Dr. D'Agostino: So, in our clinical trial that we're doing using... In non-diabetic people, they tend to be a little bit on the heavier side, but they don't have type 2 diabetes, they're using it to optimize their metabolic parameters and glycemic variability. We transition them into a ketogenic diet over four to six weeks. So, we titrate the carbohydrates down. And what we have found or my colleague has found, Dr. Allison Hull, she's at the Florida Medical Clinic and has a wellness program, that compliance and adherence to the diet and ultimately the results are better. If you take someone who's eating 300 grams of carbohydrates a day, that's standard, you know, American diet, and you drop them down to, you know, 100, and then the 75, and then 50 at about the four to six-week point, and you get a very nice improvement in many different subjective and objective, you know, biomarkers, they feel better, signs of mood are increased, anxiety using the GAD-7 test, the PHQ-9, SSQ. Sleep actually improves.

If you were to abruptly start the ketogenic diet, you're more likely to get side effects and you're more likely to get things like sleep disruption, lipid abnormalities, elevated triglycerides, you get a quick spike in LDL. This can occur if you rapidly start the ketogenic diet, especially in the context of not calorie restricting. When you calorie-restrict a ketogenic diet, it sort of mitigates many of the things that are negatively associated with high fat diets. So the transition is a lot easier if you calorie-restrict with a ketogenic diet. So that needs to be appreciated.

For a lifestyle, I would recommend, if you're not on a carbohydrate-restricted diet, to ease into it and titrate it over time if you're not in a rush, right? So, for me personally, I follow what would be considered a very modified supplemented ketogenic diet that would be more along the lines of a low glycemic index diet. So I have about...you know, 10% to some days 20% of my diet is actually carbohydrates but in the form of fibrous vegetables, right, essentially non-glycemic carbohydrates, so a lot of leafy greens. The carbohydrates that make up my ketogenic diet are on the...like typically have about one third to almost half of it is fiber and has very little impact or actually can improve glycemic variability or reduce it in that it moderates the digestion of protein and helps delay gastric absorption. So, the nutrients and things that I'm eating actually get into circulation in a protracted way. So the fiber helps to slow digestion.

And so fat and fiber together are really important for the ketogenic diet, and that's not something classically that's accepted or considered. But as we learn more about ketogenic diets, we have an appreciation for the types of fats that are in the diet and actually incorporating fiber, not only to improve digestion and protein assimilation, but to enhance and preserve the gut microbiome, which is to be appreciated. So there was a lack of that understanding 20 or 30 years ago, and it came into the conversation about 10 years ago. And now it's actually become a major focus of a lot of these dietary interventions, low carb and ketogenic diets. We need to appreciate fiber as a part of improving the diversity and maintaining the gut microbiome.

Dr. Patrick: You've just answered one of the main questions I had about, you know, being on a modified ketogenic diet and somehow intelligently designing a diet that include more fiber, you know, your thoughts on how fiber would be important. And it's really interesting to hear you say that because, you know, the other thing is that, you know, fiber, you are making butyrate in the gut when you're or your bacteria is, you know, making it, the microbiome inside your gut. And that is fueling the colonocytes, right, giving them energy.

When I was doing the ketogenic diet, I did find that...I ended up just naturally fasting more because it is so difficult. Like things I could eat, it was like, "Well, I can't eat..." I would snack on some macadamias. And after a certain point, it was like, "Well, this is like too much, the ratios of the protein in the..." So I'd have to like not eat, and then, you know, I found that I was basically just doing a lot of dietary restriction alongside the ketogenic diet.

But I also found that when I would add, like, dark leafy greens, the portions really made a difference for me. Like, for example, cooked spinach, like, you don't think about it but, like, because you're cooking it, it's like a lot more spinach than you would think it is. And so, like, a little serving of it looks small, but it's actually quite a bit. And so I noticed the cooks...if I had like a portion of cooked spinach, you know, it wouldn't totally take me out of ketosis, but it wasn't getting me into that higher level. So, you know, I would go from like 3 millimolar down to, you know, 1.

Dr. D'Agostino: So you were cooking your spinach. Yeah. If you take raw leafy greens, so the cell walls intact, but when you cook green vegetables, the heat ruptures the cell wall. So you make the carbohydrates a little more accessible, even if it's green leafy vegetables. So that's going to impact... Believe it or not, you know, in the context of a ketogenic diet, it makes a difference. If you have greens that are raw, the glycemic impact is essentially nothing, but if you cook your greens, you know, it does make it proportionately much smaller, so you're more likely to eat more, but it also makes the carbohydrates accessible because the heat is rupturing the cell wall. So similar to like juicing or a smoothie or something like that, right? Although with the smoothie, you got the fiber and stuff in with it too. So, that's a big consideration that people need to consider.

Dr. Patrick: Greater.

Dr. D'Agostino: Yeah. But volume. But with a salad like a salad that would...an example of a salad on a modified ketogenic diet or modified Atkins diet would be, you know, fatty fish like salmon, leafy greens like arugula, maybe some spinach and romaine lettuce and stuff, and extra virgin olive oil, lots of that. And I tend to mix it with MCT oil, so a combination of extra virgin MCT, we can get into that, as a ketogenic fat.

Nuts are great, but I don't go too crazy with nuts but a little bit of walnuts. So you have fatty fish, a little bit of leafy greens, and a very fatty ketogenic dressing that's made, you know, with MCT and olive oil and herbs and things like that would fit in well with a ketogenic diet. So you get monounsaturated fats, right, and you're getting polyunsaturated fats and MCTs, which are saturated but go to a different...they do not disrupt the gut microbiome in ways that other types of fatty acids do. And that's the kind of nutrition that would be no effect on a continuous glucose monitor. So your glycemic response would be like nothing, and your ketones would likely go up because of the macronutrient ratio but also because of the MCTs that are in it too. So that's a very normal kind of typical diet that I eat.

Dr. Patrick: So most of your greens or most of your carbohydrates are eaten raw for the most part. You generally not cook them.

Dr. D'Agostino: We do broccoli a lot and asparagus, so I lightly steam it or cook it, but I don't make it to the point where it's like mushy. So I lightly steam vegetables like cauliflower, broccoli, asparagus. I always have a salad with my meal. With a ketogenic diet... When you wear a continuous glucose monitor, you can observe that the order in which you eat your food will impact the glycemic response. And if you're attenuating the glycemic response by eating foods in a certain order, a certain combination, that's also reducing the insulin. So, you need to continually have a suppression of insulin signaling to maintain a state of ketosis.