Brain Inflammation and Food: Dr. Austin Perlmutter on the Gut-Brain Connection, Brain Fog, and What to Eat for Better Cognitive Health

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0:42Gemini and Chrome is here for it. Ready to make anything online make sense? There's no place like Chrome. Check responses set up required. Compatibility and availability varies 18+. Brain inflammation has been associated with worse mental health. And in particular, what we see is that systemic inflammation correlates with a higher risk for developing depression. The microbes on your food change your microbiome, which then the gut-brain connection by way of the microbiome is a major influence on the brain's immune system. Dr. Austin Perlmutter is a board-certified internal medicine physician and New York Times bestselling author.

1:21Dr. Perlmutter is leading the charge in food as medicine innovations, including cutting edge research on how plant nutrients impact human aging through epigenetics. When I look at what is going to influence the brain's immune system, the first thing I think about is viruses definitely cause brain inflammation. What else do we see as common causes? Your brain is made out of the food that you eat. And depending on what are you saying, nutrition matters. It's a funny thing, right, because it's somehow the brain is separate from the body. OK, what's the brain made of? I guess it comes from the atoms, the elements in your food.

1:54Okay, so there is an effect there. Okay. Okay, yes, fine. So the quality of the building blocks in what you eat, and really we're talking about, I'd say, fats and proteins being the most important, are going to have an impact on how your brain functions and your brain's immune system. People here will go to talking about omega-3 fats as a good example. Omega-3 fats are disproportionately represented in the brain. The brain is if you took out the water by weight, mostly fat, And it's the highest concentration of these omega-3 fats, specifically DHA and EPA, necessary for a number of things, but they're also incredibly involved in immune regulation.

2:29And so DHA, EPA can subsequently be processed into molecules called resolving mediators, which are very active in regulating the immune system. Omega-3s regulate microglial cells within the brain. Fats and proteins, I would say, are going to have an impact on brain structure and function. Right, but I'm not going to let you move on. carbohydrates yeah yeah so carbs are a little bit different because they don't even though there is this glycome and so there's individual carbs that do play roles there i would say the more important thing for people to understand is that carbohydrates probably have the most immediate impact on systemic metabolism there's still a lot of debate as to sugar and drivers of diabetes but i think it is clear that a person consuming a diet high in dietary sugar and i want to be clear here.

3:15We're talking about a difference between sugar in your brain and sugar in your food, because your brain needs sugar to function as much as people like to say, oh, well, it's terrible for the brain. Actually, your brain is running on sugar right now. But the sugar, the carbohydrates in our diet, specifically the added sugars and specifically the added sugars in beverages. And when we say added sugars, this is not fruit. This is what's on the label that they're putting additionally into your food. Which is a great thing. You can look at the actual nutrition facts panel and see if there are added sugars in your food.

3:47Basically, nobody needs added sugars. In America, it's somewhere around 70 % of foods and beverages based on data from UNC have added sweeteners of one form or another. But the biggest villain in terms of consensus is beverages because you're basically saying how far can we get from a food in which sugar exists naturally? Yeah. And so if you start with a fruit, there's sugar in there, fine, but it's got fiber and it's bound up in a matrix. Now you say, okay, well, it's a fruit juice, you've taken away all of the things that blunt the glycemic response that helped program your brain and body to versatility, and you're basically just getting a load of sugar.

4:23So to kind of bring this back to the point, I think added sugar, particularly in the context of sugar sweetened beverages, is one of the biggest villains as it relates to systemic inflammation, mostly by way of what it does to metabolic programming. And also that transfers into high risk for brain neuroinflammatory conditions, depression, dementia, as well as a host of other issues. So I would say, as we're looking at carbohydrates, yes, your brain needs carbohydrates, it doesn't necessarily mean you have to consume them in your diet, or your body is able to synthesize glucose. And also, if you eat glucose in the form of kind of more complex carbohydrates, that's more than sufficient, there's really no need, again, with an exception of certain people with diabetes and other glycemic issues who maybe sometimes need to bring up their blood sugar due to a hypoglycemic episode to consume carbs in the more simple forms.

5:15So again, fat scrubs and proteins at a first level, they have a lot to say as to how our brain works and the brain's immune system. Next group, vitamins and minerals. So these are things that influence neurotransmission. I should also say amino acids, going back to the proteins, influence neurotransmitter synthesis. So they're very important too. But vitamins and minerals, I mean, very clearly if a person is deficient in certain vitamins, B vitamins being the best example, cognition drops off a ledge. So vitamin B1 deficiency in alcoholics, vitamin B12 deficiency in people with inadequate intake.

5:48Or pernicious anemia. Correct. Have direct and strong correlations with worsened cognition. Vitamins and minerals also modulate the immune system. And so there's a lot of nuance to this, but the basic idea is that immune cells, like any other cell in the body, necessitate certain levels of certain vitamins and minerals in order to function adequately. And when they have low levels or in some cases extremely high, but mostly low levels, they're not able to do what is necessary to keep the immune system in balance. So obviously vitamins and minerals. The other group here is everything else that's in our food.

6:23And so polyphenols, which are a group of 8 ,000 plus nutrients found in plants that are part of the plant's immune system, we're now learning have an impact on our immune system and potentially even the brain's immune system. So this is research that we just had accepted into Frontiers in Nutrition journal, looking at the fact that polyphenols influence the immune system, influence glial cells in the brain by way of epigenetic pathways. So there's a lot to unpack there. But the point being, food is packed with data that influences the brain's immune system. And that's just the starting point of what you consume from your mouth, because it turns out food also has a microbiome.

7:06And the microbes on your food change your microbiome, which then the gut-brain connection by way of the microbiome is a major influence on the brain's immune system. Polyphenols. Run us through some of the sources of polyphenols for people. Yeah. So if you haven't heard of polyphenols before, you're really just thinking about plant nutrients. So they're non-caloric. They're not vitamins, minerals, and they're not fats, carbs, and proteins. What these are, are basically the elements within plants that they use to defend against insects, to defend against UV radiation. They're also what give plant foods their colors.

7:42So you see a colorful carrot or a colorful spice. Those are the polyphenols that are doing that. And so, again, they're part of the plant's immune system. But these molecules, similar to what happens within our own GI tract, actually have an interaction with microbes in the local soil. So they're able to signal using these molecules to bring in healthy bugs, healthy bacteria, and they're able to have this interaction with the microbiome of the soil. For a long time, and maybe some circles still, these polyphenols in our diet were thought as throwaway ingredients. They didn't serve a purpose. And in the last couple of decades, what we've seen is that not only do people who eat diets rich in polyphenols do better, have lower rates of dementia, lower rates of mental health conditions, but that these molecules act on pathways, including those directly related to the immune system, to kind of translate over from the plant the signals that they were using to develop resilience.

8:36So it's kind of this interspecies transfer of knowledge from plants to us. And so where do they exist within our foods? Generally speaking, colorful fruits and vegetables are going to be rich sources of polyphenols. The highest sources of polyphenols in our diet, based on the amount we consume from individual sources are going to be coffee. I mean, for some people, maybe even red wine. But coffee is actually the top of the list because we like coffee and because it's rich in polyphenols. And because it's just awesome. Coffee is awesome. I'll go on record saying that. Yeah, well, we spent enough time in the Pacific Northwest.

9:09Yeah, it is a part of the day. It is our liquid sunshine. Don't ever touch it. It doesn't have to be caffeinated, by the way. Polyphenols are still found in decaf coffee. But the most concentrated source of polyphenols by weight of food is actually spices. So spices are incredibly rich in polyphenols. And so I think this is one of the things that many cultures historically got right. And we're not talking about salt and sugar here. We're talking about, you know, rosemary and oregano and cloves and these spices that many people maybe have kind of forgotten how to use. These are incredibly concentrated sources of these nutrients.

9:41The plant that we're researching is called Himalayan tartary buckwheat. And the reason we're researching it is because it's a plant that grew up on the tops of mountains. So it had to produce really, really high levels of these polyphenols to survive compared to common buckwheat or grains. And so it's super rich in rutin and quercetin, asperidin, luteolin, other polyphenols in case people are curious. Yeah, which we've known are great for immune system regulation. Things that we use for people who have allergies, histamine issues. And then came more of the brain research on it, which has been fascinating.

10:18Right. Exactly right. So these have been used. I mean, they've been part of many cultures for millennia. But now we're starting to isolate and say, oh, well, red wine is great because of the resveratrol in it. Or green tea is great because it has EGCG, these polyphenols that have an outsized impact on health. Many academic institutions around the world now recognizing these molecules play a role in health. but the specific pathways is where we're trying to get clearer because usually people say polyphenols are antioxidants and you want antioxidants so get polyphenols i just don't think it's super accurate i think that it's actually not the main mechanism which is why this research is so interesting because historically can we really say that taking high doses of antioxidants is all that healthy not exactly yeah high levels of vitamin e which is a powerful antioxidant not necessarily great for people and so i think there's a lot more natural wisdom that transfers through when we eat plants that are rich in these molecules.

11:16That's more of a synergistic effect than just saying, I'm getting a gram of quercetin today. It's asking, what is the context in which it exists? And why is it that the plant makes that level of that polyphenol? And why does it combine it with these other polyphenols? It does something for the plant. It kind of evolved alongside plants and fungi. So maybe there's something that is important for our health as well. And when you look at how cultures have integrated these things, they often have them in traditional dishes where they're synergistically taking effect. So I think a lot about how curcumin and that like turmeric had its day.

11:55And then, you know, people were like, just put turmeric on everything. And when you go back to how it is in Indian food, well, as it turns out, the pepper that they're using, the dairy that they're using, the fats that are there, all of these things help you actually absorb it better. Absolutely. When we look at other cultures, like looking at Persian food, Middle Eastern food, Chinese, I mean, really every culture has this integration of these herbs that are so beneficial. And I want to ask your thoughts about saffron, because that's a really interesting one. Yeah. I mean, saffron has some literature suggesting benefits to mental health, right?

12:31I think it is a good example of basically pulling out a single thing. I mean, saffron is a plant. It's a spice. It's also very expensive. But, you know, if you're getting it for cheap on Amazon, it's not saffron. It's not expensive. Yeah, I think it is of the kind of medicinal plants, maybe towards the top of the list of evidence based for mental health conditions. Alongside, you know, curcumin is having its day as well. while I think it is great kind of adjunct to, I don't think it's to say, okay, well, now we have this. And so this should replace conventional medicine. Well, when it comes to mental health, it's never, it's never just the serotonin.

13:11It's never just one thing taking place. I wish we could just be like, oh, it's just your inflammation because there's also habits that form with that. There is the community component. There's so much more. And with saffron, what I find really interesting is that some of the research shows it rivals SSRIs in terms of helping with depression. But if somebody still needs the SSRI, we know one of the biggest side effects is anorgasmia, inability to orgasm, loss of libido, and saffron's been shown to help so that if you're still on, if you still feel like the SRSRI is serving you, it's not an all or nothing kind of thing.

13:49Talking about SSRIs for a second, I think they're absolutely necessary in certain people and they kind of suck as a drug class. The side effects kind of suck. Side effect profile is miserable. Withdrawal profile, which nobody talks about, is miserable. 50 % of people having these really significant side effects when they stop taking the antidepressant, a medicine which was never studied for the duration of time where most people are taking it. And so, you know, depending on the study you look at, let's just, we'll index towards benefit. SSRIs are marginally more beneficial than placebo with all the side effects.

14:20And they are essential sometimes. And, you know, being in a scenario where you have to prescribe a medication for somebody who is acutely having mental health crisis, not that it's necessarily just an SSRI, but I mean, antipsychotics and psychoactive medications are essential. And I think coming back to what you just said, I mean, when you think about the amount of time that a person is going to be experiencing these side effects that can dramatically detract from quality of life, you have to look at the data. Now, from what I know, saffron data is much, much smaller than what we have for SSRI.

14:52Of course. Incredibly small. And who's going to fund saffron? Big saffron. Yeah. I mean, just, but if you think about saffron is expensive enough, they may have the funding. It is expensive enough. Again, if you've got a saffron guy, don't hold out on me because I don't use it too much in my cooking for that exact reason. It tastes great, by the way, as just an adjunct to it. There's a whole side topic here of the microbiome. The gut is many things. Is it everything? I'm not convinced, but it is maybe most things even. As it relates to the brain, what we know is that what happens in the gut programs neurons and it programs microglial cells.

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17:44But the point being that the data from the gut and in particular the gut microbiome programs our brains. There's another kind of interesting concept here, which is the question of whether we as humans are just vehicles for the microbes that live on us. Are we just acting on what's best for them to escape? Right. But there are a couple of conduits by which the gut microbiome influences the brain's immune system. I would say the two biggest ones to know about, one is the vagus nerve. People have probably heard about the longest cranial nerve runs from the gut to the brain. Most of the connections go from the gut to the brain, which would indicate that the majority of data is running to the brain.

18:22So it's sensory interpreting what's happening in the world. The vagus nerve has all of these little tendrils, these afferent tendrils that kind of penetrate right up to about the level of the gut order. And they receive information from the bacteria in our gut. And they're able to transmit that based on rate of firing and other signaling to the brain to influence the brain's immune system. This is kind of the idea. There's even this inflammatory reflex that the vagus nerve is involved in, which helps to quell systemic inflammation based on what the vagus nerve is up to. But the cornerstone idea here being that the brain's immune system is tasked with understanding what's happening in the outside environment.

19:04We talked about stress. We talked about food. It also has to pay attention to the microbes because the microbes are honestly one of the best signals as to what is happening in the outside world. We know the microbiome changes depending on what we eat. We know it changes depending on where we live, depending on where we were born, depending on the means in which we were birthed, all of these different variables. and there is an absolutely insane amount of data there, right, that the body is responding to. The microbiome is not good or bad. It is comprised of a host of different bacteria, archaea, fungi, protists, all of these different microbes.

19:37And that data has to be transmitted through the gut and reach the rest of the body, vagus nerve being central to that. What's also really interesting, though, is that what happens in the microbiome influences the local immune cells in the gut. Historically, we've thought about the gut owning the majority of the immune cells. Some recent research suggests otherwise bone marrow, lymphatic system. But there's still a lot of immune cells in the gut. And they change in response to the signaling from the gut microbiome. So the other kind of major conduit by which what happens in the gut microbiome influences brain immunity is the bloodstream.

20:12So the changes in the local immune system within the gut can signal to systemic immunity. and that can then reach the blood-brain barrier and through a wide variety of different signaling pathways speak to the microglial cells and program the brain's immune system for the better or for the worse. So it sounds like you've already talked about P. gingivalis and what's happening in the oral microbiome and how that influences potential risk for brain health outcomes. There is so much that we still don't understand. What we do know is that there are changes in the gut microbiome seen in neuroinflammatory conditions like Alzheimer's and depression.

20:48I don't think we're quite at the level of saying, oh, we can target specific strains of microbes. There are psychobiotics. That's what they intend to do. But I don't think it quite generalizes to the point where we can say, this will treat depression. This will treat Alzheimer's. We might get there. What we do know in the interim is that the relative makeup of the gut microbiome has an effect on the brain. And it seems like one of the principal pathways is by its effect on microbial cells and regulating brain inflammation. So this gives us an opportunity to ask the question each day as to are we setting up a microbe population that is helping or hurting us?

21:28Yeah. And I kind of think about sometimes every time you eat, you're eating for$39 trillion, right? Yeah. The bite of food that you take is not just for you. It's to feed all of these little beings, creatures, whatever you want to call them, inside you so that they care for you. Because if you don't look after them, then they tend to turn on you. And again, one of the more kind of consistent integrations here is when there is dysbiosis, when there are issues with the gut immune system, then you have an increased penetrance of LPS, lipopolysaccharide. And by dysbiosis, we're talking an imbalance in the gut flora.

22:03Right. Just exactly. Basically, you have too many bad guys, not enough good guys. And this can increase the penetrance of this molecule, lipopolysaccharide, in the bloodstream. this molecule may reach the brain and is probably the single most potent instigator of microglial activation towards inflammation. So LPS is a really interesting molecule. We mentioned it earlier in the context of depression, but where it comes from in people who are not being injected with this molecule is by passing through the gut lining. And it's really not supposed to, I mean, you can have a good amount of LPS living in your gut and be okay.

22:37It's when it gets into the bloodstream that it creates all this havoc. So that is a reflection of the relative health of the microbiome. And again, it's a vote for why what we do, which we know it's not just food, it's all of our lifestyle activities, it's drugs, it's all the things we do to keep our microbiome in a relative state of balance. I am always of the mind that the best thing you can do is the next best thing, not the perfect thing. So for some people, the next best thing they can do is cutting back on sugar sweetened beverages. The optimal day, how could you start your optimal day if everything's perfect and I want everyone listening to try to find one thing out of an optimal day that they could do.

23:16Just one thing. It doesn't have to be the optimal day. The first part of the day is obviously the waking up. This is the best opportunity you have to set a plan for a day that works. So the basics, you brush your teeth. But then I do meditate. But in terms of what I think is optimal, I think meditation, mindfulness, first thing of the day, when you can, right, carve out time where the only thing you're doing is this diagnostic intervention in your brain, where you are getting a sense as to where you are. And you're also doing one of the most important things in terms of getting your brain to a place of not equanimity, but relative peace to start the day.

23:55After that, then there's a lot of opportunity for things to go in different directions. I know people have different perspectives on the timing of coffee, right? You don't want to do it for this long and that along the other. I think if you're a person that enjoys coffee, then enjoying it in the morning is the best time. And the reason is because coffee has around a six-hour half-life. So what you don't want to do is prolong your caffeine consumption into the late afternoon. So if you're going to drink coffee, I think doing it in the morning is a wonderful time to do it. And I'm not a stickler for saying you have to wait a certain amount of time after bed.

24:26I haven't necessarily seen the research to support that. I do think getting some natural light in your eyes is a good thing for your brain. It helps keep your circadian rhythms in check. I live in the Pacific Northwest. So for half of nine months out of the year, as you know, well, that might be switched out for a light that I put near my face to get some of that bright light and some of the benefits of that. And then in terms of, you know, the big stuff that I think people care about exercise, I like to exercise in the morning. I think doing it earlier in the day is great because the other important variable for brain health is, we know that as the day goes on, then after that, you know, there's a lot of opinions on breakfast.

25:07You probably have opinions on breakfast, the right timing, should you do a 18 hour fasting window, all the other things. I think I am not convinced that prolonging the window to an absurd length is all that helpful for people. There are a number of reasons for this. One is I don't think we have data in humans that 18 hours does anything for autophagy. So that's been kind of proposed as an interesting thing. I don't think it's as strong as we think. I do think it's good to give yourself a at least 12 hour window between dinner and between eating breakfast. But I'm just not as convinced that you have to prolong it quite as long as most people say.