The Supplements Episode - Part 1

Is every supplement that you've heard of great to take? Maybe not. And today on Cell to Systems, we're going to get into it, and at a provider level, which is so, so important in my opinion, because that's where you should start. Oftentimes people ask me about supplementation, and I always say you should never talk to somebody else about what they're taking. You should be talking to your provider about what you need based on your blood panel and a number of other things that your provider may be doing with you. My main man Craig is back after being so busy with patients that we missed him last week, which is completely understandable when you're in high demand like you are. Uh, those things are going to happen. So Craig, we've got a list. Uh, it's pretty extensive. We may have to break this into two episodes. There's so much. But let's try to get into it.

All right, Craig. First one is for you, and this is one that we universally agree on, which is creatine. It's just the amount in which you should take. There's all sorts of stuff being talked about. Hey, you know, the original, uh, loading phases that we used way back in the day, like 20 grams plus a bunch of sugar and stuff that was, you know, supposed to shuttle it into the cell. Um, and then it came back to, hey, just, you know, load it over time at 5 g creatine monohydrate. Uh, the question really has now come up. There are a lot of people that are talking about the cognitive benefits of creatine. And so at what point in time do you recommend creatine to somebody? What point in time do you escalate that? Where are we in this?

I think creatine is one of those supplements that is thrown about pretty often, uh, especially in the fitness industry. But yeah, as — as far as what you mentioned in terms of the cognitive benefits, there is new data to support that it can be very useful for mental acuity, cognitive sharpness. Um, you know, it's not going to be your absolute game changer or limitless pill when it comes to, uh, your brain function, but is it something that we can do, that we can incorporate into our regimen to overall continue to try to optimize our function? Yes, I — I think so. Absolutely.

I mean, what do we know about creatine? Creatine monohydrate, uh, when you take it, it increases intramuscular creatine and phosphocreatine. And those, specifically the phosphocreatine, donates a phosphate to ADP, uh, and that helps perpetuate ATP, or the synthesis of basically our energy currency. So when we think about, you know, muscle activity, when we think about brain health, when we think about the action of all of our tissues and all of our cells, we're really looking at how much energy are they consuming, what is the energy requirement, and what is the energy output. So, if we're improving ATP signaling in the body, I think that we can have absolutely some cognitive benefit.

It's interesting that you noted the — the dose, uh, variability there. A lot of people will take five grams of creatine daily. Um, there are some who regularly will utilize 10 grams of creatine daily. And as we've talked about on this podcast before, one of the interesting things that's come about recently is if you are in a sleep-deprived or growing sleep debt state, there is some signal there that taking an escalated dose of creatine monohydrate in the realm of 20 grams, um, on the morning after a bad night of sleep can help offset some of the cognitive, uh, issues, some of the, you know, brain fog or load or impaired thinking that one may experience after such a bad night of sleep. So, I do think that that is interesting. You know, it's going to be a compound that's continued to be studied for years and years and years to come. It's definitely hot right now in the fitness world.

The other thing about it is, you know, how can we use this to optimize cellular hydration, right? If we think about the performance of the cell, the resilience of the cell membrane, so much of this ultimately is going to be influenced by how hydrated our cells are. So when we think about creatine as a compound that is in fact an osmolyte and helping to, uh, bring fluid into the cell, there's obviously a benefit here. And people often experience this when they take creatine as, like, okay, I feel a little bit puffier, if you're taking a higher dose of creatine or you're taking it regularly. Uh, creatine, I think, is very beneficial, can be used pretty much across the board.

Uh, there are some things that should be noted when somebody is using creatine, and this is primarily in reference to the way that it can interfere with your basic metabolic panel or complete metabolic panel as far as kidney function goes, right? We know that, uh, creatine will increase your serum creatinine level, and in doing so it can also lower your glomerular filtration rate. So GFR, for those of you who don't know, is basically the milliliters of blood filtered through the kidney apparatus within a minute of time, and it is the marker that we use to stage things like chronic kidney disease. So, you know, ideally somebody should be, um, with a GFR that's closer to 100, let's say, uh, or even perhaps over 100. Um, once we get down below 60, we're really in the realm of, you know, stage three chronic kidney disease.

So, when you take creatine and you're sort of falsely lowering the GFR, this can be a red flag for a clinician. Oh my gosh, you know, why was this person's kidney function excellent, uh, three, four months ago when they came in for bloods, and now all of a sudden we're seeing this marked reduction in their GFR? Um, and so I tell my patients when they are using creatine, there's a much more reliable marker that we can assess. Uh, it's called cystatin C. Cystatin C is a protein that's released from virtually all nucleated cells in the body, and it is not influenced by other factors such as age, sex, someone's muscle mass, uh, a workout that they just undertook. Um, so it's a much more reliable indicator as to what their actual, uh, kidney function is. So that's one that I rely on heavily in my practice. But creatine, I think, great. Yeah, I mean, I'm — I'm big proponent of it, and I think that there's going to be new emerging data over the coming years as to additional benefits from — from creatine. I know that's one that, uh, you use and I use. So yeah.

Yeah. Yeah, certainly tons of — I mean, I think it's the most studied supplement out there. Um, and one thing you've got to realize is that when you're using creatine, you're pulling a lot of water out of the system into muscle and other areas. And so, hydration overall, super important. If you're taking five grams of creatine, you may not notice it as much. If you get up in 10, 15, 20, uh, that can cause some constipation. So, digestive issues. Super important to stay really hydrated, drinking a lot of water, maybe more than you're used to drinking, and also eating a high-fiber diet. You know, one of the things I use is chia seeds, along with everything else, the greens and all the vegetables that I'm eating, because chia seeds soak up that, and they keep everything kind of moving through, and — and keeping things, the motility happening, which I think is super important.

Creatine for men and women. Uh, often because of the fitness industry, and because creatine came out of the bodybuilder world for the most part, a lot of women are afraid of using creatine, when in fact it's really beneficial to them. Um, and there's tons of — tons of talk about that now. Um, and I know a lot of women that are starting to take it, which is pretty exciting. I think that's pretty cool.

Definitely. 100% agree with you there.

Okay. So, let's talk about — um, since we're on the topic of osmolytes, uh, when we start taking creatine, there's sort of that thought process that you need something to help shuttle it into the cell. So, it used to be you need some sort of sugar to create the insulin response that would —

Yeah.

— pull it in. Um, how true is that?

You know, I don't really know. Um, I'd have to look into that. I — I, to be quite honest with you, I don't — I don't really know. When I take my creatine, for example, I take it just in water, or I take a gummy, and, uh, you know, I don't pay too much mind as to the, uh, things that I'm taking along with it, if it — you know, any sort of substrate like a carbohydrate or, um, you know, protein or anything like that. I'm usually taking it before a workout, um, and I feel like I'm getting a good pump. Now, that may be due to other things, um, but, uh, that — that's an interesting topic. What are your — what are your thoughts on that?

Well, you know what, I — the way I use creatine is in a hydration formula that I'm drinking, usually in the morning when I'm working out, and then sometimes throughout the day, which is really supposed to — how you're supposed to use it, but difficult to carry two bottles of water around. So, you know, this particular bottle of water is 40 ounces.

Whoa.

40 ounces, and I'm on — I guess this would be technically the fourth bottle. So, you know, it's, uh, what, 12 noon here on the West Coast, 3:00 p.m. where you are. And, you know, we hit the gym. We spent an hour and 55 minutes in the gym this morning. And, you know, we're burning through a lot of water. You're going to need to be hydrated in order to stay in an anabolic state. Um, if you're not hydrated, you're going catabolic quickly. And it's funny, I just had a conversation with a doctor friend of mine who basically talks about, you know, he's drinking coffee before he goes to the gym, and then he doesn't feel very great, feels like he's got brain fog. And I'm like, well, you know, I mean, there you go. There's your hydration. He's like, yeah, you know, you're right. You know, 100% should be doing that.

So, there are a number of other things that are in that formulation. Um, so we have glycine, uh, L-alanine, um, taurine. It works really well. I really like it. I feel like, um, that's been a game changer for me. I also use salt — salt T — Salt T minerals. Um, those are daily minerals. So they have more than just the electrolytes in them. They also have some really important, um, minerals that you'll need just from a, you know, body standpoint overall.

Let's talk about magnesium glycinate. Um, and we've — I mean, in the sleep world, obviously right now I'm in a calibrate phase that I'm working heavily on with you. Uh, and this is all about tracking all of the things that I need to improve to reach that next level. One of them is sleep. And so I'm looking at every aspect of sleep, my sleep score, using my Oura Ring. Hard to sleep with a watch. So I sleep with the Oura Ring just to track it, just to see. And what I found is that, you know, there's been a lot of talk about apigenin and magnesium threonate and then, uh, L-theanine as — as a stack to be used. I've used it. It seems to work for a little bit, and then you kind of get back into this sort of, uh — your body adapts to it, and it doesn't seem to work as well. Uh, I think with any — any kind of agent like that, even a pharmaceutical-grade agent, there's some sort of drop-off in efficacy over time. So when we talk about this, it's sort of split, in my opinion, on — on magnesium glycinate. Where do you come out on this?

That's my favorite of the magnesium, you know, options that are available. I think that it has strong support for sleep. I mean, I — there — there's definitely data, uh, surrounding that, and when I say strong, let me recharacterize. I — I think that there is good evidence to support that there is a positive signal there. Um, you know, glycine can be very calming, um, as a — as a supplement, and recommended dose that I tell my patients is usually around 500 milligrams twice daily. Um, I recommend — you know, we use Mag Glycinate Chelate, which is a product from, uh, Designs for Health here. We recommend usually a mounded scoop once in the morning, once in the evening. Now, your standard sort of magnesium dose, um, is around — magnesium glycinate dose is around, you know, 3 to 400 milligrams, and I think that that is readily able to be doubled, uh, for optimal benefits. Uh, so I, you know, think that mag glycinate is — is really my go-to. Um, there's some back and forth between glycinate and threonate as to which is truly the better option for brain and nervous system health. I do tend to be a little bit more firmly planted in the glycinate camp than in the threonate camp.

There's other host of benefits from magnesium supplementation to begin with. I mean, we know that it's, uh — we know that it's calming. It can be very calming. So, it can lower anxiety. Um, it can, um, also help with smooth muscle relaxation. So, when we're talking about, you know, uh, blood pressure control, when we're talking about reducing the sensation of discomfort in our muscles, and when we have muscle strain after workouts or in and around recovery periods, uh, magnesium can be a great option for that. Magnesium is a cofactor that's necessary in all sorts of enzymatic reactions in the body. So, it's — it's critical. It's critical for heart health. Uh, it's critical for brain health. It's critical for nerve tissue. Um, so, you know, I — I'm a big pro — proponent of magnesium.

Um, one of the things that I like to discuss with my patients is that renal impairment, right? Going back to the whole idea of kidney function, you want to be careful with magnesium, um, if somebody has moderate to advanced stage renal disease. So, that needs to be something that is reviewed with your clinician. Uh, the other thing is that, you know, a lot of times in sort of a standard, uh, workup, people will just check a serum magnesium level, when what I advocate for in my practice is to check a magnesium RBC, uh, which is well thought of as sort of like an average magnesium, cellular magnesium value over a period of time.

Magnesium, a lot of people also don't know this, is really our number one, or one of the major micronutrients that is associated with insulin receptor responsiveness. Okay. So, when we think about people who are pre-diabetic or diabet — diabetic, they're having issues controlling their blood sugar. Uh, you really want to look at that mag RBC level, because it is playing a significant role in how well your insulin receptors are expressed on the cell and how responsive they are to the insulin that's secreted by the pancreas in response to blood glucose and controlling that blood sugar. So, it's one of the first things that I look to optimize in my patients. If they come in to me and they have a mag RBC level of, you know, 4.5, 4.7, something like that, I'm always looking to get them boosted up to around 5.6 at a minimum, or more optimally around six. Dr. Jim LaValle, who is a pharmacist, um, is huge on this, and that's where I learned about this topic from — from him and his lectures. And, uh, you know, if you guys have the time to check out Dr. Jim LaValle, he's big in this longevity space, and he just goes to town on, uh, you know, the importance of — of having a cellular or RBC magnesium that is, um, you know, at — at least, you know, 5.6, closer to six. Very important for overall metabolic signaling, and like I said, it's responsible for so many other enzymatic reactions in the body.

Yeah. When you — when you start to go outside the realm of sleep, it's clear, you know, you got to have it. Um, so there's no doubt about that. Which brings us into, when we're talking about anti-anxiety and sort of calming and all of those types of things, it's interesting to recognize how much omegas play a role. So, we talk about krill oil, fish oil. I know you're on the more of the fish oil camp, and you're switching me off of the, uh, krill oil into the — into the fish oil side of things. I — I think this is one that I — I — I'm taking a lot of it. Um, and it's — and it's had an impact, and we've seen it in my blood — in my blood work. So, you know, again, let's talk about it. Let's try to help people understand why you want to take this. There's been some split talk about it lately. And some people are like, I don't think so. But I do think so. And I — and I think I've seen it in my blood work.

So, yeah, omega-3s, I mean, these — these are fantastic. You — there's nutritional sources, right? I mean, you can get omega-3s from salmon, mackerel, cod, halibut, fatty fish, sardines, right? Um, great source. You can get it from walnuts, you can get it from pecans. Um, there — avocados. Um, and why are omega-3s beneficial? What do they do? Omega-3s really get the A on my list as well of supplements, because I think the data is very strong for triglyceride lowering. I mean, there is a prescription medication that is super-potency, high-strength omega-3 called Vascepa that we use for resistant hypertriglyceridemia. Uh, so we know that it has a lipid-modulating influence. Um, we also see some recent research over the past few years about its, uh, potential in reducing anxiety and depressive symptoms in people who are — who are prone to those issues.

Dosing is the type of thing that, um, you know, a lot of people routinely sort of underdose their omega-3s. You'll see anywhere from around a gram, uh, to two grams in sort of your average fish oil supplement. And again, going back to, like, what is in that supplement, right? So it's EPA and it's DHA. Now, DHA we associate a little bit more with some cognitive protection and brain health benefits, and the DHA component may be what's driving some of the relief of those anxious and depressive symptoms in those patients, in those studies. What I like to recommend for my patients is roughly a 2:1 ratio of EPA to DHA in the supplement. And depending upon their unique clinical scenario, I may be recommending upwards of 3 to four grams in total of omega-3s daily.

Now, there is some potential areas to say, hey, well, maybe that's not appropriate here. For example, somebody who's on a blood thinner. Well, we know that fish oils can have this mild potentiating effect on thinning of the blood. Uh, so it's something to be aware of, though I would not say it is an absolute contraindication. There is strong data to support the fact that higher doses of omega-3s over prolonged periods of time can absolutely contribute to an increased risk in atrial fibrillation. So, um, you know, I think that people need to be aware of that as well. Uh, if they have untreated sleep apneas, if they're dealing with, you know, thyrotoxicosis or excessive thyroid activity, if they have, um, you know, any sort of structural changes in the heart that could potentiate or precipitate, uh, atrial fibrillation, then we want to be careful there. But omega-3 is absolutely another win in my book. I think that the triglyceride lowering, uh, is a major plus, and I'm a big fan. I use them all the time in my patients.

I'm a believer, and, uh, my dose is up higher. So, I'm on the high side.

You know, the other thing is, when it — you had mentioned, like, krill oil versus fish oil, right? And I think that this really comes back to the quality of the supplement brand that you're using. You know, if it's, um — depending upon, you know, how much oxidation and — and how pure the — the fish oil is. These are things that need to be considered, and, um, be — because we are dealing with an oil, right? And — and so it needs to be evaluated, and you got to stick with the brand. I mean, you know, I — I'm not routinely recommending that people go to Walmart or even, like, CVS for their supplements. You know, you want a good quality brand, a — a practitioner-recommended brand.

Dude, I — I could not agree more. I mean, I think one of the things that's most — like, you see this where people are buying stuff, and it's like, number one, how long has it been on the shelf? Number two, you know, what's — you know, like, the lot number and all that kind of stuff. It's like, you know, you really, I think, want to be getting supplements through your provider. They may not have it in stock in their practice. Um, but they can help you to get the right stuff, like you do for me with Designs for Health.

Yeah. DFH, and their product actually, um, you know, once you open it, you really should keep it in the refrigerator, um, and — and preserve the product. So yeah, that oxidation piece is so, so important.

It's like, uh — uh, rancid vitamins, right? Uh, you know, they go rancid, they go bad, and oftentimes before you even get them. The other thing, too, that I want to point out, uh, around supplements, when we're talking about supply chain, is that — and I don't know that this is true or not. There was a rumor, so nobody can confirm this as being, uh, truth, but there are a lot of people that were talking about it, that Amazon supply chain was infiltrated by a lot of counterfeits. That's scary when you think about it, because you as a provider say to me, "Jock, you need to be taking this." Then I go to get it, and it's not what you're asking for. You know, you really want to make sure where you're getting your stuff is — is — is really important. So, getting connected the right way, either through your provider or ordering it directly from the company, rather than relying on — yeah, I know it's convenient to get Amazon Prime, and I don't have — I don't have an issue with Amazon. Uh, when it comes to this kind of stuff, I think it's important to just make sure. Also, I think it's supporting the companies that are putting out really high-quality products. Uh, it helps them, because that's obviously going to allow them to maintain more margin.

Which brings us on to one that is big on the question mark. Something I've used for a long time. Could I tell you if it made a difference or not? No way. Urolithin A. And so it's hot. It's been talked about. Gabrielle Lyon, Dr. Lyon's been all about it for a long time. Uh, Mark Hyman, Dr. Mark Hyman's been about — like, you know, who hasn't talked about urolithin and said it was fantastic? And, you know, there's one particular brand, I'm not going to name them, but they've really put out some statistics that say that it's going to increase your endurance and strength capacity over a period of time by, you know, a good percentage. Again, I think a lot of that study, those studies were — were funded by the manufacturer. So, that's something where I always am a little skeptical when it's coming. Where is that? That's something that I don't think consumers really look at. What is the primary source? Where is that, uh, RCT coming from? So, randomized control trial, where is that actually happening? Who's funding it? What's behind it? We've certainly seen that in the food industry, where, uh, you know, studies funded by certain people to achieve certain things and change the entire food pyramid — not so hot. So where do you come out on urolithin A?

Yeah. Um, you know, urolithin A, the whole philosophy behind this is mitochondrial quality control, you know, and the whole idea of what we call mitophagy. A lot of people who listen to this podcast are familiar with the term autophagy, that process that's activated by AMPK, and it's the cellular cleanup, cellular repair, getting rid of the damaged, uh, components of the cells. Um, so, you know, it's interesting that our mitochondria, which are organelles inside the cell, which are the responsible organelles for energy generation in the body, uh, also go through a similar process, right? They can, um, go through mitophagy, which is basically the cleanup of our mitochondria.

So when we think about energy issues, chronic fatigue, uh, people that have been through, you know, high-stress periods due to infection, other illness, things like that, you know, um, we're really looking at a picture of a human who's been — whose energy availability has been diminished because of the persistent oxidative or inflammatory stresses that they've been under during that time. So, one of the ways that people can target that is through, um, mitophagy and through mitochondrial cleanup, basically getting rid of the damaged mitochondria. Because mitochondria will, um — you know, there's mitochondrial fission, there's mitochondrial fusion, mitochondria want to replicate themselves, mitochondrial biogenesis, right? And so we want optimally healthy mitochondria to be, you know, duplicating themselves, in a sense. Uh, and if you're sort of doing away with the old, damaged, ill-performing, low-efficiency mitochondria, then there is a plausible mechanism there by which you can actually increase your performance, increase your overall energy expenditure, uh, and have better performance results.

So urolithin A is a compound that is found naturally in the world in pomegranates, pomegranate seeds. Um, so people that eat a lot of pomegranates, which we know is a sort of superfood, if you will, have the potential to be consuming adequate volumes of urolithin A. Now, there is a caveat to that as well, and that, the enzyme that is responsible for basically allowing — making b — uh, urolithin A bioavailable, uh, for use and for mitophagy purposes is not, um, in everybody, and — and some people are deficient in it. So, you know, having a supplement that you can take, such as urolithin A, uh, to sort of bypass that whole circuitry and make it so that you're just consuming the urolithin A, it's bioavailable to you, uh, is, I think, again, a good thing to consider. The data I'd like to see more over time. Um, but I think, you know, mechanistically it makes sense to me. There's a lot of other things that we're doing in the clinic routinely to sort of optimize mitochondrial health and performance. Um, we've talked about ketones. We've talked about these other AMPK activators, and — and just, you know, getting good sleep and exercising, eating a well-bal — balanced, uh, nutrient-dense diet. So, it's on a lower tier for me than some of the other things that we've mentioned thus far, but again, I think mechanistically it looks good, and I'll be interested to see what more comes of it in the future.

Yep, I'm with you 100%. Um, and going back to what we talked about, uh, psychiatry, metabolic psychiatry in the past, and the notion that, uh, what if — you know, if serotonin really isn't a — isn't a factor in depression, which may or may not be true, uh, and it's really just an energy issue, then — but making sure that your mitochondria are, um, you know, going through the proper process, fission and fusion, biogenesis, and making sure that you're staying healthy in the cell. It's amazing to see how the cell goes through and cleans up mitochondria, uh, those that are deficient or no longer working, that gets rid of them, and it does that. So, I think it's important to pay attention to this one as time goes on. We'll see. There's going to be — clearly there's — it's in high demand. So, there's probably going to be more and more studies, I would imagine, that are coming out on it.

Moving us on to something else that has been really hot, and not for a short period of time, but we're going on, like, about 10 years, I feel like. Collagen peptides. So whether these are bovine collagen peptides or marine collagen peptides, and there are some people that recommend that you combine them both. Um, but this is essentially the synthesis of collagen from, um, from an animal product. Um, usually what does it come from? Like tendons and things of that nature, right?

Yeah. Helps make them up. Yeah.

Yeah. So, um, and I guess in fish it would be connective tissue in some way, shape, or form. Um, but there's a lot of split, uh, talk about this, that, you know, hey, how bioavailable is this? You know, when they say that it's a protein, it's not a complete protein. Doesn't have all of the amino acids in it to give you essentials. So, it only has a certain profile there. Uh, but there's this talk that it's just great for your skin, and you should be taking this stuff all the time, particularly in conjunction with vitamin C. So, the big question is, is this something that the people should be buying bags of and taking two scoops a day? I've been told by providers that, yeah, you should absolutely do that. Um, and, you know, I've got a big bag of it — of it up at my house right now, and I — I do it, but, you know, is it really the thing?

Well, I don't do it. So, uh, I think — I think, you know, by and large, products that are — are clean collagen peptides taste terrible. I think that they integrate relatively poorly in — in a beverage. Uh, they're hard to mix. They get clumpy. It's like, you know, my kids' Silly Putty that sits out on the kitchen counter. Listen, just very superficially, I think they're nasty. I don't think they taste well. And, um, I don't use them. Uh, the products that do taste good or are tolerable, um, generally have, you know — they're — they're loaded up with, uh, things like Ace-K and other, um, things that are preservatives and — and sweeteners and whatnot. So I avoid collagen peptides for myself. I don't readily recommend them, uh, for patients. I try to encourage, uh, you know, nutrient-dense whole protein sources of — of food in the diet. I think for thousands of years humans have doing — been doing very well, uh, without taking collagen peptides. Uh, you know, the — the Romans weren't sitting around taking collagen peptides in their — in their wine or in their coffee. They were eating, you know, whole foods, right?

So it's not something that I readily recommend. You know, types one through f — one through five collagen, you know, they have proposed hair, skin, nail benefit, improving, um, you know, elastin synthesis and volumizing the skin. Uh, type five collagen has a role, undoubtedly, in bone health and the formation of — of trabecular bone. Um, so, you know, I am, uh, again going to sound off on this notion that I — I think that there's a role for them, but I think that if you're eating well and you're doing the other right things, then you don't necessarily need to incorporate collagen powder into your diet every day or what have you. It's just — I — I'm not a big fan. Um, maybe I'm doing something wrong. I'm happy to learn, but it's not my go-to, and virtually never recommended in my practice.

Yeah. Well, um, based on your education, what I know about you, and how deeply you study the science every single day, I'm going with you. Um, so the good news is my —

I could be wrong. I really could be.

Yes. Hey, we always reserve the right to be wrong, right? There's more to come, more information to be had about this. Uh, all right. The next one is definitely something that I'm skeptical on, uh, for a lot of reasons. Number one, not all methylene blue is created equal. There is a bunch of methylene blue that is out there, um, and is being touted as, like, incredible, uh, you know, uh, oxygen delivery.

Yeah.

And the reality is, there's a big difference between methylene blue that is just methylene blue and methylene blue that is food grade. Um, and then the concern I have — I mean, if you think about it, SSRIs are one of the most prescribed drugs in the United States. And I think it's dangerous when people get on to YouTube, they start listening to people talking about methylene blue, and then they're not talking to their doctor about it, or they're talking to their physician or clinician about it. Um, and they start taking these things that could have an interaction. Um, so how steep is this interaction curve with regards to methylene blue and SSRIs, and where do you come out on methylene blue as something to use?

Um, not one that I rely on heavily in my practice. Have I used it in patients before? Yes. It's been about 50/50 in those that do respond to it and do feel improvements in mood and improvements in energy. Um, and I will say that it is definitely an area that warrants caution, because we know that, um, methylene blue, uh, can be a potent, uh, MAOI, right? Um, so MAOI is — or MAO, uh, is responsible in — in part for serotonin metabolism, right? And so when we inhibit that process, the risk of precipitating something like serotonin syndrome, or excess serotonergic signaling, uh, can create symptoms for people. This can create, at its worst, you know, uh, tachyarrhythmias, heart — heart rate issues, um, elevated blood pressure. It can contribute to, you know, manic symptoms in the brain. A lot of patients at, you know, lower levels will feel some sort of anxiety associated with that. They may feel tremor, diarrhea, frequent loose stools.

So, I think that this does warrant caution for somebody who is on, um, you know, certainly if they're on, uh, an MAOI medication, or if they are on an SSRI or SNRI. If you're on one of those medications, you know what I'm talking about. Serotonin is obviously a very important, critical neurotransmitter in the body. Uh, but it needs to be balanced, right? So we don't want to be just sending excess serotonin signaling throughout the body, because it does have very real and very untoward consequences when it's in excess. So methylene blue, again, it's something that I've seen, uh, can work in some people, uh, based on anecdotal report of how patients are feeling in my practice. Um, I don't rely on it heavily, don't use it frequently, and then about the other 50% just don't really notice anything. So definitely not something you want to do outside the guidance of a provider. Um, because that's sort of a guessing game, and I — I — I don't think that's one you want to play around with.

Okay, I've got a couple more to hit you with, and we're going to get your — to your list. Um, so let's talk about, um, something that, you know, I spend a lot of time — I take these, uh, three times a day. Uh, so the ketone ester. Um, it's different than some of the other products that are out there. We don't need to go into that. What I would say is, to me, KetoneAid, uh, as a product, has been a phenomenal, uh, game changer for me in — in a number of ways. When I first learned about it, uh, few years ago, started — when I started using them, like, oh yeah, this is good stuff — difference.

Yeah, it makes a big difference.

And we've done them together. Um, so we get the cognitive benefits of that. We also get the, uh, performance and recovery benefits of them. I mean, I use them in my stair workouts, uh, 100%, and they work really well for me. But I just been doing it that way, so I'd love to hear what your take is on, uh, on ketones.

Man, I tell you what, I keep the ketone tab open in my browser through every single patient visit that I have, because I am referencing it all the time. I mean, it — it — it's crazy. It is one of those things, and my patients who are listening, anybody who's listening right now, just hear me when I say ketones, exogenous ketones, are one of those things that you can implement into your regimen that absolutely you will note the feeling of these things. A lot of times you will — you will start to experience some of the benefits of the ketones after your first trial of a ketone ester. But when you really remain consistent with it over a period of weeks to months, you're — I — I mean, you're going to be operating, in my opinion — a lot of people report back to me, uh, and I experience it myself — you start to operate just at a different level of functionality.

Um, you know, ketones are good, solid, clean energy. We make them, of course, in our body naturally as we metabolize fatty acids. Um, and so, you know, they're heavily relied upon by all tissues in — in our body. And the data here with ketones speaks for itself. I mean, um, if you go on the KetoneAid website, you'll see some really strong studies that show, uh, improvement in, you know, muscle strength and endurance. Athletes, uh, lowered lactate production, uh, through exertional activity. You'll see numbers corresponding to improved brain network stability, uh, decreases in wakefulness after sleep onset. Um, and so I'm a big fan. They — they even decrease hunger hormone, right? They have the potential to lower ghrelin levels.

So ketones are good, clean energy. When we look at what ketones as an energy source do in comparison to other things that we — that readily provide energy, uh, we know that they're generally producing less free radicals, reactive oxygen species that the body then has to counter with its own antioxidant production. Um, and so they're also helping improve, uh, overall ATP production in the body in a more efficient manner, using, um — or generating more ATP, the currency of energy, per unit of oxygen than other sources that we would use for energy generation. So ketones are a big win in my book. You can start your day with ketones. You can end your day with ketones. They do, for me and for many of my patients, give that good edge from a cognitive clarity standpoint, mental acuity, sharpness, akin to caffeine, but without the uncomfortable jitteriness or anxiety-inducing buzz that people often complain of when they think about, you know, caffeine use or excessive coffee intake, that sort of thing. So, I think that ketones are real strong. Love ketones. Talk about them all the time.

Ketones are also an excellent place to go to. I pivot to ketones all the time in my patients who are dealing with some sort of post-viral syndrome, dealing with chronic fatigue, maybe they've been on this, um, campaign of undernourishment, under-consuming calories. Uh, so for those people who are sort of metabolically deprived at one point in time or another, I'm always pivoting to ketones as, like, a starting point to say, hey, let's — let's help the mitochondria along a little bit. Let's give them a little nudge here, uh, so that we can start to improve some of these signaling, uh, pathways while really balancing everything else. You know, it's just that — it's that wind, uh, that's on your back when you're — when you're doing the bike ride or you're on a run. And I don't mean that — um, I — I mean that metaphorically, you know. It — it's just the wind in people's sails, right? And it gives them that little boost, that little edge to sort of invigorate them while they're working on addressing all the other health-related aspects.

What I could say is, once you get on them, the difference is so steep that you're not going to want to ever be without them. I mean, I do take them three times a day. I take them when I first wake up. I take some EAAs as well. Uh, that's going to be pre-workout. And then I do use some caffeine. And what I find is, like, what happens is there's, like, this second wave. You could feel it when you would normally start to drop off. It kind of, like, gives you this second capability to keep climbing. And oftentimes we're at the end of a workout, and it's like, man, there isn't anything else to do. And we're still searching for something, like, "Hey, should we add some of this in? Should we add a little more of this in?" And, you know, Zach and I, uh, are just like, "No, man. That's it." And the time says, and we got to go, and it's — and it's done. It is what it is. So, I think it's really interesting. Those are — those are phenomenal. And the reality is, you can buy them on the KetoneAid website. I think it's better to buy them from your provider, personally, because, you know, you're working with the whole patient then.

Okay. So, that's the end of part one. Those were the things that I wanted to cover with Craig, uh, in this episode. The next episode, we're going to cover Craig's list, uh, the list of things that Craig wanted to talk about, which I think is going to be super fun and exciting. And then we're probably going to have another episode of other things that we're going to talk about in the world of supplements, the unregulated world of supplements that aren't controlled or monitored by the FDA, where tons of claims are made by all sorts of people, and you don't know what's in them oftentimes, why it's so important to actually buy them from quality sources. For everyone listening, thank you so much for tuning in, and we love it when you leave comments. We love it when you like, share, and subscribe. Sharing some of this information with loved ones or just friends and, uh, other people that you know, so important right now. Uh, the world of supplementation is kind of off the wall. Um, I think we got some great information covered today by Craig. And, uh, Craig, thank you so much.

Of course. Thank you. Happy to be here.

Yeah, we'll catch you on the next episode.