658. This Is Your Brain on Supplements | Freakonomics Radio

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.”) You can find the transcript and show notes for this episode on our website here: https://freakonomics.com/podcast/this-is-your-brain-on-supplements/ FOLLOW FREAKONOMICS RADIO: YouTube: https://freak.ws/3yIl6dl Apple Podcasts: https://freak.ws/3yAvQh0 Spotify: https://freak.ws/3TsdCmV ABOUT FREAKONOMICS RADIO: Discover the hidden side of everything with host Stephen J. Dubner, co-author of the Freakonomics books. Each week, Dubner speaks with Nobel laureates and provocateurs, intellectuals and entrepreneurs, and various other underachievers to uncover things you always thought you knew (but didn’t) and things you never thought you wanted to know (but do) — from the economics of sleep to the future of education, from markets for marriage to the surprising utility of wolves. ABOUT THE FREAKONOMICS RADIO NETWORK: Freakonomics began as a book, which led to a blog, a documentary film, more books, a pair of pants, and in 2010, a podcast called Freakonomics Radio. Hosted by Stephen J. Dubner, it’s one of the most popular podcasts in the world, with a reputation for storytelling that is both rigorous and entertaining. Its archive of more than 500 episodes is available, for free, on any podcast app, and the show airs weekly on NPR stations. Freakonomics Radio is now the flagship show of the Freakonomics Radio Network, which includes the podcasts No Stupid Questions, People I (Mostly) Admire, and The Economics of Everyday Things. FREAKONOMICS RADIO NETWORK PODCASTS: Freakonomics Radio: https://freakonomics.com/series/freakonomics-radio/ No Stupid Questions: https://freakonomics.com/series/nsq/ People I (Mostly) Admire: https://freakonomics.com/series/people-i-mostly-admire/ The Economics of Everyday Things: https://freakonomics.com/series/everyday-things/ Special series: https://freakonomics.com/topics/ CONNECT WITH US: [email protected] https://twitter.com/freakonomics https://www.instagram.com/freakonomics/ https://www.facebook.com/freakonomics/ https://www.tiktok.com/@freakonomicsradio https://www.linkedin.com/company/freakonomics-media Subscribe to our newsletter: http://eepurl.com/bKm0cf

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:04Stephen J. Dubner?

  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.

• 0:16Speaker 01

  Our brains are incredible, but memory can get complicated. That's why we created new Noriba Memory 3D.

• 0:23Speaker 02

  The Alpha Brain 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.

• 0:30Speaker 03

  I started noticing the clarity wasn't there that I needed, and that was frustrating. I'd seen many commercials about Prevagen, and I thought, why not give it a try?

• 0:45Stephen J. Dubner?

  Want to know why there are so many of these ads? Apparently because they work. Around 60% of US 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.

• 1:14Speaker 04

  I take a bunch of supplements in the morning, but specifically for brain health, I take krill oil, and I also take creatine powder.

• 1:23Speaker 05

  After listening to a parenting podcast, I started taking choline, which is for fetal brain development, but also adults can take it for memory.

• 1:35Speaker 06

  The one brain supplement I take is omega-3 fish oil. I take it once a day.

• 1:41Speaker 07

  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.

• 1:54Speaker 08

  My father-in-law is taking magnesium 3 and 8.

• 1:59Speaker 08

  He has Parkinson's and we're trying to retain some of his mental clarity.

• 2:06Speaker 09

  I've been taking NAC, that's short for N-acetylcysteine, off and on for several years. 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 cured my sweet tooth. It makes me feel sort of calm and less impulsive.

• 2:34Stephen J. Dubner?

  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 DSHA, which President Clinton signed in 1994. DSHA treats supplements as a type of food, not as drugs. Many of them are made from plants or other natural matter. Does this guarantee that they're safe? Well, consider that hemlock is also natural, so are ricin and 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.

• 3:19Stephen J. Dubner?

  We will start by trying to understand the brain supplement industry.

• 3:22Speaker 10

  You can imagine, in an industry that has absolutely zero oversight and regulation, it's truly the Wild West.

• 3:28Stephen J. Dubner?

  And we will look at the scientific evidence. For instance, on a scale of zero to 10, how effective are brain supplements at preventing cognitive decline? I'm really struggling between zero and one. This is your brain on supplements, and it starts now.

• 3:57Speaker 11

  This is Freakonomics Radio, the podcast that explores the hidden side of everything with your host, Stephen Dubner.

• 4:15Stephen J. Dubner?

  We're going to speak about supplements today with not one, not two, but three physicians. Let's start with Peter Attia. He wrote the bestselling book Outlive: The Science and Art of Longevity, and he makes the Peter Attia Drive podcast. He did his medical training at Stanford and Johns Hopkins, and today he runs a high-end boutique medical practice.

• 4:36Speaker 10

  We have some patients, Stephen, that come into our practice, and I kid you not, they have a supplement list of, I mean, I've seen people come in with 100 items on their list.

• 4:46Speaker 10

  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.

• 5:10Stephen J. Dubner?

  I assume you're fairly expensive, yes?

• 5:12Speaker 10

  Yes.

• 5:13Stephen J. Dubner?

  All right. Define medicine 3.0 for me.

• 5:16Speaker 10

  I would define it as a type of medicine that focuses equally on the pursuit 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.

• 5:33Stephen J. Dubner?

  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?

• 5:57Speaker 10

  It really depends on the situation. 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 their 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.

• 6:29Stephen J. Dubner?

  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 US. What do you make of that figure?

• 6:48Speaker 10

  My intuition is that the majority of that money would be just as well flushed down a toilet.

• 6:56Stephen J. Dubner?

  Because why?

• 6:57Speaker 10

  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.

• 7:08Stephen J. Dubner?

  Harmful on what dimensions and in what way? Like, is it a dosing issue? Is it a component issue of the supplements?

• 7:15Speaker 10

  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 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.

• 7:49Stephen J. Dubner?

  A recent Consumer Reports analysis of protein powders and shakes found that 2/3 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?

• 8:03Speaker 12

  There's no testing by the FDA of supplements before they arrive on store shelves.

• 8:08Stephen J. Dubner?

  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 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.

• 8:27Speaker 12

  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.

• 8:39Stephen J. Dubner?

  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 through the wringer." If it strikes you as unfair, or at least unfortunate, that a 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 moneymakers,

• 9:22Stephen J. Dubner?

  and there is a lot of money being made in supplements. Since the passage of Duchenne 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.

• 9:39Speaker 12

  It's basically completely unpredictable what you're getting.

• 9:43Stephen J. Dubner?

  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.

• 9:57Speaker 12

  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 science?

• 10:22Stephen J. Dubner?

  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 total are?

• 10:33Speaker 12

  Yeah, I mean, it's very distorted and I'm really struggling between zero and one.

• 10:40Speaker 12

  I don't know if I can do fractions, but it would be somewhere in there.

• 10:47Stephen J. Dubner?

  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 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.

• 11:27Stephen J. Dubner?

  But if you have a good copywriter or a good AI and a good lawyer to approve the copy, the English language can be quite pliable.

• 11:38Speaker 12

  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, you know, 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, could promote our product as if it, you know, maintains a healthy memory or preserves healthy memory or memory boosting.

• 12:06Speaker 12

  All these are legal claims, even if your product has never been studied in humans at all.

• 12:14Stephen J. Dubner?

  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 Duchamp, that the first doesn't have to really have any data. What about for the pharmaceutical version?

• 12:35Speaker 12

  Yeah, the pharmaceutical is completely 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 claims that they had originally got approval for. And beyond that, they couldn't comment on the use of their drug.

• 13:10Stephen J. Dubner?

  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, and 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 function and so on. There's not much inspection. There's

• 13:54Stephen J. Dubner?

  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?

• 14:17Speaker 12

  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 controlled trials and then having proprietary control over it and being able to have the stamp of approval with FDA as a 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

• 14:56Speaker 12

  and start selling it online as a dietary supplement.

• 15:03Stephen J. Dubner?

  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 US Department of Defense runs a program called Operation Supplement Safety. Turns out that military members take more supplements than civilians. And Examine.com, a subscription website, publishes up-to-date 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.

• 15:40Speaker 12

  We have thousands of patients who end up in emergency departments due to adverse effects of supplements every year in the States.

• 15:47Stephen J. Dubner?

  Who keeps the records on that?

• 15:49Speaker 12

  Well, it was recently shut down. 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.

• 16:23Stephen J. Dubner?

  I'm looking at the data now. It says that an estimated 23,000 emergency department visits annually in the US from dietary supplement adverse effects. I feel bad for those 23,000 people, but that's relatively tiny, yeah?

• 16:36Speaker 12

  Yeah, compared to the number of people who are being misled about the claims in dietary supplements, absolutely.

• 16:41Stephen J. Dubner?

  I mean, how would that compare to alcohol overuse in ERs?

• 16:46Speaker 12

  Yes, the difference is that tobacco, alcohol, gun violence, 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.

• 17:18Stephen J. Dubner?

  So, hearing Peter Cohen talk about the problems with supplements, you might think that he is anti-supplement, but you'd be wrong.

• 17:27Speaker 12

  I couldn't practice good medicine without them.

• 17:29Stephen J. Dubner?

  Cohen, remember, is also a primary care physician.

• 17:33Speaker 12

  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.

• 17:45Stephen J. Dubner?

  Just name your top, whatever, five or 10 vitamins and minerals that you prescribe.

• 17:49Speaker 12

  Multivitamin, vitamin D, calcium, that's often combined with vitamin D, iron, screen, that's one of my favorites.

• 17:59Stephen J. Dubner?

  Indeed, for some people with vitamin deficiencies, supplements can be critical. Here is one of our listeners, Danielle Douglas.

• 18:07Speaker 13

  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 during a COVID pandemic, homeschooled three children, and worked out like a triathlete to cope with all of 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, I was able to get my brain back to functioning at optimum levels.

• 18:50Stephen J. Dubner?

  A lot of the listeners we heard from say they're using creatine to boost their brain power. Here's Peter Cohen.

• 18:57Speaker 12

  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 creatine can slightly improve one's ability to recover in between sets. Now, while that is well established, creatine is often marketed as if it'll have some sort of cognitive benefits, and there's no robust data whatsoever to support that claim.

• 19:27Stephen J. Dubner?

  Has anyone tried that you know of?

• 19:29Speaker 12

  With creatine, 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 creatine, even the very small studies are not suggestive enough.

• 19:42Stephen J. Dubner?

  Okay, what about choline?

• 19:44Speaker 12

  Choline makes a little more sense because it's a precursor of acetylcholine, and that's something that gets low in Alzheimer's disease. 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 choline, I know of no studies that have demonstrated at all that giving choline will improve memory or function.

• 20:14Stephen J. Dubner?

  How about ginkgo? And I'd love you to get into the ginkgo evaluation of memory study, if you could.

• 20:21Speaker 12

  Ginkgo biloba has been carefully investigated because it was probably the leading botanical supplement that was thought to potentially have cognitive benefits or prevent memory loss.

• 20:33Stephen J. Dubner?

  And this idea goes back probably thousands of years, right?

• 20:36Speaker 12

  Absolutely.

• 20:36Stephen J. Dubner?

  Chinese and others have been using it?

• 20:39Speaker 12

  So a lot of NIH funds has been spent on trying to understand, you know, can ginkgo biloba preserve or improve memory? And the studies are negative, basically. There's no difference between ginkgo biloba and placebo. The nice thing for a supplement manufacturer, though, is that you can take a study like that, that definitively has shown that ginkgo biloba does not prevent memory loss.

• 21:07Speaker 12

  And completely ignore it when it comes to your label. So then you can just put ginkgo biloba 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.

• 21:42Stephen J. Dubner?

  What about omega threes?

• 21:44Speaker 12

  Yeah, so with omega three, what's very interesting is that in cohort studies, so groups of people who have diets that are very rich in omega three, a lot of fatty fish and other omega three foods, there's a lower incidence of Alzheimer's disease in those populations. So it's a natural thought, but in this situation with omega three, it has been studied, I believe, up to five years in duration, and no benefit of omega three supplementation to improve cognitive function.

• 22:16Stephen J. Dubner?

  What does that say about the difference between ingesting an ingredient that's naturally occurring in a food versus a supplement version?

• 22:23Speaker 12

  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 three content, there's a lot of other things going on, exciting things when it comes to herring.

• 22:41Stephen J. Dubner?

  Talk about that. Is it about the cell structure? Is it about the other components? What are the exciting things in herring?

• 22:46Speaker 12

  You know, I'm not a herring analytical chemist expert, but I would assume that if we took a deep dive into the chemistry of herring, we would find thousands of different compounds. Some of those would be 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? 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.

• 23:22Stephen J. Dubner?

  But you're a herring fan from a nutritional perspective?

• 23:25Speaker 12

  Oh, yeah, definitely. I think the more fish we can get in our diet, the better.

• 23:29Stephen J. Dubner?

  Can you talk for just a minute about the relationship between modern supplement taking, especially botanicals and things like that, 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?

• 23:47Speaker 12

  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?

• 24:02Speaker 12

  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 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 monoclon K.

• 24:46Speaker 12

  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, and used as pharmaceutical drugs. So there's no real distinction between these. But I would say that unless you're standardizing the production of something, you really can't understand its long-term health effects.

• 25:27Stephen J. Dubner?

  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, and remember, the placebo effect is powerful. 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.

• 26:11Stephen J. Dubner?

  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 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.

• 26:56Stephen J. Dubner?

  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. We'll be right back.

• 27:39Stephen J. Dubner?

  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 Attia is also skeptical and he too makes room for exceptions.

• 27:54Speaker 10

  There are a handful of supplements that I take and by extension, there are a handful of supplements that many of our patients take.

• 28:00Stephen J. Dubner?

  Name them.

• 28:01Speaker 10

  I think for most people magnesium is a really logical choice. There are different forms that you can take magnesium in. 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 transfer 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. 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

• 28:43Speaker 10

  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. 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

• 29:24Speaker 10

  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. Not a fan of it 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

• 30:09Speaker 10

  phosphatidylserine. Phosphatidylserine suppresses cortisol output from the adrenal glands and also is just a fantastic tool when you're trying to go to bed.

• 30:20Stephen J. Dubner?

  When you describe cognitive advantages to some of these supplements, how would you assess the evidence for those advantages compared to the evidence of some pharmaceutical, maybe it's a GLP-1 agonist that we hear a lot about these days? How does one body of evidence compare to the next?

• 30:37Speaker 10

  Oh, it's not even close, Stephen. The advantage that we would have when assessing the benefits of a GLP-1 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 question is not, does a person who is obese, overweight, or have

• 31:19Speaker 10

  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 multi-billion 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 GRO protective agents, right? Something that is Actually targeting some of the fundamental metrics of aging and not doing it circuitously through weight loss or insulin sensitivity, all of which are important, but they're very distinct questions.

• 32:03Stephen J. Dubner?

  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-1s?

• 32:12Speaker 10

  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, uh, 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 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.

• 32:53Stephen J. Dubner?

  So if you were to think about comparing what is known on the market today as brain supplements, or supplements that offer 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?

• 33:16Speaker 10

  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, but in podcast land, we're really talking about biohacking. And those people are talking about everything from lion's mane 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.

• 33:58Speaker 10

  I think that there's potentially a signal there on the GLP-1 side. My intuition, though, is it is not a cognitive enhancer. It is something that prevents decline in the susceptible individual.

• 34:10Stephen J. Dubner?

  So when we think about brain function and especially brain supplements, it seems to be mostly older people who are concerned about improving or stopping the loss of memory or maybe forestalling Alzheimer's and things like that. But as you're now 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?

• 34:46Speaker 10

  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 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,

• 35:28Speaker 10

  these are decreasing by decade and so too is my cognitive performance. So then the question becomes, what can I do to offset 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,

• 36:09Speaker 10

  but you adhered to maximizing your participation on those domains, you would be incredible.

• 36:17Stephen J. Dubner?

  So you said that a lot of the spending on supplements is equivalent to flushing the money down the toilet. You, however, are an investor in a couple of companies that make supplements, yes?

• 36:26Speaker 10

  Yes.

• 36:26Stephen J. Dubner?

  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?

• 36:42Speaker 10

  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 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 is 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.

• 37:24Speaker 10

  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 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.

• 38:03Stephen J. Dubner?

  Yeah. So why not do that?

• 38:05Speaker 10

  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.

• 38:12Stephen J. Dubner?

  And then what about AG1? Same thing? What is it? How'd you get involved in it? And what does it do for you?

• 38:16Speaker 10

  AG1 is effectively a slightly overkilled multivitamin that combines a whole bunch of nutrients 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.

• 38:43Stephen J. Dubner?

  So how do you think about the difference between getting these ingredients or nutrients into your body via food versus via supplement?

• 38:52Speaker 10

  I think it entirely depends on which supplement we're talking about, and therefore it's case by case. For sodium, I don't think it matters if you're putting salt on your food versus consuming sodium in 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 you're trying to replace, I would 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

• 39:34Speaker 10

  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, 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

• 40:15Speaker 10

  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 always think it's important that people understand that, that you have to beware of a doctor you go to see who turns around and sells you an unlimited supply of supplements.

• 40:35Stephen J. Dubner?

  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.

• 40:59Stephen J. Dubner?

  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, 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, on and on.

• 41:41Stephen J. Dubner?

  On Instagram, there are roughly 12 million posts with the hashtag supplements. There are millions more on TikTok. For Peter Attia, this is frustrating.

• 41:51Speaker 10

  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 you could take this pill, most people just want the pill. They don't have the time, energy, or desire to kick the tires on it and realize that stuff Attia 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.

• 42:27Stephen J. Dubner?

  And here again is Peter Cohen, the Sherlock Holmes of the supplement world.

• 42:32Speaker 12

  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.

• 42:52Stephen J. Dubner?

  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.

• 43:04Speaker 12

  I think if we were to have access to those early tapes on Oprah, I think his advice would have been spot 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 a week and your audience is growing and growing and advertisers want more and 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.

• 43:34Stephen J. Dubner?

  In 2011, The Dr. Oz Show was preparing an episode about the HCG diet. HCG is short for human chorionic 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 recommended for a typical adult woman.

• 43:58Speaker 12

  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 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.

• 44:25Stephen J. Dubner?

  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?

• 44:33Speaker 12

  I forget what I actually said because I was so surprised by the situation. But I might have said something like, if you starve yourself, you will lose weight. And starving yourself for a diet is not healthy. That can lead to gallstone formation, 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 effects after they had started this HCG diet. But instead of being next to us on stage, they were out in the audience. But I do remember that I chatted with them, connected with them and commiserated with them as the show was going on.

• 45:10Stephen J. Dubner?

  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, 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 that kind of thing, correct?

• 45:49Speaker 12

  Correct. No one on the HCG circuit reached out to me again.

• 45:53Stephen J. Dubner?

  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.

• 46:19Speaker 12

  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 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

• 47:01Speaker 12

  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.

• 47:23Stephen J. Dubner?

  So what direction do you see the political will moving in at this moment?

• 47:28Speaker 12

  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 name actually looks vetted by the FDA.

• 47:43Stephen J. Dubner?

  And how does that intersect with what you know about the worldview of Bobby Kennedy Jr.?

• 47:48Speaker 12

  That would be very consistent with my understanding of how he's, you know, perceived supplements as if this whole world of supplements is beneficial and the whole world of pharmaceuticals is poisoning us. And that's nonsense since there's no real distinction between these two categories at all.

• 48:07Stephen J. Dubner?

  Except a lower burden of proof in one case.

• 48:09Speaker 12

  Right, exactly.

• 48:10Stephen J. Dubner?

  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?

• 48:25Speaker 12

  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 enforcing the minimal bits of the law that do exist that they could go after some particularly hazardous products or they go after adulterated products. And the FDA seems to be about choosing enforcement discretion, which is their way of saying we're just not going to enforce the law for years.

• 48:58Stephen J. Dubner?

  Is that really the FDA's position? To find out, we called up one last physician.

• 49:05Speaker 14

  Marty McCary, Commissioner of the FDA.

• 49:08Stephen J. Dubner?

  McCary 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 Blind Spots: 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 recognized as safe, which applies to food and dietary supplements. Because remember, the FDA treats supplements as a category of food, not medicine.

• 49:41Speaker 14

  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 US food supply that children are going to eat.

• 50:05Stephen J. Dubner?

  So the supplement market, it'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 FDA should be doing more.

• 50:17Speaker 14

  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.

• 51:00Stephen J. Dubner?

  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.

• 51:09Speaker 14

  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.

• 51:24Stephen J. Dubner?

  That's next time on the show, a full conversation with Commissioner McCary. 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. You can also leave a rating or review on your podcast app. And we can be reached at [email protected]. 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 publish transcripts and show notes. This episode was produced by Alina Coleman, with help from Dalvin Abawaji, and edited by Gabriel Roth. It was mixed by Jasmine Klinger, with help from Jeremy Johnston.

• 52:09Stephen J. Dubner?

  We also had recording help from Bill Pollak. Special thanks to all our listeners who shared their firsthand supplement experience. The Freakonomics Radio Network staff also includes Augusta Chapman, Eleanor Osborne, Ellen Frankman, Elsa Hernandez, Alaria Montenacort, Teo Jacobs, and Zach Lipinski. Our theme song is "Mr. Fortune" by The Hitchhikers, and our composer is Luis Guerra.

• 52:34Stephen J. Dubner?

  So wait a minute, you're saying The New York Times asked you for nutrition tips. You said make your own chicken stock and granola, and they just cut the granola part?

• 52:41Speaker 12

  Nope, they cut both. They said, "We want you to stick to the area that your expertise is in. What's your supplement tip?"

• 52:49Speaker 12

  But the reason they said that was because they didn't like my granola tip.

• 52:57Speaker 11

  The Freakonomics Radio Network, the hidden side of everything.

• 53:05Speaker 13

  Stitcher.