Reversing Chronic Disease And Aging By Fixing Insulin Resistance

Speaker 1:
Coming up on this episode of The Doctor’s Pharmacy.

Dr. Ben Bikman:
My view is don’t get your carbohydrates from bags and boxes with barcodes.

Dr. Mark Hyman:
Hey, it’s Dr. Hyman. Welcome to The Doctor’s Pharmacy. That’s pharmacy with an [inaudible 00:00:17] place for conversations that matter. If you are curious about your metabolism, how it works, why it doesn’t, how carbs and sugar are driving every chronic disease that we see and how it’s all connected to this phenomena we call insulin resistance, which by now if you listen to me you know I’m obsessed about because it is something that we can can totally fix and it’s something that’s also driving tremendous havoc, including probably responsible for the catastrophic results of COVID in America. We are 5% of the world’s population and about 20% of the cases and probably 15 to 20% of the deaths, which doesn’t make any sense, except if you understand that what we’re going to talk about today is the problem, which is insulin resistance.

Dr. Mark Hyman:
We have a great guest today, Dr. Benjamin Bikman, who’s a renowned metabolic research scientist. He’s a popular speaker on metabolism nutrition. He’s done a ton of research to help us understand this whole phenomenon of insulin resistance. I’m excited to talk to him because I always like to learn more. He’s had his Doctor of Philosophy in Bioenergetics from East Carolina University and a post doctoral fellow in metabolic disorders with Duke National University of Singapore Medical School. Welcome, welcome, welcome Benjamin.

Dr. Ben Bikman:
Hey. Hey, Mark. My pleasure. Thank you.

Dr. Mark Hyman:
Okay. Let’s get into it. Now, we’re sick. Let’s face it. 88% of Americans are in poor metabolic health. Six out of 10 Americans have a chronic disease. It’s bankrupting our healthcare system. It’s global. I could go on and on about the data. Food is the biggest driver of death around the world. Period. Not smoking or anything else. We’re dealing with all these diseases that don’t seem to be getting better, despite advances in medical care. We have more and more we’re learning, more advances in every aspect of science and medicine, and yet we’re seeing cancer rise, heart disease rise, dementia rise, diabetes rise, obesity rise. Everybody’s struggling with these issues and a whole lot more. Things like high blood pressure, weight gain, fatty liver, dementia, low testosterone sex drive, menstrual issues, infertility. I could go on and on.

Dr. Mark Hyman:
We’re down in the weeds treating all these different problems. We’re treating blood pressure issues. We’re treating hormones with a pill. We’re trying to treat dementia with a pill, which doesn’t work. We’re trying to deal with all these drugs. We’re doing downstream treatment, but we’re not really getting success in moving the needle. In fact, we’re getting more and more. It’s like being in a sinking boat and bailing the boat instead of putting your finger in the hole or patching it up. What do all these problems that I mentioned have in common and why is it such a big issue?

Dr. Ben Bikman:
Right. Yeah. I like that you started with one of the more sobering statistics, namely the one found a couple years ago where they noted that 88% of all US adults were considered metabolically unfit. In fact, the authors who published that paper, they said an alarmingly low level of metabolic fitness. That was their words in that scientific manuscript.

Dr. Mark Hyman:
Alarmingly low, yes.

Dr. Ben Bikman:
Yeah. That’s sort of to put it mildly, but what too many people will overlook is the fact that metabolic fitness or the metabolic syndrome, which is how those authors were scrutinizing metabolic health, is really a function of insulin resistance. That this most prevalent disorder that we’re sitting on, it’s this deep foundation in the United States and abroad, which is why I’ve done research at universities outside the US, but insulin resistance really underpins not only the metabolic syndrome, but every disorder you just mentioned. Where our focus on clinical medicine nowadays has been that we’re just pruning branches from this tree. We prune the branch with some drug only to have the branch continue to grow back and we have to continue to prune it. Well, if we can get to the heart of it or to the root of it, then we acknowledge that insulin resistance is a root cause underlying virtually every chronic disease. Certainly everyone you just mentioned.

Dr. Mark Hyman:
Yeah. It’s so important because if you go to your doctor, they’re not testing for insulin resistance. I’ve been doing this for 30 years. I learned about this insulin resistance phenomena decades ago. Gerald Reaven, who was the pioneer in discovering syndrome X or metabolic syndrome, I heard him speak and I learned a lot about this and began to understand this and see it in my practice. When you go to the doctor, they check your cholesterol, they check your blood pressure, they check your blood sugar, they check all these things, but they don’t actually check the thing that is at the root of all those problems, which is insulin resistance.

Dr. Mark Hyman:
They don’t measure insulin. They don’t measure a glucose tolerance test with insulin and they don’t really assess your overall metabolic health because we’re not trained to do it, and we don’t know what to do about it, except diet and maybe Metformin, but it’s just striking to me that this is the central problem facing healthcare right now today, and 90% of people who go to the doctor who have this problem, it’s not diagnosed. Why is that? Why are we just so dumb about this?

Dr. Ben Bikman:
Right. Well, I think that there are two reasons. One is scientific and one is historic. Scientifically, it’s been much easier to measure glucose. Glucose is something that we can measure so easily that we can put a little clamp, a patch… and you and I are both familiar with levels, and we can put a little glucose monitor on someone’s skin and get a continuous measurement of their glucose, but we’ve only been able to measure insulin for a handful of decades. Even then, the cheapest way to do that is actually using radioactive chemicals. Now there are easier and newer ways to do it, but there’s the scientific hurdle in measuring a very small molecule, a hormone, insulin.

Dr. Mark Hyman:
I’ve been measuring insulin for 30 years. It’s been available to measure.

Dr. Ben Bikman:
Oh, no. I know.

Dr. Mark Hyman:
It’s not expensive.

Dr. Ben Bikman:
It absolutely been available, but my view is that we got it all wrong in that we have a glucose centric view of metabolic health. When we’re tracking someone’s metabolic health, we’re obsessed with the glucose because glucose is easier to measure, and historically it was the cause of the most prevalent sign of diabetes, which was the polyuria. Someone has very high urine production because of the high glucose, and you could detect the glucose in the urine. We can kind of forgive our academic ancestors for thinking that it’s all a glucose problem, but there was an incredibly compelling paper a number of years ago talking about how one of the earlier scientists, physicians who studied diabetes, Minkowski, they noted that what if Minkowski had been ageusic or had not had a sense of taste and that when he sampled the urine, basically…

Dr. Mark Hyman:
When you drink your urine.

Dr. Ben Bikman:
Yeah. The idea was… it was kind of a funny idea, but the idea had been if these early physician scientists had not been able to detect the glucose in the urine, they might have rather noticed the acetone on the breath because of the person having such high levels of ketones. Rather than calling this a glucose problem, they might have called it a fat burning problem, and at least that would’ve gotten us one step closer to looking at insulin because insulin, of course, dictates fuel use. We have a glucose centric paradigm, I think, because of scientific precedent and historical view, but it’s unforgivable now.

Dr. Mark Hyman:
It is. We know. The data’s there. It actually reminds me of this joke, which I often tell at my lectures. There’s this guy looking for his keys under the lamp post and his friend comes by and says, “What are you doing?” He says, “I’m looking for my keys.” He says, “Where’d you lose them”? “Well, I lost them down the street.” He says, “Why are you looking over here?” He says, “Well, the light’s better over here.” The glucose is like where the light is.

Dr. Mark Hyman:
It’s easy to check, which really fascinates me and a huge ah-ha moment for me in medicine was 25 years ago. I had a patient who looked like an apple. She was just a classic giant belly, skinny leg, skinny arms. Looked like the Tasmanian devil. Not a very nice thing to say, but she was a very sweet woman. I’m like, this woman’s got problems. She’s got pre-diabetes something, something. I’m like, checked her blood sugar. Perfect. Checked her A1C, which is the average blood sugar for six weeks. Perfect. I’m like, something’s off, because she had high triglyceride, she had low HDL. She had a lot of other signs. I’m like, this is weird. Let me do a glucose tolerance test, but also measure insulin, because the truth is by the time your blood sugar goes up, by the time your A1C goes up, you’re way down the road of metabolic disaster. It’s a late stage phenomena to see your blood sugar go up fasting.

Dr. Mark Hyman:
What I did was this glucose tolerance test, but instead of just giving her a test for glucose fasting at one and two hours, I did also insulin. This is the key here. This is a test that is, I would say, almost never done except by functional medicine docs. I’ve been doing it for 30 years on almost everybody I suspect. It’s just so informative. Her blood sugar fasting was probably 85, 90. Normal, optimal. At one and two hours, never went over 110, which is amazing. Great. Her fasting insulin was 50 and it should be under five and ideally under two, and her one and two-hour insulin, her one hour, it was like 200 and something, which is just you rarely see. Hr insulin was just massively being pumped out from her pancreas to try to keep her blood sugar in control. That’s what’s happening to us.

Dr. Mark Hyman:
Now that we understand that insulin is this driver of all these downstream consequences, take us through the landscape of what high levels of insulin do to the body over time and why it ends up causing all these chronic diseases. Take us down that road.

Dr. Ben Bikman:
Yeah. Mark, by now I’m certain your audience would have a … can I take a moment and just explain how I define insulin resistance really briefly?

Dr. Mark Hyman:
Sure. Okay. Oh, yeah. Let’s talk about that. Let’s talk about that because I have ideas about that.

Dr. Ben Bikman:
Well, and I’m certain that our ideas would align, but as I have kind of had to fine tune my thinking to express this to undergraduates, I believe that, in my view, insulin resistance is a coin with two sides. On one side of the coin, there is this phenomenon of altered insulin signaling, where the hormone insulin itself isn’t acting the same way that it used to at various cells in the body. Now that’s relevant because literally every single cell in the body has insulin receptors or little doorways for insulin to come and knock on. In some of those cells, insulin isn’t working the same way that it used to. Now in some of the cells, insulin’s working as well as it ever did, but nevertheless, that’s the altered insulin signaling or the insulin resistance per se at the level of the cell. We’re talking about the whole body. When we flip the coin over, it’s this other aspect that you cannot pull apart from the insulin resistance, and that is hyperinsulinemia or the chronically elevated insulin. You just noted that you’d seen that decades ago.

Dr. Mark Hyman:
One is how the insulin works on the cell and the problems of insulin actually doing its work because the cells are resistant to the effects of insulin. Two is super high circulating levels of insulin in the blood and what that does.

Dr. Ben Bikman:
That’s right. Yep. It’s the convergence of those two things that create the insulin resistance that we’re talking about. In fact, now that’s a perfect segue to talk about some of the disorders, and you’ve mentioned many. Just for the sake of illustrative purposes, let’s just kind of highlight two. The liver. The liver becomes insulin resistant specifically to what insulin’s trying to do to glucose, and insulin doesn’t tell the liver to take in glucose, but it tells liver what to do with glucose and that’s thematic of insulin throughout the body. Insulin tells the cells what to do with energy, because otherwise truly a cell doesn’t know. I grow fat cells in my lab all the time. We have little cultured fats cells, and we can have those fat cells swimming in a sea of calories, glucose and fatty acids galore, triglycerides galore, but the fat won’t know what to do with it. The fat cells, unless there’s insulin. The moment we spike in insulin into the culture, now the cells know what to do. Then they’ll start storing the fat, turning the glucose into fat, which fats cells do absolutely, then taking fat in and storing it as a triglyceride. Stored fat.

Dr. Ben Bikman:
Now, back to the liver. The insulin tells the liver what to do with glucose. Specifically it tells it to store the glucose and inhibit the breakdown of the glucose, inhibit the glycogen breakdown, but when the liver becomes insulin resistant, even though insulin is high, blood glucose levels might even be high in this case, but insulin’s trying to tell the liver to store glucose, but it doesn’t get the message because it’s insulin resistant. Now it’s pumping out glucose, further amplifying the glucose, which is further pushing up the insulin and the whole thing keeps moving.

Dr. Mark Hyman:
That’s like a vicious cycle.

Dr. Ben Bikman:
That’s exactly right. Yeah. In contrast, the ovaries, the theca cells of the ovaries, those are the parts of the ovary that produce all the sex hormones, the estrogens and the androgens. Testosterone and estradiol, for example. Those cells do not become insulin resistant. Now they’re swimming in this sea of insulin, and insulin normally elicits this inhibitory effect on the ovary’s ability to convert androgens into estrogens, and you of course know this and your audience I’m sure knows it to a degree, but all estrogens were once androgens. They come from testosterone and there’s this enzyme called aromatase that will mediate; that will make this transition. It’ll take the testosterone and turn it into estrogens.

Dr. Ben Bikman:
Well, this high level of insulin in the body that is insulin resistant actually is inhibiting aromatase’s ability to convert these sex hormones. Now her ovaries that are desperately trying to convert testosterone to estrogens can’t, so her estrogens are too little and she has an abnormal ovulatory cycle leading to polycystic ovary syndrome, and her androgens, her testosterone levels, are too high, which is what can give a woman more facial hair or coarse hair, acne, and even male pattern baldness.

Dr. Mark Hyman:
That’s how that works. I’ve always wondered how does insulin resistance cause high testosterone in women and low testosterone in men? I think you just explained it.

Dr. Ben Bikman:
Yeah. In fact, the interesting thing in men, to make it one step further in men, oddly, when a man’s fat cells, when his subcutaneous fat cells are expanding, and this does not happen in women, his fat cells start to express higher and higher levels of aromatase, that same enzyme that the woman has high levels of in her ovaries. It’s almost like his fat cells begin to act like ovaries, converting testosterone into estrogen.

Dr. Mark Hyman:
My joke is that with too much sugar and starch from your diet, by the time women are 65 and men are 65, they look about the same because the women get hair on their face and lose the hair on their head and men get breasts and lose the hair on their face.

Dr. Ben Bikman:
Yep. Women start storing their fat. Women, because the estrogens are coming down, sex hormones tell the body where to store fat. As her estrogens are coming down to lower levels and her androgens are relatively higher, she literally starts storing her fat more where the man is storing it.

Dr. Mark Hyman:
In the belly.

Dr. Ben Bikman:
Centrally.

Dr. Mark Hyman:
In the belly. How do you know if you have this problem? You can get your insulin checked after a glucose tolerance test or fasting insulin. That’s really important. I encourage everybody to get that checked who has any idea. Fasting insulin should be just a part of any diagnostic test.

Dr. Ben Bikman:
Mark, you were so ahead of your time. The fact that you were doing dynamic insulin tests and dynamic glucose challenges, that really is the value to me. Continuous glucose monitors are valuable mostly because it gives you real time dynamic assessments where you can challenge your body and see, all right, how long does it take me to get back to normal when I ate that bagel? That’s really so illustrative and people, once they see it, they never forget it.

Dr. Mark Hyman:
It’s more complex than. This woman, she would’ve had a glucose monitor and it would’ve been normal.

Dr. Ben Bikman:
You’re right. You said it didn’t go up.

Dr. Mark Hyman:
She was really next to having a heart attack. I think there’s a huge heterogeneity in this. I think you’ve got to watch out for that. Tell us about the ways in which the insulin is actually causing the damage, because from my perspective, we now know there’s a whole downstream set of biological factors. Yes, there’s all the diseases we just mentioned. We don’t have to talk about those again, but what are the actual mechanisms, besides, for example, increasing the testosterone in women, lowering testosterone in men? What else happens? The visceral fat, more storage of fat in the cells. What’s going on biologically, because it’s so vast in terms of the mechanisms. I want you to sort of dig into that a little bit.

Dr. Ben Bikman:
Yeah.

Dr. Mark Hyman:
The reason I want you to do that is because all the hallmarks of aging, almost all the hallmarks of aging and chronic disease are driven by this mechanism. If you understand this, it’s going to help you understand how to eat and live in a way to control your insulin

Dr. Ben Bikman:
I agree. Yeah. In fact, not to pull this onto a tangent, but so much of the focus on longevity nowadays is focusing on a protein within every cell called mTOR and everyone is everyone’s going on and on about mTOR. I think that there’s justification to do that. Now, because cause we see in various experimental laboratory models, like insects and rodents, if you inhibit mTOR, the animals live longer. That’s very, very clear evidence. Now we don’t have conclusive evidence in humans that that happens, but I am comfortable assuming it’s relevant. We just can’t do that kind of study in humans, but I do think mTOR is relevant to human longevity. This has had people focusing on protein because amino acids will spike mTOR, but I think that’s unfortunate because while amino acids do spike mTOR, it’ll turn mTOR on and then it turns it off pretty quickly.

Dr. Ben Bikman:
Insulin increases mTOR far more than amino acids do and keeps it elevated longer, and we’re spiking insulin literally. Mark, most people, as you know, are spending every waking moment in the state of elevated insulin. Insulin has come down overnight because they’ve been fasting hopefully for 12 or so hours, but what do we do around the world? Not just in the US, we eat a starchy sugary breakfast, insulin spikes, and then they’re hungry again two hours later, they spike it again and again and again. Every waking moment is spent in a state of elevated insulin, which is activating mTOR, which is certainly, I would believe, promoting aging, but that chronically elevated insulin also is one of the primary drivers of insulin resistance. It’s representative of a fundamental biological process where too much of a signal will result in a resistance to that signal, so the body is inundated with insulin.

Dr. Mark Hyman:
It’s like the boy who cried wolf.

Dr. Ben Bikman:
Yeah, that’s right. Yeah. That’s exactly right. In fact, I use a joke in my family where… my wife’s an at home mom, so she’s going straight to heaven someday. She’s at home with the kids raising the kids, and when I’m home with the kids, I will notice it’s interesting dynamic where the kids will be calling out for mom or they’ll be fighting or arguing about something or calling out and my wife doesn’t hear it. She’s become deaf to the kids’ complaints and to their cries for help or whatever it may be. When I’m home, because I don’t hear it all the time, I’m exquisitely sensitive to it. They’re whining or they’re bickering and I’m immediately intervening trying to put the fire out and mom, she’s just kind of deaf to it.

Dr. Ben Bikman:
Anyway, when we appreciate, again, that insulin resistance is these two sides of the coin, we can almost go top to bottom and start to identify how insulin resistance is contributing, directly causing or exacerbating virtually every disease. My lab has recently started focusing more and more on neurophysiology and Alzheimer’s disease. We published a paper earlier this year where we actually had access to postmortem hippocampus samples. The hippocampus is the part of the brain that’s involved in memory and learning. That’s the part that’s presumed to be most compromised in Alzheimer’s disease. We found, this was in humans, that every single gene involved in glucose metabolism was significantly down compared in the people who died with Alzheimer’s disease compared to those who had died without. We compared that with the genes involved in ketone metabolism, because those are the two fuels used by the brain; glucose and ketones. The ketones metabolism genes were fine.

Dr. Ben Bikman:
The theory in the lab, and others have been looking at this too, like Steven [inaudible 00:21:32] up in Quebec, up in Canada, he’s a tremendous scientist, but we find that the brain has insulin dependent glucose transporters. This is part of what’s going on in the body. In insulin resistance, insulin is, and you noted this perfectly when you described that case earlier. High insulin but normal glucose, and then the body starts to get so resistant to the insulin that it can’t keep the glucose in control anymore. Then 10 or 20 years later, now the glucose levels start to climb. You expressed that perfectly. In the brain, the same phenomenon can start to happen. Even though the brain may be swimming in a sea of glucose, the body might be hyperglycemic, but insulin has to be working sufficiently to come to the hippocampus, the part of the brain, knock on the door, open the doors for glucose to come in and fuel the brain. That’s relevant because the brain has a very high metabolic rate. Much higher than muscle does.

Dr. Ben Bikman:
Because most people are always eating starchy, sugary foods and they’re keeping their insulin up, they never have any ketones. Ketones are essentially below the level of detection in most people, but the brain is swimming in the sea of glucose, but because insulin can’t work, it can’t get enough. The brain’s energy needs are right here, but now it can’t get enough glucose, so you have this energetic gap and that the body just can’t meet. It just can’t fill it up because insulin isn’t getting enough glucose in. You’d say well, let’s just push the ketones in to fill that gap. Well, the person doesn’t have any ketones because insulin stops the production of ketones. The brain is swimming in a sea of glucose and starving in the midst of it. That’s how insulin resistance is relevant at the brain. Maybe we’ll just pick one more like blood vessel.

Dr. Mark Hyman:
That’s why they call now dementia type three diabetes.

Dr. Ben Bikman:
That’s right. That’s exactly right. I like that term in that it evokes this metabolic origin, but I like the idea of insulin resistance of the brain. Once again, just to be really precise. Because that is the specific disorder

Dr. Mark Hyman:
To put a visual on it, literally, as your belly expands, your brain shrinks.

Dr. Ben Bikman:
Yeah. Well said.

Dr. Mark Hyman:
Big belly, small brain. Small belly, big brain. Better working brain, which affects depression, Alzheimer’s, many, many biological disorders of the brain.

Dr. Ben Bikman:
Migraines. Yep. Migraine headaches. In fact, one of the things that was so interesting for me, Mark, there are published manuscripts from the 1930s from physicians. These are MDs noting in their clinic and publishing these case reports where they would take patients with migraine headaches. There was two. One in the early 30s and one in the late 30s, I think, or maybe early 40s, but they noted that they would take these patients with frequent migraines and put them onto low carbohydrate diets and fasting regimens to increase their ketones. The migraines went away. Resolved. This is very common. Now it’s not universal. There are different types of migraines, of course, but it’s surprising to me how common it is, where you can detect it. Even in migraine, just like it is in Alzheimer’s disease, there’s this phenomenon referred to as brain glucose hypometabolism. Essentially the brain cannot metabolize glucose sufficient to meet its energetic needs, so you just start making some ketones and you fill in that gap.

Dr. Mark Hyman:
It’s really extraordinary. We’re going to talk more about how ketogenic diets and other dietary approaches can actually influence things like autism and Alzheimer’s and even other neurologic…
PART 1 OF 4 ENDS [00:25:04]

Dr. Mark Hyman:
And even other neurologic disorders that we’re seeing and how that works. But I want to get into this study that you did with my friend, David Ludwig, who’s from Harvard, where you looked at the metabolic rate from fat samples, from belly fat and found that the low carb diets had much higher increase in the metabolic rate in the fat tissue compared to the people eating high carb diets. In other words, if you eat a high fat diet, your metabolism is faster. If you eat a high carb diet, your metabolism’s slower. How did that work? What happened? What was the study?

Dr. Ben Bikman:
Yeah, yeah, yeah. So Mark [crosstalk 00:25:42].

Dr. Mark Hyman:
People are like, “I have a slow metabolism.” Well, okay, maybe they’re right. Maybe they’re right. And how is it working?

Dr. Ben Bikman:
Yeah. I just have to mention this because it’s such a fascinating history. So when David and I started collaborating on this, it was in response to some other studies that we’d been doing in my lab, looking at the differential effects of insulin and ketones on fat metabolic rate, fat cell metabolic rate. But that whole study was born from studies in the early 1900s. So just as a brief history, because I know your audience is going to find this fascinating, at least, I hope. My students sure do. So I’m sure they will.

Dr. Mark Hyman:
Sure, sure. Bring it on.

Dr. Ben Bikman:
So this is too early scientists, Elliott Joslin, who is considered the godfather of endocrinology and Francis Benedict. Francis Benedict’s really considered the godfather of metabolic rate. These two scientists-

Dr. Mark Hyman:
The Harris-Benedict equation. Yes. I remember that from medical school.

Dr. Ben Bikman:
That’s exactly, yep, yep, yep, yep [crosstalk 00:26:34].

Dr. Mark Hyman:
And the Joslin Diabetes Center at Harvard. Yes, absolutely.

Dr. Ben Bikman:
That’s right. Yeah. So that’s how well known both of these characters are. And they were legends. And they noted, working together in the early 1900s that people with type 1 diabetes, they didn’t call it type 1, it was just diabetes, people with diabetes had a metabolic rate that was about 20% higher than it was supposed to be. Because metabolic rate is connected to body weight essentially. A bigger body has a higher metabolic rate. A smaller body has a lower metabolic. And what they found in these people, metabolic rate was much higher than it was supposed to be. And then decades later, this is well into the 20th century now, late 20th century, then other scientists found the same phenomenon. These were studies done at the University of Minnesota that people with untreated type 1 diabetes … Because this was before, when Joslin and Benedict were doing this, there was no insulin yet. No discovered, not used.

Dr. Ben Bikman:
And then decades later, scientists confirmed those original findings that metabolic rate was significantly higher in type 1 diabetes, higher than it was supposed to be. And when they gave the people insulin to control the diabetes, their metabolic rate went immediately down to normal. It dropped that excess 20%, went right to where you predicted it should be. And so insulin, so that study, as my students and I were noting this and fascinated by it, we thought, “Well, let’s start looking at what happens in the fat cell in these conditions.” And so sure enough, we found in fat cell cultures and in animals, when we artificially increase the insulin, we could take the brown fat cells … So brown, all people have brown fat and white fat. And white fat is the prototypical storage fat, what we pinch and jiggle. And it has a very, very low metabolic rate, very, very low, almost [crosstalk 00:28:19].

Dr. Mark Hyman:
I don’t jiggle. I’m sorry. I don’t jiggle. I don’t jiggle. I won’t go for jiggling. I got a little bit to pinch, but that’s it.

Dr. Ben Bikman:
Yeah. So those are the people, that metabolic [crosstalk 00:28:33].

Dr. Mark Hyman:
If you jiggle, you’re in trouble. That’s what he’s saying, guys.

Dr. Ben Bikman:
Yeah, that’s right.

Dr. Mark Hyman:
Because if you jiggle, that’s the problem. [crosstalk 00:28:37]. I call it the mirror test for diagnosing, if you have this problem. You stand in the mirror with your shirt off. You jump up and down. If you jiggle, you have this problem.

Dr. Ben Bikman:
Yeah. Yeah. Well said. Yeah, that’s the poor man’s method.

Dr. Mark Hyman:
We would call it the jiggle test. We call it the jiggle test.

Dr. Ben Bikman:
So we have that white fat with a very low metabolic rate. Then all people to some degree have what’s called brown fat. And that’s typically up around in this chest area. And that has a very high metabolic rate, as high as muscle does. So 10 times higher than the white fat does. Where we found that when we artificially pushed the insulin up, the brown fat metabolic rate was depressed. It dropped to a level that was quite close to the white fat metabolic rate.

Dr. Mark Hyman:
Wow.

Dr. Ben Bikman:
In contrast, when we increased ketones, then we took the white metabolic [crosstalk 00:29:25].

Dr. Mark Hyman:
In a high fat diet.

Dr. Ben Bikman:
Yeah. Like on a ketogenic diet. Or in the lab cultures, it was just actually treating the fat cells with ketones. Then that metabolic-

Dr. Mark Hyman:
It’s injecting ketones, yeah.

Dr. Ben Bikman:
Mm-hmm (affirmative). That’s exactly right. And that metabolic rate went up about 10 times, almost to the level about of the brown fat.

Dr. Mark Hyman:
Wow.

Dr. Ben Bikman:
And then in humans, this is where the study comes in with David. Now these are unpublished data. So everyone know, please, these have not been formally peer reviewed and published. It’s in review right now.

Dr. Mark Hyman:
You hear it first here, folks.

Dr. Ben Bikman:
Yeah. That’s right. Yeah. Before it’s even hot off the press.

Dr. Mark Hyman:
Hot. Exactly.

Dr. Ben Bikman:
Yeah. So in the printer. So what David did, they had access to this population of people that they’d taken a fat biopsy from the belly at day zero and then followed it up several weeks later, about anywhere between, I think, 12 to 15 weeks after being on three diets. [crosstalk 00:30:12].

Dr. Mark Hyman:
Humans, not mice, right? Humans, not mice.

Dr. Ben Bikman:
Humans. That’s exactly right. Yeah.

Dr. Mark Hyman:
Okay. Yeah. Okay, good. All right.

Dr. Ben Bikman:
And this was something that was so important because me at a PhD at a primarily undergraduate university, it’s difficult to do this. We’ve done fat biopsies before here-

Dr. Mark Hyman:
You’re like a doctor, but you’re a mouse doctor.

Dr. Ben Bikman:
Yep. That’s right. Yep. I can tell you what’s happening in the cells much better than I can listen to someone’s heartbeat.

Dr. Mark Hyman:
So tell us. I’m so excited. I’m on the edge of my seat. What happened? I won’t interrupt anymore.

Dr. Ben Bikman:
So these three groups, people put on three different diets. They all had the same amount of protein and same amount of calories. So the caloric level between all three diets was the same. So protein was clamped. And then all it did was differ in the ratio of fat to carb. And we found that the group that had the highest carb diet had no change in their metabolic rate on their fat cells specifically. However, the two other groups that had the lower carbohydrate, higher fat, they had significant increases in their fat cell metabolic rate. Now this coincides and it went up by about two or three times [crosstalk 00:31:13].

Dr. Mark Hyman:
Now, what are you talking about with low … give us the ratios. What’s the amount of fat, amount of carbs? It was like extreme or was it-

Dr. Ben Bikman:
Yeah, yeah. So David would confirm. So I think the moderate group was for about a 40% carb and then the other group was 20% carb or so. I think it was right around there. So nothing-

Dr. Mark Hyman:
So the low carb was 20%. It wasn’t ridiculously low, like less than five grams of carbs or 50 grams a day.

Dr. Ben Bikman:
That’s right.

Dr. Mark Hyman:
It was really, it was really actually doable.

Dr. Ben Bikman:
Oh, oh, I would absolutely say that it’s very doable. [crosstalk 00:31:40].

Dr. Mark Hyman:
Okay. So it wasn’t a ketogenic diet. It was actually just a lower starch sugar diet.

Dr. Ben Bikman:
Yep. Yep. That’s right. Yep. And sure enough, the metabolic rate went up about two or three times in these people, from the same person, from their fat tissue, from the same area in their body. So it just goes to show that as much [crosstalk 00:31:58].

Dr. Mark Hyman:
So folks, what that means, folks, by the way, wait, what that folks means is if you’re sitting watching Netflix, you’re burning two or three times more calories. That’s what that means. Right?

Dr. Ben Bikman:
Yeah. Yeah, that’s right. Yeah. I would say if you are living a life where your insulin is low and there’s some hint of ketones coming up, then you absolutely are experiencing a higher than normal metabolic rate. And this is so important because in my mind, it starts to represent this convergence of what has been viewed as these two opposing ideas of human obesity. On one hand, we have the pure caloric thermodynamic enthusiasts that obesity is purely a matter of calories in, calories out. And anything else be damned. On the other hand, to sort of straw man each of these, we have this idea that no, it’s purely a matter of insulin, that it’s purely a matter of hormones, and then the energy component is less relevant. In my view, the two actually go hand in hand-

Dr. Mark Hyman:
For sure, for sure.

Dr. Ben Bikman:
… that we have to account for energy. Of course we have to. But we have to account for it through the lens of human biology. We are not these perfect little thermodynamic machines. We are complex biological organisms, and hormones tell the body what to do with energy. And when insulin is low, we have these advantages. One, we have an actually elevated metabolic rate. This has been shown in David Ludwig’s group, multiple times through multiple different tests. And even some of his detractors have shown the same thing. Others have found this where, when a person has low insulin, elevated ketones, their metabolic rate is higher.

Dr. Ben Bikman:
So one, metabolic rate is high. So the caloric output is higher. But two also, if someone has low insulin, then they’re making ketones, as we noted. And when ketones are elevated, the person is literally excreting ketones from their body. They’re breathing ketones out. They’re urinating ketones out. And every single ketone has the caloric value comparable to a molecule of glucose. So we are actually taking energetic molecules and then just dumping them from our bodies. So these are calories that didn’t have to be burned, didn’t have to be stored or burned, eat less, exercise more.

Dr. Mark Hyman:
You pee them out. You breathe them and you pee them out.

Dr. Ben Bikman:
Yeah. And you breathe them out. Because that’s what ketones are. Imagine a long string, and a ketone is when we basically cut that string into pieces. That’s what’s happening when we’re burning fat. We’re taking a big long carbon molecule, pulling off two little carbons at a time. If someone is making ketones, it’s literally those little pieces of fat that we’re splitting apart. That is what a ketone is. And so the person is literally breathing out these byproducts of fat burning or urinating these byproducts of fat burning.

Dr. Mark Hyman:
That’s really incredible. We now are really understanding this. And what I’ve seen in other studies that David has done, for example, this was a mouse study, so I don’t like animal studies, but sometimes we have to do them in medicine. What they did was fascinating. They took these mice, identical, and they gave one group a very high carb, low fat diet and another, a low carb, high fat diet. And they gave them identical calories. And then what happened was in the group, like you were saying, would be low carb, high fat, they started losing too much weight. So they wanted to keep the weight of the animals the same. So they actually had to increase the calories on the low fat group.

Dr. Mark Hyman:
And then at the end of the study, they harvested these animals. And the low fat group that was having more calories didn’t have the problems that the high carb group had, which is all this belly fat, inflammation, poor metabolic function. It was fascinating to me. And the other thing that’s so fascinating about this, and I had dinner with David once and he said, “Mark, if you look at type 1 diabetics, what happens to them, right? They lose weight because they can’t get the fuel into the cells because they have no insulin because their pancreas is basically demolished by an autoimmune disease.” And they literally come in with the classic symptom we learned in medical school, which is polyphagia, which means you eat and eat and eat and eat. So they literally could eat 10,000 calories a day or 100,000 calories a day and lose weight. Which is a-

Dr. Ben Bikman:
And they’re scrawny. Yep.

Dr. Mark Hyman:
Right. And it’s an exact example of this phenomena in an extreme situation where, if your insulin is low, it’s very hard to gain weight and it’s easy to lose weight. And I think a lot of the keys to understanding our metabolism, and by the way, there are a lot of factors that drive obesity and we’re just focusing on, I think, the biggest one. But toxins play a role. Other hormones play a role. The microbiome plays a role. Inflammation from various insults plays a role. So it’s not just this. But I would say it’s the predominant mechanism for obesity in America. And-

Dr. Ben Bikman:
I would add in type 1 diabetes, like you mentioned, this phenomenon is so known by type 1 diabetics, that insulin is controlling their fat growth, that you have this disorder nowadays called diabulimia, where you have type 1 diabetics who are-

Dr. Mark Hyman:
Diabulimia. Wow.

Dr. Ben Bikman:
Yep. These type 1 diabetics are deliberately under-dosing insulin in order to stay thin. So they learn early on. And imagine how tempting it is. You have a young teenage, usually a girl, certainly, who they have more pressure than boys do, but even still a young teenager, who’s very self-conscious of their growing bodies. And they’ve learned, imagine the temptation, they’ve learned they can eat anything they want, they can eat that cake, they can eat those brownies, those cookies, whatever, that soda. And they don’t have to go vomit. They don’t have to go through the discomfort of throwing up. All they have to do is not poke themselves with a needle-

Dr. Mark Hyman:
Insulin. Let their blood sugar be high.

Dr. Ben Bikman:
… and they can stay as thin as they want to. Oh, it’s catastrophic. They’re in ketoacidosis.

Dr. Mark Hyman:
It’s catastrophic.

Dr. Ben Bikman:
Their glucose is 800 milligrams, so they’re dying.

Dr. Mark Hyman:
Wow. Die of bulimia. Wow.

Dr. Ben Bikman:
But they look great. Yeah. But that’s just a testament. That’s just the proof of how powerful insulin is in controlling this, where you have type 1 diabetics who deliberately under-dose insulin because they know they can eat whatever they want and they’ll stay as thin as they want.

Dr. Mark Hyman:
Well, what you’re talking about also explains the phenomena of why ketogenic diets reverse type 2 diabetes better than any other treatment, and why people who do time-restricted eating and give themselves 12, 14, 16 hours between dinner and breakfast actually are more effective at losing weight, or why people who are in calorie restriction, which also does the same thing, like the fasting mimicking diets also does the same thing. So we are seeing from the science emerging that the key, if you can keep your insulin low, is that it helps to release everything. And from my experience as a doctor, the thing that insulin does is just catastrophic. One, it drives all the fuel into the fat cells, and whether it’s fats or sugars. Two, it locks them in there. It prevents them from getting out. Three, it turns these fat cells in your stomach into catastrophic hormone and cytokine producing machines that disregulate your biology, increasing inflammation.

Dr. Mark Hyman:
For example, why is COVID ravaging the obese? Because their fat cells are making IL-6 or interleukin-6, which is a powerful cytokine inflammatory molecule called the cytokine storm. That is what’s driving all of these problems. And in addition, it changes your hormones, as you mentioned, with estrogen and testosterone. It also changes your brain chemistry and makes you hungrier. And it creates a catastrophic effect on your cholesterol, on your blood pressure. It drives oxidative stress, inflammation, increases your blood clotting, it increases uric acid levels. It causes a whole series of downstream effects. It causes fatty liver. It starts to affect your kidneys and increase protein in urine. So you’ve got these massive effects that are explaining all the underlying biology of aging. And so the take home message from what you’re saying in your research and David’s research is that if you keep your insulin low by various mechanisms, right, diet, exercise, stress reduction.

Dr. Ben Bikman:
Yep.

Dr. Mark Hyman:
I mean, if you’re stressed, your blood sugar’s going to shoot up. Meditate to lose weight. That’s my new slogan, right? So this is really-

Dr. Ben Bikman:
Yeah, yeah. That’s good.

Dr. Mark Hyman:
… the biggest pandemic to actually face humanity ever. And we’re talking about COVID being a problem. But I mean, gosh, three quarters of the deaths globally, which is, I think it’s 60, 70 million a year, I mean, actually are caused by some level of this poor metabolic health. And it’s driving, of course, not just weight issues and diabetes, but cancer and dementia and depression and infertility and all these other phenomena. So your research is so important to help us tease apart these mechanisms. And the question I would have for you is, for people listening, how do we start to think about changing?

Dr. Mark Hyman:
Because not everybody wants to go on a ketogenic diet, nor is it advisable, or is it a good? Even though, by the way, you mentioned Joslin, the way they treated type 1 diabetics was a 75% fat diet, 20% protein and 5% carbohydrates. And by the way, what kept alive. But also by the way, was the way that we discovered America was through borrowing the Native Americans’ superfood packet, which was called pemmican, which was made up of basically rendered fat from bison, a few berries, and the protein. And literally a man needed a pound a day and a woman needed a half a pound a day. And so if you had 30 pounds of this stuff in your backpack, you could basically eat for a month and survive.

Dr. Ben Bikman:
Yeah. Yeah. There’s no question that you and I, of course, are aligned when it comes to having a favorable view of fat. And mark, I like what you were saying a moment ago, and you’re being careful in your language which, of course, as a scientist, I appreciate precision. You and I, we’re not claiming that insulin resistance is the cause of every disorder, but there’s little doubt that it is a key contributor. It is causing many chronic disorders and it’s contributing to virtually every other one. So my view, one of the things I hope people take away from this discussion is I can imagine someone who’s opening their medicine cabinet, not that either of us is giving any medical advice here. But they’re looking at their medications. And they see their medication for their diabetes or one or two or three medications for their diabetes.

Dr. Ben Bikman:
They may have a medication for their migraines, a medication for their fertility disorder and their blood pressure, little knowing that all of those do have a common connection with insulin resistance. And when it comes to controlling insulin resistance, you are absolutely right. There are multiple inputs into this. There are various ones. And I’ve looked at them and consider various levels of them. And to me, there are three primary causes of insulin resistance. And by primary, I mean that literally I can cause insulin resistance in isolated cells in laboratory rodent and in humans with all three of these, and that is elevated insulin itself, elevated stress hormones, and elevated inflammatory proteins or cytokines. All three of those things are considered primary in my definition, because you can just make insulin resistance happen at the cell in the rodents and in humans, all three biomedical models.

Dr. Ben Bikman:
But as you were alluding to, if we were to tell someone, “All right, here …” But there are others, like you said, like noxious toxins that can accumulate in fat cells and alter fat cell growth. Absolutely, that is relevant. So I’m not suggesting that there aren’t others. There are. But I put these ones as the holy trinity or the unholy trinity of insulin resistance. But we would tell someone, “Control your stress.” And they would say, “Well, great, Doc. How am I going to do that?” It’s a little difficult. Stress is one of those difficult things to truly wrap your head around. But even still, you’d mentioned meditation and quiet. I wholly agree with that. But even still, it’s a little difficult to fully manage stress. Same with inflammation. We would say, “Lower your inflammation.” They’d say, “Well, how do I do that?”

Dr. Ben Bikman:
We’d have to find out what are the stimuli that are inducing that increase in that immune level. But if we say, “Control your insulin,” easy, easy. That is a lever we can grab with both hands and immediately start to pull down, just through time-restricted eating and intermittent fasting, and by just managing macronutrients and altering that ratio, focusing more on the foods that have the lower effect on insulin, like in the fat and protein and controlling the starchiest of the carbohydrates or the most sugary. Now, neither you nor I are declaring war on carbohydrates. And I’d hate for someone to leave this talk, leave this discussion thinking we are. We’re not. Neither of us is advocating a carnivore diet. But we are certainly, my view is don’t get your carbohydrates from bags and boxes with barcodes. Carbohydrate-

Dr. Mark Hyman:
I love that.

Dr. Ben Bikman:
Yeah. Good. I love alliteration. So I’m glad you appreciate it. But that’s where people-

Dr. Mark Hyman:
Bags and boxes and barcodes. Right. Good.

Dr. Ben Bikman:
Yep. But that’s where people get it wrong. Right? They’re thinking, “I need to” … they have a box of crackers or a bag of chips or a box of cereal. No. Go eat fruits and vegetables. Eat them. I’m an advocate of fruits and vegetables. Eat them. But don’t drink them and don’t get them in processed foods like bags, boxes and barcodes.

Dr. Mark Hyman:
Yeah. My joke is I always say carbohydrates are the single most important food for health and longevity. Right? And what I mean by that is that plants are carbohydrates. Broccoli is a carbohydrate, asparagus is a carbohydrate. Those are the ones you want to eat. Not the ones that come from a factory or from some processed ingredients that you’re mentioning, bags and boxes and barcodes.

Dr. Ben Bikman:
Bags and boxes and barcodes.

Dr. Mark Hyman:
Yeah. So Ben, that was really brilliant conversation about the biology of insulin, how it works and the mechanisms. What I’d like to go into now is an understanding of some of the challenges and controversies around fat. I wrote a book called Eat Fat, Get Thin, where we talked a lot about this. But there’s still a sense that your cholesterol is a big problem, that saturated fat is the devil and that we should not be eating it. Butter, cream, coconut oil, animal food, saturated fat. Talk to us about the biology of what happens when we increase fat and why it doesn’t work in the same way we think. And also if you can, speak to the heterogeneity in the population, because there’s subsets of people who do great with high saturated fat diets, and those who don’t. And I’m just going to give you a quick scenario of that, and then you can riff on how we start to think about it.

Dr. Mark Hyman:
I had a woman about late 40s, woman who was struggling with her weight, inflamed, trying to do good. She exercised, she ate pretty healthy. She wasn’t off the rails with her eating. Her triglycerides were 3, 400, her cholesterol was 300, her HDL was 30, I mean, which is terrible numbers, which is classic of pre-diabetes insulin resistance. And I said, “Look. You’ve tried a lot of things. Let’s just try a ketogenic diet and see what happens. No harm, no foul.” She did it, and it was remarkable. Not only did she lose 20 pounds like that, but her levels of inflammation came down, her triglycerides dropped 2, 300 points, her HDL went up 30 points, which you never see, her total cholesterol dropped 100 points by eating butter and coconut oil.

Dr. Mark Hyman:
And yet another guy was a very thin, fit, mid-50s guy who was a really aggressive bicycle rider. He rode 30, 50 miles a day. And he decided he wanted to try it for performance reasons, not to lose weight. And his numbers went completely the opposite. He got very high levels of cholesterol, very high levels of small particles. It was just remarkable to see the difference. And it woke me up to the fact that there isn’t a one size fits all regards to this. So with that framework, take us down understanding of, if we are going to be reducing our carbohydrates, starchy sugary carbohydrates, and we’re going to be increasing our fats, how do we do that? And what’s the role of saturated fat? And should we be worried? And how does it work?

Dr. Ben Bikman:
Yeah. Yeah. That’s a great question. So my post-doctoral work really was seminal in that it scrutinized the degree to which fatty acids themselves can contribute to insulin resistance. And this is a conversation that I’m passionate about because so many people start beating this drum of saturated fats and use it as evidence against animal products, because animal products do contain saturated fats invariably. Now, they’re never completely saturated fat. And that’s important. There’s a mix of saturated, mono and polyunsaturated fats. And now what these people [crosstalk 00:48:54].

Dr. Mark Hyman:
And by the way, all saturated fats aren’t the same. There’s 10 or 12 different saturated fats. So they’re not like [crosstalk 00:48:59].

Dr. Ben Bikman:
Oh, my gosh. Yeah, yeah. Oh, there’s dozens of them. Yeah, that’s right. Yeah. So I’m a huge advocate of a full spectrum of fats, namely of saturated fats, even long chain, which we get a lot of, medium chain and then short chain. But putting that to the side there, when you incubate a cell, if you have a cell culture, whether it is muscle cells, liver cells, neurons, fat cells, and if you incubate those fat cells with palmitic acid, which is the prevalent saturated fat in the human body, certainly in circulation, palmitate or the 16 carbon saturated fat, when you incubate cells with palmitate or stearic acid even, 18 carbons, they will become insulin resistant. And so you treat them with the fats. Then you put on some insulin a little later and then measure. Then you take all the cells and measure what insulin did, and it is compromised.

Dr. Mark Hyman:
Wow.

Dr. Ben Bikman:
That doesn’t happen when you incubate the cells with monounsaturated or polyunsaturated fats, that it will not cause direct cellular insulin resistance. So I’ve done these studies myself …
PART 2 OF 4 ENDS [00:50:04]

Dr. Ben Bikman:
… Or insulin resistance, so I’ve done these studies myself, maybe the most sighted study of mine I’ve ever done was this exact series of studies, and the same thing happens in rodents. When you infuse the rodent with fat, when you’re infusing it directly IV, the saturated fat will cause insulin resistance, but the monolin saturated like olive oil, for example, doesn’t. So, there is a direct effect of saturated fats at the cell to cause insulin resistance and once you actually get into the cell itself, it’s because of how these fats will induce the accumulation of another molecule called ceramides and if anyone has ever heard ceramides in the audience, they might be thinking of it as like in lotions or shampoos and stuff, but it is a slightly different version of it, but saturated fats will induce the accumulation of these molecules called ceramides within a cell.

Dr. Ben Bikman:
And, then ceramides will directly prevent the insulin biochemical pathway from doing its job. It directly antagonizes what insulin’s trying to do. So, that’s the actual where the rubber meets the road, molecular mediator. So, now to zoom back out to the level of the whole body, some people look at those studies, even possibly my own, and will use that as evidence against saturated fat and they will say, “See, saturated fat causes insulin resistance,” but it doesn’t work. When you actually go to the whole body and look at the consumption of fat, the paradox is the vast majority, overwhelming majority of saturated fat in our blood is palmitate, but it’s not from the diet. It comes from the liver.

Dr. Ben Bikman:
The liver is the primary source of saturated fats that are circulating in the blood. When we eat saturated fats, they’re packaged into the chylomicron and there can be some depositing of that throughout the body, but it goes to the liver and then the liver will repackage all that fat and almost always the saturated fats will have two things happen to them, they get elongated by two carbon, so you’ll take that 16 carbon palmitate, which is the most prevalent saturated fat, we take that 16 carbon, we make it into an 18 carbon, and then we de-saturate it. There’s these two steps, and so we end up taking the palmitate in the diet and turning it into oleic acid or the primary-

Dr. Mark Hyman:
Olive oil.

Dr. Ben Bikman:
Olive oil and that is the primary fat that is stored in every single person’s fat cells, so 18-

Dr. Mark Hyman:
So basically, your liver makes olive oil.

Dr. Ben Bikman:
No, no, no, so the fat cells turn it into olive oil, but the liver makes palmitate. So when we eat saturated fats, the body will turn it into olive oil basically, but when the liver is making fat, it makes saturated fats, and so this is why you can take someone and put them on a ketogenic diet, low carb, high fat, and they could be eating three times more saturated fat than the other group, than the low fat high carb group, three times more saturated fat, and yet the actual composition of fatty acids in their lipoproteins in their blood is much less saturated.

Dr. Ben Bikman:
So, the actual amount of saturated fat circulating in their blood is much lower than it is if someone is eating a diet that is spiking their insulin because most of the saturated fat in the blood, which is what’s come to the cells throughout the body, the phenomenon that I mentioned a moment ago, most of that saturated fat is coming from the liver and the liver makes saturated fat when insulin is up. This is a process called lipogenesis and palmitate-

Dr. Mark Hyman:
Lipogenesis.

Dr. Ben Bikman:
Yep, lipogenesis and insulin is what turns that on and that’s paradox here really to put a kind of fine point-

Dr. Mark Hyman:
It turns on insulin.

Dr. Ben Bikman:
Starchy, refined carbs.

Dr. Mark Hyman:
Sugar and starch, right. Well, let me just recap for a sec. So, what you’re saying is that if you eat saturated fat in your diet from animal protein or dairy or coconut oil, it gets turned into olive oil in your fat cells.

Dr. Ben Bikman:
That’s right.

Dr. Mark Hyman:
If you actually eat sugar and starch, it turns on the fat production factory in your liver to make saturated fat.

Dr. Ben Bikman:
That’s right.

Dr. Mark Hyman:
So, you make it’s saturated fat that’s coming from eating sugar. People don’t get this connection. They think, oh, sugar is sugar, how does it turn to fat? But, there’s a mechanism by which these sugars cause the production of saturated fat in your blood, which is what’s causing a lot of the problem. Is that fair to say?

Dr. Ben Bikman:
It’s a one, two punch. Absolutely, it ends up being a one, two punch where these starchy, sugary carbs will both act as the skeleton. The liver will take those carbons and rearrange them to create a saturated fat, and at the same time, the starchy, sugary carbs are increasing insulin, which is what’s driving the signal. That’s the signal to tell the liver to do that in the first place because the liver will not make fat out of carbs unless insulin is elevated. It is antithetical, it is impossible for the liver to do because like every cell in the body, insulin tells the liver what to do with the energy that it has available, and when insulin is up, one of the things it wants the liver to do is turn the glucose, those carbons into fat and the only fat the liver’s making and packaging and releasing is palmitate, that’s saturated fat.

Dr. Mark Hyman:
That’s incredible. So, I want to drill down a little bit into the take homes and I sort of want to recap a little bit and then I want to ask you what we can do to fix this because it seems to me that what you’re saying is that this whole host of chronic diseases is driven by or affected by this phenomena of insulin resistance and it’s the biggest scourge causing 88% of Americans to have poor metabolic health. The second is-

Dr. Ben Bikman:
And, 90% of people with COVID to have it so bad they have to go to the hospital.

Dr. Mark Hyman:
That’s right, and the second thing is that we understand that the way in which insulin resistance is controlled is through primarily diet, and I want to go through a few of the other factors too, but primarily diet, and it’s primarily the starch in our sugar, which is enormous in this country, it’s 60, 70% of our diet, it’s usually in the form of flour and hidden sugars in our diet or added sugars. About 152 pounds of sugar and 133 pounds of flour, recently, according to USDA data, that’s almost a pound a day of sugar and flour per person, per day. It’s staggering, which our human biology never was exposed to. We would see 22 teaspoons a year if we found some berries or honey, now it’s 22 teaspoons per day for the average adult and about 35 for a kid.

Dr. Mark Hyman:
And three, that by changing the quality of our diet, in other words, reducing starchy, refined carbs, and increasing good fats, or maybe even saturated fat, we can actually stop this process, which is underlying everything that goes wrong with us at least to aging, and that there’s some heterogeneity in the population, but we need to figure out, one, how to diagnose it. I want to talk about that. Two, then how to treat it because if we understand this is the problem, what are people listening need to do to find out if they have this problem? Let’s start there.

Dr. Ben Bikman:
Well [crosstalk 00:57:35]-

Dr. Mark Hyman:
Aside from the mirror jiggle test, the jiggle test.

Dr. Ben Bikman:
Well, I will try not to be too redundant to what you said, but I would say anyone who has any potential, get your insulin measured, and you’d mentioned some wonderful metrics. I’ve always said below six, I think you said below five. I think that’s a brilliant way to do it. Now at the same time, insulin, like every hormone, has a bit of a rhythm to it. There’s a diurnal or circadian rhythm, so it’s possible someone would go get their insulin checked and maybe it’s 12 or 13 or so, and then you and I both would say, “Oh, that’s a little high. We need to be a little worried,” but it’s possible the person has measured it at a peak and that in reality, give it an hour or two later, and it would’ve gone down to five.

Dr. Ben Bikman:
It’s possible, so I think it is important to note that there are other things like challenging it in a dynamic glucose test, like you mentioned. That is absolute gold standard. Alternatively and another metric you’d mentioned is looking at lipids because insulin controls the production of fats and the regulation of lipoproteins in the body because lipoproteins are energetic molecules. And so look at the triglyceride to HDL ratio, and if a person has a triglyceride to HDL ratio and it’s above 1.5, that’s strong evidence that they’re insulin resistant. Now, that ratio doesn’t hold across all ethnicities, it starts to get a little loose.

Dr. Mark Hyman:
Sure.

Dr. Ben Bikman:
From Caucasians to Asians, to African Americans or so, but nevertheless, that ratio of 1.5 is generally going to be a pretty good indicator that if you’re lower than that, if your triglyceride HDL ratio is lower, that’s a good sign that you’re insulin sensitive. The good old fashion waist to hip ratio or the waist to height ratio. If you measure are your waist, the biggest part around your belly and if you multiply that by two, if that number is higher than your height, that’s a very, very good indicator that you have metabolic syndrome or insulin resistance to be more precise. If your waist circumference times two is less than your height, that’s a good sign that you’re generally doing okay, and then one other metric among many is what’s on the skin and there are two things people can look for on their skin, which it’s almost proof positive of insulin resistance.

Dr. Ben Bikman:
The first one is skin tags, those are these little kind of mushroom like or columns, little stalk of skin. They’re not like a flat kind of round mold, they just sort of jut right up and they’re small. I bet everyone already knows what I’m talking about. People can get them in their armpits or around their neck if they have a fat fold around their neck.

Dr. Ben Bikman:
So, those are skin tags, and in the same place especially around the neck or their armpits, anywhere where skin is rubbing, they can start to develop something called acanthosis nigricans, or these patches of skin that are a little darker pigment, and they have a kind of altered texture, kind of this velvety kind of texture to it, but that’s another one. So, I kind of joke the skin is the window to the metabolic soul, just because like every part of the body, it responds to insulin, and so we start to see these little hints of it.

Dr. Mark Hyman:
That’s really helpful. I wrote a little description of how to look at this in great detail called, How to Work with Your Doctor to Get What You Need, it’s available on my website, dr.hyman.com. It’s also available, I think, online, you can just google it, and I go through all the diagnostic tests to help you identify the ways in which either you have in insulin resistance or the content sequence of it, and the things that I tend to recommend people do is like you said, a fasting insulin is super important. The best test is… Because the fasting insulin elevation is really the second stage of the problem, the first stage is elevations of insulin after you consume a sugar drink. So, that’s a little bit more of a pain in the ass test where you have to drink a sugar drink, it’s the equivalent of two Coca-Colas and then get your blood tested either 30 minutes after or one in two hours after as well as fasting.

Dr. Mark Hyman:
That’s really important. The lipid test you mentioned are super important. I’m going to just drill down a little bit on that because there’s something called an NMR or a cardio IQ test from LabCorp Quest, which look at not just the total numbers of the weight of cholesterol, which is your milligrams per deciliter, it looks at the particle number and the particle size, which is really important. And so when you have insulin resistance, you get a perfectly normal cholesterol of 200 or 150, but your triglycerides may be 300 or HDL is 30. Your doctor says, “Oh, your cholesterol is fine. Your LDL is fine.” It may not be because you may actually have really dangerous small particles. Also, we look at the triglycerides, HDL ratios, very important. It’s something not really paid attention to much by doctors, but it’s more predictive than an LDL elevation.

Dr. Mark Hyman:
The most predictive tests are triglycerides, HDL ratio and total to HDL ratio, and the HDL ratio reflects the insulin resistance. So, we’ve always been looking at it, but not in the right way. We also look at inflammation which can happen through a CRP, we look at uric acid, which can be elevated, which David Perlmutter’s book Drop Acid was all about. We look at liver function tests, which can be abnormal. We look at male hormones, sex hormones. We look at DHEA and sulfate in women to look at the effective androgens being produced from the insulin resistance. So, we look at a whole host of things and we can get a pretty good picture of where people are in that spectrum, but the most important, like you said, is looking at the insulin fasting or after glucose tolerance test, and you mentioned the waste to hip ratio.

Dr. Mark Hyman:
That’s important, but when you look at the data on the 88% Americans who are metabolic and healthy, only 75% of us are overweight, three quarters, but what about that other, whatever, 8%. Probably about a quarter of people who are thin also have pre-diabetes, they’re what we call skinny fat or thin on the outside, fat on the inside. They’re metabolically obese, but normal weight, and that’s just because they may not gain weight, but their metabolic consequence are all the same. So, we start to look at all these factors and we get a pretty good sense of the problem and where you are in that spectrum.

Dr. Mark Hyman:
So, now that we’ve established that, what are the top things that we should tell people to do in order to reverse this problem? Because we know even if you’re far down the road, even if you’ve had this going on for 30, 40, 50 years, and you’re diabetic on insulin, that you can reverse this process, that you can reverse the damage to your beta cells, that you can increase your insulin sensitivity and you can reverse type two diabetes and not only just weight loss. So tell us, about what are the top things that people need to do from a diet, lifestyle, medication, supplement point of view in order to actually reverse this problem of insulin resistance?

Dr. Ben Bikman:
So, one of the reasons I was invited to Singapore and specifically for my post-doctoral work was because of the interest in that part of the world looking at this disparity or the inequality rather with regards to metabolic predisposition and body weight changes.

Dr. Mark Hyman:
Yes.

Dr. Ben Bikman:
So for example, in Singapore, there’s a tremendous variety of ethnicities like here in the US too, frankly, but they noted that if you looked at a Chinese ethnicity, kind of the average Singaporean, and compared that with someone of European, like Northern European, like me and you, Caucasian ethnicity, that these were individuals who could both be gaining fat and yet the Chinese ethnicity, the Chinese guy, would start to suffer insulin resistance, hypertension much, much earlier than the Caucasian guy would. He could continue to get fatter and fatter and only later would he start to experience the metabolic consequences.

Dr. Ben Bikman:
Now to varying degrees, this can happen across all ethnicities, where you’d noted that you have people who don’t really appear to be overweight at all, they have body weight. Much of this can be attributed to how the fat cells are growing. You and I were joking earlier that what you can pinch and jiggle is the fat that you have. Well, you could have people who are both gaining weight and they’re gaining weight, they both gained 20 pounds since they graduated from college when they were roommates, and yet how they’ve stored the weight, I don’t even mean where, but how they’ve stored the weight is very different because fat tissue can grow through two different processes. On one hand, you can have the number of fat cells capped and that’s how most people get fat across every ethnicity.

Dr. Ben Bikman:
The number of fat cells they have is set after puberty. Once they get to adulthood, their fat cell number is set, and so any pressure for the body to store more fat is primarily through hypertrophy of every individual fat cell.

Dr. Mark Hyman:
So, the fat cells grow.

Dr. Ben Bikman:
That’s right, they get to about four or five times bigger than a normal fat cell. In contrast, there are some people and Caucasians tend to do this a little more than other ethnicities, where they can continue to make more and more fat. So, the fat cells will get a little big and then the body just makes more fat cells, that’s a process called hyperplasia, so just multiplying the fat cells basically. That’s the difference because if you have small fat cells, even if you have a lot of them, they’re very insulin sensitive and they’re anti-inflammatory, literally secreting proteins that are anti-inflammatory.

Dr. Ben Bikman:
In contrast when fat cells start to hypertrophy, two terrible things happen. One, they become insulin resistant to try to prevent their own growth. They’re basically telling insulin, “Insulin, you want me to keep growing? I can’t grow anymore. So, I have to become resistant to you.” And so, the fat cells starts leaking free fatty acids into the blood. At the same time as the fat cell is getting so big, they’re pushing each other further and further away from capillaries, from the blood, and thus they become hypoxic or a little oxygen deficient. And so, they start releasing pro-inflammatory proteins, a whole catalog of them because some of those pro-inflammatory proteins will increase blood flow. They’ll try to increase the production of new capillaries, so that is part of what happens across people. Even though their body weight may be normal, they might not be in any category that would be problematic with waist to hip ratio or waist to height ratio, but they have more hypertrophic fat cells than someone else does and hypertrophic fat cells are insulin resistant and pro-inflammatory, so thus driving into the metabolic problems [crosstalk 01:07:38].

Dr. Mark Hyman:
And, we see that in Indians from India, the Chinese, Asians, it’s very similar.

Dr. Ben Bikman:
That’s right.

Dr. Mark Hyman:
They really don’t have to be very overweight and they can just have that teeny little belly bump and that little belly bump is kind of a hot potato.

Dr. Ben Bikman:
Yep, that’s right.

Dr. Mark Hyman:
It’s an issue. Now let’s go back. We understand the diagnostics. How do we test? How do we advise people in the confusing nutrition world today about what to eat? Because we have the vegan community saying veganism is a cure for diabetes and we have the keto folks saying keto is the cure for diabetes and we have me somewhere in the middle of saying Pegan diet is good. And so, we really have to kind of go, well, what’s the deal? How do we actually get to the end goal of reversing this? And of course, it’s going to be personalized because some people, like I said, have myriad other causes like stress or inflammation or the microbiome issues or toxins that need to be addressed as well. I’ve had a woman lose 40 pounds just like that by getting rid of a mercury, so there’s more complexity to it, but for the predominant group of people who suffer with obesity and this phenomena, what are the top recommendations from a diet, lifestyle, supplement, medication point of view?

Dr. Ben Bikman:
So with regards to exercise [crosstalk 01:09:02]-

Dr. Mark Hyman:
I know you’re not a medical doctor, I am.

Dr. Ben Bikman:
That’s right.

Dr. Mark Hyman:
But, I want to hear what you have to say about the food and what you’ve learned through your research.

Dr. Ben Bikman:
So just purely as a scientist, because you had mentioned kind of three things and I agree with them. Kind of medications, exercise and diet. With regards to exercise [crosstalk 01:09:20]-

Dr. Mark Hyman:
I said supplements too.

Dr. Ben Bikman:
Right, thank you, yes. So, with regards to exercise, my view is whatever the one is that you’ll do, do it. So, the best exercise to improving insulin resistance is the one you’ll do and there could be varying degrees there, but it really is a matter of just getting out and doing something and I would just say the only addition to that is do something after you’ve eaten your most starchy, insulin spiking meal of the day. Whatever that one is-

Dr. Mark Hyman:
Take a walk.

Dr. Ben Bikman:
That’s exactly right, go out and take a walk, and people would be dumbfounded at how much it lowers their glucose and their insulin because the moment you start moving those muscles, they don’t need insulin to tell them what to do, they just start pulling in their own glucose. They get so greedy, so demanding that they don’t have to wait for insulin to open those glucose doors, they open them on their own, driving down the blood glucose, which helps the insulin stay much than it would’ve been otherwise, so movement matters.

Dr. Mark Hyman:
15 minute walk, 10 minute, half an hour, what?

Dr. Ben Bikman:
The longer, the better, and the brisker the better, but anything is better than nothing. Now with regards to supplements, there are certainly… And you would know more about this than me, so in all sincerity, I would readily defer to you, but some that I’m aware of, supplements like berberine, no question, cinnamon also has been shown to do something, vitamin D as a vitamin, and alpha [crosstalk 01:10:44]-

Dr. Mark Hyman:
Magnesium.

Dr. Ben Bikman:
Alpha-lipoic… Magnesium, yep, that’s right. So, there are several things that people can just sprinkle in and use judiciously to help and medications, I’m not sure, maybe that’s too big [crosstalk 01:10:56]-

Dr. Mark Hyman:
Omega-3 fats probably.

Dr. Ben Bikman:
Oh, for sure.

Dr. Ben Bikman:
That’s right. Yep.

Dr. Mark Hyman:
So, omega-3 fats, vitamin D, lipoic acid, berberine, cinnamon, that’s a good start, and there’s more.

Dr. Ben Bikman:
And, you would know more about this than me.

Dr. Mark Hyman:
Biotin and chromium and many, many other nutrients are needed, B vitamins, all that, but basically if you take a good multivitamin and you supplement with some magnesium and lipoic acid and you add cinnamon in your food or maybe take berberine capsules, that can help, and there’s there more to this and I’ve written a lot about it, but I think that’s good. Talk about the next piece, which is…

Dr. Ben Bikman:
So, the next piece could be medications, but maybe that’s too much of a big black hole. Maybe I’ll just say this Metformin is the most widely used insulin sensitizing drug in the world because it’s affordable and it’s effective, but even Metformin, which is considered the best is only half as effective at improving type two diabetes and insulin resistance compared to even modest lifestyle changes. So, even if you take the very best of all the medications, a prospective study in humans found that it was only 50% as effective as lifestyle changes, so that then brings us to lifestyle-

Dr. Mark Hyman:
You got to send me that study, Ben.

Dr. Ben Bikman:
Oh yeah, for sure. So now Mark, you would be the authority with many, many other aspects to this, maybe even diet, I will only focus on nutrition just because that’s the one I’ve focused the most on. Despite my studies, looking at stress hormones like epinephrine and cortisol, which absolutely cause insulin resistance and tremendously matter, inflammation, which absolutely causes insulin resistance, and I’ve published in labs and papers on both of those topics, but to me the elephant in the room is nutrition, and I like how both of us want to be diplomatic when it comes to nutrition. In all sincerity [crosstalk 01:13:03]-

Dr. Mark Hyman:
Me, I don’t care.

Dr. Ben Bikman:
But, I think it’s appropriate for us to acknowledge-

Dr. Mark Hyman:
I want the truth.

Dr. Ben Bikman:
Same, and the truth is compared to a standard American diet, which is not totally fair to the US because it’s really a global diet of at this point, so compared to the standard diet that people are eating, any change is going to be a benefit.

Dr. Mark Hyman:
Yes.

Dr. Ben Bikman:
At the risk of oversimplifying it, this is why someone can go very strict vegan, which I think is a diet that has a problem longterm as a person may start to develop nutritional deficiencies, but even still, if you go on a vegan diet, there’s no question you will lose weight and your insulin sensitivity will improve. At the same time, there’s no question, I published a clinical paper in collaboration with a local clinic here, that you take people with full blown type two diabetes, put them on a calorie unrestricted, low carbohydrate diet, and the diabetes is gone. So, both of these clearly work, and so in my mind, the improvement, the steps to improve insulin resistance can start with one of two steps. One, controlling energy, or two controlling insulin, and on the controlling energy side, this is why a vegan diet is on my view, generally going to be successful, not always because there’s a lot of garbage that can be considered vegan, it’s because [crosstalk 01:14:15]-

Dr. Mark Hyman:
[crosstalk 01:14:16] a high carbohydrate diet.

Dr. Ben Bikman:
That’s right. For sure [crosstalk 01:14:19]-

Dr. Mark Hyman:
Grains and beans, even if they’re whole, are still more carbohydrates than eating protein and fat and vegetables.

Dr. Ben Bikman:
That’s right, very insulin spiking, yep. That’s true, so in general, if a person is eating a diet that is just overall lowering their calories, calories matter, and so if there’s a lower calorie diet, you will lower your insulin because you cannot have elevated insulin in the midst of low caloric consumption, you’ll die. Because if calories are low, but insulin stays really high, then you are clearing… Your glucose will be too low, your ketones will be too low and your brain will starve and you’ll go unconscious. So, the two are really antithetical.

Dr. Mark Hyman:
Hypoglycemia.

Dr. Ben Bikman:
So, if you’re lowering your calories and then your insulin will come down and then you’ll start to improve your insulin sensitivity, that absolute-
PART 3 OF 4 ENDS [01:15:04]

Dr. Ben Bikman:
… come down and then you’ll start to improve your insulin sensitivity. That absolutely happens. Now, however, having said that, I think that sets you up to failure. So if your first step to improving insulin sensitivity is to cut your calories or cut your energy, then you’re going to be fighting a battle with hunger and usually hunger wins. That’s my only concern in that regard, but nevertheless, it absolutely will improve insulin sensitivity.

Dr. Mark Hyman:
And by the way, just to stop you there for a second, that’s that’s what our friend David Ludwig’s book was called, Always Hungry, which explains why we’re always hungry. And if we are battling hunger and our lizard brain is in charge, which it is, which is survival, we’re not going to win. Our frontal lobe cannot match the power of our reptilian brain to search out, seek and find something to eat if our blood sugar is low and our insulin blood sugar is spiking up and down.

Dr. Ben Bikman:
Yep, that’s right. In fact, I think to be a little crass perhaps, this is why I believe you do not see reunion tours with the biggest loser TV show. That game show where you have these people going through tremendous caloric restriction by following the classic advice of eat less, exercise more and they do it to an extreme and hunger always wins and they gain it all back, and so you don’t see them two years later or so because the results are not favorable, very unfortunately. But nevertheless, there’s the low energy paradigm which fits with veganism generally because by cutting so much fat, typically calories are going to drop tremendously.

Dr. Ben Bikman:
This is why fasting will work very, very well, but on the other hand, you have this paradigm of just control your insulin. And this is what we published a paper on where these 11 women with type-two diabetes, they were told, “Don’t count your calories. If you’re hungry, eat. Eat until you’re full. When you’re not hungry, don’t eat, but just follow these three rules.” And I have an affection for alliteration and it was control carbohydrates, prioritize protein and don’t fear fat.

Dr. Ben Bikman:
And just to put a little nuance with each of them, control carbs is something you and I have been talking about which is focus on fruits and vegetables, eat them don’t drink them, and don’t get your carbs from bags and boxes with barcodes.

Dr. Mark Hyman:
Love it.

Dr. Ben Bikman:
Prioritizing protein. Let’s just make sure you’re getting high quality protein and you’re getting plenty of it, it will promote a greater sense of satiety, protein increases metabolic rate through the process of digesting it and you need it. And then lastly, don’t fear fat. My paradigm on that one, fat has no effect on spiking insulin on its own, and focus on ancestral fats, which is animal fats and fruit fats. We’ve been eating fruit fats for millennia because our ancestors-

Dr. Mark Hyman:
That’s fruit?

Dr. Ben Bikman:
… would’ve only needed to take… That’s right, yep. [crosstalk 01:17:41]

Dr. Mark Hyman:
Avocado, coconut and olives.

Dr. Ben Bikman:
Yup, and olives. That’s exactly right. Because all our ancestors had to do was take the flesh of the fruit and then just press it even with their own body weight and they would’ve gotten that oil from it. And so we’ve been using that for millennia and it’s these modern, of course, refined seed oils that have only come on the line over the last century, most especially the last 60 years or so when the war on saturated fat began, we were desperately looking for alternatives and that took us to all these refined seed oils. So be afraid of those, but don’t fear the ancestral fats.

Dr. Mark Hyman:
Why?

Dr. Ben Bikman:
So my view on seed oils-

Dr. Mark Hyman:
And I’m going to just frame this a little bit.

Dr. Ben Bikman:
Yeah.

Dr. Mark Hyman:
I have a very good friend who I love to pieces who happens to be the Dean of Tufts School of Nutrition, Science and Policy. Dr. Dariush Mozaffarian-

Dr. Ben Bikman:
Oh, Dariush. Yeah.

Dr. Mark Hyman:
… who’s published more studies than god and is one of the most brilliant and humane people I know. And we on 99% of everything except for this point. And his view is from the data, both interventional data and observational data, that high doses of refined seed and nut oils are actually helpful and are not a problem. Can you just kind of address that in the context of what you know? I don’t know if we’re going to get to the answer, but I’d love to hear your perspective.

Dr. Ben Bikman:
So I do attempt to have a bit of a nuanced view on this because I’m an insulin guy, I’m not a fatty acid, or I’m not a seed oil guy and there are people who are seed oil guys, guys and girls. So I’ll speak to what I know, which is two things. One, when linoleic acid, so we are eating 50-some thousand times more linoleic acid now than we were 100 years ago, and I think that matters. So when we eat linoleic acid which is the primary polyunsaturated fat in refined seed oils, that will accumulate in our fat cells and it gets metabolized into a molecule called 4-Hydroxynonenal or 4-HNE. Other fats do not do this. They do not go down this metabolic pathway.

Dr. Ben Bikman:
And when a fat cell is accumulating this byproduct of linoleic acid, it forces the fat cell to go down the route of hypertrophy, kind of reminiscent of what we’d spoken about before. It prevents this process of hyperplasia allowing smaller but healthier fat cells. It forces the fat cells to only grow through hypertrophy which promotes inflammation because they become hypoxic and promotes insulin resistance because they can’t grow anymore. So that absolutely happens, I can say that definitively. That is one negative.

Dr. Ben Bikman:
The other negative thing that I can speak to is similar to this, although that is admittedly more my forte, but so much of the evolution and our understanding of atherosclerosis is not just that cholesterol and fats matter, something has to happen to those fats for them to be considered pathogenic or harmful.

Dr. Mark Hyman:
Oxidized.

Dr. Ben Bikman:
For example. That’s exactly right. Yep. You can take a macrophage and have it swimming in a little bath of lipoproteins, of various fats. And the macrophage-

Dr. Mark Hyman:
So one of your white blood cells floating around all your fat cells, right?

Dr. Ben Bikman:
That’s right. Yeah. Or floating through the lipoproteins passing them in the blood. And so you have a little macrophage which is floating in the blood, and if it’s bumping into lipoproteins like LDL, for example, it will not engulf them. If the LDL is unaltered, if it’s fats and cholesterol esters are in a natural native state, they’re not considered a problem and the macrophage ignores them. This was studied by a group at UT Southwestern, a legendary group. And in fact, these guys won a Nobel prize, not for this work, but for other stuff. They found that you could only induce the macrophages to start eating these lipoproteins if the lipoproteins had oxidized fats on them.

Dr. Ben Bikman:
And now you start to create, what’s called a foam cell, and that’s one of the primary components of atherosclerotic plaque. When you actually look at the blood vessel that’s growing, you have these they look like little bubbles, they look they’re phony, they look like they have air bubbles in them because they have these little pockets of fat, and those are macrophages that start eating fats, but they only eat the fats if they’re oxidized. And Mark, you cannot turn a saturated fat into what’s called technically a peroxide, that’s what these actually are, unless you heat them up to 300 Celsius, lipid peroxide.

Dr. Mark Hyman:
Whoa, that’s hot.

Dr. Ben Bikman:
Yeah. That’s right, yeah.

Dr. Mark Hyman:
That’ll burn your tongue.

Dr. Ben Bikman:
Saturated fats they’re the most stable fats in nature, and the more you unsaturate the fat like a polyunsaturated fat, now it can become a lipid peroxide very, very readily and there are these metabolic pathways that will do that. And so we take this linoleic acid that we’re eating 56,000 times more now than we were a century ago, and now we see that as these become oxidized, macrophages sense them as problematic and they will engulf them and now you have a foam cell which becomes very pro-inflammatory, and you basically have the heart of an atherosclerotic plaque. Those are my concerns.

Dr. Mark Hyman:
So basically, those concerns just to recap is if you eat a lot of refined processed oils, which is the predominant oils used in America today, about 10% of our calories is soybean oil.

Dr. Ben Bikman:
That’s right.

Dr. Mark Hyman:
If you eat that, that pathway to metabolize that oil creates something called 4-Hydroxynonenal which actually goes into the fat cells and causes them to grow. And the second problem is that these fats are very unstable, they’re called polyunsaturated fats, but they’re very unstable so they’re easily oxidized. And oxidation happens from lack of antioxidants in our diet, basically the phytochemicals from stress, from our microbiome, from anything that triggers inflammation. So anything that causes oxidation which is a lot of radiation, that causes the lipid peroxide and that is what our immune system responds to which is what causes heart disease.

Dr. Mark Hyman:
So we now know that heart disease is in inflammatory disease and what you just described was the mechanism by which that happens, white blood cells attack fat particles running around your blood if they’re oxidized and then deposits them in your arteries which then cause heart disease.

Dr. Ben Bikman:
Yes.

Dr. Mark Hyman:
The question I have for you is are those Petri dish studies or is this broader in its application? Because what Darry says is that yes, and when you look at the actual population data and interventional data, we don’t see this. It sounds good on paper, but is it actually real?

Dr. Ben Bikman:
Yeah. So I’m admittedly a mechanistic kind of guy. So I’m definitely citing Petri dish or direct cell reactions, but even in human populations, we see the correlation if not the causality. And Mark, that’s the underlying concern with all of this. You can’t do these causality studies in humans that I’m aware of at least, I don’t know that they’ve been done. But in humans, we know that when you sample the atherosclerotic plaque, the actual amount of oxidized LDL or the circulating LDL that’s oxidized will be a predictor that will determine the degree of a person’s atherosclerotic blocking or prevalence. So we see the correlates in humans if not the causality that we can see in the cells and in the rodents.

Dr. Mark Hyman:
I mean, look, from my perspective as a doctor it’s like if there’s potential problems, why risk it? Maybe it’s okay, but we do know that olive oil, avocado oil, for most people, coconut oil, fats in their original state and animal fats, particularly grass-finished animals, wild animals, particularly nuts and seeds in their whole forms, those are fine to eat and that’s where we should be getting our fats so I think that’s a really helpful point.

Dr. Mark Hyman:
I think you just did a brilliant job of explaining what we need to do, I wish we had hours and hours to talk about this, and I think the dietary strategies of cutting on starch and sugar, don’t drink your calories, avoiding boxes, bags and Barcodes, upping your protein a little bit, high quality protein, eating the right good fats, key exercise, I think any is good. Interval training, high intensity interval training which increases VO2 max and strength training which improve mitochondrial function and muscle mass are also really critical. Meditation, stress reduction, all that stuff we talked about.

Dr. Mark Hyman:
I want to finish by talking about this whole thing that we earlier talked about which is mTOR and I don’t know how much you know about this, but probably a lot more than I do. And it is this central question that’s running around the longevity fields, and there was one large study that was done that looked at protein intake over the years of a person’s life, and it seemed like when younger fatless protein they did well, but as they got older, they didn’t, they need more protein in terms of longevity.

Dr. Mark Hyman:
And I do remember there’s one story of Emma Morano who was a Italian woman who lived to be 117 years old and Valter Longo who’s a longevity expert has written about her, talked about her, met her. And apparently when she was younger, her doctor told her she was anemic and she needed to eat three eggs a day, which she ate for her entire life. Then in her ’90s she was starting to dwindle and her doctor told her to eat a pound of meat a day, and she lived to be 117 years old. And so the question I have for you is, and this was a really brilliant new understanding for me which is that the biggest driver of increases in mTOR which is a regulator of aging, higher mTOR, faster aging, is too much insulin, which comes from too much starch and sugar.

Dr. Mark Hyman:
Also protein also will increase mTOR, right? So if you’re wondering what is the best strategy for regulating mTOR and aging, because a lot of people are saying, “Restrict protein, restrict protein, be a vegan, restrict protein. That’s going to make you live longer,” and I’m not really convinced because I look at the data, for example, on the native Americans, the Lakota, who at the turn of the 1900s were the longest lived population. They had more centenarians than any other population and all they ate was basically buffalo and few berries. So help us unpack this mTOR story in five minutes because then we have to stop.

Dr. Ben Bikman:
Yeah. So I’m thrilled to circle back. In fact, I think you framed this perfectly and I’m somewhat relieved to hear how you’re framing this because I think it means that you and I see this eye to eye. So these kinds of studies are very difficult to do in humans, of course. Everyone listening understands that you just can’t feasibly follow humans throughout their whole lives and perfectly scrutinize their diet and how it influenced their longevity, it’s so complicated.

Dr. Ben Bikman:
But more and more, in fact, the paper was just published a couple weeks ago called the InCHIANTI study that somewhat reflected what you said again that even Valter Longo’s own research found that meat consumption, animal protein consumption, the older we get had as an inverse association with mortality. In other words, the older we’re getting and the more animal protein we’re eating, the longer we’re going to live. And then there appeared to be this period in Valter Longo’s perspective kind of research or correlational studies, he found that there was this kind of at around middle age, I think it was 50 to 60 or so and you might know this more than me, they found that the people who ate the most meat did have the highest mortality, but then it ended up shifting into the exact opposite at above 65 or 70.

Dr. Ben Bikman:
And so all of this is correlational, of course, so it’s very difficult to state anything conclusive. Based on the sum of all evidence in my mind, cutting protein is a wonderful way to make sure your bones and your muscles will be more frail and you will be more frail, easier to kill so to speak. You will not live.

Dr. Mark Hyman:
And by the way, your immune system requires protein to make the antibodies. You hear about antibodies and COVID, where do you get those from? Protein.

Dr. Ben Bikman:
Yeah, you need those amino acids. Yep. That’s right. So in my view, we should not be fearing protein, we should be prioritizing it in the diet and high quality sources of it especially. And the fact is, although it’s a little inconvenient sometimes, animal protein is imminently absorbable, and you at least know you have every amino acid you need. I’m not saying that plant protein can’t be a part of this, it absolutely can, but there’s also no question animal protein is fantastic.

Dr. Ben Bikman:
Now, I appreciate there’s other issues that come into play here, moral issues and ethical issues, but even still, whatever, it may be, prioritize protein because it’s make you harder to kill including just disease and longevity. So that’s the thing about just animal protein in general. Then with mTOR-

Dr. Mark Hyman:
So how does that work with mTOR then because I think that’s what… I agree with the muscle build. I mean, you can get moves like game changers on this show, you can be vegan and be ripped, but I’ve interviewed some of these folks and one, they are pounding highly processed protein powders, vegan protein powders, because they cannot get the muscle building effect without supplementing branched amino acids and high, high doses of protein powders.

Dr. Mark Hyman:
So you cannot get… I mean, because otherwise you’ll see a lot of vegans are relatively thin and have low muscle mass over time, obviously they stay on it for a while, but the ones who are ripped are the ones who are actually eating super physiologic amounts of these plant protein that you couldn’t get by eating them, the whole plants.

Dr. Ben Bikman:
No, that’s right, that’s exactly right. Yeah. And that’s sort of reflective of my general view that the further someone’s going from animal based foods, the more they need to supplement to ensure that they don’t have any deficiencies. So mTOR is relevant and animal proteins will activate mTOR more than plant proteins will. And that matters if we are continuing to say that mTOR is the root of all aging. However, I believe it’s not relevant for longevity because when we spike mTOR with proteins in the diet, it is very transient. It comes up and it comes down and it’s based wholly on the amount of amino acids that are getting pulled into a cell. And of course, muscle cells will pull in the bulk of those amino acids because they have such a high protein demand.

Dr. Ben Bikman:
And that’s a good thing because you have to have mTOR turned on and then turned off. You have to have the cyclical mTOR activation. I have a colleague two doors down from my office right here who studies mTOR and its effects on muscle and bone growth and what he’s found in others that when you have mTOR turned on too long, you actually start to become mTOR resistant. And if muscle cell is trying to grow, but mTOR is so high for so long that its ability to promote muscle protein synthesis is compromised, and now the muscle is starting to break down its protein even though mTOR is elevated, but that happens when mTOR is elevated too much which is not the cyclical activation you get from protein consumption but rather the insulin induced mTOR activation.

Dr. Ben Bikman:
Because insulin, as I said, insulin activates mTOR much longer than amino acids do and importantly, much more ubiquitously. Because if you and I were to eat a load of amino acids, we would get significant mTOR activation in our muscles and relatively little mTOR activation in our liver or our white blood cells however because they don’t pull in amino acids very much. It’s a very modest intake of amino acids, and so that’s relevant if it’s protein induced mTOR. But insulin, when we spike our insulin, as I mentioned earlier, literally every single cell in the body responds to insulin. There’s truly no exception, I’m not being dramatic here, there’s no exception.

Dr. Ben Bikman:
And so now we have our white blood cells that are responding to this elevated insulin and our skin cells and our bone and muscle and liver and brain, and so now mTOR has been spiked and it’s staying on for longer, and right around the time mTOR is starting to turn off in response to this insulin spike, what do we do? We turn it on again and again and again by continuing to eat and drink refined starches and sugars essentially every two or three hours from the moment we wake up to of the moment we go to bed.

Dr. Mark Hyman:
Yeah, bad news.

Dr. Ben Bikman:
So if mTOR matters, then focus on insulin, not protein.

Dr. Mark Hyman:
That is a brilliant summary of something that I’ve struggled to understand because intuitively, I knew that protein, and also from the data that protein as we get older is really important for muscle mass, and sarcopenia, which we talked about in the show, the loss of muscle is the single biggest driver of age related disease because it just accelerates everything, accelerates resistance inflammation, hormonal dysregulation, a high cortisol, low growth hormone, frailty, everything else and so you need that.

Dr. Mark Hyman:
But at the same time I’m like, “Well, geez, I don’t want to messing up my longevity here by eating my grass fed rib-eye.” And the explanation of that it’s actually sugar and starch that keep mTOR elevated all the time, as opposed to the cyclical nature, which protein does is just brilliant. So the take home is cut off the starch and sugar. If you eat a lot of protein with a lot of starch and sugar, you’re a problem. If you’re eating a lot of fat, particularly saturated fat with starch and sugar, it’s a big problem. That’s a caveat I want to make, “Oh, saturated fat’s good. I can eat saturated…” No, not if you are eating starch and sugar, because then it’s like putting gasoline on a fire.

Dr. Mark Hyman:
So I think this is a brilliant conversation, I just can’t tell you, Benjamin, how inspired I am to know that you’re trying to dig into these issues, figure them out. I love your work and the fact that you’ve been able to help us elucidate some of these mechanisms by which we are getting sick and dying and how they’re beautifully unified in a way that we can actually transform a whole host of age-related chronic diseases through a simple idea of fixing insulin resistance. And you’ve written a book about it called Why We Get Sick, it’s out. I encourage everybody to get a copy, it’s brilliant and learn more about his work.

Dr. Mark Hyman:
You can learn about him, go to lifesciences.byu.edu and you’ll find him in the directory there and some of his research. So I think that Ben, your work is great. I would continue it. Don’t stop. We need to learn more about this. You need to be testifying in Congress and you need to be speaking on national public radio and you need to be on a television. You need be talking about this because this is essential feature that is not being spoken about within healthcare very much, nor within this COVID pandemic which is at the bottom of it is this poor metabolic health. And I know I’ve mentioned this before in the podcast, but 63% of hospitalizations for COVID were caused by poor diet. Think about that.

Dr. Mark Hyman:
If we could have everybody in America on a healthy diet, it would be unbelievably effective in reducing the impact of the pandemic. Someone said to meme where I was saying the government is mandating that you eat only whole foods that you exercise every day, that you sleep eight hours a day, that you meditate 20 minutes a day. And if you don’t have your card and proof that you have done that, then you can’t go to this restaurant, you can’t get on an airplane, you can’t go to work. And I’m like, “Okay, now you’re talking now you’re talking.” But anyway.

Dr. Ben Bikman:
Well, I know it’s a delicate thing, but you’re pointing a finger at what is relevant. And as much as people want to claim this is an epidemic of this or that, there’s no question that underlying metabolic health matters now more than ever.

Dr. Mark Hyman:
Yeah. Well, Ben, thank you so much for your work. Thank you for being on The Doctor’s Pharmacy. For everybody listening, if you love this podcast and I hope you did, because I certainly did, please share with your friends and family on social media, leave a comment. Describe how you’ve managed to handle your insulin resistance, if you figured out what to do. Subscribe wherever you get your podcast, leave a comment, we’d love to hear how you love the podcast in review, and we’ll see you next week on The Doctor’s Pharmacy.
Speaker 2:
Hi, everyone. I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you’re looking for help in your journey, seek out a qualified medical practitioner.
Speaker 2:
If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their Find A Practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner and can help you make changes especially when it comes to your health.
PART 4 OF 4 ENDS [01:38:33]