 Hey everybody, Dr. O here. Let's talk about ketones. Ketones are in the media a lot. People are always questions about ketones. What are they? When are they made? What can we do to stop them from being made, etc. So let's go ahead and take a look. Here we see the Krebs cycle. As long as you have enough oxaloacetate, that last step in the Krebs cycle, to meet the needs of the amount of acetyl-CoA that's being produced, the Krebs cycle is going to be responsible for the fuel. But if you get yourself in a situation where you have more acetyl-CoA than the Krebs cycle can handle, that's going to be when ketone bodies are produced. So when would that happen? Primarily if you're on a low carb or ketogenic diet or if you have uncontrolled diabetes, so all the glucose in your body is in your bloodstream instead of in your cells, you're going to bump into this situation. The reason that you would if you're on a low carbohydrate diet is because if you don't have enough glucose to meet all of your needs, then your body is going to be using a lot of beta-oxidation of fatty acids. And that's the process where you take long fatty acid tails and turn them into acetyl-CoAs. So if you're burning fat for fuel, you're going to have an abundance of acetyl-CoA. And this cycle is going to not be able to keep up with the demand, and that's going to be when you'll produce ketones. Let's go ahead and look then at how they're produced. If you take these excess acetyl-CoA, they can be converted, I don't care about the individual steps, but they can be converted into your actual ketone bodies. Right there in the middle, though, one of the intermediate steps is HMG-CoA. That's actually a precursor to cholesterol, so I think that's just kind of neat. But the two key ketone bodies are acetoacetate and beta-hydroxybutyrate. Beta-hydroxybutyrate is generally considered the primary ketone in your blood. But you're also going to see acetate. So if we have more ketones than we need to burn for fuel, they can be broken down, and acetone will be the bright product. That's going to be where that fruity breath or breath that smells like paint thinner or nail polish remover is going to be the acetone that's being released into your lungs. All right, so that's how they're produced. Let's go ahead and look at how they're actually oxidized. So beta-hydroxybutyrate can be metabolized down to acetoacetate. Notice that an NADH is created. That's going to be an electron carrier that will earn us some energy once it can run through the electron transport system. And then at the end, we're going to have our acetyl-CoA's back, and they're going to be able to run through the Krebs cycle. So if you think about it, ketones can make some energy now. But they also will, you can use these acetyl-CoA's in the Krebs cycle once there's room for them, once that traffic jam is over. What else about that? As far as how much energy is being produced, if you take that acetoacetate and fully oxidize it, it will yield 2GTP, which can create ATP, of course, and then 22ATP directly. So it's a very good fuel source. Where can this be used? It used to be thought that ketones could only be used in a few locations. We used to think the brain could only rely on glucose. We now know it's not true. I've seen studies that have shown that the heart, muscle, parts of your brain, parts of your intestines can actually run almost better on ketones than they can other fuel sources. So now the heart loves burning fatty acids, but it can certainly use ketones. What I find most interesting is how the astrocytes, one of the neurological cells in your brain, they actually take glucose and convert it into lactate, but the same shuttles that shuttling lactate to use as a fuel source can also use ketones. So that's why a lot of people that are on ketogenic diet say that their focus and their mental energy actually improves. I find that kind of interesting. Now there still are some parts of the brain that have to rely on glucose, but you certainly can use ketones. So ketones are a very viable fuel source. You see that they're generated. If you get in a situation where you're burning a whole lot of fat for fuel and we talked about how much energy they can produce. Now let's talk about the downside then, because some people are afraid of ketogenic diets or they would actually recommend that you increase your carbohydrate intake to prevent ketosis. I think it's a terminology issue more than anything. I think ketosis is actually a really good thing. Ketoacidosis is a terrible thing. So ketosis will be when you have low levels of ketones in your bloodstream because of maybe short-term fasting or you are on a ketogenic diet. That is going to be, generally speaking, someone in ketosis is going to have about five to 10 times less ketones in their bloodstream than someone that's actually at danger of what's called diabetic ketoacidosis, which absolutely can be fatal. Ketoacidosis, because ketones are acidic, can cause metabolic acidosis dropping the pH. But also, ketoacidosis comes with a dangerous level of dehydration. So if a person is going to die because of diabetic ketoacidosis, it is usually the drop in pH but the severe amount of dehydration. So if you want to save their life, getting their glucose levels up and getting the ketone levels to come down is very important. But preventing or treating the dehydration is just as important. Just to give, so I think that we have to be very careful if we mix those two words. Because I don't see anything wrong with ketosis. I do some moderate to long-term fasting. And I might fast for three, four, five, I think six and a half, seven days is the longest I've ever gone. And I monitor my blood ketone levels. And I've never seen them higher than six millimolar. So we're talking about not eating for an entire week. My ketone levels personally, this is not medical advice, have never reached a point higher than six millimolar. Whereas diabetic ketoacidosis, you are looking at ketone levels of 15 to 25 millimolar usually. So I do think that they're very careful if we put down ketogenic diets or diets that put you in ketosis because of concerns of ketoacidosis. Now, if you have an uncontrolled diabetic, I think you need to be extra careful. I wouldn't recommend putting someone that can't control their diabetes on a ketogenic diet or any diet that would generate more ketones. So just kind of worth noting. I think ketosis is actually, can have many, many benefits. Ketoacidosis is dangerous and potentially fatal. So I hope I've been very clear about that. All right, so if we are, if you are trying to generate ketones. So we've already said that ketones can be generated if you're not consuming enough carbohydrates or if you're an uncontrolled diabetic because your carbs, your glucose is all stuck in your bloodstream instead of your cells. What if you want to produce ketones and you're wondering why you can't or you can't produce enough of them? So long story short, if you want to produce ketones, you have to deplete your body of pyruvate. So getting rid of carbohydrates is the key. If you're consuming enough carbohydrates where the Krebs cycle keeps running, then you're going to have problems. But there are other issues here. And you'll see that's why I chose this picture. You'll see there's lots of different intermediates, especially these amino acids here that can enter the Krebs cycle. So this would be why, I think one of the biggest mistakes is when people compare or think that a low carb diet and a ketogenic diet are the same thing. Low carb diets are low carb, but they can be moderate to even high in protein. Ketogenic diets have to be low carb, but also need to be moderate to lower in protein, not reaching malnutrition. But if you consume too much protein on a quote unquote ketogenic diet, you see right here that the proteins are going to be able to keep creating oxaloacetate. They're going to keep running the Krebs cycle. So you're not going to be producing ketones or at least not producing as many as maybe you're hoping for. So that's why it's very important to monitor protein intake on a ketogenic diet. I've had a lot of students that didn't know that. I think other things, things that are going to increase gluconeogenesis or the creation of glucose in your body would also make this very difficult. I think the two biggest ones here are going to be sleep and stress. So if you're sleep deprived or you're under a lot of stress, then your stress hormone cortisol is going to be trying to prop up your blood glucose in any way it can. And that's going to keep the Krebs cycle running. So that can be a big problem. So if you're on a ketogenic diet, and again, this is not medical advice. If you're on a ketogenic diet, make sure you keep an eye on how changes in protein intake are going to determine whether or not you are in ketosis and that can be monitored from breath tests. And I guess you're into some extent blood tests as well. And then sleep issues and stress are both also going to make it a lot harder for you to produce ketones. So that's ketones. It's what they do. It's the energy we get from them. That's how to stop them from happening if you want to stop ketosis and that's how to make it happen if you're trying to make it. I hope this helps. Have a wonderful day. Be blessed.