#029 Jed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Moringa & Sulforaphane Supplementation

Sulforaphane: Cancer

In my last podcast, I talked about the effects of a group of compounds known as isothiocynates that are produced by the brassica family of vegetables, including broccoli, kale, cauliflower, and so many others.

"Hello again. In my last podcast, I talked about the effects of a group of compounds known as isothiocynates that are produced by the brassica family of vegetables, including broccoli, kale, cauliflower, and so many others. In the podcast, which actually centered around one particularly well-researched isothiocynate known as sulforaphane, was over 45 minutes long. I talked about so much in the context of these plants and compounds, including changes in cancer risk in humans, reductions in inflammation causing significant detoxification of air pollutants, animal and human studies and various neurological disorders such as autism, schizophrenia, Alzheimer's disease, traumatic brain injury, and more. I talked about changes in animal models for stress-induced depression. I talked about heart disease and all-cause mortality and aging in general, and also about DNA damage. This is exactly why we're going back in for round two today. This time, however, I bring in someone fresh into the discussion, someone that is actually an authority on this research. Today's guest is Dr. Jed Fahey, a multi-decade veteran in this field of research and director of the Coleman Chemoprotection Center at Johns Hopkins. As you'll quickly learn from listening to this interview, Dr. Fahey has for many years been at the center, along with his colleagues, of a whirlwind of this type of research. There is hardly a topic in which we discuss in which he doesn't have an anecdote about a study he was involved in, or in some cases, interesting tribal knowledge that may not even be published, but is nonetheless interesting and an important part of the story that is unique to his particular vantage point. His lab and those of his colleagues, in a way, have served as a critical infrastructure for the rest of the research community, often helping to facilitate a broad range of studies to get the access they need to broccoli extracts and much more. This becomes especially impactful when you realize in 2016 alone, there were over 150 new studies that were published on this extremely promising compound sulforaphane. For this reason, I've decided that for the month of January 2017, in other words, this month, I will be contributing 10% of my subscriber crowdfunding, including any new crowdfunders that sign up between now and the end of the month, to their center at Johns Hopkins. I encourage anyone after listening, if you find this work as exciting and profound as I have, to go look up the Coleman Chemoprotection Center at chemoprotectioncenter.org and click the donate button, either as a one-time donation or a recurring donation. These funds will go towards research in the areas of autism spectrum disorder, schizophrenia, progeria, breast cancer prevention, and air pollution injury, just to name a few. As you'll learn in this interview, Dr. Fahey and his colleagues have already demonstrated their ample ability to create fundamentally world-changing paradigm shifts, especially in opening up new, promising, and fruitful avenues for tackling cancer and much more. This type of work stands in stark contrast to so much research out there that sucks up funding, makes a headline, and disappears a month later, never to be heard from again. As a final note before we kick things off, I'd also like to thank my contributing subscribers for allowing me the amazing opportunity to be able to afford to fly out and visit Johns Hopkins and meet amazing people like Dr. Fahey and also to be able to send a little bit of support to the Coleman Chemoprotection Center personally as well. To learn how you can participate in supporting this podcast as over a thousand people now do every single month, visit foundmyfitness.com forward slash crowd sponsor. That's foundmyfitness.com forward slash C-R-O-W-D-S-P-O-N-S-O-R crowd sponsor. Now onto the podcast. Hello everyone. I'm sitting here with Dr. Jed Fahey, who is an assistant professor and a clinical biochemist here at Johns Hopkins. Jed played a huge role in discovering that broccoli sprouts contain very high amounts of the precursor to sulforaphane called glucoraphanin. Since then, he has made huge contributions to the field and has studied sulforaphane and glucoraphanin and broccoli sprouts and from everything from cancer to the microbiome to the brain. So I'm very excited to have a conversation with him today. So Jed, maybe you can sort of kick it off by telling people a little bit about what glucoraphanin and sulforaphane is and some of the history behind discovering it. Sure. Be happy to. So sulforaphane is a small molecule that was discovered in broccoli by Paul Talalay and Yushin Zhang, his student at the time, in 1992 or so. They published on it, and it was of interest in particular because it was a huge inducer of protective enzymes in people. Of course, it wasn't known that this occurred in people at the time, but in cell cultures and in animals, they showed that it upregulated the protective enzyme, cytoprotective enzyme system, known by some as the phase 2 enzyme system. And Paul then, who was one of the grandfathers of chemoprotection, and it really helped make people stand up and pay attention to the fact that you could potentially prevent diseases like cancer. Paul asked me to join the group in 1993, and the challenge was, can you get broccoli with more sulforaphane? I came from a background in plant biotechnology, and of course, I said, yes, we should be able to. And we started trying to breed and cross broccolis to get higher levels of sulforaphane. Quickly became obvious that it was very difficult to predict how much sulforaphane a broccoli plant would have based on things like smell, touch, color. You pretty much had to run it through an HPLC to measure levels of sulforaphane. What's more is we realized that sulforaphane is not what's present in the intact plant. So what's present in the plant is something called glucoraphanin, and that is a thioglucose-conjugated molecule, not to get too heavily into the biochemistry of it, but it's a bigger molecule. It's a precursor, and it's very stable. Sulforaphane is not at all stable. It's highly reactive. And so at any rate, it turned out that the intact broccoli plants had glucoraphan at various levels, ranged all over the map, couldn't figure out exactly how much one had without doing chemical analyses. And we were going out to the field in the eastern shore of Maryland. And eventually winter came along and we couldn't go out to the fields and get broccoli anymore. So we started growing them in incubators in the lab, starting from seeds. And lo and behold, it turns out that broccoli sprouts had much higher levels of the precursor of sulforaphane, glucoraphanin, than did the mature plants, the heads of broccoli that you buy in the market. So we then determined that if you grow broccoli sprouts all the same way, which you pretty much do if you're a home sprouter or a commercial sprouter, you add a certain amount of light, you add fresh water, you grow them for a certain amount of time at a certain temperature. So if you did that with a whole slew of different cultivars, that's the different sub-varieties of broccoli, you got a range of different activities, different amounts of glucoraphanin. Anyway, bottom line is by selecting the appropriate genotypes, the appropriate broccoli genetics, if you will, we identified some varieties that had very high levels of glucoraphanin. Paul and I made a conscious decision at that time that we were going to promote the use of broccoli sprouts, not broccoli seeds, because it turns out the seeds have the highest amount on a per gram basis of glucoraphanin. But at the time, no one had eaten broccoli seeds. They weren't green. They didn't have the sort of cachet or the appearance of eating healthy green vegetables. So we focused on sprouts, which had much higher levels than the mature plants, although lower levels than the seeds. And it turns out that then there is an enzyme that the plant tissue contains called myrosinase. And that enzyme converts glucoraphanin, the precursor, which is stored in vacuoles in the plant cells, to sulforaphane. And typically in nature, the plant does that as a protective mechanism. If an insect starts chewing on the leaf of a broccoli plant, for example, it breaks open cells, right? And so those cells then release their glucoraphanin and the enzyme that's present at the same site hydrolyzes glucoraphanin and forms sulforaphane. And sulforaphane repels those bugs or is, in some cases, toxic to those bugs. So they go, and they fly away or they crawl away. But it turns out that sulforaphane is also a foreign compound for our cells, but in the process of being recognized and chucked out of the cell, if you will, it upregulates the protective enzymes in those cells. And so that's why it's so special. Like a hormetic effect. Like a hormetic effect. Yeah. Yeah. So clearly, if all you ate was sulforaphane, you'd be in trouble. Yeah. But the same with just about anything you can suggest. So it gears up or it cranks up the protective mechanisms of the cells. and one of those I guess one of the main projective It gears up or it cranks up the protective mechanisms of the cells. And one of those, I guess, one of the main protective mechanisms would be the NRF2 pathway. Yeah. So I have a feeling that sulforaphane would be just another interesting phytochemical if at almost the same time we, and I use the term we loosely because I was only very peripherally involved with this, but a number of people at Johns Hopkins and in Japan discovered, and Japan and England I should say, but a small number of people discovered this NRF2 pathway and really fleshed out all the details of it. And this happened in parallel to the interest in sulforaphane and broccoli. And it turns out that the NRF2 pathway is an extremely important pathway for upregulating the protective enzymes and protective proteins, including perhaps the heat shock proteins in cells, so that they can protect themselves against various insults. It's an integral part of protection against a variety of chronic diseases. And as I say, Tom Kensler, Paul Talalay, Albana Dunkova-Kostova, all at Hopkins, Masi Yamamoto in Japan, John Hayes in England. Excuse me. And I'm certainly leaving out a few people, but a small number of people initially put this pathway on the map. And it turns out that the NRF2 pathway controls something between 3% and 5% of our cellular proteins. So it's very important. Wow, I didn't realize it that much. Yeah, and why is it important? It's important because it recognizes molecules like sulforaphane through a system, a biochemical system, that I hesitate to explain without props and graphs, and also because I'm not the world's expert on this, certainly, but it recognizes sulforaphane or other similar molecules as they enter cells in the cytoplasm of the cells. Then there is actually a chaperone protein that's in the cytoplasm. It's called KEEP1. That molecule, when it binds to sulforaphane or vice versa, changes in conformation and it releases NRF2, which then migrates to the nucleus and turns on or upregulates the antioxidant response element, which is responsible for the transcription, for initiating transcription of a whole series of protective genes or genes encoding for a bunch of protective enzymes. So, it's a, and this happens very quickly, this protective response, and it's quite efficient. So to get back to sulforaphane, sulforaphane was discovered, and then everybody started searching for the mechanism by which it acted. NRF2, the KEEP1 NRF2 mechanism was discovered, and they sort of both developed a following, if you will, in parallel, and it turns out that sulforaphane is still probably the most potent activator of NRF2 to be found naturally from the natural world. There have been synthetic activators that are more potent that have been produced, been made chemically, but sulforaphane still sort of takes the cake in terms of its protective ability and ability to upregulate protective enzymes. I should, you know, when I give lectures to students, I frequently make the point out to them how they're doing this glucoraphanin to sulforaphane conversion. So I'll do it for this webinar. When you chew on a red radish, you're familiar with the fact that the first sensation is cool and crunchy, and then within 20, 30 seconds, you develop heat, you start tearing, your nose starts running, it has a lacrimating effect. So what you're doing is you're acting like that insect that I told you lands on the leaf of a broccoli plant. You're breaking the plant cells by crunching on the radish. You're releasing a compound that's very, very similar to glucoraphanin. It's actually called glucoraphanin in radishes. It happens to be more of a lacrimator. It's got a more mucus-inducing effect in people. And you're letting myrosinase in those radish tissues act on glucoraphanin and form sulforaphene and some other related isothiocyanates. That's the broad name for that category. So it happens that fast when you chew on fresh vegetables that contain this system. Does sulforaphene also activate NRF2? It does, but to a lesser degree than sulforaphane. So many of these isothiocyanates also activate NRF2, but not to the same degree as sulfur phane. They do. And just in case you're about to ask me, you find this system, it's been dubbed the mustard oil bomb by some 20 or 30 years ago. You find this system in almost exclusively in cruciferous vegetables or brassica vegetables or coal crops, they're sometimes called, depending upon where you come from, where you hail from. In Eastern Europe, they typically call them coal crops. So this happens to be a very large family of, I don't know, five or 600 genera, many, many thousands of species. Yeah, I know like maybe 10 of them. Well, we know maybe 20, but there are very many of them. And they grow worldwide, although the brassica or the coal crops that we're familiar with in the United States are all temperate climate crops. They're common to areas where there's a cold winter or freeze in the winter. There are some interesting relatives we can talk about later or now, if you'd like, which are tropical. Moringa is the one which has gotten most attention recently and we've been interested in for about 20 years. It's a relative of broccoli, but it's a tropical plant. It's actually a tree. And it, too, has this system of glucosinolate, myrosinase, and isothiocyanate, the former being the storage form in the plant, the latter being the biologically active form. Okay. Yeah, maybe we can get to that a little bit later, but talk a little bit more about the sulforaphane and the broccoli sprouts. I wanted to ask you something because you mentioned it really piqued my attention. As you said, the broccoli seeds actually had a higher amount of glucoraphanin than the sprout. If I were to say take those broccoli seeds, because I sprout, if I were to take those broccoli seeds, add a little water and blend them in a blender, would that activate myrosinase within the seed, the crushing of the seed? You bet. So I could actually get a higher, more potent amount of sulforaphane, theoretically, if I were to just take the seeds. Because, man, that would be easier than sprouting, in a way. That's true. So, interestingly, when we discovered that, and this was published in 1997, so it's ancient history. It's probably before you were born, right? So when we discovered that broccoli sprouts and seeds were such a potent source of sulforaphane or its precursor, we weren't aware that anybody had eaten broccoli seeds. People eat all sorts of seeds, poppy seeds and rapeseed or canola seed, in fact, are used to express oil, and they're a close relative. But no one had eaten broccoli seeds. And when we tried them, they're quite bitter. But interestingly, if you bake them just gently, don't scorch them, if you bake them, they're a very nutty taste, and they're sort of pleasant tasting. The problem is if you bake them, you kill the enzyme, you kill myrosinase. Right, so that's an important dimension. Yeah, so there actually have been some epidemiologic studies, and I'm getting off topic a bit, but some epidemiologic studies suggesting that people who eat certain amounts of cruciferous vegetables have reduced risks of various cancers. Breast cancer and lung cancer are high on the list of cancers that have been studied. And it turns out that if you eat raw cruciferous vegetables, you're a bit better protected, again, based on the epidemiology. This has not been the subject of interventions of randomized clinical trials, for example. But it looks like the protective effect is greater if you eat raw vegetables. But now a lot of people don't like to eat raw cauliflower or broccoli or, well, radishes they do. So at any rate, you asked about the content in broccoli seeds. And indeed, they have much more glucoraphanin, and they have plenty of active myrosinase. But I have a feeling, I've never made a smoothie from raw broccoli seeds. I have a feeling it'd be pretty bitter. I'll let you know, because I'm going to try it. I thought you might. But you made a really important point for people, and that is that the myrosinase enzyme is heat-s sensitive. And as you pointed out, most people like to cook their cauliflower and broccoli or slightly steam it. And their tradeoff for that is maybe it tastes a little better, but also it inactivates the myrosinase enzyme. So they're not actually getting as much sulforaphane from the glucoraphanin as they would if they were to just chew on that raw broccoli. But what about the myrosinase enzyme? Is the stability the same throughout all the cruciferous families? So if you look at the broccoli sprouts versus the mature broccoli or kale? So myrosinase appears to be about as stable throughout the family. There are differences, subtle differences to the protein composition of myrosinases in different cruciferous vegetables, to be sure. Subtle enough so that I can't even describe them to you. I mean, they're minor differences, but they certainly must confer increased or decreased stability or catalytic ability on those molecules. Interestingly, if you ingest glucoraphanin or glucosinolates without myrosinase at all, you then can count on the bacteria in your gut, in your intestines primarily, to do that, to make that conversion. And you know, sometimes scientists think they're so darn smart. We, just to back up just a little bit, we observed that when you deliver just glucoraphanin to people, just give them one dose, one reasonable amount, that which they would get in a serving of broccoli. And then we collected their urine for 24 hours. We asked them to collect their urine for 24 hours. So you get a full 24-hour collection, which pretty much spans the period during which the enzyme myrosinase acts. Sulforaphane goes into cells, gets recognized, turns on Nrf2, gets spit back out, and then gets excreted in the urine. So by collecting a 24-hour urine, we can pretty much, we can get a very good idea of how much bioavailability there is, how much metabolism and availability. And it turns out that if we looked at 100 different people, and we did, after giving them one dose of glucoraphanin, their bioavailability, the amount they gave back to us in their urine, was all over the map. It ranged from very, very little, but always something, to 40 or 50 or even 60 or 70% of what we gave them. But the mean was pretty low. It was about 10%. So most people converted and metabolized and excreted only about 10% of what they were given. So when you give sulforaphane itself, the end product, the active ingredient, if you will, we get more like 70%, 75%, 80% bioavailability. Still a bit of variability person to person. But since we're up sort of near maximum, it appeared to be not as great. And well, it was not as great in terms of a percent of the whole. So that sounds a little convoluted. But essentially, most sulforaphane came back at us in the urine and was available. So in our infinite wisdom, we thought, ah, if we co-deliver myrosinase, if we give these people active myrosinase in addition to glucoraphanin, they're all going to give back 70% to 90% of the metabolites. And we'll get rid of the variability person to person. Didn't happen that way. Really? Really. It didn't happen that way. What did happen is that we moved the bar up so that instead of 10% bioavailability or 70%, we had about 35% or 40%. So the average moved up substantially. It was about three times, three or four times more. But there was still quite large person-to-person variability. So we have to sort of step back a little bit and say, yes, this is due to intrinsic myrosinase activity in the gut because certainly we hadn't done anything to get rid of that. That was still acting on these molecules. But also just innate mammalian genetics, differences between you and me and the way we process these metabolites once they're formed, differences in absorption, differences in distribution and metabolism. So there's a lot we still don't know. There's a whole lot we still don't know. But as a result of this sort of cocky thinking that we could abolish this variability and at least have a very predictable amount delivered to people, we did learn that we can greatly increase bioavailability by delivering it with myrosinase. And in fact, there are now companies that are selling glucoraphanin plus myrosinase. You have to be careful if you buy those supplements because it's not a given that they're going to be as stable as multivitamins and things that you can just leave on the shelf for years. And so you need to pay attention to the expiration dates on those products that have live active enzyme. I'm not in the supplement business, but I've become more and more familiar with it. Most supplement makers, it appears, don't like to sell stuff that has to be refrigerated or put in a freezer. I think it increases their cost. And so most of the supplements that I'm aware of are made to be shelf-stable. But I think it won't...if you were to buy a supplement that has active myrosinase or that says they have active myrosinase, I think it wouldn't hurt to put them in a refrigerator, treat them as you would treat a probiotic supplement. And you've actually measured the content of glucoraphanin and or sulforaphane in some of these supplements that are found on the market. Is that correct? We have. And you found that there's only a really small amount of supplements that actually contain what they say they contain. Yes."

Gut Microbiome: Diet

They're one of a number of companies that have a decent, I shouldn't say that have a decent one.

"They're one of a number of companies that have a decent, I shouldn't say that have a decent one. They're probably, you know, if you put this on a webinar, there are probably going to be 10 companies that say, we have a decent one too."

Alzheimer Prevention Discussion

Since we got our grant, there's a very interesting and I think quite important publication from Tom Mestelli's group at the NIH showing that, in fact, NRF2 is very intimately related to this process in...

"And there's even some, as it's called, crosstalk between the NRF2 pathway and the NF-kappa B pathway, so the inflammatory and the cytoprotective pathway. Sulforfane also upregulates the so-called heat shock response. And I'll try to tie these together in a second, but there are a number of other pathways in which it's active. The mTOR pathway is another. So with all of these biochemical pathways that sulforaphane targets, many of them seemed to come together in a few of the neurodegenerative or neurodevelopmental diseases. And so autism was really the first one that I guess I can say was put in our lap or came to our attention. So Dr. Andy Zimmerman, a colleague who was at the time at Harvard Medical School in the Mass General Hospital, came to Paul Tallalea back, I don't know exactly when, 2008 or 9 or 10 or somewhere in that range. And Andy Zimmerman had shown previously, this was published in 2007, that the so-called fever response of children with autism was real. He sort of codified it and got it in print. Apparently, psychiatrists and caregivers had been commenting anecdotally for a long time that some of their charges, their kids or the people they were giving care to who had autism, when they got a fever, they got better. Their symptoms reversed or relapsed. So autism is characterized by a number of things, including repetitive motions, not making eye contact, social and behavioral impairment, if you will. And so a lot of these characteristics got a lot better when kids had fevers. And so back to Dr. Zimmerman, he knew that we and others had shown that sulforaphane was effective in upregulating the heat shock response. And so his question to Paul was, hey, why don't we see if sulforaphane also helps autism? Because in half of the kids, when they get a fever, the symptoms go away, or they don't go away, but they improve. And that's likely related to this heat shock response. Wouldn't it be interesting if sulforaphane has an effect? Now, as all of us got thinking about it, there were clearly a number of other mechanisms by which sulforaphane could be acting, including reduction of inflammation and enhancement of the antioxidant enzymes, more effective clearance of oxidative reactive oxygen and reactive nitrogen species. Right. I never thought about heat shock proteins playing a role in autism. That's very interesting. I mean, neurodegenerative diseases for sure, but that's an interesting connection he was making that I wouldn't have made. But I can see how he's making it. Yes, so the paper is 2007 Curran, C-U-R-R-A-N, is the first author."

Sulforaphane: Cancer

One thing that I can tell you is that in the quest for that answer, quite recently, Kitty Stevenson, who works here with us, and I started looking at the ability of sulforaphane to inhibit...

"Biomarker rich, then there's a washout period, and then everybody goes on the sulforaphane product, the Abmacol, for another 15 weeks. Dr. Hua Liu and I, she's doing most of the biomarker work here at Hopkins."

Alzheimer Prevention Discussion

The supposition is that markers of NRF2 activation are going to go up, and heat shock protein markers are going to go up.

"We would love for it to be true. But same thing with autism. I guess if it were cheap and easy to do and nobody cared about the subjects involved, there'd be a lot of trials. A lot of them would be lousy trials. and a lot of people would have their hopes raised only to maybe 10 or 15 years down the road find out that, yeah, those trials weren't really done that well. So all of the oversight, all of the self-criticism and the peer criticism is probably worth it because I think it does serve a purpose. Anyway, back to the story. So enough philosophizing. So we have this follow-up trial underway. Interestingly, there are four additional autism trials all using Avmacol. And this is, you know, if it doesn't work, I'm to blame because I identified it as something that looked like it was the best of what was out there. And I got the company to agree. I mean, this is something that's available for people right now. It's available. And we know that it produces sulforaphane and we know that it's a decent product. And it's been through all sorts of quality assurance. But so, you know, when people who came to us and said we'd like to do an autism trial, we'd like to model it after Andy's original trial, essentially try to replicate the findings, we want more of that sulforaphane that you produced for it. And my answer has had to be, I don't have any more. And I'll show you as my witness, I'll show you our freezer and show you that we don't have any more in our clinical freezer. So we just can't produce it anymore. And so we had to suggest that people switch to something commercial. So four other studies. One of them has finished its patient accruals at UCSF, and we're in the process now of evaluating biomarkers, and they're using metabolomics to evaluate biomarkers. They're looking at small molecules produced by the various metabolic pathways that are either induced or upregulated or not, and hope to be able to make some correlations with symptom reduction and biochemistry. There is a trial just starting at University of North Carolina. There is a trial at Rutgers that's...I'm not sure how far along they are, pretty far along, I think. And all three of those trials are about the same order of magnitude as our original trial, 20 to 50 patients or subjects. The other trial is in China, and there are, I'm going to get this wrong, there are either 120 or 180 subjects. And that's just starting. The study drug or supplement is there. And this is at a school for autistic kids in Changsha, China. And you can read the descriptions of most of these trials, I think all of them, on clinicaltrials.gov, which is the government's database for clinical trials. So again, all these studies are looking at biomarkers of inflammation. As you say, IL-6 is one of the key markers that people are looking at, COX-2, TNF-alpha. The supposition is that those markers are going to go down. The supposition is that markers of NRF2 activation are going to go up, and heat shock protein markers are going to go up. We'll see. Right. Well, I mean, it's been shown in people that don't have autism that are given sulforaphane, at least. I guess it may depend on the dose, but that has been shown. The heat shock protein, that really caught my attention. I came across it when I was reading about sulforaphane and how it can be neuroprotective for Alzheimer's disease, Parkinson's, and even Huntington's. These are all diseases of protein aggregation, of which heat shock proteins play a major role in repairing and preventing both. They do both. So I was very surprised. I guess it wasn't that shocking once I found out that sulforaphane activates because it is a stress response pathway. Heat shock proteins do respond to stress like heat stress. So I guess I wasn't that shocked, but I was a little surprised at first to see that it plays a role. And possibly that's how it's helping prevent and protect against some of these neurodegenerative diseases."

Sulforaphane: Cancer

Another question, just to get back to some of what you were initially saying about how this plant, which is growing in some of these tropical regions and more developed nations and how it can...

"I think it's probably the sulforaphane. So when you blend it and drink it immediately, you probably haven't given enough time for all of the glucosinolates to be converted to sulforaphane. Do you have any idea how long, what the temporal sort of timeline would be? Probably a couple of minutes to... Yeah. I mean, so when we did these conversions in big vats, 600... I think there were 600, no, 200 or 300-gallon steam kettles at Argon freeze-dry, we added daikon sprouts, homogenized, and let the stew sit for two hours to get complete hydrolysis. If you actually, you can do the calculation of sort of the half-life of the enzyme and how fast it works. And so it certainly takes a matter of many minutes. So in your particular case with your broccoli sprouts, maybe it was 10 minutes or maybe it takes a half hour to get completely converted. So probably what you were doing is chugging the not-so-nasty tasting glucosinolatesates. It does get more foul-tasting as you would have said it. Yeah, exactly. And so the conversion is happening on the way down the tubes, and then when it gets to your intestines, probably more happens. And I should mention, speaking of intestines, we have no idea where most of the myrosinase activity is. Most of the bacteria in your guts are in your large intestine, but I wouldn't rule out the fact that a fair amount of conversion occurs in the small intestine too. Really? Yeah. And I say that based on the fact on the pharmacokinetics that we see because we know that we see the metabolites of sulforaphane occur or appear in the blood within 10 minutes of ingestion. And when you talk to gastroenterologists about gut transit time, it certainly stands That's a reason that it takes more than 10 minutes to get or 15 minutes to get all the way to your large intestine and undergo a chemical reaction. So, of course, it's very difficult to access the small intestine of a person experimentally. It's been done. Do you know how long, so for example, if I drink my broccoli sprout on Monday, I'm going to activate Nrf2. I'll have some of these metabolites, glutathione, things like that. How long does that reaction occur before then? So I've been taking this broccoli smoothie when we're not traveling and we're home, we're getting it like probably five days a week."

Sulforaphane: Cancer

is going to be flush from your system and the pharmacokinetics look like this and they're there, it's there, it appears, its metabolites appear and it's gone.

"Well, indeed. And I'm just wondering if there's anything we were thinking about before we sat down together that we sort of missed. And yeah, I've got one. We missed something. Urinary health."

Cancer Prevention Discussion

is going to be flush from your system and the pharmacokinetics look like this and they're there, it's there, it appears, its metabolites appear and it's gone.

"Well, indeed. And I'm just wondering if there's anything we were thinking about before we sat down together that we sort of missed. And yeah, I've got one. We missed something. Urinary health."