How Much LONGER Will You Live By Eating Sulforaphane? David Roberts & John Gildea | 1175

I just took 15 of these. I'm feeling like a noticeable shift in energy. I'm kind of liking this. Is this placebo? I mean, it seems pretty fast.

Yeah, there's a lot of people that love the brain buzz.

It feels like neurotropic E. I mean.

That'S one of the benefits. Sultry of fame is the brain derived nootropic factor bdnf.

You ruined my joke. I was gonna say. So I hear you guys are into bdsm.

Yeah.

And then it was like, what? And then I was, oh, I mean, bdnf. Sorry. Thanks for ruining my joke. Sorry. You're listening to the Human Upgrade with Dave as Asprey. You're listening to the Human Upgrade with Dave Asprey. Today is a super nerd longevity muscle performance episode, and it's because we're going to talk about sulforaphane and NRF2 activation. It's a live interview, which are my favorites here in Austin, Texas at my studios. And if you're watching on YouTube or any of the video channels, you recognize that there's two guys here. One of them is Dr. John Gilday, Johns Hopkins trained PhD with only 60 scientific publications from 20 NIH studies. So he's just getting going in his career. He's an expert in cell culture and exosomes, which you've heard me talk about on the show before, related to stem cells and things like that. And he's the guy who figured out how to stabilize the sulforaphane compounds, which you might have heard of, especially if you read my longevity book called Superhuman. I talk a lot about NRF too. Well, it's. It's kind of an honor to have the people who did the work in the labs and have done all the things that aren't in their papers. So I'm going to get to go deep and you're going to get to participate and understand what could you do if you're nrf. Two pathways and what would be in it for you? And our second guest here is David Roberts, a master's in public health from Johns Hopkins, master's in biochemical engineering, and 20 years of public health experience on three different continents. So we have some guys who are, well, we'll say, very experienced in the field. And part of my job for you on the Human Upgrade is to find people maybe who haven't written books and are deep in the trenches, but have deep knowledge that they can share with you that are going to help you make better decisions so you're more in control of Your own biology. And the company that they work with is called Brock Elite, which is really the only way to get the stabilized mix of things that is shown to work in studies. So, John and David, welcome. It's an honor to have you in the studio.

Yeah, that's great.

Thank you, Dave.

Thanks for having us.

All right. Should kids really eat their broccoli? If so, why kids should eat their broccoli?

Yes. I mean, just because we have a supplement, we. We don't say, hey, skip your broccoli. Part of it is, you know, if you think about it, there are benefits outside of sulforaphane and especially with microbiome. So, yeah, I'd say it's. We're fans of broccoli kinds of mature broccoli.

Okay.

You'll hear us talk a lot about synergies, and one of the ones that, when this topic comes up, we'll often talk about is that sulforaphane is the. Is the most. Most published molecule from. From that plant. But there are. There are many others, and we were interested in really stabilizing all of them if all the ones that are made by the one enzyme called myrosinase. And so in the adult broccoli is our two compounds that have been shown in papers to be synergistic with sulforaphane. And that's dim any 3C. And so even if you're taking our product, we would say eat some adult broccoli because you're getting two compounds that aren't in ours.

Why not broccoli sprouts?

I was going to say, actually, before you ask, that is, we're also big fans of broccoli sprouts.

Okay. So I heard a dull broccoli several times, that just because it's more studied or it's bulkier or.

I mean, it depends on what you're going after. I mean, most people won't necessarily be disciplined enough to grow broccoli sprouts.

If you are, then that's the way.

To go, because the broccoli sprouts actually have about 50 to 100 times more of the good chemical, which is sulpurane, than the mature broccoli. And it's easy to do. Super easy to do. But, you know, I mean, not everybody will do it.

So I've seen studies on thyroid suppression from isothiocyanates from excessive Brassica consumption. In fact, it happened to me when I was a raw vegan and ate stupid amounts of kale and broccoli raw and all that stuff. Are you concerned about isothiocyanates which is.

An ingredient in broccoli, as interesting as the bad guys are the adult versions of the chemicals. So I3C and DIM are the major culprits for that. But sulforaphane can. Those studies that you're talking about, where they talked about decreased function of thyroid only happens when you have low iodine. In that context, you can decrease thyroid function. But there's a number of papers that show that sulforaphane itself, if you don't have iodine, actually improves thyroid function.

Oh, this is interesting. So there's two compounds on there, and if you're getting the sulforaphane, which is the, I would say, the most precious molecule in broccoli, you're getting it.

That's correct.

I've taught people for years that when you eat cooked broccoli, you ought to have a piece of uncooked broccoli or a piece of radish, which will do the same thing and kind of smash it for a minute and then eat just one bite of that. Can you tell me why that is good advice?

Yeah.

Yeah. So the. You. Why don't you take this one? I can go too deep and reveal secrets.

Yeah, Well, I mean, part of it has to do with the whole chemical reaction that's happening. So basically, most of the broccoli supplements on the market have what's called glucoraphanin, which is also called sulforaphane glucosinolate, kind of to throw people off to think it's sulforaphane is my opinion on that. But it's the precursor molecule, so it's stable, which. So you can put it into capsules. So in that mature head of broccoli, you take a bite of it that's raw, you start chewing it, and it breaks down the cell wall, which has myrosinase in it. That myrosinase gets released, it has a chemical reaction with the glucoraphanin, and produces sulforaphane. And so you swallow it, you get the benefit. So, you know, the just having the glucoraphan in products, though, out there, which is the vast majority of the broccoli supplements. There is one other sulforaphane product on the market that's from France. So we are the. We say we're the only naturally derived stabilized sulforaphane product, that they derive theirs through chemicals and sulfate solvents. But basically the glucoraphanin, you know, those supplement companies say you swallow the glucoraphanin and your gut bacteria can convert it into sulforaphane.

Don't magically do that if you have the gut bacteria. Yeah.

And so, I mean, our hypothesis is that the people who really need that conversion don't have the right gut bacteria and pro. And so it's. It's a crapshoot.

It.

It's a common thing that supplement companies will do. You'll see these vegan companies say we have vegan omega 3s, guys, it takes 45 grams of those to convert to 1 gram of EP and DHA if you have all the enzymes and cofactors, which you don't because you're vegan, so you're starved of minerals. So, like, you can hope it'll happen. I also see people use wild yam extract because you can make progesterone from yams. It takes seven steps in a laboratory that is not in your gut to do that. Wild yams don't affect progesterone, but supplement companies do this. And so what you guys have done, clearly you have a little bit of science backing what you're doing. So with broccoli, you put together the actual sulforaphane and then you stabilize it in a way that's unique. Can you talk about why only you guys can do that or is that like a trade secret?

Yeah, I mean, we, we purposefully. Because it's pretty hard to do. Yeah, Trade secreted it. And in fact, we were the ones who were making it all the time. And it's like, it's pretty backbreaking. And, and so, yeah, you hear about putting patents in and then the Chinese ripping it off. And so, you know, we were like.

I'm not asking you to disclose. If you can, it's fine. Yeah, Joe. Joe Rogan did that to me. He's like, tell me how you make bulletproof coffee. Because he's an investor in a company that was trying to copy bulletproof coffee. And I'm like, you know, coke doesn't give you the recipe and neither am I. And it's a fair answer. But we'll say you've discovered a proprietary way to stabilize it that no one else can do. So I don't have to count on maybe my gut bacteria and breaking this down. And guys, if you're not, you're saying, I don't want to take another supplement. Fine, Go out and buy a pound of broccoli. Look at how much that costs and then cut off a little bit of it, smush it up, cook your broccoli, or do whatever torturous thing you're going to do. I recommend steaming and then blending it with butter instead of olive oil. And then eat your bitter broccoli stuff and eat the thing. Okay, cool. You got some sulforaphane. That's the way to make it. I just don't do it that often, although I have at times in life.

We estimate about 5 pounds mature broccoli in one serving, which is 2 calories.

So just be vegan because you know there's protein in broccoli, right?

Just very little.

You're angering the vegans. You can't, you can't say there's not protein in broccoli.

So it was interesting when, when you're talking about your, your biohack of getting some sulforaphane from adult broccoli. That's the first time I've heard of that. And it makes sense because the enzyme is heat unstable, right? And the product is heat unstable. And so by cooking the broccoli well, you're probably breaking down some of that cellular material and so that you can release the heat stable version of the precursor. And, and then you're taking the live broccoli where you'll get the active myrosinase. And it's a very active enzyme.

It's very processed, it's super active. So when I was running the Upgrade Cafe in Santa Monica for about eight years at a restaurant based on my recipes, anytime you got cooked broccoli and cauliflower and stuff like that, there was always a piece of watermelon radish on top because that contains the same enzymes, right? And people didn't know why they were doing that, but it was to release the sulforaphane from it. Because this is a really potent NRF2 activator, by the way. So is coffee, right?

I don't know. That was the caffeine acid.

There's, I'm trying to think of the studies in Superhuman and it was Alberto Viodo, who's a drug discovery guy in the jungle turned shaman after he's like, well, no one has heart disease. Screw that. I'm staying here to learn why. And We've talked about NRF2 activation and I believe it's either fasting and coffee, something like that.

But that's interesting.

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I think the clearest data, I mean, because I'm a Drosophila person, a fruit fly person in my PhD. We're sort of elitists in the respect that we think the only way to really study biology well is to do a genetic screen, completely unbiased screen. You find a phenotype that you're interested in, you knock out one gene at a time in a gigantic screen. And then all the genes that are involved in that end up being the things that are, that are pointing towards that effect, that phenotype. And so I think in the longevity field C. Elegans is, is really has been way out in front and there are two, two C. Elegans people at Hopkins when I was there. So I got a lot of C. Elegans related training what, what that means.

To translate for people who are less laboratory oriented. You can basically do experiments in bacteria and stuff like that. You can do research in nematodes and then fruit flies. So in sort of the hierarchy of longevity research and after fruit flies in Usually you do mice and then after that you might as well just do some human trials and measure it with an aging clock. And that's kind of the how a drug or even a supplement might be tested. We discover it in these low level creatures and we move up. And so you worked out basically step two of that process.

Yeah. So I think a really interesting set of studies, a very complete set of studies for the longevity and C. Elegans is they, they have nine major genetic groups that show longevity and so they added sulforaphane, got, got extra life in the end and in the C. Elegans, this little worm and then they knocked out those nine pathways one at a time. And it was one of them that completely blocked the benefit.

Wait, is Elegans the worm or the fruit fly?

C. Elegans is the worm.

I was confused. What's the name of the fruit fly? That's the drosophilia one. Yeah, I got it back. Anyway guys, what I just said there, I switched the first two. So it's worms. You're at level one, basically.

Yeah. So this one is C. Elegans and so that pathway is igf, so it's the insulin pathway and IGF one. And so from just as a little bit of background in IGF1 that is in the, in the diabetes world, your, your insulin level is high, you're fast aging, you're speeding up aging. Insulin resistance of course is terrible thing. You know, more than half population probably is insulin resistant.

And you would Measure this by HbA1c if you're using Upgrade Health. It's one of the markers that we, that we measured for you, which measures like what's the average level of blood sugar and therefore insulin over the last couple months. And you want it under 4.9.

Yeah, perfect. So, so though you can make that, that jump between this little tiny worm that only has 800 and something cells in it the whole way to humans, that, that there's consistency all the way along all of the model systems. And so because insulin term IGF1 signaling turned out to be the major factor in, in, in C. Elegans, you know that that's one of the main ways that it works in humans. And so insulin is how you get glucose into the cells and so it's driving function. And when you do that, well, you're, you're, you're driving, driving function well. And that whole pathway that's downstream of it is, is all related to all the other things that we talk about, how mitochondria work, you know, how you utilize oxygen, all the big things. So when you try to go right to humans, then we can show that if you take sulforaphane, your blood sugar comes down quickly, stays down. And if you do it for a while, your insulin comes down over time. And so that is one of the main pathways. And I like that one just because it's so consistent across all of the genetic models and in humans.

And longevity for you, if you're listening to that going, that's a lot. Insulin, if it's high is dangerous. Insulin if it's low, is actually more correlated with all cause mortality. In other words, if your insulin is too high or too low, your chances of dying go up. So you want to be able to use insulin or its cousin, insulin, like growth factor for what they do. That's good. They put on muscle, they cause tissue growth. So it's okay to have some insulin go up after you work out, for instance, because that's when you'd want to build muscle. But what's not clear is what is the relationship between NRF2 and IGF1 or.

Insulin like growth factor, at least in my mind, is because of the major pathways that at the cellular level, what it does. So NRF2 is working on this. Sulforaphane works on this pathway where nrf2 is a transcription factor, but its basal state is to be degraded. So it's down and then it's waiting for some kind of insult before it's upregulated and then takes care of the toxins, the extra reactive oxygen species. So it's, it's down normally and if you take a toxin, it'll be up, but that's obviously just taking care of that toxin. But if you can get that NRF2 to start signaling, because we're in this world that's swimming with toxins at all times, right? You're basically preemptively turning on this system without an injury. And it's doing the op. It's doing what it normally would do is mop up things. And so it, it turns on a whole set of enzymes. Because everybody talks about reactive oxygen species where you can take vitamin C, get one vitamin C, one reactive ox species, they're canceled out. This turns on a couple of hundred enzymes and each one of those enzymes is doing tens of thousands of reversal of reactive oxygen species over and over and over again. So it's really different than taking an antioxidant, which there's a lot of studies showing it actually blocks exercise recovery if you do it during exercise.

So will NRF2 block exercise recovery the way antioxidants do?

So we don't know that answer. But I wouldn't take it right before.

I take it after.

Good work done. You take it after because afterwards it'll.

It'Ll help you recover faster. Got it. One of the things that's interesting about NRF2, like you said, if it's higher and it's not because you got poisoned, then when you do get poisoned by pretty much being on an airplane or walking into an office building or smelling that person in Chanel number five or that that kid bathed in perfume because they haven't learned that people don't like that yet, all of those actually are system level insults that go to your liver and your, your kidneys and your cellular detox systems. So if your NRF2 levels are higher, your ability to be more resilient in the face of a toxic insult, even from an endotoxin from just, you know, eating the wrong burrito kind of a thing, like you're systemically going to be more resilient, which correlates with longevity.

That's a great example. And I think a lot of people don't realize that however many times you've, you've got one of those giant reactive oxygen species storm and made double stand breaks in your DNA is how many times you've, you've recruited all the factors that maintain your genome are recruited over to repair that double stranded break. And you see you're distracting who you're supposed to stay as. You know your development happens, you get all the genes turned on and off correctly. The rest of your life is forgetting what happened during development.

Yep.

And I mean, there's so many ways to get toxins. You know, you can eat them, breathe them, like you said you can. You know, there's a study in the 2000s, when I was coming out of public health school of women.

Who were.

Breastfeeding who had flame retardant in their breast milk.

Oh my gosh. Thank you California for forcing that and everything.

Yeah. And so it's. And they got it from sitting on couches that had the flame retardant. And so having the NRF2, so Sulforaphane being the best natural molecule at turning on NRF2, having that NRF2 on, it's the best that helps with phase two detox, basically. And so being able to clear those toxins. One of my favorite studies on detox is out of China. Hopkins was there. And you know, all these municipalities, these big cities, chock filled with all These pretty horrible. Yeah, you get black snot basically if you walk outside. And so they show just a broccoli sprout beverage taken once you peed out all these like benzenes, you know, and so it, it works fast and it does, it does clear the toxins.

So in my biohacking picture, when I teach people how to be more resilient in the face of toxins and I mean I fly all over the world and I have a, pretty, well most people say a high stress lifestyle. So I've, I've conquered circadian biology. I don't get jet lag anywhere on the planet. I control color and angle of light and food timing and all this weird stuff and I teach people how to do that. And then I look at glutathione as my front line protector because it just gets rid of a lot of stuff in the liver. And then I look at calcium D glucarate for that phase two because it's glucarination. Guys, you're taking notes on this, right? It's in all my books and all, but whatever. And then there's NRF2. So in those three, in terms of detox, do I do all three? Is NRF2 more important than the calcium D glucarate? Like walk me through like a real, real world, Highly resilient. I walked into a cloud of auto exhaust and it fell to the ground around me and I conquered. Give me that vibe.

Yeah. I mean, John, I can go into more detail, but basically when he was talking about the antioxidant response element that nrf2 turns on, it's a 200 genes that create these antioxidants. Well, the glutathione S is it transferase, gst, gst. So basically those are some of the enzymes produced.

So if you're taking NRF2, you might not take glutathione because you're just going to make it anyway and you'll make it inside the cells. And most of the glutathione supplements you can take, unless there's certain micelles or liposomes, they're going to primarily go into the liver, which means if you took Tylenol or drank alcohol, good for you. But if you wanted the longevity effects of glutathione, it's harder to get it in. And I've had a few experts on glutathione with some nanoparticles and different ways to get it inside cells. And you're like, why add it? You just grow it by taking broccoli to upregulate NRF2? Yes. Okay.

Yeah. So, similarly to the first thing, the analogy of turning on antioxidant enzymes, same thing as with all the phase two detoxification enzymes. So NRF2 is the major inducer of those sets of genes. It's a whole program made to get rid of toxins. So it blocks the reactive oxygen species that happens from a toxin, and it also turns on the detox pathway, where if those toxins, they get bound by glutathione, then it's the whole process of binding to glutathione, making sure it's in its reduced state. So GSH to GSSG is. Is whether it's in its reduced state. So glutathione only works in its reduced state. It'll bind the toxin, and then glutathione S transferases are made to. To conjugate those two together. So it turns on all six glutathione as transparases, and then it turns on all of these processes that you were talking about. Glucuronidation, sulfation, and quinylation. So there's a whole set of things that are meant to carry that out of your body. So it'll get it out of the cell soluble, transported into the. Into the interstitial fluid.

And most people talk about it at three phases of detox. So basically, sulforaphane works in all three phases.

If you've been listening to the human upgrade for even a little while, you know that alcohol isn't good for you. Also, if you're like 99% of people out there, you probably do drink on occasion because it's a social experience and it tastes good, and let's face it, it feels good. So what do you do about it? Well, the thing I'm most excited about is a product called ZBiotics, because ZBiotics makes a genetically engineered probiotic drink. And you have this before you have alcohol, and for the next 24 hours, it helps to protect you from the toxic breakdown of alcohol. And it's genetically engineered, but it's not the kind of genetically engineered crop stuff we're dealing with. It's actually an edited bacteria that can't reproduce. And what it does is it just breaks alcohol down into something that's not toxic. It was invented by PhD scientists to tackle rough mornings after drinking, because you know how those PhDs are. Here's why it works. When you drink, alcohol gets converted into a toxic byproduct called aldehyde. In your gut. It's that product, not dehydration that's making you feel like crap the next day. Zebiotics produces an enzyme that breaks that toxic byproduct down. All you have to do is remember to make Zebiotics your first drink of the night and then you'll feel so much better tomorrow. Every time I serve alcohol at parties at my house, I put Zbiotics out and everyone says, wow, I feel so different. And when I have sake with my sushi, I take zebiotic. So if you're planning a little partying this summer, definitely take care of your liver and take care of your aging with zbiotic. Go to zbiotics.com Dave to get 15% off your first order. Zebiotics has a hundred percent money back guarantee, so if you are unsatisfied for any reason, they'll give your money back, no questions asked. This stuff really works. This is really cool because I think everyone listening to the show knows there's a lot of toxins now that didn't exist 10 years ago and there's from 10 years before that. And it's weird, people aren't fertile anymore. When I was 30, which wasn't that long ago, I sure hope that she doesn't get pregnant. My 30 year old friends today are going, I hope I can get pregnant and our fertility has dropped. And I know that a major part of that, not the only part, but a major part of that is just an increase in toxins. And because I had a lot of mold toxins as a kid, a lot of other things going on, and I was £300 and had hormone disruption, I've paid careful attention for years to getting toxins out of my body, which has made me incredibly resilient, especially given where I came from. But one of the things that stood out with sulforaphanes is reducing symptoms as lethargy and irritability in autistic people. They have detox pathway problems. I know I used to have Asperger's syndrome until I got, you know, upregulated my mitochondrial function, got my detox pathways working and reprogrammed my nervous system, which is a huge amount of work. It's better to just not have autistic kids if you can avoid it. Maybe by nrf2. What do we know about autism and its kissing cousin, ADHD and NRF2?

Beautiful study. We've talked about it a number of times and as far as we know.

Let'S focus on the NRF too.

Yeah, yeah.

No claims for broccoli made by the scientists behind Broccoli. This is a study that you guys didn't do. We're talking about a study of what NRF2 did for autism. And there is no. No correlation implied that broccoli does anything for autism. Except as the host of the show, I can say. Seems intriguing there. Did I cover all of your bases?

Yeah, I'm sweating.

I'm sweating.

All right, tell me about autism and NRF2.

So the Hopkins study is they used a particular version of autism that's really recalcitrant. So it's older autistic kids. So it's hard to get IRB approval to study very young kids. So they started a broccoli sprout extract experiment on these older autistic, like 7, 8. Older or 15, 10 to 22. Something.

29 was the oldest.

Wow.

And so they gave him this broccoli sprout extract for eight weeks and 12 weeks. Twelve weeks, was it?

Yeah.

And it was something like 70% reduction in a whole host of. Of measurable.

Whoa.

Yeah, they did. They basically did two different autistic scale scores, so written scores or written tests that they could score.

Yeah.

And there was as high as 70, but the average was a 30% improvement, basically.

That's insane. I have a couple employees with adult autistic kids, and I did not reverse mine mostly until I was about 35. And people are saying, hey, you can't reverse it. Whatever, guys. Like, get your detox pathways working, fix your mitochondria, fix the lining on your nerves by changing your cell membranes out, and then retrain your hearing, your vision, and the way you move and a bunch of other stuff, and magically, you can recover at almost any time as long as you know the original insult that caused it. And it's not just one cause. Right. It's. There's a whole bunch of things that cause neuroimmunity and cause cellular dysfunction. Right. So whether it's metals or molds or flame retardants or whatever else, like, you remove the insult, fix the system, retrain the system. But if just by getting the toxins out. And I've seen this lots of times, you know, you. You detox a kid, and then two weeks later, they're much better. This is fascinating because you're the only thing I know of that does all three pathways at once. I mean, I take a handful of supplements every day for detox, but this is cool.

Yeah.

And.

And, I mean, one of the things that. That, you know, it's good to mention with that paper is once they stop the broccoli sprout beverage, they returned to baseline and so it was, so, yeah, it was pretty interesting. Yeah. But kind of, you know, along the lines of. And it's really related to the conversation.

The.

A lot of the reactive oxygen species in the mitochondria get dealt with by nrf2, which helps the mitochondria and so it helps nrf2 helps keep the mitochondria in that balance.

Wow. So then they're doing their own job of making their own built in antioxidants. You're inspiring me to take it. I've been using broccolite for a long time and I've probably been out for the last six months. And when we're done with the show, I'll walk you guys through my supplement ruin. And it looks like, you know, a pharmacy, but I take about 150 supplements a day. And every now and then like I'll run out of something and I won't put it in the reorder me now box. And then it falls off the spreadsheet. And for about six months I've not been taking broccoli, but I've taken it consistently for like four years.

You might be in a category that matches a paper. And, and it was that in mice, they, they, they took NRF2 for a relatively long time, longer than normally you do with mice. And they found out that after a decent time, the NRF2 stayed on for six months.

Oh, interesting.

And in a mouse, that's a lot longer than six months in humans.

And even if you don't take it that long, if you take one serving, it'll keep NRF2 on for 72 hours.

Wow. So that's a long period of time. So should I eat this packet?

Yeah.

We encourage you to keep the desiccant.

Packet in the bottle.

Desiccant. All right, but I'm out of water, you guys. Where's that bottle of water? Mads, we grabbing some more water? I am, actually. I'm feeling inspired to take some. And by the way, guys, if you're feeling inspired to take some too, I've got a code for you. Mara-Labs M A R A-Labs.com. dave, they'll give you up to 28% off. And here's what I want you to know. 100 day, no questions asked guarantee. So you can try it. You save money and if you don't feel anything after a month, you can just send, I know you send an empty bottle, just say you didn't like it, whatever yeah, there you go. So they believe in what they're doing, which is cool. And like I said, I've been taking this for years before I met you guys, because doing the research on NRF2 was good. Should I stick, like, 10 of them?

Yeah, here we go.

So how many do I have here? 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. I guess they're right.

So early on, we were noticing a difference in our inflammatory. Like, in our inflammation. Like, I play guitar. I'm not great at it, but I enjoy it. And I'd stop playing and start playing again and. And could only play for a couple minutes, start once we got the broccoli in the capsule, took it, and pretty quickly that, like, instead of being able to play three minutes, I could play as long as I wanted. And so we're like, internally, the. You know, we're wondering, like, how long. How quickly does this work? And so John created a study looking at IL6 and urine. So interleukin 6.

Yeah.

And so two capsules reduced IL6 30% in 24 hours.

Wow. So during this last three, four years of public policy insanity, which shall not be named for algorithmic things.

Thank you.

I did write a long blog post listing the compounds that reduce IL6, because it turns out this inflammatory cytokine, which I've had issues with for years because of toxic mold, almost any infection is going to raise IL6, which causes systemic inflammation. And if you suppress IL6 or what's known as a cytokine storm, then you have less symptoms of whatever current thing is in the air. God, this is great. I feel like I'm in the land of double plus good double speak. And by the way, if you're under 30, the school stopped having you read the book that that is from, which is 1984. And if you haven't read that, like, download it, you'll like it. All right, so I've successfully said things without saying them, possibly in a way that can fool our AI overlords. Do you think I did a good enough job? I think so. All right, good deal. So anyway, suppressing IL6 is a preeminent way of being resilient, not getting sick or having less symptoms when you do get sick and living longer. In my experience of longevity. Do you guys agree with that?

Yeah, it's amazing. It's the middle of everything.

30% suppression of one of the most important cytokines from a couple capsules of sulforaphane that's stabilized. Yep.

And that was a internal study, and it was Done with friends and family. So take it for what you.

As you ate.

Yeah. And what's interesting is, you know, we, when we, we do podcasts, talking about the big movers is we do reactive oxygen species. So it turns on a whole bunch of genes that take care of reactive oxygen species and nitrogen species, and then turning on the especially phase two and three detox pathways. And the third is blocking nrf, I mean, NF Kappa B. And so it does all three of those really well. And there's thousands of papers on it.

Wow. So. So you guys have heard me talk about hydrogen water for years. And one of the reasons hydrogen water is interesting is it blocks peroxy nitrite, which is the nitrogen species you talked about. I've had issues with this for years because there's three kinds of nitric oxide in the body. There's the endothelial. That's good. That's why you take stuff like N101 to increase the stuff that helps your blood vessels. And then there's the neural, which is good for your brain and is hard to induce. And then there's inos or inducible nos, which goes to peroxy nitrite. And it's bad for you. So if your pathways are broken or you don't have the ability to quench those free radicals because your cells are working, then you tend to get migraines and you get all sorts of cellular dysfunction. And it's one of the more pernicious and mean of the pro oxidants. And you're saying that sulforaphane quenches peroxy nitrite?

Yeah. So that's part of phase two detoxification. It's actually pretty strongly induced by sulforaphane.

Wow, I did not know that part.

Yeah. And NF kappa B is classically. Other supplements are known for it. But remember, sulforaphane is really bioavailable, so it might get to places where some of the other supplements might not get to.

And sulforaphane is both water and fat soluble, like MCT oil is.

That's right.

Okay. And most compounds, they either love water or they hate water. And the fact this does both is, is really helpful. It's one of the reasons MCT is such a powerful compound for driving other things through the gut. Is there any reason I should take this with MCT oil?

Wow, that's super interesting. So I think that a beautiful if, if I were to try and step into biohacking world would be since sulforaphane lowers your glucose levels, you're going to get into ketosis faster.

Oh, interesting.

And then maybe add some of your C8. That's been shown to do great things. And it would for sure be synergistically activated.

Okay, now. Okay. I've spent six months of my life in one week segments with electrodes glued to my head, learning advanced meditations. One of my companies called 40 Years of Zen does that for executives. So I have these weird systems, mostly because I didn't know there was anything below my neck that mattered till I was 30. So I had to just relearn all this weird stuff. I'm feeling, like, a noticeable shift in energy that I. I'm actually a little bit surprised by. It gets kind of spreading out. Is this placebo? I mean, it seems pretty fast. The capsule should have opened by now.

Yeah, there's a lot of people that are. No troping. People that love the brain buzz.

It feels like neurotropic E. Yeah.

I mean, that's one of the benefits.

I'm kind of liking this sulfur Fame.

Is the brain drive nootropic factor. Bdnf.

Oh, man, you ruined my joke. I was gonna say. So I hear you guys are into bdsm. Yeah. And then he was like, what? And then I was like, oh, I mean, bdnf. Anyway, sorry. Thanks for ruining my joke, man. Sorry. Yeah, no. So bdnf. My book called Headstrong. New York Times monthly science bestseller about here's all the stuff you can do for your brain, and it's like half mitochondrial function and half BDNF and nerve growth factor induction. Just do those two things, and you have a young brain again. And I did not have any idea that broccoli would upregulate bdnf, because normally it's a good extract of lion's mane. By the way, I've never seen one in coffee. Like, they're using an extract of lion's mane that doesn't do anything. I've been disappointed for years till I found out to heat and alcohol extract and all that. And then there's a bunch of other things like fasting and whatever. So compare what broccoli does for BDNF with BDNF focused supplements. Is this like a strong effect or a weak effect?

John has a answer to that. But one of the ways we know. So early on, I was doing customer service for the.

I was doing everything as entrepreneurs do. Yeah.

I get a customer, I want my money back. It's not working. And so, like.

Sure.

Let me just ask you One question. Have you had vivid dreams? And they're like, no way. No way. That's this. And I was like, yeah. So that's, that's the bdnf.

That's how you tell. So few people know that. So, so you can tell whether your lion's mane is garbage or not is in that if you take it and you don't have it. The dreams. It probably didn't work because I, I had literally given up on lion's man. I used to put it in coffee. I tried all these different forms until I tried a form in tincture before bed that worked. And most of the time it's just like the mycelium, but they don't give you the parts that are effective.

Yeah. And I will say not, you know, it does work, but not everybody either get has the dreams or remembers the dreams. And so about 25% of the people will say, yeah, we have lipid traits.

And interestingly, most psychedelics. And my new book has a lot of info on psychedelics in it. It'll be out next year. Most psychedelics and in particular ketamine induce large changes in bdnf. So we've started using ketamine at my neuroscience clinic at 40 years of Zen as an optional add on to increase neuroplasticity during deep brain training. And there's no reason that I shouldn't be adding broccolit into my stack for people. So people who come, guys, we're gonna give you a, a, a big stack to take before you get there so that you're properly lubricated in the brain. We'll say, okay, this is a more broad spectrum than I realized, which is kind of cool. I've been taking it for a while because I knew about the longevity effects. But all three phases of detox plus IL6 for inflammation plus peroxy nitrite plus inducing neuroplasticity. That's kind of cool. Let's talk microbiome. I've, I've been a huge fan of the microbiome for years. I've been an advisor and investor in Biome who's been measuring that. What do you guys see sulforaphane does for gut bacteria?

I don't know where to start because it's kind of a big, it's a big world that we play in there.

But to start, let's talk microbiome. I've, I've been a huge fan of the microbiome for years. I've been an advisor and investor in Biome who's Been measuring that. What do you guys see Sulforaphane does for gut bacteria.

I don't know where to start because it's kind of a big. It's a big world that we play in there. But to start off with, I think maybe it's helpful to know that we were part of the startup for what's called Restore. Okay, so gut supplement that closes tight junctions.

Oh, the one with Zach Bush.

Yes.

Oh, yeah, Zach's been on the show. He's been a friend for years. Okay. Yeah, I like that stuff.

So John bedded Restore.

Oh, no kidding. So I use Humic and Fulvic in endangered coffee. It's in there different form than in Restore. But Restore is a really, really cool product. Yeah.

Yeah. So every cell type I've looked at so far at Titans tight junctions. And so we know that the pathway to tighten tight junctions is NRF2. So the first thing to know is that the place where you're buying off with, I think maybe it's helpful to. To know that we were part of the startup for what's called Restore. Okay, so Gut supplement that closes tight junction. Microbiome resides is in a. In a small cage. And in that microbiome are some things that can be. Can be dangerous, most likely lps. And so if they get out of that. That box, they can cause damage. And so because that happens.

Oh, the one with Zach Bush.

Yes.

Oh, yeah, Zach's been on the show. He's been a friend for years. Okay. Yeah, I like that.

People have leaky gut and because they have dysbiosis, you have LPS leaking all the time. And so we like to start there because as soon as you tighten tight junctions, your microbiome remodels, and it remodels pretty fast.

So that's a new perspective for me. So fixing the loose junctions in the gut causes changes in the bacteria. It's not changes in bacteria that cause the. The tight junction. What about things like zonulin? I just had an episode where we talked about that. Does Zonulin go down on Sulforaphane?

We haven't measured that directly, so we don't know that answer. But it does tighten tight junctions.

Okay.

And in many cell types, you can do any form of nrfto, induction, bold, tight and tight junctions. They're basically, there's whole review articles that talk about all the things that are able to tighten tight junctions. Every one of them that does it does it through NRF2.

I found a study out there that showed that if they use Sulforaphane on old versus young mice. It gave the old mice, young mice bacteria levels. And listeners might remember I've talked about this. You can predict someone's age by looking at the number of species of bacteria in the gut. I quadrupled my number of species by using prebiotics when I was riding Superhuman. And it's one of those many markers of aging you could measure. But you're showing that just sulforaphane without any other changes is giving you a bigger diversity or bigger volume of species.

So all we know is that naturally David has done a lot of work in this area personally.

So John bedded restore.

Oh no kidding. So I use humic and fulvia.

You can change your diet and how fast your microbiome changes.

Three days, right?

Yeah, yeah, it's fast.

And use my me and my kids.

Oh yeah. The best guinea pigs of all our family. My, my kids have been victims of testing for a long time.

So I think that whole business of, of whether you're able to make butyrate in your, in your by your microbiome is going to then go backwards and affect your, your enterocytes and your neuroendocrine cells there. And so all of those, you know, there's multiple layers there and they're all talking to each other. But I think that the really great part about that is if you just tighten the tight junctions, some of the inflammation that's getting sensed by your gut associated lymphoid tissue is calmed down and then the microbiome without the inflammation there changes pretty dramatically. And then you start getting these feedback and forth the enterocytes start feeding or.

Making better look in endangered coffee. It's in there a different form than in Restore. But Restore is a really, really cool product.

Yeah yeah. So every cell type I've looked at so far at titans tight junctions and so we know that the pathway mucus layer better separation from the microbiome itself. The microbiome way to tighten tight junctions nrf2 so the first thing to know is that the place where your bio starts because of the change in its composition it starts eating different food. So when you're introducing the foods that you know will change your microbiome, your indigestible fibers and your phyto microbiome resides is in a small cage. And in that region, I mean not what's the phytonutrients in general will be started to acted on by the microbiome. And so that snowball effect starts and it starts pretty fast.

And then on the opposite in the opposite direction. If you think, like, how does a old mouse get old? Micro. Old microbiome. It's the opposite, right, that the tight junctions get loose. There's lps, there's. There's just unhealth in general. And the microbiome shifts.

This is fascinating. I. I mean, I, I feel like broccoli extract, or in this case specifically, sulforaphane, that's. That's stabilized. It almost feels like an old supplement for longevity in my world, because I.

Microbiome are some things that can be. Can be dangerous, most likely lps. And so if they get out of that box, they can cause damage. And so because that's happening, people have leaky gut and because they have dysbiosis, you have LPS leaking all the time.

Do all the weird stuff. And I've been taking it for a long time, mostly because I just knew some of the things about NRF too, just for longevity. But the stuff about autistic kids and BDNF and all three phases of detox, this hits a lot of the stuff in my longevity book and my cognitive function book in a way I didn't know until this interview. And I'm actually really intrigued. So you've inspired me to make sure that.

And so we like to start there because as soon as you tighten tight junctions, your microbiome remodels.

I have this back in my stack and I'm unquestionably feeling those 10 capsules I just took. Oh, wow. I didn't mention this ahead of time, but a couple days ago, because we're doing ketamine assisted neurofeedback at 40 years of Zen. I was. I've been working with our medical doctor on proper dosing. Right. And so I tried a much heavier dose than we would use at the clinic ever. And my brain wasn't that happy this morning as a result of that. And I feel like all of that fog just lifted. So that's really cool. And like I said, ketamine's a neuroplasticity inducing agent. I do not use it every day. If someone's trying to get you to use ketamine, like for 30 days or something, that's. And it remodels pretty fast, so that's a new perspective for me. So fixing the loose junctions in the gut causes changes in the bacteria. It's not changes in bacteria that cause the. The tight junction. What about things like Zonulin? I just had an episode where we. Bad news for many things like this is occasional use with doctors. You can do ceremonial work, whatever, but I'm not promoting talked about that. Does zonulin go down on sulforaphane party use of it? I think that's actually not a good, a good drug for that. But just you know the, the little thing to talk about that. But the fact my brain works now in a different way is evidence enough for me that something's going on in there. The one thing we haven't talked about in my notes is mitophagy, which is another fetish that I have and listeners know that I'm all about autophagy and mitophagy. Can you explain mitophagy and what and how sulforaphane does to affect it?

So most studies that are related to mitophagy will often talk about. We haven't measured that directly so we don't know that answer. But it does tighten tight junctions and in many cell types you can, you can do any form of NRFTO induction bold, tighten tight junctions. They're basically there's whole review articles that talk about all the transcription factor that's made in your own genome that then talks to your, to your mitochondria. And the master control transcription factor for that is called PGC1 Alpha. And so inducing PGC1 Alpha has to be a part of your mitochondrial maintenance. And there's so many different ways to do it. Things that are able to tighten tight junctions, every one of them that does it does it through NRF2. And the way I like to, to, to, to introduce this topic is I, I sit down with a lot of people that are just that are sick and they've been to the doctor a million times and they just want some, a little bit of help. And so a really good place to start with that is just a few supplements that are able to induce your energy production. So induction of PGC1 Alpha is a great place to start and a few little supplements there and then they find themselves moving a little bit more and then they're sleeping a little bit better, they're more likely to go to the gym. And so it's like a little inducer in that area.

I found a study out there that showed that if they use sulforaphane on old versus young mice, it gave them. So sulforaphane raises PGC1 alpha, the old mice, young mice, bacteria levels and, and.

It does it in indirect ways.

Okay.

So like one possible pathway that you could think about it doing is one of the best inducers of NAD is butyrate beta hydroxybutyric acid raising listeners might.

Remember, I've talked about this. You can predict someone's age by looking.

At the number NAD is known to induce PG1, PGC1 Alpha, same like fasting also is another pathway that feeds into NAD and PGC1 alpha and mitophagy. So we think of it as sulforaphane as a, a stress that's not a stress. And so your body's response to it.

Number of species of bacteria in the gut. I quadrupled my number of species by using prebiotics when I was is to.

Is to increase the, the number of mitochondria. So that's induction. There's, there's also fission where they'll move together and then there's elongation. And so there's been a number of studies showing sulforaphane effects on all three. And so you can, you can get rid of under functioning mitochondria. That's a lot like a very high stressful exercise routine. And it'll get rid of under functioning.

Or a longer fast will do that as well.

Yeah, longer. And we think of it that way as like if you can't do a four day fast, maybe try a one day fast and take sulforaphane. And then we think that those two are, are working together to make it a more effective fast. And so there's many papers showing mitophagy.

Induction and writing Superhuman and it's one of those many markers of aging you could measure, but you're showing that just.

That is a component of, of, of how it works.

Got it. PGC1 Alpha is something I wrote about in Superhuman. And guys, if you haven't read that, it's a preeminent longevity book and it tells you exactly why there are proven ways to extend lifespan. Even though there's some doctors out there hitting the pavement right now saying it's not possible to extend human life, ignoring the fact that our lforaphane without any other changes is giving you a bigger diversity or bigger volume of species.

So all we know is that naturally David has done a lot of work in this area personally where you can change your diet and how fast your.

Microbiome lifespan extended by 6.5 years already in the last 30 years. So I think we're doing it and you have to be maybe a little bit traumatized to be blind to that. So whatever's going on there, I don't know. But I firmly believe based on evidence more than a thousand studies that that this is possible. And there's only $600 billion being invested in longevity this year, maybe some of that's going to work. And NRF2 is one of those pathways because it's what happens when you exercise. So my two favorite NRF2 inducers are longevity drugs. One is called GW 501566 or Carterine. And this is exercise and a pill. It's a, it's a performance enhancing drug that's banned. Of course. All the stuff that's good is banned by sporting bodies. So that's how you know it works. Right, for longevity. Because they want athletes to get old to make space for new ones. Apparently. I don't know. But 40 year old athletes should be on testosterone for God's sake. Anyway. Three days, right?

Yeah, yeah. It's fast.

And use my, me and my kids.

I digress. PGC1 Alpha, you want to raise it. This drug does it. It also causes you to grow new mitochondria, which is kind of good. Like 30% more. And of course it's a research grade thing, but why not? Oh yeah. The best guinea pigs of all are family. My kids have been victims of testing for a long time.

So I think that whole business of whether you're able to make butyrate microbiome is gonna.

There's also this other thing that mimics exercise that is a longevity drug. And I'm gonna piss you guys off. Are you ready?

Pharmaceutical nicotine then go backwards and affect your, your enterocyte.

I saw, I saw the flinch. So, so here's the kicker. Tobacco's not good for longevity. We all know that. But 1 to 5 milligrams very low dose. A cigarette has 20 milligrams very low dose. Pharmaceutically extracted raises PGC1 Alpha. And people who smoke don't get Alzheimer's or Parkinson's. Very, very low. But they get cancer and cardiovascular disease. You take those out by getting rid of the tobacco and you just have this pure drug. It turns out it's a potent nootropic and it's an exercise mimetic. And if you ever go down to South America, you wonder how these, these people are so thin. Well, it's because they smoke like Jimnies, which is bad for you. So I've been recommending over age 41-5mg of pharmaceutical nicotine. Apart from smoking, the effects on PGC1 Alpha and on cognitive function and nicotinic acid receptors are actually really interesting and probably beneficial, especially at the 1 to 2. But it's all because PGC1 Alpha. So there you go. What do you think am I crazy?

I had no idea that that was, that was true. Send your neuroendocrine cells there. And so all of those, you know, there's multiple layers there and they're all talking to each other. But I think that the really great part about that is, is if you just. But I can put two papers together that I know of that I can see how it supports tighten to tight junctions some of the inflammation that's getting sensed by your gut associated lymphoid tissue. Yeah. Because I used it as a control in an experiment one time to induce prostaglandin E2.

Oh wow.

And so does Bohb and so does PQQ.

Yep. That's one of the long standing supplements I've recommend. In fact, the first PQQ on the market. I used to make a specialized form when I ran bulletproo that was stable in stomach acid of pqq.

Super cool. So is that, is that the hack is nicotine pqq and if you want to launch.

Yeah, that's a great stack right there. And if to save money on pqq, take a little baking soda with it because stomach acid causes it to precipitate, it doesn't do anything. So if you have an alkaline environment in the stomach, you'll absorb PQQ and then take a little spray or a little sachet without the bad sweeteners and have a shot of espresso and oh my God, you'll write a novel or maybe another New York Times bestseller could or go on stage. And it's not just me saying this is calmed down.

And then the microbiome without the inflammation there changes pretty dramatically. And then you start getting these feedback.

And I found a guy, I call him Dr. Nicotine if memory serves.

Fourth, the enterocytes start feeding, are making better.

It's been a couple hundred episodes. Andrew Newcomb, I think from Vanderbilt. He's been publishing since 1980.

Mucus Layer, better separation from the microbiome itself. The microbiome.

Six reliable studies on Alzheimer's and nicotine. But everyone says, oh, tobacco nicotine, same thing. They're not the same. So it's all about the dose. So I, I do that as a part of my longevity practice. I'll use like a quarter, half of a patch. I probably have one on right now, unless it fell off. Let's see. See the patch right there?

Yeah.

So there's my nicotine for the day. Part of that is because I don't want to get Alzheimer's. My grandmother passed at 101 and she had Alzheimer's in the last few years. It doesn't sound fun. Rather not. So being proactive, but now I've got my sulforaphane, I'm going to keep doing my nicotine and I'll do this weird thing called exercise with AI and thank you. Upgrade labs and have enough time left over to go have fun. Right. That's the plan. By the way, I'm doing another five of these.

I feel like you unlocked a little bit. Like I have a bunch of papers swimming in my head. Yeah, there's some connection with nicotine and, and reduction in some cancers, right?

Oh, yeah. Surprisingly, there's also an increase in some at higher doses. And most of those papers, though, is because they were smoking. And you just, you. Anytime you burn stuff, I don't care if it's pot or plastic, you shouldn't breathe it or, or meat. Like, it turns out the number two source of indoor air pollution is you didn't have a good vent hood on your stove. Right. So I have air quality monitors that turn up my air filters throughout the house. And as soon as I cook anything, even with the, the hood on that sounds like a jet taking off, they all turn yellow and start cleaning the air. That means I'm breathing secondhand smoke from bacon or something. So I usually cook outdoors. I don't want my lungs to affect, to be affected by that. So no burning. And then I also make sure that I, I do a little bit of nicotine because mitochondrial enhancement is good for stopping cancer. That's why pqq, that's why MCT oil, almost any of the things that upregulate mitochondria, downregulate cancer. So, yeah, check out Andrew Newcomb from Vanderbilt. Interesting guy. You are both a little bit different as research scientists. When I talk to Dr. Nicotine, like.

Some starts because of the change in its composition, it starts eating different food. So what's your favorite form?

You know, you talked to me about typing speed, all these benefits.

But when you, you, you're, you're introducing the foods that you know will change your microbiome, your, your indigestible fibers, and your phytostero. Phytoestrogen. I mean, not what's the phytonutrients in general will be.

Are you on the patch? Do you use a spray? And he goes, oh, I've never tried it. Like, I wouldn't want to bias myself. And I'm like, how can you study something without trying it? So you obviously are willing to use sulforaphane. How much broccoli do you each take per day? You have unlimited supplies of this? I just took 15 of these.

How would you do.

I do two professionals in the morning, which is 15.

Is that professionals versus plus? What's the difference? It has, it has good support.

He started to acted on by the microbiome. And so that snowball effects starts. And it starts pretty fast.

Okay. So you're basically doing three of the consumer grades. Okay. And then one at night. So four per day. And Nightingale.

I'll do eight at night and probably eight in the morning.

All right. We can be friends, David.

And then on the opposite, in the opposite direction, if you think like, how does a old mouse.

I'm just kidding. There is this thing that we all have. It's a cognitive bias.

Get old micro. Old microbiome. It's. It's the opposite, right, that the digestions.

Get loose because our brains are trying to save electricity. That says if something good, more better. And it turns out it's not true for almost anything. In the case of sulforaphane, is there an upper limit?

Um, there's lps, there's. There's just unhealth in general. And the microbiome shifts where you get.

Less returns or where it turns dark.

I don't know that answer. I know they've, they've done quite a few studies with much higher doses.

Yeah.

Like 600 micro.

This is fascinating. I. I mean, I. I feel like.

Broccoli extra milk, which is. That's a lot. Maybe 130 milligrams. So that would be 20 pills or something like that.

I just did 15. So we'll see what happens to me.

And the only side effect they see in those studies is gastrointestinal upset.

Okay. Yeah.

I mean maybe the first cells that see the sulforaphane are seeing a lot at once.

Okay.

So the plus in the broccoli plus is we add the cousin molecule from watercress called P. EITC Phenethyl isopiocyanate and.

Part of the retract or in this case specifically sulforaphane, that's, that's stabilized. It almost feels like an old supplement for longevity in my world because I do all the weird stuff and I've been taking it for a long time mostly because I just knew some of.

The things and for that is John is seeing an like. Like you. There's an upper limit in the blood. Even if you take 15.

If you take 10. Yeah. Max out. Okay.

You max out.

And so about NRF too, just for longevity.

But the stuff about from NRF2 standpoint, even the other stabilized sultry product on the market, he's done a test on buccal swabs and it doesn't induce an RF2. And so, and we think that the synergy, the P, E, I, T, C plus the sulfur plus the other molecules that are from the seed, there are.

Five other isotopes, autistic kids and BDNF and all three phases of detox. This hits a lot of the stuff in my longevity book, Cyanides in the seed.

All those work in synergy to induce.

ARF2 and my cognitive function book in a way I didn't know until this interview. And I'm actually really intrigued. So you've inspired me to make sure that I, so I, I found a study out there, 30% more NRF too because you have the watercress extract in there as well. So you're really potently pushing that. And it, it kind of reminds me of what's going on in the beet industry as a supplement guy. So many people I have beets, I have this back in my stack and I'm unquestionably feeling those 10 capsules. They don't do anything to raise N1 to, to raise nitric oxide. It just doesn't. So I just took. Oh wow. I didn't mention this ahead of time, but a couple days ago I had like the lead scientist for 25 years of that stuff and he tells you exactly why inactivated eats out there just don't do stuff. And, and he has, you know, $60,000 gas chromatograph says well let's see if it induces it. And what do you know, There are ways to do it. N101 is the brand that, that tested highest. Of course it's his brand, but I've seen him do the tests and so just because it has beets doesn't mean it does anything. Just because it has broccoli doesn't mean it does anything. It's about whether it was stabilized because we're doing ketamine assisted neurofeedback at 40 years of Zen I was, I've been working with or whether if you're not using broccoli, whether you magically have the right gut bacteria and it turns out our medical doctor on proper dose, you probably don't. Just like people who've listened for a long time. There's something called urolithin A that's made by healthy gut bacteria from pomegranate so like if you eat five pounds of pomegranates and you're one of the few people with the gut bacteria and you don't mind all that sugar and oxalate, then you would make urolithinate or you could take the supplement and with broccoli, well, five pounds of broccoli with some radish or raw broccoli along the sizing, right? And so I tried a much heavier dose than we would use at the clinic ever. And my brain wasn't that happy this morning. I said, and there you go. Now you got some NRF or you do the pills and then eat your broccoli or you don't. So I'm, we'll say I'm, I'm definitely a fan. Like I said, I've taken this stuff for years and I think it's a result of that. And I feel like all of it's potent and useful. And guys, if you're saying this might, might be worth it for you, MARA M A R A-Labs.com forward slash Dave to learn more.

Up to 28.

There you go. That's actually a good savings. And the fact you have a 100 day guarantee is good. And so guys, you're saying, well, Dave just told me I should take another supplement. Here's the deal, just to be really upfront about it, you have X number of pills you're willing to swallow every day. You have that fog just lifted. So that's really cool. And like I said, ketamine's a neuroplasticity inducing agent. I do X number of minutes you're willing to spend doing stuff to live longer. And you have X number of effort, do not use it every day. If someone's trying to get you to use ketamine like for 30 days or something that's or pain you're willing to do. So if I told you punch yourself in the face 10 times a day, bad news for many things like this is occasional use and you'll live forever. No one's going to do it because it sucks, right? So there's an amount of suffering, amount of time and an amount of money that you're willing to spend. And it's my job to teach you this tool for longevity. I don't care if it's a laser or a supplement, it has this effect biologically. And it's your job to say, all right, is detox with doctors, you can do ceremonial work, whatever, but I'm not promoting the focus of my strategy. If so, then broccoli yes. But if you're saying neuroplasticity is my thing, well, it turns out broccoli might be a good thing. So the more avenues that a supplement can address for you then the more it's worth it financially. And swallowing the pills, but only you know your goals. I don't know your goals. So you have to make that decision for yourself. And you could do what I do, which is take everything I talk about. But I'm a professional longevity guy. I've been doing this for 25 years. And Frank Lamb willing to swallow 150 pills a day. So there's that. Anyway, Mara M A R A dash Labs forward slash Dave. And you save some money. I tell you that if you take 10 of them you're going to feel it because I'm really feeling it. Guys, thanks for making the trip out to Austin.

Dave, thanks so much for having us.

Yeah, it's a pleasure.

You're listening to the Human Upgrade with Dave Asprey Party use of it. I think that's actually not a good, a good drug for that. But just you know the, the little thing to talk about that, but the fact my brain works now in a different way is evidence enough for me that something's going on in there. The one thing we haven't talked about in my notes is mitophagy, which is another fetish that I have and listeners know that I'm all about autophagy and mitophagy. Can you explain mitophagy and what and how sulforaphane does to affect it?

Yeah. So most studies that are related to mitophagy will often talk about transcription factor that's made in your own genome that then talks to your mitochondria. And the master control transcription factor for that is called PGC1 Alpha. And so inducing PGC1 Alpha has to be a part of your mitochondrial maintenance. And there's so many different ways to do it. And the way I like to introduce this topic is I sit down with a lot of people that are just that are sick and they've been to the doctor a million times and they just want some a little bit of help. And so a really good place to start with that is just a few supplements that are able to induce your energy production. So induction of PGC1 Alpha is a great place to start. And a few little supplements there and then they find themselves moving a little bit more and then they're sleeping a little bit better, they're more likely to go to the gym and so it's like a little inducer in that area.

So Sulforaphane raises PGC1 Alpha and it.

Does it in indirect ways. Okay, so like one possible pathway that you could think about it doing is one of the best inducers of NAD is butyrate beta hydroxybutyric acid. So raising NAD is known to induce PGC1 alpha. Same like fasting also is, is another pathway that feeds into NAD and PGC1 alpha and mitophagy. So we think of it as sulforaphane as a, a stress. That's not a stress. And so your body's response to it is to, is to increase the, the number of mitochondria. So that's induction. There's, there's also fission where they'll move together and then there's elongation. And so there's been a number of studies showing sulforaphane effects on all three. And so you can, you can get rid of under functioning mitochondria. That's a lot like a very high stressful exercise routine. And it'll get rid of under functioning.

Or a longer fast will do that as well.

Yeah, longer. And we think of it that way as like, if you can't do a four day fast, maybe try a one day fast and take sulforaphane. And then we think that those two are working together to make it a more effective fast. And so there's many papers showing mitophagy induction and that is a component of how it works.

Got it. PGC1 Alpha is something I wrote about in Superhuman. And guys, if you haven't read that, it's a preeminent longevity book.