Dr. Rhonda Patrick: Let's kind of shift gears and talk about some solutions here, protocols to maybe enhance insulin sensitivity. People that are, you know, we talked, we started this conversation talking about people who are a large population of people that are actually pre-pre-diabetic. They might be, you know, on their way to insulin resistance or already insulin resistant. Yeah. And not even really know it. Um, what, what are some of the best strategies people can do now to really make a difference? and, you know, dietary strategies, you know, stress reduction, physical activity, but also how soon can they expect to see changes and what should they look at to see and monitor those changes?

Dr. Ben Bikman: Yeah, well, in fact, I'll start with that last part of your question, which is how quickly can it turn around? We published a clinical report. So, working, collaborating with a local clinic in Utah, we took 11 women with newly diagnosed type 2 diabetes, And their A1C was 8.9%. So very much diabetic range. And the physician, who's very much on board, had given these patients 2 options. And he said, you can leave the office with a prescription for an anti-diabetic drug like metformin, or you can meet with a nutritionist and go through this lifestyle nutrition counseling. And in just 90 days, their A1C went down. The average A1C, the average was 8.9, and it went to 5.6. So no sign of diabetes whatsoever after just 90 days without a pill popped or a needle injected. So I have often taken that 90-day span as a very reasonable amount of time to reverse insulin resistance. Now, depending on the scope of the problem, it may take a little longer to get rid of all of the consequences of the insulin resistance, but I think 90 days is a very reasonable, justified timeline. Again, I say justified based on our own—

Dr. Rhonda Patrick: Research.

Dr. Ben Bikman: Now, what did we tell them? That could sort of segue into the first part of your question. We gave them, in fact, just 3 pieces of advice based on the 3 macronutrients. And I've actually kind of already alluded to this, which the first one is control carbs. And that was simply this admonition to eat whole fruits and vegetables. You don't even need to count it, just whole fruits and vegetables. But in the case of these type 2 diabetics, We said try to be mindful of the most sugary fruits and veggies or the starchy fruits and vegetables. So the tropical fruits, we said, please be careful with like bananas, pineapples, mangoes, and then the starchy. If the vegetable grows in the ground, eat less of it relatively. But all other fruits and vegetables, and that's still a lot, enjoy liberally and then prioritize protein and don't fear the fat that comes with that protein. And that was an important caveat because we didn't want them to be drinking fat. But we wanted them to acknowledge that in nature, all protein comes with fat. Don't be afraid of that fat. When humans eat fat with the protein, we digest the protein better and it's more anabolic. There's, there are studies in humans to show that people work out, give them protein, they'll have a certain degree of muscle protein synthesis. If you give them protein and fat, it's even higher than it was with just the protein alone.

Dr. Rhonda Patrick: Yeah, and that's—

Dr. Ben Bikman: most people don't appreciate that bile, when the gallbladder from the liver releases the bile into the intestines, we always just think of that as being relevant to fat digestion, and it's critical for that, but it also enhances proteolytic enzymes. It makes the proteolytic enzymes more active, better, they work better, so we digest the protein better. And that may be the mechanism that explains the enhanced muscle protein synthesis from the combination. So that was the dietary advice we gave them, and I would just say that for people that, Manage your macros, control carbs, prioritize protein, don't fear fat. And then when it comes to eating time, I'd mentioned it earlier, the more you can stack your meals earlier in the day, or at least the bulk of the calories coming earlier in the day, the better, so that you can taper off through evening. And by all means, or please don't eat within that 3 to 4 hour window before bed. As much as you can, don't eat. And then exercise. And my view on exercise, as much as we both are, I am an enormous advocate of exercise. I was a personal trainer back in the day during my master's degree, and I hated every minute of it, but I did it. And I appreciate the role of exercise, and I enjoy exercising every day. If people are wondering what's the best exercise, my somewhat pithy answer is the one you'll do. Just do something. If you can do the sort of higher intense strength training that we were talking about, then please do it. But if this is like some 80-year-old grandma who just likes walking around with the girlfriends, just walk around with your girlfriends. Keep doing that habit. Whatever exercise you can do and you're going to do, then just do it. But there is something to be said for timing it where perhaps you can do your exercise session. If it is a walk around the block a few times with the gals, do that after your your biggest meal, where if you just do 10 to 15 minutes of physical activity after your biggest glucose-spiking meal, you will blunt that glucose excursion by half, if not even better. So what would've been a huge, big, long glucose spike and a commensurate insulin dose as well, you're going to cut that down substantially if you did— if you do time that little bit of physical activity. And maybe that would be one other comment. If that's not your main exercise, then have that kind of exercise snack where You had your big meal, maybe hopefully it was lunch, go on a 10 or 15-minute walk. Even those of us that, you know, I'm a professor at a university, I can eat my lunch and still just go on a little walk around the campus. My building is so big that in bad weather, I can walk around my building, even like around the hallways.

Dr. Rhonda Patrick: And so just find a way to get up and do something in little bits, little bits of activity throughout the day, but then still as much as a person can try to have that concentrated time of, All right, I'm working out right now and I'm gonna sweat and I'm gonna get tired from it. Yeah, I love the exercise snacks. I like to do bodyweight squats. That's something that I'll, you know, try to do after a meal, particularly when I'm on vacation and get the gelato that I never, ever, ever eat unless I'm in Rome.

Dr. Ben Bikman: Yeah, well, that's the place to do it.

Dr. Rhonda Patrick: The gelato that I never, ever, ever eat unless I'm in Rome.

Dr. Ben Bikman: Yeah, well, that's the place to do it.

Dr. Rhonda Patrick: But okay, well, that's great. Many people ask about these supplements and, you know, are there these supplements that can improve insulin sensitivity? So they, you know, you hear everything from magnesium to alpha-lipoic acid to berberine, apple cider vinegar, and if, if there's any merit to that or taking it before a meal, or, or is this just like dropping like a drop of water on the, in the pool to like try to fill the pool up?

Dr. Ben Bikman: Yeah. Well, in fact, every one you just mentioned works. Um, frankly, the one I like to talk about the most, because the evidence is so compelling and it's so easy to get, So berberine is undoubtedly effective. No doubt it works. Berberine absolutely works. I love apple cider vinegar as a personal favorite. Maybe it's because of my old man palate where I like really tart things the older I'm getting. So I just love the taste when I dilute it in water or sparkling water. But apple cider vinegar, that really, that's the shortest of all short-chain fats, that acetic acid. And the short-chain in the human diet, as much as we eat a lot of fat, Most of it is from seed oils and soybean oil, but we lose out on the full spectrum of fats because we don't really eat a lot of fermented foods anymore. So we don't get the medium-chain fats. And because we don't eat any much fermentation, fermented foods, we don't get any short-chain fats for the most part. So short-chain fatty acids, which is what apple cider vinegar is, is a really— that's a small little molecule that punches well above its weight, where The acetic acid will reduce hepatic gluconeogenesis to help control glucose, which is very relevant in a person with diabetes, especially type 2. There's so much glucagon always in their bloodstream. It's constantly pushing the liver to make more glucose. Apple cider vinegar will inhibit that. And so it helps the blood glucose by just having the liver dump less glucose into the blood, but it also stimulates AMPK. And you'd mentioned GLUT4 at the muscle. The reason exercise is able to open GLUT4 or translocate it and get the glucose in without insulin is because of AMPK. So it's that interesting paradox of exercise where insulin comes down and yet glucose is taking in more— the muscle's taking in more glucose than it ever was. It's because of this kind of backdoor of the muscle exercising. AMPK gets turned on through a series of events that moves GLUT4 Well, apple cider vinegar will do the same thing in the absence of exercise, albeit to a more modest degree. So that's a couple mechanisms among others, including mitochondrial biogenesis and a little bit of uncoupling, where apple cider vinegar is one of my favorites, where if you take a couple tablespoons before your most starchy meal, you absolutely could compare the glucose curve from one day to the next, and you'll see that it's significantly lower. With just that tart little bit of drinking.