Leptin Resistance & Gluconeogenesis - Dr. Chaffee & Richard Smith

[00:00:00]Absolutely. And you know, you mentioned leptin resistance, which is that one's that one's just crazy to me because you know, I I treat this I've I've I've looked at hundreds and hundreds and hundreds of people's blood work over the years. I do check leptin and if someone's having stubborn weight loss or they're metabolically ill, I will check their leptin. And it's it's it's the exact opposite. You know, we see people with these massively elevated leptin levels that have they have extreme leptin resistance, which will will suppress your metabolic state.

[00:00:31]If you have leptin resistance, basically it mean even though your leptin levels are high, it means your brain can't see the leptin. If it can't then your leptin comes from your fat stores, goes to your brain, basically tells your brain how much energy you have. It's like a running gas gauge. And so, if you have very little leptin or your brain can't see the leptin, it thinks you're emaciated and dying and says, "Okay, we need to slow down our metabolism so that we can survive whatever famine that we're in and and increase appetite. So, we need to eat more and whatever we get in, we need to store it." And so, that's that's a hallmark of of a of slowing a metabolism. And so, and that's what causes that slow metabolism or one of the factors that causes slow a slowing of a metabolism.

[00:01:10]Also, elevated insulin does exactly the same thing or slows metabolism you I should say. And so, you know, when you when you have leptin available, your brain sees that as, "Ooh, hey, we've got an abundance of this. We have an abundance of energy.

[00:01:25]Great. Let's turn on the metabolism.

[00:01:27]Let's open up these floodgates to start using this energy and build, heal, repair, and run, and play, and mate, and reproduce, and all that sort of stuff."

[00:01:37]Um you know, then it it opens things up. It raises your metabolism. It says, "Hey, we we can actually dampen down our our hunger signals." And so and so satiety signals change as well.

[00:01:49]When you block that, it means even though you have high leptin, your brain can't see that.

[00:01:55]And so, your brain, even though you have high your brain thinks you have basically no or or low leptin. And so you actually suppress your metabolism. So there are six major things that that block leptin and cause leptin resistance. Insulin blocks leptin.

[00:02:12]Uh fructose, the sweet part of sugar, directly blocks leptin but also, you know, will raise usually comes with glucose, which raises blood which raises insulin and also fructose will eventually raise insulin as well. So it hits you twice. Alcohol, again, will will block it directly and uh disrupt insulin as well. And then lectins, the plant toxins uh that can bind to insulin receptors five times as tightly as insulin. They can do all the things that insulin can do and then some like block leptin. Um and so then you have So right there off the bat, four of those things are addressed on a on a plant-free ketogenic carnivore diet. You've just knocked out four of the main factors in blocking leptin. So some of the the other two being cortisol, so high stress, poor sleep will raise your cortisol, and that can disrupt your leptin cause leptin resistance and and a slowing of the metabolism, central adiposity, those sorts of things, difficulty putting on muscle and lean body mass.

[00:03:08]And uh then funny enough, blue light. So all these stupid screens that we're on all the time, these awful things that we have on here. I try to use natural light all the time if I can. It's just getting dark now, so I can't. And so uh but in my office, I I almost never have the lights on unless I have to.

[00:03:24]Um you know, so that the natural light can come in the window and um because the blue light, the highest, you know, the certain spectrums of blue light actually get into your eyes and actually can block leptin at the level of the hypothalamus and cause leptin resistance and metabolic dysfunction. So it's very serious. And um and and most people don't recognize that. But for my patients, when I say, "Hey, go on a carnivore diet," their leptin comes down invariably.

[00:03:51]You know, there's a there's the odd customer that has uh has very high stress situation.

[00:03:57]You know, or they've always been a bad sleeper. They only get a few or they have babies and kids and things like that. So, they're just you know, a 3-hour night is is good, you know? And so, that's just something they'll have to contend with. When they get out of that situation, just comes right down.

[00:04:11]Takes months, but it comes down.

[00:04:13]And and then the light, you know, I mean, I before even understood about how impactful, you know, natural light was and artificial light was to us. Um and and recommended people, you know, change their their approach to light hygiene.

[00:04:29]I still saw leptin come right down. I still saw all these improvements happen.

[00:04:32]And then you add that that in and that that can just help that even further.

[00:04:36]So, I I have I've never once seen any of these people with massively elevated leptins have that have just come right down to completely normal levels, lose all this weight, completely reverse all their metabolic issues.

[00:04:49]And then suddenly somehow just all that just start coming back again and going back the other direction. That doesn't really make sense. You know, if you can undo all these metabolic issues and harms and and reverse all these issues, how are people arguing that those exact same interventions are now just going to all of a sudden start causing the problems that they cured? That doesn't make any sense.

[00:05:11]>> Yeah, 100% and it's yeah, it's a common I mean, it's interesting that you mentioned about the lectins bind into the insulin receptor causing, you know, more leptin resistance. But you're right, it's it's lifestyle factor. What about you know, people mention about lack of of glucose, for example, and our argument is well, we make all the glucose we need via gluconeogenesis, to which their response would be well, gluconeogenesis is a stress response.

[00:05:39]Mhm. That it's only a stress response if you're new to this way of living, isn't it? Um should we get into that really briefly about the different pathways of how you and I produce glucose via gluconeogenesis through through different pathways.

[00:05:53]>> Yeah, and you know and the thing is is that it that you you know just because cortisol can initiate gluconeogenesis doesn't and and and and high stress situations can increase cortisol does not mean that gluconeogenesis is a stress state. Those things do not follow. That's not That's not the same thing because you can have cortisol fluctuate for a number of different reasons that have nothing to do with the stress state and is is completely physiologically normal and healthy.

[00:06:20]And that could influence gluconeogenesis one way or the other. But the fact of the matter is is that we are making we are going through gluconeogenesis at all times day and night regardless of what we eat. We are making anywhere you know from 40 to 60 70 g of glucose per day when eating carbs. That doesn't stop. We you know gluconeogenesis is is is happening. And that's because normally our body's saying, "Hey, well, we need to do this to to support this baseline level of of glucose utilizing cells such as your red blood cells that don't have mitochondria and they need glucose cuz you need mitochondria to to burn ketones.

[00:07:01]So, when you stop eating carbohydrates, your body still makes that exact same amount of of glucose. It doesn't change. And so, that's not a stress state and there are multiple different pathways that have nothing to do with cortisol.

[00:07:16]There's like the glycerol pathway which is the main pathway. So, people say, "Well, this is a stress state." And and you know what you know what you're referring to is we do see in early phases of fasting and fat adaptation, we do see a marginal rise in cortisol that does not actually go outside of of the physiological bounds. It's still within the normal physiological range. It's just a little bit higher. And when people have metabolic resist metabolic disease and metabolic syndrome, that's actually known to suppress cortisol actually have it be too low, which is also not physiological. Uh if you have your cortisol is too low or gets extremely low, it's called Addison's disease, which can kill you.

[00:07:58]So you need cortisol, you just need it in a certain range. And so having metabolic illness actually suppresses your cortisol below where you would you would want it. And then reversing that metabolic syndrome, it can actually go up normally healthy because you're actually recovering and improving. And so when you're first going into a ketogenic state, you can have a little bit of a rise in that cortisol, and then after about 72 hours, it starts actually coming down. You go into more of a cholesterol pathway.

[00:08:26]And that that happens when you're burning triglycerides. So you have a triglyceride, so it's a glycerol backbone and three fatty acids. That's your major fat storage form, and then you pop off those three fatty acids, and then you have glycerol. And that glycerol gets turned into glucose and glycogen at a set rate. So the harder you work, if you're exercising, you're pumping out a lot of a lot of exertion and and you have a high energy demand, you're going to start burning a lot of fat. You're going to be popping off a lot of those triglycerides and and making glycerol available. So you're for you're going to make a set amount of glucose. You're going to have a set amount of glucose and glycogen available for whatever activity level you are. It just perfectly ramps up and matches your exertion level.

[00:09:15]Um and that costs no cortisol. You do not need cortisol for that. In fact, glucagon is the main hormonal driver of gluconeogenesis that drives that glycerol pathway, and which [clears throat] is why in hospital settings when someone has taken too too insulin and they're hypoglycemic and they're in a coma because their their blood sugar's so low and they're not in ketosis, so they don't have ketones.

[00:09:43]We don't give them a shot of cortisol, right? To to spark gluconeogenesis, right? We give them a shot of glucagon.

[00:09:51]And that, bam, all of a sudden they'll wake up in a in a couple of minutes. So, you know, that that's what's going on.

[00:09:56]Well, then it that then glucagon must be a stress state then. Why? Why? What are you talking about? You're you're saying that gluconeogenesis is a stress state.

[00:10:05]Therefore, anything involved with it is also a stress state. It's just it circular logic. You know, they say, you know, they they they you know, they're they're using aspects of the same argument to to prove the core thesis.

[00:10:18]Um but again, you're making you're making blood sugar all the time.

[00:10:22]Uh in or out of ketosis, you are producing glucose.

[00:10:28]And the other thing is is that when you know, this is the this is the misconception that people have when they don't sort of look into bio bio biochemistry uh or just don't know about it or don't have sort of a you know, a a you know, a gym life sort of version of of biochemistry without ever actually opening a book.

[00:10:48]Um you know, they um they think that well, when you're when you're working out, when you run out of carbohydrates, if you're eating a whole bunch of carbohydrates, you'll start catabolizing your muscles to try to to make energy and glucose and things like that. Um if you're eating carbohydrates and your insulin is so high that you've blocked lipolysis and it's physically and chemically impossible to access your fat stores, what else is available? The only thing you can access is your is your protein stores and your muscle stores. When you are in ketosis, you're running on your fat, and you actually will never Oh, would you run out of carb You don't You're not running on carbs, you're running on fat. So, you know, you're fat and carbs, but you're you're producing both from your fat from the triglycerides.

[00:11:35]And so it you will not start catabolizing and breaking down your muscles for protein for energy if you're in ketosis until and unless you completely run out of fat. And even a small person, 140 150 lb individual with 6% body fat has can only store about 2400 kcal of energy in their muscles and liver with just eating pizza and pasta all week.

[00:12:02]Maximum.

[00:12:03]But that same 6 kilo 6 um 6% body fat individual at 150 lb that 6% body fat has over 35,000 kcal of of energy available to us. So it's over 15 times the amount of energy for a small slender person. Okay. So what if you're 240 lb and 10% body fat like me?

[00:12:23]I I've got over 100,000 calories available. I don't need to eat this month. Really. And that's before my body will even touch my muscles.

[00:12:34]>> 100%. I'm 6% ish and and I still don't eat carb. And the interesting thing there is that you you know, you mentioned about muscle glycogen, but the lactate we we recycle the lactate also at a higher rate and we basically we send that lactate. So when we feel the burn in the gym, the people chase that that actually shows an inefficiency because it shows an inefficiency of our body to buffer the hydrogen ions. What you and I do is we never feel that burn because we send that lactate to the liver and again through gluconeogenesis, which is almost a reverse glycolysis pathway except for three enzymes, I think, isn't it? And then we send that glucose back to the muscle at a higher rate and we can replenish through dietary carbohydrate.

[00:13:18]So it's our requirement for an exogenous form is is literally zero. And even if we look I remember Um James Di Nicolantonio did something recently about um something that I did.

[00:13:30]Um which Bart Kay did a rebuttal to also and it led to this whole thing. Anyway, and I like James. He's a nice guy, but I just think he's um he's just misinformed with a few things. But one of the things he mentioned is the brain's requirement and the red blood cell requirement.

[00:13:43]Well, 95% of the brain's requirement of energy can be fueled by ketones given enough time to upregulate the transporters involved. Uh and the red blood cells, if we look at the 25 trillion red blood cells based on the the molecular weight of glucose, you know, we can we can establish that the body's requirement actually for for glucose is is very very low and it it's around eight teaspoons a day. So, we need one teaspoon in circulation any one time, but it's it's around eight eight to 13 depending on on the person. Um and our bodies in a natural state will produce 20 to 30 through gluconeogenesis comfortably. And then it it becomes demand driven. If we need more, we make more. So, quite literally, our bodies make more glucose than we need anyway.

[00:14:29]We don't need any exogenous form of of glucose.

[00:14:33]>> Yeah. No, yeah, we definitely don't. I mean, and that and that is Yeah, I I obviously demonstrated and evidenced by the fact that there are populations that have never eaten carbohydrates, have never even really had access to carbohydrates like the Inuit in the in the northern regions of of Canada.