The Peter Attia Drive - #340 - AMA #69： Scrutinizing supplements： creatine, fish oil, vitamin D, and more—a framework for understanding effectiveness, quality, and individual need

00:00:00.000 Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.

00:00:16.320 I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access

00:00:20.780 the AMA episodes in full, along with a ton of other membership benefits we've created,

00:00:25.400 or you can learn more now by going to peteratiyahmd.com forward slash subscribe.

00:00:31.100 So without further delay, here's today's sneak peek of the ask me anything episode.

00:00:39.340 Welcome to ask me anything AMA episode number 69. In today's episode, we cover supplements. As this

00:00:47.420 is a very complex topic, we wanted to approach it first by proposing a framework that you can use

00:00:53.440 to evaluate supplements that we can't make blanket recommendations on since everyone has their own

00:00:59.260 individual health circumstances. To me, the framework is very important here because if

00:01:04.260 I were to just dive into this podcast and give you my point of view on a random collection of

00:01:09.360 supplements, it would be akin to giving you a bunch of fish when in reality, what I want to do is make

00:01:14.420 sure you, of course, know how to fish. But not just giving you the framework, we also want to give you

00:01:19.820 a few fish. And so we want to use the framework to cover a handful of studies for some popular

00:01:25.420 supplements. We covered creatine, fish oil, vitamin D, vitamin B, or many of the vitamin Bs,

00:01:32.840 and ashwagandha. We also talk about how to look at supplement quality, and we hope that this episode

00:01:38.320 gives you an ability to take said framework and apply it to any supplement you encounter in the

00:01:44.680 future. If you're a subscriber and you want to watch the full video of this podcast, you can find it on

00:01:48.860 the show notes page. If you're not a subscriber, you can watch the sneak peek on our YouTube page.

00:01:54.200 So without further delay, I hope you'll enjoy AMA 69.

00:02:03.500 Peter, welcome to another AMA. How are you doing?

00:02:06.360 Great. Thank you for having me again.

00:02:07.980 Always, always welcome. I know sometimes it's tough to get you to clear your schedule, but we're always

00:02:12.440 happy you show up. Haven't missed one yet, so that's always a good thing. So today we're hitting a

00:02:17.800 topic, which is one we get asked about a lot, which is supplements. And this can vary greatly

00:02:23.820 depending on the person, depending on the supplements. And the hard part with supplements

00:02:27.240 is that while everyone is interested in it, it's so variable person to person, and not even all your

00:02:34.140 patients are taking the same supplements or the same amount and all of that. And so it's really

00:02:39.360 hard to talk about it in a way that makes it applicable to everyone without being like, take this,

00:02:44.500 don't take this, which is something that you've never really done because of how you look at this

00:02:49.400 topic. What we decided to do today was instead look at a framework for how you think about supplements

00:02:54.920 and then go through case studies of a variety of supplements to talk through it, to hopefully allow

00:03:00.660 the person listening or watching to then be able to apply it in their own life so they can just get a

00:03:06.120 better understanding, be smarter when it comes to this topic. So we tried to pick ones that we get

00:03:11.480 asked about a lot for the case studies, which is creatine, fish oil, vitamin D, B vitamins, and

00:03:17.140 ashwagandha. So the hope is after this, not only will people understand those specific supplements

00:03:22.220 better that we're going to do the case studies on, but also how they can apply this framework to their

00:03:27.600 own life. With all that said, when patients come into the practice, what percent of the supplements

00:03:34.020 are they taking that you recommend they continue to take? Obviously any patient that's coming into the

00:03:38.880 practice, we're trying to gather as much information about them as we can through their medical history.

00:03:43.620 And an important component of that is understanding all medications, supplements, hormones, anything

00:03:48.420 they take. I call this the bucket of exogenous molecules. So generally we know this on the way in

00:03:54.560 and there's a ton of variety. There's people who come in who are taking nothing. They don't take any

00:03:59.080 medicine by prescription. They don't take any supplements. Conversely, there are patients who come in

00:04:03.360 on no medications, but a list of supplements that might be two pages long and everything in

00:04:09.220 between. Our view is generally to approach this the way the kidney approaches the filtration of

00:04:16.860 glucose, sodium, and potassium, which is you dump everything out and then ask the question,

00:04:22.380 what should be added back in? And I don't mean we literally stop everything, but I'm saying that's

00:04:27.060 kind of the mental model for how we go about thinking about it. Because a lot of times when we ask

00:04:32.100 patients, why are you taking this or why are you taking that? They don't know. They just say, oh,

00:04:36.400 you know, I started this a couple of years ago because I saw somebody on Instagram talking about

00:04:41.080 it. Or, you know, I saw this doctor a few years ago who told me to take this, but I have no idea why.

00:04:46.740 So there's just a couple of things worth acknowledging before we jump into this. And it

00:04:51.480 comes from discussions that I've had many times, which goes something like this. Hey, I don't believe

00:04:58.300 in taking any medicine, just so you know, only natural supplements. Now, my response to that is,

00:05:05.640 tell me the difference. There is a difference, but I just want to make sure you as the consumer of

00:05:10.640 this understand the difference. And it's really a question of regulation. So supplements are not

00:05:17.260 regulated. By definition, the FDA has tacitly referred to them as generally regarded as safe.

00:05:25.560 But the process by which that's determined is not entirely that rigorous. And pharmaceutical

00:05:31.640 products, while far from perfect, do have more in the way of regulation and oversight.

00:05:37.720 There are places where these overlap. I'll encounter a patient who says, listen, I will never

00:05:43.300 take a statin to lower my ApoB, but I will definitely happily take red rice yeast, at which point you have

00:05:50.960 to sort of explain to them, that a very high dose of red rice yeast is effectively a modest dose of

00:05:56.940 pravastatin. So I think it's just helpful for patients not to get ideologically wrapped up in the idea of

00:06:03.980 over-the-counter supplement versus pharmaceutical agent, and instead to just analyze any molecule you put in

00:06:11.700 your body through the framework we're going to talk about today. Today, we're going to limit it to over-the-counter

00:06:17.080 supplements because these are the things we get asked the most questions about. And frankly, it's

00:06:21.780 the area in which it's harder to do the type of analysis we're doing today. So the type of analysis

00:06:26.540 we're doing today is so much easier to do in the pharma space because of the regulatory hurdles that

00:06:33.100 must be cleared by a drug to be approved. So it's almost like shooting fish in a barrel. It's still a

00:06:38.420 great exercise to do, but doing it the way we're going to do it today is really how you develop the

00:06:43.340 muscle for doing this type of work. I think with that said, do you just want to run over

00:06:48.240 real quick the questions you asked to determine whether or not a supplement is worthwhile?

00:06:54.000 And I think just giving this overview will be helpful because as we said in the beginning,

00:06:57.700 when we go through the case studies, we'll stick to these questions and answer them

00:07:02.100 along the way. And so to kick it off, do you just want to run through what those questions are?

00:07:07.140 I think this is the single most important thing I'm hopefully transmitting throughout this episode.

00:07:11.120 I mean, the heavy lifting is actually showing you how we go through this, but this is the punchline.

00:07:16.500 Anytime you're considering taking a supplement or someone is suggesting a supplement, you should ask

00:07:21.320 the following questions or something that approximates them. So the first question I'm asking is,

00:07:25.300 are you taking this to correct a deficiency or are you trying to achieve supranormal levels of

00:07:32.860 fill in the blank? Second question, are you taking this molecule because you believe that it's going

00:07:40.260 to improve your lifespan or your health span or potentially both? The third question is,

00:07:46.640 if it is lifespan, is it because this molecule is targeting a specific disease and presumably

00:07:53.820 reducing your risk of that disease? Or do we believe it's more broadly geroprotective?

00:07:58.180 In the supplement landscape, that's pretty rare to find, but obviously you can see examples in the

00:08:03.320 pharma space where we might see certain drugs that we think have geroprotective benefits versus

00:08:08.260 those that have lifespan benefits, but only on one disease. Of course, the other question that is

00:08:14.700 the corollary of that is if you're taking it for health span, can you speak to which apparatus of

00:08:20.920 health span? Do you think this is something that is improving physical performance, cognitive

00:08:24.160 performance, or emotional health? The fourth question is, is there a biomarker that you can track

00:08:29.760 to suggest that you are getting the appropriate amount of the supplement or that you might be

00:08:35.720 in the therapeutic window? The fifth question is, do you understand the mechanism of action?

00:08:42.160 Now, again, I want to be clear. You don't have to answer every one of these questions in the

00:08:46.800 affirmative for it to make sense. For example, there are countless things that we use for which we might

00:08:52.760 not fully understand the mechanism of action, but we might feel confident enough on some of these

00:08:57.280 other dimensions to move forward. The final question is, what is the balance of risk to reward,

00:09:02.560 including potential side effects, the magnitude of the effect, the confidence we have in the data

00:09:10.280 that speak to its safety, and the quality of the supplement itself? And this last point

00:09:15.460 is especially important here. We know from previous podcasts that I've done, including the one with

00:09:21.240 Catherine Eban, that even in the pharma world, the quality of the drug is not to be taken as a given.

00:09:27.880 That episode, which is several years old and we'll link to it, really called into question the quality

00:09:33.560 of some of the pharmacologic agents out there, especially generic brands. But whatever amount

00:09:39.240 of nefarious behavior exists over there, I think you're safe multiplying that by 10 or 100 to

00:09:46.740 understand the magnitude by which that's happening in the supplement space. So I guess before we jump

00:09:51.320 into this, Nick, I just want to make sure we've pulled together a lot of information on the six

00:09:55.180 supplements you mentioned. For the sake of time, flow, making this conversational, I'm not going

00:10:03.040 to go deep into each study that we talk about. Rather, I'm going to try to cover the important

00:10:08.220 details, but we will heavily cite, link to, and explain the details of the studies in the show notes.

00:10:14.980 So if you're listening to this because you just want to see how the framework works, great. But if

00:10:19.440 you're like, actually, for those supplements, I want to go deeper, the show notes is where to go.

00:10:23.360 Perfect. So I think let's get started with the first one, creatine. Going through the questions

00:10:29.740 in the framework, are you using creatine to correct for deficiency or trying to achieve

00:10:36.960 super maximal levels? With creatine, it's clearly the latter. I'm sure there's somebody walking around

00:10:43.200 out there with a creatine deficiency, but that's not really the use case. So when people like myself,

00:10:47.780 and I do take creatine, it's because we believe that supraphysiologic levels are preferential.

00:10:56.160 We take this primarily to improve athletic performance, potentially increasing lean mass

00:11:02.140 slightly. There are some emerging studies that suggest that it may also ameliorate cognitive decline.

00:11:09.260 And basically, research shows that once muscle stores are fully maximized,

00:11:14.340 which can be achieved with three to five grams per day, you've flattened out that curve. In other

00:11:20.980 words, you don't need to go much beyond that. Although, as we've talked about on this podcast,

00:11:25.320 there was a day for those of us that are old enough to remember when the zeitgeist was to do

00:11:31.000 a period of loading at much, much higher doses in the neighborhood of 20 grams per day before

00:11:35.640 falling to a maintenance dose of five. But today, people that are taking it are usually just taking

00:11:40.560 three to five grams per day. As far as taking it for lifespan, healthspan,

00:11:46.520 which one are people usually taking it for? Well, we certainly see no direct evidence on

00:11:51.560 lifespan. I think most people who would take this, if being confronted with the granularity of this

00:11:56.380 question in this way, would say, look, I'm taking this for healthspan. I'm maximizing the benefits of

00:12:00.080 my exercise, especially with respect to resistance training, and maybe potentially warding off

00:12:06.260 cognitive impairment. Now, of course, indirectly, I would say that those are also benefits on

00:12:10.740 lifespan. But I would say that that's probably the way to think about this.

00:12:16.180 And you kind of talked about this earlier on, but is there a specific biomarker that people can use

00:12:22.020 to track to see if the supplement's quote unquote working or not?

00:12:26.400 No, there's not a biomarker for this. And again, what do I mean by a biomarker? Well,

00:12:30.960 if you're taking a medication to lower your blood pressure, measuring your blood pressure

00:12:35.220 actually becomes a biomarker for the thing you're taking. Am I taking enough or too much?

00:12:41.260 If you're taking a drug that lowers your ApoB, the ApoB itself serves as the biomarker.

00:12:48.640 We don't have a way outside of a lab commercially to measure tissue creatine levels. So we do not have

00:12:55.060 a biomarker for this. And that's why people who take it are just sort of adhering to a protocol.

00:12:59.620 On the mechanism of action, do we have any understanding of the mechanism of action for

00:13:06.260 creatine, whether it relates to the physical or the cognitive side?

00:13:11.260 On the physical side, meaning on the muscle performance side, it's certainly pretty clear.

00:13:15.840 People will recall how energy currency is delivered. So ATP, adenosine triphosphate,

00:13:25.120 is the richest form of energy currency, and it liberates energy. So it's spent by liberating

00:13:32.660 a phosphate. So ATP becomes adenosine diphosphate, ADP. Of course, that process works in reverse. So as

00:13:40.760 we want to build up and replenish our ATP stores, we need a phosphate donor. And this is where

00:13:47.120 phosphocreatine comes in. So we do naturally have phosphocreatine. In fact, when you start to think

00:13:52.840 about the various energy systems, if I asked you, Nick, to do something that was an all-out effort

00:13:58.380 for 10 seconds, that would not require oxygen. You're not tapping into your VO2 max or your

00:14:05.520 oxygen delivery system. It's frankly not even an anaerobic activity, meaning you're not actually

00:14:11.560 turning glucose into pyruvate, into lactate, etc. If you're doing something that is such a short burst

00:14:17.820 of activity, you are really relying on the phosphocreatine system to generate the ATP for that

00:14:23.360 activity. So if you're doing a 40-yard dash, you're relying on phosphocreatine. But of course,

00:14:27.900 phosphocreatine itself is a phosphate donor, and therefore, anything that boosts the supply of

00:14:33.740 phosphocreatine boosts the supply of ATP. And it's our belief that that's effectively what it is doing,

00:14:40.620 and therefore that it's helpful with anything that requires bursts of activity. But even beyond just

00:14:46.740 the super short, extending into the anaerobic, I don't know that there are really any proven benefits

00:14:52.320 that this augments aerobic performance. So once you get into the purely oxidative phosphorylation

00:14:59.780 pathway, I mean, maybe someone will correct us, but I'm not really aware that there are benefits of

00:15:03.860 creatine in that regard. I think it's more in the first two energy systems, the phosphocreatine system

00:15:08.220 and the anaerobic system. On the cognitive side, we know that a small amount of creatine is synthesized

00:15:13.260 in the brain, and that creatine can cross the blood-brain barrier. But the brain certainly

00:15:18.460 does not take up creatine to the same extent as the muscles do. So while we have, again,

00:15:24.720 some evidence to suggest that creatine is efficacious for cognitive function, it might turn

00:15:30.040 out to be the case that you need higher doses of it. I think that's still an open question as far

00:15:34.720 as I'm concerned. You mentioned earlier that we'll put a lot of more detailed information on the data

00:15:40.140 in the show notes, but looking at a high level, what does the data around creatine say about efficacy

00:15:46.220 of it? This is a supplement that has been quite readily studied. There's reasonable evidence to

00:15:51.560 suggest, and again, we'll link to lots of it, that creatine does help improve various parameters of

00:15:57.280 muscle performance. And it's not that subtle. I mean, it's typically in the range of 5, 10, maybe even

00:16:02.500 15%. So these include things like power and hypertrophy. Again, the power shouldn't be that surprising

00:16:08.260 when you understand the mechanism of action. The hypertrophy seems to be due to the, not just the

00:16:12.840 increase in the myofibril thickness, but also in the retention of water within the muscle. And of

00:16:17.820 course, that's still considered lean mass. As I alluded to, kind of physical performance in short,

00:16:22.880 intense burst activities, and potentially some benefits in slowing down the aging phenotype of muscle

00:16:29.820 mass. Again, like I said, it's really probably best suited for high intensity and anaerobic

00:16:36.080 activities. But the one meta-analysis we'll cite to found that creatine did not really improve

00:16:42.320 endurance events in trained athletes. Again, you always could argue, well, maybe it's because they

00:16:49.480 were really well-trained and their mitochondria were well-honed. But it's possible that there's

00:16:54.280 a study where you took completely untrained athletes, had them do an aerobic task with and without

00:16:59.620 creatine, and you might indeed see a benefit there. So again, I think we're still kind of in early

00:17:03.560 days on some of this stuff. There was a 2017 review that got quite a bit of attention that

00:17:08.700 we'll link to that concluded that creatine may help with the prevention and recovery from injury.

00:17:14.160 And there have been a number of meta-analyses looking at cognition. The most recent one, which

00:17:18.440 was this year, looked at 16 RCTs and found that creatine had a positive effect on memory.

00:17:25.500 I would say long and short of it is a lot of this stuff looks very promising. There's also some

00:17:30.840 evidence that women in particular might benefit more than even men. Women have lower stores because 1.00

00:17:38.080 muscle mass is the predominant store. Women have less muscle, therefore less stores. But there might 1.00

00:17:43.360 also be less consumption through diet. So it, again, at least leads to the hypothesis that women may 1.00

00:17:49.700 benefit even disproportionately to men. There's some, I think, rather weak data that suggests that

00:17:56.320 it may help reduce depression in women. And there's some evidence to suggest that it may be helpful

00:18:01.800 during periods of rapid hormonal change. And that could be within the monthly period of a menstrual

00:18:08.780 cycle, pregnancy, perimenopause, and menopause. So you might ask, why is that the case? Well,

00:18:15.000 the creatine and phosphocreatine pathways are impacted by hormonal changes. And of course, during all of those

00:18:21.280 periods that I just mentioned, you're seeing rapid hormonal changes. So it's not

00:18:24.680 really that surprising that supplementing to supernormal levels of creatine could offset some

00:18:32.380 of those impacts. Pregnancy is a question I get asked about a lot, Nick. I would say I remain a

00:18:38.040 little bit unclear and would probably suggest that it's probably safe during pregnancy, but we just don't

00:18:44.380 have enough human data to form a strong point of view. So in my mind, the wise thing to do is to avoid

00:18:50.260 anything that is not absolutely necessary during pregnancy. So just to give an example,

00:18:54.780 when we have women in our practice that are preparing for pregnancy or pregnant themselves,

00:18:59.120 I mean, no matter what they're taking, if they're taking medication for something that they can live

00:19:03.620 without for nine months, we would absolutely stop it. So yeah, I would say women should probably dose 1.00

00:19:08.980 it at about the same doses as men, but of course they'll get more bang for that buck because they're

00:19:13.760 on average smaller. Rounding out everything we talked about with creatine, what is the balance

00:19:18.780 of risk-reward to how you see it? Seems like a lot of stuff we talked about was a lot of reward,

00:19:24.020 but how do you think about this to summarize it? I would put this in the low-risk, modest-reward

00:19:30.360 category. We do have, I think, really robust safety data here, and it looks good. If the muscle stores

00:19:36.860 are already full, the liver is probably going to metabolize the delta. The kidneys will clear the

00:19:42.280 excess. There is one thing to keep in mind. If you're a person who doesn't have perfect kidney

00:19:48.060 function, you do probably want to talk with your doctor before you take it. And this is very

00:19:53.420 important. You want to make sure that they know you're taking it before they do any blood tests to

00:19:59.740 measure your creatinine because high doses of creatine can impact serum doses of creatinine, which

00:20:07.900 we would use as one of the metrics to determine kidney function. So in our patients that have

00:20:13.680 anything but perfect kidney function, if they're taking creatine, we typically have them stop 0.97

00:20:19.380 for a couple of weeks before we do a blood test. Creatine monohydrate really is the version to take.

00:20:26.560 I don't even know if they sell anything else. They used to sell a creatine phosphate a long time ago. I

00:20:31.340 don't think that there's anybody selling that anymore. I don't think it matters, but there's just no

00:20:36.000 evidence that you need to be taking anything other than creatine monohydrate. It's wildly inexpensive

00:20:42.200 and you should be looking for the purest product only that has nothing in it. The only ingredient

00:20:47.500 should be creatine monohydrate. No fillers, no extra ingredients, unless there's some flavoring agent

00:20:52.860 that you want. But I just mix this in with an electrolyte drink. So I want nothing other than

00:20:58.220 the creatine monohydrate in the sample. Anything else you want to say on creatine before we move to the

00:21:03.980 next one, which is fish oil. Nope. Perfect. Fish oil. Another supplement that we get asked about a ton.

00:21:11.420 We've done some podcasts on it. A lot of questions on it. Seems like a lot of people take it.

00:21:16.200 And so going through the questions with fish oil. First one is, are you correcting for deficiency or are

00:21:22.140 you trying to achieve super maximal levels when it comes to fish oil? Thank you for listening to today's

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The Peter Attia Drive - March 17, 2025

#340 - AMA #69： Scrutinizing supplements： creatine, fish oil, vitamin D, and more—a framework for understanding effectiveness, quality, and individual need

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