Full Transcript 0:00 The foods that we consume are determining the expression of our life code. 0:04 In 1978 a study by Graham showing that there was a halving of the risk of colorectal cancer associated with about two servings a day of cruciferous vegetables. 0:15 The diet that we're eating these days is not keeping up with our environmental stressors. 0:18 We are facing an unprecedented rise in various neurodegenerative conditions like Alzheimer's, like Parkinson's. 0:24 If you live near a place where paraquat is sprayed, your risk for Parkinson developing it may be as high as 60% increased. 0:38 Hey everyone, welcome back to The Empowering Neurologist. 0:41 I'm Dr. 0:41 David Perlmutter. 0:42 This program today is gonna deal with our ability to defend the brain against the threats imposed across the lifespan. 0:49 My guest is Dr Jed Fahey, a world recognized scientist, and he's best known for his pioneering research in the area of what we're going to explore deeply today, 0:59 which is called sulforaphane. 1:01 And this is a bioactive compound that is found in, for example, broccoli sprouts. 1:06 It's why broccoli spouts are so good for us in a time when we are facing an unprecedented rise in various neurodegenerative conditions like Alzheimer's, 1:15 like Parkinson's. 1:16 And when still lack truly meaningful disease modifying therapies and sulforaphane is a powerful and remarkable example of how a simple dietary compound 1:29 from nature can act as a biological switch. 1:32 And turning on what you need to remember, this nRF2 pathway activates more than 100 genes that help defend our bodies against things like oxidative stress, 1:43 environmental toxins and even chronic inflammation. 1:46 And then when you grasp that, you really gain agency over your body's future and certainly your brain's futures. 1:53 So I'm very excited about our interview today with Dr. 1:56 Jed Fahey. 1:57 Let's jump right in. 1:58 Well, Dr. 1:59 Jed Fahey, I want to tell you at the outset here that it's a real honor to have you here on The Empowering Neurologist. 2:06 And really, the information I think you're going to share with us is going be exactly that, empowering and related to the brain, 2:14 especially vis-a-vis much of your recent work. 2:17 But let's first go back and here you are studying bioactive materials coming from plants. 2:24 Why sulforaphane? 2:26 What was it about sulforaphane that jumped out at you as being so valuable? 2:31 Yeah. 2:31 I started out my professional life actually wanting to be a classical musician, but I went to college and then got a master's degree in botany and specifically 2:42 studied algal metabolites, microalgal products. 2:49 which we nowadays call phytochemicals. 2:52 And then I moved on and worked in the biotech industry for a number of years and everything was related to crop yield. 3:01 When you talk about crop yields, you're talking about components and outputs that include the macronutrients that we as humans and nutritionists and so 3:10 on are familiar with, and vitamins and minerals, right? 3:14 But not phytochemicals, And in fact, plant breeders, other than the fact that they bred for disease resistance and inadvertently bred certain phytochemical content, 3:28 They didn't know nothing about phytochemicals. 3:32 Then I went to Johns Hopkins in 1993, immediately realized I needed to get a doctorate to have any credibility and did so in nutritional biochemistry. 3:45 During that process, realized that the neglected part of nutrition was the so-called phytonutrients. 3:55 And these were dubbed somewhere, I don't know, 10 or 15 years ago by someone older and wiser than me as the dark matter of Nutrition. 4:05 actually talking about right now that there's so much beyond the micron macronutrients that we are just really beginning to understand. 4:14 Yeah. 4:14 I mean, I think that moniker of the dark matter of nutrition is so fitting. 4:20 Back in the early 90s when I sort of entered this intersection of plant biology and human biology, there were thought to be, 4:31 by knowledgeable phytochemists, about 50,000 phytochemicals in the world of edible plants. 4:37 Now, the estimate's up to about five million. 4:40 And a lot of that's based on work that a company, which I advise out on the West Coast, has done. 4:50 So there are so many phyrochemicals. 4:53 What we know, what I know and what many of us in this space know I would say it's not universally accepted though, is that the vitamins and minerals and macronutrients, 5:06 you know, proteins, carbs, fats, fiber, they can affect lifespan. 5:10 Sure, we got that. 5:12 But phytochemicals can and do profoundly affect healthspan. 5:17 And I'm sure you've used the word health span in your last 10 or 15 years of dialogue, probably not before that. 5:29 It's come into the vernacular fairly recently. 5:32 I went to Johns Hopkins in 1993 to a pharmacology department, and my mentor, Paul Talalay, had just discovered sulfurophane, 5:42 this compound sulfurphane in broccoli, and its potency as an inducer of what at the time were called phase two enzymes. 5:53 I now prefer to call them detoxification and antioxidant enzymes, many of them are linked to this so-called the nRF2 pathway or nrf2 path. 6:04 We can talk about that later, but Sulphuraphane found in broccoli in very small quantities. 6:11 Paul brought me in thinking I knew something about botany and therefore could help him find broccoli that had higher levels of sulforaphene. 6:20 What I did discover was that there's a huge range of Sulforophane content in Broccolis of Commerce. 6:28 But then because this was in Baltimore, Maryland and you don't grow broccoli outside year round or even in a greenhouse, 6:37 I then discovered that broccoli sprouts were a far more potent source of sulforaphane. 6:43 And again, we can talk about this down the line a little bit, but it turns out that sulforaphane is not what is contained in abundance in broccoli or broccoli sprouts. 6:55 It's its precursor, which is called glucoraphanin. 6:59 And depending on how nerdy you want us to get, how into the details, we can talk about that conversion because it is important. 7:08 But it does turn out that sulforaphane to this day is the most potent inducer of this suite of detoxication enzymes and we refer to as the Nrf2 pathway. 7:24 known to us. 7:25 Sure, there are more potent synthetics, but they all come with their own baggage. 7:30 So, in fact, they are. 7:32 You know, Tecfidera is a drug that was developed for the treatment of multiple sclerosis and targets the nRF2 pathway. 7:42 It's not like pharmaceutical concerns are not aware of this pathway and in, fact have developed here a patentable drug. 7:49 patented drug available to reduce inflammation to, reduce oxidative damage, to help with detoxification and all of the things that Mother Nature is providing 7:59 us through this sulforaphane. 8:01 And I think your point is well taken that people might mistakenly say that, oh, I eat broccoli and broccoli sprouts because they're high in sulphoraphene. 8:10 That the reality is, well, they really not. 8:12 They're higher in the precursor glucoraphanin. 8:15 then when we macerate or chew, or you put it in a blender, whatever you do, the interaction of this enzyme, myrosinase, converts then the glucoraphanin, 8:25 then you get the availability of the sulforaphane. 8:28 So there seems to be kind of a, I'm gonna clarify this on the front end, because then we'll unpack sulforphane a little bit more, 8:35 that people seem to think, at least in conversation, oh, well that's why cruciferous vegetables are good for us. 8:41 But I think you've made it clear over the years that This is really pretty much confined to broccoli and broccoli sprouts that across the spectrum of cruciferous vegetables, 8:53 while they may be good for us for other reasons, there really isn't a lot of sulforaphane in that discussion. 8:58 So crucifers vegetables by and large I would say are extremely useful from a detoxification perspective as foods. 9:08 It turns out that all cruciferous vegetables have isothiocyanates. 9:13 That's the broad class in which sulforaphane exists. 9:18 It's a class of about 130 naturally occurring compounds. 9:23 But it turns that sulforephane is the best of them in these chemoprotective attributes. 9:32 And there's shades of gray in that because it's the best in most assays that have been run. 9:38 However, if you look at sulforaphane and, for example, the isothiocyanate from moringa, a tropical vegetable which I'm quite interested in, 9:46 and put them head to head in various contests. 9:50 In some cases, the moringa is more potent. 9:55 For example, it's just as potent in inhibiting helicobacter pylori, causative agent of ulcers and also some stomach cancers. 10:11 And then there are other isothiocyanates like phenyl ethyl iso-thiacinate from watercress and benzyl Isothio-cyanate and allyl Iso thio cyanate From mustard seed, 10:21 you know, and of these have potencies. 10:24 Some of them may actually be better than others in certain biomedical activities. 10:33 For example, allyl and benzyl isothiocyanate may actually be better inducers or better protectors against bladder cancer. 10:44 Are you seeing an image? 10:47 I sure am. 10:49 You know what we're looking at here. 10:51 I do. 10:53 Yeah, and you just teed that one up perfectly for me. 10:55 So tell everybody, because we are going to focus on cellophane and broccoli, of course, but look at the tree in my backyard. 11:02 That's our Moringa tree. 11:04 Wow. 11:06 This is a treasure of a plant. 11:11 Unfortunately, it only grows in, you know, down around Homestead and the most southern reaches of Florida and Southern California. 11:21 It's a tropical plant. 11:22 it doesn't withstand winters in the temperate climates. 11:27 Moringa is actually not a cruciferous vegetable. 11:31 This is one of the very few other plant groups, plant families that contain isothiocyanates and that have edible representatives. 11:41 And I love it because it is a potent, its isothiocyanate acts very similarly to sulforaphane. 11:50 It grows like a weed, as I'm sure you can attest to. 11:54 We cut it back and it goes even more so, crazy. 11:58 As bad as bamboo if you don't like it, right? 12:00 And if do like, you've got a forest in a few years. 12:05 I think I've read, in fact, I have seen in Ghana, it puts on between 10 and 20 feet in a year, or can put on 10 to 20. So anyway, 12:22 jumping ahead of ourselves here, but in the US, and a temperate climate in Europe, our food does not include moringa. 12:32 Our food choices typically don't. 12:34 And it's because of availability of plants that are grown in this region. 12:39 Moringa doesn't grow here. 12:41 It's very difficult to import fresh moringa from the tropics because the leaves don't last long. 12:49 They get moldy very quickly, although you can dry it and then import it. 12:56 And I actually consult for a company that does that, also out in California. 13:03 But in terms of fresh veg, moringa doesn't really cut it in this country. 13:08 However, assume that some of your clinical trials actually work and show what you're hoping they show with broccoli sprouts or with moringa. 13:18 Well then, having moringo as a viable alternative to broccoli, to sulforaphane, opens up a whole world of possibilities in underserved areas in the tropics. 13:32 Moringa grows like a weed as you've just attested to because you have to whack it back every year. 13:38 Yeah, and I think you you stated in the past that you think one of the best applications of moringa from a supplement perspective or even as a food perspective 13:49 is in area of metabolic health and specifically as it might relate to diabetes or perhaps the consequences of that metabolic issues related to Diabetes. 14:00 Yes, yes. 14:01 And that's, unfortunately, whereas, you know, we can get into some detail on sulforaphane and broccoli and the work that has been done clinically with it, 14:11 there's been very little well documented clinical work on moringa, a lot of animal models, some cell culture work. 14:23 One of the things I was struck with, and I've said this a number of times before, but at the first or second or something International Moringa Congress 14:32 in Ghana, in Accra, probably was that, 10 or 15 years ago? 14:41 Anyway, I was there and spoke with physician after physician who in a very underserved setting had a lot of patients with diabetes. 14:58 And some of them actually had been on metformin and then couldn't afford that anymore. 15:04 Many of these doctors had heard from traditional medicine and so on that moringa was helpful for use in people controlling blood sugar. 15:15 And they tried it and they gave their prescribed fresh moringa to their subjects. 15:19 And many of them had remarkable recoveries. 15:24 A number of these were Western-trained doctors that went back to the country of origin, their African country-of-origin that I spoke to, 15:33 and it was quite impressive. 15:35 And I remembered that quite vividly since then. 15:39 So it turns out that, yes, in vitro and in animal models, moringa is quite effective, as is sulforaphane. 15:45 What we have done, I've been involved with a number clinical trials on diabetes with sul foraphene and broccoli sprout extracts. 15:53 So a disclaimer I think would be appropriate here that, you know, we're not saying to any of our viewers, throw away your anti-diabetic medications and 16:04 start taking Moringa. 16:05 Obviously you need to talk about these things with your healthcare provider. 16:09 But on the other hand, your work has shown that Meringa has some pretty potent in vitro effects as it relates to regulating things like metabolism inflammation 16:22 and therefore should be the subject of further research. 16:25 We can certainly leave it at that. 16:27 But let's go back to, and we can go to it too. 16:31 Let's get back sulfurophane though. 16:32 And more recently, I think, you've done some, discussed and participated in some really groundbreaking work that relates, 16:43 so forth, to an area you talked about earlier, which is detoxification by augmenting various detoxication pathways. 16:50 We call them phase two. 16:52 Parts of the phase one, phase 2 detoxing pathways, that part that deals with the water solubilization so we can excrete these. 17:00 toxins and shown and at least described work that indicates that having sulforaphene on board in our very toxic world might be a good plan now that we 17:14 are more and more exposed to things like pesticides, herbicides, perhaps even PM2.5 particles, Let's first talk about this in the context of the research 17:27 done in China as it relates to air pollution and what was found in that research dealing with excretion of certainly toxic entities like benzene in those 17:40 who are given sulforaphane. 17:41 It was a series of studies that we did in China. 17:44 My very recently deceased colleague, Tom Kensler, led these and we found that giving sulforaphane increased the excretion of metabolites of benzene and 18:02 acrolein And to a much lesser extent, crotonaldehyde. 18:04 These are common constituents of the air pollution that was rampant there. 18:10 This was a trial done outside of Shanghai in the Shanghai region. 18:16 And we could see a correlation, in fact, between the amount of excretion of these metabolites and the monitored measured air-pollution in that region at 18:28 that time. 18:29 And this was related to sulforaphane dose. 18:32 We've shown that there's a dose efficacy relationship. 18:37 That kind of thing had been demonstrated in animal models. 18:40 But this is really the first demonstration that in human beings that are exposed to environmental toxins, i.e. 18:49 air pollution, we could see a reduction potentially in risk. 18:58 Well, I should say a reduction in risk. 18:59 I mean, this set of studies that Tom Kensler inaugurated in the 1990s actually first focused on liver cancer. 19:10 And they were looking at aflatoxin, which is a potent liver carcinogen, and the levels of aflotoxin B1 work through the roof extraordinarily high in this 19:21 agricultural region north of Shanghai. 19:25 Over time, and sort of as I came into this study team, the levels of aflatoxin started getting reduced dramatically because of the globalization of trade 19:37 and this heavily infested corn and peanuts that were grown in this region of China. 19:43 wound up being distributed throughout the trading network in China and they brought in other food sources. 19:50 So, whereas this had been really a subsistence crop initially, it sort of got diluted out. 19:57 Of course, at the same time, awareness of the extraordinary amounts of air pollution was gaining on our consciousness and we started looking at them as 20:08 a sort ancillary outcome and then we ended up focusing on them over time. 20:13 Hey guys, we're going to get right back to the podcast, but I do have a very important message for you. 20:18 I think many of you will recall a conversation I had here on the Podcast with Dr. 20:22 Michael Leone. 20:23 He is a University of California Irvine neuroscientist and what he studied and we talked about on The Podcast is what is called olfaction, 20:31 our sense of smell and how Things that stimulate our sense of smell are directly wired into the brain's hippocampus and amygdala, 20:38 and these are the same circuits that govern things like memory and emotion. 20:42 You know, most of our sensory inputs get routed through a bunch of relay stations, but our senses smell actually doesn't. 20:49 line in through the centers that I just described. 20:52 And Dr. 20:53 Leon's work takes full advantage of that pathway and enriches this olfactory pathway with a variety of scents presented to you during your sleep. 21:02 That's when your brain is already doing its nightly work of clearing out the metabolic debris, things like beta amyloid and other accumulated misfolded 21:11 proteins Dr. 21:12 Leon has done some wonderful clinical research on the idea of stimulating the brain with a variety of different scents during the course of the night. 21:20 And he has demonstrated that using this approach in some of his research has shown as much as a 226 percentage increase in memory function and 22 minutes 21:32 in addition of sleep with his results published across healthy adults, older adults. 21:38 And yes, even people who are suffering from what is called mild cognitive impairment, MCI, what we consider to be the harbinger for further brain decline. 21:47 So he and his research team have built a device around this research and that device is call memory air. 21:54 It isn't a pill. 21:55 It's not a supplement. 21:56 You put it on your nightstand and it does its work while basically you're sleeping at night. 22:00 Their website is memoryair.com. 22:03 I've been working now with memory air and have developed a relationship such that you can get a 15% reduction in cost of your memory or device. 22:12 Should you choose to buy one, you use the code pearl mutter, and this is also going to get you free shipping and a 60 day money back guarantee. 22:20 These statements have not been evaluated by the Food and Drug Administration, and this product is not intended to diagnose, 22:27 treat, or cure or prevent any disease. 22:29 Let's get right back to our podcast. 22:32 We had on the podcast, actually twice, but quite recently, Dr. 22:36 Ray Dorsey, a neurologist, And he has been very vocal about information relating environmental exposure to Parkinson's risk. 22:47 He's looked at something called trichloroethylene, which is used industrially as a cleaner and also in dry cleaning. 22:54 But more recently, there's been a lot of discussion about paraquat exposure. 23:00 and the fact that if you live near a place where Paraquat is sprayed and that your risk for Parkinson's developing it may be as high as 60% increased. 23:11 That said, here in America, because of Roundup resistance, there's really been an explosion of the usage of ParaQuat as an herbicide. 23:20 And I think some of literature, I perhaps that you've even published, has shown that sulforaphane may actually be quite protective as it relates to Paraquat 23:32 exposure in terms of allowing a higher level of excretion. 23:35 Yes, indeed. 23:36 And although I've not worked directly with ParaQuat, I cited it in a review paper we just published this year. 23:45 Certainly, you hit the nail on the head. 23:48 The increase in Parkinson's disease diagnoses and the appearance of Paraquat in our food and our foods sources are parallel. 24:00 Animal models very clearly show that ParaQuat, Tributyltin, Rotenone, and a number of other pesticides can be targeted by sulforaphane for detoxification. 24:15 A lot of these detoxication pathways are, as we mentioned earlier, involve the NRF2 pathway, induction of protective enzymes, 24:25 and when you detoxify a lot these compounds, you conjugate them and render them more readily excreted urine and flush from the body. 24:36 So this is a really important I mean, obviously, detoxication has been important forever in human evolution, but so much more so nowadays when we throw 24:53 tens or hundreds of thousands of synthetic compounds that the body's never seen into the mix. 24:59 I mean, I won't even bring up PFAS, the forever chemicals. 25:03 I want to go back to the beginning and talk about why the plants produce something like sulforaphane. 25:11 And I love the story, and I hope you can tell us a story about how, you know, when an insect is eating the leaf or whatever, 25:20 let's talk why even the plant makes this chemical compound. 25:25 How does that translate to being helpful for us? 25:27 The whole story is quite magnificent. 25:30 Well, the link to how it becomes useful to us is less clear. 25:34 We surmise a lot, but the broader story, is why do plants produce phytochemicals at all? 25:42 What are these things all about? 25:44 It takes a lots of energy, and there's some bizarre structures that the plants create. 25:49 So you have to remember that, first of all, a plant sits still, by and large, in the ground and can be attacked by whatever wants to eat it, 25:59 bugs, animals, and microorganisms. 26:06 So when we look at plants, what do we see? 26:08 We see a wonderful array of different colors. 26:11 This is a botanist speaking, of course. 26:12 I get excited about them, but different color, different shapes, And just those two things, the odors and the colors, those are all controlled by phytochemicals, 26:25 by a huge array of them. 26:27 So those were two of the main functions of phytochemicals. 26:31 Different colors and different shapes attract pollinators, perhaps repel some of orchids, mimic wasps or bees. 26:40 different shapes repel certain predators. 26:42 In terms of the smells, we can only imagine, as human beings, that we don't have very good sniffers compared to most animals. 26:52 But then also, these compounds are involved in really strict defense of a plant, so that when a predator eats a leaf, it backs away, 27:04 it goes to another plant, goes another species. 27:07 And that's where I think this glucosinolate converted to sulforaphane pathway comes in to anisothiocyanate. 27:17 So envision a beetle, a cabbage looper or some specific beetle that eats a specific cruciferous plant. 27:26 lands on the leaf, takes a bite, glucosinolates or glucoraphanin, which is present in the leave, is benign. 27:34 It has little or no taste and it doesn't seem to bother most insects or bacteria. 27:41 But as soon as the cell is broken of the plant, because it gets chomped on, it releases myrosinase that is present in those same plant leaves or flowers. 27:51 The myosinases converts the compound to the isothiocyanate, sulforaphane, or in the case of mustard, for example, something called allyl isothiocyanate, 28:03 which is what makes your eyes water and makes mustard hot. 28:07 Same thing with wasabi and horseradish. 28:10 All those hot tastes are from iso-thiacinates. 28:16 It grosses out the beetle and it goes and flies somewhere else. 28:22 In terms of bacteria and fungi, there's direct antibacterial or antifungal activity. 28:30 There's also antiviral activity in people, which we should get to later. 28:34 So anyway, that's in large part why these isothiocyanates are made because they don't provide color or smell really to the plant. 28:43 And they taste bad, basically. 28:45 They're pretty challenging. 28:46 I mean, anyone who's eating broccoli sprouts knows that once you start chewing them, it's a bit of a challenge. 28:53 It's not the most delectable thing you can eat, right? 28:56 Depends on the person and your training, right? 29:00 I mean, if you grew up eating steak and potatoes, you probably would take some work to get used to broccoli sprouts. 29:07 Later in your career, You really began to delve deeply into neurodevelopmental and neurodegenerative conditions vis-a-vis the relationship to sulforaphane 29:22 and why there might be some application of sulforephane science in these conditions. 29:28 First of all, let's broadly talk about why that pivot occurred, and then we'll break down between neurodevelopmental because there's some really fascinating 29:37 work done in the field of ASD, autism spectrum disorder. 29:41 And then let's look at perhaps the implications as related to neurodegenerative conditions like Alzheimer's and Parkinson's. 29:47 Then we can talk about your incredible new 2025 report. 29:51 First, let us talk what was it about the findings in terms of the mechanisms of sulforaphane that let you have that aha moment that maybe the brain is 30:02 something we should be looking at. 30:03 I will tell you that. 30:05 Can I be a little obnoxious and ask if we put a pin in that and go back to the previous question though? 30:10 Okay, sure. 30:11 You know what? 30:12 It's our show. 30:13 Somebody's bothered by that, don't turn on something else. 30:17 Okay. 30:17 Well, I want to give you a little bit more context for the, you know, the reason we started looking at sulforaphane. 30:26 And this really has to do with, to your full credit to Paul Talalay, again, my mentor and very much my senior, he had just discovered when I was brought 30:41 into the group, that sulforaphane was present in broccoli. 30:45 But the reason he discovered that is because in looking at cancer chemo protection or ways to protect against cancers, which is what he was completely 30:57 focused on, There was this intriguing observation in the epidemiologic literature going back to the 70s, 1970s that there was a very strong association 31:11 between cruciferous vegetable intake or consumption and the risk of a variety of cancers. 31:18 In particular, in 1978, a study by Graham showing that there was a halving of the risks of colorectal cancer associated with about two servings a day of 31:32 cruciferous vegetables. 31:33 So, and there's a lot of other stuff. 31:36 Especially these days with colerectial cancer being so prevalent in younger people. 31:43 It is, but there was a lot of other evidence. 31:46 I won't go into it, it's reviewed in various places. 31:50 Paul's aha moment was, okay, we ought to take a bunch of fruits and vegetables and smash them up and put them in this bioassay that we have. 32:01 They did that. 32:02 And they found that broccoli was the best inducer in this particular system they used. 32:08 And then, in fact, then that led them to isolate sulforaphane. 32:12 So anyway, that's sort of the backstory. 32:16 Why is this a particular compound or set of compounds able to be repurposed in human beings for their protection? 32:27 I don't think we want to go into the molecular details of how the NRF2 pathway is upregulated. 32:34 It happens that sulforaphane fits on a chaperone protein that keeps Nrf2 out of the nucleus called KEEP1, and it binds to two reactive cysteines on that 32:50 protein and changes their conformation. 32:51 It happened to fit. 32:53 it happens to work. 32:54 Do we co-evolve that ability with the plants evolving? 33:03 I don't know. 33:04 It's going too far out on a limb, but that's what happens. 33:06 You're not, it isn't. 33:07 I mean, that the kind of stuff that you think about as you're falling asleep at night. 33:10 But suffice it to say that this L-4-phain through the activation of this NRF2 pathway activates hundreds of gene pathways involved in inflammation reduction, 33:22 detoxification, free radical scavenging, increasing brain drive neurotrophic factor, just a variety of issues that it does that are salubrious, 33:34 that're good for us. 33:36 And as we're then maybe if we can take the pin out of that, maybe that to the brain because, you know, clearly those are issues, 33:43 uh, are really fundamentally important for brain health. 33:50 segue into how that might impact the polarization of the brain's immune cells, the microglial cells which we've talked about on this program actually quite 33:58 a bit. 33:59 So it's a really good thing. 34:01 Detoxification, free radical quenching, anti-inflammatory, which certainly plays a role in cancer, upregulation of trophic factors in the So then that 34:13 seems like it would then propel work to be done even through the microbiome effects as well. 34:20 But looking at, for example, a neurodevelopmental issue like autism, and in fact, there are human trials using sulforaphane in autism. 34:30 And what did those reveal? 34:33 So I'll tell you what they revealed and that's also sort of what got us involved in the neurodevelopmental and neurodegenerative conditions study of them clinically. 34:46 We didn't know a lot about, or we weren't thinking a lots about the modes of action that you just sort of went through of sulforaphane at the time, 34:57 but we were talking to a friend, neurologist, pediatric neurologists at The Mass General, Andy Zimmerman, and he made the observation, 35:10 he came to Paul and me and said, You know, there's a study that shows that in vitro, I believe it was, that show that sulforaphane has an effect on heat 35:27 shock proteins. 35:28 And he said, and I and my group recently discovered or made an association between autism and the fever response or the febrile response in kids with autism. 35:44 And the observation, which is confirmed by others who treat autism, is that when certain kids have fevers, kids with autism, 35:55 severe autism is a wide array of symptoms in many cases. 35:59 Their symptoms are dramatically attenuated. 36:03 In fact, there's an anecdote from a family, a child with Autism, that the whole family came down with the flu, they all had fever, 36:13 and they were all miserable. 36:16 But this kid with autism who was, I believe, nonverbal, wound up sort of taking over and taking care of the family in ways that you wouldn't imagine. 36:27 And then when the fevers relapsed on all of them, he went back to his prior condition. 36:35 So Andy Zimmerman's comment or question was this is a really interesting potential connection And we know that sulforaphane affects the heat shock proteins. 36:49 Let's do a small clinical trial. 36:51 And so that's what led us to the trial that we published in 2014. Singh is the first author. 37:02 In that, we showed, I think, a fairly dramatic effect on certain commonly measured parameters of autistic behavior. 37:13 We monitored the effects at four, I think four eight and 16 weeks and then we did a washout period and so those effects persisted and Then after the wash 37:27 out period they returned more or less to baseline. 37:32 We were, of course, very excited. 37:34 It was a very low-budget study, but we had sufficient statistical power to make these determinations. 37:41 We weren't able to look at any blood biomarkers. 37:47 But so then we, with Andy's group, which then he moved to UMass Medical Center, and so with his group we did a follow-up study that we published in 2021, 37:58 I think. 38:01 in which we showed an effect of sulforaphane. 38:04 It wasn't as dramatic. 38:07 The material we used to dose with was different. 38:09 You know, the population was a younger cohort, male and female. 38:15 So there were all sorts of excuses and reasons for why it didn't exactly mimic the first study. 38:21 But there was, in fact. 38:23 And there have been something like eight or 10 subsequent studies. 38:27 I was actually also involved in an autism study, quite large, I think a hundred or so kids in China. 38:34 Uh, it wasn't, uh, wasn t directly involved with the intervention. 38:39 Um, and there was an effect shown there. 38:41 And I, think out of the eight, or ten studies, there, was, one that claimed no effect. 38:48 When you looked at their methodology, it was in my mind flawed. 38:56 You don't do one study and claim victory, but the consensus that's so far developing and the anecdotes for sure among the parent community of autism caregivers 39:10 is dramatic. 39:11 And of course, you have to take all these anecdotes with a grain of salt. 39:18 Let me mention the paper. 39:20 I'm The paper I never thought I'd be involved with writing, which was a follow-up observational study on that first series of subjects we looked at with 39:35 Andy's study in 2014. There's not a lot of hard data in it, but what happened is... 39:46 Something like two-thirds of the, I can get the facts for you, but it's been a while. 39:52 Something two thirds of subjects who showed an effect with sulforaphane in the initial study wanted to keep taking sulforephane. 40:03 And of course, when you do a study like this, and I made, my technicians and made the sulphoraphene prep that we used for the intervention. 40:14 at the university, that's not sustainable or really replicable in long term. 40:21 So we felt obliged to direct them to a number of good supplements that produce sulforaphane. 40:27 We did that. 40:29 Many of them took these supplements for three to four years, or I should say they may still be taking them, but after three or four We got permission from 40:38 our IRB to go back to them and query them, and something like two-thirds of them had sustained dramatic effects on the symptoms of autism. 40:56 You could say what you will of this paper we did. 40:58 It's not highly cited. 41:00 Lynch is the first author if you want to look it up or send it to you. 41:05 But when you get thousands of anecdotes, you've got to start listening to them and do a proper clinical study then. 41:14 For close to 40 years, I have found myself in examining rooms watching a family struggle through the loss of a loved one. 41:21 Not because that loved on aged, but because, that love one had lost his or her cognitive function. 41:28 And, you know, basically I think we were all told that there was nothing that could be done. 41:31 In fact, they even parroted that narrative for quite some time. 41:34 But ultimately I found my self in a place of not being able to accept that. 41:39 I'm Dr. 41:39 David Perlmutter. 41:42 And Brain Defenders is my new book, clearly the book that I have spent my entire career building. 41:48 It's officially launched and it's available for order right now. 41:52 And I truly believe that this is the most important work that i've ever done. 41:57 Inside what you will find are the hidden threats that are working against your brain right, now and also the exact science-backed actions that you can 42:06 take to protect your memory, to your independence, your ability to interact with other people starting today, not someday, 42:15 but actually starting to date. 42:17 For those of you who want to be all in, I'm excited to announce that we now have the Brain Defenders Immersion Course, which is a guided path to put the 42:26 very work that was described in the book Brain defenders into action. 42:30 step by step so that protecting your brain isn't something that you just read about, it's something you actually participate in, 42:36 something actually do. 42:37 Your brain's future is actually being decided right now by the choices you are making today. 42:43 So order Brain Defenders and join the Immersion Course today and you can get all this information by visiting my website which is drpearlmutter.com, 42:52 that's drperlmuter. 42:54 com to learn more about both the immersion course and the book. 42:58 I wrote this book for you and for everyone you love. 43:01 Let's defend your brain together and defend the brains of everyone. 43:05 You love as well. 43:06 Remember the time to defend. 43:07 Your brain is right now. 43:14 You indicated that one of the possible explanations was the induction bisulforphane of heat shock protein. 43:23 And I just think for our viewers, I'd like to unpack that a little bit, that this is a protein that is produced when people are exposed to either high 43:31 temperature or low temperature. 43:31 So nowadays, there's a tendency to call it thermal shock proteins, which helps with reducing inflammation, yes, but also with misfolding of proteins that 43:45 is a characteristic of many neurodegenerative conditions. 43:48 And I'm thinking about an interview that I have for the Dr. 43:53 Abreu from Yale, now he's in Florida doing research, who was quoted as saying about a month ago, with one patient that he has cured ALS, 44:05 amyotrophic lateral sclerosis, or Lou Gehrig's disease. 44:08 That's bold, but here's what he did. 44:12 He has created technology that allows very careful monitoring of the brain in terms of temperature, raises body temperature in patients with really challenging disorders. 44:24 I think we'd all agree ALs is almost uniformly fatal, so certainly challenging. 44:30 is able to keep brain temperature just below the threshold where injury and or seizure would occur and is engaged in this heat therapy and has a confirmed 44:41 bona fide ALS patient seen by multiple neurologists with examinations, EMG, nerve conduction velocity testing, all the things that you do to confirm that diagnosis, 44:52 even tongue fasciculations, All of which went away. 44:56 And this is a Yale-trained physician, you know, really making a claim here. 45:02 And, we can't turn our backs on an N of one. 45:05 There's another N-of-one set of experiments that came out of the blue to me. 45:12 This is, there's a guy named Albert Wright, Dr. 45:16 Albert, PhD in glass chemistry or something like that in Europe. 45:23 And he called me in 2018, maybe 2019, and he said, I've been looking at your work on sulforaphane and I started using it. 45:37 I have Parkinson's disease, it was just diagnosed. 45:41 Anyway, the long and the short of it is we became friendly very quickly. 45:45 Albert has unfortunately passed away early this year of heart attack, I think, not related to Parkinson's, but he found with himself that if he made a 46:00 broccoli seed extract, seeds are even more concentrated sources, in his kitchen, took a certain amount. 46:08 His non-motor symptoms of Parkinson's were dramatically improved. 46:15 And most people don't realize this, but in addition to Parkinson producing symptoms like tremors, which are obviously visible to everybody around a person 46:26 with Parkinson's. 46:27 There are a lot of non-motor symptoms that are really distressing. 46:31 I won't go into them now, but they really affect quality of life. 46:34 And many of these were relieved. 46:36 Being a scientist, Albert quantified them, made charts, make tables, screwed around with a dose, and then became convinced that this was real. 46:47 He asked me for a calibrated source of broccoli seeds with a known amount of glucoraphanin, the precursor of sulforaphane. 46:58 I sent him a bunch, and then he started sharing them with people in his Parkinson's network, his self-help group. 47:09 in Europe, and had a number of people do the same thing, record their observations. 47:15 I mean, it's broccoli, right? 47:17 Just take it, add it on to whatever you're taking. 47:22 And he ultimately wound up publishing the results in a paper in an obscure journal. 47:30 It was an N of 1 series. 47:32 And I think, honestly, to get it published, he didn't even really include that in the title. 47:37 You know, it was a new theory of Parkinson's and how to measure Parkinson. 47:47 And he's since, I should say, he has since replicated his network to the US. 47:53 And I'm quite friendly with the group here, headquartered in New Hampshire, that's doing a similar set of, you know, their feeling is, 48:08 look, we've got this disease. 48:10 It may be fast progressing. 48:13 Sure, we'd love it if someone wants to do a proper clinical trial on it and spend the years and raise the millions of dollars that are required to it. 48:21 But we're not going to wait. 48:22 We can do this at home ourselves. 48:24 And you can take supplements containing sulforaphane or glucoraphanin, or you could make the extracts yourself. 48:32 So they're doing it, and many of them have found dramatic effects also. 48:38 One of the things that you've made so clear is that the potential for sulforaphane to be helpful for the brain, especially in the context of a neurodegenerative condition, 48:48 has to do with its upregulation of reduced glutathione production and availability. 48:56 The idea that the Parkinson's brain is low on glutothione has been known since around 2005. In 2012, We published a study in the journal Movement Disorders, 49:10 a double-blind trial on rating Parkinson's patients on a standardized Parkinson functionality scale, one group receiving saline, 49:20 and one receiving intravenous glutathione. 49:23 The results were profound in terms of motor functionality in that glutothione And in fact, I have, it was the early days thereafter of YouTube, 49:35 a very young Dr. 49:37 David Perlmutter of a patient pre and post-IV glutathione. 49:40 I don't even recognize myself, but the results we were observing were really quite profound. 49:45 So I think that helps explain it. 49:47 The other thing I would say is that it's interesting we're having this conversation because yesterday in the journal Neurology, 49:56 was a publication indicating that the GLP-1 agonist drugs do not seem to impart any motor functionality improvement in Parkinson's patients. 50:10 But that comes on the heels of a study in April of 2024 in the New England Journal that treated Parkinson's patients over a three-year period, 50:20 200 patients, and found that those who received a particular GLP-1 agonist that's a metabolic enhancer, like sulforaphane would be in terms of mitochondrial function, 50:32 had a virtual arrest of their decline. 50:35 They stopped getting worse. 50:37 Published in the New England Journal of Medicine, I think we'd all agree that's a respectable journal. 50:42 So the idea is that when we target mitochondrial function, we have two very important pathways here, glutathione upregulation and direct mitochondria up 50:52 regulation as well. 50:53 For you to be discussing this individual's report as an end of one makes complete sense. 51:00 And I think that, let's make it clear to all of our viewers that you are promising them that later in our discussion, you're going to tell them how to 51:08 get sulforaphane, either by supplement or growing your broccoli sprouts, where to gets seeds. 51:13 I don't know if we can really cover that because I that's kind of a challenge, but how we get more sulphoraphene in your lives. 51:20 But what I would like to do, is go to your 2025 review. 51:26 What a powerful thing to do at this stage in your career to take sulforaphane to the brain. 51:35 You know, obviously for me, I'm incredibly thrilled that you did it, but why did you do that? 51:41 What compelled you at the stage of your careers to go the the to brain like that and do such an incredible overview? 51:48 Starting with our work on autism and then on Parkinson's, I became more aware of all of the publications that were coming out in, 51:58 we have to say this, in animal models and cell culture mostly, but looking at models, Alzheimer's Parkinson, Huntington disease, 52:09 traumatic brain injury and spinal cord injury, which we did some work, ischemia reperfusion injury. 52:16 I mean, these are all published reports, not all clinical, but mostly preclinical, stroke, alcohol-related disorders, even sleep disorders and things like epilepsy. 52:31 Mood disorders, depression, anxiety, schizophrenia, certainly, and we've done some clinical trials on that. 52:43 Diabetes-related cognitive function. 52:45 We become specialists in our professional careers and as specialists, you try to stay current in some things, right? 52:53 So, I try stay fairly up-to-date in the self-harping literature and I just seeing this work on neurodevelopmental and degenerative disorders. 53:08 And it was very clear from the work that I had done on autism and schizophrenia and Parkinson's that there was a lot more out there. 53:17 So I don't know what the number of clinical studies is, but the review that you're talking about that we just did, there are hundreds of papers referring 53:28 to the mostly to pre-clinical testing. 53:34 And I think the thing that gives a lot of people additional hope is that sulforaphane very much passes the blood-brain barrier, 53:45 whereas many pharmaceuticals don't, in terms of chemicals for that matter. 53:50 Sulforapane does cross the brain barrier and that's important because although now that sulforaphane has effects on cells, 54:00 you know, in the brain, it's not an effect on Nrf2 in liver, which then has a secondary effect in brain. 54:11 So you mentioned an incredible array of seemingly very disparate disease states from head trauma to Alzheimer's, Parkinson's viral issues, 54:20 etc., but it seems that everything ultimately converges on mitochondria and metabolism and therefore opens the door for sulforaphane to play an important role. 54:33 But we shouldn't forget that there are other direct effects, immune response activation, direct anti-inflammatory, and direct detoxication of advanced 54:48 glycation end products which are more and more present in our food and our environment. 54:53 And brought on by our elevated blood sugars, for sure. 54:56 I'm going to try to do a screen share here and see if we can look at this image. 55:03 Are you seeing that image? 55:04 So this is actually taken from your report. 55:08 And maybe you can walk us through what's on our screen. 55:11 Yeah. 55:11 So, I mean, this was just really recapping some of the things I listed for you on the right-hand side. 55:20 On the bottom left, these are some of the main pathways that we should be focused on when we talk about disorders of brain and spinal system. 55:36 The NRF2 pathway we've talked about, we can flood listeners if they don't already know with information on that pathway. 55:45 It's been extremely well documented by colleagues of mine in the U.S. 55:52 and Japan over the last couple of decades, We mentioned the blood-brain barrier. 55:59 This is critical. 56:02 It's probably, I should say, critical that sulforaphane can cross it. 56:06 I don't know if it would be having the dramatic effects that it does if couldn't cross and help maintain the integrity of the the brain barrier, 56:16 maintain those cell-to-cell connections. 56:21 Oxidative stress, this is associated with Detoxication, neuroprotection, a lot of it again regulated by the nRF2 pathway. 56:32 It is useful to talk about oxidative stress and detoxication. 56:38 How these function to protect cells. 56:43 When the NrF 2 pathway is induced, when NRf2 is upregulated thanks to sulforaphane or a variety of other phytochemicals, 56:54 it It triggers the increased production of a variety, as you said earlier, David, of variety of enzymes, almost exclusively enzymes. 57:09 There are, I think, five enzymes in the glutathione biosynthetic pathway as well as the enzymes that recycle glutothione from reduced to oxidative state. 57:18 or oxidized state. 57:20 So all of these enzymes have a half-life, right? 57:24 And that half life is hours to days, even weeks in some cases. 57:30 Whereas the antioxidant, if you just give something like vitamin C, It goes into the body, it's oxidized, its used, does its thing, 57:42 and it is excreted in the urine within a couple of hours. 57:46 The peak is within couple hours, the same thing happens to sulforaphane. 57:51 It's used and excrete, but the thing that it does is to induce all of these protective enzymes and they last. 58:00 They last for days. 58:03 You don't have to have sulforaphane on board all the time. 58:07 Sulforophane is, in many regards, a hormetic compound. 58:13 The body sees it as a foreign, as exogenous. 58:18 And so it enters cells readily. 58:22 It is conjugated and spit back out and excreted as sulforephane conjugates of glutathione. 58:30 But in the process, it activates the Nrf2 pathway and does a variety of other things that we've mentioned. 58:36 Let's go back to glutathione for just one more moment. 58:38 I think that in a context of this being such a protective tripeptide in brain that this declines with age and really even beginning in our 20s. 58:53 it seems reasonable that we should do whatever we can to preserve glutathione in the body and the brain. 58:59 And this seems like one of the, you know, really powerful inroads that can utilize, right? 59:05 I certainly think so. 59:07 Yes, as we get older, glutothione levels decline in brain, a lot of other things happen, and you and I both are becoming acutely aware of it, 59:15 but we're on that side of this slope. 59:19 But I think the fact that you can increase glutathione levels in the brain. 59:28 is really, it makes it important for us to think about supplementation. 59:36 As we get older, like it or not, we wind up not being as active. 59:41 I mean, I like to fly in the face of that and bike and hike all the time. 59:46 But at some point as you get old, your activity level falls off and your food consumption falls, off your dietary intake falls. 59:55 So it's really hard to eat 10 or 20 different fruits and vegetables a day, right? 1:00:01 And your dietary variety in your diet, I think, declines. 1:00:08 I'm not an expert on this. 1:00:09 But therefore, supplementation with something like sulforaphane, is appropriate. 1:00:18 We showed, working with Tom Sedlak and Akira Sawa at Hopkins a number of years ago, that when you supplemented, this is a clinical study now, 1:00:28 supplementing people with sulforaphane and then looked at their brains with a 7-Tesla MRI, the glutathione levels in the brains increased. 1:00:41 And there are other studies in rodents that show the same kind of thing. 1:00:48 I think it makes a case for supplementation certainly later in life. 1:00:53 If I may get up on my soap box a little bit, having said that, I also would encourage us all not to neglect the very first part of life. 1:01:06 The first couple of slides that I sent over to you might be appropriate to look at here. 1:01:16 We think about interventions in kids and adolescents as maybe they're done a lot less, but when is it important to get kids acclimated to good diets early 1:01:29 in life. 1:01:31 Should we be pushing broccoli and broccoli sprouts early life? 1:01:35 Yes. 1:01:36 I'm working with a company that's pushing, I use that word fondly of course, pushing multiple fruits and vegetables in a preserved shelf stable form in 1:01:50 very young kids, just to get them used to the smells and tastes of different fruits, and not so much the textures, but the, 1:01:58 the smell and the taste and colors. 1:02:01 So, you know, I think although we can argue that interventions with compounds like phytochemicals like cell forfein are important later in life, 1:02:15 I think starting those habits early is so critical that we should make the argument on both ends of the lifespan. 1:02:24 And then why not the middle also? 1:02:25 Because that's when everybody's most stressed. 1:02:28 For over four decades, I've worked as a neurologist. 1:02:31 The more I have studied the brain, the more this notion of inflammation keeps turning up as common thread. 1:02:37 It's certainly something we discussed in great detail way back in Grain Brain. 1:02:42 a brain maker looking at the microbiome, and now definitely a central focus of my latest book, Brain Defenders, which looks at brain's immune cells called microglia. 1:02:52 And what I've learned is that how your genes handle inflammation and the role that genes play in inflammation shapes whether these micro glial cells are 1:03:01 going to be protecting your brain or quietly wearing it down. 1:03:04 And that's exactly the thinking with respect to why I recommend 3x4 genetics really across the board. 1:03:13 I'm selective about what I put my name behind, and 3X4 is one name that I trust completely. 1:03:19 One cheek swab looks at 35 different pathways across 10 areas of your health, including the very inflammation that is central to basically what makes a 1:03:30 good brain go bad. 1:03:32 These pathways sit at the center of what I'm writing about in the new book, Brain Defenders. 1:03:37 From there, you get this personalized genes first plan that'll explore what foods are working for your biology, personalized medicine, 1:03:46 what level of training fits your geology, and even what supplements are actually worth taking. 1:03:52 So your daily choices are working for your brain instead of against it. 1:03:56 So go to 3x4genetics.com forward slash Dr. 1:04:02 Perlmutter for a very special offer when you sign up to decode your genetics and get this personalized science back health recommendation that they offer. 1:04:13 Now let's get right back to our podcast. 1:04:17 What can you tell our viewers they can do right now? 1:04:19 Everybody I think who has spent time with us today is going to want to know, I want more sulforaphane in my body. 1:04:27 What do I do? 1:04:28 What's the answer? 1:04:30 I think it's threefold. 1:04:33 You can eat more broccoli. 1:04:35 It's easy, unless you don't like broccoli, and a lot of people don' And so then there are supplements. 1:04:43 I'll get to them in a second. 1:04:44 The second approach, which I hardly endorse, is to make your own broccoli sprouts and eat them at home. 1:04:55 I eat broccoli sprouts probably five days a week. 1:04:59 They're going on our counter all the time. 1:05:02 It's cheap, it's safe, and it is easy. 1:05:08 Full disclosure, I also consult for a company that is promoting sprouting at home. 1:05:15 And they've developed a sprouter that just makes it, look, it's very easy to do it with a big mason jar and a piece of screen on the top. 1:05:25 It's even easier to use the kind that the sprouting companies made. 1:05:30 which you buy it on Amazon or buy directly and it comes to your house and you don't have to put any parts together and has a little thing that you tilt 1:05:43 the bottle on. 1:05:44 They also sell the seeds and that actually becomes an important part of it. 1:05:49 Because we showed 100 years ago that broccoli termplasm, the seeds, vary all over the map in terms of their glucoraphanin content, 1:06:04 it's important to know, if you're eating it for health purposes, is it important if it is a high-glucorafanin broccoli seed or a low-gluco... 1:06:19 And unfortunately, as a consumer you can't just take a sample and send it off to a lab to have it tested. 1:06:25 Or if you did, you'd be testing it every time you get a pound of seed from Amazon and it's quite expensive. 1:06:33 So anyway, the company that sells these sprouting kits also sells certified seeds with certified levels of glucoraphanin. 1:06:43 And I've helped them make sure that they're doing that properly. 1:06:48 So my only point here is it's really easy to grow sprouts at home. 1:06:52 I grow a mixture of sprouts all the time and you mix flavors. 1:06:57 We can absolutely say the name of the company. 1:06:59 There's no reason why not. 1:07:00 It's The Sprouting Company and it is out in California. 1:07:07 We got market stage broccoli, regular broccoli. 1:07:10 We've got sprouts. 1:07:11 There's still a lot of people who are not going to like them. 1:07:14 So yes, other cruciferous vegetables or dried moringa is quite readily available in this country, are good sources of protective isothiocyanates. 1:07:27 But we've mentioned supplements a number of times, and supplements are sort of the You know, they're in vogue. 1:07:35 Americans love to take pills instead of doing other things for themselves. 1:07:40 So there are a lot of supplements in pills and in drinks now that contain glucoraphanin. 1:07:47 There's another one that's just hit the market that I'm familiar with from a company called Press Juice. 1:07:54 They make these shots that are rich in glucroraphenin There might even be gummies, I'm not sure. 1:08:02 So if they're rich in glucoraphanin, then as far as the myrosinase part of the story, you're then fully dependent on what you have from your gut bacteria 1:08:11 to metabolize it into sulforaphane? 1:08:13 Yeah, it depends on the supplement. 1:08:15 20 years ago, almost all the supplements were glucroraphinin only. 1:08:20 Now, a lot of them have myosinases also. 1:08:26 And I co-founded a company in 1997 called Brassica Protection Products. 1:08:33 Brasica is the genus name of broccoli. 1:08:36 And they have been making the certified standardized ingredient that goes into a lot of the supplements that are on the market nowadays. 1:08:47 And with our coaxing, they have introduced myrosinase, mustard seed myosinases into their line. 1:08:57 So a lot of the supplements nowadays are including both glucoraphan and myrocinase. 1:09:05 You mentioned that the seeds are rich in glucroraphan, broccoli seeds. 1:09:10 Could you not just chew the broccoli seed? 1:09:12 Because I end up doing that sometimes. 1:09:16 The problem with doing that is, first of all, you need to make sure they're cleaned because broccoli seeds coming in from the field, 1:09:26 they are blow dried or whatever the proper term is. 1:09:30 They're sifted and sorted, but they sanitized. 1:09:34 So to the extent that various living mammals in the field, uh, defecate in a field. 1:09:42 You know, these E. 1:09:43 coli and other pathogens can, can get on the seeds. 1:09:47 so you should clean them first. 1:09:50 They don't taste very good. 1:09:51 you may disagree. 1:09:52 I was going to say, you agree. 1:09:54 No, they're bitter, but you can bake them. 1:09:59 And the glucoraphanin is preserved, but the myrosinase is killed. 1:10:04 But baking is a knife's edge endeavor. 1:10:08 You can't do it too long or they scorch and they burn. 1:10:11 So you almost have to. 1:10:13 put the light on in the oven and watch them. 1:10:16 But baking them is a way to make them taste nuttier and better. 1:10:22 Actually, you can certainly make your own extract of broccoli seeds, but then again you go back to the question of, well, 1:10:28 what's the amount of glucoraphanin in them? 1:10:32 So in terms of supplements, yeah, many of the supplements are moving towards glucroraphenin plus myrosinase. 1:10:41 leads me to a very quick discussion of bioavailability. 1:10:45 Since glucoraphanin is converted by myrosinase to sulforaphane, when you ingest it without added myosinases, you're counting on your gut bacteria to do 1:10:56 all of the conversion. 1:10:59 And all us have bacteria in our guts that do that conversion, they have myrocinase in them. 1:11:07 When you ingest added myrosinase, we first did this in the late 90s, I think, and we thought we were brilliant because we felt what that was going to do 1:11:20 is reduce the variability person to person on bioavailability as measured in blood and urine. 1:11:29 Well, our brilliant idea wasn't that brilliant. 1:11:32 It did not do that. 1:11:33 The variability person to person is every bit as high, but the mean or the average was up substantially from about 10% of the glucoraphanin to about 40%. 1:11:46 And we showed that in trials in China also. 1:11:51 It is true that if you just deliver sulforaphane, you get an even higher yield, as it were, higher bioavailability. 1:12:00 However, sul foraphene is very unstable. 1:12:05 when given as a supplement, ideally you have to freeze it in a minus 80 freezer if you if have it an extract. 1:12:14 Various people have tried to stabilize it and with I'd say very low success and there are a lot of supplements on the market that claim they have sulforaphane 1:12:24 and we've measured them and they don't or they had much lower levels than they say. 1:12:28 So I would my advice to people Eat broccoli, eat broccoli sprouts, take a supplement that has glucoraphanin or glucaraphenin and myrosinase. 1:12:38 And all of the respectable supplement companies have them, Zymogen, Thorne, Nutri-Max. 1:12:46 Abmacol, Prostaphane. 1:12:49 Yep, Ab macol. 1:12:52 was, there's a story there, prostaphane was a compound that was stabilized sulforaphene sold in France and we did a clinical study with it and it worked 1:13:03 in a prostate cancer study in men. 1:13:07 It reduced the PSA trajectory The doubling time. 1:13:11 Doubling time, yeah. 1:13:12 It had to be stored in a freezer, a refrigerator or freezer by the consumer. 1:13:19 And it had a shelf life of a couple of years, and it was pretty good. 1:13:23 it compressed into a tablet and whatever they used to do that. 1:13:27 We actually started buying it in America through some shady international arrangement to test it. 1:13:38 But then there was a company in the U.S. 1:13:41 that started claiming it made licensed prostaphane or something, but they changed the formulation completely. 1:13:48 They turned it from a tablet into a big green gel cap. 1:13:53 with bright green. 1:13:56 They claimed on their website that it was prostaphane. 1:14:00 What we tested did not have the activity they said it did. 1:14:05 So I personally stay away from that. 1:14:09 I've never used that in our clinical studies. 1:14:11 And I prefer to stick with glucoraphan and myrosinase. 1:14:17 You mentioned something earlier, you said that you take broccoli sprouts about five times a week, and I think it gets back to the point that When you're 1:14:28 upregulating these transcription factors that you are creating an ongoing production in your body of detoxification enzymes, 1:14:36 of antioxidants, anti-inflammatory compounds, unlike what you mentioned with vitamin C where it's consumed and it is done. 1:14:44 So you really don't have to be necessarily dosing every day with broccoli sprouts in that there seems to some lingering effects for a longer period of time. 1:14:55 Absolutely correct. 1:14:56 And we don't have a clear, concise dosing schedule to suggest. 1:15:03 But there are a few things I'd like to tell you about that. 1:15:06 So yeah, probably three times a week or every other day is more than sufficient. 1:15:13 Americans that take pills, except perhaps people that are on HIV medications and some others with a sort of odd schedule, 1:15:23 Most Americans that take supplements like to take one a day or maybe two a days, right? 1:15:28 But having a staggered schedule doesn't work too well. 1:15:35 Frankly, I think the supplement companies have just opted to it. 1:15:40 If you look at the price of so many supplements on the internet, they're $30 to $60 a bottle. 1:15:47 And you take 1 or 2 a and it's a per day dosage. 1:15:52 If you look at the dose in, for example, glucoraphanin supplements, I would argue that instead of taking one a day every day, 1:16:02 double that dose or triple it and take it every other day. 1:16:06 I personally, in addition to eating broccoli sprouts many times a week, take 100 milligrams of glucroraphenin, which is about 230 micromoles a days in 1:16:20 a supplement. 1:16:22 Is it an insurance policy? 1:16:24 Yeah, that's the way I look at it. 1:16:28 Back to your point about inducing these protective enzymes, we know that the activity of these enzymes lasts, as I said, 1:16:35 for days or perhaps in some cases even longer. 1:16:39 And because of that, I guess that knowledge induced us to look in our trials in China at the longevity of the response. 1:16:50 Okay, you can induce this compound, but after a week or two or three, does that response fall off? 1:16:58 And it didn't. 1:16:59 So we ran our, I think the longest trial we did in China was for three months. 1:17:05 There may have been some slight diminution over that time, But essentially, the benzene and acrolein detoxication persisted over the period. 1:17:17 And this has been shown in animal models too. 1:17:19 The response is robust and it remains. 1:17:25 You don't fatigue the system. 1:17:27 Wow. 1:17:29 This has been really very, very empowering. 1:17:32 And I know that people who watched us today are going to want more information and certainly probably want to start sprouting or at least eating more broccoli. 1:17:45 So this is very very helpful. 1:17:47 I just want commend you for your life's work, because this brings such a high level of useful information to so many people. 1:17:57 I just want to also thank you, for spending time with us today. 1:18:00 Well, thank-you so much for having me. 1:18:05 Retiring from the active faculty in academia, leads to the question, what are you going to do now? 1:18:12 What's your value? 1:18:14 Yeah. 1:18:15 And what I have decided is to more things like we're doing now and try to talk to folks who are interested in their health, 1:18:24 but perhaps not scientists. 1:18:27 Many of them are not scientist, I'm sure. 1:18:30 Try to translate, as you do so well, David, try and translate the complicated stuff that we talk about to a more manageable bites. 1:18:42 I should tell you that one of the things I hope I'm able to accomplish or I see in my lifetime does have to do with sulforaphane. 1:18:53 My sort of dreamscape is that When you as a patient or a subject go to your allopathic physician and she or he reviews your medication and supplement list, 1:19:06 they don't glaze over when you come to sulforaphane or glucoraphanin and ask you to explain it to them. 1:19:12 They don�t go, duh, or just sort of look the other way. 1:19:18 Unfortunately, I've had to make a number of physician visits over the years that I wish I didn't. 1:19:24 But every time you go to your physician, that's one of the things they want to go over with you. 1:19:29 And it should be vitamins and drugs. 1:19:33 What do you take? 1:19:34 Supplements. 1:19:36 I don't think I've ever had that conversation with a specialist or a generalist when there has been a complete lack of knowledge of what sulforapine is. 1:19:49 People tend to be down on what they're not up on, I would say. 1:19:52 Yeah, but I think if you and I and others in this space do our jobs well, then at least maybe the consuming public won't be as knowledgeable still. 1:20:04 But if the physicians who hopefully are encouraging them to change their behaviors know a little bit more, than maybe we'll have done our job well. 1:20:13 Yeah, and it is a supplement, meaning it adds to what would be considered a good diet. 1:20:24 And do we need a supplements these days? 1:20:26 Yes, because I think that the standard diet that we're eating these day is not keeping up with our environmental stressors. 1:20:32 I mean, you know, we've talked about what's in the environment and we need a little help. 1:20:37 And this is a very, very powerful, deeply validated approach to ramping up our ability to confront our environment. 1:20:46 So, what I would say, visiting your clinician and mentioning sulforaphane, say just go to chat GPT and spend two minutes and learn about this. 1:20:55 Then we'll have a discussion or watch this podcast or any of the number. 1:21:00 that you've been able to do over recent years. 1:21:03 Again, thank you, and I look forward to connecting in the future. 1:21:07 This has been really very important and educational for me. 1:21:13 Well, I hope we can, again, thanks so much. 1:21:16 I'd love to talk again. 1:21:18 Okay, we'll talk soon. 1:21:20 Be well. 1:21:21 Thanks. 1:21:22 So much gratitude that Dr. 1:21:24 Fahey had the opportunity to join us today on the Empowering Neurologist podcast. 1:21:28 His work has really illuminated something profoundly important and that is that nutrition isn't just passive and the food you eat just isn' t the fuel 1:21:38 to empower your body. 1:21:39 You know, it's more than the macronutrients of fat, carbohydrates and protein. 1:21:44 The food that we eat is information, as Dr. 1:21:47 Jeffrey Bland has been telling us for decades. 1:21:51 Dr Fahey's research shows us that compounds like sulforaphane, like we talked about today, actively engage our biology and influence our genetic expression. 1:22:01 In other words, the foods that we consume are determining the expression of our life code. 1:22:08 The foods are involved in our cellular defense systems, involved with regulating inflammation and even metabolic health in ways that are really very much 1:22:19 related to brain function and long-term cognitive resilience. 1:22:23 I'm very grateful for the clarity that Dr. 1:22:27 Fahey has brought to the science and to all of us today. 1:22:30 It really cuts through a lot of the hype that we see on social media and grounds us in evidence and helps us understand not only what works, 1:22:40 but why it works at the molecular level. 1:22:42 And these are insights that are really, I think, essential for all of us as we rethink how we approach the whole notions of prevention and aging and how 1:22:53 look at neurodegenerative diseases that so prevalent and so threatening in a world that urgently needs better answers. 1:23:01 So, to Dr. 1:23:02 Fahey again, we are so appreciative of your decades of rigorous research. 1:23:07 your commitment to translational science. 1:23:10 In other words, taking this basic science that you've so well elucidated and allowing the translation to human health and for sharing your knowledge so 1:23:22 generously with us today. 1:23:24 And to our listeners, again, I'm always appreciative that you join us here on our program, The Empowering Neurologist. 1:23:30 If you found today's conversation valuable, please share it. 1:23:33 Please subscribe and continue to explore how small and deeply informed choices can have a profound effect on your brain's destiny, 1:23:43 your body's, destiny and your overall health. 1:23:46 I'm Dr. 1:23:46 David Perlmutter and until next time stay empowered, stay curious, Stay healthy and we will be back soon here at the Empowering Neurologist. 1:23:55 Bye for now.
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