Dr. D'Agostino: But then we started tinkering with the ketone salts and putting ketone salts and mixing that with MCT. So, ketone salts alone or mixed with MCT seem to have a lot of favorable effects on glycemic regulation, anti-anxiety effects. You know, they also have an anti-seizure effect, maybe not as strong as the ketone esters, which are just more powerful on a per gram basis. But I personally would not... I have access to these things. Even if ketone esters tasted great, I would not be consuming them day in and day out. Just for the same reasons, I don't think it's good to spike glucose throughout the day. I don't think it's really favorable to throw a lot of energy in the system in a way, especially if ketones get high, you do get a metabolic acidosis that you can... We see pH drop in our animals. So we measure like, you know, our pH levels and blood gases and things like that, and we see that the pH level will drop typically when the ketones get above about 3 millimolar. So that's probably not a good thing.

So, I'm of the opinion personally and experimentally by...you know, in the idea of keeping exogenous ketones within like an elevation of 1 to 3 millimolar. I think it's pretty optimal unless you're managing like a very serious form of epilepsy, or you have glucose transporter type 1 deficiency syndrome or some other inborn error metabolism where having higher ketones can be favorable because you have a decrease in other metabolic pathways or transporters like in the case of glucose transporters deficiency.

Dr. Patrick: It sounds like though... For my own personal anecdote when I was trying the ketone esters, you know, at first, it was like, "Oh, maybe more is better. I want to get, you know, at least above 3 millimolar." You know, I got like 3.5 with consuming about 30 mils of, I believe the 1-3...

Dr. D'Agostino: Yeah. Monoester.

Dr. Patrick: Yeah, that formulation. Like I said, you know, 30 mils, that's a lot. So, you know, there's people that might be doing that like every couple of hours even, and it sounds like that could potentially be a dangerous thing to do, especially if they're getting in that range where there could be a pH change. And if they're not measuring it, you know, no one's going to know. So, it's something...

Dr. D'Agostino: I don't think we know, and I think it's like... If you have like type 2 diabetes, if you have Alzheimer's disease, you know, cancer, I think it's better to spread out the dose too. So, I think from my perspective, I'd rather take something that's also delivering electrolytes that my body can use and also that tastes good. And the 1,3-butanediol is also a consideration, right, because the liver has to work harder, so it uses the alcohol, the dehydrogenase pathway. And I noticed, you know, playing around with these things over time just 1,3-butanediol, which the ketone esters, if I consume that at a certain dose for two weeks and then get blood work, my liver enzymes are elevated. They're still within normal range, but they creep up into that upper range of normal consuming, for example, like 1 gram per kilogram per day. That's the amount that's needed to sustain hyperketonemia equivalent to a ketogenic diet.

I feel intuitively that it's probably better to take a more natural form of ketones where it's just ionically bound to a monovalent or divalent cation like electrolytes, which our body tend to deplete anyway when you're on a state of ketosis. So, I use the product LMNT. But once we got the ketone formulation kind of figured out, you can deliver the same electrolytes that are bound to ketones. So I think it's a good adjuvant or a good supplement to add to a low-carb diet to ketogenic diet.

Dr. Patrick: How often do you do...? Is this a daily electrolyte sort of supplemental thing that's...? Okay.

Dr. D'Agostino: Yeah. And I just use maybe like a small dose in the morning and I combine it with like creatine, acetyl-L-carnitine, and a couple other like taurine. There's some supplements that I think are really beneficial with the ketogenic diet. They can help boost ketosis. And then, when you're on a ketogenic diet, you're oxidizing so much fat, you tend to be deficient in carnitine, and we see this like in kids that are on...so I think carnitine is like really important. The selenium, some studies may show up that that's really important, but I think that's more of the type of foods that you're consuming.

Dr. Patrick: I mean, a standard multivitamin too also would be...

Dr. D'Agostino: Yeah, multivitamin, but I think you can get a lot of nutrition from, you know, a lot of eggs and sardines and fish and oysters and things like that that are very rich and some things that may be depleted in other people at least clinically. So I take a little bit of ketone salts in the morning, and then later in the day like midday as a pick me up, like I'll do the other two-thirds of a packet, you know. I feel it [crosstalk 00:58:09].

Dr. Patrick: Any other supplements that you take or that, you know, encourage?

Dr. D'Agostino: Yeah. You know, from listening to you a lot, the omega-3s, DHA, EPA, carnitine because that's really important kind of aspect. If I wasn't taking ketone salts, I would be taking more electrolytes, but I take magnesium, "Magnesium 3 and 8". And also BiOptimizers makes a magnesium breakthrough product, which is like magnesium in like five different forms or six different forms. So I've measured my blood levels of magnesium, and it goes up pretty high with that.

I take vitamin D, which was actually low even though I get tons of sun and I was supplementing 4,000 to 8,000 IUs a day. And I got a blood test done, and I was on the lower end of normal, which was really confusing. So I got another blood test that confirmed, the other blood test that I was on a low end of normal. So I got prescription vitamin D, which is vitamin D2. But then I ran out of that, and I was using another vitamin D supplement from another maker. I think it was Mindbodygreen. I was supplementing with that. And then got another vitamin D test after and I stayed elevated in the upper range of normal. So maybe I was using a well-known vitamin D formulation, but it was like from Walgreens or CVS. And I was taking 8,000 IUs a day, and I was still in the low end of normal even though I'm getting a lot of sun exposure. So this was probably one of the most weirdest things.

Dr. Patrick: It could have been a polymorphism or...

Dr. D'Agostino: I was thinking about that. Yeah.

Dr. Patrick: ...you know, because there are polymorphisms that some people require, you know, in some cases, two to three times the normal dose to actually just bring you up to like a normal level of like 30 to 48 nanograms per mil. But the other would be that there's been a variety of studies now over the years showing if you just randomly take different vitamin D supplements off the shelves like Walgreens, you know, in grocery stores, that the actual concentration of vitamin D3 in each supplement varies so widely that you'll often get a supplement that says it's, you know, 4,000 IU, but it's more like 400 IU. And it's really a big problem, honestly. So it is good to like kind of find some go-to reliable brands. Maybe third-party sites have tested the concentration of the vitamin D3. I know Labdoor does one, and then ConsumerLab, they actually go around and test the actual concentration of whatever active ingredient, in this case, vitamin D3 in a variety of pretty, you know, readily available supplements. That could have been it as well, right?