wrap up the conversation today. This is probably a question you haven’t been asked fairly recently, but what do you think in terms of foods in our food supply here in the United States, where 60% to 70% of us are eating hyper-processed, hyperpalatable foods, what do you think is worse, seed oils or high fructose corn syrup? Do you have an opinion on that? 

Dr. Ben Bikman: [00:48:32] [chuckles] Yeah. I have looked at this discussion/debate with some degree of interest. I’ll start my answer by saying I wish there were studies that directly compared the two. Because in the absence of those studies, we are all just left to cite studies one side or the other. In other words, someone who firmly believes that the seed oils are the greater pathogenic contributor will cite seed oil studies. In contrast, someone who believes it’s more high fructose corn syrup and this fructose, or maybe even to expand it out, if you’ll allow me to just to say refined starches and sugars, they will cite those papers. In the end, I’m going to give a non-answer, not because I’m a politician. I have no aspirations to debase [Cynthia laughs] myself like that. But I will say that, I believe both of them are relevant and they just happen to almost always come together. The more we’re eating processed starches and sugars, the more they have been loaded with some seed oil of some kind. It would be almost impossible to split those two apart at a population level. 

[00:49:38] But again, in the absence of a study that compares them head-to-head, I just don’t want to commit because everyone is speculating, if they’re trying to put one over the other. Both of them have skyrocketed. Refined starches and sugars has skyrocketed sugar consumption. So has seed oils over the past century. The fact is, with seed oils, what I don’t think everyone appreciates is that you can burn seed oil. Linoleic acid can be burned. In fact, Dr. Steven Koonin’s work suggests that the brain will burn linoleic acid at such a high rate that it’s actually the most ketogenic fat for the brain itself, where the brain makes its own ketones from linoleic acid. Not that he’s stating it as a defense. I don’t believe he is, although I have enormous amount of respect for Dr. Koonin. I know him and really revered him, a wonderful guy and very smart. 

[00:50:31] But it’s important for people to know that linoleic acid is not purely pathogenic. It doesn’t have to turn into these lipid peroxides or these aldehydes like 4-HNE. Now, when they do, they are very pathogenic. So linoleic acid has a very dark side based on which pathway it commits to. Does it commit to the path–? I’m going to be very precise with my language. Does it commit to the path of oxidation which is burning it up as energy? We often use that term in place of the more accurate term, peroxidation. When it becomes a lipid peroxide, which is the absolute harmful molecules like 4-HNE, acrolein and a host of other very, very problematic molecules. Those molecules are absolutely problematic, and we eat way too much of linoleic acid to handle it just through burning it. There’s no question we’re overloading the body so much that we’re committing much of it to this pathway of peroxidation. 

[00:51:23] Now, at the same time, there’s no question that we’re over consuming fructose. And my good friend, Rick Johnson, at the University of Colorado has abundantly explored the role of fructose as a contributor to uric acid, and then the contribution of uric acid to insulin resistance, if I just stay on that topic, which allow me to stay on that topic, because each of these has relevance outside of the metabolic realm of insulin resistance. But again, I will say this. There is evidence of uric acid. And within the realm, within the conversation of high refined starches and sugars, much of what I focus on is the effect of elevated insulin. And chronic elevations insulin is, I believe, the main contributor to insulin resistance. And that paradigm has been validated in every biomedical model, whether it’s cell cultures, whether it’s rodents in a lab, or whether it’s humans. There’s evidence, both with uric acid and high insulin causing insulin resistance in all three biomedical models. 

[00:52:25] When it comes to linoleic acid and seed oils, there is evidence of them causing insulin resistance in isolated cells, there’s evidence of it causing insulin resistance and worse metabolic outcomes in rodents. But I am unaware of clinical studies, unlike the other side, that has shown the direct contribution of linoleic acid in causing insulin resistance in humans. I have heard that there are human studies, but I’ve not seen one. And until I do, I confess I can’t help but tip a little more on favor of the refined starches and sugars, simply because if I stack up the sum of all of the direct evidence either, including clinical trials in humans, I know there’s clinical trial evidence on this side. I just haven’t seen the seed oil human evidence. I know there’s correlational evidence at a population level, but of course, we need to go one step further. 

[00:53:17] So I guess to sum it up, in lack of a direct head-to-head comparison, I’m left relying on just the sum of all of their respective evidence. I believe it tips a little more in favor of refined starches and fructose, particularly in the context of insulin resistance. Now, a seed oil advocate may go further than that into other pathologies, but I can’t do that. I need to stay with what I know, and so I will in my answer. 

Cynthia Thurlow: [00:53:43] Well, I can’t think of a better way to end the conversation today. Dr. Bikman, please let people know how to connect with you on social media. You have a vibrant Instagram account. You have a wonderful podcast. Please let people know how they can connect with you and learn more about your work. 

Dr. Ben Bikman: [00:53:58] Right. Yeah, I appreciate it. Yeah, I’m active on social media @benbikmanphd. But also more and more, everything I do is at one website called insuliniq.com. So please go to insuliniq.com, and you can learn all about what I have going on now and what I have coming up in the future. 

Cynthia Thurlow: [00:54:14] Thank you so much. 

Dr. Ben Bikman: [00:54:15] My pleasure. 

Cynthia Thurlow: [00:54:18] If you love this podcast episode, please leave a rating and review, subscribe, and tell a friend.