Scrutinizing supplements: creatine, fish oil, vitamin D, and more (AMA 69 Sneak Peek)

1. 0:00 – 1:36

   Intro

   1. PAPeter Attia0:00

      "I don't believe in taking any medicine, just so you know, um, only natural supplements." My response to that is, "Tell me the difference." I mean, there is a difference, but I just wanna make sure you as the consumer of this understand the difference.

   2. SPSpeaker0:14

      So today we're hitting a topic which is one we get asked about a lot, which is supplements. We tried to pick ones that we get asked about a lot for the case studies, which is creatine-

   3. PAPeter Attia0:24

      There's reasonable evidence to suggest, and again, we'll, we'll link to lots of it, that, that creatine does help improve various parameters of muscle performance, and it's not that subtle. I mean, it's typically in the range of 5, 10, maybe even 15%.

   4. SPSpeaker0:38

      Fish oil.

   5. PAPeter Attia0:38

      Yeah. I mean, obviously you have to watch out for poor quality rancid supplements. They're, they are unfortunately common. The smaller the fish, the better.

   6. SPSpeaker0:47

      Vitamin D.

   7. PAPeter Attia0:48

      In other words, it's not easy for me to say, "Nick, if you go outside today with your shirt off for 20 minutes, it's the equivalent of taking this much vitamin D."

   8. SPSpeaker0:58

      B vitamins.

   9. PAPeter Attia0:59

      These are typically more associated with B12 injections rather than oral supplements. We tend to just rely on oral, uh, supplementation. You get a more smoothed out dose.

   10. SPSpeaker1:09

       Ashwagandha.

   11. PAPeter Attia1:10

       So it's, it's like an evergreen shrub that has historically been used in traditional Indian medicine for a variety of indications, uh, such as sleep, stress, immune health. But I, I hope that people can use this framework liberally as they try to kind of adjudicate and interrogate their own supplement list. [upbeat music] Hey, everyone. Welcome to the Drive Podcast. I'm your host, Peter Attia.

2. 1:36 – 3:12

   Overview of episode topics

   1. SPSpeaker1:39

      Peter, welcome to another AMA. How you doing?

   2. PAPeter Attia1:42

      Great. How are you?

   3. SPSpeaker1:44

      I'm doing good. I'm doing good. [laughs] Thanks for, thanks for joining us. You had some enthusiasm in that. Great. I could feel it.

   4. PAPeter Attia1:51

      [laughs]

   5. SPSpeaker1:53

      Um, so today we're hitting a topic which is one we get asked about a lot, which is supplements. And this can vary greatly depending on the person, depending on the supplements. And the hard part with supplements is that while everyone is interested in it, it's so variable person to person, and not even all your patients are taking the same supplements or the same amount and all of that. And so it's really hard to talk about it in a way that makes it applicable to everyone without being like, "Take this, don't take this," which is something that you've never really done because of how you look at this topic. And so what we decided to do today was instead look at a framework for how you think about supplements, and then go through case studies of a variety of supplements to talk through it to hopefully allow the person listening or watching to then be able to apply it in their own life so they can just get a better understanding, be smarter when it comes to this topic. And so we tried to pick ones that we get asked about a lot for the case studies, which is creatine, fish oil, vitamin D, B vitamins, ashwagandha. So kind of a variety of supplements as well that we'll go through, which will hopefully kinda give a full picture of how to apply this in someone's own life. So with all that said, anything you want to add before we get rolling?

   6. PAPeter Attia3:10

      Nope. Let's get started.

3. 3:12 – 7:12

   How Peter evaluates patients’ supplement regimens, and common misconceptions about supplements vs. pharmaceuticals

   1. SPSpeaker3:12

      So when patients come to you, like when they first start in the practice, how are you looking at their supplements? I'm sure there's a variety of some people have a lot of supplements, some not as much. So are you taking audit of that? How are you having that conversation with them when you first meet someone?

   2. PAPeter Attia3:31

      You know, obviously any patient that's coming into the practice, we're trying to gather as much information about them as we can through, you know, uh, their medical history. And a important component of that is understanding all medications, supplements, hormones, anything they take, right? You know, I call this the bucket of exogenous molecules. Um, so, you know, generally we know this on the way in, and there's a ton of variety, right? There's people who come in who are taking nothing. They don't take any medicine by prescription. They don't take any supplements. Conversely, there are patients who come in on no medications, but a list of supplements that, uh, you know, might be two pages long, uh, and everything in between. Um, our view is generally to approach this kind of the way the kidney approaches the filtration of glucose, sodium, and potassium, which is you dump everything out and then ask the question, what should be added back in? Um, and I don't mean we literally stop everything, but I'm saying that's kind of the mental model for how we, how we go about thinking about it. Um, uh, because a lot of times when we ask patients, "Why are you taking this?" or, "Why are you taking that?" They don't know. They just say, "Oh, you know, I started this a couple of years ago because I saw somebody on Instagram talking about it," or, you know, "I saw this doctor a few years ago who told me to take this, but I have no idea why." So, um, I think, you know, there's just a couple of things worth acknowledging before we jump into this, and, um, it, it, it comes from discussions that I've had many times, which go something like this. Um, "Hey, you know, I don't believe in taking any medicine, just so you know. Um, only natural supplements." Um, now my response to that is, "Tell me the difference." I mean, uh, there is a difference, but I just wanna make sure you as the consumer of this understand the difference. Um, and it, it, it, it's really a question of regulation, right? So supplements are not regulated. Uh, by definition, the FDA has sort of tacitly referred to them as, you know, generally regarded as safe. Um, but the process by which that's determined is, is not entirely that rigorous. Um, and pharmaceutical products, while far from perfect, do have more in the way of regulation and oversight. Um, there are places where these overlap. Again, I'll encounter a patient who says, "Listen, I will never take, you know, a statin to lower my, um, ApoB, but, you know, I will definitely happily take red rice yeast." At which point you have to sort of explain to them that a very high dose of red yeast rice is effectively, uh, a modest dose of pravastatin. So, um, I, I think it's just helpful for patients not to get ideologically wrapped up in the idea of over-the-counter supplement versus pharmaceutical agent, um, and instead to just analyze the, any molecule you put in your body through the framework we're gonna talk about today. Today, we're going to limit it to over-the-counter supplements because these are the things we get asked the most questions about, and frankly, it's the area in which it's harder to do the type of analysis we're doing today. So the type of analysis we're doing today is so much easier to do in the pharma space because of the regulatory hurdles that must be cleared by a drug to be approved. So it's almost like shooting fish in a barrel. Still a great exercise to do, uh, but, but doing it the way we're gonna do it today is, is really how you develop the muscle for doing this type of work.

   3. SPSpeaker7:11

      And so I think

4. 7:12 – 11:17

   A framework for evaluating supplements

   1. SPSpeaker7:12

      with that said, do you just want to run over real quick kind of the questions you ask to determine whether or not a supplement is worthwhile? And I think kind of just giving this overview will be helpful because as we said in the beginning, when we go through the case studies, we'll kind of stick to these questions and answer them along the way. And so to kick it off, do you just want to run through what those questions are?

   2. PAPeter Attia7:34

      I think this is the single most important thing I'm hopefully transmitting throughout this episode. I mean, the heavy lifting is actually showing you how we go through this, but, but this is, this is the punchline, right? So anytime you're considering taking a supplement or someone is suggesting a supplement, you, you should ask, you know, the following questions or, or, or something that approximates them. So the first question I'm asking is, are you taking this to correct a deficiency, or are you trying to achieve supranormal levels of fill in the blank? Okay. Second question, are you taking this molecule because, uh, you believe that it's going to improve your lifespan or your healthspan, or potentially both? Third question is, if it is lifespan, is it because this marg- this, uh, this, this molecule is targeting a specific disease and presumably reducing your risk of that disease, or do we believe it's more broadly geroprotective? Again, in the supplement landscape, that's pretty rare to find, but obviously you can see examples in the pharma space where we might see certain drugs that we think have geroprotective benefits versus those that have lifespan benefits, but only on one, uh, disease. The, of course, the other question that is the corollary of that is, if you're taking it for healthspan, can you speak to which apparatus of healthspan? Do you think this is something that is improving physical performance, cognitive performance, or emotional health? The fourth question is, is there a biomarker that you can track to suggest that you are getting the appropriate amount of the supplement or that you might be in the therapeutic window? The fifth question is, do you understand the mechanism of action? Now again, I want to be clear. You don't have to answer every one of these questions in the affirmative for it to make sense. Uh, for example, there are countless things that we use for which we might not fully understand the mechanism of action, uh, but we might feel confident enough on some of these other dimensions to move forward. Uh, the final question is, what is the balance of risk to reward, including potential side effects, the magnitude of the effect, um, the confidence we have in the data that speak to its safety, and the quality of the supplement itself? And this last point is especially important here. Um, we know from previous podcasts that I've done, including the one with Catherine Eban, that even in the pharma world, the quality of the drug is not to be taken as a given. Um, that, that episode, uh, which is several years old and we'll link to it, um, really called into question the quality of some of the pharmacologic agents out there, especially generic brands. Um, but whatever, um, amount of nefarious behavior exists over there, I think you're safe multiplying that by 10 or 100 to the, uh, to understand the magnitude by which that's happening in the supplement space. Um, so I guess before we jump into this, Nick, I just want to make sure we, you know, we've, we've pulled together a lot of information on the six supplements you mentioned. For the sake of time, flow, making this sort of conversational, um, I'm not gonna go deep into each study that we talk about. Rather, I'm gonna try to cover the important details, um, but we will heavily cite, link to, and explain the details of the studies in the show notes. So, um, if you're listening to this because you just want to see how the framework works, great. But if you're like, "Actually, for those six supplements, I want to go deeper," the show notes is where to go.

   3. SPSpeaker11:15

      Perfect. So I think let's

5. 11:17 – 14:19

   Evaluating creatine: purpose of supplementation, dosing, and mechanism of action

   1. SPSpeaker11:17

      get started with the first one, creatine. And so kind of going through the questions in the framework, are you using creatine to correct for deficiency or trying to achieve super maximal levels?

   2. PAPeter Attia11:32

      With creatine, it's clearly the latter. Um, you know, I'm, I'm sure there's somebody walking around out there with a creatine deficiency, but that's not really the use case. So when people like myself, and I do take creatine, um, take creatine, it's because we believe that supraphysiologic levels are, uh, preferential. Um, so again, we take this primarily to improve, um, athletic performance, uh, potentially increasing lean mass slightly. There are some emerging, um, studies that suggest that it may also ameliorate cognitive decline. Um, and, and basically research shows that once muscle stores are fully maximized, um you know, which can be achieved with three to five grams per day, um, you're, you're, you're sort of y- you've, you've, you've flattened out that curve. So, um, you don't-- in other words, you don't need to go much beyond that. Although, as we've talked about on this podcast, there was a day, for those of us that are old enough to remember, when the zeitgeist was to do a period of loading at much, much higher doses in the neighborhood of twenty grams per day before, um, uh, falling to a, a maintenance dose of five. But today, people that are taking it are usually just taking three to five grams per day.

   3. SPSpeaker12:52

      And then as far as taking it for lifespan, healthspan, which one are people usually taking it for?

   4. PAPeter Attia12:59

      Well, we certainly see, um, no direct evidence on lifespan. I, I think most, most people who would take this, if being confronted with the, the granularity of this question in this way, would say, "Look, I'm taking this for healthspan. I'm maximizing the benefits of my exercise, especially with respect to resistance training, um, and maybe potentially, uh, warding off cognitive impairment." Now, of course, indirectly, I would say that those are also benefits on lifespan. Uh, but I would say that that's probably the way to think about this.

   5. SPSpeaker13:31

      And you kinda talked about this earlier on, but is there a specific biomarker that people can use to track to see if the supplement's, quote-unquote, "working or not?"

   6. PAPeter Attia13:41

      No, there's not a biomarker for this. And again, what do I mean by a biomarker? Well, uh, you know, if you're taking a, a medication to lower your blood pressure, um, measuring your blood pressure actually becomes a biomarker for the thing you're taking. Is-- am I taking enough or too much? Um, if you're taking a drug that lowers your ApoB, the ApoB itself serves as the biomarker. Um, we don't have a way outside of a lab, uh, commercially to measure tissue creatine, uh, levels, so we do not have a biomarker for this, and that's why people who take it are just sort of adhering to a protocol.

   7. SPSpeaker14:18

      And

6. 14:19 – 21:42

   Creatine: proven benefits for muscle performance, potential cognitive benefits, and why women may benefit more

   1. SPSpeaker14:19

      then on the mechanism of action, do we have any understanding of the mechanism of action for creatine, whether it relates to the physical or the cognitive side?

   2. PAPeter Attia14:31

      On the physical side, meaning on the muscle performance side, it's, it's, it's certainly pretty clear. Um, you know, again, people will recall th- how energy, uh, currency is delivered. So ATP, adenosine triphosphate, uh, is the, is the richest form of, of energy currency, and it liberates energy, so it, it's spent by liberating, uh, a phosphate. So ATP becomes adenosine diphosphate, A, uh, ADP. Um, of course, that process works in reverse. So as we want to build up and replenish our ATP stores, we need a phosphate donor, and this is where, uh, phosphocreatine comes in. So we do naturally have phosphocreatine. In fact, when you start to think about the various energy systems, if I asked you, Nick, to do something that was an all-out effort for ten seconds, that would not require oxygen, right? You're not tapping into your VO2 max or your oxygen delivery system. It's frankly not even an anaerobic activity, meaning you're not actually turning glucose into pyruvate, into lactate, et cetera. If you're doing something that is such a short burst of activity, you are really relying on the phosphocreatine system to generate the ATP for that activity. So if you're doing a forty-yard dash, you're relying on phosphocreatine. Uh, but of course, phosphocreatine itself is a phosphate donor, and therefore, anything that boosts the supply of phosphocreatine boosts the supply of ATP. And it's our belief that that's effectively what it is doing, um, and therefore that it's helpful, um, with, you know, anything that requires bursts of activity, but even beyond just the super short, extending into the anaerobic. I don't know that there are really any proven benefits that this augments aerobic performance. So once you get into the purely, um, oxidative phosphorylation pathway, I d- I, I-- I mean, maybe someone will correct us, but I, I'm not really aware that there are benefits of creatine in that regard. I think it's more in the first two energy systems, the phosphocreatine system and the anaerobic system. On the cognitive side, we know that a small amount of creatine is synthesized in the brain, and that creatine can cross the blood-brain barrier. But, um, the brain certainly does not take up creatine to the same extent as the muscles do. Um, so w- while we have, again, some evidence to suggest that, that creatine is, is, is efficacious for cognitive, uh, function, it, it might turn out to be the case that you need higher doses of it. Um, I think that's still, um, an open question as far as I'm concerned.

   3. SPSpeaker17:10

      You mentioned earlier that we'll put a lot of more detailed information on the data in the show notes, but kind of looking at a high level, what does the data around creatine say about efficacy of it?

   4. PAPeter Attia17:22

      There's actually-- This is, you know, a supplement that has been quite readily studied and, and there's, uh, there's, there's, there's reasonable evidence to suggest, and again, we'll, we'll link to lots of it, that, that creatine does help improve various parameters of muscle performance. And it's not that subtle. I mean, it's typically in the range of five, ten, maybe even fifteen percent. So these includes things like power and hypertrophy. Again, the power shouldn't be that surprising when you understand the mechanism of action. The hypertrophy seems to be, uh, due to the, you know, it-- n- not just the, um, uh, the increase in the myofibril thickness, but also in the retention of water within the, within the muscle, and of course, that's still considered lean mass. Um, as I alluded to, kind of physical performance in short, intense burst activities, um, and potentially some benefits in slowing down the aging phenotype of, of, of muscle mass. Um, a- again, like I said, it's, it's really probably best suited for high intensity and anaerobic activities. Um- But, um, you know, the one meta-analysis we'll cite too found that creatine did not really improve endurance, um, events in trained athletes. Again, you always could argue, well, maybe it's because they were really well-trained and their mitochondria were well-honed. But I, you know, it's possible that there's a study where you took completely untrained athletes, had them do an aerobic task with and without creatine, and you might indeed see a benefit there. So again, I think we're, we're still kind of in early days on some of this stuff. Um, you know, there was a 2017 review that, um, that got quite a bit of attention that we'll link to that concluded that creatine may help with the prevention and recovery from injury. Um, and there have been a number of, of meta-analyses looking at cognition. The most recent one, which was this year, looked at 16 RCTs and found that creatine had a positive effect on memory. Um, so again, I would say long and short of it is a lot of this stuff looks very promising. Um, there's also some evidence that women in particular might benefit more than even men. Um, women have lower stores because muscle mass, uh, is the predominant store. Women have less muscle, therefore less stores. Uh, but there might also be less consumption through diet. So it, again, at least leads to the hypothesis that women may benefit even disproportionately to men. Um, th- there's some, I think, rather weak data that suggests that, um, it help, it may help reduce dementia... uh, pardon me, it may help reduce depression in women. Um, and there's some evidence to suggest that it may be helpful during periods of, you know, sort of rapid hormonal change. Um, and that could be sort of within the monthly period of, um, a, a menstrual cycle, uh, pregnancy, perimenopause, and menopause. So, um, you know, you might ask, why is that the case? Well, it, the creatine and phosphocreatine pathways are impacted by hormonal changes, and of course, during all of those periods that I just mentioned, you're seeing rapid hormonal changes. So it's not really that surprising, uh, that supplementing to supernormal levels of creatine, um, could offset some of those impacts. Um, you know, pregnancy is a question I get asked about a lot, Nick. Um, I'm not, I would say f- I, I would say I f- remain a little bit, um, unclear and would probably, um, r- you know, suggest that there's probably, it's probably safe during, um, pregnancy, uh, but we just don't have enough human data to, to form a strong point of view. So obviously the, the, the, you know, in my mind, the, the wise thing to do is to avoid anything that is not absolutely necessary during pregnancy. So just to give you an example, like when we have women in our practice that are preparing for pregnancy or, uh, pregnant themselves, I mean, I, no matter what they're taking, if they're taking, you know, medication for, for something that is, that they can live without for nine months, we would, we would absolutely stop it. Um, so yeah, I would say, uh, women should probably dose it at about the same dose as, as men, but of course they'll get kind of more bang for that buck because they're on average smaller.

7. 21:42 – 23:56

   Creatine: risk vs. reward, kidney concerns, and choosing the right supplement

   1. SPSpeaker21:42

      So kind of rounding out everything we talked about with creatine, you know, what is the balance of risk reward to how you see it? Seems like a lot of stuff we talked about was a lot of reward, but kind of how do you think about this to summarize it?

   2. PAPeter Attia21:57

      I would put this in the low risk, modest reward, um, category. We do have, I think, really robust safety data here, and it looks good. Um, if the muscle stores are already full, the liver's probably gonna metabolize the delta. The kidneys will clear the excess. Um, there is, you know, one thing to kind of keep in mind, if you're a person who doesn't have perfect kidney function, you do probably want to talk with your doctor before you take it, and this is very important, you want to make sure that they know you're taking it before they do any blood tests to measure your creatinine, um, because high doses of creatine can impact serum doses of creatinine, which we would, um, we would use as one of the metrics to, to determine kidney function. So in our patients that have anything but perfect kidney function, if they're taking, um, creatine, we typically have them stop, uh, for a couple of weeks before we do a blood test. Um, creatine monohydrate really is the version to take. I don't even know if they sell anything else. They used to sell a creatine phosphate a long time ago. I don't think that there's anybody selling that anymore, and I don't think it matters. Um, but a- again, there's just no evidence that, that you need to be, uh, taking anything other than creatine monohydrate. Um, it's wildly inexpensive, and you should be looking for the purest, uh, product only that has nothing in it. The only ingredient should be creatine monohydrate. No fillers, no extra ingredients, uh, unless there's some flavoring agent that you want. But again, uh, I just mix this in with an electrolyte drink, so I want nothing in other than the creatine monohydrate in the sample.

   3. SPSpeaker23:46

      Perfect. Anything else you want to say on creatine before we move to the next one, which is fish oil?

   4. PAPeter Attia23:52

      Nope.

   5. SPSpeaker23:54

      Perfect. Fish oil, another

8. 23:56 – 27:24

   Evaluating fish oil: its primary purpose as a supplement and how to track levels

   1. SPSpeaker23:57

      supplement that we get asked about a ton. We've done some podcasts on it, lot of questions on it. Seems like a lot of people take it. And so kind of starting through again, going through the questions with fish oil, first one is, are you correcting for deficiency or are you trying to achieve super maximal levels when it comes to fish oil?

   2. PAPeter Attia24:17

      Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a premium member It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. So if you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. Premium membership includes several benefits. First, comprehensive podcast show notes that detail every topic, paper, person, and thing that we discuss in each episode. And the word on the street is nobody's show notes rival ours. Second, monthly Ask Me Anything or AMA episodes. These episodes are comprised of detailed responses to subscriber questions, typically focused on a single topic, and are designed to offer a great deal of clarity and detail on topics of special interest to our members. You'll also get access to the show notes for these episodes, of course. Third, delivery of our premium newsletter, which is put together by our dedicated team of research analysts. This newsletter covers a wide range of topics related to longevity and provides much more detail than our free weekly newsletter. Fourth, access to our private podcast feed that provides you with access to every episode, including AMAs, sans the spiel you're listening to now and in your regular podcast feed. Fifth, The Qualies, an additional member only podcast we put together that serves as a highlight reel featuring the best excerpts from previous episodes of The Drive. This is a great way to catch up on previous episodes without having to go back and listen to each one of them. And finally, other benefits that are added along the way. If you want to learn more and access these member only benefits, you can head over to peterattiamd.com/subscribe. You can also find me on YouTube, Instagram, and Twitter, all with the handle PeterAttiaMD. You can also leave us a review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit peterattiamd.com/about, where I keep an up-to-date and active list of all disclosures. [outro music]

Episode duration: 27:24