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
Mon, 17 Mar 2025
View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this "Ask Me Anything" (AMA) episode, Peter explores the complex world of supplements by introducing a practical framework for evaluating their effectiveness and relevance to individual health needs. Rather than providing a simple list of recommendations, Peter aims to equip listeners with the tools to critically assess supplements on their own. He then applies this framework to discuss research on several popular supplements, including creatine, fish oil, vitamin D, B vitamins, and ashwagandha. Additionally, he covers key factors in assessing supplement quality, helping listeners develop a deeper understanding of how to make informed decisions based on their personal health goals. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #69 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of episode topics [1:45]; How Peter evaluates patients’ supplement regimens, and common misconceptions about supplements vs. pharmaceuticals [3:00]; A framework for evaluating supplements [6:15]; Evaluating creatine: purpose of supplementation, dosing, and mechanism of action [10:00]; Creatine: proven benefits for muscle performance, potential cognitive benefits, and why women may benefit more [15:15]; Creatine: risk vs. reward, kidney concerns, and choosing the right supplement [18:45]; Evaluating fish oil: its primary purpose as a supplement and how to track levels [20:45]; Fish oil: how omega-3s impact inflammation, heart health, and brain function, and the strengths and limitations of current research [26:30]; Fish oil: the risks of supplementation, guidance on selecting high-quality products, and how to determine whether supplementation is appropriate [37:30]; Evaluating vitamin D: understanding deficiency and optimal levels [45:15]; Vitamin D: role in bone health, immune function, potential longevity impact, and biomarker limitations [51:15]; Vitamin D: efficacy, safety, and balancing risk vs. reward [58:15]; Evaluating B vitamins: function, consequences of deficiency, and key biomarkers to assess whether supplementation is necessary [1:02:15]; B vitamins: risks for CVD and dementia associated with deficiency, and limited evidence for general population supplementation [1:07:15]; Evaluating ashwagandha: background, uses, and mechanism of action [1:15:30]; Ashwagandha: current evidence for its effects on sleep, stress, and anxiety [1:19:15]; Ashwagandha: evaluating supplement quality, safety profile, and the risk-reward balance [1:22:15]; The importance of using a structured evaluation framework to assess any supplement [1:26:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
Chapter 1: What framework should I use to evaluate supplements?
Hey everyone, welcome to a sneak peek, Ask Me Anything, or AMA episode of The Drive Podcast. I'm your host, Peter Attia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peterattiamd.com forward slash subscribe.
So without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything AMA episode number 69. In today's episode, we cover supplements.
As this is a very complex topic, we wanted to approach it first by proposing a framework that you can use to evaluate supplements that we can't make blanket recommendations on since everyone has their own individual health circumstances.
To me, the framework is very important here because if I were to just dive into this podcast and give you my point of view on a random collection of supplements, it would be akin to giving you a bunch of fish when in reality, what I want to do is make sure you, of course, know how to fish. But not just giving you the framework, we also want to give you a few fish.
And so we want to use the framework to cover a handful of studies for some popular supplements. We covered creatine, fish oil, vitamin D, vitamin B, or many of the vitamin Bs, and ashwagandha. We also talk about how to look at supplement quality, and we hope that this episode gives you an ability to take said framework and apply it to any supplement you encounter in the future.
If you're a subscriber and you want to watch the full video of this podcast, you can find it on the show notes page. If you're not a subscriber, you can watch the sneak peek on our YouTube page. So without further delay, I hope you'll enjoy AMA 69.
Peter, welcome to another AMA. How are you doing? Great. Thank you for having me again. Always, always welcome. I know sometimes it's tough to get you to clear your schedule, but we're always happy you show up. Haven't missed one yet, so that's always a good thing. 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. What we decided to do today was instead look at a framework for how you think about supplements and then go through case studies to
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Chapter 2: What are the proven benefits of creatine?
So the hope is after this, not only will people understand those specific supplements better that we're going to do the case studies on, but also how they can apply this framework. to their own life. With all that said, when patients come into the practice, what percent of the supplements are they taking that you recommend they continue to take?
Obviously, any patients coming into the practice, we're trying to gather as much information about them as we can through their medical history. And an important component of that is understanding all medications, supplements, hormones, anything they take. I call this the bucket of exogenous molecules. So generally, we know this on the way in, and there's a ton of variety.
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 might be two pages long and everything in between.
Our view is generally to approach this 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? And I don't mean we literally stop everything, but I'm saying that's kind of the mental model for how we go about thinking about it.
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 there's just a couple of things worth acknowledging before we jump into this. And it comes from discussions that I've had many times, which go something like this. Hey, I don't believe in taking any medicine, just so you know, only natural supplements. Now, my response to that is, tell me the difference.
There is a difference, but I just want to make sure you as the consumer of this understand the difference. And it's really a question of regulation. So supplements are not regulated. By definition, the FDA has tacitly referred to them as generally regarded as safe supplements. But the process by which that's determined is not entirely that rigorous.
And pharmaceutical products, while far from perfect, do have more in the way of regulation and oversight. There are places where these overlap. I'll encounter a patient who says, listen, I will never take a statin to lower my ApoB, but 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 rice yeast is effectively a modest dose of pravastatin.
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Chapter 3: How does fish oil affect health?
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, but doing it the way we're going to do it today is really how you develop the muscle for doing this type of work.
I think with that said, do you just want to run over real quick the questions you asked to determine whether or not a supplement is worthwhile? And I think just giving this overview will be helpful because as we said in the beginning, when we go through the case studies, we'll 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?
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 this is the punchline. Anytime you're considering taking a supplement or someone is suggesting a supplement, you should ask the following questions 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 supernormal levels of fill in the blank? Second question, are you taking this molecule because you believe that it's going to improve your lifespan or your health span or potentially both?
The third question is, if it is lifespan, is it because this molecule is targeting a specific disease and presumably reducing your risk of that disease, or do we believe it's more broadly geroprotective?
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 disease.
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?
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Chapter 4: What should I know about vitamin D supplementation?
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?
On the physical side, meaning on the muscle performance side, it's certainly pretty clear. People will recall how energy currency is delivered. ATP, adenosine triphosphate, is the richest form of energy currency, and it liberates energy. It's spent by liberating a phosphate. ATP becomes adenosine diphosphate, ADP. 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 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 10 seconds... That would not require oxygen.
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, etc., 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 40-yard dash, you're relying on phosphocreatine. 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, and therefore that it's helpful with 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.
Once you get into the purely oxidative phosphorylation pathway, maybe someone will correct us, but 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 the brain certainly does not take up creatine to the same extent as the muscles do.
So while we have, again, some evidence to suggest that creatine is efficacious for cognitive function, it might turn out to be the case that you need higher doses of it. I think that's still an open question as far as I'm concerned.
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Chapter 5: Why are B vitamins important for my health?
And that could be within the monthly period of a menstrual cycle, pregnancy, perimenopause, and menopause. So you might ask, why is that the case? Well, 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 that supplementing to supernormal levels of creatine could offset some of those impacts. pregnancy is a question I get asked about a lot, Nick. I would say I remain a little bit unclear and would probably suggest that it's probably safe during pregnancy, but we just don't have enough human data to form a strong point of view.
So in my mind, the wise thing to do is to avoid anything that is not absolutely necessary during pregnancy. So just to give an example, when we have women in our practice that are preparing for pregnancy or pregnant themselves, I mean, No matter what they're taking, if they're taking medication for something that they can live without for nine months, we would absolutely stop it.
So yeah, I would say women should probably dose it at about the same doses as men. But of course, they'll get more bang for that buck because they're on average smaller.
Rounding out everything we talked about with creatine, 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 how do you think about this to summarize it?
I would put this in the low risk, modest reward category. We do have, I think, really robust safety data here, and it looks good. If the muscle stores are already full, the liver is probably going to metabolize the delta. The kidneys will clear the excess. There is one thing to 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.
because high doses of creatine can impact serum doses of creatinine, which we would use as one of the metrics to determine kidney function. So in our patients that have anything but perfect kidney function, if they're taking creatine, we typically have them stop for a couple of weeks before we do a blood test. 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. I don't think it matters. But there's just no evidence that you need to be taking anything other than creatine monohydrate. It's wildly inexpensive, and you should be looking for the purest product only that has nothing in it.
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Chapter 6: What are the benefits of ashwagandha?
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