Freakonomics Radio - 658. This Is Your Brain on Supplements

Episode Date: January 9, 2026

We all want to stay sharp, and forestall the cognitive effects of aging. But do brain supplements actually work? Are they safe? And why doesn’t the F.D.A. even know what’s in them? (Part one of �...�The Freakonomics Radio Guide to Getting Better.”) SOURCES:Marty Makary, commissioner of the Food and Drug Administration.Peter Attia, physician, author, and host of The Peter Attia Drive.Pieter Cohen, associate professor of medicine at Harvard Medical School, physician at the Cambridge Health Alliance. RESOURCES:"Protein Powders and Shakes Contain High Levels of Lead," by Paris Martineau (Consumer Reports, 2025)."Accuracy of Labeling of Galantamine Generic Drugs and Dietary Supplements," by Pieter Cohen, Bram Jacobs, Koenraad Van Hoorde, and Céline Vanhee (JAMA, 2024).Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health, by Marty Makary (2024).Outlive: The Science and Art of Longevity, by Petter Attia (2023)."Revealing the hidden dangers of dietary supplements," by Jennifer Couzin-Frankel (Science, 2015). EXTRAS:"China Is Run by Engineers. America Is Run by Lawyers." by Freakonomics Radio (2025)."How to Fix the Hot Mess of U.S. Healthcare," by Freakonomics Radio (2021). Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Transcript
Discussion (0)
Starting point is 00:00:01 If you ever watch TV or use the internet, you've probably seen advertisements for products that are supposed to help your focus, improve your memory, and prevent the cognitive effects of aging. Our brains are incredible, but memory can get complicated. That's why we created new NERIVA Memory 3D. AlphaBrain is one of the most important supplements that I've ever found ever in my life, if not the most important one, and the one that I cherish the most. I started noticing the clarity wasn't there that I needed. And that was frustrating. I'd seen many commercials about Previgen, and I thought, why not give it a try? Want to know why there are so many of these ads? Apparently because they work.
Starting point is 00:00:51 Around 60% of U.S. adults take at least one dietary supplement, the most common being a multivitamin. Brain supplements are one of the fastest growing segments of the market. It has doubled over the past seven years, and it's projected to double again in the next seven to around $25 billion a year. We asked Freakonomics Radio listeners to tell us what they take and why. I take a bunch of supplements in the morning, but specifically for brain health, I take krill oil and I also take creatine powder. After listening to a parenting podcast, I started taking coline, which is for, fetal brain development, but also adults can take it from memory. The one brain supplement I take is omega-3 fish oil.
Starting point is 00:01:40 I take it once a day. Currently, I'm taking 20 to 25 grams of creatine a day for cognitive benefits. I take a good amount of fish oil every day. I take three tablespoons of MCT oil every day. My father-in-law is taking magnesium three in eight. He has Parkinson's, and we're... We're trying to retain some of his mental clarity. I've been taking NAC, that's short for N, acetyl, cysteine, off and on for several years.
Starting point is 00:02:14 The reason I take it is because I found a really interesting article on PubMed about how it reduces obsessive and compulsive behavior. And it, like, cured my sweet tooth. It makes me feel sort of calm and less impulsive. In case you're wondering, these supplements are not regulated by the Food and Drug Administration, the way that pharmaceuticals are, both prescription and over-the-counter pharma products. That is thanks to the Dietary Supplement Health and Education Act, or DeShay, which President Clinton signed in 1994. DeShea treats supplements as a type of food, not as drugs. Many of them are made from plants or other natural matter.
Starting point is 00:03:00 Does this guarantee that they're safe? Well, consider that hemlock is also natural, so are ricin anthrax? Okay, but do these brain supplements at least work? Today on the show, we kick off a month-long series we're calling the Freakonomics Radio Guide to Getting Better. We will start by trying to understand the brain supplement industry. You can imagine in an industry that has absolutely zero oversight and regulation, it's truly the Wild West. And we will look at the scientific evidence. For instance, on a scale of 0 to 10, how effective are brain supplements at preventing cognitive decline?
Starting point is 00:03:38 I'm really struggling between 0 and 1. This is your brain on supplements, and it starts now. This is Freakonomics Radio, the podcast that explores the hidden side of everything with your host, Stephen Dubner. We're going to speak about supplements today with not one, not two, but three physicians. Let's start with Peter. Atia. He wrote the best-selling book, Outlive, The Science and Art of Longevity, and he makes the Peter Atia Drive podcast. He did his medical training at Stanford and Johns Hopkins, and today he runs a high-end boutique medical practice. We have some patients, Stephen, that come into our
Starting point is 00:04:38 practice, and I kid you not, they have a supplement list of, I mean, I've seen people come in with a hundred items on their list. My practice is pretty small. I only see 75 patients. It's a virtual practice, except for some of the evaluation we do at our facility in Austin, Texas, where we have people come out at least once a year for a two-day, expansive exercise testing. We're not providing primary care. We're really just applying this Medicine 3.0 playbook. I assume you're fairly expensive, yes? Yes. All right. Define Medicine 3.0 for me?
Starting point is 00:05:16 I would define it as a type of medicine that focuses equally on the pursuit of. of lengthening life as it does on reducing the decline of health span and also takes a more personalized approach based on all the best available evidence. The five main domains of Medicine 3.0, exercise, nutrition, sleep, emotional health, and exogenous molecules, assuming that exogenous molecules are at least close to equal importance of the others, how do you think about that category, not for yourself, as a human or as an investor or as a podcaster, but as a physician particularly? It really depends on the situation.
Starting point is 00:05:59 There are some people for whom the drugs and supplements or hormones really play a minor role. And then there are other scenarios whereby the difference between life and death. If a person has hypertension, high blood pressure that is otherwise just completely recalcitrant to the normal measures of weight loss and exercise, being able to use a drug to lower their blood pressure is going to have a dramatic impact. on the risk of heart disease and stroke. And then for other people, you're going to get 90% of the lift out of the other four levers. I want to talk mostly about supplements, particularly brain supplements or what are at least advertised as brain supplements. The supplement industry, and these measurements are all a little murky, but the supplement industry is now estimated to be at around $45 billion a year in the U.S. what do you make of that figure? My intuition is that the majority of that money would be just as well flushed down a toilet.
Starting point is 00:06:56 Because why? I think at best most supplements are unhelpful and some of them are probably harmful, not because of malice, but just incompetence on the part of the people who are making them. Harmful on what dimensions and in what way? Like, is it a dosing issue? Is it a component issue of the supplements? I think there's two ways in which this can occur. The first is when an active ingredient is there, but it's in a much, much higher quantity than it should be. Obviously, you can have the opposite problem, which is equally likely or maybe more likely where it's in a significantly lower level
Starting point is 00:07:32 than what they're telling you, in which case it's just a homeopathic, useless treatment. But then, of course, you have the problem where impurities show up, most notably heavy metals. You think you're buying melatonin, and what you're getting is melatonin with lead or something like that. A recent consumer reports analysis of protein powders and shakes found that two-thirds of them contained more lead in a single serving than you should consume in a day, in some cases more than 10 times as much. How does this kind of contamination happen? There's no testing by the FDA of supplements before they arrive on store shelves. And that is Peter Cohen. He's a professor at Harvard Medical School and a physician at the Cambridge Health Alliance, where he also runs the
Starting point is 00:08:15 supplement research program. Science magazine once described Cohen as a mix of Indiana Jones and Sherlock Holmes in the supplement world. He and his colleagues collaborate with research labs all over the world. There's been a lot of questions over the decades about the quality of products, in part because of studies like ours, demonstrating that everything is not exactly as it might appear on the label. Cohen and his colleagues once found an unapproved amphetamine-like stimulant in several weight loss supplements, and they published their findings. One of the supplement makers sued Cohen for libel, claiming $200 million in damages. The case went to trial. The jury found in Cohen's favor, but the week-long trial, he later said, put my family
Starting point is 00:08:59 through the ringer. If it strikes you as unfair, or at least unfortunate, the scientific researcher finds himself in a situation like that. Well, you may want to go back and listen to an episode we made a few months ago, number 647, about the degree to which the United States is a lawyerly society. Whenever there is money to be made, there will be lawyers to protect the money makers, and there is a lot of money being made in supplements. Since the passage of DeShay in 1994, the number of supplements on the market has grown from around 4,000 to 90,000. And none of them, remember, are getting any kind of health agency approval. It's basically completely unpredictable what you're getting.
Starting point is 00:09:43 There are some nonprofit organizations that review manufacturing practices and run some tests before supplements go to market. But these are not mandatory reviews. The manufacturer has to opt in. And the testing is limited. These groups are only looking at the chemical compounds found in the supplement. and are not making any assessment of the health claims or structure function claims or you name it. I don't know of a single organization that's doing that in any sort of accurate way. You know, taking a look at the labels and saying, is this truthful or is this supported by solid signs?
Starting point is 00:10:22 If you had to say on a scale of zero to 10, how reliable would you say that the claims, the medical, nutritional claims about supplements in toto are? Yeah, I mean, it's very distorted and I'm really struggling between zero and one. I don't know if I can do fractions, but it would be somewhere there. In the first year of the second Trump administration, there have been substantial shifts in food and drug policy and in public health policy. In some cases, there's more regulation, in some cases less. There have also been cuts to scientific funding and staffing, including at the CDC, the Centers for Disease Control. So all of these targets are moving. The FDA does regulate what a manufacturer can write on a supplement label.
Starting point is 00:11:13 And the FTC, the Federal Trade Commission, does regulate advertising and marketing. For instance, a supplement manufacturer cannot claim that their product can diagnose, treat, cure, or prevent any disease. But if you have a good copywriter or a good AI and a good lawyer to approve the copywriter, the English language can be quite pliable. As long as the manufacturer avoids mentioning a specific disease, like Alzheimer's disease, they can suggest that their product has that health benefit, the same one that anyone with Alzheimer's disease or with a loved one with Alzheimer's disease would be thinking about. So the manufacturer, if we were manufacturing supplements,
Starting point is 00:11:57 could promote our product as if it maintains a healthy memory or preserves healthy memory or memory boosting. All these are legal claims, even if your product has never been studied in humans at all. So let's say there is a supplement that promotes itself as being good for your brain, and there's a similar pharmaceutical product with similar claims. What's the difference in how those claims are arrived at? You've already explained how under DeShay that the first doesn't have to really have any data,
Starting point is 00:12:33 what about for the pharmaceutical version? Yeah, the pharmaceutical is completely a different situation. In order for a pharmaceutical to make a claim, it would have to have been approved by the FDA. Large clinical trials need to be conducted. The FDA needs to first approve the pharmaceutical for human use. And when they do that, they'll also be clear on what the approved uses are. And traditionally manufacturers have been required to stick with the
Starting point is 00:13:03 claims that they had originally got approval for. And beyond that, they couldn't comment on the use of their drug. I'd like to ask you a very naive question, but why is it that we're a country that has, you know, an FDA, Food and Drug Administration, an FTC, Federal Trade Commission? And if I'm a pharmaceutical firm and I want to sell my drug, then I need to go through a long established standard, which, you know, is problematic in many ways. We all know that. And there's a lot of advocacy for change in many directions there, but there is a standard. But if I'm a different kind of entrepreneur and I want to sell a supplement, let's say, that is essentially making identical claims to the pharmaceutical about brain health, memory health, retaining cognitive
Starting point is 00:13:51 function and so on, there's not much inspection, there's not much guarantee of consistency or even ingredients. The odds are very good that I'll manufacture in China, by the way. I can make these similar claims and sell them on the open market and the FDA and the FTC don't touch it. I literally just don't understand how that makes sense. Am I naive? Am I stupid? Am I missing something? What's going on? No, you've got it completely correct. How a manufacturer can look at it is if they have some compound, they want to sell some health compound, they just need to decide which is the more profitable route. It might be that doing large randomized control trials and then having proprietary control over it and being able to have the stamp of approval with the FDA as a
Starting point is 00:14:40 prescription drug and then being able to sell that globally will be the most profitable. But if they think that that might not be a good use of resources, then exactly. Take the second path that you mentioned and go directly to market, just tone down the claims and start selling it online is a dietary supplement. Peter Cohen and his colleagues at the Supplement Research Program are not the only people concerned with supplement safety and efficacy. The NIH has an office of dietary supplements that publishes fact sheets about supplements. The U.S. Department of Defense runs a program called Operation Supplement Safety.
Starting point is 00:15:21 Turns out that military members take more supplements than civilians. And Examine.com, a subscription website publishes up-to-date supplements. supplement research, but with 90,000 different supplements on the market, there's a real scarcity of good data, and that can have serious consequences. We have thousands of patients who end up in emergency departments do the adverse effects of supplements every year in the States. Who keeps the records on that? Well, it was recently shut down.
Starting point is 00:15:52 The research that looks at how many people end up in emergency departments is based on a series of Sentinel emergency departments that was set up and operated in part by the CDC. And the collection of that data could also detect adverse effects of dietary supplements. So that was the only representative way to take a look and get an estimate of how many people are actually ending up in emergency departments. I'm looking at the data now. It says that an estimated 23,000 emergency department visits annually in the U.S. from dietary supplement adverse effects.
Starting point is 00:16:32 I feel bad for those 23,000 people, but that's relatively tiny, yeah? Yeah, compared to the number of people who are being misled about the claims in dietary supplements, absolutely. I mean, how would that compare to, you know, alcohol overuse in ERs? Yes, the difference is that tobacco, alcohol, gun violence,
Starting point is 00:16:50 in those situations, no one is using those products to improve their health. So here we have situations where there's no information for consumers that they're going to find about the risks of these products, and they're taking that to improve their health. And then to end up in the emergency department, tens of thousands or hospitalized, that's serious. So hearing Peter Cohen talk about the problems with supplements,
Starting point is 00:17:22 you might think that he is anti-supplement, but you'd be wrong. I couldn't practice good medicine without them. Cohen, remember, is also a primary care physician. I recommend supplements to my patients all the time. These are vitamins and mineral supplements or combinations of those, and they're key to medical care. Just name your top whatever five or ten vitamins and minerals that you prescribe. Multivitamin, vitamin D, calcium that's often combined with vitamin D. Iron's great.
Starting point is 00:17:56 It's one of my favorites. Indeed, for some people with vitamin deficiencies, supplements can be critical. Here's one of our listeners, Danielle Douglas. Hi, as a 44-year-old emergency medicine physician, my brain needed to be a Ferrari and not a Toyota, and it wasn't anymore. I was doing everything right or so I thought. But as I worked in the busiest ER in San Diego County
Starting point is 00:18:20 during a COVID pandemic, homeschooled three children and worked out like a triathlete to cope with all the stress, my nutrient stores were depleted, and cortisol levels completely strained. Through lab testing, I realized my stress vitamins and minerals like magnesium and B vitamins were in the toilet. Fortunately, through supplementation with GMP NSF certified supplements and obtaining them through well-vetted distributors,
Starting point is 00:18:44 I was able to get my brain back to functioning at optimum levels. A lot of the listeners we heard from say they're using creatine to boost their brain power. Here's Peter Cohen. Yeah, so creatine is, it's not really part of medical care, but it's something that can help a specific type of athletic performance. If one's doing repetitive weightlifting, for example, taking creatin can slightly improve one's ability to recover in between sets. Now, while that is well established, creatin is often marketed as if it'll have some sort of cognitive benefits, and there's no robust data whatsoever
Starting point is 00:19:25 to support that claim. Has anyone tried that you know of? With creatin, I believe there's been a few small studies. And usually when you have just a few small studies, you can publish the ones that look promising. But with creatin, even the very small studies, are not suggestive enough. Okay. What about coline? Colleen makes a little more sense because it's a precursor of acetylcholine, and that's something that gets low in Alzheimer's disease.
Starting point is 00:19:53 So it makes some sense that let's put something that can get converted in the body into something that you might be deficient in when you have memory loss. But with coline, I know of no studies that have demonstrated at all that giving coline will improve memory or function. How about ginkgo? And I'd love you to get into the ginkgo evaluation of memory study, if you could. Ginkgo-Beloba has been carefully investigated because it was probably the leading botanical supplement that was thought to potentially have cognitive benefits or prevent memory. And this idea goes back probably thousands of years, right? Absolutely.
Starting point is 00:20:36 Chinese and others have been using. So a lot of NIH funds has been spent on trying to understand, you know, can Ginkobloba preserve or improve memory? And the studies are negative, basically. There's no difference between Ginkobloba and placebo. The nice thing for a supplement manufacturer, though, is that you can take a study like that that definitively is. shown that Ginkobeloba does not prevent memory loss and completely ignore it when it comes to your
Starting point is 00:21:10 label. So then you can just put Ginko Bolova into your supplement and then sell it as memory enhancement. This is how crazy the current advertising, marketing environment is. There's just a disconnect between how supplements can be promoted and the proven benefits. And that's because the law basically gives manufacturers a pathway to communicate just about any health benefit to consumers without having to demonstrate anything that their product actually works or even have studied their product in humans. What about omega-3s? Yeah, so with omega-3, what's very interesting is that in cohort studies, so groups of people who have diets that are very rich in omega-3, a lot of fatty fish and other omega-3 foods, there's a lower incidence of Alzheimer's disease in those.
Starting point is 00:22:00 population. So it's a natural thought. But in this situation with omega-3, it has been studying, I believe, up to five years in duration and no benefit of omega-3 supplementation to improve cognitive function. What does that say about the difference between ingesting an ingredient that's naturally occurring in a food versus a supplement version? Right. It probably says a lot because this reductionist approach to nutrition might not be the most beneficial. So if we're just reducing herring to its omega-3 content,
Starting point is 00:22:36 there's a lot of other things going on, exciting things when it comes to herring. Talk about that. Is it about the cell structure? Is it about the other components? What are the exciting things in herring? You know, I'm not a herring analytical chemist expert,
Starting point is 00:22:49 but I would assume that if we took a deep dive in the chemistry of herring, we would find thousands of different compounds. Some of those would be, you know, fascinating to study. And they're all combined together. With food, there's also the tradition of how we eat it, right? Like with the herring, how is it preserved? Is it in vinegar or the sugar?
Starting point is 00:23:11 And how do those preservatives affect either positively or negatively our health? And then, of course, what are we putting the herring on, right? So a lot's going on there. But you're a herring fan from a nutritional perspective. Oh, yeah, definitely. I think the more fish we can get in our diet, the better. Can you talk for just a minute about the relationship between modern supplement taking, especially botanicals and things like that,
Starting point is 00:23:38 and the development of medicines generally? How do you think about knowing what's valuable and what's not from the natural world versus the pharmaceutical world? I think that what we've learned from decades of high quality, studies is that it's really the details that matter. It's not so much the origin of something did it come from a lab or did it come from a plant. It's what are the precise components in that health product? If there's more than one, what's the ratio of those? If there's one, precisely how much there is. How is that ingredient or ingredients absorbed into the body? And then once that's
Starting point is 00:24:17 standardized we can understand its health effects. There is no clear distinction between pharmaceutical drugs and botanical preparations. Red yeast rice is a great example. Red yeast rice is a fermented rice product, kind of like making beer. You combine yeast with rice and make red yeast rice. And one of the fermentation byproducts, there's a compound called monocolon K. And that compound is precisely the same chemical as lovastatin, which is a statin drug. That's a perfect example of this overlap between precisely the same chemical. And we've done research on a similar plant alkaloid like that called galantamine, where it's found in plants and has been part of some traditional botanical remedies, those plants have. And it's also isolated, synthesized,
Starting point is 00:25:12 and uses pharmaceutical drugs. So there's no real distinction between the is, but I would say that unless you're standardizing the production of something, you really can't understand its long-term health facts. This is a subtle but important point that Cohen is making. Drugs that have gained FDA approval, including over-the-counter drugs like ibuprofen, fall into what is called evidence-based medicine. Many supplements, meanwhile, fall into what you might call gossip-based medicine. You may hear from a friend that a certain supplement worked great for them, but you don't know what else they're taking. You don't really know what it did for them. Remember, the placebo effect is powerful.
Starting point is 00:25:57 You also don't know if maybe 10 other friends took the same supplement and found that it didn't help or maybe even harmed them. Medicine and nutrition science are hard enough even when you have good data. With supplements, it can be hard to even know the dose you're getting. The drug that Cohen mentioned a minute ago, galantamine, is an FDA-approved prescription treatment for mild to moderate dementia caused by Alzheimer's. According to the FDA, galantamine isn't legally supposed to be sold as a dietary supplement, but it is as a non-prescription treatment for memory retention and cognitive function. Peter Cohen and his colleagues analyzed pharmaceutical versions of the drug versus several supplement versions. They found that the pharma version,
Starting point is 00:26:45 versions were properly labeled. They contained between 98 and 104% of the quantity listed on the labels. In other words, what it says is what you get. The supplement versions, meanwhile, ranged from less than 2% to 110% of the quantity listed on the label. And they found that a third of the supplements were contaminated with bacteria associated with gastrointestinal illness. So if you are in favor of supplements, you might like to move them into the evidence-based realm. Coming up after the break, is that going to happen? I'm Stephen Dubner. This is the Freakonomics Radio Guide to Getting Better.
Starting point is 00:27:27 We'll be right back. So the physician Peter Cohen is skeptical of many dietary supplements, but he does use some in taking care of his patients. The physician Peter Atia is also skeptical, and he too makes room for exceptions. There are a handful of supplements that I take, and by extension, there are a handful of supplements that many of our patients take. Name them. I think for most people, magnesium is a really logical choice. There are different forms that you can take magnesium in.
Starting point is 00:28:08 You can take it in a form that is really rapidly absorbed. You can take it in a form that is very slowly absorbed, and they actually achieve totally different things. And so we don't consider those mutually exclusive. There's also a form that is bound to another molecule that enables transatlanticism. for across the blood-brain barrier. And there's reasonable, though, because it's only a supplement. It's not subject to the same level of testing. But there's reasonable evidence that it's got some protection in the brain and augments sleep.
Starting point is 00:28:36 So you have three completely different types of magnesium, and I think there's benefit in all three of those. I think another supplement that makes sense for almost everybody is creatine monohydrate. There's physical advantages to that. There's cognitive advantages to that. Are they massive? No, they're not massive. but you always have to weigh the cost, both economic and risk, of taking something to the potential benefit. And so if you do it on an ROI basis, I actually think creatine makes a ton of sense.
Starting point is 00:29:01 I would say those are probably the two closest supplements that I would put in the almost no-brainer camp. I would put EPA and DHA, which are the two omega-3 fatty acids found in fatty fish. Most people, maybe 90% of people, 80% of people probably don't consume enough fatty fish. to achieve the levels that we believe, and when I say we, I don't mean me personally, I mean the epidemiologists and people who study this that we think produce the optimal levels of cardiovascular and brain health. And so for most people, myself included, taking a high-quality EPA and DHA supplement is a great way to supplement the amount of fish we eat. Maybe another one I would throw in there is for jet lag. I think melatonin can be very helpful. I'm not a fan of it
Starting point is 00:29:48 at all for daily use, because it does seem to downregulate endogenous production of melatonin. But when you're hopping, in my experience, more than six or seven hours of a time zone, melatonin can be a wonderful tool to help reset circadian rhythm, along with another supplement that I only use during those periods, which is called phosphatidilcerine. Phosphotidyl serene suppresses cortisol output from the adrenal glands, and also is just a fantastic tool when you're trying to go to bed. When you describe cognitive advantages to some of these supplements,
Starting point is 00:30:24 how would you assess the evidence for those advantages compared to the evidence of some pharmaceutical, maybe it's a GLP1 agonist that we hear a lot about these days? How does one body of evidence compare to the next? Oh, it's not even close, Stephen.
Starting point is 00:30:39 The advantage that we would have when assessing the benefits of a GLP1 agonist are so much more because the studies are so much larger, they're so much more robust. It's interesting that you brought up GLP-1s because everybody understands the efficacy that these drugs have when it comes to weight loss and type 2 diabetes. But there are all sorts of sub-analyses that are looking at other questions, right? How does this drug stack up in patients with heart failure? How does this drug stack up in patients with MCI or mild cognitive impairment? It is that indication of MCI that I think is the most interesting right now. Because the jugular
Starting point is 00:31:13 question is not, does a person who is obese, overweight, or have type 2 diabetes, who takes this drug, and therefore ameliorates those conditions, does that improve MCI? The answer is, obviously, yes, it does, because anything that takes weight off and improves insulin sensitivity, improves cognitive function. The more important question, and the multibillion-dollar question is, independent of the weight loss and the improving insulin sensitivity, do these things improve cognition? And if the answer to that is yes, we would elevate this drug from its current status into the pantheon of what we call giroprotective agents, right? Something that is actually targeting some of the fundamental metrics of aging and not doing
Starting point is 00:31:58 it circuitously through weight loss or insulin sensitivity, all of which are important, but they're very distinct questions. What is your sense based on what you've read and learned so far about the mechanisms by which there's a cognitive boost to the gLP ones? We actually recently did a podcast on this. About twice a year, we do a podcast called, what is it called? I think we call it proven, promising, fuzzy, nonsense. Like, we basically take a bunch of drugs and supplements and run them through our framework and put them into five categories. So, GLP-1s came out in that assessment as promising. And promising is a high bar for us. Like, we're sticklers. And where I landed on that, Stephen, was the data look pretty good at the moment, but the definitive study still has. hasn't been done. I don't see any evidence that a person with normal cognition, normal risk factors, insulin sensitive and of normal weight, would benefit from them. So if you were to think about comparing what is known on the market today as brain supplements or supplements that offer
Starting point is 00:33:00 cognitive benefits of some kind, if you compare that whole kind of murky pool of supplements to the cognitive benefit effects of GLP-1s, how do you think about those two pools of treatments differently? So these are spoken about in very different circles. The discussion that you and I are having about GLP-1s is the discussion that's happening with physicians and scientists. And these are really interesting questions. I don't pay that much attention to the podcast sphere,
Starting point is 00:33:33 but in podcast land, we're really talking about biohacking, and those people are talking about everything from Lions, Maine, to beeswax, to all sorts of God knows what, there's virtually no overlap in those discussions that I can see. I've spent a lot of time looking at both of these things, and from where I sit and have no bias, because I couldn't care less, I'm just interested in what works. I think that there's potentially a signal there on the GLP one side. My intuition, though, is it is not a cognitive enhancer. It is something that prevents decline in the susceptible individual. So when we think about brain function and especially brain supplements, it seems to be mostly older people who are concerned about improving or
Starting point is 00:34:19 stopping the loss of memory or maybe forestalling Alzheimer's and things like that. But as you're not talking about the relationship between cognitive function and physical function, I wonder if you can talk a bit about what's included in cognitive function as you see it. As a physician, primarily. What's the relationship between cognitive function and mental health? What's the relationship between cognitive function, not just memory, but things like decision-making and so on? We think of cognitive function broadly in terms of executive function, which would include decision-making, memory, which is both short and long-term, and then there are lots of subtypes of memory, visual, spatial memory, et cetera, and then processing speed. Those are the three
Starting point is 00:35:01 pillars of cognition, and they can all be measured. Unfortunately, we don't have great off-the-shelf ways to measure this. There aren't, like, amazing apps that do this, but a really good clinician who's well-versed in how to do cognitive testing can measure and assess your performance on those domains. We still have to accept the fact that as we age, our cognitive performance declines, just as our physical performance does. So my VO2 max is getting lower by decade, my muscle mass, my strength, these are decreasing by decade, and so too is my cognitive performance.
Starting point is 00:35:32 So then the question becomes, what can I do to offset the? that. What I really want people to understand is all the supplement stuff you're doing is a little bit of rearranging the deck chairs on the Titanic. You earn the right to worry about that stuff once you have the stuff that provides 90% of cognitive function taken care of. And that's going to come down to sleep, exercise, nutrition, intellectual and social engagement, and learning. These are the pillars of maintaining cognitive function. And if you never took a supplement for the rest of your life, but you adhered to maximizing your participation on those domains, you would be incredible. So you said that a lot of the spending on supplements is equivalent to flushing the money down the
Starting point is 00:36:21 toilet. You, however, are an investor in a couple companies that make supplements, yes? Yes. These include Element and AG1, both of which are pretty well known. Walk me through those. Start with Element. Describe what it is and why you invest in it, and I assume that it's not in the category of supplements that you'd be better off flushing your money down the toilet, correct? Correct. So Element is a company that makes an electrolyte drink. It's effectively sodium, chloride, salt, with flavoring. This was actually a topic I was never really interested in until four years ago when I had a couple of repeated bouts of lightheadedness, including one that resulted in a
Starting point is 00:37:02 a really significant face plant that required multiple stitches to a bunch of lacerations across my face. And when I got home, this happened while I was traveling and my doctor took my blood pressure and sort of confirmed what I had always known, which was I had sort of low blood pressure. And it was exacerbated by things like traveling or, for example, if I gave blood or if I was exercising a lot. The obvious solution to that is to hydrate more. And that got me really deep down the rabbit hole of hydration, I basically bought every product on the market. And the one that I liked that I found palatable enough was element. I reached out to the founder of the company and made a small investment. And I want to be clear, I don't think there's anything magical about any
Starting point is 00:37:45 electrolyte drink. What you're really trying to do is identify a way that you can easily deliver something on a frequent basis. And so what you're titrating towards is compliance at the lowest cost. If I were to drink more water and put more salt on my food, I could achieve a similar benefit. Yeah, so why not do that? It's just going to be much harder to be compliant than to take a little simple pack, throw it in my bottle every time I go to the gym, which is every day. And then what about AG1? Same thing. What is it? How'd you get involved in it? What does it do for you? AG1 is effectively a slightly overkilled multivitamin that combines a whole bunch of nutrients
Starting point is 00:38:22 that you would otherwise be getting if you're eating a great diet that's well balanced. So I think of it as kind of a belt and suspenders for me because, I don't know, maybe four days a week, Stephen, I can hit the metrics and I'm eating a really great diet. And on the days I don't, I'm totally fine overdoing it a little bit and making sure I have a little bit more. So how do you think about the difference between getting these ingredients or nutrients into your body via food versus via supplement? I think it entirely depends on which supplement we're talking about and therefore it's case. case by case. For sodium, I don't think it matters if you're putting salt on your food versus consuming sodium and something else, provided you're not consuming a bunch of other junk with it. For the fruits and vegetables and the phytochemicals and things like that that that you're trying to replace, I would
Starting point is 00:39:11 say you are assuredly better off getting it in food because by definition, if you're consuming it in food, you're getting a ton of fiber and you're getting water as well. And you can't replace the fiber in a supplement at nearly the same efficacy. If we were going to talk about protein, I would say the same thing. I think you're always better off getting your protein in food, but I'm sitting here supplementing protein with a protein shake or a protein bar most days, because otherwise I'm just not going to hit my protein target. So the answer, I think, is it's usually better to achieve these things in food. And for some people, life is straightforward enough that they can always do that. My patients live in the real world. And despite their luxuries,
Starting point is 00:39:53 even most of them have a hard time day in and day out hitting their targets. And I know that if my patients have to rely on supplementation here and there, probably most people do. One of the things I always tell somebody is, you know, make sure anybody who's selling you anything has a really clear line of conflict disclosures around. You've mentioned a couple of things that I'm involved in and my patients are very clear on where my conflicts are. And we're not actually selling anything to anybody. So I was I think it's important that people understand that. You have to beware of a doctor you go to see who turns around and sells you an unlimited supply of supplements. Coming up after the break, where is the FDA heading with supplement regulation? I'm Stephen Dubner. This is Freakonomics Radio. We'll be right back. When you think about brain supplements, you're really thinking about the brain. And the brain, as much as we love it and appreciate it,
Starting point is 00:41:08 The fact is, we really don't know it all that well. It reminds me of the ocean. It's right there in front of us. We use it all the time, but there is still so much to learn. So, where do most people learn about brain function and brain supplements? When we asked Freakonomics Radio listeners where they get their information, the results were pretty much what you would expect, a wide-ranging blend of physician advice, reading, podcasts, social media, friends, and friends of friends, online.
Starting point is 00:41:40 On Instagram, there are roughly 12 million posts with the hashtag supplements. There are millions more on TikTok. For Peter Atiyah, this is frustrating. Let's be honest, our species is becoming lazier and lazier. If I sat here and gave you an hour-long dissertation on how much I could improve your brain health by exercising, and then you heard some guy talk for 30 seconds on a TikTok video about how much. how you could take this pill. Most people just want the pill.
Starting point is 00:42:11 They don't have the time, energy, or desire to kick the tires on it and realize that stuff Atio was talking about is going to make like a 50% improvement in my cognition. And what this other guy's talking about is going to do nothing, but he sounds better and it's easier. And here again is Peter Cohen,
Starting point is 00:42:29 the Sherlock Holmes of the supplement world. It does seem like the current social media environment makes it very difficult. to get accurate and useful tips and advice to stay at the forefront. But this isn't just a problem that started with TikTok. I'm sort of reminded of the evolution of the Dr. Oz show. Dr. Mehmet Oz is a cardiothoracic surgeon who now runs the Centers for Medicare and Medicaid Services. He got his start on big-time TV as a recurring guest on the Oprah Winfrey show.
Starting point is 00:43:04 I think if we were to have access to those early tapes, when Oprah, I think his advice would have been spawn on. Terrific. Increase your vegetables, get more exercise, avoid empty calories, you name it. But then something happens when you need to produce a show or more or a week and your audience is growing and growing and advertisers want more and more and more and it's hard to say every day like get some more exercise, eat some more fruits and vegetables. Do more home cooking. In 2011, the Dr. Oz show was preparing an episode about the HCG diet. HCG is short for human corionic gonadotropin, which is a hormone produced by women during pregnancy. For the diet, patients take HCG and eat only 500 calories a day. That is roughly one-fourth, the daily calories
Starting point is 00:43:55 recommended for a typical adult woman. When he did his show on that, he asked me to come as a guest, and I assumed it was going to be a show that was good about debunking this weight loss practice. And instead, I felt a bit ambushed because I remember one of these weight loss docs came out of her stretch limo with multiple patients outside the studio. And the whole show was then designed to say, hey, you know, maybe there's something there. Maybe you should give it a try. What did you say? Did you just say, well, I haven't seen any evidence that this works, and therefore we should go slow, or were you a little bit more aggressive than that? I forget what I actually said because I was so surprised by the situation.
Starting point is 00:44:39 But I might have said something like, if you starve yourself, you will lose weight. In starving yourself or a diet is not healthy. That can lead to gallstone formation and a lot of other problems. So I don't recommend this. I remember that there were two patients who had actually suffered some sort of adverse facts after they had started this HG diet. But instead of being next us on stage, they were out in the audience.
Starting point is 00:45:04 But I do remember that I chatted with them, connected with them, and commiserated with them as the show was going on. Now, what you're describing is something that I've observed for a long time. I mean, it's probably been happening since the history of humankind, which is that the bolder predictions,
Starting point is 00:45:22 positive or negative, are the ones that tend to get our attention. It could be in the realm of politics, CNN or Fox News, or MSNBC. And if I come on and say, you know, this and that about the end of the Republic or fascism, I'm going to likely be considered a good and spicy guest and I will be invited back. However, Peter Cohen comes on there and says, well, yeah, if you starve yourself, you're going to lose weight. I'm guessing you weren't invited back, at least as an advocate of
Starting point is 00:45:47 that kind of thing, correct? Correct. No one on the HG circuit that reached out to me again. The FDA has approved HCG as a prescription drug to treat female infertility and some other conditions. Companies that sell it as an over-the-counter weight loss remedy have received warning letters from the FDA and the FTC. Warning letters are one way the FDA tries to exert its regulatory reach over supplements and make them more reliable. Peter Cohen has some other ideas. There are some very thoughtful ways that we could. improve the quality of these products. If the political will was there, we could also quickly get a handle on the health claims. So the idea that's been floated around is to have an FDA registry
Starting point is 00:46:35 of legal permitted dietary supplement products. For example, if a product label came to the FDA and it contained ingredients that were not legal supplement ingredients, the FDA would simply not post it. If there were suspicious things, maybe the FDA could require additional testing, or maybe the FDA could require additional testing of all products before they posted it on their website by a high-quality third party. If there was political will, they could say, listen, we're not going to put any health claims on our website that are not supported by science, and then requiring that that's the only information that can be available on the label. If you were to do that, then consumers could make more accurate decisions about what to put in their body.
Starting point is 00:47:23 So what direction do you see the political will moving in at this moment? Yeah, just the opposite. The manufacturers are advocating for more ability to make more health claims. And somehow to figure out a way to get the FDA's name on the label so the health claim actually looks vetted by the FDA. And how does that intersect with what you know about the worldview of Bobby Kennedy Jr.? That would be very consistent with my understanding of how he's perceived supplements as if this whole world of supplements is beneficial in the whole world of pharmaceuticals is poisoning us. And that's nonsense since there's no real distinction between these two categories at all. Except a lower burden of proof in one case.
Starting point is 00:48:09 Right, exactly. But on the other hand, what I've been hearing is that supplement manufacturers particularly have been chagrined by the lack of movement. in that direction so far in the second Trump administration. Is it coming and we just haven't seen it yet? Or is it maybe not coming? Well, I think part of the problem for the manufacturers to get excited is that they have had it so good for so many years. They've basically had a situation where the FDA has not been forcing the minimal bits of the law that do exist that they could go after some particularly hazardous products or they could go after adulterated products. And the FDA says, seems to be about choosing enforcement discretion, which is their way of saying we're just
Starting point is 00:48:53 not going to enforce the law for years. Is that really the FDA's position? To find out, we called up one last physician. Marty McCarrie, Commissioner of the FDA. McCarrie has been on Freakonomics Radio a few times in the past. He was a surgical director and health policy scholar at Johns Hopkins. He's also written a few books, including Blindspot, when medicine gets it wrong and what it means for our health. Running the FDA is his first job in government. I asked him now about a proposed change to what is called the grass standard, or generally
Starting point is 00:49:31 recognized as safe, which applies to food and dietary supplements. Because remember, the FDA treats supplements as a category of food, not medicine. Yeah, we've announced that we are challenging the grass standard, which basically says food companies can put a new chemical in food if they generally recognize it as safe. And we're saying, look, guilty until proven innocent, you have to show us that something is safe if you want to add a newly engineered chemical into the U.S. food supply that children are going to eat. So the supplement market that's really exploding. And it is remarkable to me how unregulated that industry is. I wonder what your position is on that and whether you think the
Starting point is 00:50:15 FDA should be doing more. We have to look at all of it. We have to look at every aspect. Now, for example, we know that if you drink a can of soda, the caffeine can have a slight positive impact on your short-term memory. Now, are we going to crack down on a social media influencer who says, you know, I drank this caffeinated drink to help me with my memory? We have to prioritize what is safeguarding the public versus what's simply cracking down for cracking down's sake. And so we've got to look at all of it and then come up with a priority list of where to start. It turns out that the FDA's priority list is pretty long. So next time on the show, we will cover as much of that as we can.
Starting point is 00:51:09 The FDA today is not going to be an FDA in a receive-only mode. We're not going to be stingy librarians. We're going to go into the pipeline, find out what sounds promising, and bring that to the forefront. That's next time on the show, a full conversation with Commissioner McCarrie. Until then, take care of yourself. And if you can, someone else, too. And if you found this episode useful or interesting, please tell a friend about Freakonomics Radio. That is the single best way to support our show.
Starting point is 00:51:42 You could also leave a rating or review on your podcast app. and we can be reached at radio at Freakonomics.com. Freakonomics Radio is produced by Stitcher and Renbud Radio. You can find our entire archive on any podcast app, also at Freakonomics.com, where we published transcripts and show notes. This episode was produced by Alina Coleman with help from Dalvin Abouaji and edited by Gabriel Roth. It was mixed by Jasmine Klinger with help from Jeremy Johnston. We also had recording help from Bill Pollock.
Starting point is 00:52:11 Special thanks to all our listeners who shared their firsthand supplements. supplement experience. The Freakonomics Radio Network staff also includes Augusta Chapman, Eleanor Osborne, Ellen Frankman, Elsa Hernandez, Elaria Montenicourt, Teo Jacobs, and Zach Lipinski. Our theme song is Mr. Fortune by the hitchhikers and our composer is Luis Guerra. So wait a minute, you're saying the New York Times asks you for nutrition tips. You said make your own chicken stock and granola and they just cut the granola part. Nope, they cut both. They said, we want you to stick to the area that you're expertise on. What's your supplement tip? But the reason they said that was because they didn't like my granola tip.
Starting point is 00:52:57 The Freakonomics Radio Network, the hidden side of everything. Stitcher.

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