Longevity Doctors Rank the Most Hyped Supplements (AMA with Dr. Kaeberlein and Dr. Byrne)

This person asked, "What is Matt specifically referring to about the misrepresentations of research on sirtuins and resveratrol and Mark Hyman?" >> Resveratrol is a potent activator of sirtuins, not true, [music] and that sirtuins are sort of master regulators of longevity, not true. That's been debunked. I have become pretty disillusioned with Mark Hyman in general [music] lately. >> Creatine, the way it's metabolized, will increase creatinine. An increase in creatinine does not mean that you have a decrease in kidney [music] function. There are actually some studies now where they're taking dialysis patients and they're giving them creatine in [music] dialysis. Thank you, whoever posted that question, cuz I hadn't thought of that, but it's actually spot-on. [music] People taking an SGLT2 inhibitor have about 20 to 40% loss of lithium. So, I am going to up my dose [music] from 5 mg to 10 mg based on this. >> Someone who is super anti-metformin, and then we found out they were taking berberine. >> Yeah, we see that a lot with patients who are anti-statin, but [music] then take red yeast rice. >> totally get the idea that natural is better than pharmaceutical, but when it comes down to the actual molecule, [music] right? I think it's helpful to just kind of take a step back and try to be completely rational about it. What do you take for longevity? >> Magnesium, omega-3s, vitamin D, and then I take a hair vitamin because [music] I want luxurious hair. I've been on it for years, it doesn't do anything. Hey everyone, welcome to the Optispan podcast. Today, we're going to do something fun. We've got an AMA from your questions, and I'm joined by Nick Arapis and our clinical director, Dr. Nikki Byrne. Uh Nikki and I are going to field your questions, and we'll see what we come up with. So, let's jump into it. So, you've put together a set of questions that have come in through YouTube, Instagram, I don't know where you get maybe you made some of them up. All right. So, let's see what we got. This is And this episode's going to be focused around supplements, right? Okay. Great. So, the first one was actually from the episode of you talking about your supplements that you're currently taking, which ones are winners, which ones are scams out there. And the question is, "How about CoQ10 for those who take statins?" Okay, I'll let Nikki field this one cuz it has to do with an interaction between a supplement and medication. Well, sort of. So, I think it's interesting because statins do interfere with the endogenous production of CoQ10. So, if you look at circulating CoQ10, we can see lower levels in patients who take statins. Um but what's interesting is does is that even clinically useful? And so, one of the proposed mechanisms for CoQ10 with statins is in patients who have statin-induced muscle aches. Um and so, the data's on that kind of mixed. So, there's one meta-analysis that shows if you take this CoQ10 with it, people had a reduction in symptoms. Interestingly, their CK levels didn't change, so I don't know how much it's >> CK is creatine kinase. >> Yes. So, I don't know how much it's doing on a molecular level. Um and another study that showed that there was no change. So, at least in the medical world, expert consensus says patients who are on a statin don't blanketly take CoQ10. Um but if for some reason you can't tolerate a statin and and you can't tolerate alternatives, then it would be worthwhile taking CoQ10 as a supplement. >> So, if you can't tolerate statins >> So, if you can't So, if you can't tolerate a statin due to the muscle aches from it, and you can't tolerate an alternative. So, let's say you had an aversion to needles and you couldn't do Repatha. Rather than scrapping the statin entirely, that's when a medical provider would recommend saying, "Okay, now you Now you might want to try CoQ10 as a supplement to see if it does improve it." >> I see. So, the >> mixed. >> So, the idea is that uh statins are HMG-CoA reductase inhibitors, right? That's part of the CoQ10 or that when you inhibit that, you have less CoQ10 precursor, so you get less CoQ10, right? >> It's involved in the endogenous production. I haven't looked into see where in that pathway. >> Right. And that's been shown, right? That people who take statins, you can see a reduction in circulating CoQ10. What's less clear is whether that's actually important. People have talked about CoQ10 for a long time as a a mitochondrial So, so for for maintaining mitochondrial health. So, so CoQ10's in the mitochondrial electron transport chain, right? So, people have talked about it for a long time. I just think like a lot of these supplements, the actual quality evidence from clinical trials is is mixed and pretty weak. So, maybe. Maybe. Yeah. Well, I think the other thing to think about though is if you're on a statin and we know that it decreases it and there are these pathways towards anti-inflammatory antioxidants, is it necessarily going to do you harm? So, when we talk about the risks and the benefits of different supplements, CoQ10 is one that's pretty benign, so we don't tend to see a lot of side effects from it. Um so, I don't think it would be unreasonable for a patient on a statin to say, "I want to take CoQ10. I want to bring that back up." It's just not something that we routinely recommend. And it's kind of subjective, right? You don't have a biomarker you can look at and say, "Yep, CoQ10's fixed your whatever the problem is." Other than you could measure CoQ10. All right. So, next question from the same episode, "You didn't put taurine on the list, certainly hyped a lot." Right. So, yeah, so so taurine, I don't take taurine. Um taurine, I mean, it's been around for a long time as a as a supplement, amino acid. Um I think the enthusiasm comes from a a couple of studies in the last few years, one of which I I was involved in as a co-author, where taurine has been implicated in the aging process. So, the study that I was involved in, uh taurine supplementation was shown to increase lifespan in yeast, worms, flies, mice, and then there was evidence that in non-human primates, mice, and humans that taurine levels decline with age. So, I mean, that creates a plausible case that this is a metabolite naturally occurring, declines with age. If you supplement, there may be some benefits in the context of of aging. Having said that, there have been studies that have come out since then, I think calling into question at least the aspect of that idea that taurine generally declines with age in non-human primates or or in humans. So, you know, my view is it's early evidence, it's intriguing, it's yet to be really replicated, the longevity benefits. It hasn't been shown by the Interventions Testing Program, got my nice ITP water bottle here, uh to extend lifespan uh in mice reproducibly. So, it's not to the level that I'm like this is a tier one supplement. That's why I I didn't put it in my list. If people want to take it, there's probably not a lot of downside, but I think the the evidence that you're definitely going to get a benefit is also pretty low at this point. And taurine's usually added to a lot of energy drinks, right? Is that the idea? It is, yeah. I Again, you know, the evidence that that's actually useful in the context of energy drinks, it's probably one of the less harmful ingredients in energy drinks. Okay. Next question. "What is your take on astaxanthin? Every study points positive results." Well, so first of all, I think it it it is certainly not true that every study posts positive results. I would say most of the evidence for astaxanthin right now is is preclinical. Um the human clinical data that we've got come from short clinical trials, usually focused on surrogate biomarkers like oxidative stress or inflammation or lipids rather than, you know, like does this have real strong health outcomes. And when, you know, multiple small clinical trials are run on surrogate endpoints, you tend to get papers that report the results as positive, right? And I'm not saying that's a bad thing, but that's just the reality. So, you can get these situations where you where you have what feels like a whole bunch of studies showing positive effects when the actual data, when you look at it as a whole, is sort of moderately convincing, right? So, that's kind of where I put the astaxanthin evidence at this point. Um it's intriguing, definitely has biological activities. Will it translate through to meaningful results in the average person in the real world? I don't know. Coin flip, maybe, right? We just don't know. So, for me, that's kind of where I would say it's a second-tier supplement. It doesn't get to that level where I feel like the evidence is is strong enough for me to start taking it, but it's an interesting molecule. It's probably towards the the top end of my second-tier supplement list, I guess. I don't know if you've come across astaxanthin a lot in the clients that you see or or in clinic. Yeah, and it's a it's a handful. But one of the things I did want to double-click on that you mentioned with supplements is we tend to look at these studies that they're small, they're short, and they have things that are easy to measure, like blood pressure, do we see a change in liver enzymes, whatnot. But we don't have the hard evidence, and I think that's what's really missing when we talk about clinical trials with supplements because there's a lot of medicines out there that early studies showed it decreased blood pressure, it decreases hemoglobin A1C, and then when you look at long-term outcomes, it doesn't actually improve patient outcomes. And so, I think we have to keep that in consideration when we're talking about preclinical studies, then we're talking about early human studies, what does this actually mean for someone long-term cuz it may not mean a lot. >> Yeah, I think you said that really well, and I think that's where my natural skepticism to to not jump on the bandwagon from one or two small human clinical trials comes from cuz most of the time, things that look promising early on when the larger rigorous studies are done don't end up showing any any significant effect. I also think it's worth mentioning that part of the reason why we see so many supplements where you have five, six, seven small human clinical trials is because in the academic world, it's much easier to get funding for and to execute those kinds of clinical trials on natural products and supplements than it is on pharmaceuticals. So, because you don't usually have to go through the regulatory burden of getting approval from FDA to do those clinical trials, right? So, I think there's a structural component where in sometimes the less interesting science is done because it's just easier. So, we get a lot of stuff on supplements, which doesn't really move the needle in terms of confidence, unfortunately, which leaves us with probably, you know, half the stuff that we're going to talk about today, it's like, "Ah, there's some evidence. I don't know if I believe it or not." Well, and the other thing is is even if we're seeing evidence with these individuals, the thing I always think about is what happens when you put them all on top of each other. You know, when someone gets prescribed a medication, we put it through something with a pharmacy or in your EHR that looks for interactions. When people go to the pharmacy and they're picking up their own supplements, there's no there's no even thought to are these cross-reacting? They're all small molecules that all have that same potential. And so, I do worry about that. You see early clinical trials, you see some potential benefit, but we don't know what the actual harm is because they're not doing these trials combined with a bunch of other supplements. So, this episode comes from your episode about creatine, so why omega-3 creatine is a waste of time. So, in general, is it more important for people on a plant-based diet to take creatine? Why should people with kidney issues not take creatine while others should? Yeah, I mean, I think so people it's been shown that that vegetarians and vegans have lower creatine levels, right? So, it's plausible that that supplementing creatine would be more beneficial in those people. I think there have been a few studies. I don't know Nikki, if you want to add anything to that. You probably can comment on the chronic kidney disease components in particular. Yeah, there have been some studies. I honestly haven't gone into the depth of them to see how whether they were quality studies looking at using creatine in vegetarians and vegans, but it did show some outcome some positive outcomes in terms of muscle strength, I believe in lean tissue as well as cognition. And [snorts] so, I think you know, we talk about using creatine in most of our patients and so I think if you were a vegetarian or a vegan, it would be no different. We would still be recommending it. I don't see a reason why we would have to take higher doses of creatine. But, something I you know, cuz when you're talking about how much you take in for diet versus a supplement, the 5 g is already significantly higher. The conversation on creatine and CKD is interesting. So, there's two things at play. One is that creatine the way it's metabolized will increase creatinine and so it makes doctors a little bit nervous when we start seeing creatinine go up. An increase in creatinine does not mean that you have a decrease in kidney function. So, we use creatinine, we use age, we use sex and we put into a calculation and it gives us an eGFR or estimated glomerular filtration rate. And so, just because if something falsely increases the creatinine, it's going to make it look like the kidney function declined and it's going to make the doctor's work a little bit harder to figure that out. There's now kind of an easy fix to that and that you can follow a cystatin C. You're laughing, but there's a couple medical recommendations I can think of that the reason they tell patients to do something is literally because it makes the doctor's job of monitoring more hard. >> Sure. And this I think is one of them because then when we go and actually look at where does the data come from that creatinine is harmful in patients with CKD and there's a couple patients a couple case studies that have come out showing that it has allergic nephritis. So, interstitial allergic nephritis. It's a couple case studies. It's not a lot. And is that enough to say that all patients with CKD shouldn't be using creatine? The other thing that I find really interesting and this is by no means uh medical advice for anyone, but the way that creatine is endogenously made is in the kidneys. And so, chronic kidney disease patients have lower creatine and as they progress through the stages of kidney dysfunction, they have significantly lower muscle mass and significantly lower strength to the point that there actually some studies now where they're taking dialysis patients and they're giving them creatine in dialysis and we've seen improvements in nutrition, lean mass compared to placebo. And so, it may be that kidney disease patients would benefit more from creatine than the general population. But again, not medical advice as all expert consensus is don't take creatine if you have CKD. So, so are those dialysis studies like like randomized anyway? Are these just like one-off case reports? They're small and I believe they are randomized. >> Okay. So, I mean, that should answer the question even if it's a small number of people at least as to whether creatine supplementation is generally harmful in the context of chronic kidney disease. >> Well, it's not because we're looking at end-stage renal disease patients and they're on dialysis. So, the dialysis is doing all the work. >> they've already gotten to the point where where okay, got So, but you know, what we're doing in our practice is if I have a chronic kidney disease patient, I can think of one in particular who's got stage 3B and we tried putting him on creatine. We monitored his his eGFR both with the creatinine and a cystatin C and we didn't see a change. The specific patient that I have in mind went off of the creatinine. I don't know why. But, he was on it for a couple months and we didn't see a change. So, you know, it's definitely not something you should do on your own. Yeah. But, if your physician is comfortable, I don't see a reason that you couldn't try it. And again, I think this is an area that we will have more research, but to me it seems like kidney disease patients would probably benefit from creatine more than others. Yeah, that makes sense. Well, just so people are interested, you're on 2.5 g a day? You're on five? And I'm on 10, so I'm probably My 2.5 is very variable. I think I did five today cuz I drank my whole coffee. So, 2.5 to five depending. Depending on how much of my coffee I drink. And you're doing 10 just because you feel like you're a bigger person and >> you. Yes. >> [laughter] >> I I've been on I literally was on 5 g a day from age 15 until like a year ago and then maybe it's cuz all the I don't know. But, because of yeah, I guess that I weigh more. I'm like, "Well, 5 g is for someone like Nikki's size, shouldn't I be on more?" is my thought process. Yeah, but the reality is most of the 5 g data is done on larger people. So, if anything, Nikki's should back off. I mean, there's so many assumptions built in there that who knows, right? Yeah, I I mean, I think 10 10 five 2.5 I probably we're all going to get to the same steady-state level based on our physiology at least where you sort of maxed out your creatine buffer. >> Makes sense. It just might get there faster if you take a higher dose. >> I see. Well, I don't want to waste money, so I might be makes sense to back off a little bit. >> taking the premium expensive one? >> That's micronized Amazon. Yeah, decent. All right, next question. Still about supplements though. Where did you get that optimal range for vitamin D? My test shows the normal range as lower than that. >> There's a lot of confusion around vitamin D. So, I mean, a couple things to say. The the reference ranges often are lower. Reference ranges do not equal optimum in the vast majority of cases. Those are population-based ranges, right? And then you try to you you you tend to map the reference range against pathology, right? So, that's just one thing to understand. Just because you know, the number that it shows on the report that you get from LabCorp request is a range, it's not necessarily optimal. Vitamin D, I don't think we really know like most things what truly optimal is. So, you have to in the absence of randomized clinical trials, you have to go based on epidemiology and that's kind of where I think the recommendations come from. I I shoot for 60, right? Personally and a range of you know, 50 to 80, which I think maps pretty well to what to what you tell Opt to spend. >> mean, we have our 50 to 80, but honestly, if I have someone in the 40s, I tell them just keep taking what you're taking. So, I should probably just make my range a little bit bigger. Cuz I'm not making I'm not making changes to a vitamin D supplementation if they're 46. Right. So, 40 to 80? That about there? Yeah, and I mean, again, that that brings up the other point, which is a lot of people ask, "Well, how much should I take?" And it's so variable based on your individual physiology and environment and how much sun you get that you kind of have to I think start with the range or the target that you're after and then experiment with the supplementation to get there recognizing that it takes a few months before you're going to see your steady-state level when you change the amount you're taking from supplementation. So, you can't just start taking vitamin D, go in the next day and it's going to show you on your blood test where you're going to end up. And I mean, I've had this experience. I think I've talked about it before where, you know, I started supplementing, I waited a little while to get the blood test, I was still low and then I started really taking a high dose and I ended up, you know, just over 100, which is too high. So, you need to kind of wait a while and back off. So, I assume the advice that Nikki would give is start low and slow and then test routinely to to get to to the range that you're going for. Yeah, and vitamin D is one of those fat-soluble vitamins, so it's not like it comes down quickly either. So, once it's in, you know, it's not like you can really overdo it and then say, "Oh, I'm just going to back off and I'll be down tomorrow like a B12 or something like that. >> Okay. Next question. So, any thoughts on vitamin K2? No. Nikki? Yeah. >> [laughter] >> So, I think that there is a misconception when we see the vitamin D and K2 supplements together, people tend to think that the vitamin K2 helps with absorption. That is not my understanding. My understanding is the vitamin K2 helps in two different ways. One, it helps with actual bone mineral density, so it's a I'm not going to know the actual pathway in this, but it's some sort of a cofactor in a pathway that puts down bone. And so, having the vitamin D and the K2, you can better utilize the vitamin D. And then the other thought is is that the K2 helps prevent vascular calcifications. So, that's the concern with taking high doses of vitamin D is that you can get vascular calcifications and that the K2 will help change where calcium is absorbed and so you wouldn't get the same vascular calcifications. Yeah, I mean, I I think vitamin K2 is one of those supplements where the the biology like the the rationale for higher vitamin K2 is really strong. The epidemiology is pretty suggestive, but again, the clinical trial evidence is limited. This goes back to what we were talking about before, which you know, for a lot of these supplements don't have a ton. But, higher dietary K2, so Nikki mentioned the vascular calcification. So, higher dietary K2 in epidemiology is associated with with lower vascular calcification and lower coronary heart disease or at least death from coronary heart disease. So, can you get those same benefits from supplementing? I think we can make this ask that question about vitamin D and omega-3 and all you know, a bunch of stuff, but it's reasonable um that that you might be able to. Do you think in general the fat soluble vitamins, so A, D, E, and K, people should be more careful about not taking too much of them versus >> 100% >> where the water soluble ones you'll just pee it out. Is that kind of the idea? >> Yeah, I mean one of the big ones to think about is vitamin A. You take a lot of vitamin A and you can get hepatotoxicity. Um so you can land yourself in the hospital with sky-high liver enzymes. So, definitely need to be more more uh careful with those vitamins. I think the flip side of that though is that you can trust the measurements more, right? In other words, understanding that that you're not going to see the super rapid changes up and down in blood work that that you're going to get more of a steady state measurement with these things. Um you can trust those measurements more, whereas some of the other water soluble vitamins, you know, what you see on a blood measurement is going to be determined by whether you took your supplement the day before. Measurements outside the reference range may not actually represent true steady state deficiencies in those. So, it's a you know, there's two components to that. Yeah, that makes sense. What's wrong with sulforaphane? Surely he means taking a supplement versus just eating the broccoli sprouts, etc., right? I don't honestly remember the context here, but let me start telling you what's wrong with sulforaphane. The sulforaphane is super interesting. So, um first of all, like eating broccoli and broccoli sprouts is a good thing independent of sulforaphane. Like you should eat your broccoli. Um Uh I think kind of where I land on sulforaphane as a supplement is that it's mostly influencer mostly influencer hype at this point. And I think I you know, unfortunately in the world that we live in, uh a lot of these people who make their living on YouTube and that's all they do have to keep presenting people with shiny objects. Like to to to to capture interest. And so one of the consequences of that is that they often talk about these things as though the evidence is is really way ahead of where it's actually at and start making strong recommendations for everybody. And I kind of feel like sulforaphane falls into that category where the hype has gotten a little bit ahead of the real science. Um there is good data there, but it's just not a lot of it. So, so here's I think where I would land on sulforaphane. Um well, first of all, sulforaphane itself is not present in broccoli. So, this is actually important when you start talking about supplement. So, there's a precursor of sulforaphane, um which is a different molecule called glucoraphanin. That's what's found in broccoli and cruciferous vegetables, and there's an enzyme for called myrosinase that is necessary to convert glucoraphanin into sulforaphane, okay? So, this will become important when we talk about the supplement. So, like when you chew broccoli, it damages the vegetables. That releases the enzyme. That actually converts the glucoraphanin into sulforaphane, and that allows it to be taken up by the gut. So, the reason why that's thought to be beneficial is that sulforaphane is an activator of an enzyme called NRF2. And NRF2's been studied a lot in biomedical research uh even in longevity um because it activates uh antioxidant capacity, detoxification capacity pathways. And so the idea that if you get enough sulforaphane into the system to activate NRF2, you're going to have better antioxidant and better detoxification. That's pretty plausible. There's good biology to back it up. There's good human cell data that if you treat human cells with sulforaphane, you activate NRF2. There's good animal data that if you do that, you can activate NRF2 and some benefits accrue from doing that, including potentially benefits in the context of aging. Not a ton of evidence in people, okay? And I think again, that's where we kind of, you know, often hit the barrier with a lot of these supplements. Um so there have been some human clinical trials with things like I don't know, broccoli sprout extract, right? Showing that if you give that to people, you can detect biomarkers of higher NRF2 activity, and maybe that translates through to some benefits. That's kind of I think where we're at with with sulforaphane. When it comes to supplements though, most of the sulforaphane that the supplements that are branded as sulforaphane don't actually have much active ingredient. It's not particularly stable. This goes back to why I took you through that whole, you know, glucoraphanin to sulforaphane exercise. So, I think just taking a sulforaphane supplement doesn't make any sense. Uh glucoraphanin alone, there are supplements that are sold that way, also doesn't really lead to much sulforaphane uptake because you don't have the myrosinase enzyme. So, there are supplements that combine them. Um I can't remember the name. Uh Avmacol is one of them, right? Where it's so it's a a gluco uh glucoraphanin myrosinase combination. Um So, I guess if you're going to take a supplement, doing that makes the most sense. Uh you know, will it activate NRF2 in your body? Will that eventually be a good thing? I don't know. And this gets back to I think different people have different philosophies on how much evidence do you want to see before you decide you're going to put this into your supplement stack, right? So, for me, I kind of would put something like Avmacol somewhere in tier two supplement. I'm not ready to to to to, you know, start taking it. Um the again, the biological rationale is plausible, but there's not a ton of good data that it actually leads to benefits in people at this point. Well, you suggest just eat broccoli. Just eat Yeah, definitely eat the broccoli and you know, you'll get some sulforaphane. You'll get a bunch of other good stuff. Um so yeah, I mean again, if you'd asked me 20 years ago about broccoli, I'd be like, I'mma pass. But uh I've learned to love broccoli. So, yeah, broccoli's broccoli's good. Yeah, the influencers that I have seen have suggested for the reaction they're talking about chopping up the broccoli into small pieces, leaving it for 30 minutes to get the most sulfur. I just to me that just doesn't seem like a logical way to practice life. Like I don't have 30 minutes to wait from when I chopped the broccoli. >> Yes. So, certain longevity influencers talk about like the vegetables have hormesis chemicals like resveratrol is a popular one. Is this type of same category? That's a nice idea and whether there's any real biological truth to that. So, it is it is the case that that lots of plants create uh or have molecules that are defense mechanisms, right? That can that can um be used to actually cause toxic outcomes in other insects that will eat them, right? That's where this hormesis idea comes from. Some of these chemicals that are true truly toxic, at least to insects, at low doses might actually have benefits, right? It's a wonderful idea that people really like. Not a ton of evidence that that's actually the mechanism for putative health benefits in people from eating those. Okay. I got caffeine's a great example, right? A caffeine could kill a bug if they eat a coffee bean. >> Almost anything can kill you though if you eat too much of it, right? So again, it's really easy to make these kind of cool arguments without needing a lot of like critical thought behind it. Yeah, makes sense. All right. Hey Matt, you mentioned that you supplement with fish oil, but you also eat a lot of fish. What's the thinking behind this? Thanks in advance. Great content. Love the show. Well, thank you. I appreciate that. >> [laughter] >> Uh I mean, it really comes down to the epidemiology around omega index, which is DHA plus plus EPA in red blood cells. So, pretty good actually very good epidemiological evidence that having a higher omega index is associated with lower all-cause mortality and a bunch of other good health outcomes. So, personally I and I think these are the general recommendations. Nikki, you can tell me if I'm wrong. I think, you know, an omega index above eight is kind of where the standards have been set. In in my reading, the epidemiology actually suggests even higher than that, maybe even 12 uh is a good target. So, that's what I base it on. If I I I measure my omega index and if it's less than eight, I'm going to supplement with fish oil to get up there. Okay, great. >> Yeah, and it's also really tough to get an omega index of eight through diet alone. I don't think I've ever seen that. >> in Korea, I think the there's there's that's where some of the epidemiology comes from where people are eating a lot of seafood. You can find those levels in the population, but yeah, I think in the in the US, probably pretty rare. What's the highest you've seen? In the clinic? Have you seen like a 12? I don't think I've seen 12. >> Interesting. Even with supplementation. >> Even with I mean, even with supplementation, the vast majority of people don't have eight with just taking one fish oil pill. Do you guys know what yours is about? Um oh, that's a good question. I don't remember my last measurement, but it was probably around eight or I would remember if it was lower than that. >> My last measurement, I was not taking a fish oil and it was not near eight. Uh and I'm now since on a fish oil. >> Okay, so you got to retest it. >> We should we should we should come back and and show what what my measurement was cuz I yeah, I don't remember for sure. Okay, so this is from the episode with Brad Stanfield. This person asked, "What is Matt specifically referring to about the uh misrepresentations of research on sirtuins and resveratrol and Mark Hyman?" So, this I mean, first thing I should say is I think a lot of what Mark Hyman says or on diet and exercise is good advice, okay? So, uh and um specifically, I heard him give a talk at a at a conference where he was talking started talking about longevity, which is not his area of expertise, and he was talking about kind of stuff that has been well debunked in the field, the science, as if it was true. And including comments around how resveratrol is a potent activator of sirtuins, not true, uh and that sirtuins are sort of master regulators of longevity, not true. That's been debunked. Um so that's what I was referring to there. I will say, I mean, again, maybe I shouldn't say this, but oh well. Um I have become pretty disillusioned with with Mark Hyman in general lately, um and in particular how he advertises for supplements that he's making money off of without not actually making it clear that he's advertising, right? So, I think that's that's not unique to Mark. I think there are lots of people in the field who do that, but I think it's problematic. And there was a pretty good article in the blog Aging with Strength by Paul von Ziehlbauer on this. Uh, the title of that article was something like is your longevity doctor scamming you? I didn't say that, Paul said that. But I thought it was pretty good and it really laid out the case in this in this particular instance of a blog post by Mark about a supplement called fatty 15, which really again has very little evidence in people. I mean, really little evidence in people for benefits that this is something everybody should be taking. And he's selling it on his site and getting a cut of the profits. It's very common in influencer world, but it's a conflict of interest and it's problematic. Um, so personally I I that that for me is a red flag when I see people do that and it's one of the things I look at when I say, "Okay, I can't trust that person anymore." Fatty 13, that's the one related to dolphins somehow? >> Yeah. Yeah. But it can be found in, um, just cheese and whole full-fat dairy. So, I mean, if you really wanted to get it, then you could just eat cheese or dairy. Yeah, I understand. And I'm I'm not saying there's I'm not saying one way or the other about fatty 15. Like, could it potentially have value? Yeah, it could. I'm just saying the actual evidence for it is way low compared to a lot of the stuff we talk about. But I wonder though, when you think about it, cuz there is some evidence for full-fat dairy and long-term brain health. And I wonder if if fatty 15 or if that that's involved at all or not. >> Certainly possible. That's why we do it experiments to find out. Yeah, it's a reasonable hypothesis. We should go test it before we start telling people that they ought to take this cuz they're going to, you know, preserve their brain and not get dementia, right? That's the kind of, you know, getting ahead of the data, yeah. Okay, so we got a couple questions on lithium to wrap this up. So, the next one is, "Hey Matt, great content. Question for you. Since you take an SGLT2 inhibitor, which in addition to increasing sodium and glucose excretion also massively increases urinary excretion of lithium, how do you manage your lithium dose? Uh, would you just be pissing away lithium benefit?" >> This is a really good question and I have to say, first of all, thank you whoever posted that question cuz I hadn't thought of that. But it's actually it spot-on. So, yes, taking an SGLT2 inhibitor will cause the kidneys to take up less glucose, so you'll see glucose in the urine. It will also cause the kidneys to take up other molecules less efficiently, including lithium. So, there's actually pretty good evidence that that people taking an SGLT2 inhibitor who are taking, uh, doses of lithium that are higher, right? So, for for psychological, psychiatric, uh, conditions have about 20 to 40% loss of lithium. So, yeah, it's absolutely possible, plausible, probably likely that I'm achieving less bioavailable lithium from being on the SGLT2 inhibitor and I had not considered that. So, I am going to up my dose from 5 mg. I said milligrams. Uh, to 10 mg based on this. Again, I I don't I don't know if there's any data showing that at those doses of lithium that you do lose some, but it makes perfect sense. I mean, pretty cool. Logically in how how SGLT2 inhibitors work, there should be no difference. The same percentage should be excreted regardless of whether you take a high or a low dose. Do you do lithium? I do not. >> not. Okay. Yeah, I was telling them before the show I take it, but I just because you do. So, um, Yeah, I still think at the end we should go through your supplements. You should tell us why you're taking each one. >> We should also have the audience comment on whether or not they've noticed a change in my mood stabilization since I started. There we go. Yeah, we're going to actually up you to, >> [laughter] >> uh, 500. All right. Uh, then actually you kind of covered this one. So, this person said, "I'm assuming he meant 10 mg of lithium, not 10 g." >> Yes, I apologize if I said that I take 10 g of lithium. I do not take 10 g of lithium. I I was taking 5 mg and as we just touched on, I'm increasing that to 10 mg. 10 mg of lithium orotate. And 10 g would be you were saying like a bipolar level dose, potentially? Yeah. That'd be over even a bipolar >> pretty too very high. But it But I think the the bipolar dose is about a hundred to to a few hundred times higher than what we're talking about, yeah. So, ballpark. Perfect. Okay, next question. I keep reading about orotate orotic acid being a liver carcinogen. Is a dose of 5 mg lith ort something to be concerned about? No. Um, so and I mean, it's a good it's a reasonable question. This is one of those things we often see where people do animal studies in mice at at super physiological doses that are way above what people are getting exposed to in diet or or supplements. So, first of all, um, lithium orotate and orotic acid are the conjugate base and acid. So, same molecule just with or without a a proton, okay? So, they're natural metabolites, um, involved in in, uh, mitochondrial metabolism. So, what was done was studies in mice and rats. These are probably 70s or 80s where they gave them like 50 g a day or something super high, right? Or at least the mouse equivalent of human 50 g a day, 1% in the diet. And saw that those mice develop fatty liver. I don't know if the mechanisms were ever figured out, but it probably has to do with with somehow changing mitochondrial metabolism and Krebs cycle. Um, so you induce fatty liver in the mice and that leads to downstream consequences in including liver cancer. Again, super high doses, you know, we just talked about. So, 50 g compared to 5 mg, right? Where I don't think there's any reason to believe or any evidence that 5 mg a day of lithium orotate is going to do anything consequential to the liver. I don't know if you've ever heard of anything related to liver function, but Not at low doses. >> Yeah. I guess the one thing I would add is if you're taking the approach that that that we philosophically align on here, you're also going to be monitoring your blood work and you would see if there's a change in liver enzymes, yeah. Perfect. Okay, next question. Is there anything over the counter that folks can take for health span slash longevity? >> There's lots of stuff you can take. I think fundamentally it comes down to what is the stuff you should take, right? And there's no right or wrong answer. So, again, I mean, I've said this before, it's all probabilistic. We can make probabilistic arguments about what the likelihood is that a certain, uh, over the counter intervention is going to be beneficial across the population and for the individual depending on the data that we've got, right? So, we can talk about and we have talked about what we each do, but I don't think we can say with confidence everybody should take X for longevity. You need to know their blood work where they're starting at. Okay. Yeah, I mean, when we talk about that over the counter, there's a lot of supplements that we can measure. We can see if you're low and we can get you up, but I don't I don't think that's what this question is saying. >> a lot of those today, right? Vitamin D and omega-3 and things like that. I'm I might be think looking too much into it, but I almost assume this question this person's looking for like an over the counter rapamycin, an over the counter like something that is, uh, So, again, whether that's going to be beneficial for longevity is a part of it. Not a lot that we can say with 100% certainty is. And then and then, uh, you know, is there something that could mimic rapamycin? So, that's an interesting twist on this question. Not really for rapamycin. There's lots of things that are talked about as mTOR inhibitors, but nothing that's going to be anywhere as potent as rapamycin. The case that comes into my head is berberine and metformin though. So, I very much believe that berberine is just an unregulated form of metformin and you can get pretty much exactly the same activity from the doses of metformin people are taking, or I'm sorry, berberine that people are taking as a supplement. And actually, I need to do an episode on this. There's pretty interesting data that those doses of of berberine might actually be more effective at at inhibiting the electron transport chain than than pharmaceutical doses of metformin. So, that's an example where there is actually a natural product that's that matches a a pharmaceutical. Yeah, I remember you and you and I were talking to someone who was super anti-metformin and then we found out they were taking berberine and he didn't have a logical reason why and it was kind of like an awkward like, "Oh, okay." Yeah. >> We see that a lot with patients who are anti-statin, but then take red yeast rice. Yeah. Wait. Which has statin [laughter] in it. Yep. Yeah. Again, I not to make fun of people. I mean, I totally get the idea that natural is better than pharmaceutical and lots of people distrust the pharmaceutical industry for good reason, but when it comes down to the actual molecule, right? I think it's it's helpful to just kind of take a step back and try to be completely rational about it. But, um, I wish I could tell you guys what what you should take for longevity. Look, if if I knew, I'd take it. So, but we can talk about what we take, right? I think that and and we have. So, um, I don't know, Nick, what do you take for longevity? Yeah. Put you on the spot. I'd have to look at my list. But Is that big? You don't even remember your list? Yeah, I mean, I do D3, I do omega, I do, um, lithium orotate. >> Solid. I do the folate cuz I've got that that one gene for it. And I assume you measured at some point. >> methylfolate? >> Yeah, methylfolate, astaxanthin, creatine, TMG for the same reason as as I take the folate. Actually, Thomas DeLauer is the one that got me doing that. So, so far I line up completely except for the astaxanthin and the TMG. Yeah, I mean, But for someone with an MTHFR mutation, the TMG might not be a bad idea to decrease homocysteine, as long as you don't have CKD. I do. Also, mix my I do finasteride, 5 mg of, of, what is that? You it's Cialis? What's sildenafil? Yeah. I do finasteride. Sildenafil, yeah. I used to do tadalafil. Interesting. I was going to ask about that, but there's a reason you stopped taking it? Mostly I just didn't notice anything and and so I try, you know, everybody knows I try to like keep my stack minimalist. And actually, tadalafil's not a bad idea, but I I didn't I didn't even feel like the good stuff I was hoping for, you know? >> [laughter] >> You're already maxed out, I mean, you maxed >> I know, right? When you're up here, it's hard to see an improvement. No. Uh, so I don't have a good rational. I actually think tadalafil makes a lot of sense. You're You're pretty young, but I think, you know, in terms of like improving circulation and cerebral blood flow and things like that, perfectly reasonable thing for people to do. Yeah. I But I do worry about interactions and so again, I try to balance, you know, what I take with likelihood of of benefit. But tadalafil feels pretty reasonable. But tadalafil is a good one, especially for men as you get older because so many men want something for their prostate anyways, and so you can put it on for the prostate and then get this benefit versus, you know, two different agents. So far I don't have any prostate issues. So again, maybe that would tip me if I did. And then I think I have to do a multi as well. Yeah, I I don't typically do a multi vitamin. You eat vegetables. I eat a lot of vegetables. >> Was that a slight towards the I made no comment. >> [laughter] >> Yeah, but I might be missing one or two, but that's that's the bulk of it. Okay. Yeah. All right, that's pretty solid. I mean, that's not not bad. All right, you're Uh magnesium. We should do a whole episode on magnesium, but we'll we'll table that for now. Yeah. Uh omega-3s, vitamin D, and then I take a hair vitamin because I would want luxurious hair. I've been on it for years. It doesn't do anything. [clears throat] >> What is What is it? Biotin or hyaluronic acid? I switch, so it used to be like an over-the-counter hair, skin, and nails. I recently got um decided to try Nutrafol cuz I've heard good things about it. I've also heard it's a scam from dermatologist, but the dose is really high, so I only take So I only take two tabs instead of four. I don't know. Awesome. Okay. Well, so so that's there you go. That's Nikki's uh longevity hack. Uh Nutrafol. Nutrafol, yeah, there we go. Awesome. This has been fun. We're going to do more of these. I think we'd mentioned magnesium. We really need to do a deep dive on that. But uh we'll come back and do that next time, maybe. All right. 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